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Variants in five genes signal TNBC risk
Women with germline pathogenic variants in five genes are at high risk for developing triple-negative breast cancer, and have a greater than 20% lifetime risk for breast cancer in general, results of a large study suggest.
Multigene testing of nearly 11,000 women with triple-negative breast cancer (TNBC; lacking estrogen, progesterone, and human epidermal growth factor receptors) showed that germline pathogenic variants in BARD1, BRCA1, BRCA2, PALB2, and RAD51D were associated with risk for clinical TNBC ranging from nearly sixfold to more than 16-fold higher than that of women without the genetic variants, reported Fergus J. Couch, PhD, of the Mayo Clinic, Rochester, Minn., and his colleagues.
“The results suggest that all TNBC patients should undergo multigene panel testing, regardless of age at diagnosis or family history of cancer, for improved cancer risk assessment and because of the ongoing development of targeted therapeutic approaches for TNBC patients with mutations in predisposition genes,” they wrote. Their report is in the Journal of the National Cancer Institute.
Although National Comprehensive Cancer Network guidelines recommend testing for the cancer predisposition genes BRCA1 and BRCA2 in women with a TNBC diagnosis at age 60 or younger or those with a family history of breast and/or ovarian cancer, the picture is less clear regarding genetic predisposition to TNBC, the authors noted.
“[R]ecommendations for testing of other genes are not fully established because the risks of TNBC associated with mutations in cancer predisposition genes have not been established. Thus, a better understanding of gene-specific risks for TNBC is needed to identify the genes that should be tested in the setting of TNBC,” they wrote.
The investigators looked for associations between deleterious mutations in cancer predisposition genes and TNBC among 8,753 patients with TNBC testing with a 21-gene assay, and among 2,148 women tested for 17 genes in studies conducted by the Triple Negative Breast Cancer Consortium.
They found that among white women, germline pathogenic variants were associated with the following odds ratios (OR) for TNBC (all P values less than .0001):
- BRCA2 = 5.42
- BARD1 = 5.92
- RAD51D = 6.97
- PALB2 = 14.41
- BRCA1 = 16.27
Although there were insufficient data on the risks for African American women, an exploratory analysis showed that risks for TNBC associated with specific pathogenic variants were similar to those for white women, the authors said.
The pathogenic variants were detected in 12% of all patients in the study.
“Continued study of gene-specific risks for breast cancer subtypes may lead to tailored medical management recommendations for PV [pathogenic variant] carriers. Consistent with this hypothesis, initial studies evaluating intensified screening in high-risk women have suggested that a decrease in mortality from TNBC can be achieved,” they wrote.
The study was supported in part by the National Institutes of Health and the Breast Cancer Research Foundation, and was sponsored by Ambry Genetics Inc. The authors reported having no conflicts of interest.
SOURCE: Shimelis H et al. J Natl Cancer Inst. 2018 Aug 7. doi: 10.1093/jnci/djy106.
Women with germline pathogenic variants in five genes are at high risk for developing triple-negative breast cancer, and have a greater than 20% lifetime risk for breast cancer in general, results of a large study suggest.
Multigene testing of nearly 11,000 women with triple-negative breast cancer (TNBC; lacking estrogen, progesterone, and human epidermal growth factor receptors) showed that germline pathogenic variants in BARD1, BRCA1, BRCA2, PALB2, and RAD51D were associated with risk for clinical TNBC ranging from nearly sixfold to more than 16-fold higher than that of women without the genetic variants, reported Fergus J. Couch, PhD, of the Mayo Clinic, Rochester, Minn., and his colleagues.
“The results suggest that all TNBC patients should undergo multigene panel testing, regardless of age at diagnosis or family history of cancer, for improved cancer risk assessment and because of the ongoing development of targeted therapeutic approaches for TNBC patients with mutations in predisposition genes,” they wrote. Their report is in the Journal of the National Cancer Institute.
Although National Comprehensive Cancer Network guidelines recommend testing for the cancer predisposition genes BRCA1 and BRCA2 in women with a TNBC diagnosis at age 60 or younger or those with a family history of breast and/or ovarian cancer, the picture is less clear regarding genetic predisposition to TNBC, the authors noted.
“[R]ecommendations for testing of other genes are not fully established because the risks of TNBC associated with mutations in cancer predisposition genes have not been established. Thus, a better understanding of gene-specific risks for TNBC is needed to identify the genes that should be tested in the setting of TNBC,” they wrote.
The investigators looked for associations between deleterious mutations in cancer predisposition genes and TNBC among 8,753 patients with TNBC testing with a 21-gene assay, and among 2,148 women tested for 17 genes in studies conducted by the Triple Negative Breast Cancer Consortium.
They found that among white women, germline pathogenic variants were associated with the following odds ratios (OR) for TNBC (all P values less than .0001):
- BRCA2 = 5.42
- BARD1 = 5.92
- RAD51D = 6.97
- PALB2 = 14.41
- BRCA1 = 16.27
Although there were insufficient data on the risks for African American women, an exploratory analysis showed that risks for TNBC associated with specific pathogenic variants were similar to those for white women, the authors said.
The pathogenic variants were detected in 12% of all patients in the study.
“Continued study of gene-specific risks for breast cancer subtypes may lead to tailored medical management recommendations for PV [pathogenic variant] carriers. Consistent with this hypothesis, initial studies evaluating intensified screening in high-risk women have suggested that a decrease in mortality from TNBC can be achieved,” they wrote.
The study was supported in part by the National Institutes of Health and the Breast Cancer Research Foundation, and was sponsored by Ambry Genetics Inc. The authors reported having no conflicts of interest.
SOURCE: Shimelis H et al. J Natl Cancer Inst. 2018 Aug 7. doi: 10.1093/jnci/djy106.
Women with germline pathogenic variants in five genes are at high risk for developing triple-negative breast cancer, and have a greater than 20% lifetime risk for breast cancer in general, results of a large study suggest.
Multigene testing of nearly 11,000 women with triple-negative breast cancer (TNBC; lacking estrogen, progesterone, and human epidermal growth factor receptors) showed that germline pathogenic variants in BARD1, BRCA1, BRCA2, PALB2, and RAD51D were associated with risk for clinical TNBC ranging from nearly sixfold to more than 16-fold higher than that of women without the genetic variants, reported Fergus J. Couch, PhD, of the Mayo Clinic, Rochester, Minn., and his colleagues.
“The results suggest that all TNBC patients should undergo multigene panel testing, regardless of age at diagnosis or family history of cancer, for improved cancer risk assessment and because of the ongoing development of targeted therapeutic approaches for TNBC patients with mutations in predisposition genes,” they wrote. Their report is in the Journal of the National Cancer Institute.
Although National Comprehensive Cancer Network guidelines recommend testing for the cancer predisposition genes BRCA1 and BRCA2 in women with a TNBC diagnosis at age 60 or younger or those with a family history of breast and/or ovarian cancer, the picture is less clear regarding genetic predisposition to TNBC, the authors noted.
“[R]ecommendations for testing of other genes are not fully established because the risks of TNBC associated with mutations in cancer predisposition genes have not been established. Thus, a better understanding of gene-specific risks for TNBC is needed to identify the genes that should be tested in the setting of TNBC,” they wrote.
The investigators looked for associations between deleterious mutations in cancer predisposition genes and TNBC among 8,753 patients with TNBC testing with a 21-gene assay, and among 2,148 women tested for 17 genes in studies conducted by the Triple Negative Breast Cancer Consortium.
They found that among white women, germline pathogenic variants were associated with the following odds ratios (OR) for TNBC (all P values less than .0001):
- BRCA2 = 5.42
- BARD1 = 5.92
- RAD51D = 6.97
- PALB2 = 14.41
- BRCA1 = 16.27
Although there were insufficient data on the risks for African American women, an exploratory analysis showed that risks for TNBC associated with specific pathogenic variants were similar to those for white women, the authors said.
The pathogenic variants were detected in 12% of all patients in the study.
“Continued study of gene-specific risks for breast cancer subtypes may lead to tailored medical management recommendations for PV [pathogenic variant] carriers. Consistent with this hypothesis, initial studies evaluating intensified screening in high-risk women have suggested that a decrease in mortality from TNBC can be achieved,” they wrote.
The study was supported in part by the National Institutes of Health and the Breast Cancer Research Foundation, and was sponsored by Ambry Genetics Inc. The authors reported having no conflicts of interest.
SOURCE: Shimelis H et al. J Natl Cancer Inst. 2018 Aug 7. doi: 10.1093/jnci/djy106.
FROM JOURNAL OF THE NATIONAL CANCER INSTITUTE
Key clinical point: Pathogenic variants in five cancer predisposition genes are associated with significantly increased risk for triple negative breast cancer (TNBC).
Major finding: Pathogenic variants in BRCA1 were associated with a more than 16-fold risk for TNBC.
Study details: Retrospective review of multigene assay testing in 10,901 women with TNBC.
Disclosures: The study was supported in part by the National Institutes of Health and the Breast Cancer Research Foundation, and was sponsored by Ambry Genetics Inc. The authors reported having no conflicts of interest.
Source: Shimelis H et al. J Natl Cancer Inst. 2018 Aug 7. doi: 10.1093/jnci/djy106.
RT linked with better survival in DCIS
Treatment with lumpectomy and radiotherapy was associated with a significant reduction in breast cancer mortality in patients with ductal carcinoma in situ (DCIS), compared with a lumpectomy alone or a mastectomy alone, investigators reported in JAMA Oncology.
Among women who received adjuvant radiation, there was an associated 23% reduced risk of dying of breast cancer. This extrapolated to a cumulative mortality of 2.33% for those treated with lumpectomy alone and 1.74% for women treated with lumpectomy and radiotherapy at 15 years (adjusted hazard ratio, 0.77; 95% confidence interval, 0.67-0.88; P less than .001).
“Although the clinical benefit is small, it is intriguing that radiotherapy has this effect, which appears to be attributable to systemic activity rather than local control,” wrote Vasily Giannakeas, MPH, of the Women’s College Research Institute, Toronto, and colleagues.
Emerging evidence suggests that adding radiotherapy to breast conserving surgery can reduce the risk of breast cancer mortality among women with DCIS and lower the risk of local recurrence. Because of the low rate of mortality associated with DCIS, the authors noted that it has been difficult to investigate deaths related to DCIS. The association of adjuvant radiotherapy with breast cancer survival in this population has also not yet been clearly established.
To determine the extent to which radiotherapy is associated with reduced risk of breast cancer mortality in patients treated for DCIS and identify patient subgroups who might derive the most benefit from radiotherapy, the authors conducted a historical cohort study using the Surveillance, Epidemiology, and End Results database. A total of 140,366 women diagnosed with first primary DCIS between 1998 and 2014 were identified, and three separate comparisons were made using 1:1 matching: lumpectomy with radiation versus lumpectomy alone, lumpectomy alone versus mastectomy, and lumpectomy with radiation therapy versus mastectomy.
A total of 35,070 women (25.0%) were treated with lumpectomy alone, 65,301 (46.5%) were treated with lumpectomy and radiotherapy, and 39,995 (28.5%) were treated with mastectomy.
The overall cumulative mortality for the entire cohort from breast cancer at 15 years was 2.03%. The actuarial 15-year mortality rate for the mastectomy group (2.26%) was similar to those who had lumpectomy without radiotherapy (2.33%).
The adjusted HR for death for mastectomy versus lumpectomy alone (based on 20,832 propensity-matched pairs) was 0.91 (95% CI, 0.78-1.05). The adjusted hazard ratios for death were 0.77 (95% CI, 0.67-0.88) for lumpectomy and radiotherapy versus lumpectomy alone (29,465 propensity-matched pairs), 0.91 (95% CI, 0.78-1.05) for mastectomy alone versus lumpectomy alone (20,832 propensity-matched pairs), and 0.75 (95% CI, 0.65-0.87) for lumpectomy and radiotherapy versus mastectomy (29,865 propensity-matched pairs).
When looking at subgroups and the effect of radiotherapy on mortality, the authors found the following: The HR was 0.59 (95% CI, 0.43-0.80) for patients aged younger than 50 years and 0.86 (95% CI, 0.73- 1.01) for those aged 50 years and older; it was 0.67 (95% CI, 0.51-0.87) for patients with ER-positive cancers, 0.50 (95% CI, 0.32-0.78) for ER-negative cancers, and 0.93 (95% CI, 0.77-1.13) for those with unknown ER status.
“How exactly radiotherapy affects survival is an important question that should be explored in future studies,” the authors concluded.
There was no outside funding source reported. Mr. Giannakeas is supported by the Canadian Institutes of Health Research Frederick Banting and Charles Best Doctoral Research Award.
SOURCE: Giannakeas V et al. JAMA Network Open. 2018 Aug 10. doi:10.1001/jamanetworkopen.2018.1100.
In an accompanying editorial, Mira Goldberg, MD, and Timothy J. Whelan, BM, BCh, of the department of oncology at McMaster University, Hamilton, Ont., noted that the primary goal of using adjuvant radiotherapy in patients with ductal carcinoma in situ (DCIS) is to reduce the risk of local recurrence of DCIS or of invasive breast cancer.
Despite widespread screening with mammography, along with improvements in technology so as to detect even smaller lesions, “there is increased concern about the overdiagnosis of DCIS,” they wrote. Results from recent studies generally suggest that patients with good prognostic factors and who have a low risk of local recurrence at 10 years (10%) are unlikely to gain any major benefit from being treated with radiotherapy.
They also pointed out that there is growing interest in the use of molecular markers as a means to help detect patients who are at a lower risk of recurrence and thus who may not benefit from radiotherapy.
“The results of the study by Giannakeas and colleagues are reassuring,” the editorialists wrote, as it demonstrated that the risk of breast cancer mortality in patients with DCIS is very low, and the potential absolute benefit of radiotherapy is also quite small. (The number of patients that need to be treated to prevent a breast cancer death was 370.) These data continue to support a strategy for low-risk DCIS of omitting radiotherapy after lumpectomy. This is especially pertinent when “one considers the negative effects of treatment: the cost and inconvenience of 5-6 weeks of daily treatments, acute adverse effects such as breast pain and fatigue, and potential long-term toxic effects of cardiac disease and second cancers.”
The editorialists also highlighted the authors’ speculation that there could be additional systemic effects of radiotherapy, possibly resulting from an elicited immune response or radiation scatter to distant tissues. While this hypothesis is theoretically possible, their results could also be explained by confounding factors, such as a higher use of endocrine therapy in patients who received adjuvant radiotherapy.
Dr. Whelan has received research support from Genomic Health. This editorial accompanied the article by Giannakeas et al. (JAMA Network Open. 2018;1[4]e181102). No other disclosures were reported.
In an accompanying editorial, Mira Goldberg, MD, and Timothy J. Whelan, BM, BCh, of the department of oncology at McMaster University, Hamilton, Ont., noted that the primary goal of using adjuvant radiotherapy in patients with ductal carcinoma in situ (DCIS) is to reduce the risk of local recurrence of DCIS or of invasive breast cancer.
Despite widespread screening with mammography, along with improvements in technology so as to detect even smaller lesions, “there is increased concern about the overdiagnosis of DCIS,” they wrote. Results from recent studies generally suggest that patients with good prognostic factors and who have a low risk of local recurrence at 10 years (10%) are unlikely to gain any major benefit from being treated with radiotherapy.
They also pointed out that there is growing interest in the use of molecular markers as a means to help detect patients who are at a lower risk of recurrence and thus who may not benefit from radiotherapy.
“The results of the study by Giannakeas and colleagues are reassuring,” the editorialists wrote, as it demonstrated that the risk of breast cancer mortality in patients with DCIS is very low, and the potential absolute benefit of radiotherapy is also quite small. (The number of patients that need to be treated to prevent a breast cancer death was 370.) These data continue to support a strategy for low-risk DCIS of omitting radiotherapy after lumpectomy. This is especially pertinent when “one considers the negative effects of treatment: the cost and inconvenience of 5-6 weeks of daily treatments, acute adverse effects such as breast pain and fatigue, and potential long-term toxic effects of cardiac disease and second cancers.”
The editorialists also highlighted the authors’ speculation that there could be additional systemic effects of radiotherapy, possibly resulting from an elicited immune response or radiation scatter to distant tissues. While this hypothesis is theoretically possible, their results could also be explained by confounding factors, such as a higher use of endocrine therapy in patients who received adjuvant radiotherapy.
Dr. Whelan has received research support from Genomic Health. This editorial accompanied the article by Giannakeas et al. (JAMA Network Open. 2018;1[4]e181102). No other disclosures were reported.
In an accompanying editorial, Mira Goldberg, MD, and Timothy J. Whelan, BM, BCh, of the department of oncology at McMaster University, Hamilton, Ont., noted that the primary goal of using adjuvant radiotherapy in patients with ductal carcinoma in situ (DCIS) is to reduce the risk of local recurrence of DCIS or of invasive breast cancer.
Despite widespread screening with mammography, along with improvements in technology so as to detect even smaller lesions, “there is increased concern about the overdiagnosis of DCIS,” they wrote. Results from recent studies generally suggest that patients with good prognostic factors and who have a low risk of local recurrence at 10 years (10%) are unlikely to gain any major benefit from being treated with radiotherapy.
They also pointed out that there is growing interest in the use of molecular markers as a means to help detect patients who are at a lower risk of recurrence and thus who may not benefit from radiotherapy.
“The results of the study by Giannakeas and colleagues are reassuring,” the editorialists wrote, as it demonstrated that the risk of breast cancer mortality in patients with DCIS is very low, and the potential absolute benefit of radiotherapy is also quite small. (The number of patients that need to be treated to prevent a breast cancer death was 370.) These data continue to support a strategy for low-risk DCIS of omitting radiotherapy after lumpectomy. This is especially pertinent when “one considers the negative effects of treatment: the cost and inconvenience of 5-6 weeks of daily treatments, acute adverse effects such as breast pain and fatigue, and potential long-term toxic effects of cardiac disease and second cancers.”
The editorialists also highlighted the authors’ speculation that there could be additional systemic effects of radiotherapy, possibly resulting from an elicited immune response or radiation scatter to distant tissues. While this hypothesis is theoretically possible, their results could also be explained by confounding factors, such as a higher use of endocrine therapy in patients who received adjuvant radiotherapy.
Dr. Whelan has received research support from Genomic Health. This editorial accompanied the article by Giannakeas et al. (JAMA Network Open. 2018;1[4]e181102). No other disclosures were reported.
Treatment with lumpectomy and radiotherapy was associated with a significant reduction in breast cancer mortality in patients with ductal carcinoma in situ (DCIS), compared with a lumpectomy alone or a mastectomy alone, investigators reported in JAMA Oncology.
Among women who received adjuvant radiation, there was an associated 23% reduced risk of dying of breast cancer. This extrapolated to a cumulative mortality of 2.33% for those treated with lumpectomy alone and 1.74% for women treated with lumpectomy and radiotherapy at 15 years (adjusted hazard ratio, 0.77; 95% confidence interval, 0.67-0.88; P less than .001).
“Although the clinical benefit is small, it is intriguing that radiotherapy has this effect, which appears to be attributable to systemic activity rather than local control,” wrote Vasily Giannakeas, MPH, of the Women’s College Research Institute, Toronto, and colleagues.
Emerging evidence suggests that adding radiotherapy to breast conserving surgery can reduce the risk of breast cancer mortality among women with DCIS and lower the risk of local recurrence. Because of the low rate of mortality associated with DCIS, the authors noted that it has been difficult to investigate deaths related to DCIS. The association of adjuvant radiotherapy with breast cancer survival in this population has also not yet been clearly established.
To determine the extent to which radiotherapy is associated with reduced risk of breast cancer mortality in patients treated for DCIS and identify patient subgroups who might derive the most benefit from radiotherapy, the authors conducted a historical cohort study using the Surveillance, Epidemiology, and End Results database. A total of 140,366 women diagnosed with first primary DCIS between 1998 and 2014 were identified, and three separate comparisons were made using 1:1 matching: lumpectomy with radiation versus lumpectomy alone, lumpectomy alone versus mastectomy, and lumpectomy with radiation therapy versus mastectomy.
A total of 35,070 women (25.0%) were treated with lumpectomy alone, 65,301 (46.5%) were treated with lumpectomy and radiotherapy, and 39,995 (28.5%) were treated with mastectomy.
The overall cumulative mortality for the entire cohort from breast cancer at 15 years was 2.03%. The actuarial 15-year mortality rate for the mastectomy group (2.26%) was similar to those who had lumpectomy without radiotherapy (2.33%).
The adjusted HR for death for mastectomy versus lumpectomy alone (based on 20,832 propensity-matched pairs) was 0.91 (95% CI, 0.78-1.05). The adjusted hazard ratios for death were 0.77 (95% CI, 0.67-0.88) for lumpectomy and radiotherapy versus lumpectomy alone (29,465 propensity-matched pairs), 0.91 (95% CI, 0.78-1.05) for mastectomy alone versus lumpectomy alone (20,832 propensity-matched pairs), and 0.75 (95% CI, 0.65-0.87) for lumpectomy and radiotherapy versus mastectomy (29,865 propensity-matched pairs).
When looking at subgroups and the effect of radiotherapy on mortality, the authors found the following: The HR was 0.59 (95% CI, 0.43-0.80) for patients aged younger than 50 years and 0.86 (95% CI, 0.73- 1.01) for those aged 50 years and older; it was 0.67 (95% CI, 0.51-0.87) for patients with ER-positive cancers, 0.50 (95% CI, 0.32-0.78) for ER-negative cancers, and 0.93 (95% CI, 0.77-1.13) for those with unknown ER status.
“How exactly radiotherapy affects survival is an important question that should be explored in future studies,” the authors concluded.
There was no outside funding source reported. Mr. Giannakeas is supported by the Canadian Institutes of Health Research Frederick Banting and Charles Best Doctoral Research Award.
SOURCE: Giannakeas V et al. JAMA Network Open. 2018 Aug 10. doi:10.1001/jamanetworkopen.2018.1100.
Treatment with lumpectomy and radiotherapy was associated with a significant reduction in breast cancer mortality in patients with ductal carcinoma in situ (DCIS), compared with a lumpectomy alone or a mastectomy alone, investigators reported in JAMA Oncology.
Among women who received adjuvant radiation, there was an associated 23% reduced risk of dying of breast cancer. This extrapolated to a cumulative mortality of 2.33% for those treated with lumpectomy alone and 1.74% for women treated with lumpectomy and radiotherapy at 15 years (adjusted hazard ratio, 0.77; 95% confidence interval, 0.67-0.88; P less than .001).
“Although the clinical benefit is small, it is intriguing that radiotherapy has this effect, which appears to be attributable to systemic activity rather than local control,” wrote Vasily Giannakeas, MPH, of the Women’s College Research Institute, Toronto, and colleagues.
Emerging evidence suggests that adding radiotherapy to breast conserving surgery can reduce the risk of breast cancer mortality among women with DCIS and lower the risk of local recurrence. Because of the low rate of mortality associated with DCIS, the authors noted that it has been difficult to investigate deaths related to DCIS. The association of adjuvant radiotherapy with breast cancer survival in this population has also not yet been clearly established.
To determine the extent to which radiotherapy is associated with reduced risk of breast cancer mortality in patients treated for DCIS and identify patient subgroups who might derive the most benefit from radiotherapy, the authors conducted a historical cohort study using the Surveillance, Epidemiology, and End Results database. A total of 140,366 women diagnosed with first primary DCIS between 1998 and 2014 were identified, and three separate comparisons were made using 1:1 matching: lumpectomy with radiation versus lumpectomy alone, lumpectomy alone versus mastectomy, and lumpectomy with radiation therapy versus mastectomy.
A total of 35,070 women (25.0%) were treated with lumpectomy alone, 65,301 (46.5%) were treated with lumpectomy and radiotherapy, and 39,995 (28.5%) were treated with mastectomy.
The overall cumulative mortality for the entire cohort from breast cancer at 15 years was 2.03%. The actuarial 15-year mortality rate for the mastectomy group (2.26%) was similar to those who had lumpectomy without radiotherapy (2.33%).
The adjusted HR for death for mastectomy versus lumpectomy alone (based on 20,832 propensity-matched pairs) was 0.91 (95% CI, 0.78-1.05). The adjusted hazard ratios for death were 0.77 (95% CI, 0.67-0.88) for lumpectomy and radiotherapy versus lumpectomy alone (29,465 propensity-matched pairs), 0.91 (95% CI, 0.78-1.05) for mastectomy alone versus lumpectomy alone (20,832 propensity-matched pairs), and 0.75 (95% CI, 0.65-0.87) for lumpectomy and radiotherapy versus mastectomy (29,865 propensity-matched pairs).
When looking at subgroups and the effect of radiotherapy on mortality, the authors found the following: The HR was 0.59 (95% CI, 0.43-0.80) for patients aged younger than 50 years and 0.86 (95% CI, 0.73- 1.01) for those aged 50 years and older; it was 0.67 (95% CI, 0.51-0.87) for patients with ER-positive cancers, 0.50 (95% CI, 0.32-0.78) for ER-negative cancers, and 0.93 (95% CI, 0.77-1.13) for those with unknown ER status.
“How exactly radiotherapy affects survival is an important question that should be explored in future studies,” the authors concluded.
There was no outside funding source reported. Mr. Giannakeas is supported by the Canadian Institutes of Health Research Frederick Banting and Charles Best Doctoral Research Award.
SOURCE: Giannakeas V et al. JAMA Network Open. 2018 Aug 10. doi:10.1001/jamanetworkopen.2018.1100.
FROM JAMA ONCOLOGY
Key clinical point: Lumpectomy and adjuvant radiotherapy together was superior to lumpectomy or mastectomy alone.
Major finding: The 15-year breast cancer mortality rate was 2.33% for lumpectomy alone, 1.74% for lumpectomy and radiation, and 2.26% for mastectomy.
Study details: A historical cohort study using Surveillance, Epidemiology, and End Results data that included 140,366 women diagnosed with first primary ductal carcinoma in situ.
Disclosures: There was no outside funding source reported. Mr. Giannakeas is supported by the Canadian Institutes of Health Research Frederick Banting and Charles Best Doctoral Research Award. No other disclosures were reported.
Source: Giannakeas V et al. JAMA Network Open. 2018 Aug 10. doi: 10.1001/jamanetworkopen.2018.1100.
Acute Leukemia of Ambiguous Lineage in Elderly Patients: A SEER-Medicare Database Analysis (FULL)
About Research in Context
In this article, the authors of recent scholarship have been asked to discuss the implications of their research on federal health care providers and specifically the veteran and active-duty service member patient populations. Because the article does not include new research and cannot be blinded, it has undergone an abbreviated peer review process. The original article can be found at Guru Murthy GS, Dhakal I, Lee JY, Mehta P. Acute leukemia of ambiguous lineage in elderly patients - analysis of survival using surveillance epidemiology and end results-Medicare database. Clin Lymphoma Myeloma Leuk. 2017;17(2):100-107.
Acute leukemia of ambiguous lineage (ALAL) is a rare disorder in adults, constituting about 3% to 5% of acute leukemia cases. Unlike acute myeloid leukemia (AML) or acute lymphoblastic leukemia (ALL), ALAL cannot be clearly differentiated into a single subtype based on immunophenotyping. The diagnostic criteria for accurately identifying ALAL has evolved over time. There is paucity of information regarding the outcomes and management of this rare leukemia especially in elderly patients, and it is unclear whether treatment improves survival in these patients.
We performed a retrospective analysis of the Surveillance, Epidemiology, and End Results (SEER)-Medicare linked database to describe the outcomes of ALAL in the elderly population in U.S.1 Patients included in the analysis were aged > 65 years, with a pathologically confirmed diagnosis of ALAL, diagnosed between 1992-2010, and on active follow-up. Information on patient demographics, treatment, chemotherapeutic agents used in treatment, and survival was obtained and analyzed using appropriate statistical methods. A total of 705 patients with a median age of 80 years were included. There was a higher proportion of males than females and a higher proportion of white patients compared with African Americans and other races. We found that the overall survival (OS) declined significantly with increasing age, and treatment with chemotherapy improved the survival. However, factors such as gender, race, or type of chemotherapy received (ALL based, AML based, or other regimens) did not significantly influence the survival.
Even in the current era, the optimal therapy for ALAL is not well established. Although options such as AML-based or ALL-based chemotherapy are available, the best chemotherapy regimen and its sequence is unknown as prior studies have demonstrated varying results.2-5 Among elderly patients, numerous factors such as performance status, comorbidities, and ability to tolerate therapy influence the treatment decision. In light of the poor prognosis in elderly patients, a question often arises in the clinician’s mind about whether chemotherapy would provide any benefit for the patient.
Our study results showed that chemotherapy likely improves survival in these patients. However, due to the smaller number of patients, caution is needed in interpreting the result that there was no significant difference between AML-directed or ALL-directed chemotherapy. Another factor highlighted in the study was that only about 21.5% of patients had been treated with chemotherapy. Due to the inherent nature of the database, we could not identify the factors that may have influenced treatment decisions in these patients. Additionally, patients with stem cell transplantation-related claims could not be included in the analysis due to noncontinuous Medicare coverage during the study period. Hence, the role of stem cell transplantation in these patients could not be determined.
Implications Among Veterans
Actual incidence of ALAL among veterans is not known. Whether the incidence of ALAL relates to exposures to chemicals or toxins during military training and service also is unknown. However, ALAL is likely to be at least as prevalent as it is in the nonveteran population and perhaps more so because of exposures and stresses during military training and service.
It is unclear whether veterans attending VA hospitals receive less or different treatment given the higher comorbidities. Finally, it also is not known whether the outcomes for veterans would be different with or without treatment.
Our findings suggest that treatment should be seriously considered in all patients (veterans or not) who are healthy enough to receive chemotherapy regardless of their age. More research is needed to determine the disease incidence and prevalence among veterans and to evaluate whether there are specific etiologic correlations between ALAL and military exposures, whether the natural history is similar to other populations, and to delineate responsiveness to treatment.
Conclusion
This study suggests a poor survival for elderly patients with ALAL in the U.S. Although treatment is associated with an improvement in survival, only 21.5% of patients have received therapy. The optimal choice of chemotherapy for this disease is still not known and warrants prospective studies.
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1. Guru Murthy GS, Dhakal I, Lee JY, Mehta P. Acute leukemia of ambiguous lineage in elderly patients—analysis of survival using surveillance epidemiology and end results—Medicare database. Clin Lymphoma Myeloma Leuk. 2017;17(2):100-107.
2. Rubnitz JE, Onciu M, Pounds S, et al. Acute mixed lineage leukemia in children: the experience of St Jude Children’s Research Hospital. Blood. 2009;113(21):5083-5089.
3. Matutes E, Pickl WF, Van’t Veer M, et al. Mixed phenotype acute leukemia: clinical and laboratory features and out-come in 100 patients defined according to the WHO classification. Blood. 2011;117(11):3163-3171.
4. Wolach O, Stone RM. How I treat mixed-phenotype acute leukemia. Blood. 2015;125(16):2477-2485.
5. Lee JH, Min YH, Chung CW, et al; Korean Society of Hematology AML/MDS Working Party. Prognostic implications of the immunophenotype in biphenotypic acute leukemia. Leuk Lymphoma. 2008;49(4):700-709.
About Research in Context
In this article, the authors of recent scholarship have been asked to discuss the implications of their research on federal health care providers and specifically the veteran and active-duty service member patient populations. Because the article does not include new research and cannot be blinded, it has undergone an abbreviated peer review process. The original article can be found at Guru Murthy GS, Dhakal I, Lee JY, Mehta P. Acute leukemia of ambiguous lineage in elderly patients - analysis of survival using surveillance epidemiology and end results-Medicare database. Clin Lymphoma Myeloma Leuk. 2017;17(2):100-107.
Acute leukemia of ambiguous lineage (ALAL) is a rare disorder in adults, constituting about 3% to 5% of acute leukemia cases. Unlike acute myeloid leukemia (AML) or acute lymphoblastic leukemia (ALL), ALAL cannot be clearly differentiated into a single subtype based on immunophenotyping. The diagnostic criteria for accurately identifying ALAL has evolved over time. There is paucity of information regarding the outcomes and management of this rare leukemia especially in elderly patients, and it is unclear whether treatment improves survival in these patients.
We performed a retrospective analysis of the Surveillance, Epidemiology, and End Results (SEER)-Medicare linked database to describe the outcomes of ALAL in the elderly population in U.S.1 Patients included in the analysis were aged > 65 years, with a pathologically confirmed diagnosis of ALAL, diagnosed between 1992-2010, and on active follow-up. Information on patient demographics, treatment, chemotherapeutic agents used in treatment, and survival was obtained and analyzed using appropriate statistical methods. A total of 705 patients with a median age of 80 years were included. There was a higher proportion of males than females and a higher proportion of white patients compared with African Americans and other races. We found that the overall survival (OS) declined significantly with increasing age, and treatment with chemotherapy improved the survival. However, factors such as gender, race, or type of chemotherapy received (ALL based, AML based, or other regimens) did not significantly influence the survival.
Even in the current era, the optimal therapy for ALAL is not well established. Although options such as AML-based or ALL-based chemotherapy are available, the best chemotherapy regimen and its sequence is unknown as prior studies have demonstrated varying results.2-5 Among elderly patients, numerous factors such as performance status, comorbidities, and ability to tolerate therapy influence the treatment decision. In light of the poor prognosis in elderly patients, a question often arises in the clinician’s mind about whether chemotherapy would provide any benefit for the patient.
Our study results showed that chemotherapy likely improves survival in these patients. However, due to the smaller number of patients, caution is needed in interpreting the result that there was no significant difference between AML-directed or ALL-directed chemotherapy. Another factor highlighted in the study was that only about 21.5% of patients had been treated with chemotherapy. Due to the inherent nature of the database, we could not identify the factors that may have influenced treatment decisions in these patients. Additionally, patients with stem cell transplantation-related claims could not be included in the analysis due to noncontinuous Medicare coverage during the study period. Hence, the role of stem cell transplantation in these patients could not be determined.
Implications Among Veterans
Actual incidence of ALAL among veterans is not known. Whether the incidence of ALAL relates to exposures to chemicals or toxins during military training and service also is unknown. However, ALAL is likely to be at least as prevalent as it is in the nonveteran population and perhaps more so because of exposures and stresses during military training and service.
It is unclear whether veterans attending VA hospitals receive less or different treatment given the higher comorbidities. Finally, it also is not known whether the outcomes for veterans would be different with or without treatment.
Our findings suggest that treatment should be seriously considered in all patients (veterans or not) who are healthy enough to receive chemotherapy regardless of their age. More research is needed to determine the disease incidence and prevalence among veterans and to evaluate whether there are specific etiologic correlations between ALAL and military exposures, whether the natural history is similar to other populations, and to delineate responsiveness to treatment.
Conclusion
This study suggests a poor survival for elderly patients with ALAL in the U.S. Although treatment is associated with an improvement in survival, only 21.5% of patients have received therapy. The optimal choice of chemotherapy for this disease is still not known and warrants prospective studies.
Click here to read the digital edition.
About Research in Context
In this article, the authors of recent scholarship have been asked to discuss the implications of their research on federal health care providers and specifically the veteran and active-duty service member patient populations. Because the article does not include new research and cannot be blinded, it has undergone an abbreviated peer review process. The original article can be found at Guru Murthy GS, Dhakal I, Lee JY, Mehta P. Acute leukemia of ambiguous lineage in elderly patients - analysis of survival using surveillance epidemiology and end results-Medicare database. Clin Lymphoma Myeloma Leuk. 2017;17(2):100-107.
Acute leukemia of ambiguous lineage (ALAL) is a rare disorder in adults, constituting about 3% to 5% of acute leukemia cases. Unlike acute myeloid leukemia (AML) or acute lymphoblastic leukemia (ALL), ALAL cannot be clearly differentiated into a single subtype based on immunophenotyping. The diagnostic criteria for accurately identifying ALAL has evolved over time. There is paucity of information regarding the outcomes and management of this rare leukemia especially in elderly patients, and it is unclear whether treatment improves survival in these patients.
We performed a retrospective analysis of the Surveillance, Epidemiology, and End Results (SEER)-Medicare linked database to describe the outcomes of ALAL in the elderly population in U.S.1 Patients included in the analysis were aged > 65 years, with a pathologically confirmed diagnosis of ALAL, diagnosed between 1992-2010, and on active follow-up. Information on patient demographics, treatment, chemotherapeutic agents used in treatment, and survival was obtained and analyzed using appropriate statistical methods. A total of 705 patients with a median age of 80 years were included. There was a higher proportion of males than females and a higher proportion of white patients compared with African Americans and other races. We found that the overall survival (OS) declined significantly with increasing age, and treatment with chemotherapy improved the survival. However, factors such as gender, race, or type of chemotherapy received (ALL based, AML based, or other regimens) did not significantly influence the survival.
Even in the current era, the optimal therapy for ALAL is not well established. Although options such as AML-based or ALL-based chemotherapy are available, the best chemotherapy regimen and its sequence is unknown as prior studies have demonstrated varying results.2-5 Among elderly patients, numerous factors such as performance status, comorbidities, and ability to tolerate therapy influence the treatment decision. In light of the poor prognosis in elderly patients, a question often arises in the clinician’s mind about whether chemotherapy would provide any benefit for the patient.
Our study results showed that chemotherapy likely improves survival in these patients. However, due to the smaller number of patients, caution is needed in interpreting the result that there was no significant difference between AML-directed or ALL-directed chemotherapy. Another factor highlighted in the study was that only about 21.5% of patients had been treated with chemotherapy. Due to the inherent nature of the database, we could not identify the factors that may have influenced treatment decisions in these patients. Additionally, patients with stem cell transplantation-related claims could not be included in the analysis due to noncontinuous Medicare coverage during the study period. Hence, the role of stem cell transplantation in these patients could not be determined.
Implications Among Veterans
Actual incidence of ALAL among veterans is not known. Whether the incidence of ALAL relates to exposures to chemicals or toxins during military training and service also is unknown. However, ALAL is likely to be at least as prevalent as it is in the nonveteran population and perhaps more so because of exposures and stresses during military training and service.
It is unclear whether veterans attending VA hospitals receive less or different treatment given the higher comorbidities. Finally, it also is not known whether the outcomes for veterans would be different with or without treatment.
Our findings suggest that treatment should be seriously considered in all patients (veterans or not) who are healthy enough to receive chemotherapy regardless of their age. More research is needed to determine the disease incidence and prevalence among veterans and to evaluate whether there are specific etiologic correlations between ALAL and military exposures, whether the natural history is similar to other populations, and to delineate responsiveness to treatment.
Conclusion
This study suggests a poor survival for elderly patients with ALAL in the U.S. Although treatment is associated with an improvement in survival, only 21.5% of patients have received therapy. The optimal choice of chemotherapy for this disease is still not known and warrants prospective studies.
Click here to read the digital edition.
1. Guru Murthy GS, Dhakal I, Lee JY, Mehta P. Acute leukemia of ambiguous lineage in elderly patients—analysis of survival using surveillance epidemiology and end results—Medicare database. Clin Lymphoma Myeloma Leuk. 2017;17(2):100-107.
2. Rubnitz JE, Onciu M, Pounds S, et al. Acute mixed lineage leukemia in children: the experience of St Jude Children’s Research Hospital. Blood. 2009;113(21):5083-5089.
3. Matutes E, Pickl WF, Van’t Veer M, et al. Mixed phenotype acute leukemia: clinical and laboratory features and out-come in 100 patients defined according to the WHO classification. Blood. 2011;117(11):3163-3171.
4. Wolach O, Stone RM. How I treat mixed-phenotype acute leukemia. Blood. 2015;125(16):2477-2485.
5. Lee JH, Min YH, Chung CW, et al; Korean Society of Hematology AML/MDS Working Party. Prognostic implications of the immunophenotype in biphenotypic acute leukemia. Leuk Lymphoma. 2008;49(4):700-709.
1. Guru Murthy GS, Dhakal I, Lee JY, Mehta P. Acute leukemia of ambiguous lineage in elderly patients—analysis of survival using surveillance epidemiology and end results—Medicare database. Clin Lymphoma Myeloma Leuk. 2017;17(2):100-107.
2. Rubnitz JE, Onciu M, Pounds S, et al. Acute mixed lineage leukemia in children: the experience of St Jude Children’s Research Hospital. Blood. 2009;113(21):5083-5089.
3. Matutes E, Pickl WF, Van’t Veer M, et al. Mixed phenotype acute leukemia: clinical and laboratory features and out-come in 100 patients defined according to the WHO classification. Blood. 2011;117(11):3163-3171.
4. Wolach O, Stone RM. How I treat mixed-phenotype acute leukemia. Blood. 2015;125(16):2477-2485.
5. Lee JH, Min YH, Chung CW, et al; Korean Society of Hematology AML/MDS Working Party. Prognostic implications of the immunophenotype in biphenotypic acute leukemia. Leuk Lymphoma. 2008;49(4):700-709.
Abstinence and Heavy Drinking May Increase Dementia Risk
Risk increases in a linear fashion at higher levels of consumption.
People who abstain from alcohol or consume more than 14 units per week during middle age are at increased risk of developing dementia, according to a study published online ahead of print August 1 in BMJ. However, the underlying mechanisms are likely to be different in the two groups.
Continuously increasing life expectancy and, according to World Health Organization estimates, an expected tripling of dementia prevalence by 2050 have increased the importance of understanding the impact of alcohol consumption on aging outcomes. Previous studies have indicated that moderate drinking is associated with a reduced risk of dementia, whereas abstinence and heavy drinking are associated with an increased risk. The evidence is far from conclusive, however, and the reasons underlying these associations remain unclear.
Drinking Patterns Analyzed
A team of researchers from France and the United Kingdom investigated the association between midlife alcohol consumption and risk of dementia into early old age. They also examined whether cardiometabolic disease affects this association. Their findings are based on data from 9,087 British civil servants who were between ages 35 and 55 in 1985 and took part in the ongoing Whitehall II Study, which is looking at the impact of social, behavioral, and biologic factors on long-term health.
Participants’ alcohol consumption and alcohol dependence were assessed at regular intervals between 1985 and 1993 (average age, 50). Alcohol consumption trajectories between 1985 and 2004 were also used to examine the association of long-term alcohol consumption and risk of dementia from midlife to early old age. Admissions for alcohol-related chronic diseases and cases of dementia from 1991 to 2017, and the role of cardiometabolic disease, were identified from hospital records.
Among the 9,087 participants, 397 cases of dementia were recorded over an average follow-up period of 23 years. Average age at dementia diagnosis was 76.
After adjusting for sociodemographic, lifestyle, and health-related factors that could have affected the results, the researchers found that abstinence in midlife or drinking more than 14 units per week was associated with a higher risk of dementia, compared with drinking one to 14 units of alcohol per week. Among those drinking more than 14 units per week of alcohol, every seven-unit-per-week increase in consumption was associated with a 17% increase in dementia risk.
History of hospital admission for alcohol-related chronic diseases was associated with a quadrupled risk of dementia. The researchers showed that some of the excess dementia risk in abstainers resulted from a greater risk of cardiometabolic disease.
Alcohol consumption trajectories showed similar results, with long-term abstainers, those reporting decreased consumption, and long-term consumers of more than 14 units per week at a higher risk of dementia, compared with long-term consumers of one to 14 units per week.
Further analyses to test the strength of the associations produced broadly consistent findings, suggesting that the results are robust. Taken together, these results suggest that abstention and excessive alcohol consumption are associated with an increased risk of dementia, said lead author Séverine Sabia, PhD, a research associate at Inserm, U1018, Centre for Research in Epidemiology and Population Health, Université Paris-Saclay, France and Hôpital Paul Brousse in Villejuif, France, and colleagues.
According to the researchers, no firm conclusions regarding cause and effect can be drawn from this observational study, and the researchers said they cannot rule out the possibility that some of the risk may result from confounding factors. However, the findings “strengthen the evidence that excessive alcohol consumption is a risk factor for dementia” and “encourage use of lower thresholds of alcohol consumption in guidelines to promote cognitive health at older ages,” they said. The findings “should not motivate people who do not drink to start drinking, given the known detrimental effects of alcohol consumption for mortality, neuropsychiatric disorders, cirrhosis of the liver, and cancer,” they added.
Some Questions Answered, Some Questions Remain
This study fills gaps in knowledge, “but we should remain cautious and
Dr. Yasar called for further studies and, ideally, a government-funded randomized clinical trial with close monitoring of adverse outcomes to answer pressing questions about the possible protective effects of light-to-moderate alcohol use on risk of dementia and about the mediating role of cardiovascular disease. “Alcohol consumption of one to 14 units per week may benefit brain health; however, alcohol choices must take into account all associated risks, including liver disease and cancer.”
Suggested Reading
Sabia S, Fayosse A, Dumurgier J, et al. Alcohol consumption and risk of dementia: 23 year follow-up of Whitehall II cohort study. BMJ. 2018;362:k2927.
Yasar S. Relation between alcohol consumption in midlife and dementia in late life. BMJ. 2018;362:k3164.
Risk increases in a linear fashion at higher levels of consumption.
Risk increases in a linear fashion at higher levels of consumption.
People who abstain from alcohol or consume more than 14 units per week during middle age are at increased risk of developing dementia, according to a study published online ahead of print August 1 in BMJ. However, the underlying mechanisms are likely to be different in the two groups.
Continuously increasing life expectancy and, according to World Health Organization estimates, an expected tripling of dementia prevalence by 2050 have increased the importance of understanding the impact of alcohol consumption on aging outcomes. Previous studies have indicated that moderate drinking is associated with a reduced risk of dementia, whereas abstinence and heavy drinking are associated with an increased risk. The evidence is far from conclusive, however, and the reasons underlying these associations remain unclear.
Drinking Patterns Analyzed
A team of researchers from France and the United Kingdom investigated the association between midlife alcohol consumption and risk of dementia into early old age. They also examined whether cardiometabolic disease affects this association. Their findings are based on data from 9,087 British civil servants who were between ages 35 and 55 in 1985 and took part in the ongoing Whitehall II Study, which is looking at the impact of social, behavioral, and biologic factors on long-term health.
Participants’ alcohol consumption and alcohol dependence were assessed at regular intervals between 1985 and 1993 (average age, 50). Alcohol consumption trajectories between 1985 and 2004 were also used to examine the association of long-term alcohol consumption and risk of dementia from midlife to early old age. Admissions for alcohol-related chronic diseases and cases of dementia from 1991 to 2017, and the role of cardiometabolic disease, were identified from hospital records.
Among the 9,087 participants, 397 cases of dementia were recorded over an average follow-up period of 23 years. Average age at dementia diagnosis was 76.
After adjusting for sociodemographic, lifestyle, and health-related factors that could have affected the results, the researchers found that abstinence in midlife or drinking more than 14 units per week was associated with a higher risk of dementia, compared with drinking one to 14 units of alcohol per week. Among those drinking more than 14 units per week of alcohol, every seven-unit-per-week increase in consumption was associated with a 17% increase in dementia risk.
History of hospital admission for alcohol-related chronic diseases was associated with a quadrupled risk of dementia. The researchers showed that some of the excess dementia risk in abstainers resulted from a greater risk of cardiometabolic disease.
Alcohol consumption trajectories showed similar results, with long-term abstainers, those reporting decreased consumption, and long-term consumers of more than 14 units per week at a higher risk of dementia, compared with long-term consumers of one to 14 units per week.
Further analyses to test the strength of the associations produced broadly consistent findings, suggesting that the results are robust. Taken together, these results suggest that abstention and excessive alcohol consumption are associated with an increased risk of dementia, said lead author Séverine Sabia, PhD, a research associate at Inserm, U1018, Centre for Research in Epidemiology and Population Health, Université Paris-Saclay, France and Hôpital Paul Brousse in Villejuif, France, and colleagues.
According to the researchers, no firm conclusions regarding cause and effect can be drawn from this observational study, and the researchers said they cannot rule out the possibility that some of the risk may result from confounding factors. However, the findings “strengthen the evidence that excessive alcohol consumption is a risk factor for dementia” and “encourage use of lower thresholds of alcohol consumption in guidelines to promote cognitive health at older ages,” they said. The findings “should not motivate people who do not drink to start drinking, given the known detrimental effects of alcohol consumption for mortality, neuropsychiatric disorders, cirrhosis of the liver, and cancer,” they added.
Some Questions Answered, Some Questions Remain
This study fills gaps in knowledge, “but we should remain cautious and
Dr. Yasar called for further studies and, ideally, a government-funded randomized clinical trial with close monitoring of adverse outcomes to answer pressing questions about the possible protective effects of light-to-moderate alcohol use on risk of dementia and about the mediating role of cardiovascular disease. “Alcohol consumption of one to 14 units per week may benefit brain health; however, alcohol choices must take into account all associated risks, including liver disease and cancer.”
Suggested Reading
Sabia S, Fayosse A, Dumurgier J, et al. Alcohol consumption and risk of dementia: 23 year follow-up of Whitehall II cohort study. BMJ. 2018;362:k2927.
Yasar S. Relation between alcohol consumption in midlife and dementia in late life. BMJ. 2018;362:k3164.
People who abstain from alcohol or consume more than 14 units per week during middle age are at increased risk of developing dementia, according to a study published online ahead of print August 1 in BMJ. However, the underlying mechanisms are likely to be different in the two groups.
Continuously increasing life expectancy and, according to World Health Organization estimates, an expected tripling of dementia prevalence by 2050 have increased the importance of understanding the impact of alcohol consumption on aging outcomes. Previous studies have indicated that moderate drinking is associated with a reduced risk of dementia, whereas abstinence and heavy drinking are associated with an increased risk. The evidence is far from conclusive, however, and the reasons underlying these associations remain unclear.
Drinking Patterns Analyzed
A team of researchers from France and the United Kingdom investigated the association between midlife alcohol consumption and risk of dementia into early old age. They also examined whether cardiometabolic disease affects this association. Their findings are based on data from 9,087 British civil servants who were between ages 35 and 55 in 1985 and took part in the ongoing Whitehall II Study, which is looking at the impact of social, behavioral, and biologic factors on long-term health.
Participants’ alcohol consumption and alcohol dependence were assessed at regular intervals between 1985 and 1993 (average age, 50). Alcohol consumption trajectories between 1985 and 2004 were also used to examine the association of long-term alcohol consumption and risk of dementia from midlife to early old age. Admissions for alcohol-related chronic diseases and cases of dementia from 1991 to 2017, and the role of cardiometabolic disease, were identified from hospital records.
Among the 9,087 participants, 397 cases of dementia were recorded over an average follow-up period of 23 years. Average age at dementia diagnosis was 76.
After adjusting for sociodemographic, lifestyle, and health-related factors that could have affected the results, the researchers found that abstinence in midlife or drinking more than 14 units per week was associated with a higher risk of dementia, compared with drinking one to 14 units of alcohol per week. Among those drinking more than 14 units per week of alcohol, every seven-unit-per-week increase in consumption was associated with a 17% increase in dementia risk.
History of hospital admission for alcohol-related chronic diseases was associated with a quadrupled risk of dementia. The researchers showed that some of the excess dementia risk in abstainers resulted from a greater risk of cardiometabolic disease.
Alcohol consumption trajectories showed similar results, with long-term abstainers, those reporting decreased consumption, and long-term consumers of more than 14 units per week at a higher risk of dementia, compared with long-term consumers of one to 14 units per week.
Further analyses to test the strength of the associations produced broadly consistent findings, suggesting that the results are robust. Taken together, these results suggest that abstention and excessive alcohol consumption are associated with an increased risk of dementia, said lead author Séverine Sabia, PhD, a research associate at Inserm, U1018, Centre for Research in Epidemiology and Population Health, Université Paris-Saclay, France and Hôpital Paul Brousse in Villejuif, France, and colleagues.
According to the researchers, no firm conclusions regarding cause and effect can be drawn from this observational study, and the researchers said they cannot rule out the possibility that some of the risk may result from confounding factors. However, the findings “strengthen the evidence that excessive alcohol consumption is a risk factor for dementia” and “encourage use of lower thresholds of alcohol consumption in guidelines to promote cognitive health at older ages,” they said. The findings “should not motivate people who do not drink to start drinking, given the known detrimental effects of alcohol consumption for mortality, neuropsychiatric disorders, cirrhosis of the liver, and cancer,” they added.
Some Questions Answered, Some Questions Remain
This study fills gaps in knowledge, “but we should remain cautious and
Dr. Yasar called for further studies and, ideally, a government-funded randomized clinical trial with close monitoring of adverse outcomes to answer pressing questions about the possible protective effects of light-to-moderate alcohol use on risk of dementia and about the mediating role of cardiovascular disease. “Alcohol consumption of one to 14 units per week may benefit brain health; however, alcohol choices must take into account all associated risks, including liver disease and cancer.”
Suggested Reading
Sabia S, Fayosse A, Dumurgier J, et al. Alcohol consumption and risk of dementia: 23 year follow-up of Whitehall II cohort study. BMJ. 2018;362:k2927.
Yasar S. Relation between alcohol consumption in midlife and dementia in late life. BMJ. 2018;362:k3164.
Open Clinical Trials for Patients With Renal Cell Carcinoma (FULL)
Providing access to clinical trials for veteran and active-duty military patients can be a challenge, but a significant number of trials are now recruiting from those populations. Many trials explicitly recruit patients from the VA, the military, and IHS. The VA Office of Research and Development alone sponsors more than 430 research initiatives, and many more are sponsored by Walter Reed National Medical Center and other major defense and VA facilities. The clinical trials listed below are all open as of July 24, 2017; have at least 1 VA, DoD, or IHS location recruiting patients; and are focused on treatment for kidney cancer/renal cell carninoma. For additional information and full inclusion/exclusion criteria, please consult clinicaltrials.gov.
NCI-MATCH: Targeted Therapy Directed by Genetic Testing in Treating Patients With Advanced Refractory Solid Tumors, Lymphomas, or Multiple Myeloma
This phase II trial studies how well treatment that is directed by genetic testing works in patients with solid tumors or lymphomas that have progressed following at least 1 line of standard treatment or for which no agreed upon treatment approach exists. Genetic tests look at the unique genetic material (genes) of patients’ tumor cells. Patients with genetic abnormalities (such as mutations, amplifications, or translocations) may benefit more from treatment that targets their tumor’s particular genetic abnormality. Identifying these genetic abnormalities first may help doctors plan better treatment for patients with solid tumors, lymphomas, or multiple myeloma.
ID: NCT02465060
Sponsor: National Cancer Institute
Locations (contact): Naval Medical Center-San Diego, California (Preston S. Gable); VA Connecticut Healthcare System-West Haven Campus (Herta H. Chao); Durham VAMC, North Carolina (Michael J. Kelley); Walter Reed National Military Medical Center, Bethesda, Maryland (Jeremy G. Perkins)
Bevacizumab, Sorafenib Tosylate, and Temsirolimus in Treating Patients With Metastatic Kidney Cancer
This randomized phase II trial studies different combinations of bevacizumab, temsirolimus, and sorafenib tosylate to see how well they work compared with bevacizumab alone in treating patients with kidney cancer that has spread to other places in the body. Monoclonal antibodies, such as bevacizumab, may interfere with the ability of tumor cells to grow and spread. Bevacizumab and sorafenib tosylate may stop the growth of tumor cells by blocking blood flow to the tumor. Temsirolimus and sorafenib tosylate may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth. Giving different combinations of bevacizumab, sorafenib tosylate, and temsirolimus may be more effective than bevacizumab alone in treating metastatic kidney cancer.
ID: NCT00378703
Sponsor: National Cancer Institute
Locations: VA San Diego Medical Center, California; Jesse Brown VAMC, Chicago, Illinois; Richard L. Roudebush VAMC, Indianapolis, Indiana; VA New Jersey Health Care System East Orange; Dayton VAMC, Ohio; Michael E. DeBakey VAMC, Houston, Texas
Everolimus in Treating Patients With Kidney Cancer Who Have Undergone Surgery (S0931)
Everolimus may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth or by blocking blood flow to the tumor. This phase III trial is studying everolimus to see how well it works in treating patients with kidney cancer who have undergone surgery.
ID: NCT01120249
Sponsor: Southwest Oncology Group
Locations: Central Arkansas Veterans Healthcare System, Little Rock; Denver VAMC, Colorado; Hines VA Hospital, Illinois; Richard L. Roudebush VAMC Indianapolis, Indiana; VAMC Baltimore, Maryland; Minneapolis VeteransMedical Center, Minnesota; VA New Jersey Health Care System, East Orange; VA New York Harbor Healthcare System-Brooklyn Campus; Wright-Patterson, Medical Center, Ohio; Michael E.DeBakey VAMC, Houston, Texas; Audie L. Murphy VA Hospital, San Antonio, Texas
Cabozantinib-s-malate or Sunitinib Malate in Treating Patients With Previously Untreated Locally Advanced or Metastatic Kidney Cancer
This randomized phase II trial studies how well cabozantinib-s-malate works compared to sunitinib malate in treating patients with previously untreated kidney cancer that has spread from where it started to nearby tissue or lymph nodes or to other places in the body. Cabozantinib-s-malate and sunitinib malate may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth. It is not yet known whether cabozantinib-s-malate is more effective than sunitinib malate in treating patients with kidney cancer.
ID: NCT01835158
Sponsor: National Cancer Institute
Locations: VA San Diego Medical Center, California; Minneapolis Veterans Medical Center, Minnesota; VAMC Columbia, Missouri; VA Western New York Health Care System, Buffalo
Everolimus With or Without Bevacizumab in Treating Patients With Advanced Kidney Cancer That Progressed After First-Line Therapy
This randomized phase III trial studies giving everolimus together with bevacizumab to see how well it works compared to everolimus alone in treating patients with advanced kidney cancer that progressed after first-line therapy. Everolimus may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth. Monoclonal antibodies, such as bevacizumab, can interfere with tumor growth by blocking the ability of tumor cells to grow and spread. Everolimus and bevacizumab may also stop the growth of kidney cancer by blocking blood flow to the tumor. It is not yet known whether giving everolimus together with bevacizumab is better than everolimus alone in treating patients with advanced kidney cancer that has progressed after first-line therapy.
Sponsor: National Cancer Institute
ID: NCT01198158
Locations: Jesse Brown VAMC, Chicago, Illinois; Walter Reed National Military Medical Center, Bethesda, Maryland; VA Western New York Health Care System, Buffalo
Tivantinib With or Without Erlotinib Hydrochloride in Treating Patients With Metastatic or Locally Advanced Kidney Cancer That Cannot Be Removed by Surgery
This randomized phase II trial studies how well tivantinib with or without erlotinib hydrochloride works in treating patients with metastatic or locally advanced kidney cancer that cannot be removed by surgery. Tivantinib and erlotinib hydrochloride may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth.
Sponsor: National Cancer Institute (NCI)
ID: NCT01688973
Locations: Hines VA Hospital, Illinois; VA New Jersey Health Care System, East Orange; Audie L. Murphy VA Hospital, San Antonio, Texas
Bioequivalence & Food Effect Study in Patients With Solid Tumor or Hematologic Malignancies
This study will enroll approximately 60 subjects in stage I and 60 subjects in stage II with hematologic or solid tumor malignancies, excluding gastrointestinal tumors and tumors that have originated or metastasized to the liver for which no standard treatment exists or have progressed or recurred following prior therapy. Subjects must not be eligible for therapy of higher curative potential where an alternative treatment has been shown to prolong survival in an analogous population. Approximately 23 sites in the U.S. and 2 in Canada will participate in this study.
Sponsor: Celgene
ID: NCT02223052
Location: VAMC Kansas City, Missouri
Gemcitabine Hydrochloride and Cisplatin With or Without Bevacizumab in Treating Patients With Advanced Urinary Tract Cancer
This randomized phase III trial studies gemcitabine hydrochloride, cisplatin, and bevacizumab to see how well they work compared with gemcitabine hydrochloride and cisplatin in treating patients with urinary tract cancer that has spread to other places in the body. Drugs used in chemotherapy, such as gemcitabine hydrochloride and cisplatin, work in different ways to stop the growth of tumor cells, either by killing the cells, by stopping them from dividing, or by stopping them from spreading. Monoclonal antibodies, such as bevacizumab, may interfere with the ability of tumor cells to grow and spread. It is not yet known whether gemcitabine hydrochloride and cisplatin are more effective when given with or without bevacizumab in treating patients with urinary tract cancer.
Sponsor: National Cancer Institute
ID: NCT00942331
Locations: Central Arkansas Veterans Healthcare System, Little Rock; Denver VAMC, Colorado; Baltimore VAMC, Maryland; Columbia VA, Missouri; VA New Jersey Health Care System, East Orange; VA New York Harbor Healthcare System-Brooklyn Campus; VA Western New York Health Care System, Buffalo; Dayton VAMC, Ohio
Eribulin Mesylate in Treating Patients With Locally Advanced or Metastatic Cancer of the Urothelium and Kidney Dysfunction
This phase I/II trial studies the side effects and best dose of eribulin mesylate and to see how well it works in treating patients with cancer of the urothelium that has spread to nearby tissue or to other places in the body and kidney dysfunction. Drugs used in chemotherapy, such as eribulin mesylate, work in different ways to stop the growth of tumor cells, either by killing the cells, by stopping them from dividing, or by stopping them from spreading. Chemotherapy drugs may have different effects in patients who have changes in their kidney function.
Sponsor: National Cancer Institute
ID: NCT00365157
Location: VA Hospital-Martinez, California
Click here to read the digital edition.
Providing access to clinical trials for veteran and active-duty military patients can be a challenge, but a significant number of trials are now recruiting from those populations. Many trials explicitly recruit patients from the VA, the military, and IHS. The VA Office of Research and Development alone sponsors more than 430 research initiatives, and many more are sponsored by Walter Reed National Medical Center and other major defense and VA facilities. The clinical trials listed below are all open as of July 24, 2017; have at least 1 VA, DoD, or IHS location recruiting patients; and are focused on treatment for kidney cancer/renal cell carninoma. For additional information and full inclusion/exclusion criteria, please consult clinicaltrials.gov.
NCI-MATCH: Targeted Therapy Directed by Genetic Testing in Treating Patients With Advanced Refractory Solid Tumors, Lymphomas, or Multiple Myeloma
This phase II trial studies how well treatment that is directed by genetic testing works in patients with solid tumors or lymphomas that have progressed following at least 1 line of standard treatment or for which no agreed upon treatment approach exists. Genetic tests look at the unique genetic material (genes) of patients’ tumor cells. Patients with genetic abnormalities (such as mutations, amplifications, or translocations) may benefit more from treatment that targets their tumor’s particular genetic abnormality. Identifying these genetic abnormalities first may help doctors plan better treatment for patients with solid tumors, lymphomas, or multiple myeloma.
ID: NCT02465060
Sponsor: National Cancer Institute
Locations (contact): Naval Medical Center-San Diego, California (Preston S. Gable); VA Connecticut Healthcare System-West Haven Campus (Herta H. Chao); Durham VAMC, North Carolina (Michael J. Kelley); Walter Reed National Military Medical Center, Bethesda, Maryland (Jeremy G. Perkins)
Bevacizumab, Sorafenib Tosylate, and Temsirolimus in Treating Patients With Metastatic Kidney Cancer
This randomized phase II trial studies different combinations of bevacizumab, temsirolimus, and sorafenib tosylate to see how well they work compared with bevacizumab alone in treating patients with kidney cancer that has spread to other places in the body. Monoclonal antibodies, such as bevacizumab, may interfere with the ability of tumor cells to grow and spread. Bevacizumab and sorafenib tosylate may stop the growth of tumor cells by blocking blood flow to the tumor. Temsirolimus and sorafenib tosylate may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth. Giving different combinations of bevacizumab, sorafenib tosylate, and temsirolimus may be more effective than bevacizumab alone in treating metastatic kidney cancer.
ID: NCT00378703
Sponsor: National Cancer Institute
Locations: VA San Diego Medical Center, California; Jesse Brown VAMC, Chicago, Illinois; Richard L. Roudebush VAMC, Indianapolis, Indiana; VA New Jersey Health Care System East Orange; Dayton VAMC, Ohio; Michael E. DeBakey VAMC, Houston, Texas
Everolimus in Treating Patients With Kidney Cancer Who Have Undergone Surgery (S0931)
Everolimus may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth or by blocking blood flow to the tumor. This phase III trial is studying everolimus to see how well it works in treating patients with kidney cancer who have undergone surgery.
ID: NCT01120249
Sponsor: Southwest Oncology Group
Locations: Central Arkansas Veterans Healthcare System, Little Rock; Denver VAMC, Colorado; Hines VA Hospital, Illinois; Richard L. Roudebush VAMC Indianapolis, Indiana; VAMC Baltimore, Maryland; Minneapolis VeteransMedical Center, Minnesota; VA New Jersey Health Care System, East Orange; VA New York Harbor Healthcare System-Brooklyn Campus; Wright-Patterson, Medical Center, Ohio; Michael E.DeBakey VAMC, Houston, Texas; Audie L. Murphy VA Hospital, San Antonio, Texas
Cabozantinib-s-malate or Sunitinib Malate in Treating Patients With Previously Untreated Locally Advanced or Metastatic Kidney Cancer
This randomized phase II trial studies how well cabozantinib-s-malate works compared to sunitinib malate in treating patients with previously untreated kidney cancer that has spread from where it started to nearby tissue or lymph nodes or to other places in the body. Cabozantinib-s-malate and sunitinib malate may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth. It is not yet known whether cabozantinib-s-malate is more effective than sunitinib malate in treating patients with kidney cancer.
ID: NCT01835158
Sponsor: National Cancer Institute
Locations: VA San Diego Medical Center, California; Minneapolis Veterans Medical Center, Minnesota; VAMC Columbia, Missouri; VA Western New York Health Care System, Buffalo
Everolimus With or Without Bevacizumab in Treating Patients With Advanced Kidney Cancer That Progressed After First-Line Therapy
This randomized phase III trial studies giving everolimus together with bevacizumab to see how well it works compared to everolimus alone in treating patients with advanced kidney cancer that progressed after first-line therapy. Everolimus may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth. Monoclonal antibodies, such as bevacizumab, can interfere with tumor growth by blocking the ability of tumor cells to grow and spread. Everolimus and bevacizumab may also stop the growth of kidney cancer by blocking blood flow to the tumor. It is not yet known whether giving everolimus together with bevacizumab is better than everolimus alone in treating patients with advanced kidney cancer that has progressed after first-line therapy.
Sponsor: National Cancer Institute
ID: NCT01198158
Locations: Jesse Brown VAMC, Chicago, Illinois; Walter Reed National Military Medical Center, Bethesda, Maryland; VA Western New York Health Care System, Buffalo
Tivantinib With or Without Erlotinib Hydrochloride in Treating Patients With Metastatic or Locally Advanced Kidney Cancer That Cannot Be Removed by Surgery
This randomized phase II trial studies how well tivantinib with or without erlotinib hydrochloride works in treating patients with metastatic or locally advanced kidney cancer that cannot be removed by surgery. Tivantinib and erlotinib hydrochloride may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth.
Sponsor: National Cancer Institute (NCI)
ID: NCT01688973
Locations: Hines VA Hospital, Illinois; VA New Jersey Health Care System, East Orange; Audie L. Murphy VA Hospital, San Antonio, Texas
Bioequivalence & Food Effect Study in Patients With Solid Tumor or Hematologic Malignancies
This study will enroll approximately 60 subjects in stage I and 60 subjects in stage II with hematologic or solid tumor malignancies, excluding gastrointestinal tumors and tumors that have originated or metastasized to the liver for which no standard treatment exists or have progressed or recurred following prior therapy. Subjects must not be eligible for therapy of higher curative potential where an alternative treatment has been shown to prolong survival in an analogous population. Approximately 23 sites in the U.S. and 2 in Canada will participate in this study.
Sponsor: Celgene
ID: NCT02223052
Location: VAMC Kansas City, Missouri
Gemcitabine Hydrochloride and Cisplatin With or Without Bevacizumab in Treating Patients With Advanced Urinary Tract Cancer
This randomized phase III trial studies gemcitabine hydrochloride, cisplatin, and bevacizumab to see how well they work compared with gemcitabine hydrochloride and cisplatin in treating patients with urinary tract cancer that has spread to other places in the body. Drugs used in chemotherapy, such as gemcitabine hydrochloride and cisplatin, work in different ways to stop the growth of tumor cells, either by killing the cells, by stopping them from dividing, or by stopping them from spreading. Monoclonal antibodies, such as bevacizumab, may interfere with the ability of tumor cells to grow and spread. It is not yet known whether gemcitabine hydrochloride and cisplatin are more effective when given with or without bevacizumab in treating patients with urinary tract cancer.
Sponsor: National Cancer Institute
ID: NCT00942331
Locations: Central Arkansas Veterans Healthcare System, Little Rock; Denver VAMC, Colorado; Baltimore VAMC, Maryland; Columbia VA, Missouri; VA New Jersey Health Care System, East Orange; VA New York Harbor Healthcare System-Brooklyn Campus; VA Western New York Health Care System, Buffalo; Dayton VAMC, Ohio
Eribulin Mesylate in Treating Patients With Locally Advanced or Metastatic Cancer of the Urothelium and Kidney Dysfunction
This phase I/II trial studies the side effects and best dose of eribulin mesylate and to see how well it works in treating patients with cancer of the urothelium that has spread to nearby tissue or to other places in the body and kidney dysfunction. Drugs used in chemotherapy, such as eribulin mesylate, work in different ways to stop the growth of tumor cells, either by killing the cells, by stopping them from dividing, or by stopping them from spreading. Chemotherapy drugs may have different effects in patients who have changes in their kidney function.
Sponsor: National Cancer Institute
ID: NCT00365157
Location: VA Hospital-Martinez, California
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Providing access to clinical trials for veteran and active-duty military patients can be a challenge, but a significant number of trials are now recruiting from those populations. Many trials explicitly recruit patients from the VA, the military, and IHS. The VA Office of Research and Development alone sponsors more than 430 research initiatives, and many more are sponsored by Walter Reed National Medical Center and other major defense and VA facilities. The clinical trials listed below are all open as of July 24, 2017; have at least 1 VA, DoD, or IHS location recruiting patients; and are focused on treatment for kidney cancer/renal cell carninoma. For additional information and full inclusion/exclusion criteria, please consult clinicaltrials.gov.
NCI-MATCH: Targeted Therapy Directed by Genetic Testing in Treating Patients With Advanced Refractory Solid Tumors, Lymphomas, or Multiple Myeloma
This phase II trial studies how well treatment that is directed by genetic testing works in patients with solid tumors or lymphomas that have progressed following at least 1 line of standard treatment or for which no agreed upon treatment approach exists. Genetic tests look at the unique genetic material (genes) of patients’ tumor cells. Patients with genetic abnormalities (such as mutations, amplifications, or translocations) may benefit more from treatment that targets their tumor’s particular genetic abnormality. Identifying these genetic abnormalities first may help doctors plan better treatment for patients with solid tumors, lymphomas, or multiple myeloma.
ID: NCT02465060
Sponsor: National Cancer Institute
Locations (contact): Naval Medical Center-San Diego, California (Preston S. Gable); VA Connecticut Healthcare System-West Haven Campus (Herta H. Chao); Durham VAMC, North Carolina (Michael J. Kelley); Walter Reed National Military Medical Center, Bethesda, Maryland (Jeremy G. Perkins)
Bevacizumab, Sorafenib Tosylate, and Temsirolimus in Treating Patients With Metastatic Kidney Cancer
This randomized phase II trial studies different combinations of bevacizumab, temsirolimus, and sorafenib tosylate to see how well they work compared with bevacizumab alone in treating patients with kidney cancer that has spread to other places in the body. Monoclonal antibodies, such as bevacizumab, may interfere with the ability of tumor cells to grow and spread. Bevacizumab and sorafenib tosylate may stop the growth of tumor cells by blocking blood flow to the tumor. Temsirolimus and sorafenib tosylate may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth. Giving different combinations of bevacizumab, sorafenib tosylate, and temsirolimus may be more effective than bevacizumab alone in treating metastatic kidney cancer.
ID: NCT00378703
Sponsor: National Cancer Institute
Locations: VA San Diego Medical Center, California; Jesse Brown VAMC, Chicago, Illinois; Richard L. Roudebush VAMC, Indianapolis, Indiana; VA New Jersey Health Care System East Orange; Dayton VAMC, Ohio; Michael E. DeBakey VAMC, Houston, Texas
Everolimus in Treating Patients With Kidney Cancer Who Have Undergone Surgery (S0931)
Everolimus may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth or by blocking blood flow to the tumor. This phase III trial is studying everolimus to see how well it works in treating patients with kidney cancer who have undergone surgery.
ID: NCT01120249
Sponsor: Southwest Oncology Group
Locations: Central Arkansas Veterans Healthcare System, Little Rock; Denver VAMC, Colorado; Hines VA Hospital, Illinois; Richard L. Roudebush VAMC Indianapolis, Indiana; VAMC Baltimore, Maryland; Minneapolis VeteransMedical Center, Minnesota; VA New Jersey Health Care System, East Orange; VA New York Harbor Healthcare System-Brooklyn Campus; Wright-Patterson, Medical Center, Ohio; Michael E.DeBakey VAMC, Houston, Texas; Audie L. Murphy VA Hospital, San Antonio, Texas
Cabozantinib-s-malate or Sunitinib Malate in Treating Patients With Previously Untreated Locally Advanced or Metastatic Kidney Cancer
This randomized phase II trial studies how well cabozantinib-s-malate works compared to sunitinib malate in treating patients with previously untreated kidney cancer that has spread from where it started to nearby tissue or lymph nodes or to other places in the body. Cabozantinib-s-malate and sunitinib malate may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth. It is not yet known whether cabozantinib-s-malate is more effective than sunitinib malate in treating patients with kidney cancer.
ID: NCT01835158
Sponsor: National Cancer Institute
Locations: VA San Diego Medical Center, California; Minneapolis Veterans Medical Center, Minnesota; VAMC Columbia, Missouri; VA Western New York Health Care System, Buffalo
Everolimus With or Without Bevacizumab in Treating Patients With Advanced Kidney Cancer That Progressed After First-Line Therapy
This randomized phase III trial studies giving everolimus together with bevacizumab to see how well it works compared to everolimus alone in treating patients with advanced kidney cancer that progressed after first-line therapy. Everolimus may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth. Monoclonal antibodies, such as bevacizumab, can interfere with tumor growth by blocking the ability of tumor cells to grow and spread. Everolimus and bevacizumab may also stop the growth of kidney cancer by blocking blood flow to the tumor. It is not yet known whether giving everolimus together with bevacizumab is better than everolimus alone in treating patients with advanced kidney cancer that has progressed after first-line therapy.
Sponsor: National Cancer Institute
ID: NCT01198158
Locations: Jesse Brown VAMC, Chicago, Illinois; Walter Reed National Military Medical Center, Bethesda, Maryland; VA Western New York Health Care System, Buffalo
Tivantinib With or Without Erlotinib Hydrochloride in Treating Patients With Metastatic or Locally Advanced Kidney Cancer That Cannot Be Removed by Surgery
This randomized phase II trial studies how well tivantinib with or without erlotinib hydrochloride works in treating patients with metastatic or locally advanced kidney cancer that cannot be removed by surgery. Tivantinib and erlotinib hydrochloride may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth.
Sponsor: National Cancer Institute (NCI)
ID: NCT01688973
Locations: Hines VA Hospital, Illinois; VA New Jersey Health Care System, East Orange; Audie L. Murphy VA Hospital, San Antonio, Texas
Bioequivalence & Food Effect Study in Patients With Solid Tumor or Hematologic Malignancies
This study will enroll approximately 60 subjects in stage I and 60 subjects in stage II with hematologic or solid tumor malignancies, excluding gastrointestinal tumors and tumors that have originated or metastasized to the liver for which no standard treatment exists or have progressed or recurred following prior therapy. Subjects must not be eligible for therapy of higher curative potential where an alternative treatment has been shown to prolong survival in an analogous population. Approximately 23 sites in the U.S. and 2 in Canada will participate in this study.
Sponsor: Celgene
ID: NCT02223052
Location: VAMC Kansas City, Missouri
Gemcitabine Hydrochloride and Cisplatin With or Without Bevacizumab in Treating Patients With Advanced Urinary Tract Cancer
This randomized phase III trial studies gemcitabine hydrochloride, cisplatin, and bevacizumab to see how well they work compared with gemcitabine hydrochloride and cisplatin in treating patients with urinary tract cancer that has spread to other places in the body. Drugs used in chemotherapy, such as gemcitabine hydrochloride and cisplatin, work in different ways to stop the growth of tumor cells, either by killing the cells, by stopping them from dividing, or by stopping them from spreading. Monoclonal antibodies, such as bevacizumab, may interfere with the ability of tumor cells to grow and spread. It is not yet known whether gemcitabine hydrochloride and cisplatin are more effective when given with or without bevacizumab in treating patients with urinary tract cancer.
Sponsor: National Cancer Institute
ID: NCT00942331
Locations: Central Arkansas Veterans Healthcare System, Little Rock; Denver VAMC, Colorado; Baltimore VAMC, Maryland; Columbia VA, Missouri; VA New Jersey Health Care System, East Orange; VA New York Harbor Healthcare System-Brooklyn Campus; VA Western New York Health Care System, Buffalo; Dayton VAMC, Ohio
Eribulin Mesylate in Treating Patients With Locally Advanced or Metastatic Cancer of the Urothelium and Kidney Dysfunction
This phase I/II trial studies the side effects and best dose of eribulin mesylate and to see how well it works in treating patients with cancer of the urothelium that has spread to nearby tissue or to other places in the body and kidney dysfunction. Drugs used in chemotherapy, such as eribulin mesylate, work in different ways to stop the growth of tumor cells, either by killing the cells, by stopping them from dividing, or by stopping them from spreading. Chemotherapy drugs may have different effects in patients who have changes in their kidney function.
Sponsor: National Cancer Institute
ID: NCT00365157
Location: VA Hospital-Martinez, California
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Depression Screening and Treatment: A Missed Opportunity in Lung Cancer Care (FULL)
About Research in Context
In this article, the authors of recent scholarship have been asked to discuss the implications of their research on federal health care providers and specifically the veteran and active-duty service member patient populations. Because the article does not include new research and cannot be blinded, it has undergone an abbreviated peer review process. The original article can be found at Sullivan DR, Forsberg CW, Ganzini L, et al. Longitudinal changes in depression symptoms and survival among patients with lung cancer: a national cohort assessment. J Clin Oncol. 2016;34(33):3984-3991.
Although depression is common among patients with cancer, patients with lung cancer are at particularly high risk. The prevalence of major depressive disorder (MDD) among patients with cancer can be as high as 13%, whereas up to 44% of patients with lung cancer experience depression symptoms at some point following their cancer diagnosis.1-3 These estimates are consistently higher than those of other types of cancer, possibly related to the stigma of the disease and the associated morbidity and mortality that are its hallmarks.4-8 This potentially life-threatening cancer diagnosis often evokes psychological distress; however, additional stressors contribute to the development of depression, including the effects of chemotherapeutic agents, surgical procedures, radiotherapy, and the consequences of physical symptoms and paraneoplastic syndromes.
In addition to the crippling effects of comorbid depression on patients’ quality of life (QOL), severe and persistent depression among patients with cancer is associated with prolonged hospital stays, worse treatment adherence, physical distress and pain, and increased desire for hastened death.9-11 During treatment, depression can amplify physical symptoms and interfere with effective coping.12,13
Depression also is likely a significant factor for the risk of suicide, which is 4 times higher in patients with lung cancer than that of the general population.14 Most important, as our recent study demonstrated, depression that develops at cancer diagnosis or during cancer treatment may contribute to worse survival. This effect was strongest among patients with early stage disease, in other words, the patients who are most likely to achieve cure.3 This association with early stage disease also has been observed in a strictly veteran population from the northwest U.S.15
Another key finding of our study was the similar survival among patients who experienced a remission of their depression and those who were never depressed. This finding reinforces the importance of effective depression treatment, which has the potential to reduce depression-related mortality; however, depression treatment was not fully captured and could not be directly compared in our study. Unfortunately, comorbid depression often goes undiagnosed and untreated in cancer patients as they report unmet emotional needs and a desire for psychological support during and after completion of cancer treatment.16,17
Given the general lack of depression treatment that occurs in patients with cancer, the negative consequences of depression can be sustained well into survivorship—defined clinically as someone who is free of any sign of cancer for 5 years. Cancer survivors frequently report fatigue, mood disturbance, sleep disruption, pain, and cognitive limitations that significantly impact QOL and are associated with disability and increased health care use.18 These symptoms likely are intertwined with and contribute to the development and persistence of depression. The ramifications of untreated depression on long-term cancer survivor outcomes are not completely understood, as few high-quality studies of depression in cancer survivors exist. However, in a mixed group of patients with cancer, there was a 2-fold risk of mortality in survivors with depression symptoms when these patients were assessed from 1 to 10 years into survivorship.19 The impact of depression on cancer survivorship is an important aspect of cancer care that deserves significantly more attention from both a research and clinical perspective.
Special Considerations for Veterans
There is a higher prevalence of mental health diagnoses in veterans than that in the general population, and depressive disorders are the most common.20-22 According to the VA National Registry for Depression, 11% of veterans aged ≥ 65 years have a diagnosis of MDD, a rate more than twice that in the general population of a similar age.23 However, the actual rate of depression among veterans may be even higher, as studies suggest depression is underdiagnosed in the veteran population.24 In addition to depression, veterans experience other disabling psychological illnesses, such as posttraumatic stress disorder (PTSD) related to deployment and combat duty or combat-related injuries, such as traumatic brain injuries. The negative consequences of PTSD on cancer outcomes are largely unexplored, but PTSD can contribute to increased health care utilization and costs.25,26 A similar psychological construct, cancer-related posttraumatic stress (PTS), which develops as a result of a cancer diagnosis or treatment, is associated with missed medical appointments and procedures, which could impact survival.27
Depression Screening and Treatment
Given the negative consequences of comorbid mental illness, professional oncology societies have started developing guidelines regarding the assessments and care of patients with cancer who are experiencing symptoms of depression and/or anxiety.11,28,29 Among these, the American Society of Clinical Oncology (ASCO) has adapted the Pan-Canadian Practice Guideline on Screening, Assessment, and Care of Psychosocial Distress (Depression, Anxiety) in Adults With Cancer.28 Per ASCO, the target audience for these guidelines is health care providers (eg, medical, surgical, and radiation oncologists; psychiatrists; psychologists; primary care providers; nurses; and others involved in the delivery of care for adults with cancer) as well as patients with cancer and their family members and caregivers.28 These guidelines address the optimum screening, assessment, and psychosocial-supportive care interventions for adults with cancer who are identified as experiencing symptoms of depression. Among the most imperative recommendations are periodic assessments across the trajectory of cancer care, including after cure, as well as employing institutional and community resources for depression treatment.
In clinical practice in a VA setting, implementing these guidelines might involve various interventions. First, it is vital for providers to conduct depression screening during periodic health care encounters. Given the high prevalence of depression in patients with lung cancer, we suggest using the 9-item Patient Health Questionnaire (PHQ-9) as an initial screening tool.30 Unlike the abridged 2-item PHQ-2 commonly used in the VA, the PHQ-9 provides an assessment of the full range of depressive symptoms. An elevated PHQ-9 score (≥ 10) is consistent with a major depressive episode and should trigger next steps.30
Once clinically significant depression is identified, initiation of treatment should occur next. The VA is well suited to assist and support non-mental health clinicians—particularly primary care—in treatment initiation and monitoring. This model of partnership is frequently called collaborative care, or integrated care, and it is well positioned to help patients with lung cancer with concomitant depression. In the VA, this model of care is called primary care-mental healthintegration (PC-MHI). One PC-MHI resource is called TIDES (Translating Initiatives for Depression into Effective Solutions), and when a patient is referred, a mental health nurse care manager helps to track the patients’ antidepressant adherence and treatment response while reporting results to primary care clinicians, who are generally responsible for initiating and continuing the antidepressant prescription. For patients preferring nonpharmacologic approaches or for whom an antidepressant may be contraindicated, PC-MHI can provide other assistance. For example, psychologists working in PC-MHI are equipped to provide a brief course of cognitive behavioral therapy sessions, another first-line, evidence-based treatment for clinical depression.
Clinician follow-up to ensure patient adherence, response, and satisfaction, and to adjust treatment as needed is essential. Besides ongoing coordination with PC-MHI services, including mental health clinicians as part of multidisciplinary cancer clinics could offer substantial added value to patients’ comprehensive cancer care. Indeed, the initiation of multicomponent depression care has been shown to improve QOL and role functioning in patients with cancer.31 Besides the established benefits on QOL, patients with lung cancer who achieve depression symptom remission also may enjoy a significant survival benefit over patients whose depression symptoms remain untreated during lung cancer treatment as our study suggests.3
Conclusion
Depression is a common comorbid disease among patients with lung cancer with important negative implications for QOL and survival. When it occurs after a cancer diagnosis, depression is expected to impact all phases of a patient’s life through treatment and survivorshi —ultimately affecting long-term survival. Veterans may be at particularly high risk given the increased prevalence of mental illness, including depression and PTSD in this group compared with that of the general population. Early detection and prompt treatment can promote depression remission, prevent relapse, and reduce the eventual emotional and financial burden of the disease. This approach may ultimately diminish the prevalence and persistence of depression symptoms and decrease the associated negative effects of this disease on patients with lung cancer.
The importance of integrated systems of depression treatment for patients with cancer as part of comprehensive cancer care cannot be overstated. Development and implementation of these systems should be a priority of lung cancer clinicians and treatment centers. The integrated system within the VA is well positioned to be a leader in this area, and VA clinicians who care for patients with lung cancer are encouraged to take advantage of available mental health resources. Additional research is urgently needed to explore optimal implementation of depression screening and subsequent treatment delivery to improve cancer patient outcomes in VA and non-VA health care settings.
Overall, there is minimal evidence that depression treatment can improve lung cancer survival; however, the lack of high-quality studies is a considerable limitation. Given the significant impact of depression on survival among patients with lung cancer, additional funding and resources are urgently needed to combat this debilitating comorbid disease.
Acknowledgments
This project was supported in part by the National Cancer Institute of the National Institutes of Health under award K07CA190706 to Dr. Sullivan, a Career Development Award from the Veterans Health Administration Health Service Research and Development (CDA 14-428) to Dr. Teo and the HSR&D Center to Improve Veteran Involvement in Care (CIVIC) (CIN 13-404) at the VA Portland Health Care System.
Author disclosures
The authors report no actual or potential conflicts of interest with regard to this article.
Disclaimer
The VA had no role in the design and conduct of the study; collection, management, analysis, and interpretation of the data; preparation, review, or approval of the manuscript; or decision to submit the manuscript for publication. The opinions expressed herein are those of the authors and do not necessarily reflect those of Federal Practitioner, Frontline Medical Communications Inc., the U.S. Government, or any of its agencies.
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1. Derogatis LR, Morrow GR, Fetting J, et al. The prevalence of psychiatric disorders among cancer patients. JAMA. 1983;249(6):751-757.
2. Walker J, Holm Hansen C, Martin P, et al. Prevalence of depression in adults with cancer: a systematic review. Ann Oncol. 2013;24(4):895-900.
3. Sullivan DR, Forsberg CW, Ganzini L, et al. Longitudinal changes in depression symptoms and survival among patients with lung cancer: a national cohort assessment. J Clin Oncol. 2016;34(33):3984-3991.
4. Linden W, Vodermaier A, Mackenzie R, Greig D. Anxiety and depression after cancer diagnosis: prevalence rates by cancer type, gender, and age. J Affect Disord. 2012;141(2-3):343-351.
5. Massie MJ. Prevalence of depression in patients with cancer. J Natl Cancer Inst Monogr. 2004;(32):57-71.
6. Brown Johnson CG, Brodsky JL, Cataldo JK. Lung cancer stigma, anxiety, depression, and quality of life. J Psychosoc Oncol. 2014;32(1):59-73.
7. Cataldo JK, Jahan TM, Pongquan VL. Lung cancer stigma, depression, and quality of life among ever and never smokers. Eur J Oncol Nurs. 2012;16(3):264-269.
8. Howlader N, Noone AM, Krapcho M, et al. SEER cancer statistics review, 1975-2010. https://seer.cancer.gov/archive/csr/1975_2010/. Revised February 21, 2014. Accessed July 12, 2017.
9. Li M, Boquiren V, Lo C, et al. Depression and anxiety in supportive oncology. In: Davis M, Feyer P, Ortner P, Zimmermann C, eds. Supportive Oncology. 1st ed. Philadelphia, PA: Elsevier; 2011:528-540.
10. Brown LF, Kroenke K, Theobald DE, Wu J, Tu W. The association of depression and anxiety with health-related quality of life in cancer patients with depression and/or pain. Psychooncology. 2010;19(7):734-741.
11. Lazenby M, Ercolano E, Grant M, Holland JC, Jacobsen PB, McCorkle R. Supporting Commission on Cancer-mandated psychosocial distress screening with implementation strategies. J Oncol Pract. 2015;11(3):e413-e420.
12. Mystakidou K, Tsilika E, Parpa E, Katsouda E, Galanos A, Vlahos L. Psychological distress of patients with advanced cancer: influence and contribution of pain severity and pain interference. Cancer Nurs. 2006;29(5):400-405.
13. Passik SD, Dugan W, McDonald MV, Rosenfeld B, Theobald DE, Edgerton S. Oncologists’ recognition of depression in their patients with cancer. J Clin Oncol. 1998;16(4):1594-1600.
14. Rahuma M, Kamel M, Nasar A, et al. Lung cancer patients have the highest malignancy-associated suicide rate in USA: a population based analysis. Am J Respir Crit Care Med. 2017;195:A6730.
15. Sullivan DR, Ganzini L, Duckart JP, et al. Treatment receipt and outcomes among lung cancer patients with depression. Clin Oncol (R Coll Radiol). 2014;26(1):25-31.
16. Merckaert I, Libert Y, Messin S, Milani M, Slachmuylder JL, Razavi D. Cancer patients’ desire for psychological support: prevalence and implications for screening patients psychological needs. Psychooncology. 2010;19(2):141-149.
17. Harrison JD, Young JM, Price MA, Butow PN, Solomon MJ. What are the unmet supportive care needs of people with cancer? A systematic review. Support Care Cancer. 2009;17(8):1117-1128.
18. Wu HS, Harden JK. Symptom burden and quality of life in survivorship: a review of the literature. Cancer Nurs. 2015;38(1):E29-E54.
19. Mols F, Husson O, Roukema JA, van de Poll-Franse LV. Depressive symptoms are a risk factor for all-cause mortality: results from a prospective population-based study among 3,080 cancer survivors from the PROFILES registry. J Cancer Surviv. 2013;7(3):484-492.
20. Hoge CW, Castro CA, Messer SC, McGurk D, Cotting DI, Koffman RL. Combat duty in Iraq and Afghanistan, mental health problems, and barriers to care. N Engl J Med. 2004;351(1):13-22.
21. Fortney JC, Curran GM, Hunt JB, et al. Prevalence of probable mental disorders and help-seeking behaviors among veteran and non-veteran community college students. Gen Hosp Psychiatry. 2016;38:99-104.
22. Pickett T, Rothman D, Crawford EF, Brancu M, Fairbank JA, Kudler HS. Mental health among military personnel and veterans. N C Med J. 2015;76(5):299-306.
23. U.S. Department of Veterans Affairs, Veterans Health Administration. One in ten older vets is depressed. https://www.va.gov/health/NewsFeatures/20110624a.asp. Updated April 17, 2015. Accessed July 12, 2017.
24. Fontana A, Rosenheck R. Treatment-seeking veterans of Iraq and Afghanistan: comparison with veterans of previous wars. J Nerv Ment Dis. 2008;196(7):513-521.
25. Kessler RC. Posttraumatic stress disorder: the burden to the individual and to society. J Clin Psychiatry. 2000;61(suppl 5):4-12; discussion, 13-14.
26. Kartha A, Brower V, Saitz R, Samet JH, Keane TM, Liebschutz J. The impact of trauma exposure and post-traumatic stress disorder on healthcare utilization among primary care patients. Med Care. 2008;46(4):388-393.
27. National Cancer Institute. Cancer-related post-traumatic stress (PDQ®)–Patient version. https://www.cancer.gov/about-cancer/coping/survivorship/new-normal/ptsd-pdq. Updated July 7, 2015. Accessed July 12, 2017.
28. Andersen BL, DeRubeis RJ, Berman BS, et al; American Society of Clinical Oncology. Screening, assessment, and care of anxiety and depressive symptoms in adults with cancer: an American Society of Clinical Oncology guideline adaptation. J Clin Oncol. 2014;32(15):1605-1619.
29. Howell D, Keller-Olaman S, Oliver TK, et al. A pan-Canadian practice guideline and algorithm: screening, assessment, and supportive care of adults with cancer-related fatigue. Curr Oncol. 2013;20(3):e233-e246.
30. Kroenke K, Wu J, Bair MJ, Krebs EE, Damush TM, Tu W. Reciprocal relationship between pain and depression: a 12-month longitudinal analysis in primary care. J Pain. 2011;12(9):964-973.
31. Walker J, Hansen CH, Martin P, et al; SMaRT (Symptom Management Research Trials) Oncology-3 Team. Integrated collaborative care for major depression comorbid with a poor prognosis cancer (SMaRT oncology-3): a multicentre randomised controlled trial in patients with lung cancer. Lancet Oncol. 2014;15(10):1168-1176.
About Research in Context
In this article, the authors of recent scholarship have been asked to discuss the implications of their research on federal health care providers and specifically the veteran and active-duty service member patient populations. Because the article does not include new research and cannot be blinded, it has undergone an abbreviated peer review process. The original article can be found at Sullivan DR, Forsberg CW, Ganzini L, et al. Longitudinal changes in depression symptoms and survival among patients with lung cancer: a national cohort assessment. J Clin Oncol. 2016;34(33):3984-3991.
Although depression is common among patients with cancer, patients with lung cancer are at particularly high risk. The prevalence of major depressive disorder (MDD) among patients with cancer can be as high as 13%, whereas up to 44% of patients with lung cancer experience depression symptoms at some point following their cancer diagnosis.1-3 These estimates are consistently higher than those of other types of cancer, possibly related to the stigma of the disease and the associated morbidity and mortality that are its hallmarks.4-8 This potentially life-threatening cancer diagnosis often evokes psychological distress; however, additional stressors contribute to the development of depression, including the effects of chemotherapeutic agents, surgical procedures, radiotherapy, and the consequences of physical symptoms and paraneoplastic syndromes.
In addition to the crippling effects of comorbid depression on patients’ quality of life (QOL), severe and persistent depression among patients with cancer is associated with prolonged hospital stays, worse treatment adherence, physical distress and pain, and increased desire for hastened death.9-11 During treatment, depression can amplify physical symptoms and interfere with effective coping.12,13
Depression also is likely a significant factor for the risk of suicide, which is 4 times higher in patients with lung cancer than that of the general population.14 Most important, as our recent study demonstrated, depression that develops at cancer diagnosis or during cancer treatment may contribute to worse survival. This effect was strongest among patients with early stage disease, in other words, the patients who are most likely to achieve cure.3 This association with early stage disease also has been observed in a strictly veteran population from the northwest U.S.15
Another key finding of our study was the similar survival among patients who experienced a remission of their depression and those who were never depressed. This finding reinforces the importance of effective depression treatment, which has the potential to reduce depression-related mortality; however, depression treatment was not fully captured and could not be directly compared in our study. Unfortunately, comorbid depression often goes undiagnosed and untreated in cancer patients as they report unmet emotional needs and a desire for psychological support during and after completion of cancer treatment.16,17
Given the general lack of depression treatment that occurs in patients with cancer, the negative consequences of depression can be sustained well into survivorship—defined clinically as someone who is free of any sign of cancer for 5 years. Cancer survivors frequently report fatigue, mood disturbance, sleep disruption, pain, and cognitive limitations that significantly impact QOL and are associated with disability and increased health care use.18 These symptoms likely are intertwined with and contribute to the development and persistence of depression. The ramifications of untreated depression on long-term cancer survivor outcomes are not completely understood, as few high-quality studies of depression in cancer survivors exist. However, in a mixed group of patients with cancer, there was a 2-fold risk of mortality in survivors with depression symptoms when these patients were assessed from 1 to 10 years into survivorship.19 The impact of depression on cancer survivorship is an important aspect of cancer care that deserves significantly more attention from both a research and clinical perspective.
Special Considerations for Veterans
There is a higher prevalence of mental health diagnoses in veterans than that in the general population, and depressive disorders are the most common.20-22 According to the VA National Registry for Depression, 11% of veterans aged ≥ 65 years have a diagnosis of MDD, a rate more than twice that in the general population of a similar age.23 However, the actual rate of depression among veterans may be even higher, as studies suggest depression is underdiagnosed in the veteran population.24 In addition to depression, veterans experience other disabling psychological illnesses, such as posttraumatic stress disorder (PTSD) related to deployment and combat duty or combat-related injuries, such as traumatic brain injuries. The negative consequences of PTSD on cancer outcomes are largely unexplored, but PTSD can contribute to increased health care utilization and costs.25,26 A similar psychological construct, cancer-related posttraumatic stress (PTS), which develops as a result of a cancer diagnosis or treatment, is associated with missed medical appointments and procedures, which could impact survival.27
Depression Screening and Treatment
Given the negative consequences of comorbid mental illness, professional oncology societies have started developing guidelines regarding the assessments and care of patients with cancer who are experiencing symptoms of depression and/or anxiety.11,28,29 Among these, the American Society of Clinical Oncology (ASCO) has adapted the Pan-Canadian Practice Guideline on Screening, Assessment, and Care of Psychosocial Distress (Depression, Anxiety) in Adults With Cancer.28 Per ASCO, the target audience for these guidelines is health care providers (eg, medical, surgical, and radiation oncologists; psychiatrists; psychologists; primary care providers; nurses; and others involved in the delivery of care for adults with cancer) as well as patients with cancer and their family members and caregivers.28 These guidelines address the optimum screening, assessment, and psychosocial-supportive care interventions for adults with cancer who are identified as experiencing symptoms of depression. Among the most imperative recommendations are periodic assessments across the trajectory of cancer care, including after cure, as well as employing institutional and community resources for depression treatment.
In clinical practice in a VA setting, implementing these guidelines might involve various interventions. First, it is vital for providers to conduct depression screening during periodic health care encounters. Given the high prevalence of depression in patients with lung cancer, we suggest using the 9-item Patient Health Questionnaire (PHQ-9) as an initial screening tool.30 Unlike the abridged 2-item PHQ-2 commonly used in the VA, the PHQ-9 provides an assessment of the full range of depressive symptoms. An elevated PHQ-9 score (≥ 10) is consistent with a major depressive episode and should trigger next steps.30
Once clinically significant depression is identified, initiation of treatment should occur next. The VA is well suited to assist and support non-mental health clinicians—particularly primary care—in treatment initiation and monitoring. This model of partnership is frequently called collaborative care, or integrated care, and it is well positioned to help patients with lung cancer with concomitant depression. In the VA, this model of care is called primary care-mental healthintegration (PC-MHI). One PC-MHI resource is called TIDES (Translating Initiatives for Depression into Effective Solutions), and when a patient is referred, a mental health nurse care manager helps to track the patients’ antidepressant adherence and treatment response while reporting results to primary care clinicians, who are generally responsible for initiating and continuing the antidepressant prescription. For patients preferring nonpharmacologic approaches or for whom an antidepressant may be contraindicated, PC-MHI can provide other assistance. For example, psychologists working in PC-MHI are equipped to provide a brief course of cognitive behavioral therapy sessions, another first-line, evidence-based treatment for clinical depression.
Clinician follow-up to ensure patient adherence, response, and satisfaction, and to adjust treatment as needed is essential. Besides ongoing coordination with PC-MHI services, including mental health clinicians as part of multidisciplinary cancer clinics could offer substantial added value to patients’ comprehensive cancer care. Indeed, the initiation of multicomponent depression care has been shown to improve QOL and role functioning in patients with cancer.31 Besides the established benefits on QOL, patients with lung cancer who achieve depression symptom remission also may enjoy a significant survival benefit over patients whose depression symptoms remain untreated during lung cancer treatment as our study suggests.3
Conclusion
Depression is a common comorbid disease among patients with lung cancer with important negative implications for QOL and survival. When it occurs after a cancer diagnosis, depression is expected to impact all phases of a patient’s life through treatment and survivorshi —ultimately affecting long-term survival. Veterans may be at particularly high risk given the increased prevalence of mental illness, including depression and PTSD in this group compared with that of the general population. Early detection and prompt treatment can promote depression remission, prevent relapse, and reduce the eventual emotional and financial burden of the disease. This approach may ultimately diminish the prevalence and persistence of depression symptoms and decrease the associated negative effects of this disease on patients with lung cancer.
The importance of integrated systems of depression treatment for patients with cancer as part of comprehensive cancer care cannot be overstated. Development and implementation of these systems should be a priority of lung cancer clinicians and treatment centers. The integrated system within the VA is well positioned to be a leader in this area, and VA clinicians who care for patients with lung cancer are encouraged to take advantage of available mental health resources. Additional research is urgently needed to explore optimal implementation of depression screening and subsequent treatment delivery to improve cancer patient outcomes in VA and non-VA health care settings.
Overall, there is minimal evidence that depression treatment can improve lung cancer survival; however, the lack of high-quality studies is a considerable limitation. Given the significant impact of depression on survival among patients with lung cancer, additional funding and resources are urgently needed to combat this debilitating comorbid disease.
Acknowledgments
This project was supported in part by the National Cancer Institute of the National Institutes of Health under award K07CA190706 to Dr. Sullivan, a Career Development Award from the Veterans Health Administration Health Service Research and Development (CDA 14-428) to Dr. Teo and the HSR&D Center to Improve Veteran Involvement in Care (CIVIC) (CIN 13-404) at the VA Portland Health Care System.
Author disclosures
The authors report no actual or potential conflicts of interest with regard to this article.
Disclaimer
The VA had no role in the design and conduct of the study; collection, management, analysis, and interpretation of the data; preparation, review, or approval of the manuscript; or decision to submit the manuscript for publication. The opinions expressed herein are those of the authors and do not necessarily reflect those of Federal Practitioner, Frontline Medical Communications Inc., the U.S. Government, or any of its agencies.
Click here to read the digital edition.
About Research in Context
In this article, the authors of recent scholarship have been asked to discuss the implications of their research on federal health care providers and specifically the veteran and active-duty service member patient populations. Because the article does not include new research and cannot be blinded, it has undergone an abbreviated peer review process. The original article can be found at Sullivan DR, Forsberg CW, Ganzini L, et al. Longitudinal changes in depression symptoms and survival among patients with lung cancer: a national cohort assessment. J Clin Oncol. 2016;34(33):3984-3991.
Although depression is common among patients with cancer, patients with lung cancer are at particularly high risk. The prevalence of major depressive disorder (MDD) among patients with cancer can be as high as 13%, whereas up to 44% of patients with lung cancer experience depression symptoms at some point following their cancer diagnosis.1-3 These estimates are consistently higher than those of other types of cancer, possibly related to the stigma of the disease and the associated morbidity and mortality that are its hallmarks.4-8 This potentially life-threatening cancer diagnosis often evokes psychological distress; however, additional stressors contribute to the development of depression, including the effects of chemotherapeutic agents, surgical procedures, radiotherapy, and the consequences of physical symptoms and paraneoplastic syndromes.
In addition to the crippling effects of comorbid depression on patients’ quality of life (QOL), severe and persistent depression among patients with cancer is associated with prolonged hospital stays, worse treatment adherence, physical distress and pain, and increased desire for hastened death.9-11 During treatment, depression can amplify physical symptoms and interfere with effective coping.12,13
Depression also is likely a significant factor for the risk of suicide, which is 4 times higher in patients with lung cancer than that of the general population.14 Most important, as our recent study demonstrated, depression that develops at cancer diagnosis or during cancer treatment may contribute to worse survival. This effect was strongest among patients with early stage disease, in other words, the patients who are most likely to achieve cure.3 This association with early stage disease also has been observed in a strictly veteran population from the northwest U.S.15
Another key finding of our study was the similar survival among patients who experienced a remission of their depression and those who were never depressed. This finding reinforces the importance of effective depression treatment, which has the potential to reduce depression-related mortality; however, depression treatment was not fully captured and could not be directly compared in our study. Unfortunately, comorbid depression often goes undiagnosed and untreated in cancer patients as they report unmet emotional needs and a desire for psychological support during and after completion of cancer treatment.16,17
Given the general lack of depression treatment that occurs in patients with cancer, the negative consequences of depression can be sustained well into survivorship—defined clinically as someone who is free of any sign of cancer for 5 years. Cancer survivors frequently report fatigue, mood disturbance, sleep disruption, pain, and cognitive limitations that significantly impact QOL and are associated with disability and increased health care use.18 These symptoms likely are intertwined with and contribute to the development and persistence of depression. The ramifications of untreated depression on long-term cancer survivor outcomes are not completely understood, as few high-quality studies of depression in cancer survivors exist. However, in a mixed group of patients with cancer, there was a 2-fold risk of mortality in survivors with depression symptoms when these patients were assessed from 1 to 10 years into survivorship.19 The impact of depression on cancer survivorship is an important aspect of cancer care that deserves significantly more attention from both a research and clinical perspective.
Special Considerations for Veterans
There is a higher prevalence of mental health diagnoses in veterans than that in the general population, and depressive disorders are the most common.20-22 According to the VA National Registry for Depression, 11% of veterans aged ≥ 65 years have a diagnosis of MDD, a rate more than twice that in the general population of a similar age.23 However, the actual rate of depression among veterans may be even higher, as studies suggest depression is underdiagnosed in the veteran population.24 In addition to depression, veterans experience other disabling psychological illnesses, such as posttraumatic stress disorder (PTSD) related to deployment and combat duty or combat-related injuries, such as traumatic brain injuries. The negative consequences of PTSD on cancer outcomes are largely unexplored, but PTSD can contribute to increased health care utilization and costs.25,26 A similar psychological construct, cancer-related posttraumatic stress (PTS), which develops as a result of a cancer diagnosis or treatment, is associated with missed medical appointments and procedures, which could impact survival.27
Depression Screening and Treatment
Given the negative consequences of comorbid mental illness, professional oncology societies have started developing guidelines regarding the assessments and care of patients with cancer who are experiencing symptoms of depression and/or anxiety.11,28,29 Among these, the American Society of Clinical Oncology (ASCO) has adapted the Pan-Canadian Practice Guideline on Screening, Assessment, and Care of Psychosocial Distress (Depression, Anxiety) in Adults With Cancer.28 Per ASCO, the target audience for these guidelines is health care providers (eg, medical, surgical, and radiation oncologists; psychiatrists; psychologists; primary care providers; nurses; and others involved in the delivery of care for adults with cancer) as well as patients with cancer and their family members and caregivers.28 These guidelines address the optimum screening, assessment, and psychosocial-supportive care interventions for adults with cancer who are identified as experiencing symptoms of depression. Among the most imperative recommendations are periodic assessments across the trajectory of cancer care, including after cure, as well as employing institutional and community resources for depression treatment.
In clinical practice in a VA setting, implementing these guidelines might involve various interventions. First, it is vital for providers to conduct depression screening during periodic health care encounters. Given the high prevalence of depression in patients with lung cancer, we suggest using the 9-item Patient Health Questionnaire (PHQ-9) as an initial screening tool.30 Unlike the abridged 2-item PHQ-2 commonly used in the VA, the PHQ-9 provides an assessment of the full range of depressive symptoms. An elevated PHQ-9 score (≥ 10) is consistent with a major depressive episode and should trigger next steps.30
Once clinically significant depression is identified, initiation of treatment should occur next. The VA is well suited to assist and support non-mental health clinicians—particularly primary care—in treatment initiation and monitoring. This model of partnership is frequently called collaborative care, or integrated care, and it is well positioned to help patients with lung cancer with concomitant depression. In the VA, this model of care is called primary care-mental healthintegration (PC-MHI). One PC-MHI resource is called TIDES (Translating Initiatives for Depression into Effective Solutions), and when a patient is referred, a mental health nurse care manager helps to track the patients’ antidepressant adherence and treatment response while reporting results to primary care clinicians, who are generally responsible for initiating and continuing the antidepressant prescription. For patients preferring nonpharmacologic approaches or for whom an antidepressant may be contraindicated, PC-MHI can provide other assistance. For example, psychologists working in PC-MHI are equipped to provide a brief course of cognitive behavioral therapy sessions, another first-line, evidence-based treatment for clinical depression.
Clinician follow-up to ensure patient adherence, response, and satisfaction, and to adjust treatment as needed is essential. Besides ongoing coordination with PC-MHI services, including mental health clinicians as part of multidisciplinary cancer clinics could offer substantial added value to patients’ comprehensive cancer care. Indeed, the initiation of multicomponent depression care has been shown to improve QOL and role functioning in patients with cancer.31 Besides the established benefits on QOL, patients with lung cancer who achieve depression symptom remission also may enjoy a significant survival benefit over patients whose depression symptoms remain untreated during lung cancer treatment as our study suggests.3
Conclusion
Depression is a common comorbid disease among patients with lung cancer with important negative implications for QOL and survival. When it occurs after a cancer diagnosis, depression is expected to impact all phases of a patient’s life through treatment and survivorshi —ultimately affecting long-term survival. Veterans may be at particularly high risk given the increased prevalence of mental illness, including depression and PTSD in this group compared with that of the general population. Early detection and prompt treatment can promote depression remission, prevent relapse, and reduce the eventual emotional and financial burden of the disease. This approach may ultimately diminish the prevalence and persistence of depression symptoms and decrease the associated negative effects of this disease on patients with lung cancer.
The importance of integrated systems of depression treatment for patients with cancer as part of comprehensive cancer care cannot be overstated. Development and implementation of these systems should be a priority of lung cancer clinicians and treatment centers. The integrated system within the VA is well positioned to be a leader in this area, and VA clinicians who care for patients with lung cancer are encouraged to take advantage of available mental health resources. Additional research is urgently needed to explore optimal implementation of depression screening and subsequent treatment delivery to improve cancer patient outcomes in VA and non-VA health care settings.
Overall, there is minimal evidence that depression treatment can improve lung cancer survival; however, the lack of high-quality studies is a considerable limitation. Given the significant impact of depression on survival among patients with lung cancer, additional funding and resources are urgently needed to combat this debilitating comorbid disease.
Acknowledgments
This project was supported in part by the National Cancer Institute of the National Institutes of Health under award K07CA190706 to Dr. Sullivan, a Career Development Award from the Veterans Health Administration Health Service Research and Development (CDA 14-428) to Dr. Teo and the HSR&D Center to Improve Veteran Involvement in Care (CIVIC) (CIN 13-404) at the VA Portland Health Care System.
Author disclosures
The authors report no actual or potential conflicts of interest with regard to this article.
Disclaimer
The VA had no role in the design and conduct of the study; collection, management, analysis, and interpretation of the data; preparation, review, or approval of the manuscript; or decision to submit the manuscript for publication. The opinions expressed herein are those of the authors and do not necessarily reflect those of Federal Practitioner, Frontline Medical Communications Inc., the U.S. Government, or any of its agencies.
Click here to read the digital edition.
1. Derogatis LR, Morrow GR, Fetting J, et al. The prevalence of psychiatric disorders among cancer patients. JAMA. 1983;249(6):751-757.
2. Walker J, Holm Hansen C, Martin P, et al. Prevalence of depression in adults with cancer: a systematic review. Ann Oncol. 2013;24(4):895-900.
3. Sullivan DR, Forsberg CW, Ganzini L, et al. Longitudinal changes in depression symptoms and survival among patients with lung cancer: a national cohort assessment. J Clin Oncol. 2016;34(33):3984-3991.
4. Linden W, Vodermaier A, Mackenzie R, Greig D. Anxiety and depression after cancer diagnosis: prevalence rates by cancer type, gender, and age. J Affect Disord. 2012;141(2-3):343-351.
5. Massie MJ. Prevalence of depression in patients with cancer. J Natl Cancer Inst Monogr. 2004;(32):57-71.
6. Brown Johnson CG, Brodsky JL, Cataldo JK. Lung cancer stigma, anxiety, depression, and quality of life. J Psychosoc Oncol. 2014;32(1):59-73.
7. Cataldo JK, Jahan TM, Pongquan VL. Lung cancer stigma, depression, and quality of life among ever and never smokers. Eur J Oncol Nurs. 2012;16(3):264-269.
8. Howlader N, Noone AM, Krapcho M, et al. SEER cancer statistics review, 1975-2010. https://seer.cancer.gov/archive/csr/1975_2010/. Revised February 21, 2014. Accessed July 12, 2017.
9. Li M, Boquiren V, Lo C, et al. Depression and anxiety in supportive oncology. In: Davis M, Feyer P, Ortner P, Zimmermann C, eds. Supportive Oncology. 1st ed. Philadelphia, PA: Elsevier; 2011:528-540.
10. Brown LF, Kroenke K, Theobald DE, Wu J, Tu W. The association of depression and anxiety with health-related quality of life in cancer patients with depression and/or pain. Psychooncology. 2010;19(7):734-741.
11. Lazenby M, Ercolano E, Grant M, Holland JC, Jacobsen PB, McCorkle R. Supporting Commission on Cancer-mandated psychosocial distress screening with implementation strategies. J Oncol Pract. 2015;11(3):e413-e420.
12. Mystakidou K, Tsilika E, Parpa E, Katsouda E, Galanos A, Vlahos L. Psychological distress of patients with advanced cancer: influence and contribution of pain severity and pain interference. Cancer Nurs. 2006;29(5):400-405.
13. Passik SD, Dugan W, McDonald MV, Rosenfeld B, Theobald DE, Edgerton S. Oncologists’ recognition of depression in their patients with cancer. J Clin Oncol. 1998;16(4):1594-1600.
14. Rahuma M, Kamel M, Nasar A, et al. Lung cancer patients have the highest malignancy-associated suicide rate in USA: a population based analysis. Am J Respir Crit Care Med. 2017;195:A6730.
15. Sullivan DR, Ganzini L, Duckart JP, et al. Treatment receipt and outcomes among lung cancer patients with depression. Clin Oncol (R Coll Radiol). 2014;26(1):25-31.
16. Merckaert I, Libert Y, Messin S, Milani M, Slachmuylder JL, Razavi D. Cancer patients’ desire for psychological support: prevalence and implications for screening patients psychological needs. Psychooncology. 2010;19(2):141-149.
17. Harrison JD, Young JM, Price MA, Butow PN, Solomon MJ. What are the unmet supportive care needs of people with cancer? A systematic review. Support Care Cancer. 2009;17(8):1117-1128.
18. Wu HS, Harden JK. Symptom burden and quality of life in survivorship: a review of the literature. Cancer Nurs. 2015;38(1):E29-E54.
19. Mols F, Husson O, Roukema JA, van de Poll-Franse LV. Depressive symptoms are a risk factor for all-cause mortality: results from a prospective population-based study among 3,080 cancer survivors from the PROFILES registry. J Cancer Surviv. 2013;7(3):484-492.
20. Hoge CW, Castro CA, Messer SC, McGurk D, Cotting DI, Koffman RL. Combat duty in Iraq and Afghanistan, mental health problems, and barriers to care. N Engl J Med. 2004;351(1):13-22.
21. Fortney JC, Curran GM, Hunt JB, et al. Prevalence of probable mental disorders and help-seeking behaviors among veteran and non-veteran community college students. Gen Hosp Psychiatry. 2016;38:99-104.
22. Pickett T, Rothman D, Crawford EF, Brancu M, Fairbank JA, Kudler HS. Mental health among military personnel and veterans. N C Med J. 2015;76(5):299-306.
23. U.S. Department of Veterans Affairs, Veterans Health Administration. One in ten older vets is depressed. https://www.va.gov/health/NewsFeatures/20110624a.asp. Updated April 17, 2015. Accessed July 12, 2017.
24. Fontana A, Rosenheck R. Treatment-seeking veterans of Iraq and Afghanistan: comparison with veterans of previous wars. J Nerv Ment Dis. 2008;196(7):513-521.
25. Kessler RC. Posttraumatic stress disorder: the burden to the individual and to society. J Clin Psychiatry. 2000;61(suppl 5):4-12; discussion, 13-14.
26. Kartha A, Brower V, Saitz R, Samet JH, Keane TM, Liebschutz J. The impact of trauma exposure and post-traumatic stress disorder on healthcare utilization among primary care patients. Med Care. 2008;46(4):388-393.
27. National Cancer Institute. Cancer-related post-traumatic stress (PDQ®)–Patient version. https://www.cancer.gov/about-cancer/coping/survivorship/new-normal/ptsd-pdq. Updated July 7, 2015. Accessed July 12, 2017.
28. Andersen BL, DeRubeis RJ, Berman BS, et al; American Society of Clinical Oncology. Screening, assessment, and care of anxiety and depressive symptoms in adults with cancer: an American Society of Clinical Oncology guideline adaptation. J Clin Oncol. 2014;32(15):1605-1619.
29. Howell D, Keller-Olaman S, Oliver TK, et al. A pan-Canadian practice guideline and algorithm: screening, assessment, and supportive care of adults with cancer-related fatigue. Curr Oncol. 2013;20(3):e233-e246.
30. Kroenke K, Wu J, Bair MJ, Krebs EE, Damush TM, Tu W. Reciprocal relationship between pain and depression: a 12-month longitudinal analysis in primary care. J Pain. 2011;12(9):964-973.
31. Walker J, Hansen CH, Martin P, et al; SMaRT (Symptom Management Research Trials) Oncology-3 Team. Integrated collaborative care for major depression comorbid with a poor prognosis cancer (SMaRT oncology-3): a multicentre randomised controlled trial in patients with lung cancer. Lancet Oncol. 2014;15(10):1168-1176.
1. Derogatis LR, Morrow GR, Fetting J, et al. The prevalence of psychiatric disorders among cancer patients. JAMA. 1983;249(6):751-757.
2. Walker J, Holm Hansen C, Martin P, et al. Prevalence of depression in adults with cancer: a systematic review. Ann Oncol. 2013;24(4):895-900.
3. Sullivan DR, Forsberg CW, Ganzini L, et al. Longitudinal changes in depression symptoms and survival among patients with lung cancer: a national cohort assessment. J Clin Oncol. 2016;34(33):3984-3991.
4. Linden W, Vodermaier A, Mackenzie R, Greig D. Anxiety and depression after cancer diagnosis: prevalence rates by cancer type, gender, and age. J Affect Disord. 2012;141(2-3):343-351.
5. Massie MJ. Prevalence of depression in patients with cancer. J Natl Cancer Inst Monogr. 2004;(32):57-71.
6. Brown Johnson CG, Brodsky JL, Cataldo JK. Lung cancer stigma, anxiety, depression, and quality of life. J Psychosoc Oncol. 2014;32(1):59-73.
7. Cataldo JK, Jahan TM, Pongquan VL. Lung cancer stigma, depression, and quality of life among ever and never smokers. Eur J Oncol Nurs. 2012;16(3):264-269.
8. Howlader N, Noone AM, Krapcho M, et al. SEER cancer statistics review, 1975-2010. https://seer.cancer.gov/archive/csr/1975_2010/. Revised February 21, 2014. Accessed July 12, 2017.
9. Li M, Boquiren V, Lo C, et al. Depression and anxiety in supportive oncology. In: Davis M, Feyer P, Ortner P, Zimmermann C, eds. Supportive Oncology. 1st ed. Philadelphia, PA: Elsevier; 2011:528-540.
10. Brown LF, Kroenke K, Theobald DE, Wu J, Tu W. The association of depression and anxiety with health-related quality of life in cancer patients with depression and/or pain. Psychooncology. 2010;19(7):734-741.
11. Lazenby M, Ercolano E, Grant M, Holland JC, Jacobsen PB, McCorkle R. Supporting Commission on Cancer-mandated psychosocial distress screening with implementation strategies. J Oncol Pract. 2015;11(3):e413-e420.
12. Mystakidou K, Tsilika E, Parpa E, Katsouda E, Galanos A, Vlahos L. Psychological distress of patients with advanced cancer: influence and contribution of pain severity and pain interference. Cancer Nurs. 2006;29(5):400-405.
13. Passik SD, Dugan W, McDonald MV, Rosenfeld B, Theobald DE, Edgerton S. Oncologists’ recognition of depression in their patients with cancer. J Clin Oncol. 1998;16(4):1594-1600.
14. Rahuma M, Kamel M, Nasar A, et al. Lung cancer patients have the highest malignancy-associated suicide rate in USA: a population based analysis. Am J Respir Crit Care Med. 2017;195:A6730.
15. Sullivan DR, Ganzini L, Duckart JP, et al. Treatment receipt and outcomes among lung cancer patients with depression. Clin Oncol (R Coll Radiol). 2014;26(1):25-31.
16. Merckaert I, Libert Y, Messin S, Milani M, Slachmuylder JL, Razavi D. Cancer patients’ desire for psychological support: prevalence and implications for screening patients psychological needs. Psychooncology. 2010;19(2):141-149.
17. Harrison JD, Young JM, Price MA, Butow PN, Solomon MJ. What are the unmet supportive care needs of people with cancer? A systematic review. Support Care Cancer. 2009;17(8):1117-1128.
18. Wu HS, Harden JK. Symptom burden and quality of life in survivorship: a review of the literature. Cancer Nurs. 2015;38(1):E29-E54.
19. Mols F, Husson O, Roukema JA, van de Poll-Franse LV. Depressive symptoms are a risk factor for all-cause mortality: results from a prospective population-based study among 3,080 cancer survivors from the PROFILES registry. J Cancer Surviv. 2013;7(3):484-492.
20. Hoge CW, Castro CA, Messer SC, McGurk D, Cotting DI, Koffman RL. Combat duty in Iraq and Afghanistan, mental health problems, and barriers to care. N Engl J Med. 2004;351(1):13-22.
21. Fortney JC, Curran GM, Hunt JB, et al. Prevalence of probable mental disorders and help-seeking behaviors among veteran and non-veteran community college students. Gen Hosp Psychiatry. 2016;38:99-104.
22. Pickett T, Rothman D, Crawford EF, Brancu M, Fairbank JA, Kudler HS. Mental health among military personnel and veterans. N C Med J. 2015;76(5):299-306.
23. U.S. Department of Veterans Affairs, Veterans Health Administration. One in ten older vets is depressed. https://www.va.gov/health/NewsFeatures/20110624a.asp. Updated April 17, 2015. Accessed July 12, 2017.
24. Fontana A, Rosenheck R. Treatment-seeking veterans of Iraq and Afghanistan: comparison with veterans of previous wars. J Nerv Ment Dis. 2008;196(7):513-521.
25. Kessler RC. Posttraumatic stress disorder: the burden to the individual and to society. J Clin Psychiatry. 2000;61(suppl 5):4-12; discussion, 13-14.
26. Kartha A, Brower V, Saitz R, Samet JH, Keane TM, Liebschutz J. The impact of trauma exposure and post-traumatic stress disorder on healthcare utilization among primary care patients. Med Care. 2008;46(4):388-393.
27. National Cancer Institute. Cancer-related post-traumatic stress (PDQ®)–Patient version. https://www.cancer.gov/about-cancer/coping/survivorship/new-normal/ptsd-pdq. Updated July 7, 2015. Accessed July 12, 2017.
28. Andersen BL, DeRubeis RJ, Berman BS, et al; American Society of Clinical Oncology. Screening, assessment, and care of anxiety and depressive symptoms in adults with cancer: an American Society of Clinical Oncology guideline adaptation. J Clin Oncol. 2014;32(15):1605-1619.
29. Howell D, Keller-Olaman S, Oliver TK, et al. A pan-Canadian practice guideline and algorithm: screening, assessment, and supportive care of adults with cancer-related fatigue. Curr Oncol. 2013;20(3):e233-e246.
30. Kroenke K, Wu J, Bair MJ, Krebs EE, Damush TM, Tu W. Reciprocal relationship between pain and depression: a 12-month longitudinal analysis in primary care. J Pain. 2011;12(9):964-973.
31. Walker J, Hansen CH, Martin P, et al; SMaRT (Symptom Management Research Trials) Oncology-3 Team. Integrated collaborative care for major depression comorbid with a poor prognosis cancer (SMaRT oncology-3): a multicentre randomised controlled trial in patients with lung cancer. Lancet Oncol. 2014;15(10):1168-1176.
Herceptin linked to doubling of HF risk in women with breast cancer
Adding more evidence to an ongoing debate, a large new study suggests that patients with breast cancer who take trastuzumab (Herceptin) may face double the adjusted risk of developing heart failure, with older women at highest risk.
The study also found that most patients who took trastuzumab didn’t receive recommended cardiac screening.
The researchers said their findings are unique because they tracked both younger and older patients. “By examining the rates of both cardiac monitoring and cardiotoxicity, we could begin to address the controversial issue of whether cardiac monitoring is warranted in young breast cancer patients,” wrote Mariana Chavez-MacGregor, MD, MSC, of the University of Texas MD Anderson Cancer Center, and her associates. The report was published in JACC: Cardiovascular Imaging.
While Trastuzumab has boosted breast cancer survival rates for patients with HER2-positive tumors, it’s also raised concerns about cardiotoxicity that could be an indicator of subsequent congestive heart failure (Cochrane Database Syst Rev. 2014 Jun 12;(6):CD006242).
According to the new study, the risk of trastuzumab risk is linked to damage to cardiac myocytes that can cause reversible cardiotoxicity.
The prescribing information for trastuzumab advises patients to undergo cardiac monitoring before treatment with trastuzumab and every 3 months during treatment. Recommendations by medical organizations have varied.
Now, as a 2016 report put it, it’s “increasingly unclear” whether frequent routine monitoring is appropriate for all patients (J Clin Oncol. 2016 Apr 1;34[10]:1030-3).
For the current study, Dr. Chavez-MacGregor and her associates identified 16,456 adult women in the United States who were diagnosed with nonmetastatic invasive breast cancer from 2009 to 2014. Researchers tracked the group, with a median age of 56, through as late as 2015.
The women were treated with chemotherapy within 6 months of diagnosis, and 4,325 received trastuzumab.
Of all the subjects, 692 patients (4.2%) developed heart failure following chemotherapy. The rate among patients treated with trastuzumab was higher, at 8.3%, compared with 2.7% for those not treated with trastuzumab (P less than .001).
The researchers also looked at anthracycline users and found that they were slightly more likely to develop HF (4.6% vs. 4.0% among nonusers, P = .048).
Increased age boosted the risk of HF in the trastuzumab-treated patients, and the risk was highest in those treated with both anthracyclines and trastuzumab. Other factors linked to more risk were comorbidities, hypertension, and valve disease.
After adjusting for confounders, the researchers estimated that those treated with trastuzumab were 2.01 times more likely to develop HF (HR, 2.01; 95% confidence interval, 1.72-2.36), and those who took anthracycline were 1.53 times more likely (HR, 1.53; 95% CI, 1.30-1.80)
The researchers also examined medical records for evidence that subjects underwent cardiac screening at least once every 4 months, not 3 months, as the prescribing information recommends. The study team chose to focus on 4-month intervals “to compensate for differences in scheduling, resources, or levels of accessibility to medical care.”
Medical records suggest that 73.5% of patients who took trastuzumab underwent cardiac screening at the beginning of therapy, but only 46.2% continued to do so at least every 4 months.
An adjusted model linked more screening to the use of anthracyclines and taxanes, radiation treatment, and living in the Northeast vs. the West.
“HF was more frequently identified among patients undergoing recommended cardiac monitoring (10.4% compared with 6.5%, respectively; P less than.001), suggesting that, as more patients are screened, more patients are likely to be found having HF,” the researchers reported.
However, they added that “our sensitivity analysis using inpatient claims allowed us to determine that the HF identified using cardiac monitoring was not severe enough to require hospitalization and was likely asymptomatic. The clinical implications of the diagnosis of asymptomatic HF are hard to determine and are beyond the scope of this study.”
The researchers also noted that the findings suggest that screening has become more common in recent years.
“The number of cancer survivors is expected to increase over time, and we will continue to see patients develop treatment-related cardiotoxicity,” the researchers wrote. “Thus, more research, evidence-based guidelines, and tools for prediction of cancer treatment–related cardiotoxicity are needed.”
The National Cancer Institute and Cancer Prevention and Research Institute of Texas funded the study. Two study authors reported grant funding from the Susan G. Komen Breast Cancer Foundation, and one reports consulting for Pfizer and Roche. The other authors reported no disclosures.
SOURCE: Chavez-MacGregor M et al. JACC: Cardiovasc Imaging. 2018 Aug;11[8]1084-93.
While trastuzumab clearly benefits patients with HER2-positive breast cancer at various stages of progression, concerns about heart failure persist. Studies have suggested that the drug doesn’t boost the risk of late cardiac events, but it’s not clear if this is due to mandated screening in these trials. The new study provides more evidence that adherence to screening guidelines is limited, and recent trials offer evidence that the general cardiac risk may be overblown. Future studies could be designed to offer insight into the wisdom of adjusting screening regimens based on stratification of risk. A meta-analysis could also be helpful, and the upcoming results of the SAFE-HEART study will provide information about the safety of anti-HER2 antibody therapy in patients with low but asymptomatic left-ventricular ejection fraction.
These comments are excerpted from a commentary by Chau T. Dang, MD, of Memorial Sloan Kettering Cancer Center, New York, and her associates (JACC: Cardiovasc Imaging. 2018 Aug;11[8]:1094-7). Most of the commentary authors report various disclosures.
While trastuzumab clearly benefits patients with HER2-positive breast cancer at various stages of progression, concerns about heart failure persist. Studies have suggested that the drug doesn’t boost the risk of late cardiac events, but it’s not clear if this is due to mandated screening in these trials. The new study provides more evidence that adherence to screening guidelines is limited, and recent trials offer evidence that the general cardiac risk may be overblown. Future studies could be designed to offer insight into the wisdom of adjusting screening regimens based on stratification of risk. A meta-analysis could also be helpful, and the upcoming results of the SAFE-HEART study will provide information about the safety of anti-HER2 antibody therapy in patients with low but asymptomatic left-ventricular ejection fraction.
These comments are excerpted from a commentary by Chau T. Dang, MD, of Memorial Sloan Kettering Cancer Center, New York, and her associates (JACC: Cardiovasc Imaging. 2018 Aug;11[8]:1094-7). Most of the commentary authors report various disclosures.
While trastuzumab clearly benefits patients with HER2-positive breast cancer at various stages of progression, concerns about heart failure persist. Studies have suggested that the drug doesn’t boost the risk of late cardiac events, but it’s not clear if this is due to mandated screening in these trials. The new study provides more evidence that adherence to screening guidelines is limited, and recent trials offer evidence that the general cardiac risk may be overblown. Future studies could be designed to offer insight into the wisdom of adjusting screening regimens based on stratification of risk. A meta-analysis could also be helpful, and the upcoming results of the SAFE-HEART study will provide information about the safety of anti-HER2 antibody therapy in patients with low but asymptomatic left-ventricular ejection fraction.
These comments are excerpted from a commentary by Chau T. Dang, MD, of Memorial Sloan Kettering Cancer Center, New York, and her associates (JACC: Cardiovasc Imaging. 2018 Aug;11[8]:1094-7). Most of the commentary authors report various disclosures.
Adding more evidence to an ongoing debate, a large new study suggests that patients with breast cancer who take trastuzumab (Herceptin) may face double the adjusted risk of developing heart failure, with older women at highest risk.
The study also found that most patients who took trastuzumab didn’t receive recommended cardiac screening.
The researchers said their findings are unique because they tracked both younger and older patients. “By examining the rates of both cardiac monitoring and cardiotoxicity, we could begin to address the controversial issue of whether cardiac monitoring is warranted in young breast cancer patients,” wrote Mariana Chavez-MacGregor, MD, MSC, of the University of Texas MD Anderson Cancer Center, and her associates. The report was published in JACC: Cardiovascular Imaging.
While Trastuzumab has boosted breast cancer survival rates for patients with HER2-positive tumors, it’s also raised concerns about cardiotoxicity that could be an indicator of subsequent congestive heart failure (Cochrane Database Syst Rev. 2014 Jun 12;(6):CD006242).
According to the new study, the risk of trastuzumab risk is linked to damage to cardiac myocytes that can cause reversible cardiotoxicity.
The prescribing information for trastuzumab advises patients to undergo cardiac monitoring before treatment with trastuzumab and every 3 months during treatment. Recommendations by medical organizations have varied.
Now, as a 2016 report put it, it’s “increasingly unclear” whether frequent routine monitoring is appropriate for all patients (J Clin Oncol. 2016 Apr 1;34[10]:1030-3).
For the current study, Dr. Chavez-MacGregor and her associates identified 16,456 adult women in the United States who were diagnosed with nonmetastatic invasive breast cancer from 2009 to 2014. Researchers tracked the group, with a median age of 56, through as late as 2015.
The women were treated with chemotherapy within 6 months of diagnosis, and 4,325 received trastuzumab.
Of all the subjects, 692 patients (4.2%) developed heart failure following chemotherapy. The rate among patients treated with trastuzumab was higher, at 8.3%, compared with 2.7% for those not treated with trastuzumab (P less than .001).
The researchers also looked at anthracycline users and found that they were slightly more likely to develop HF (4.6% vs. 4.0% among nonusers, P = .048).
Increased age boosted the risk of HF in the trastuzumab-treated patients, and the risk was highest in those treated with both anthracyclines and trastuzumab. Other factors linked to more risk were comorbidities, hypertension, and valve disease.
After adjusting for confounders, the researchers estimated that those treated with trastuzumab were 2.01 times more likely to develop HF (HR, 2.01; 95% confidence interval, 1.72-2.36), and those who took anthracycline were 1.53 times more likely (HR, 1.53; 95% CI, 1.30-1.80)
The researchers also examined medical records for evidence that subjects underwent cardiac screening at least once every 4 months, not 3 months, as the prescribing information recommends. The study team chose to focus on 4-month intervals “to compensate for differences in scheduling, resources, or levels of accessibility to medical care.”
Medical records suggest that 73.5% of patients who took trastuzumab underwent cardiac screening at the beginning of therapy, but only 46.2% continued to do so at least every 4 months.
An adjusted model linked more screening to the use of anthracyclines and taxanes, radiation treatment, and living in the Northeast vs. the West.
“HF was more frequently identified among patients undergoing recommended cardiac monitoring (10.4% compared with 6.5%, respectively; P less than.001), suggesting that, as more patients are screened, more patients are likely to be found having HF,” the researchers reported.
However, they added that “our sensitivity analysis using inpatient claims allowed us to determine that the HF identified using cardiac monitoring was not severe enough to require hospitalization and was likely asymptomatic. The clinical implications of the diagnosis of asymptomatic HF are hard to determine and are beyond the scope of this study.”
The researchers also noted that the findings suggest that screening has become more common in recent years.
“The number of cancer survivors is expected to increase over time, and we will continue to see patients develop treatment-related cardiotoxicity,” the researchers wrote. “Thus, more research, evidence-based guidelines, and tools for prediction of cancer treatment–related cardiotoxicity are needed.”
The National Cancer Institute and Cancer Prevention and Research Institute of Texas funded the study. Two study authors reported grant funding from the Susan G. Komen Breast Cancer Foundation, and one reports consulting for Pfizer and Roche. The other authors reported no disclosures.
SOURCE: Chavez-MacGregor M et al. JACC: Cardiovasc Imaging. 2018 Aug;11[8]1084-93.
Adding more evidence to an ongoing debate, a large new study suggests that patients with breast cancer who take trastuzumab (Herceptin) may face double the adjusted risk of developing heart failure, with older women at highest risk.
The study also found that most patients who took trastuzumab didn’t receive recommended cardiac screening.
The researchers said their findings are unique because they tracked both younger and older patients. “By examining the rates of both cardiac monitoring and cardiotoxicity, we could begin to address the controversial issue of whether cardiac monitoring is warranted in young breast cancer patients,” wrote Mariana Chavez-MacGregor, MD, MSC, of the University of Texas MD Anderson Cancer Center, and her associates. The report was published in JACC: Cardiovascular Imaging.
While Trastuzumab has boosted breast cancer survival rates for patients with HER2-positive tumors, it’s also raised concerns about cardiotoxicity that could be an indicator of subsequent congestive heart failure (Cochrane Database Syst Rev. 2014 Jun 12;(6):CD006242).
According to the new study, the risk of trastuzumab risk is linked to damage to cardiac myocytes that can cause reversible cardiotoxicity.
The prescribing information for trastuzumab advises patients to undergo cardiac monitoring before treatment with trastuzumab and every 3 months during treatment. Recommendations by medical organizations have varied.
Now, as a 2016 report put it, it’s “increasingly unclear” whether frequent routine monitoring is appropriate for all patients (J Clin Oncol. 2016 Apr 1;34[10]:1030-3).
For the current study, Dr. Chavez-MacGregor and her associates identified 16,456 adult women in the United States who were diagnosed with nonmetastatic invasive breast cancer from 2009 to 2014. Researchers tracked the group, with a median age of 56, through as late as 2015.
The women were treated with chemotherapy within 6 months of diagnosis, and 4,325 received trastuzumab.
Of all the subjects, 692 patients (4.2%) developed heart failure following chemotherapy. The rate among patients treated with trastuzumab was higher, at 8.3%, compared with 2.7% for those not treated with trastuzumab (P less than .001).
The researchers also looked at anthracycline users and found that they were slightly more likely to develop HF (4.6% vs. 4.0% among nonusers, P = .048).
Increased age boosted the risk of HF in the trastuzumab-treated patients, and the risk was highest in those treated with both anthracyclines and trastuzumab. Other factors linked to more risk were comorbidities, hypertension, and valve disease.
After adjusting for confounders, the researchers estimated that those treated with trastuzumab were 2.01 times more likely to develop HF (HR, 2.01; 95% confidence interval, 1.72-2.36), and those who took anthracycline were 1.53 times more likely (HR, 1.53; 95% CI, 1.30-1.80)
The researchers also examined medical records for evidence that subjects underwent cardiac screening at least once every 4 months, not 3 months, as the prescribing information recommends. The study team chose to focus on 4-month intervals “to compensate for differences in scheduling, resources, or levels of accessibility to medical care.”
Medical records suggest that 73.5% of patients who took trastuzumab underwent cardiac screening at the beginning of therapy, but only 46.2% continued to do so at least every 4 months.
An adjusted model linked more screening to the use of anthracyclines and taxanes, radiation treatment, and living in the Northeast vs. the West.
“HF was more frequently identified among patients undergoing recommended cardiac monitoring (10.4% compared with 6.5%, respectively; P less than.001), suggesting that, as more patients are screened, more patients are likely to be found having HF,” the researchers reported.
However, they added that “our sensitivity analysis using inpatient claims allowed us to determine that the HF identified using cardiac monitoring was not severe enough to require hospitalization and was likely asymptomatic. The clinical implications of the diagnosis of asymptomatic HF are hard to determine and are beyond the scope of this study.”
The researchers also noted that the findings suggest that screening has become more common in recent years.
“The number of cancer survivors is expected to increase over time, and we will continue to see patients develop treatment-related cardiotoxicity,” the researchers wrote. “Thus, more research, evidence-based guidelines, and tools for prediction of cancer treatment–related cardiotoxicity are needed.”
The National Cancer Institute and Cancer Prevention and Research Institute of Texas funded the study. Two study authors reported grant funding from the Susan G. Komen Breast Cancer Foundation, and one reports consulting for Pfizer and Roche. The other authors reported no disclosures.
SOURCE: Chavez-MacGregor M et al. JACC: Cardiovasc Imaging. 2018 Aug;11[8]1084-93.
FROM JACC: CARDIOVASCULAR IMAGING
Key clinical point: Women with breast cancer who take trastuzumab (Herceptin) may face double the adjusted risk of heart failure, but most aren’t screened frequently.
Major finding: Patients who took trastuzumab were 2.01 times more likely to develop HF (HR, 95% CI, 1.72-2.36) than were those who didn’t. Of all patients who took the drug, fewer than half received recommended frequency of screening.
Study details: Analysis of 16,456 U.S. adult women with nonmetastatic breast cancer diagnosed from 2009 to 2014 and tracked through 2015. Of those, 4.2% developed HF.
Disclosures: The National Cancer Institute and Cancer Prevention and Research Institute of Texas funded the study. Two study authors report grant funding from the Susan G. Komen Breast Cancer Foundation, and one reports consulting for Pfizer and Roche. The other authors report no disclosures.
Source: Chavez-MacGregor M et al. JACC: Cardiovasc Imaging 2018 Aug;11[8]1084-93.
New MS criteria may create more false positives
The revised McDonald criteria for multiple sclerosis (MS) has led to more diagnoses in patients with clinically isolated syndrome (CIS), but a new study of the criteria has suggested that they may lead to a number of false positive MS diagnoses among patients with a less severe disease state.
“In our data, specificity of the 2017 criteria was significantly lower than for the 2010 criteria,” Roos M. van der Vuurst de Vries, MD, from the department of neurology at Erasmus Medical Center in Rotterdam, the Netherlands, and her colleagues wrote in JAMA Neurology. “Earlier data showed that the previous McDonald criteria lead to a higher number of MS diagnoses in patients who will not have a second attack.”
Dr. van der Vuurst de Vries and her colleagues analyzed data from 229 patients with a CIS who underwent an MRI of the spinal cord to assess for dissemination in space (DIS); of these, 180 patients were scored for both DIS and dissemination in time (DIT) and had a “baseline MRI scan that included T1 images after gadolinium administration or scans that did not show any T2 hyperintense lesions.” Some patients also underwent a baseline lumbar puncture if clinically required.
Patients were assessed using both the 2010 and 2017 McDonald criteria for MS, and results were measured using sensitivity, specificity, positive predictive and negative predictive values, and accuracy at 1-year, 3-year, and 5-year follow-up. “The most important addition is that the new criteria allow MS diagnosis when the MRI scan meets criteria for DIS and unique oligoclonal bands (OCB) are present in [cerebrospinal fluid], even in absence of DIT on the MRI scan,” the researchers wrote. “The other major difference is that not only asymptomatic but also symptomatic lesions can be used to demonstrate DIS and DIT on MRI. Furthermore, cortical lesions can be used to demonstrate dissemination in space.”
The researchers found that 124 patients met 2010 DIS criteria (54%) and that 74 patients (60%) went on to develop clinically definite MS, while 149 patients (65%) met 2017 DIS criteria, and 89 patients (60%) went on to clinically definite MS. There were 46 patients (26%) who met 2010 DIT criteria, and 33 of those patients (72%) were diagnosed with clinically definite MS; 126 patients (70%) met 2017 DIT criteria, and 76 of those patients (60%) had clinically definite MS. The sensitivity for the 2010 criteria was 36% (95% confidence interval, 27%-47%)versus 68% for the 2017 criteria (95% CI, 57%-77%; P less than .001). However, specificity for the 2017 criteria was lower (61%; 95% CI, 50%-71%) when compared with the 2010 criteria (85%; 95% CI, 76%-92%; P less than .001). Researchers found more baseline MS diagnoses with the 2017 criteria than with the 2010 criteria, but they noted that 14 of 22 patients (64%) under the 2010 criteria and 26 of 48 patients (54%) under the 2017 criteria with MS had a second attack within 5 years.
The study was supported by the Dutch Multiple Sclerosis Research Foundation. One or more authors received compensation from Teva, Merck, Roche, Sanofi Genzyme, Biogen, and Novartis in the form of honoraria, for advisory board membership, as travel grants, or for participation in trials.
SOURCE: van der Vuurst de Vries RM, et al. JAMA Neurol. 2018 Aug 6. doi: 10.1001/jamaneurol.2018.2160.
The revised McDonald criteria for multiple sclerosis (MS) has led to more diagnoses in patients with clinically isolated syndrome (CIS), but a new study of the criteria has suggested that they may lead to a number of false positive MS diagnoses among patients with a less severe disease state.
“In our data, specificity of the 2017 criteria was significantly lower than for the 2010 criteria,” Roos M. van der Vuurst de Vries, MD, from the department of neurology at Erasmus Medical Center in Rotterdam, the Netherlands, and her colleagues wrote in JAMA Neurology. “Earlier data showed that the previous McDonald criteria lead to a higher number of MS diagnoses in patients who will not have a second attack.”
Dr. van der Vuurst de Vries and her colleagues analyzed data from 229 patients with a CIS who underwent an MRI of the spinal cord to assess for dissemination in space (DIS); of these, 180 patients were scored for both DIS and dissemination in time (DIT) and had a “baseline MRI scan that included T1 images after gadolinium administration or scans that did not show any T2 hyperintense lesions.” Some patients also underwent a baseline lumbar puncture if clinically required.
Patients were assessed using both the 2010 and 2017 McDonald criteria for MS, and results were measured using sensitivity, specificity, positive predictive and negative predictive values, and accuracy at 1-year, 3-year, and 5-year follow-up. “The most important addition is that the new criteria allow MS diagnosis when the MRI scan meets criteria for DIS and unique oligoclonal bands (OCB) are present in [cerebrospinal fluid], even in absence of DIT on the MRI scan,” the researchers wrote. “The other major difference is that not only asymptomatic but also symptomatic lesions can be used to demonstrate DIS and DIT on MRI. Furthermore, cortical lesions can be used to demonstrate dissemination in space.”
The researchers found that 124 patients met 2010 DIS criteria (54%) and that 74 patients (60%) went on to develop clinically definite MS, while 149 patients (65%) met 2017 DIS criteria, and 89 patients (60%) went on to clinically definite MS. There were 46 patients (26%) who met 2010 DIT criteria, and 33 of those patients (72%) were diagnosed with clinically definite MS; 126 patients (70%) met 2017 DIT criteria, and 76 of those patients (60%) had clinically definite MS. The sensitivity for the 2010 criteria was 36% (95% confidence interval, 27%-47%)versus 68% for the 2017 criteria (95% CI, 57%-77%; P less than .001). However, specificity for the 2017 criteria was lower (61%; 95% CI, 50%-71%) when compared with the 2010 criteria (85%; 95% CI, 76%-92%; P less than .001). Researchers found more baseline MS diagnoses with the 2017 criteria than with the 2010 criteria, but they noted that 14 of 22 patients (64%) under the 2010 criteria and 26 of 48 patients (54%) under the 2017 criteria with MS had a second attack within 5 years.
The study was supported by the Dutch Multiple Sclerosis Research Foundation. One or more authors received compensation from Teva, Merck, Roche, Sanofi Genzyme, Biogen, and Novartis in the form of honoraria, for advisory board membership, as travel grants, or for participation in trials.
SOURCE: van der Vuurst de Vries RM, et al. JAMA Neurol. 2018 Aug 6. doi: 10.1001/jamaneurol.2018.2160.
The revised McDonald criteria for multiple sclerosis (MS) has led to more diagnoses in patients with clinically isolated syndrome (CIS), but a new study of the criteria has suggested that they may lead to a number of false positive MS diagnoses among patients with a less severe disease state.
“In our data, specificity of the 2017 criteria was significantly lower than for the 2010 criteria,” Roos M. van der Vuurst de Vries, MD, from the department of neurology at Erasmus Medical Center in Rotterdam, the Netherlands, and her colleagues wrote in JAMA Neurology. “Earlier data showed that the previous McDonald criteria lead to a higher number of MS diagnoses in patients who will not have a second attack.”
Dr. van der Vuurst de Vries and her colleagues analyzed data from 229 patients with a CIS who underwent an MRI of the spinal cord to assess for dissemination in space (DIS); of these, 180 patients were scored for both DIS and dissemination in time (DIT) and had a “baseline MRI scan that included T1 images after gadolinium administration or scans that did not show any T2 hyperintense lesions.” Some patients also underwent a baseline lumbar puncture if clinically required.
Patients were assessed using both the 2010 and 2017 McDonald criteria for MS, and results were measured using sensitivity, specificity, positive predictive and negative predictive values, and accuracy at 1-year, 3-year, and 5-year follow-up. “The most important addition is that the new criteria allow MS diagnosis when the MRI scan meets criteria for DIS and unique oligoclonal bands (OCB) are present in [cerebrospinal fluid], even in absence of DIT on the MRI scan,” the researchers wrote. “The other major difference is that not only asymptomatic but also symptomatic lesions can be used to demonstrate DIS and DIT on MRI. Furthermore, cortical lesions can be used to demonstrate dissemination in space.”
The researchers found that 124 patients met 2010 DIS criteria (54%) and that 74 patients (60%) went on to develop clinically definite MS, while 149 patients (65%) met 2017 DIS criteria, and 89 patients (60%) went on to clinically definite MS. There were 46 patients (26%) who met 2010 DIT criteria, and 33 of those patients (72%) were diagnosed with clinically definite MS; 126 patients (70%) met 2017 DIT criteria, and 76 of those patients (60%) had clinically definite MS. The sensitivity for the 2010 criteria was 36% (95% confidence interval, 27%-47%)versus 68% for the 2017 criteria (95% CI, 57%-77%; P less than .001). However, specificity for the 2017 criteria was lower (61%; 95% CI, 50%-71%) when compared with the 2010 criteria (85%; 95% CI, 76%-92%; P less than .001). Researchers found more baseline MS diagnoses with the 2017 criteria than with the 2010 criteria, but they noted that 14 of 22 patients (64%) under the 2010 criteria and 26 of 48 patients (54%) under the 2017 criteria with MS had a second attack within 5 years.
The study was supported by the Dutch Multiple Sclerosis Research Foundation. One or more authors received compensation from Teva, Merck, Roche, Sanofi Genzyme, Biogen, and Novartis in the form of honoraria, for advisory board membership, as travel grants, or for participation in trials.
SOURCE: van der Vuurst de Vries RM, et al. JAMA Neurol. 2018 Aug 6. doi: 10.1001/jamaneurol.2018.2160.
FROM JAMA NEUROLOGY
Key clinical point: The 2017 McDonald criteria for MS may diagnose more patients with a clinically isolated syndrome, but a lower specificity may also capture more patients who do not have a second CIS event.
Major finding: The sensitivity for the 2017 criteria was greater at 68%, compared with 36% in the 2010 criteria; however, specificity was significantly lower in the 2017 criteria at 61%, compared with 85% in the 2010 criteria.
Data source: An original study of 229 patients from the Netherlands with CIS who underwent an MRI scan within 3 months of symptoms.
Disclosures: The study was supported by the Dutch Multiple Sclerosis Research Foundation. One or more authors received compensation from Teva, Merck, Roche, Sanofi Genzyme, Biogen, and Novartis in the form of honoraria, for advisory board membership, as travel grants, or for participation in trials.
Source: van der Vuurst de Vries RM et al. JAMA Neurol. 2018 Aug 6. doi: 10.1001/jamaneurol.2018.2160.
Treatment of relapsing progressive MS may reduce disability progression
Superimposed relapses were associated with a significantly reduced risk of disability progression in a longitudinal, prospective cohort study of 1,419 multiple sclerosis patients (MS) of the progressive-onset type.
To determine the role of inflammatory relapses on disability in the progressive-relapsing phenotype of progressive-onset MS, the researchers collected data from MSBase, an international, observational cohort of MS patients, from January 1995 to February 2017. The study population included 1,419 adults with MS (553 in the relapse subgroup, 866 in a nonrelapse subgroup) from 83 centers in 28 countries; the median prospective follow-up period was 5 years. The patients included in the analysis had adult-onset disease, at least three clinic visits with Expanded Disability Status Scale (EDSS) score recorded, and a time frame of more than 3 months between the second and last visit.
Overall, patients with relapses had significantly less risk of disability progression after adjusting for confounding variables (adjusted hazard ratio, 0.83; 95% confidence interval, 0.74-0.94; P = .003). Disease progression was defined as worsening of the EDSS score.
In addition, the researchers examined the data in a stratified model and found a 4% relative decrease in the hazard of confirmed disability progression events for each 10% increment of follow-up time for receiving disease-modifying therapy (DMT). However, DMT did not reduce disease progression risk in progressive-onset MS patients without relapse.
“This suggests that relapses in progressive-onset MS, as a clinical correlate of episodic inflammatory activity, represent a positive prognostic marker and provide an opportunity to improve disease outcomes through prevention of relapse-related disability accrual,” the researchers wrote.
Interferon-beta was the most common DMT, given to 73% of the relapse patients and 56% of the nonrelapse patients, followed by glatiramer acetate (20% and 13%, respectively), and fingolimod (12% and 16%, respectively).
The study’s main limitation was the use of the EDSS as a measure of disability, as well as the absence of quantifiable disability change to confirm relapse, the researchers noted. However, “these findings provide further evidence for a progressive-onset MS phenotype with acute episodic inflammatory changes, thereby identifying patients who may respond to existing immunotherapies.”
The study was supported by grants from the National Health and Medical Research Council of Australia and the MSBase Foundation, a nonprofit organization that itself receives support from multiple companies, including Merck, Novartis, and Sanofi. Dr. Hughes had no financial conflicts to disclose, but most coauthors disclosed relationships with multiple companies including Merck, Novartis, Sanofi. Genzyme, and Biogen.
SOURCE: Hughes J et al. JAMA Neurol. 2018 Aug 6. doi: 10.1001/jamaneurol.2018.2109.
This study is important because it addresses an area of controversy in management of patients with a progressive multiple sclerosis (MS) phenotype. The role of superimposed relapses in patients with progressive MS has long been debated, with some studies reporting no impact on long-term disability accrual and other reporting a negative impact of relapses. Treatment of progressive MS remains controversial as well, with only one therapy approved by the Food and Drug Administration for any form of progressive MS. There is considerable ongoing debate about whether MS disease-modifying therapies (MSDMT) are effective in progressive forms of MS, and whether clinical or MRI evidence of active inflammation predicts a better chance of response.
This study has several important strengths and limitations. The large sample size allowed statistical power to detect relatively small differences in disability progression risk between progressive MS subtypes. The better prognosis in progressive patients with superimposed relapses contradicts some earlier studies that suggested a worse prognosis or no difference in prognosis between progressive patients with and without relapses. This study also supports a role for MSDMT in progressive MS patients, at least those with clinical evidence of relapses, and possibly MRI evidence of inflammatory disease activity (although this was not specifically addressed in the current study). Limitations of the study include the observational nature of the database, variable periods of follow-up, lack of objective verification of recorded relapses either with EDSS scores or MRI confirmation, and lack of an untreated control group. Therefore, no conclusions can be drawn as to whether MSDMT exposure had a favorable impact on the whole cohort of progressive patients versus no treatment.
Jonathan L. Carter, MD , is an MS specialist at the Mayo Clinic in Scottsdale, Ariz. He had no relevant disclosures to report.
This study is important because it addresses an area of controversy in management of patients with a progressive multiple sclerosis (MS) phenotype. The role of superimposed relapses in patients with progressive MS has long been debated, with some studies reporting no impact on long-term disability accrual and other reporting a negative impact of relapses. Treatment of progressive MS remains controversial as well, with only one therapy approved by the Food and Drug Administration for any form of progressive MS. There is considerable ongoing debate about whether MS disease-modifying therapies (MSDMT) are effective in progressive forms of MS, and whether clinical or MRI evidence of active inflammation predicts a better chance of response.
This study has several important strengths and limitations. The large sample size allowed statistical power to detect relatively small differences in disability progression risk between progressive MS subtypes. The better prognosis in progressive patients with superimposed relapses contradicts some earlier studies that suggested a worse prognosis or no difference in prognosis between progressive patients with and without relapses. This study also supports a role for MSDMT in progressive MS patients, at least those with clinical evidence of relapses, and possibly MRI evidence of inflammatory disease activity (although this was not specifically addressed in the current study). Limitations of the study include the observational nature of the database, variable periods of follow-up, lack of objective verification of recorded relapses either with EDSS scores or MRI confirmation, and lack of an untreated control group. Therefore, no conclusions can be drawn as to whether MSDMT exposure had a favorable impact on the whole cohort of progressive patients versus no treatment.
Jonathan L. Carter, MD , is an MS specialist at the Mayo Clinic in Scottsdale, Ariz. He had no relevant disclosures to report.
This study is important because it addresses an area of controversy in management of patients with a progressive multiple sclerosis (MS) phenotype. The role of superimposed relapses in patients with progressive MS has long been debated, with some studies reporting no impact on long-term disability accrual and other reporting a negative impact of relapses. Treatment of progressive MS remains controversial as well, with only one therapy approved by the Food and Drug Administration for any form of progressive MS. There is considerable ongoing debate about whether MS disease-modifying therapies (MSDMT) are effective in progressive forms of MS, and whether clinical or MRI evidence of active inflammation predicts a better chance of response.
This study has several important strengths and limitations. The large sample size allowed statistical power to detect relatively small differences in disability progression risk between progressive MS subtypes. The better prognosis in progressive patients with superimposed relapses contradicts some earlier studies that suggested a worse prognosis or no difference in prognosis between progressive patients with and without relapses. This study also supports a role for MSDMT in progressive MS patients, at least those with clinical evidence of relapses, and possibly MRI evidence of inflammatory disease activity (although this was not specifically addressed in the current study). Limitations of the study include the observational nature of the database, variable periods of follow-up, lack of objective verification of recorded relapses either with EDSS scores or MRI confirmation, and lack of an untreated control group. Therefore, no conclusions can be drawn as to whether MSDMT exposure had a favorable impact on the whole cohort of progressive patients versus no treatment.
Jonathan L. Carter, MD , is an MS specialist at the Mayo Clinic in Scottsdale, Ariz. He had no relevant disclosures to report.
Superimposed relapses were associated with a significantly reduced risk of disability progression in a longitudinal, prospective cohort study of 1,419 multiple sclerosis patients (MS) of the progressive-onset type.
To determine the role of inflammatory relapses on disability in the progressive-relapsing phenotype of progressive-onset MS, the researchers collected data from MSBase, an international, observational cohort of MS patients, from January 1995 to February 2017. The study population included 1,419 adults with MS (553 in the relapse subgroup, 866 in a nonrelapse subgroup) from 83 centers in 28 countries; the median prospective follow-up period was 5 years. The patients included in the analysis had adult-onset disease, at least three clinic visits with Expanded Disability Status Scale (EDSS) score recorded, and a time frame of more than 3 months between the second and last visit.
Overall, patients with relapses had significantly less risk of disability progression after adjusting for confounding variables (adjusted hazard ratio, 0.83; 95% confidence interval, 0.74-0.94; P = .003). Disease progression was defined as worsening of the EDSS score.
In addition, the researchers examined the data in a stratified model and found a 4% relative decrease in the hazard of confirmed disability progression events for each 10% increment of follow-up time for receiving disease-modifying therapy (DMT). However, DMT did not reduce disease progression risk in progressive-onset MS patients without relapse.
“This suggests that relapses in progressive-onset MS, as a clinical correlate of episodic inflammatory activity, represent a positive prognostic marker and provide an opportunity to improve disease outcomes through prevention of relapse-related disability accrual,” the researchers wrote.
Interferon-beta was the most common DMT, given to 73% of the relapse patients and 56% of the nonrelapse patients, followed by glatiramer acetate (20% and 13%, respectively), and fingolimod (12% and 16%, respectively).
The study’s main limitation was the use of the EDSS as a measure of disability, as well as the absence of quantifiable disability change to confirm relapse, the researchers noted. However, “these findings provide further evidence for a progressive-onset MS phenotype with acute episodic inflammatory changes, thereby identifying patients who may respond to existing immunotherapies.”
The study was supported by grants from the National Health and Medical Research Council of Australia and the MSBase Foundation, a nonprofit organization that itself receives support from multiple companies, including Merck, Novartis, and Sanofi. Dr. Hughes had no financial conflicts to disclose, but most coauthors disclosed relationships with multiple companies including Merck, Novartis, Sanofi. Genzyme, and Biogen.
SOURCE: Hughes J et al. JAMA Neurol. 2018 Aug 6. doi: 10.1001/jamaneurol.2018.2109.
Superimposed relapses were associated with a significantly reduced risk of disability progression in a longitudinal, prospective cohort study of 1,419 multiple sclerosis patients (MS) of the progressive-onset type.
To determine the role of inflammatory relapses on disability in the progressive-relapsing phenotype of progressive-onset MS, the researchers collected data from MSBase, an international, observational cohort of MS patients, from January 1995 to February 2017. The study population included 1,419 adults with MS (553 in the relapse subgroup, 866 in a nonrelapse subgroup) from 83 centers in 28 countries; the median prospective follow-up period was 5 years. The patients included in the analysis had adult-onset disease, at least three clinic visits with Expanded Disability Status Scale (EDSS) score recorded, and a time frame of more than 3 months between the second and last visit.
Overall, patients with relapses had significantly less risk of disability progression after adjusting for confounding variables (adjusted hazard ratio, 0.83; 95% confidence interval, 0.74-0.94; P = .003). Disease progression was defined as worsening of the EDSS score.
In addition, the researchers examined the data in a stratified model and found a 4% relative decrease in the hazard of confirmed disability progression events for each 10% increment of follow-up time for receiving disease-modifying therapy (DMT). However, DMT did not reduce disease progression risk in progressive-onset MS patients without relapse.
“This suggests that relapses in progressive-onset MS, as a clinical correlate of episodic inflammatory activity, represent a positive prognostic marker and provide an opportunity to improve disease outcomes through prevention of relapse-related disability accrual,” the researchers wrote.
Interferon-beta was the most common DMT, given to 73% of the relapse patients and 56% of the nonrelapse patients, followed by glatiramer acetate (20% and 13%, respectively), and fingolimod (12% and 16%, respectively).
The study’s main limitation was the use of the EDSS as a measure of disability, as well as the absence of quantifiable disability change to confirm relapse, the researchers noted. However, “these findings provide further evidence for a progressive-onset MS phenotype with acute episodic inflammatory changes, thereby identifying patients who may respond to existing immunotherapies.”
The study was supported by grants from the National Health and Medical Research Council of Australia and the MSBase Foundation, a nonprofit organization that itself receives support from multiple companies, including Merck, Novartis, and Sanofi. Dr. Hughes had no financial conflicts to disclose, but most coauthors disclosed relationships with multiple companies including Merck, Novartis, Sanofi. Genzyme, and Biogen.
SOURCE: Hughes J et al. JAMA Neurol. 2018 Aug 6. doi: 10.1001/jamaneurol.2018.2109.
FROM JAMA NEUROLOGY
Key clinical point: Disease-modifying therapy was significantly associated with less disability progression in multiple sclerosis patients with superimposed relapses, compared with those without relapses.
Major finding: Progressive-onset multiple sclerosis patients with superimposed relapses were significantly less likely to have confirmed disability progression (adjusted hazard ratio, 0.83).
Study details: The data came from a longitudinal, prospective cohort study of 1,419 adults with progressive-onset multiple sclerosis.
Disclosures: The study was supported by grants from the National Health and Medical Research Council of Australia and the MSBase Foundation, a nonprofit organization that itself receives support from multiple companies, including Merck, Novartis, and Sanofi. Dr. Hughes had no financial conflicts to disclose, but most coauthors disclosed relationships with multiple companies, including Merck, Novartis, Sanofi, Genzyme, and Biogen.
Source: Hughes J et al. JAMA Neurol. 2018 Aug 6. doi: 10.1001/jamaneurol.2018.2109.
Systems Automation for Cancer Surveillance: A Lean Six Sigma Project for Tracking Care of Patients With Head and Neck Cancer (FULL)
The American Cancer Society estimates that there were 1.68 million newly diagnosed cases of cancer in the U.S. in 2016, with an associated 595,690 deaths.1 Of this number, about 3% was attributable to head and neck cancer (HNC), with 48,330 new cases and 9,570 deaths in 2016. Cancer is among the leading causes of death worldwide, and veterans have a prevalence of HNC nearly twice that of the general population.2 The number of people living with and beyond a cancer diagnosis in the U.S. has risen to an estimated 15.5 million survivors.
Head and neck cancer comprises several subsites, including the oral cavity (lips, buccal mucosa, anterior tongue, floor of mouth, hard palate, and gingiva), the pharynx (nasopharynx, oropharynx, and hypopharynx), the larynx (supraglottis, glottis, and subglottis), the nasal cavity, paranasal sinuses, and the saliva glands.3 The economic burden for HNC treatment was estimated at $3.64 billion in 2010.4
Treatment is based on primary site and staging, and staging is according to the tumor node metastasis system of the American Joint Committee on Cancer.5 In general, lower stages (in situ, stages I and II) are treated with single modalities of organ-sparing surgery or radiation, whereas higher stages (stages III and IV) are treated with multiple modalities, which may include radiation combined with chemotherapy or surgery before or after radiation/chemotherapy.
Survival rate after treatment varies by primary site, cancer stage at diagnosis, histopathologic cell type, viral association, tobacco use, chemical exposure, and treatment modality; survival ranges from 24% to 90% at 5 years based on these variables.6 There is not yet a reliable blood test or other biochemical marker for recurrence, and serial radiologic examinations are expensive and expose the survivor to large amounts of additional ionizing radiation.7,8 Surveillance for recurrence after treatment consists primarily of physical examination and reported symptoms, which may be difficult for the primary care provider (PCP) to perform and distinguish from treatment sequelae.9,10 Thus, HNC survivors are followed in the ear, nose, and throat (ENT) otolaryngology clinic on a decreasing frequency schedule based on risk of relapse, second primaries, treatment sequelae, and toxicities (every 1-3 months in year 1, 2-6 months in year 2, 4-8 months in years 3-5, and every 12 months after 5 years) according to the National Comprehensive Cancer Network (NCCN) guidelines.11
Adherence with posttreatment surveillance in HNC recently was associated with length of survival; however, this observation at a single tertiary academic center was discordant with earlier published reports.12-15 About 80% to 90% of all postcurative intent treatment recurrences and second primary cancers occur within the first 4 years, with a better functional outcome if the recurrence is surgically salvageable or amenable to adjuvant radiation or combined radiation and chemotherapy.16,17 Nonadherence is generally associated with worse clinical and acute care utilization outcomes.18
Problem
At the Raymond G. Murphy VAMC, a tertiary care center in Albuquerque, New Mexico, there was a propensity of veteran HNC patients who missed scheduled surveillance appointments or were lost to follow-up. An informal review of several VA ENT departments revealed similar issues without any consistent method to solve the problem. In an effort to recapture these patients, in 2011 an ENT registered nurse (RN) was added to the team as cancer care coordinator (CCC). After several weeks of chart review of clinic records, it was determined that 31% of HNC patients had missed 1 or more ongoing surveillance appointments, either by patient no-show, clinic cancellations that failed to reschedule patients, or patient cancellation without rescheduling. The CCC was tasked with recapturing these lost patients, returning them to regular follow-up per NCCN guidelines, and tracking new cancer patients as they were diagnosed and progressed through treatment and surveillance. As there had been no one previously in this role in the ENT clinic, there was no guidance about how to proceed.
The mechanism in place for rescheduling no-show patients at that time consisted of a mailed postcard reminder sent by a medical support assistant who requested that the veteran contact the clinic to reschedule. Veterans reported that these reminders often appeared in their mail mingled with so-called junk mail and were discarded without reading. The CCC spent several more weeks examining clinic records in the computerized patient record system (CPRS), looking for patients with cancer in the 5-year surveillance period, and compiling a database of survivors and newly diagnosed patients. This database was compiled initially on paper and then converted to a spreadsheet. Patients who had missed appointments were contacted by the CCC and rescheduled, which resulted in a 100% recovery rate.
Unfortunately, although the manual tracking process was successful, it was laborious and time consuming. Weekly and sometimes daily examination of CPRS clinic records for new patients and survivor adherence was followed by tedious data entry into the spreadsheet. The manual tracking system was deemed suboptimal and a Lean Six Sigma process improvement project was initiated. The project goal was to produce a dashboard database tool that was patient centered to improve the quality of cancer care to veterans.
Methods
Lean Six Sigma is a combination of 2 improvement processes and is embraced by large business and government entities with the goal of improving efficiencies, reducing waste, decreasing errors, and generating cost savings.19 The first improvement process, Six Sigma, is a statistical concept with the goal of producing no more than 3.4 defects per million opportunities.20Using specific tools, Six Sigma identifies the cause of the problem to help develop effective solutions. Six Sigma also helps uncover defects and problems by using a standardized and systematic method for each process improvement project in a sequence of steps known as DMAIC (Define, Measure, Analyze, Improve, and Control) to ensure a defect-free product at a rate of 99.99966%. Define, the first step, contains a written statement defining the problem and the goals; Measure scrutinizes the current baseline of the project in measureable data to identify possible contributing factors; Analyze uses data and tools to understand the cause-and-effect relationships in the process; Improve uses creative developments and changes that lead to process improvements; and Control takes measures to ensure the improvements are implemented, reliable, and constant.
Although slightly different but complementary, Lean focuses on streamlining improvement processes by identifying and eliminating waste that has little or no value to the customer. The 8 most common forms of waste are identified through the mnemonic DOWNTIME (Defects, Overproduction, Waiting, Not utilizing human talent, Transportation, Inventory excess, Motion excess, and Excess processing).21 When both Lean and Six Sigma are used together, the synergistic effects have a powerful impact on the complete quality improvement process and yield consistent reliability. The combined process then includes several methodologic tools for systems redesign, including root-cause analysis, defining waste barriers, measuring current and expected performance, analyzing the data collected, improving the target process, and controlling the improvements. Though already existing and used within the VA system, Lean Six Sigma training was included as a mandatory component of new employee orientation in a memo issued in August 2015 from the assistant secretary for human resources and administration (VA access-only memo VAIQ 7595924).
Root-cause analysis was accomplished using the “5 Why” technique adapted into Lean and Six Sigma from the Toyota Motor Corporation. For example, the question “Why do patients miss appointments?” was asked 5 different ways, and it was determined that many patients lacked transportation, some were not able to reschedule at the time they called to cancel their appointment, those with multiple same-day appointments at the tertiary medical center were not able to wait to schedule a follow-up appointment for fear of missing or being late to their next appointment, and others were placed on recall lists with appointment reminders that failed to accomplish the purpose of self-scheduling by veterans. Thus, the common denominator and answer to the question “why” was that there was no tracking system in place to identify and reschedule missed follow-ups, and before employing a dedicated coordinator, no one accountable for the process (Figure 1).
Wasteful barriers to efficiency were examined with particular attention to the rescheduling process. Rescheduling produced immediate duplication of work for scheduling staff and increased wait time for future appointments. There was potential for additional health care expenses related to costs of late and progressive salvage treatment or for less-than-timely correction of HNC treatment sequelae, such as scarring, lymphedema, or dysphagia. Ear, nose, and throat providers were concerned about missing occult recurrence or residual cancer.
In 2013, the Lean Six Sigma process was used again to critique efforts by the CCC to identify and track HNC patients. One suggestion was to automate the process, and the Information Resource Management (IRM) office was contacted via work order to explore options for mining CPRS data. Working with a committed health information analyst, further discussion was aimed at pulling in additional data that would simultaneously track required posttreatment laboratory results and imaging. It was decided that a secure dashboard format would provide greater utility than would an online report that the CCC had to request and generate daily.
Integrated technologist Stephen Few defines a data dashboard as “… a visual display of the most important information needed to achieve one or more objectives; consolidated and arranged on a single screen so the information can be monitored at a glance.”22 The Head & Neck Cancer Tracking Dashboard (HNC Dashboard), designed by the IRM analyst, queries the VA Corporate Data Warehouse each night to identify all patients recently diagnosed with HNC by examining outpatient visit and inpatient discharge International Classification of Disease (ICD) codes entered by providers when coding encounter notes in CPRS. It also adds those with a HNC diagnosis in the VistA problem list and the HNC pathology department Systematized Nomenclature of Medicine (SNOMED) codes (Figure 2).
The automated ENT cancer tracking dashboard prototype debuted in 2014, but several months of trial and error took place to reanalyze ICD codes and narrow the list. The dashboard underwent multiple tests to ensure accuracy. Identified patients are presented using an interactive report hosted on a secure SharePoint (Redmond,WA) site, which reduced the risk of a data breach as access requires multi-authenticated user identification from a VA computer.
Another characteristic of the dashboard’s format is the ability to add custom features as needed. Several features now included in the dashboard are location of residence, diagnosis date, ICD code, date captured in the tracking system, most recent ENT clinic visit, future scheduled ENT clinic appointment, date of last thyroid stimulating hormone (TSH) laboratory test, and date of last position emission tomography scan. In addition, cancellations, no-shows, and patients overdue for TSH testing are highlighted in bold. Highlighted fields alert the CCC to reschedule patients in a timely manner and can alert providers to order needed follow-up tests and procedures.
Among the merits of the ENT cancer tracking dashboard is ease of use. The CCC uses a simple ABC acronym to describe utilization:
- A—added: The CCC daily edits new patients added to the dashboard with a HNC diagnosis. Several times recently the CCC saw a new diagnosis before the provider had been notified by pathology of biopsy results (Figure 3).
- B—browse: The dashboard format allows for rapid perusal of critical information at a glance (Figure 4). Recent labs and imaging can be discussed with providers immediately or at weekly ENT team cancer update meetings. Notification to clinicians can be rapid if the results show suspicion for residual/recurrent disease, a second primary site, metastasis, or there is need to notify the patient’s primary care provider to treat elevated TSH levels (hypothyroidism incidence after head and neck radiation is reportedly as high as 44%, with most patients being asymptomatic or simply fatigued).10,23
- C—check: Appointments are checked for those in the future, cancelled without rescheduling, or no-show dates. Empty fields under the “Next ENT Appointment” header alert the CCC to reschedule a follow-up appointment within NCCN guidelines. Alerting providers to upcoming surveillance appointments allows timely coordination with other care providers and departments, including speech pathology, nutrition, audiology, and social work. The “ENT Recall Date” has a unique time-sensitive feature and will visually display a bold type font when ready to be scheduled for a physical appointment (Figure 5).
Results
The cancer dashboard has demonstrated its success by supporting consistent and reliable monthly data. Results recorded over a 24-month period (from January 1, 2015 through December 31, 2016) showed that the electronic tracker identified 101 new HNC patients. During this period, 1,067 HNC patients were scheduled for follow-up appointments for cancer surveillance. Of these, the authors found that 112 HNC patients had missed their appointments due to calling and cancelling or not showing up as scheduled; resulting in a no-show status. This yielded an appointment nonadherence rate of 10%. The authors also found that 73 (7%) HNC patients did not have an elected scheduled appointment to return to the clinic for continued cancer surveillance. This number comprises all HNC patients whose appointments were cancelled by clinic cancellation, self-cancellation, no-show appointments, or those who left the clinic without scheduling a subsequent follow-up appointment. The electronic tracker identified 100% of these patients as missing and needing a future appointment. These patients may have otherwise been lost through manual tracking.
Implementation and utilization of a robust automated dashboard format HNC patient tracking system has been rewarding for the ENT department. The CCC has saved an estimated 600 to 800 hours per year of chart review and data entry. Although a time study was never conducted to measure the work process of this task, it is reasonable to conclude based on the following multiple manual step-by-step processes that the CCC had to perform frequently were now performed within the dashboard: reviewing consults for HNC diagnosis, recording new patient profile data on the spreadsheet; reviewing VA hospital pathology reports for new HNC diagnoses, reviewing the clinic schedule to track patient appointment adherence, updating and recording recent appointment activity, and reviewing the electronic medical records daily for recommended treatment plan and follow-up.
A side-by-side comparison of the functional features of tracking both manually and with automation showed that automation outnumbers the function of manual tracking by 36% and offers improved efficiency (Table). This has allowed time for the CCC to participate in simultaneous HNC care initiatives, including facilitating interfacility telehealth referrals for complex cancer surgery, scheduling and monitoring rural cancer surveillance telehealth appointments, and development of an ENT Survivorship Care Plan. These programs optimize time and workflow, reduce waste, reduce expenditures related to costly treatment modalities associated with advanced stages of malignancy, and improve the veteran experience. Further benefits to the veteran HNC patient population include increased self-efficacy and awareness for disease management through continuity of care, reduced cost associated with travel expense, and reduced potential copays due to additional medical care related to advanced stages of recurrent or residual disease.
In-house development of the HNC tracking dashboard has contributed to further cost savings for the VA. Specialized third-party acquired software can cost thousands of dollars for purchase and implementation and often includes ongoing fees for use. The Sustain and Spread concept of Lean Six Sigma is proven by a 100% recapture rate of HNC patients in the ENT clinic that potentially would have been lost to follow-up. The success in Spreading this innovation forward has resulted in adoption by other VAMCs for current use and implementation. After sharing information regarding the dashboard at 2 national conferences via presentations and poster, other VAMCs in neighboring states have requested the software and initiated custom versions. Because of this success and further demand, dashboard use is currently under consideration by the VA for nationwide availability.
Conclusion
Deficiencies in tracking cancer patients in the VA system exist in part due to little or no sophisticated electronic tracking systems that could perform multiple task functions to identify new cancer patients, the type of cancer, when appointments are missed, and notification when the required labs and procedures are completed. Often, the CCC is dependent on the arduous task of inputting of data to keep him/her up-to-date with patient care and coordination in a timely manner. As new VA policies attempts to perfect and streamline the scheduling process by way of providers placing “return to clinic” orders for patient follow-up care, there remains a potential risk of those patients not getting scheduled without a vigilant tracking process in place to monitor and ensure that all patients are scheduled.
The dashboard has proved to be an easy to use and vital tool in tracking HNC patients by the CCC. It will continue to assist in the identification of new HNC patients, provide ready access to patient information and follow-up care, and help facilitate CCC and provider communication on a daily basis, thereby meeting the goal of a patient-centered product that proves to improve the quality of cancer care of veterans.
Acknowledgment
The authors thank Mr. Dominic B. Ruiz, Visual Information Specialist, at the Raymond Murphy VAMC, who created images in high resolution for this article.
Author disclosures
The authors report no actual or potential conflicts of interest with regard to this article.
Disclaimer
The opinions expressed herein are those of the authors and do not necessarily reflect those of Federal Practitioner , Frontline Medical Communications Inc., the U.S. Government, or any of its agencies.
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1. Siegel RL, Miller KD, Jemal A. Cancer statistics, 2016. CA Cancer J Clin. 2016;66(1):7-30.
2. Patil RD, Meinzen-Derr JK, Hendricks BL, Patil YJ. Improving access and timelines of care for veterans with head and neck squamous cell carcinoma: a multidisciplinary team’s approach. Laryngoscope. 2016;126(3):627-631.
3. Wissinger E, Griebsch I, Lungershausen J, Foster T, Pashos CL. The economic burden of head and neck cancer: a systematic literature review. Pharmacoeconomics. 2014;32(9):865-882.
4. Mariotto AB, Yabroff KR, Shao Y, Feuer EJ, Brown ML. Projections of the cost of cancer care in the United States: 2010-2020. J Natl Cancer Inst. 2011;103(2):117-128.
5. Edge SB, Byrd DR, Compton CC, Fritz AG, Greene FL, Trotti A III, eds. American Joint Committee on Cancer Staging Manual. 7th ed. New York, NY: Springer-Verlag; 2010.
6. Cancer.net. Head and neck cancer: statistics. http://www.cancer.net/cancer-types/head-and-neck-cancer/Statistics. Updated September 2016. Accessed April 12, 2017.
7. Rachidi S, Wallace K, Wrangle JM, Day TA, Alberg AJ, Li Z. Neutrophil-to-lymphocyte ratio and overall survival in all sites of head and neck squamous cell carcinoma. Head Neck. 2016;38(suppl 1):E1068-E1074.
8. Cheung PK, Chin RY, Eslick GD. Detecting residual/recurrent head neck squamous cell carcinomas using PET or PET/CT: systematic review and meta-analysis. Arch Otolaryngol Head Neck Surg. 2016;154(3):421-432.
9. Haddad RI, Limaye S. Overview of approach to long-term survivors of head and neck cancer. http://www .uptodate .com/contents/overview-of-approach-to-long-term-survivors-of-head-and-neck-cancer. Updated October 26, 2016. Accessed April 12, 2017.
10. Manikantan K, Khode S, Dwivedi RC, et al. Making sense of post-treatment surveillance in head and neck cancer: when and what of follow-up. Cancer Treat Rev. 2009;35(8):744-753.
11. National Comprehensive Cancer Network. NCCN Clinical practice guidelines in onclology:head and neck cancers(2.2017).2017. Updated May 8, 2017. https://www.nccn.org/professionals/physician_gls/f_/pdf/head-and-neck.pdf. Accessed July 18, 2017.
12. Deutschmann MW, Sykes KJ, Harbison J, Cabrera-Muffly C, Schnayder Y. The impact of compliance in post treatment surveillance in head and neck squamous cell carcinoma. JAMA Otolaryngol Head Neck Surg. 2015;141(6):519-525.
13. Merkx MA, van Gulick JJ, Marres HA, et al. Effectiveness of routine follow-up of patients treated for T1-2N0 oral squamous cell carcinomas of the floor of mouth and tongue. Head Neck. 2006:28(1):1-7.
14. Ritoe SC, de Vegt F, Scheike IM, et al. Effect of routine follow-up after treatment for laryngeal cancer on life expectancy and mortality: results of a Markov model analysis. Cancer. 2007;109(2):239-247.
15. Agrawal A, Hammond TH, Young GS, Avon AL, Ozer E, Schuller DE. Factors affecting long-term survival in patients with recurrent head and neck cancer may help define the role of post-treatment surveillance. Laryngoscope. 2009;119(11):2135-2140.
16. Roland NJ, Bradley PJ. The role of surgery in the palliation of head and neck cancer. Curr Opin Otolaryngol Head Neck Surg. 2014;22(2):101-108.
17. Riaz N, Hong JC, Sherman EJ, et al. A nomogram to predict loco-regional control after re-irradiation for head and neck cancer. Radiother Oncol. 2014;111(3):382-387.
18. Hwang AS, Atlas SJ, Cronin P, et al. Appointment “no-shows” are an independent predictor of subsequent quality of care and resource utilization outcomes. J Gen Intern Med. 2015;30(10):1426-1433.
19. Healthcare Daily Online. VA healthcare system adopts lean six sigma. http://www.healthcaredailyonline.com/news/va-lean-six-sigma-in-healthcare. Updated December 7, 2015. Accessed April 12, 2017.
20. Gygi C, Williams B. Six Sigma for Dummies. 2nd edition. Hoboken, NJ: John Wiley & Sons; 2012.
21. Kavanagh S, Krings D. The 8 sources of waste and how to eliminate them: improving performance with LEAN management techniques. http://www.gfoa.org/sites/default /files/GFR_DEC_11_18.pdf. Updated December, 2011. Accessed April 14, 2017.
22. Few S. What is a dashboard? In: Wheeler C, ed. Information Dashboard Design: The Effective Visual Communication of Data. 1st ed. Sebastopol, CA: O’Reilly Media; 2006:34.
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The American Cancer Society estimates that there were 1.68 million newly diagnosed cases of cancer in the U.S. in 2016, with an associated 595,690 deaths.1 Of this number, about 3% was attributable to head and neck cancer (HNC), with 48,330 new cases and 9,570 deaths in 2016. Cancer is among the leading causes of death worldwide, and veterans have a prevalence of HNC nearly twice that of the general population.2 The number of people living with and beyond a cancer diagnosis in the U.S. has risen to an estimated 15.5 million survivors.
Head and neck cancer comprises several subsites, including the oral cavity (lips, buccal mucosa, anterior tongue, floor of mouth, hard palate, and gingiva), the pharynx (nasopharynx, oropharynx, and hypopharynx), the larynx (supraglottis, glottis, and subglottis), the nasal cavity, paranasal sinuses, and the saliva glands.3 The economic burden for HNC treatment was estimated at $3.64 billion in 2010.4
Treatment is based on primary site and staging, and staging is according to the tumor node metastasis system of the American Joint Committee on Cancer.5 In general, lower stages (in situ, stages I and II) are treated with single modalities of organ-sparing surgery or radiation, whereas higher stages (stages III and IV) are treated with multiple modalities, which may include radiation combined with chemotherapy or surgery before or after radiation/chemotherapy.
Survival rate after treatment varies by primary site, cancer stage at diagnosis, histopathologic cell type, viral association, tobacco use, chemical exposure, and treatment modality; survival ranges from 24% to 90% at 5 years based on these variables.6 There is not yet a reliable blood test or other biochemical marker for recurrence, and serial radiologic examinations are expensive and expose the survivor to large amounts of additional ionizing radiation.7,8 Surveillance for recurrence after treatment consists primarily of physical examination and reported symptoms, which may be difficult for the primary care provider (PCP) to perform and distinguish from treatment sequelae.9,10 Thus, HNC survivors are followed in the ear, nose, and throat (ENT) otolaryngology clinic on a decreasing frequency schedule based on risk of relapse, second primaries, treatment sequelae, and toxicities (every 1-3 months in year 1, 2-6 months in year 2, 4-8 months in years 3-5, and every 12 months after 5 years) according to the National Comprehensive Cancer Network (NCCN) guidelines.11
Adherence with posttreatment surveillance in HNC recently was associated with length of survival; however, this observation at a single tertiary academic center was discordant with earlier published reports.12-15 About 80% to 90% of all postcurative intent treatment recurrences and second primary cancers occur within the first 4 years, with a better functional outcome if the recurrence is surgically salvageable or amenable to adjuvant radiation or combined radiation and chemotherapy.16,17 Nonadherence is generally associated with worse clinical and acute care utilization outcomes.18
Problem
At the Raymond G. Murphy VAMC, a tertiary care center in Albuquerque, New Mexico, there was a propensity of veteran HNC patients who missed scheduled surveillance appointments or were lost to follow-up. An informal review of several VA ENT departments revealed similar issues without any consistent method to solve the problem. In an effort to recapture these patients, in 2011 an ENT registered nurse (RN) was added to the team as cancer care coordinator (CCC). After several weeks of chart review of clinic records, it was determined that 31% of HNC patients had missed 1 or more ongoing surveillance appointments, either by patient no-show, clinic cancellations that failed to reschedule patients, or patient cancellation without rescheduling. The CCC was tasked with recapturing these lost patients, returning them to regular follow-up per NCCN guidelines, and tracking new cancer patients as they were diagnosed and progressed through treatment and surveillance. As there had been no one previously in this role in the ENT clinic, there was no guidance about how to proceed.
The mechanism in place for rescheduling no-show patients at that time consisted of a mailed postcard reminder sent by a medical support assistant who requested that the veteran contact the clinic to reschedule. Veterans reported that these reminders often appeared in their mail mingled with so-called junk mail and were discarded without reading. The CCC spent several more weeks examining clinic records in the computerized patient record system (CPRS), looking for patients with cancer in the 5-year surveillance period, and compiling a database of survivors and newly diagnosed patients. This database was compiled initially on paper and then converted to a spreadsheet. Patients who had missed appointments were contacted by the CCC and rescheduled, which resulted in a 100% recovery rate.
Unfortunately, although the manual tracking process was successful, it was laborious and time consuming. Weekly and sometimes daily examination of CPRS clinic records for new patients and survivor adherence was followed by tedious data entry into the spreadsheet. The manual tracking system was deemed suboptimal and a Lean Six Sigma process improvement project was initiated. The project goal was to produce a dashboard database tool that was patient centered to improve the quality of cancer care to veterans.
Methods
Lean Six Sigma is a combination of 2 improvement processes and is embraced by large business and government entities with the goal of improving efficiencies, reducing waste, decreasing errors, and generating cost savings.19 The first improvement process, Six Sigma, is a statistical concept with the goal of producing no more than 3.4 defects per million opportunities.20Using specific tools, Six Sigma identifies the cause of the problem to help develop effective solutions. Six Sigma also helps uncover defects and problems by using a standardized and systematic method for each process improvement project in a sequence of steps known as DMAIC (Define, Measure, Analyze, Improve, and Control) to ensure a defect-free product at a rate of 99.99966%. Define, the first step, contains a written statement defining the problem and the goals; Measure scrutinizes the current baseline of the project in measureable data to identify possible contributing factors; Analyze uses data and tools to understand the cause-and-effect relationships in the process; Improve uses creative developments and changes that lead to process improvements; and Control takes measures to ensure the improvements are implemented, reliable, and constant.
Although slightly different but complementary, Lean focuses on streamlining improvement processes by identifying and eliminating waste that has little or no value to the customer. The 8 most common forms of waste are identified through the mnemonic DOWNTIME (Defects, Overproduction, Waiting, Not utilizing human talent, Transportation, Inventory excess, Motion excess, and Excess processing).21 When both Lean and Six Sigma are used together, the synergistic effects have a powerful impact on the complete quality improvement process and yield consistent reliability. The combined process then includes several methodologic tools for systems redesign, including root-cause analysis, defining waste barriers, measuring current and expected performance, analyzing the data collected, improving the target process, and controlling the improvements. Though already existing and used within the VA system, Lean Six Sigma training was included as a mandatory component of new employee orientation in a memo issued in August 2015 from the assistant secretary for human resources and administration (VA access-only memo VAIQ 7595924).
Root-cause analysis was accomplished using the “5 Why” technique adapted into Lean and Six Sigma from the Toyota Motor Corporation. For example, the question “Why do patients miss appointments?” was asked 5 different ways, and it was determined that many patients lacked transportation, some were not able to reschedule at the time they called to cancel their appointment, those with multiple same-day appointments at the tertiary medical center were not able to wait to schedule a follow-up appointment for fear of missing or being late to their next appointment, and others were placed on recall lists with appointment reminders that failed to accomplish the purpose of self-scheduling by veterans. Thus, the common denominator and answer to the question “why” was that there was no tracking system in place to identify and reschedule missed follow-ups, and before employing a dedicated coordinator, no one accountable for the process (Figure 1).
Wasteful barriers to efficiency were examined with particular attention to the rescheduling process. Rescheduling produced immediate duplication of work for scheduling staff and increased wait time for future appointments. There was potential for additional health care expenses related to costs of late and progressive salvage treatment or for less-than-timely correction of HNC treatment sequelae, such as scarring, lymphedema, or dysphagia. Ear, nose, and throat providers were concerned about missing occult recurrence or residual cancer.
In 2013, the Lean Six Sigma process was used again to critique efforts by the CCC to identify and track HNC patients. One suggestion was to automate the process, and the Information Resource Management (IRM) office was contacted via work order to explore options for mining CPRS data. Working with a committed health information analyst, further discussion was aimed at pulling in additional data that would simultaneously track required posttreatment laboratory results and imaging. It was decided that a secure dashboard format would provide greater utility than would an online report that the CCC had to request and generate daily.
Integrated technologist Stephen Few defines a data dashboard as “… a visual display of the most important information needed to achieve one or more objectives; consolidated and arranged on a single screen so the information can be monitored at a glance.”22 The Head & Neck Cancer Tracking Dashboard (HNC Dashboard), designed by the IRM analyst, queries the VA Corporate Data Warehouse each night to identify all patients recently diagnosed with HNC by examining outpatient visit and inpatient discharge International Classification of Disease (ICD) codes entered by providers when coding encounter notes in CPRS. It also adds those with a HNC diagnosis in the VistA problem list and the HNC pathology department Systematized Nomenclature of Medicine (SNOMED) codes (Figure 2).
The automated ENT cancer tracking dashboard prototype debuted in 2014, but several months of trial and error took place to reanalyze ICD codes and narrow the list. The dashboard underwent multiple tests to ensure accuracy. Identified patients are presented using an interactive report hosted on a secure SharePoint (Redmond,WA) site, which reduced the risk of a data breach as access requires multi-authenticated user identification from a VA computer.
Another characteristic of the dashboard’s format is the ability to add custom features as needed. Several features now included in the dashboard are location of residence, diagnosis date, ICD code, date captured in the tracking system, most recent ENT clinic visit, future scheduled ENT clinic appointment, date of last thyroid stimulating hormone (TSH) laboratory test, and date of last position emission tomography scan. In addition, cancellations, no-shows, and patients overdue for TSH testing are highlighted in bold. Highlighted fields alert the CCC to reschedule patients in a timely manner and can alert providers to order needed follow-up tests and procedures.
Among the merits of the ENT cancer tracking dashboard is ease of use. The CCC uses a simple ABC acronym to describe utilization:
- A—added: The CCC daily edits new patients added to the dashboard with a HNC diagnosis. Several times recently the CCC saw a new diagnosis before the provider had been notified by pathology of biopsy results (Figure 3).
- B—browse: The dashboard format allows for rapid perusal of critical information at a glance (Figure 4). Recent labs and imaging can be discussed with providers immediately or at weekly ENT team cancer update meetings. Notification to clinicians can be rapid if the results show suspicion for residual/recurrent disease, a second primary site, metastasis, or there is need to notify the patient’s primary care provider to treat elevated TSH levels (hypothyroidism incidence after head and neck radiation is reportedly as high as 44%, with most patients being asymptomatic or simply fatigued).10,23
- C—check: Appointments are checked for those in the future, cancelled without rescheduling, or no-show dates. Empty fields under the “Next ENT Appointment” header alert the CCC to reschedule a follow-up appointment within NCCN guidelines. Alerting providers to upcoming surveillance appointments allows timely coordination with other care providers and departments, including speech pathology, nutrition, audiology, and social work. The “ENT Recall Date” has a unique time-sensitive feature and will visually display a bold type font when ready to be scheduled for a physical appointment (Figure 5).
Results
The cancer dashboard has demonstrated its success by supporting consistent and reliable monthly data. Results recorded over a 24-month period (from January 1, 2015 through December 31, 2016) showed that the electronic tracker identified 101 new HNC patients. During this period, 1,067 HNC patients were scheduled for follow-up appointments for cancer surveillance. Of these, the authors found that 112 HNC patients had missed their appointments due to calling and cancelling or not showing up as scheduled; resulting in a no-show status. This yielded an appointment nonadherence rate of 10%. The authors also found that 73 (7%) HNC patients did not have an elected scheduled appointment to return to the clinic for continued cancer surveillance. This number comprises all HNC patients whose appointments were cancelled by clinic cancellation, self-cancellation, no-show appointments, or those who left the clinic without scheduling a subsequent follow-up appointment. The electronic tracker identified 100% of these patients as missing and needing a future appointment. These patients may have otherwise been lost through manual tracking.
Implementation and utilization of a robust automated dashboard format HNC patient tracking system has been rewarding for the ENT department. The CCC has saved an estimated 600 to 800 hours per year of chart review and data entry. Although a time study was never conducted to measure the work process of this task, it is reasonable to conclude based on the following multiple manual step-by-step processes that the CCC had to perform frequently were now performed within the dashboard: reviewing consults for HNC diagnosis, recording new patient profile data on the spreadsheet; reviewing VA hospital pathology reports for new HNC diagnoses, reviewing the clinic schedule to track patient appointment adherence, updating and recording recent appointment activity, and reviewing the electronic medical records daily for recommended treatment plan and follow-up.
A side-by-side comparison of the functional features of tracking both manually and with automation showed that automation outnumbers the function of manual tracking by 36% and offers improved efficiency (Table). This has allowed time for the CCC to participate in simultaneous HNC care initiatives, including facilitating interfacility telehealth referrals for complex cancer surgery, scheduling and monitoring rural cancer surveillance telehealth appointments, and development of an ENT Survivorship Care Plan. These programs optimize time and workflow, reduce waste, reduce expenditures related to costly treatment modalities associated with advanced stages of malignancy, and improve the veteran experience. Further benefits to the veteran HNC patient population include increased self-efficacy and awareness for disease management through continuity of care, reduced cost associated with travel expense, and reduced potential copays due to additional medical care related to advanced stages of recurrent or residual disease.
In-house development of the HNC tracking dashboard has contributed to further cost savings for the VA. Specialized third-party acquired software can cost thousands of dollars for purchase and implementation and often includes ongoing fees for use. The Sustain and Spread concept of Lean Six Sigma is proven by a 100% recapture rate of HNC patients in the ENT clinic that potentially would have been lost to follow-up. The success in Spreading this innovation forward has resulted in adoption by other VAMCs for current use and implementation. After sharing information regarding the dashboard at 2 national conferences via presentations and poster, other VAMCs in neighboring states have requested the software and initiated custom versions. Because of this success and further demand, dashboard use is currently under consideration by the VA for nationwide availability.
Conclusion
Deficiencies in tracking cancer patients in the VA system exist in part due to little or no sophisticated electronic tracking systems that could perform multiple task functions to identify new cancer patients, the type of cancer, when appointments are missed, and notification when the required labs and procedures are completed. Often, the CCC is dependent on the arduous task of inputting of data to keep him/her up-to-date with patient care and coordination in a timely manner. As new VA policies attempts to perfect and streamline the scheduling process by way of providers placing “return to clinic” orders for patient follow-up care, there remains a potential risk of those patients not getting scheduled without a vigilant tracking process in place to monitor and ensure that all patients are scheduled.
The dashboard has proved to be an easy to use and vital tool in tracking HNC patients by the CCC. It will continue to assist in the identification of new HNC patients, provide ready access to patient information and follow-up care, and help facilitate CCC and provider communication on a daily basis, thereby meeting the goal of a patient-centered product that proves to improve the quality of cancer care of veterans.
Acknowledgment
The authors thank Mr. Dominic B. Ruiz, Visual Information Specialist, at the Raymond Murphy VAMC, who created images in high resolution for this article.
Author disclosures
The authors report no actual or potential conflicts of interest with regard to this article.
Disclaimer
The opinions expressed herein are those of the authors and do not necessarily reflect those of Federal Practitioner , Frontline Medical Communications Inc., the U.S. Government, or any of its agencies.
Click here to read the digital edition.
The American Cancer Society estimates that there were 1.68 million newly diagnosed cases of cancer in the U.S. in 2016, with an associated 595,690 deaths.1 Of this number, about 3% was attributable to head and neck cancer (HNC), with 48,330 new cases and 9,570 deaths in 2016. Cancer is among the leading causes of death worldwide, and veterans have a prevalence of HNC nearly twice that of the general population.2 The number of people living with and beyond a cancer diagnosis in the U.S. has risen to an estimated 15.5 million survivors.
Head and neck cancer comprises several subsites, including the oral cavity (lips, buccal mucosa, anterior tongue, floor of mouth, hard palate, and gingiva), the pharynx (nasopharynx, oropharynx, and hypopharynx), the larynx (supraglottis, glottis, and subglottis), the nasal cavity, paranasal sinuses, and the saliva glands.3 The economic burden for HNC treatment was estimated at $3.64 billion in 2010.4
Treatment is based on primary site and staging, and staging is according to the tumor node metastasis system of the American Joint Committee on Cancer.5 In general, lower stages (in situ, stages I and II) are treated with single modalities of organ-sparing surgery or radiation, whereas higher stages (stages III and IV) are treated with multiple modalities, which may include radiation combined with chemotherapy or surgery before or after radiation/chemotherapy.
Survival rate after treatment varies by primary site, cancer stage at diagnosis, histopathologic cell type, viral association, tobacco use, chemical exposure, and treatment modality; survival ranges from 24% to 90% at 5 years based on these variables.6 There is not yet a reliable blood test or other biochemical marker for recurrence, and serial radiologic examinations are expensive and expose the survivor to large amounts of additional ionizing radiation.7,8 Surveillance for recurrence after treatment consists primarily of physical examination and reported symptoms, which may be difficult for the primary care provider (PCP) to perform and distinguish from treatment sequelae.9,10 Thus, HNC survivors are followed in the ear, nose, and throat (ENT) otolaryngology clinic on a decreasing frequency schedule based on risk of relapse, second primaries, treatment sequelae, and toxicities (every 1-3 months in year 1, 2-6 months in year 2, 4-8 months in years 3-5, and every 12 months after 5 years) according to the National Comprehensive Cancer Network (NCCN) guidelines.11
Adherence with posttreatment surveillance in HNC recently was associated with length of survival; however, this observation at a single tertiary academic center was discordant with earlier published reports.12-15 About 80% to 90% of all postcurative intent treatment recurrences and second primary cancers occur within the first 4 years, with a better functional outcome if the recurrence is surgically salvageable or amenable to adjuvant radiation or combined radiation and chemotherapy.16,17 Nonadherence is generally associated with worse clinical and acute care utilization outcomes.18
Problem
At the Raymond G. Murphy VAMC, a tertiary care center in Albuquerque, New Mexico, there was a propensity of veteran HNC patients who missed scheduled surveillance appointments or were lost to follow-up. An informal review of several VA ENT departments revealed similar issues without any consistent method to solve the problem. In an effort to recapture these patients, in 2011 an ENT registered nurse (RN) was added to the team as cancer care coordinator (CCC). After several weeks of chart review of clinic records, it was determined that 31% of HNC patients had missed 1 or more ongoing surveillance appointments, either by patient no-show, clinic cancellations that failed to reschedule patients, or patient cancellation without rescheduling. The CCC was tasked with recapturing these lost patients, returning them to regular follow-up per NCCN guidelines, and tracking new cancer patients as they were diagnosed and progressed through treatment and surveillance. As there had been no one previously in this role in the ENT clinic, there was no guidance about how to proceed.
The mechanism in place for rescheduling no-show patients at that time consisted of a mailed postcard reminder sent by a medical support assistant who requested that the veteran contact the clinic to reschedule. Veterans reported that these reminders often appeared in their mail mingled with so-called junk mail and were discarded without reading. The CCC spent several more weeks examining clinic records in the computerized patient record system (CPRS), looking for patients with cancer in the 5-year surveillance period, and compiling a database of survivors and newly diagnosed patients. This database was compiled initially on paper and then converted to a spreadsheet. Patients who had missed appointments were contacted by the CCC and rescheduled, which resulted in a 100% recovery rate.
Unfortunately, although the manual tracking process was successful, it was laborious and time consuming. Weekly and sometimes daily examination of CPRS clinic records for new patients and survivor adherence was followed by tedious data entry into the spreadsheet. The manual tracking system was deemed suboptimal and a Lean Six Sigma process improvement project was initiated. The project goal was to produce a dashboard database tool that was patient centered to improve the quality of cancer care to veterans.
Methods
Lean Six Sigma is a combination of 2 improvement processes and is embraced by large business and government entities with the goal of improving efficiencies, reducing waste, decreasing errors, and generating cost savings.19 The first improvement process, Six Sigma, is a statistical concept with the goal of producing no more than 3.4 defects per million opportunities.20Using specific tools, Six Sigma identifies the cause of the problem to help develop effective solutions. Six Sigma also helps uncover defects and problems by using a standardized and systematic method for each process improvement project in a sequence of steps known as DMAIC (Define, Measure, Analyze, Improve, and Control) to ensure a defect-free product at a rate of 99.99966%. Define, the first step, contains a written statement defining the problem and the goals; Measure scrutinizes the current baseline of the project in measureable data to identify possible contributing factors; Analyze uses data and tools to understand the cause-and-effect relationships in the process; Improve uses creative developments and changes that lead to process improvements; and Control takes measures to ensure the improvements are implemented, reliable, and constant.
Although slightly different but complementary, Lean focuses on streamlining improvement processes by identifying and eliminating waste that has little or no value to the customer. The 8 most common forms of waste are identified through the mnemonic DOWNTIME (Defects, Overproduction, Waiting, Not utilizing human talent, Transportation, Inventory excess, Motion excess, and Excess processing).21 When both Lean and Six Sigma are used together, the synergistic effects have a powerful impact on the complete quality improvement process and yield consistent reliability. The combined process then includes several methodologic tools for systems redesign, including root-cause analysis, defining waste barriers, measuring current and expected performance, analyzing the data collected, improving the target process, and controlling the improvements. Though already existing and used within the VA system, Lean Six Sigma training was included as a mandatory component of new employee orientation in a memo issued in August 2015 from the assistant secretary for human resources and administration (VA access-only memo VAIQ 7595924).
Root-cause analysis was accomplished using the “5 Why” technique adapted into Lean and Six Sigma from the Toyota Motor Corporation. For example, the question “Why do patients miss appointments?” was asked 5 different ways, and it was determined that many patients lacked transportation, some were not able to reschedule at the time they called to cancel their appointment, those with multiple same-day appointments at the tertiary medical center were not able to wait to schedule a follow-up appointment for fear of missing or being late to their next appointment, and others were placed on recall lists with appointment reminders that failed to accomplish the purpose of self-scheduling by veterans. Thus, the common denominator and answer to the question “why” was that there was no tracking system in place to identify and reschedule missed follow-ups, and before employing a dedicated coordinator, no one accountable for the process (Figure 1).
Wasteful barriers to efficiency were examined with particular attention to the rescheduling process. Rescheduling produced immediate duplication of work for scheduling staff and increased wait time for future appointments. There was potential for additional health care expenses related to costs of late and progressive salvage treatment or for less-than-timely correction of HNC treatment sequelae, such as scarring, lymphedema, or dysphagia. Ear, nose, and throat providers were concerned about missing occult recurrence or residual cancer.
In 2013, the Lean Six Sigma process was used again to critique efforts by the CCC to identify and track HNC patients. One suggestion was to automate the process, and the Information Resource Management (IRM) office was contacted via work order to explore options for mining CPRS data. Working with a committed health information analyst, further discussion was aimed at pulling in additional data that would simultaneously track required posttreatment laboratory results and imaging. It was decided that a secure dashboard format would provide greater utility than would an online report that the CCC had to request and generate daily.
Integrated technologist Stephen Few defines a data dashboard as “… a visual display of the most important information needed to achieve one or more objectives; consolidated and arranged on a single screen so the information can be monitored at a glance.”22 The Head & Neck Cancer Tracking Dashboard (HNC Dashboard), designed by the IRM analyst, queries the VA Corporate Data Warehouse each night to identify all patients recently diagnosed with HNC by examining outpatient visit and inpatient discharge International Classification of Disease (ICD) codes entered by providers when coding encounter notes in CPRS. It also adds those with a HNC diagnosis in the VistA problem list and the HNC pathology department Systematized Nomenclature of Medicine (SNOMED) codes (Figure 2).
The automated ENT cancer tracking dashboard prototype debuted in 2014, but several months of trial and error took place to reanalyze ICD codes and narrow the list. The dashboard underwent multiple tests to ensure accuracy. Identified patients are presented using an interactive report hosted on a secure SharePoint (Redmond,WA) site, which reduced the risk of a data breach as access requires multi-authenticated user identification from a VA computer.
Another characteristic of the dashboard’s format is the ability to add custom features as needed. Several features now included in the dashboard are location of residence, diagnosis date, ICD code, date captured in the tracking system, most recent ENT clinic visit, future scheduled ENT clinic appointment, date of last thyroid stimulating hormone (TSH) laboratory test, and date of last position emission tomography scan. In addition, cancellations, no-shows, and patients overdue for TSH testing are highlighted in bold. Highlighted fields alert the CCC to reschedule patients in a timely manner and can alert providers to order needed follow-up tests and procedures.
Among the merits of the ENT cancer tracking dashboard is ease of use. The CCC uses a simple ABC acronym to describe utilization:
- A—added: The CCC daily edits new patients added to the dashboard with a HNC diagnosis. Several times recently the CCC saw a new diagnosis before the provider had been notified by pathology of biopsy results (Figure 3).
- B—browse: The dashboard format allows for rapid perusal of critical information at a glance (Figure 4). Recent labs and imaging can be discussed with providers immediately or at weekly ENT team cancer update meetings. Notification to clinicians can be rapid if the results show suspicion for residual/recurrent disease, a second primary site, metastasis, or there is need to notify the patient’s primary care provider to treat elevated TSH levels (hypothyroidism incidence after head and neck radiation is reportedly as high as 44%, with most patients being asymptomatic or simply fatigued).10,23
- C—check: Appointments are checked for those in the future, cancelled without rescheduling, or no-show dates. Empty fields under the “Next ENT Appointment” header alert the CCC to reschedule a follow-up appointment within NCCN guidelines. Alerting providers to upcoming surveillance appointments allows timely coordination with other care providers and departments, including speech pathology, nutrition, audiology, and social work. The “ENT Recall Date” has a unique time-sensitive feature and will visually display a bold type font when ready to be scheduled for a physical appointment (Figure 5).
Results
The cancer dashboard has demonstrated its success by supporting consistent and reliable monthly data. Results recorded over a 24-month period (from January 1, 2015 through December 31, 2016) showed that the electronic tracker identified 101 new HNC patients. During this period, 1,067 HNC patients were scheduled for follow-up appointments for cancer surveillance. Of these, the authors found that 112 HNC patients had missed their appointments due to calling and cancelling or not showing up as scheduled; resulting in a no-show status. This yielded an appointment nonadherence rate of 10%. The authors also found that 73 (7%) HNC patients did not have an elected scheduled appointment to return to the clinic for continued cancer surveillance. This number comprises all HNC patients whose appointments were cancelled by clinic cancellation, self-cancellation, no-show appointments, or those who left the clinic without scheduling a subsequent follow-up appointment. The electronic tracker identified 100% of these patients as missing and needing a future appointment. These patients may have otherwise been lost through manual tracking.
Implementation and utilization of a robust automated dashboard format HNC patient tracking system has been rewarding for the ENT department. The CCC has saved an estimated 600 to 800 hours per year of chart review and data entry. Although a time study was never conducted to measure the work process of this task, it is reasonable to conclude based on the following multiple manual step-by-step processes that the CCC had to perform frequently were now performed within the dashboard: reviewing consults for HNC diagnosis, recording new patient profile data on the spreadsheet; reviewing VA hospital pathology reports for new HNC diagnoses, reviewing the clinic schedule to track patient appointment adherence, updating and recording recent appointment activity, and reviewing the electronic medical records daily for recommended treatment plan and follow-up.
A side-by-side comparison of the functional features of tracking both manually and with automation showed that automation outnumbers the function of manual tracking by 36% and offers improved efficiency (Table). This has allowed time for the CCC to participate in simultaneous HNC care initiatives, including facilitating interfacility telehealth referrals for complex cancer surgery, scheduling and monitoring rural cancer surveillance telehealth appointments, and development of an ENT Survivorship Care Plan. These programs optimize time and workflow, reduce waste, reduce expenditures related to costly treatment modalities associated with advanced stages of malignancy, and improve the veteran experience. Further benefits to the veteran HNC patient population include increased self-efficacy and awareness for disease management through continuity of care, reduced cost associated with travel expense, and reduced potential copays due to additional medical care related to advanced stages of recurrent or residual disease.
In-house development of the HNC tracking dashboard has contributed to further cost savings for the VA. Specialized third-party acquired software can cost thousands of dollars for purchase and implementation and often includes ongoing fees for use. The Sustain and Spread concept of Lean Six Sigma is proven by a 100% recapture rate of HNC patients in the ENT clinic that potentially would have been lost to follow-up. The success in Spreading this innovation forward has resulted in adoption by other VAMCs for current use and implementation. After sharing information regarding the dashboard at 2 national conferences via presentations and poster, other VAMCs in neighboring states have requested the software and initiated custom versions. Because of this success and further demand, dashboard use is currently under consideration by the VA for nationwide availability.
Conclusion
Deficiencies in tracking cancer patients in the VA system exist in part due to little or no sophisticated electronic tracking systems that could perform multiple task functions to identify new cancer patients, the type of cancer, when appointments are missed, and notification when the required labs and procedures are completed. Often, the CCC is dependent on the arduous task of inputting of data to keep him/her up-to-date with patient care and coordination in a timely manner. As new VA policies attempts to perfect and streamline the scheduling process by way of providers placing “return to clinic” orders for patient follow-up care, there remains a potential risk of those patients not getting scheduled without a vigilant tracking process in place to monitor and ensure that all patients are scheduled.
The dashboard has proved to be an easy to use and vital tool in tracking HNC patients by the CCC. It will continue to assist in the identification of new HNC patients, provide ready access to patient information and follow-up care, and help facilitate CCC and provider communication on a daily basis, thereby meeting the goal of a patient-centered product that proves to improve the quality of cancer care of veterans.
Acknowledgment
The authors thank Mr. Dominic B. Ruiz, Visual Information Specialist, at the Raymond Murphy VAMC, who created images in high resolution for this article.
Author disclosures
The authors report no actual or potential conflicts of interest with regard to this article.
Disclaimer
The opinions expressed herein are those of the authors and do not necessarily reflect those of Federal Practitioner , Frontline Medical Communications Inc., the U.S. Government, or any of its agencies.
Click here to read the digital edition.
1. Siegel RL, Miller KD, Jemal A. Cancer statistics, 2016. CA Cancer J Clin. 2016;66(1):7-30.
2. Patil RD, Meinzen-Derr JK, Hendricks BL, Patil YJ. Improving access and timelines of care for veterans with head and neck squamous cell carcinoma: a multidisciplinary team’s approach. Laryngoscope. 2016;126(3):627-631.
3. Wissinger E, Griebsch I, Lungershausen J, Foster T, Pashos CL. The economic burden of head and neck cancer: a systematic literature review. Pharmacoeconomics. 2014;32(9):865-882.
4. Mariotto AB, Yabroff KR, Shao Y, Feuer EJ, Brown ML. Projections of the cost of cancer care in the United States: 2010-2020. J Natl Cancer Inst. 2011;103(2):117-128.
5. Edge SB, Byrd DR, Compton CC, Fritz AG, Greene FL, Trotti A III, eds. American Joint Committee on Cancer Staging Manual. 7th ed. New York, NY: Springer-Verlag; 2010.
6. Cancer.net. Head and neck cancer: statistics. http://www.cancer.net/cancer-types/head-and-neck-cancer/Statistics. Updated September 2016. Accessed April 12, 2017.
7. Rachidi S, Wallace K, Wrangle JM, Day TA, Alberg AJ, Li Z. Neutrophil-to-lymphocyte ratio and overall survival in all sites of head and neck squamous cell carcinoma. Head Neck. 2016;38(suppl 1):E1068-E1074.
8. Cheung PK, Chin RY, Eslick GD. Detecting residual/recurrent head neck squamous cell carcinomas using PET or PET/CT: systematic review and meta-analysis. Arch Otolaryngol Head Neck Surg. 2016;154(3):421-432.
9. Haddad RI, Limaye S. Overview of approach to long-term survivors of head and neck cancer. http://www .uptodate .com/contents/overview-of-approach-to-long-term-survivors-of-head-and-neck-cancer. Updated October 26, 2016. Accessed April 12, 2017.
10. Manikantan K, Khode S, Dwivedi RC, et al. Making sense of post-treatment surveillance in head and neck cancer: when and what of follow-up. Cancer Treat Rev. 2009;35(8):744-753.
11. National Comprehensive Cancer Network. NCCN Clinical practice guidelines in onclology:head and neck cancers(2.2017).2017. Updated May 8, 2017. https://www.nccn.org/professionals/physician_gls/f_/pdf/head-and-neck.pdf. Accessed July 18, 2017.
12. Deutschmann MW, Sykes KJ, Harbison J, Cabrera-Muffly C, Schnayder Y. The impact of compliance in post treatment surveillance in head and neck squamous cell carcinoma. JAMA Otolaryngol Head Neck Surg. 2015;141(6):519-525.
13. Merkx MA, van Gulick JJ, Marres HA, et al. Effectiveness of routine follow-up of patients treated for T1-2N0 oral squamous cell carcinomas of the floor of mouth and tongue. Head Neck. 2006:28(1):1-7.
14. Ritoe SC, de Vegt F, Scheike IM, et al. Effect of routine follow-up after treatment for laryngeal cancer on life expectancy and mortality: results of a Markov model analysis. Cancer. 2007;109(2):239-247.
15. Agrawal A, Hammond TH, Young GS, Avon AL, Ozer E, Schuller DE. Factors affecting long-term survival in patients with recurrent head and neck cancer may help define the role of post-treatment surveillance. Laryngoscope. 2009;119(11):2135-2140.
16. Roland NJ, Bradley PJ. The role of surgery in the palliation of head and neck cancer. Curr Opin Otolaryngol Head Neck Surg. 2014;22(2):101-108.
17. Riaz N, Hong JC, Sherman EJ, et al. A nomogram to predict loco-regional control after re-irradiation for head and neck cancer. Radiother Oncol. 2014;111(3):382-387.
18. Hwang AS, Atlas SJ, Cronin P, et al. Appointment “no-shows” are an independent predictor of subsequent quality of care and resource utilization outcomes. J Gen Intern Med. 2015;30(10):1426-1433.
19. Healthcare Daily Online. VA healthcare system adopts lean six sigma. http://www.healthcaredailyonline.com/news/va-lean-six-sigma-in-healthcare. Updated December 7, 2015. Accessed April 12, 2017.
20. Gygi C, Williams B. Six Sigma for Dummies. 2nd edition. Hoboken, NJ: John Wiley & Sons; 2012.
21. Kavanagh S, Krings D. The 8 sources of waste and how to eliminate them: improving performance with LEAN management techniques. http://www.gfoa.org/sites/default /files/GFR_DEC_11_18.pdf. Updated December, 2011. Accessed April 14, 2017.
22. Few S. What is a dashboard? In: Wheeler C, ed. Information Dashboard Design: The Effective Visual Communication of Data. 1st ed. Sebastopol, CA: O’Reilly Media; 2006:34.
23. Murthy V, Narang K, Ghosh-Laskar S, Gupta T, Budrukkar A, Agrawal JP. Hypothyroidism after 3-dimensional conformal radiotherapy and intensity-modulated radiotherapy for head and neck cancers: prospective data from 2 randomized controlled trials. Head Neck. 2014;36(11):1573-1780.
1. Siegel RL, Miller KD, Jemal A. Cancer statistics, 2016. CA Cancer J Clin. 2016;66(1):7-30.
2. Patil RD, Meinzen-Derr JK, Hendricks BL, Patil YJ. Improving access and timelines of care for veterans with head and neck squamous cell carcinoma: a multidisciplinary team’s approach. Laryngoscope. 2016;126(3):627-631.
3. Wissinger E, Griebsch I, Lungershausen J, Foster T, Pashos CL. The economic burden of head and neck cancer: a systematic literature review. Pharmacoeconomics. 2014;32(9):865-882.
4. Mariotto AB, Yabroff KR, Shao Y, Feuer EJ, Brown ML. Projections of the cost of cancer care in the United States: 2010-2020. J Natl Cancer Inst. 2011;103(2):117-128.
5. Edge SB, Byrd DR, Compton CC, Fritz AG, Greene FL, Trotti A III, eds. American Joint Committee on Cancer Staging Manual. 7th ed. New York, NY: Springer-Verlag; 2010.
6. Cancer.net. Head and neck cancer: statistics. http://www.cancer.net/cancer-types/head-and-neck-cancer/Statistics. Updated September 2016. Accessed April 12, 2017.
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