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Cancer screening in elderly: When to just say no
ESTES PARK, COLO. – A simple walking speed measurement over a 20-foot distance is an invaluable guide to physiologic age as part of individualized decision making about when to stop cancer screening in elderly patients, according to Jeff Wallace, MD, professor of geriatric medicine at the University of Colorado at Denver.
“If you have one measurement to assess ‘am I aging well?’ it’s your gait speed. A lot of us in geriatrics are advocating evaluation of gait speed in all patients as a fifth vital sign. It’s probably more useful than blood pressure in some of the older adults coming into our clinics,” he said at a conference on internal medicine sponsored by the University of Colorado.
Dr. Wallace also gave a shout-out to the ePrognosis cancer-screening decision tool, available free at www.eprognosis.org, as an aid in shared decision-making conversations regarding when to stop cancer screening. This tool, developed by researchers at the University of California, San Francisco, allows physicians to plug key individual patient characteristics into its model, including comorbid conditions, functional status, and body mass index, and then spits out data-driven estimated benefits and harms a patient can expect from advanced-age screening for colon or breast cancer.
Of course, guidelines as to when to stop screening for various cancers are available from the U.S. Preventive Services Task Force, the American Cancer Society, and specialty societies. However, it’s important that nongeriatricians understand the serious limitations of those guidelines.
“We’re not guidelines followers in the geriatrics world because the guidelines don’t apply to most of our patients,” he explained. “We hate guidelines in geriatrics because few studies – and no lung cancer or breast cancer trials – enroll patients over age 75 with comorbid conditions. Also, most of these guidelines do not incorporate patient preferences, which probably should be a primary goal. So we’re left extrapolating.“
Regrettably, though, “it turns out most Americans are drinking the Kool-Aid when it comes to patient preferences. It’s amazing how much cancer screening is going on in this country. We’re doing a lot more than we should,” said Dr. Wallace.
All of that is clearly overscreening. Experts unanimously agree that if someone is not going to live for 10 years, that person is not likely to benefit from cancer screening. The one exception is lung cancer screening of high-risk patients, where there are data to show that annual low-dose CT screening is beneficial in those with even a 5-year life expectancy.
As part of the Choosing Wisely program, the American Geriatric Society has advocated that physicians “don’t recommend screening for breast, colorectal, prostate, or lung cancer without considering life expectancy and the risks of testing, overdiagnosis, and overtreatment.”
That’s where gait speed and ePrognosis come in handy in discussions with patients regarding what they can realistically expect from cancer screening at an advanced age.
The importance of gait speed was highlighted in a pooled analysis of nine cohort studies totaling more than 34,000 community-dwelling adults aged 65 years and older with 6-21 years of follow-up. Investigators at the University of Pittsburgh identified a strong relationship between gait speed and survival. Every 0.1-m/sec made a significant difference (JAMA. 2011 Jan 5;305[1]:50-8).
A gait speed evaluation is simple: The patient is asked to walk 20 feet at a normal speed, not racing. For men age 75, the Pittsburgh investigators found, gait speed predicted 10-year survival across a range of 19%-87%. The median speed was 0.8 m/sec, or about 1.8 mph, so a middle-of-the-pack walker ought to stop all cancer screening by age 75. A fast-walking older man won’t reach a 10-year remaining life expectancy until he’s in his early to mid-80s; a slow walker reaches that life expectancy as early as his late 60s, depending upon just how slow he walks. A woman at age 80 with an average gait speed has roughly 10 years of remaining life, factoring in plus or minus 5 years from that landmark depending upon whether she is a faster- or slower-than-average walker, Dr. Wallace explained.
The U.S. Preventive Services Task Force currently recommends colon cancer screening routinely for 50- to 75-year-olds, declaring in accord with other groups that this strategy has a high certainty of substantial net benefit. But the USPSTF also recommends selective screening for those aged 76-85, with a weaker C recommendation (JAMA. 2016 Jun 21;315[23]:2564-75).
What are the practical implications of that recommendation for selective screening after age 75?
Investigators at Harvard Medical School and the University of Oslo recently took a closer look. Their population-based, prospective, observational study included 1,355,692 Medicare beneficiaries aged 70-79 years at average risk for colorectal cancer who had not had a colonoscopy within the previous 5 years.
The investigators demonstrated that the benefit of screening colonoscopy decreased with age. For patients aged 70-74, the 8-year risk of colorectal cancer was 2.19% in those who were screened, compared with 2.62% in those who weren’t, for an absolute 0.43% difference. The number needed to be screened to detect one additional case of colorectal cancer was 283. Among those aged 75-79, the number needed to be screened climbed to 714 (Ann Intern Med. 2017 Jan 3;166[1]18-26).
Moreover, the risk of colonoscopy-related adverse events also climbed with age. These included perforations, falls while racing to the bathroom during the preprocedural bowel prep, and the humiliation of fecal incontinence. The excess 30-day risk for any adverse event in the colonoscopy group was 5.6 events per 1,000 patients aged 70-74 and 10.3 per 1,000 in 75- to 79-year-olds.
In a similar vein, Mara A. Schonberg, MD, of Harvard Medical School, Boston, has shed light on the risks and benefits of biannual mammographic screening for breast cancer in 70- to 79-year-olds, a practice recommended in American Cancer Society guidelines for women who are in overall good health and have at least a 10-year life expectancy.
She estimated that 2 women per 1,000 screened would avoid death due to breast cancer, for a number needed to screen of 500. But roughly 200 of those 1,000 women would experience a false-positive mammogram, and 20-40 of those false-positive imaging studies would result in a breast biopsy. Also, roughly 30% of the screen-detected cancers would not otherwise become apparent in an older woman’s lifetime, yet nearly all of the malignancies would undergo breast cancer therapy (J Am Geriatr Soc. 2016 Dec;64[12]:2413-8).
Dr. Schonberg’s research speaks to Dr. Wallace.
“It’s breast cancer therapy: It’s procedures; it’s medicalizing the patient’s whole life and creating a high degree of angst when she’s 75 or 80,” he said.
As to when to ‘just say no’ to cancer screening, Dr. Wallace said his answer is after age 65 for cervical cancer screening in women with at least two normal screens in the past 10 years or a prior total hysterectomy for a benign indication. All of the guidelines agree on that, although the American Congress of Obstetricians and Gynecologists recommends in addition that women with cervical intraepithelial neoplasia 2 be screened for the next 20 years.
For prostate cancer, Dr. Wallace recommends his colleagues just say no to screening at age 70 and above because harm is more likely than benefit to ensue.
“I don’t know about you, but I have a ton of patients over age 70 asking me for PSAs. That’s one place I won’t do any screening. I tell them I know you’re in great shape for 76 and you think it’s a good idea, but I think it’s bad medicine and I won’t do it. Even the American Urological Association says don’t do it after age 70,” he said.
For prostate cancer screening at age 55-69, however, patient preference rules the day, he added.
He draws the line at any cancer screening in patients aged 90 or over. Mean survival at age 90 is another 4-5 years. Only 11% of 90-year-old women will reach 100.
“Everybody has to die eventually,” he mused.
Dr. Wallace reported having no financial conflicts regarding his presentation.
ESTES PARK, COLO. – A simple walking speed measurement over a 20-foot distance is an invaluable guide to physiologic age as part of individualized decision making about when to stop cancer screening in elderly patients, according to Jeff Wallace, MD, professor of geriatric medicine at the University of Colorado at Denver.
“If you have one measurement to assess ‘am I aging well?’ it’s your gait speed. A lot of us in geriatrics are advocating evaluation of gait speed in all patients as a fifth vital sign. It’s probably more useful than blood pressure in some of the older adults coming into our clinics,” he said at a conference on internal medicine sponsored by the University of Colorado.
Dr. Wallace also gave a shout-out to the ePrognosis cancer-screening decision tool, available free at www.eprognosis.org, as an aid in shared decision-making conversations regarding when to stop cancer screening. This tool, developed by researchers at the University of California, San Francisco, allows physicians to plug key individual patient characteristics into its model, including comorbid conditions, functional status, and body mass index, and then spits out data-driven estimated benefits and harms a patient can expect from advanced-age screening for colon or breast cancer.
Of course, guidelines as to when to stop screening for various cancers are available from the U.S. Preventive Services Task Force, the American Cancer Society, and specialty societies. However, it’s important that nongeriatricians understand the serious limitations of those guidelines.
“We’re not guidelines followers in the geriatrics world because the guidelines don’t apply to most of our patients,” he explained. “We hate guidelines in geriatrics because few studies – and no lung cancer or breast cancer trials – enroll patients over age 75 with comorbid conditions. Also, most of these guidelines do not incorporate patient preferences, which probably should be a primary goal. So we’re left extrapolating.“
Regrettably, though, “it turns out most Americans are drinking the Kool-Aid when it comes to patient preferences. It’s amazing how much cancer screening is going on in this country. We’re doing a lot more than we should,” said Dr. Wallace.
All of that is clearly overscreening. Experts unanimously agree that if someone is not going to live for 10 years, that person is not likely to benefit from cancer screening. The one exception is lung cancer screening of high-risk patients, where there are data to show that annual low-dose CT screening is beneficial in those with even a 5-year life expectancy.
As part of the Choosing Wisely program, the American Geriatric Society has advocated that physicians “don’t recommend screening for breast, colorectal, prostate, or lung cancer without considering life expectancy and the risks of testing, overdiagnosis, and overtreatment.”
That’s where gait speed and ePrognosis come in handy in discussions with patients regarding what they can realistically expect from cancer screening at an advanced age.
The importance of gait speed was highlighted in a pooled analysis of nine cohort studies totaling more than 34,000 community-dwelling adults aged 65 years and older with 6-21 years of follow-up. Investigators at the University of Pittsburgh identified a strong relationship between gait speed and survival. Every 0.1-m/sec made a significant difference (JAMA. 2011 Jan 5;305[1]:50-8).
A gait speed evaluation is simple: The patient is asked to walk 20 feet at a normal speed, not racing. For men age 75, the Pittsburgh investigators found, gait speed predicted 10-year survival across a range of 19%-87%. The median speed was 0.8 m/sec, or about 1.8 mph, so a middle-of-the-pack walker ought to stop all cancer screening by age 75. A fast-walking older man won’t reach a 10-year remaining life expectancy until he’s in his early to mid-80s; a slow walker reaches that life expectancy as early as his late 60s, depending upon just how slow he walks. A woman at age 80 with an average gait speed has roughly 10 years of remaining life, factoring in plus or minus 5 years from that landmark depending upon whether she is a faster- or slower-than-average walker, Dr. Wallace explained.
The U.S. Preventive Services Task Force currently recommends colon cancer screening routinely for 50- to 75-year-olds, declaring in accord with other groups that this strategy has a high certainty of substantial net benefit. But the USPSTF also recommends selective screening for those aged 76-85, with a weaker C recommendation (JAMA. 2016 Jun 21;315[23]:2564-75).
What are the practical implications of that recommendation for selective screening after age 75?
Investigators at Harvard Medical School and the University of Oslo recently took a closer look. Their population-based, prospective, observational study included 1,355,692 Medicare beneficiaries aged 70-79 years at average risk for colorectal cancer who had not had a colonoscopy within the previous 5 years.
The investigators demonstrated that the benefit of screening colonoscopy decreased with age. For patients aged 70-74, the 8-year risk of colorectal cancer was 2.19% in those who were screened, compared with 2.62% in those who weren’t, for an absolute 0.43% difference. The number needed to be screened to detect one additional case of colorectal cancer was 283. Among those aged 75-79, the number needed to be screened climbed to 714 (Ann Intern Med. 2017 Jan 3;166[1]18-26).
Moreover, the risk of colonoscopy-related adverse events also climbed with age. These included perforations, falls while racing to the bathroom during the preprocedural bowel prep, and the humiliation of fecal incontinence. The excess 30-day risk for any adverse event in the colonoscopy group was 5.6 events per 1,000 patients aged 70-74 and 10.3 per 1,000 in 75- to 79-year-olds.
In a similar vein, Mara A. Schonberg, MD, of Harvard Medical School, Boston, has shed light on the risks and benefits of biannual mammographic screening for breast cancer in 70- to 79-year-olds, a practice recommended in American Cancer Society guidelines for women who are in overall good health and have at least a 10-year life expectancy.
She estimated that 2 women per 1,000 screened would avoid death due to breast cancer, for a number needed to screen of 500. But roughly 200 of those 1,000 women would experience a false-positive mammogram, and 20-40 of those false-positive imaging studies would result in a breast biopsy. Also, roughly 30% of the screen-detected cancers would not otherwise become apparent in an older woman’s lifetime, yet nearly all of the malignancies would undergo breast cancer therapy (J Am Geriatr Soc. 2016 Dec;64[12]:2413-8).
Dr. Schonberg’s research speaks to Dr. Wallace.
“It’s breast cancer therapy: It’s procedures; it’s medicalizing the patient’s whole life and creating a high degree of angst when she’s 75 or 80,” he said.
As to when to ‘just say no’ to cancer screening, Dr. Wallace said his answer is after age 65 for cervical cancer screening in women with at least two normal screens in the past 10 years or a prior total hysterectomy for a benign indication. All of the guidelines agree on that, although the American Congress of Obstetricians and Gynecologists recommends in addition that women with cervical intraepithelial neoplasia 2 be screened for the next 20 years.
For prostate cancer, Dr. Wallace recommends his colleagues just say no to screening at age 70 and above because harm is more likely than benefit to ensue.
“I don’t know about you, but I have a ton of patients over age 70 asking me for PSAs. That’s one place I won’t do any screening. I tell them I know you’re in great shape for 76 and you think it’s a good idea, but I think it’s bad medicine and I won’t do it. Even the American Urological Association says don’t do it after age 70,” he said.
For prostate cancer screening at age 55-69, however, patient preference rules the day, he added.
He draws the line at any cancer screening in patients aged 90 or over. Mean survival at age 90 is another 4-5 years. Only 11% of 90-year-old women will reach 100.
“Everybody has to die eventually,” he mused.
Dr. Wallace reported having no financial conflicts regarding his presentation.
ESTES PARK, COLO. – A simple walking speed measurement over a 20-foot distance is an invaluable guide to physiologic age as part of individualized decision making about when to stop cancer screening in elderly patients, according to Jeff Wallace, MD, professor of geriatric medicine at the University of Colorado at Denver.
“If you have one measurement to assess ‘am I aging well?’ it’s your gait speed. A lot of us in geriatrics are advocating evaluation of gait speed in all patients as a fifth vital sign. It’s probably more useful than blood pressure in some of the older adults coming into our clinics,” he said at a conference on internal medicine sponsored by the University of Colorado.
Dr. Wallace also gave a shout-out to the ePrognosis cancer-screening decision tool, available free at www.eprognosis.org, as an aid in shared decision-making conversations regarding when to stop cancer screening. This tool, developed by researchers at the University of California, San Francisco, allows physicians to plug key individual patient characteristics into its model, including comorbid conditions, functional status, and body mass index, and then spits out data-driven estimated benefits and harms a patient can expect from advanced-age screening for colon or breast cancer.
Of course, guidelines as to when to stop screening for various cancers are available from the U.S. Preventive Services Task Force, the American Cancer Society, and specialty societies. However, it’s important that nongeriatricians understand the serious limitations of those guidelines.
“We’re not guidelines followers in the geriatrics world because the guidelines don’t apply to most of our patients,” he explained. “We hate guidelines in geriatrics because few studies – and no lung cancer or breast cancer trials – enroll patients over age 75 with comorbid conditions. Also, most of these guidelines do not incorporate patient preferences, which probably should be a primary goal. So we’re left extrapolating.“
Regrettably, though, “it turns out most Americans are drinking the Kool-Aid when it comes to patient preferences. It’s amazing how much cancer screening is going on in this country. We’re doing a lot more than we should,” said Dr. Wallace.
All of that is clearly overscreening. Experts unanimously agree that if someone is not going to live for 10 years, that person is not likely to benefit from cancer screening. The one exception is lung cancer screening of high-risk patients, where there are data to show that annual low-dose CT screening is beneficial in those with even a 5-year life expectancy.
As part of the Choosing Wisely program, the American Geriatric Society has advocated that physicians “don’t recommend screening for breast, colorectal, prostate, or lung cancer without considering life expectancy and the risks of testing, overdiagnosis, and overtreatment.”
That’s where gait speed and ePrognosis come in handy in discussions with patients regarding what they can realistically expect from cancer screening at an advanced age.
The importance of gait speed was highlighted in a pooled analysis of nine cohort studies totaling more than 34,000 community-dwelling adults aged 65 years and older with 6-21 years of follow-up. Investigators at the University of Pittsburgh identified a strong relationship between gait speed and survival. Every 0.1-m/sec made a significant difference (JAMA. 2011 Jan 5;305[1]:50-8).
A gait speed evaluation is simple: The patient is asked to walk 20 feet at a normal speed, not racing. For men age 75, the Pittsburgh investigators found, gait speed predicted 10-year survival across a range of 19%-87%. The median speed was 0.8 m/sec, or about 1.8 mph, so a middle-of-the-pack walker ought to stop all cancer screening by age 75. A fast-walking older man won’t reach a 10-year remaining life expectancy until he’s in his early to mid-80s; a slow walker reaches that life expectancy as early as his late 60s, depending upon just how slow he walks. A woman at age 80 with an average gait speed has roughly 10 years of remaining life, factoring in plus or minus 5 years from that landmark depending upon whether she is a faster- or slower-than-average walker, Dr. Wallace explained.
The U.S. Preventive Services Task Force currently recommends colon cancer screening routinely for 50- to 75-year-olds, declaring in accord with other groups that this strategy has a high certainty of substantial net benefit. But the USPSTF also recommends selective screening for those aged 76-85, with a weaker C recommendation (JAMA. 2016 Jun 21;315[23]:2564-75).
What are the practical implications of that recommendation for selective screening after age 75?
Investigators at Harvard Medical School and the University of Oslo recently took a closer look. Their population-based, prospective, observational study included 1,355,692 Medicare beneficiaries aged 70-79 years at average risk for colorectal cancer who had not had a colonoscopy within the previous 5 years.
The investigators demonstrated that the benefit of screening colonoscopy decreased with age. For patients aged 70-74, the 8-year risk of colorectal cancer was 2.19% in those who were screened, compared with 2.62% in those who weren’t, for an absolute 0.43% difference. The number needed to be screened to detect one additional case of colorectal cancer was 283. Among those aged 75-79, the number needed to be screened climbed to 714 (Ann Intern Med. 2017 Jan 3;166[1]18-26).
Moreover, the risk of colonoscopy-related adverse events also climbed with age. These included perforations, falls while racing to the bathroom during the preprocedural bowel prep, and the humiliation of fecal incontinence. The excess 30-day risk for any adverse event in the colonoscopy group was 5.6 events per 1,000 patients aged 70-74 and 10.3 per 1,000 in 75- to 79-year-olds.
In a similar vein, Mara A. Schonberg, MD, of Harvard Medical School, Boston, has shed light on the risks and benefits of biannual mammographic screening for breast cancer in 70- to 79-year-olds, a practice recommended in American Cancer Society guidelines for women who are in overall good health and have at least a 10-year life expectancy.
She estimated that 2 women per 1,000 screened would avoid death due to breast cancer, for a number needed to screen of 500. But roughly 200 of those 1,000 women would experience a false-positive mammogram, and 20-40 of those false-positive imaging studies would result in a breast biopsy. Also, roughly 30% of the screen-detected cancers would not otherwise become apparent in an older woman’s lifetime, yet nearly all of the malignancies would undergo breast cancer therapy (J Am Geriatr Soc. 2016 Dec;64[12]:2413-8).
Dr. Schonberg’s research speaks to Dr. Wallace.
“It’s breast cancer therapy: It’s procedures; it’s medicalizing the patient’s whole life and creating a high degree of angst when she’s 75 or 80,” he said.
As to when to ‘just say no’ to cancer screening, Dr. Wallace said his answer is after age 65 for cervical cancer screening in women with at least two normal screens in the past 10 years or a prior total hysterectomy for a benign indication. All of the guidelines agree on that, although the American Congress of Obstetricians and Gynecologists recommends in addition that women with cervical intraepithelial neoplasia 2 be screened for the next 20 years.
For prostate cancer, Dr. Wallace recommends his colleagues just say no to screening at age 70 and above because harm is more likely than benefit to ensue.
“I don’t know about you, but I have a ton of patients over age 70 asking me for PSAs. That’s one place I won’t do any screening. I tell them I know you’re in great shape for 76 and you think it’s a good idea, but I think it’s bad medicine and I won’t do it. Even the American Urological Association says don’t do it after age 70,” he said.
For prostate cancer screening at age 55-69, however, patient preference rules the day, he added.
He draws the line at any cancer screening in patients aged 90 or over. Mean survival at age 90 is another 4-5 years. Only 11% of 90-year-old women will reach 100.
“Everybody has to die eventually,” he mused.
Dr. Wallace reported having no financial conflicts regarding his presentation.
EXPERT ANALYSIS FROM THE ANNUAL INTERNAL MEDICINE PROGRAM
Wide variability found in invasive mediastinal staging rates for lung cancer
COLORADO SPRINGS – Significant variability exists between hospitals in Washington state in their rates of invasive mediastinal staging for lung cancer, Farhood Farjah, MD, reported at the annual meeting of the Western Thoracic Surgical Association.
“We found evidence of a fivefold variation in hospital-level rates of invasive mediastinal staging not explained by chance or case mix,” according to Dr. Farjah of the University of Washington, Seattle.
“This has led to substantial concerns about quality of thoracic surgical care in the community at large,” he noted.
The Washington study is the first to show hospital-by-hospital variation in rates of invasive mediastinal staging.
Invasive mediastinal staging for lung cancer is considered important because imaging is known to have a substantial false-negative rate, and staging results have a profound impact on treatment recommendations, which can range from surgery alone to additional chemoradiation therapy.
Yet the meaning of the hospital-level huge variability in practice observed in the Washington study remains unclear.
“Our understanding of the underutilization of invasive mediastinal staging is further complicated by the fact that patterns of invasive mediastinal staging are highly variable across hospitals staffed by at least one board-certified thoracic surgeon with a noncardiac practice,” Dr. Farjah explained. “This variability could be a marker of poor-quality care. However, because the guidelines are not supported by level 1 evidence, it’s equally plausible that this variability might represent uncertainty or even disagreement with the practice guidelines – and specifically about the appropriate indication for invasive staging.”
He presented a retrospective cohort study of 406 patients whose non–small cell lung cancer was resected during July 2011–December 2013 at one of five Washington hospitals, each with at least one board-certified thoracic surgeon with a noncardiac practice on staff. The four participating community hospitals and one academic medical center were involved in a National Cancer Institute–funded, physician-led quality improvement initiative.
Overall, 66% of the 406 patients underwent any form of invasive mediastinal staging: 85% by mediastinoscopy only; 12% by mediastinoscopy plus endobronchial ultrasound-guided nodal aspiration (EBUS); 3% by EBUS only; and the remaining handful by mediastinoscopy, EBUS, and esophageal ultrasound-guided nodal aspiration. The invasive staging was performed at the time of resection in 64% of cases. A median of three nodal stations were sampled.
After statistical adjustment for random variation and between-hospital differences in clinical stage, rates of invasive staging were all over the map. While an overall mean of 66% of the lung cancer patients underwent invasive mediastinal staging, the rates at the five hospitals were 94%, 84%, 31%, 80%, and 17%.
Dr. Farjah and his coinvestigators are now conducting provider interviews and focus groups in an effort to understand what drove the participating surgeons’ wide variability in performing invasive mediastinal staging.
Discussant Jane Yanagawa, MD, of the University of California, Los Angeles, commented, “I think this is a really interesting study because, historically, lower rates of mediastinoscopy are assumed to be a reflection of low-quality care – and you suggest that might not be the case, that it might be more complicated than that.”
Dr. Yanagawa sketched one fairly common scenario that might represent a surgeon’s reasonable avoidance of guideline-recommended invasive mediastinal staging: a patient who by all preoperative imaging appears to have stage IA lung cancer and wishes to avoid the morbidity, time, and cost of needle biopsy, instead choosing to go straight to the operating room for a diagnosis by wedge resection, followed by a completion lobectomy based upon the frozen section results. Could such a pathway account for the variability seen in the Washington study?
“I think it could have,” Dr. Farjah replied. “I would say that’s probably one driver of variability.”
As for the generalizability of the findings of a five-hospital study carried out in a single state, Dr. Farjah said he thinks the results are applicable to any academic or community hospital with at least one board-certified thoracic surgeon with a noncardiac practice.
He reported having no financial conflicts of interest regarding the study.
M. Patricia Rivera, MD, FCCP, comments: Staging of lung cancer is essential to select the best treatment strategy for a given patient. However, despite multiple guideline recommendations 
M. Patricia Rivera, MD, FCCP, comments: Staging of lung cancer is essential to select the best treatment strategy for a given patient. However, despite multiple guideline recommendations
M. Patricia Rivera, MD, FCCP, comments: Staging of lung cancer is essential to select the best treatment strategy for a given patient. However, despite multiple guideline recommendations
COLORADO SPRINGS – Significant variability exists between hospitals in Washington state in their rates of invasive mediastinal staging for lung cancer, Farhood Farjah, MD, reported at the annual meeting of the Western Thoracic Surgical Association.
“We found evidence of a fivefold variation in hospital-level rates of invasive mediastinal staging not explained by chance or case mix,” according to Dr. Farjah of the University of Washington, Seattle.
“This has led to substantial concerns about quality of thoracic surgical care in the community at large,” he noted.
The Washington study is the first to show hospital-by-hospital variation in rates of invasive mediastinal staging.
Invasive mediastinal staging for lung cancer is considered important because imaging is known to have a substantial false-negative rate, and staging results have a profound impact on treatment recommendations, which can range from surgery alone to additional chemoradiation therapy.
Yet the meaning of the hospital-level huge variability in practice observed in the Washington study remains unclear.
“Our understanding of the underutilization of invasive mediastinal staging is further complicated by the fact that patterns of invasive mediastinal staging are highly variable across hospitals staffed by at least one board-certified thoracic surgeon with a noncardiac practice,” Dr. Farjah explained. “This variability could be a marker of poor-quality care. However, because the guidelines are not supported by level 1 evidence, it’s equally plausible that this variability might represent uncertainty or even disagreement with the practice guidelines – and specifically about the appropriate indication for invasive staging.”
He presented a retrospective cohort study of 406 patients whose non–small cell lung cancer was resected during July 2011–December 2013 at one of five Washington hospitals, each with at least one board-certified thoracic surgeon with a noncardiac practice on staff. The four participating community hospitals and one academic medical center were involved in a National Cancer Institute–funded, physician-led quality improvement initiative.
Overall, 66% of the 406 patients underwent any form of invasive mediastinal staging: 85% by mediastinoscopy only; 12% by mediastinoscopy plus endobronchial ultrasound-guided nodal aspiration (EBUS); 3% by EBUS only; and the remaining handful by mediastinoscopy, EBUS, and esophageal ultrasound-guided nodal aspiration. The invasive staging was performed at the time of resection in 64% of cases. A median of three nodal stations were sampled.
After statistical adjustment for random variation and between-hospital differences in clinical stage, rates of invasive staging were all over the map. While an overall mean of 66% of the lung cancer patients underwent invasive mediastinal staging, the rates at the five hospitals were 94%, 84%, 31%, 80%, and 17%.
Dr. Farjah and his coinvestigators are now conducting provider interviews and focus groups in an effort to understand what drove the participating surgeons’ wide variability in performing invasive mediastinal staging.
Discussant Jane Yanagawa, MD, of the University of California, Los Angeles, commented, “I think this is a really interesting study because, historically, lower rates of mediastinoscopy are assumed to be a reflection of low-quality care – and you suggest that might not be the case, that it might be more complicated than that.”
Dr. Yanagawa sketched one fairly common scenario that might represent a surgeon’s reasonable avoidance of guideline-recommended invasive mediastinal staging: a patient who by all preoperative imaging appears to have stage IA lung cancer and wishes to avoid the morbidity, time, and cost of needle biopsy, instead choosing to go straight to the operating room for a diagnosis by wedge resection, followed by a completion lobectomy based upon the frozen section results. Could such a pathway account for the variability seen in the Washington study?
“I think it could have,” Dr. Farjah replied. “I would say that’s probably one driver of variability.”
As for the generalizability of the findings of a five-hospital study carried out in a single state, Dr. Farjah said he thinks the results are applicable to any academic or community hospital with at least one board-certified thoracic surgeon with a noncardiac practice.
He reported having no financial conflicts of interest regarding the study.
COLORADO SPRINGS – Significant variability exists between hospitals in Washington state in their rates of invasive mediastinal staging for lung cancer, Farhood Farjah, MD, reported at the annual meeting of the Western Thoracic Surgical Association.
“We found evidence of a fivefold variation in hospital-level rates of invasive mediastinal staging not explained by chance or case mix,” according to Dr. Farjah of the University of Washington, Seattle.
“This has led to substantial concerns about quality of thoracic surgical care in the community at large,” he noted.
The Washington study is the first to show hospital-by-hospital variation in rates of invasive mediastinal staging.
Invasive mediastinal staging for lung cancer is considered important because imaging is known to have a substantial false-negative rate, and staging results have a profound impact on treatment recommendations, which can range from surgery alone to additional chemoradiation therapy.
Yet the meaning of the hospital-level huge variability in practice observed in the Washington study remains unclear.
“Our understanding of the underutilization of invasive mediastinal staging is further complicated by the fact that patterns of invasive mediastinal staging are highly variable across hospitals staffed by at least one board-certified thoracic surgeon with a noncardiac practice,” Dr. Farjah explained. “This variability could be a marker of poor-quality care. However, because the guidelines are not supported by level 1 evidence, it’s equally plausible that this variability might represent uncertainty or even disagreement with the practice guidelines – and specifically about the appropriate indication for invasive staging.”
He presented a retrospective cohort study of 406 patients whose non–small cell lung cancer was resected during July 2011–December 2013 at one of five Washington hospitals, each with at least one board-certified thoracic surgeon with a noncardiac practice on staff. The four participating community hospitals and one academic medical center were involved in a National Cancer Institute–funded, physician-led quality improvement initiative.
Overall, 66% of the 406 patients underwent any form of invasive mediastinal staging: 85% by mediastinoscopy only; 12% by mediastinoscopy plus endobronchial ultrasound-guided nodal aspiration (EBUS); 3% by EBUS only; and the remaining handful by mediastinoscopy, EBUS, and esophageal ultrasound-guided nodal aspiration. The invasive staging was performed at the time of resection in 64% of cases. A median of three nodal stations were sampled.
After statistical adjustment for random variation and between-hospital differences in clinical stage, rates of invasive staging were all over the map. While an overall mean of 66% of the lung cancer patients underwent invasive mediastinal staging, the rates at the five hospitals were 94%, 84%, 31%, 80%, and 17%.
Dr. Farjah and his coinvestigators are now conducting provider interviews and focus groups in an effort to understand what drove the participating surgeons’ wide variability in performing invasive mediastinal staging.
Discussant Jane Yanagawa, MD, of the University of California, Los Angeles, commented, “I think this is a really interesting study because, historically, lower rates of mediastinoscopy are assumed to be a reflection of low-quality care – and you suggest that might not be the case, that it might be more complicated than that.”
Dr. Yanagawa sketched one fairly common scenario that might represent a surgeon’s reasonable avoidance of guideline-recommended invasive mediastinal staging: a patient who by all preoperative imaging appears to have stage IA lung cancer and wishes to avoid the morbidity, time, and cost of needle biopsy, instead choosing to go straight to the operating room for a diagnosis by wedge resection, followed by a completion lobectomy based upon the frozen section results. Could such a pathway account for the variability seen in the Washington study?
“I think it could have,” Dr. Farjah replied. “I would say that’s probably one driver of variability.”
As for the generalizability of the findings of a five-hospital study carried out in a single state, Dr. Farjah said he thinks the results are applicable to any academic or community hospital with at least one board-certified thoracic surgeon with a noncardiac practice.
He reported having no financial conflicts of interest regarding the study.
AT THE WTSA ANNUAL MEETING
Key clinical point:
Major finding: Rates of invasive mediastinal staging after adjustment for clinical stage ranged from a low of 17% at one hospital to as high as 94% at another.
Data source: This retrospective cohort study included 406 patients.
Disclosures: Dr. Farjah reported having no financial conflicts of interest.
Thirdhand smoke shaping up as potential health hazard
DENVER – Thirdhand smoke – the persistent residue that collects on indoor surfaces where people have smoked – is “clearly” a potentially hazardous exposure, John M. Rogers, PhD, said at the annual meeting of the Teratology Society.
Everyone knows about the hazards of secondhand smoke, which have led to widespread bans on smoking in public spaces. Still, the Centers for Disease Control and Prevention estimates that 58 million nonsmokers in the United States are exposed to secondhand smoke on a regular basis. And where there is secondhand smoke, there is typically exposure to thirdhand smoke as well.
“If you walk into a hotel room you were told is a nonsmoking room and you take one breath and you know it’s not nonsmoking, that’s thirdhand smoke. Thirdhand smoke is all over the place where smokers have been,” explained Dr. Rogers, director of the toxicity assessment division at the Environmental Protection Agency in Research Triangle Park, N.C.
The main potential health risk is to young children, who ingest thirdhand smoke by the hand-to-mouth route and skin contact.
Thirdhand smoke is a much newer concept than secondhand smoke and has not yet actually been shown to pose a significant health risk. . But that is likely to change.
Thirdhand smoke has become an area of intensive research interest, with California leading the way. The Tobacco-Related Disease Research Program, a state agency funded by a tax on the sale of tobacco products, has created a research consortium on thirdhand smoke, with studies underway investigating thirdhand smoke’s precise chemical composition, cytotoxicity, genotoxicity, and true impact on public health (www.trdrp.org).
Concern regarding thirdhand smoke’s potential public health impact ramped up in response to a study in which investigators at the University of York, England, measured levels of various tobacco-specific nitrosamines, N-nitrosamines, and nicotine in house dust samples from the homes of smokers. The researchers estimated that years of early life exposure to these compounds at the levels they detected could result in one excess case of cancer per 1,000 exposed individuals (Environ Int. 2014 Oct;71:139-47).
In addition to his update on thirdhand smoke, Dr. Rogers also touched on other recent tobacco-related developments, including a determination by the Food and Drug Administration that there has been no decline in tobacco use in the last 5 years in adolescents and young adults. While cigarette smoking by young people decreased, this was offset by a large increase in the use of electronic cigarettes and a smaller rise in the use of hookah tobacco. Indeed, e-cigarette use is now about double that of cigarettes among youth.
Also of concern is evidence of a striking socioeconomic disparity in smoking prevalence: Low-education, low-income Americans have far higher tobacco use rates.
“That’s pretty alarming,” he said. “I think a lot of people in this audience probably don’t see a lot of smoking these days, but it’s still around.”
Dr. Rogers drew attention to updated evidence reviews on the reproductive and developmental effects of smoking contained in the U.S. Surgeon General’s voluminous 2014 report on the health consequences of smoking. The report concluded that there is now sufficient evidence to infer a causal relationship between maternal smoking in pregnancy, ectopic pregnancy, and orofacial clefts. The available evidence is “suggestive but not sufficient” to infer causality between maternal smoking in pregnancy and atrial septal defects, clubfoot, gastroschisis, and attention-deficit/hyperactivity disorder and other disruptive behavior disorders.
Dr. Rogers reported having no financial disclosures related to his presentation, which he noted did not necessarily reflect the views and policies of the EPA.
DENVER – Thirdhand smoke – the persistent residue that collects on indoor surfaces where people have smoked – is “clearly” a potentially hazardous exposure, John M. Rogers, PhD, said at the annual meeting of the Teratology Society.
Everyone knows about the hazards of secondhand smoke, which have led to widespread bans on smoking in public spaces. Still, the Centers for Disease Control and Prevention estimates that 58 million nonsmokers in the United States are exposed to secondhand smoke on a regular basis. And where there is secondhand smoke, there is typically exposure to thirdhand smoke as well.
“If you walk into a hotel room you were told is a nonsmoking room and you take one breath and you know it’s not nonsmoking, that’s thirdhand smoke. Thirdhand smoke is all over the place where smokers have been,” explained Dr. Rogers, director of the toxicity assessment division at the Environmental Protection Agency in Research Triangle Park, N.C.
The main potential health risk is to young children, who ingest thirdhand smoke by the hand-to-mouth route and skin contact.
Thirdhand smoke is a much newer concept than secondhand smoke and has not yet actually been shown to pose a significant health risk. . But that is likely to change.
Thirdhand smoke has become an area of intensive research interest, with California leading the way. The Tobacco-Related Disease Research Program, a state agency funded by a tax on the sale of tobacco products, has created a research consortium on thirdhand smoke, with studies underway investigating thirdhand smoke’s precise chemical composition, cytotoxicity, genotoxicity, and true impact on public health (www.trdrp.org).
Concern regarding thirdhand smoke’s potential public health impact ramped up in response to a study in which investigators at the University of York, England, measured levels of various tobacco-specific nitrosamines, N-nitrosamines, and nicotine in house dust samples from the homes of smokers. The researchers estimated that years of early life exposure to these compounds at the levels they detected could result in one excess case of cancer per 1,000 exposed individuals (Environ Int. 2014 Oct;71:139-47).
In addition to his update on thirdhand smoke, Dr. Rogers also touched on other recent tobacco-related developments, including a determination by the Food and Drug Administration that there has been no decline in tobacco use in the last 5 years in adolescents and young adults. While cigarette smoking by young people decreased, this was offset by a large increase in the use of electronic cigarettes and a smaller rise in the use of hookah tobacco. Indeed, e-cigarette use is now about double that of cigarettes among youth.
Also of concern is evidence of a striking socioeconomic disparity in smoking prevalence: Low-education, low-income Americans have far higher tobacco use rates.
“That’s pretty alarming,” he said. “I think a lot of people in this audience probably don’t see a lot of smoking these days, but it’s still around.”
Dr. Rogers drew attention to updated evidence reviews on the reproductive and developmental effects of smoking contained in the U.S. Surgeon General’s voluminous 2014 report on the health consequences of smoking. The report concluded that there is now sufficient evidence to infer a causal relationship between maternal smoking in pregnancy, ectopic pregnancy, and orofacial clefts. The available evidence is “suggestive but not sufficient” to infer causality between maternal smoking in pregnancy and atrial septal defects, clubfoot, gastroschisis, and attention-deficit/hyperactivity disorder and other disruptive behavior disorders.
Dr. Rogers reported having no financial disclosures related to his presentation, which he noted did not necessarily reflect the views and policies of the EPA.
DENVER – Thirdhand smoke – the persistent residue that collects on indoor surfaces where people have smoked – is “clearly” a potentially hazardous exposure, John M. Rogers, PhD, said at the annual meeting of the Teratology Society.
Everyone knows about the hazards of secondhand smoke, which have led to widespread bans on smoking in public spaces. Still, the Centers for Disease Control and Prevention estimates that 58 million nonsmokers in the United States are exposed to secondhand smoke on a regular basis. And where there is secondhand smoke, there is typically exposure to thirdhand smoke as well.
“If you walk into a hotel room you were told is a nonsmoking room and you take one breath and you know it’s not nonsmoking, that’s thirdhand smoke. Thirdhand smoke is all over the place where smokers have been,” explained Dr. Rogers, director of the toxicity assessment division at the Environmental Protection Agency in Research Triangle Park, N.C.
The main potential health risk is to young children, who ingest thirdhand smoke by the hand-to-mouth route and skin contact.
Thirdhand smoke is a much newer concept than secondhand smoke and has not yet actually been shown to pose a significant health risk. . But that is likely to change.
Thirdhand smoke has become an area of intensive research interest, with California leading the way. The Tobacco-Related Disease Research Program, a state agency funded by a tax on the sale of tobacco products, has created a research consortium on thirdhand smoke, with studies underway investigating thirdhand smoke’s precise chemical composition, cytotoxicity, genotoxicity, and true impact on public health (www.trdrp.org).
Concern regarding thirdhand smoke’s potential public health impact ramped up in response to a study in which investigators at the University of York, England, measured levels of various tobacco-specific nitrosamines, N-nitrosamines, and nicotine in house dust samples from the homes of smokers. The researchers estimated that years of early life exposure to these compounds at the levels they detected could result in one excess case of cancer per 1,000 exposed individuals (Environ Int. 2014 Oct;71:139-47).
In addition to his update on thirdhand smoke, Dr. Rogers also touched on other recent tobacco-related developments, including a determination by the Food and Drug Administration that there has been no decline in tobacco use in the last 5 years in adolescents and young adults. While cigarette smoking by young people decreased, this was offset by a large increase in the use of electronic cigarettes and a smaller rise in the use of hookah tobacco. Indeed, e-cigarette use is now about double that of cigarettes among youth.
Also of concern is evidence of a striking socioeconomic disparity in smoking prevalence: Low-education, low-income Americans have far higher tobacco use rates.
“That’s pretty alarming,” he said. “I think a lot of people in this audience probably don’t see a lot of smoking these days, but it’s still around.”
Dr. Rogers drew attention to updated evidence reviews on the reproductive and developmental effects of smoking contained in the U.S. Surgeon General’s voluminous 2014 report on the health consequences of smoking. The report concluded that there is now sufficient evidence to infer a causal relationship between maternal smoking in pregnancy, ectopic pregnancy, and orofacial clefts. The available evidence is “suggestive but not sufficient” to infer causality between maternal smoking in pregnancy and atrial septal defects, clubfoot, gastroschisis, and attention-deficit/hyperactivity disorder and other disruptive behavior disorders.
Dr. Rogers reported having no financial disclosures related to his presentation, which he noted did not necessarily reflect the views and policies of the EPA.
EXPERT ANALYSIS FROM TERATOLOGY SOCIETY 2017
LIFSCREEN data support broader cancer screening in Li-Fraumeni syndrome
Broader cancer screening of individuals with Li-Fraumeni syndrome (LFS), with or without whole-body magnetic resonance imaging, has a good diagnostic yield and identifies a wide range of cancers, according to a preliminary analysis of the ongoing LIFSCREEN phase 3, randomized, controlled trial.
Investigators led by Olivier Caron, MD, chair of the oncogenetics committee, department of medical oncology, at the Gustave Roussy University Hospital in Villejuif, France, enrolled in the trial 107 individuals from 75 families carrying a TP53 mutation, a genetic aberration commonly present in LFS that confers heightened risk of a variety of malignancies.
Participants had a median age at baseline of 32.9 years, with a range from 5 to 67 years. Fully 98% had a family history of cancer, and 48% had a personal history of cancer.
The participants were assigned to 5 years of standard screening – annual clinical examination, abdomen and pelvis ultrasound, brain MRI, complete blood cell count, and, for women older than 20 years, breast ultrasound and MRI – or intensive screening, entailing the addition of diffusion whole-body MRI.
At the time of the preliminary analysis, 15 patients had undergone only one round of screening; 35, two rounds; 19, three rounds; 24, four rounds; and 7, five rounds, Dr. Caron and associates reported in a research letter (JAMA Oncol. 2017; Aug 3 doi: 10.1001/jamaoncol.2017.1358).
Collectively, this amounted to 226.4 person-years of follow-up.
Screening with either trial strategy (with or without whole-body MRI) led to diagnosis of 23 new primary cancers in 20 patients. Nearly half of the total (12 cancers) were detected at the first round. Patients had a median age of 39.8 at the new cancer diagnosis, with a range from 6 to 70 years.
Of the new cancers, 10 belonged to the core LFS spectrum of breast cancer, sarcoma, and brain tumors. However, the other 13 were outside that spectrum, for example, lung adenocarcinomas, all seen in never or light smokers, and leukemias. Screening also detected three relapses of previous cancers.
Analyses further showed that prior cancer diagnosis was not a reliable marker for risk of new primaries. Although 12 of the patients with a screening-detected new primary had a personal cancer history, 8 did not (P = .22).
“The proportion and diversity of off–core LFS spectrum cancers detected in TP53 mutation carriers as reported by others give growing evidence of a broader LFS spectrum, in agreement with the permissive role of TP53 mutations,” write Dr. Caron and colleagues, who report having no relevant disclosures. “Our observations seem to support recent moves toward broader cancer screening in TP53 mutation carriers.”
The investigators continue to collect data in LIFSCREEN and plan to undertake main analysis later this year. “Our final analysis will help to determine the benefits and drawbacks (mostly related to false-positive test results) of whole-body MRI in TP53 mutation carrier surveillance,” they conclude. “Studies focused on TP53 mutation penetrance, using methods limiting selection bias, are required to refine cancer risks to improve TP53 mutation carrier management.”
Broader cancer screening of individuals with Li-Fraumeni syndrome (LFS), with or without whole-body magnetic resonance imaging, has a good diagnostic yield and identifies a wide range of cancers, according to a preliminary analysis of the ongoing LIFSCREEN phase 3, randomized, controlled trial.
Investigators led by Olivier Caron, MD, chair of the oncogenetics committee, department of medical oncology, at the Gustave Roussy University Hospital in Villejuif, France, enrolled in the trial 107 individuals from 75 families carrying a TP53 mutation, a genetic aberration commonly present in LFS that confers heightened risk of a variety of malignancies.
Participants had a median age at baseline of 32.9 years, with a range from 5 to 67 years. Fully 98% had a family history of cancer, and 48% had a personal history of cancer.
The participants were assigned to 5 years of standard screening – annual clinical examination, abdomen and pelvis ultrasound, brain MRI, complete blood cell count, and, for women older than 20 years, breast ultrasound and MRI – or intensive screening, entailing the addition of diffusion whole-body MRI.
At the time of the preliminary analysis, 15 patients had undergone only one round of screening; 35, two rounds; 19, three rounds; 24, four rounds; and 7, five rounds, Dr. Caron and associates reported in a research letter (JAMA Oncol. 2017; Aug 3 doi: 10.1001/jamaoncol.2017.1358).
Collectively, this amounted to 226.4 person-years of follow-up.
Screening with either trial strategy (with or without whole-body MRI) led to diagnosis of 23 new primary cancers in 20 patients. Nearly half of the total (12 cancers) were detected at the first round. Patients had a median age of 39.8 at the new cancer diagnosis, with a range from 6 to 70 years.
Of the new cancers, 10 belonged to the core LFS spectrum of breast cancer, sarcoma, and brain tumors. However, the other 13 were outside that spectrum, for example, lung adenocarcinomas, all seen in never or light smokers, and leukemias. Screening also detected three relapses of previous cancers.
Analyses further showed that prior cancer diagnosis was not a reliable marker for risk of new primaries. Although 12 of the patients with a screening-detected new primary had a personal cancer history, 8 did not (P = .22).
“The proportion and diversity of off–core LFS spectrum cancers detected in TP53 mutation carriers as reported by others give growing evidence of a broader LFS spectrum, in agreement with the permissive role of TP53 mutations,” write Dr. Caron and colleagues, who report having no relevant disclosures. “Our observations seem to support recent moves toward broader cancer screening in TP53 mutation carriers.”
The investigators continue to collect data in LIFSCREEN and plan to undertake main analysis later this year. “Our final analysis will help to determine the benefits and drawbacks (mostly related to false-positive test results) of whole-body MRI in TP53 mutation carrier surveillance,” they conclude. “Studies focused on TP53 mutation penetrance, using methods limiting selection bias, are required to refine cancer risks to improve TP53 mutation carrier management.”
Broader cancer screening of individuals with Li-Fraumeni syndrome (LFS), with or without whole-body magnetic resonance imaging, has a good diagnostic yield and identifies a wide range of cancers, according to a preliminary analysis of the ongoing LIFSCREEN phase 3, randomized, controlled trial.
Investigators led by Olivier Caron, MD, chair of the oncogenetics committee, department of medical oncology, at the Gustave Roussy University Hospital in Villejuif, France, enrolled in the trial 107 individuals from 75 families carrying a TP53 mutation, a genetic aberration commonly present in LFS that confers heightened risk of a variety of malignancies.
Participants had a median age at baseline of 32.9 years, with a range from 5 to 67 years. Fully 98% had a family history of cancer, and 48% had a personal history of cancer.
The participants were assigned to 5 years of standard screening – annual clinical examination, abdomen and pelvis ultrasound, brain MRI, complete blood cell count, and, for women older than 20 years, breast ultrasound and MRI – or intensive screening, entailing the addition of diffusion whole-body MRI.
At the time of the preliminary analysis, 15 patients had undergone only one round of screening; 35, two rounds; 19, three rounds; 24, four rounds; and 7, five rounds, Dr. Caron and associates reported in a research letter (JAMA Oncol. 2017; Aug 3 doi: 10.1001/jamaoncol.2017.1358).
Collectively, this amounted to 226.4 person-years of follow-up.
Screening with either trial strategy (with or without whole-body MRI) led to diagnosis of 23 new primary cancers in 20 patients. Nearly half of the total (12 cancers) were detected at the first round. Patients had a median age of 39.8 at the new cancer diagnosis, with a range from 6 to 70 years.
Of the new cancers, 10 belonged to the core LFS spectrum of breast cancer, sarcoma, and brain tumors. However, the other 13 were outside that spectrum, for example, lung adenocarcinomas, all seen in never or light smokers, and leukemias. Screening also detected three relapses of previous cancers.
Analyses further showed that prior cancer diagnosis was not a reliable marker for risk of new primaries. Although 12 of the patients with a screening-detected new primary had a personal cancer history, 8 did not (P = .22).
“The proportion and diversity of off–core LFS spectrum cancers detected in TP53 mutation carriers as reported by others give growing evidence of a broader LFS spectrum, in agreement with the permissive role of TP53 mutations,” write Dr. Caron and colleagues, who report having no relevant disclosures. “Our observations seem to support recent moves toward broader cancer screening in TP53 mutation carriers.”
The investigators continue to collect data in LIFSCREEN and plan to undertake main analysis later this year. “Our final analysis will help to determine the benefits and drawbacks (mostly related to false-positive test results) of whole-body MRI in TP53 mutation carrier surveillance,” they conclude. “Studies focused on TP53 mutation penetrance, using methods limiting selection bias, are required to refine cancer risks to improve TP53 mutation carrier management.”
FROM JAMA ONCOLOGY
Key clinical point:
Major finding: A total of 23 new primary cancers were diagnosed in 20 patients; more than half were outside the core spectrum of Li-Fraumeni syndrome.
Data source: A preliminary analysis of a phase 3, randomized, controlled trial comparing standard and intensive screening among 107 individuals with Li-Fraumeni syndrome carrying a TP53 mutation (LIFSCREEN trial).
Disclosures: The investigators report having no relevant disclosures. The trial was funded by the French Ligue Contre le Cancer.
Abdominal Compression by Prone Position in Lung SBRT— A Technical Note
Purpose: In stereotactic body radiation therapy (SBRT) of lung tumors, to reduce the target motion and to minimize lung volume treated, the generally accepted procedure is to use abdominal compression, but sometimes abdominal compression is not enough to reduce target motion, particularly the lower lobe lesions.
Methods: When we didn’t have abdominal compression device in our department at the start of our SBRT program, to reduce the target motion, we did CT simulation of patients in both supine and prone position to see if there would be any reduction in the target motion. We planned
and treated four patients in a prone position taking the substantial reduction in target motion into consideration.
Results: It was observed that there was a significant reduction in the target motion ranging from 1.5 cm to 3.0 cm in prone position, the reduction in motion of target is seen mostly in middle and particularly lower lobe lesions, and there was not much change in target motion in upper lobe lesions.
Conclusions: Abdominal compression is both patient and operator oriented and could be uncomfortable to the patient depending on the pressure exerted with compression, whereas prone position is only patient oriented and self-adjusting and settling in a comfortable position prior to CT simulation and prior to initiation of treatment which is verified by image guided radiation therapy (cone based CT). It may not be practical in every patient but could be an option in some patients and particularly in for lower lobe lesions.
Purpose: In stereotactic body radiation therapy (SBRT) of lung tumors, to reduce the target motion and to minimize lung volume treated, the generally accepted procedure is to use abdominal compression, but sometimes abdominal compression is not enough to reduce target motion, particularly the lower lobe lesions.
Methods: When we didn’t have abdominal compression device in our department at the start of our SBRT program, to reduce the target motion, we did CT simulation of patients in both supine and prone position to see if there would be any reduction in the target motion. We planned
and treated four patients in a prone position taking the substantial reduction in target motion into consideration.
Results: It was observed that there was a significant reduction in the target motion ranging from 1.5 cm to 3.0 cm in prone position, the reduction in motion of target is seen mostly in middle and particularly lower lobe lesions, and there was not much change in target motion in upper lobe lesions.
Conclusions: Abdominal compression is both patient and operator oriented and could be uncomfortable to the patient depending on the pressure exerted with compression, whereas prone position is only patient oriented and self-adjusting and settling in a comfortable position prior to CT simulation and prior to initiation of treatment which is verified by image guided radiation therapy (cone based CT). It may not be practical in every patient but could be an option in some patients and particularly in for lower lobe lesions.
Purpose: In stereotactic body radiation therapy (SBRT) of lung tumors, to reduce the target motion and to minimize lung volume treated, the generally accepted procedure is to use abdominal compression, but sometimes abdominal compression is not enough to reduce target motion, particularly the lower lobe lesions.
Methods: When we didn’t have abdominal compression device in our department at the start of our SBRT program, to reduce the target motion, we did CT simulation of patients in both supine and prone position to see if there would be any reduction in the target motion. We planned
and treated four patients in a prone position taking the substantial reduction in target motion into consideration.
Results: It was observed that there was a significant reduction in the target motion ranging from 1.5 cm to 3.0 cm in prone position, the reduction in motion of target is seen mostly in middle and particularly lower lobe lesions, and there was not much change in target motion in upper lobe lesions.
Conclusions: Abdominal compression is both patient and operator oriented and could be uncomfortable to the patient depending on the pressure exerted with compression, whereas prone position is only patient oriented and self-adjusting and settling in a comfortable position prior to CT simulation and prior to initiation of treatment which is verified by image guided radiation therapy (cone based CT). It may not be practical in every patient but could be an option in some patients and particularly in for lower lobe lesions.
Navigator Driven Process to Coordinate Multi-Disciplinary Visits for Advanced Lung Cancer Patients
Purpose: A multiphased QI project to increase multidisciplinary team member (social work, dietician, mental health and palliative care) visits for patients with stage IV lung cancer receiving antineoplastic therapy.
Background: The Commission on Cancer program standards require an active multidisciplinary team to meet the needs of the patient. Prior to the addition of oncology navigators at the Minneapolis VA, patients received supportive services through consults placed by the oncologist, infusion clinic nurses or patient requests. Patients were not receiving care from these disciplines for a variety of reasons, including lack of a standardized process to trigger the initiation of a consult, physicians focusing on antineoplastic therapy, lack of room space in the clinic, and the stigma associated with mental health and palliative care to the layperson. It was thought that navigators may be able to assume the role of initiating the consults and coordinating the visits because they typically meet with each patient for chemo education.
Methods: The ACCESS database used to track oncology consults was reviewed for stage IV lung cancer patients receiving parental antineoplastic treatment from January 2015 through April 2017. Patients transferring care before the completion of therapy were excluded. Charts were reviewed to determine time from consult to therapy, visits with a social worker, dietician, mental health provider and palliative care consults. A contact included any visit both inpatient or outpatient during the treatment period.
Results: There were 191 lung cancer patients, 78 met the inclusion criteria. Ninety percent (70/78) of patients had contact with a navigator. 76% of the patients received palliative care, 69% contact with a social worker, 39% received a mental health provider visit and 64% received
a consult with a dietician.
Conclusions: It is feasible for a nurse navigator to coordinate visits among multiple specialties. Coordinating the visits in the infusion center leads to increased utilization of the specialty services, freed up rooms the provider clinic and normalized the inclusion of mental health and palliative care early in the treatment course.
Purpose: A multiphased QI project to increase multidisciplinary team member (social work, dietician, mental health and palliative care) visits for patients with stage IV lung cancer receiving antineoplastic therapy.
Background: The Commission on Cancer program standards require an active multidisciplinary team to meet the needs of the patient. Prior to the addition of oncology navigators at the Minneapolis VA, patients received supportive services through consults placed by the oncologist, infusion clinic nurses or patient requests. Patients were not receiving care from these disciplines for a variety of reasons, including lack of a standardized process to trigger the initiation of a consult, physicians focusing on antineoplastic therapy, lack of room space in the clinic, and the stigma associated with mental health and palliative care to the layperson. It was thought that navigators may be able to assume the role of initiating the consults and coordinating the visits because they typically meet with each patient for chemo education.
Methods: The ACCESS database used to track oncology consults was reviewed for stage IV lung cancer patients receiving parental antineoplastic treatment from January 2015 through April 2017. Patients transferring care before the completion of therapy were excluded. Charts were reviewed to determine time from consult to therapy, visits with a social worker, dietician, mental health provider and palliative care consults. A contact included any visit both inpatient or outpatient during the treatment period.
Results: There were 191 lung cancer patients, 78 met the inclusion criteria. Ninety percent (70/78) of patients had contact with a navigator. 76% of the patients received palliative care, 69% contact with a social worker, 39% received a mental health provider visit and 64% received
a consult with a dietician.
Conclusions: It is feasible for a nurse navigator to coordinate visits among multiple specialties. Coordinating the visits in the infusion center leads to increased utilization of the specialty services, freed up rooms the provider clinic and normalized the inclusion of mental health and palliative care early in the treatment course.
Purpose: A multiphased QI project to increase multidisciplinary team member (social work, dietician, mental health and palliative care) visits for patients with stage IV lung cancer receiving antineoplastic therapy.
Background: The Commission on Cancer program standards require an active multidisciplinary team to meet the needs of the patient. Prior to the addition of oncology navigators at the Minneapolis VA, patients received supportive services through consults placed by the oncologist, infusion clinic nurses or patient requests. Patients were not receiving care from these disciplines for a variety of reasons, including lack of a standardized process to trigger the initiation of a consult, physicians focusing on antineoplastic therapy, lack of room space in the clinic, and the stigma associated with mental health and palliative care to the layperson. It was thought that navigators may be able to assume the role of initiating the consults and coordinating the visits because they typically meet with each patient for chemo education.
Methods: The ACCESS database used to track oncology consults was reviewed for stage IV lung cancer patients receiving parental antineoplastic treatment from January 2015 through April 2017. Patients transferring care before the completion of therapy were excluded. Charts were reviewed to determine time from consult to therapy, visits with a social worker, dietician, mental health provider and palliative care consults. A contact included any visit both inpatient or outpatient during the treatment period.
Results: There were 191 lung cancer patients, 78 met the inclusion criteria. Ninety percent (70/78) of patients had contact with a navigator. 76% of the patients received palliative care, 69% contact with a social worker, 39% received a mental health provider visit and 64% received
a consult with a dietician.
Conclusions: It is feasible for a nurse navigator to coordinate visits among multiple specialties. Coordinating the visits in the infusion center leads to increased utilization of the specialty services, freed up rooms the provider clinic and normalized the inclusion of mental health and palliative care early in the treatment course.
Comparison of PFT Before and After Radiation Therapy for Lung Cancer
Background: Radiation therapy (RT) for lung cancer is a standard of care. Radiation exposure to normal lung tissue can cause loss of function due to pneumonitis and fibrosis. We evaluated subjectively and objectively with pulmonary function tests (PFT) for toxicity following RT.
Objective: The purpose of our retrospective study was to correlate post radiation PFT changes and symptoms.
Methods: We studied retrospectively 18 patients with lung cancer treated at the Jackson VAMC between 2014 and 2016. All patients had pretreatment and posttreatment PFTs. Symptoms of dyspnea were graded using the Common Terminology Criteria for Adverse Events (CTCAE).
Results: Sixteen received SBRT; (15 with 50 Gy in 5 fractions; one 48 Gy in 4 fractions); one 60 Gy in 6 weeks and one 45 Gy in 30 bid fractions. Sites of treatment included 13 (72%) upper lobe, 2 (11%) right middle lobe and 3 (17%) lower lobe. The median drop in FEV1 posttreatment was 0.15. While 8 (44%) patients had grade I/II dyspnea prior to treatment, 14 (78%) patients had the same after treatment. Only 1 patient who received both SBRT to LUL and Conventional XRT to the mediastinum developed grade II dyspnea. His FEV1 dropped 37% or 0.37 from baseline. Symptomatically 11 (61%) had no increased dyspnea with a median FEV1 drop of 3% or 0.06 from baseline; while 7 (39%) patients had worsening of dyspnea after treatment with a median drop of 0.23 (11%) from baseline in FEV1. Patients treated in the middle and lower lobes had a median FEV1 drop of 0.43 from baseline There was no significant median change (+0.04) when treating the upper lobe. 38% of patients who had an upper lobe treated complained of worsening dyspnea, while 66% of patients with lower lobe treated reported worsening dyspnea.
Conclusions: After definitive XRT, 39% of patients had worsening in symptoms with a median drop of 11% in the FEV1, compared to only a 3% drop in FEV1 in patients who did not report a worsening of symptoms. Patients with lower lobe tumors had greater PFT changes with worsening dyspnea.
Background: Radiation therapy (RT) for lung cancer is a standard of care. Radiation exposure to normal lung tissue can cause loss of function due to pneumonitis and fibrosis. We evaluated subjectively and objectively with pulmonary function tests (PFT) for toxicity following RT.
Objective: The purpose of our retrospective study was to correlate post radiation PFT changes and symptoms.
Methods: We studied retrospectively 18 patients with lung cancer treated at the Jackson VAMC between 2014 and 2016. All patients had pretreatment and posttreatment PFTs. Symptoms of dyspnea were graded using the Common Terminology Criteria for Adverse Events (CTCAE).
Results: Sixteen received SBRT; (15 with 50 Gy in 5 fractions; one 48 Gy in 4 fractions); one 60 Gy in 6 weeks and one 45 Gy in 30 bid fractions. Sites of treatment included 13 (72%) upper lobe, 2 (11%) right middle lobe and 3 (17%) lower lobe. The median drop in FEV1 posttreatment was 0.15. While 8 (44%) patients had grade I/II dyspnea prior to treatment, 14 (78%) patients had the same after treatment. Only 1 patient who received both SBRT to LUL and Conventional XRT to the mediastinum developed grade II dyspnea. His FEV1 dropped 37% or 0.37 from baseline. Symptomatically 11 (61%) had no increased dyspnea with a median FEV1 drop of 3% or 0.06 from baseline; while 7 (39%) patients had worsening of dyspnea after treatment with a median drop of 0.23 (11%) from baseline in FEV1. Patients treated in the middle and lower lobes had a median FEV1 drop of 0.43 from baseline There was no significant median change (+0.04) when treating the upper lobe. 38% of patients who had an upper lobe treated complained of worsening dyspnea, while 66% of patients with lower lobe treated reported worsening dyspnea.
Conclusions: After definitive XRT, 39% of patients had worsening in symptoms with a median drop of 11% in the FEV1, compared to only a 3% drop in FEV1 in patients who did not report a worsening of symptoms. Patients with lower lobe tumors had greater PFT changes with worsening dyspnea.
Background: Radiation therapy (RT) for lung cancer is a standard of care. Radiation exposure to normal lung tissue can cause loss of function due to pneumonitis and fibrosis. We evaluated subjectively and objectively with pulmonary function tests (PFT) for toxicity following RT.
Objective: The purpose of our retrospective study was to correlate post radiation PFT changes and symptoms.
Methods: We studied retrospectively 18 patients with lung cancer treated at the Jackson VAMC between 2014 and 2016. All patients had pretreatment and posttreatment PFTs. Symptoms of dyspnea were graded using the Common Terminology Criteria for Adverse Events (CTCAE).
Results: Sixteen received SBRT; (15 with 50 Gy in 5 fractions; one 48 Gy in 4 fractions); one 60 Gy in 6 weeks and one 45 Gy in 30 bid fractions. Sites of treatment included 13 (72%) upper lobe, 2 (11%) right middle lobe and 3 (17%) lower lobe. The median drop in FEV1 posttreatment was 0.15. While 8 (44%) patients had grade I/II dyspnea prior to treatment, 14 (78%) patients had the same after treatment. Only 1 patient who received both SBRT to LUL and Conventional XRT to the mediastinum developed grade II dyspnea. His FEV1 dropped 37% or 0.37 from baseline. Symptomatically 11 (61%) had no increased dyspnea with a median FEV1 drop of 3% or 0.06 from baseline; while 7 (39%) patients had worsening of dyspnea after treatment with a median drop of 0.23 (11%) from baseline in FEV1. Patients treated in the middle and lower lobes had a median FEV1 drop of 0.43 from baseline There was no significant median change (+0.04) when treating the upper lobe. 38% of patients who had an upper lobe treated complained of worsening dyspnea, while 66% of patients with lower lobe treated reported worsening dyspnea.
Conclusions: After definitive XRT, 39% of patients had worsening in symptoms with a median drop of 11% in the FEV1, compared to only a 3% drop in FEV1 in patients who did not report a worsening of symptoms. Patients with lower lobe tumors had greater PFT changes with worsening dyspnea.
Failure Patterns After Stereotactic Body Radiation Therapy for Early Non-Small Cell Lung Cancer and Their Implications for Future Management
Objective: Stereotactic body radiation therapy (SBRT) is an effective modality for patients with early stage nonsmall cell lung cancer (NSCLC) who are unsuitable for surgical management. We performed a retrospective review to evaluate the clinical outcomes and patterns of failure of patients who completed SBRT for early stage NSCLC.
Methods: Twenty-five veteran patients from G.V. Sonny Montgomery VA Medical Center, Jackson, MS (G.V. VAMC) with T1-3N0 NSCLC were referred to the neighboring University of Mississippi Medical Center for treatment with SBRT between July 2010 and June 2014. After completion of therapy, the patient’s care was then transferred back to G.V. VAMC for subsequent follow-up visits and surveillance imaging. All patients received a prescription of > 100 Gy biologically effective dose (BED). Fifty Gray (Gy) in 5 fractions was prescribed to 19 (76%) of the patients, while 3 (12%) patients received 60 Gy in 3 fractions, and another 3 (12%) patients received 48 Gy in 4 fractions. Clinical response was evaluated using RECIST 1.1 criteria. The primary endpoints included assessment of overall survival (OS), disease free survival (DFS), local control (LC), regional failure (RF), and distant failure (DF) rates.
Results: The median follow-up was 37 months and the median OS and DFS rates were 50 months and 45.3 months, respectively. The three-year OS, DFS, LC, RF, and DF rates were 68.2%, 64.7%, 78.6%, 35.3%, and 8.3%, respectively. Eleven (44%) patients failed. Two (8%) with LF alone, 4 (16%) with RF, and 3 (12%) patients had LR, RF and DF. Of the 5 LFs, 2 of the patients failed within the planning target volume (PTV), while 3 patients had failures outside the PTV. There were a total of 12 deaths at last follow-up. Three patients died due to the malignancy, while 1 patient died from complications with radiation-related pneumonitis.
Conclusions: Our results were comparable to several larger reported series. While LC is excellent, failure within the same lobe is a problem with SBRT. Strategies such as tighter constraints of normal structures need to be applied, as about a third of these patients will require retreatment of a new lesion in the same lobe that was outside the previously irradiated field.
Objective: Stereotactic body radiation therapy (SBRT) is an effective modality for patients with early stage nonsmall cell lung cancer (NSCLC) who are unsuitable for surgical management. We performed a retrospective review to evaluate the clinical outcomes and patterns of failure of patients who completed SBRT for early stage NSCLC.
Methods: Twenty-five veteran patients from G.V. Sonny Montgomery VA Medical Center, Jackson, MS (G.V. VAMC) with T1-3N0 NSCLC were referred to the neighboring University of Mississippi Medical Center for treatment with SBRT between July 2010 and June 2014. After completion of therapy, the patient’s care was then transferred back to G.V. VAMC for subsequent follow-up visits and surveillance imaging. All patients received a prescription of > 100 Gy biologically effective dose (BED). Fifty Gray (Gy) in 5 fractions was prescribed to 19 (76%) of the patients, while 3 (12%) patients received 60 Gy in 3 fractions, and another 3 (12%) patients received 48 Gy in 4 fractions. Clinical response was evaluated using RECIST 1.1 criteria. The primary endpoints included assessment of overall survival (OS), disease free survival (DFS), local control (LC), regional failure (RF), and distant failure (DF) rates.
Results: The median follow-up was 37 months and the median OS and DFS rates were 50 months and 45.3 months, respectively. The three-year OS, DFS, LC, RF, and DF rates were 68.2%, 64.7%, 78.6%, 35.3%, and 8.3%, respectively. Eleven (44%) patients failed. Two (8%) with LF alone, 4 (16%) with RF, and 3 (12%) patients had LR, RF and DF. Of the 5 LFs, 2 of the patients failed within the planning target volume (PTV), while 3 patients had failures outside the PTV. There were a total of 12 deaths at last follow-up. Three patients died due to the malignancy, while 1 patient died from complications with radiation-related pneumonitis.
Conclusions: Our results were comparable to several larger reported series. While LC is excellent, failure within the same lobe is a problem with SBRT. Strategies such as tighter constraints of normal structures need to be applied, as about a third of these patients will require retreatment of a new lesion in the same lobe that was outside the previously irradiated field.
Objective: Stereotactic body radiation therapy (SBRT) is an effective modality for patients with early stage nonsmall cell lung cancer (NSCLC) who are unsuitable for surgical management. We performed a retrospective review to evaluate the clinical outcomes and patterns of failure of patients who completed SBRT for early stage NSCLC.
Methods: Twenty-five veteran patients from G.V. Sonny Montgomery VA Medical Center, Jackson, MS (G.V. VAMC) with T1-3N0 NSCLC were referred to the neighboring University of Mississippi Medical Center for treatment with SBRT between July 2010 and June 2014. After completion of therapy, the patient’s care was then transferred back to G.V. VAMC for subsequent follow-up visits and surveillance imaging. All patients received a prescription of > 100 Gy biologically effective dose (BED). Fifty Gray (Gy) in 5 fractions was prescribed to 19 (76%) of the patients, while 3 (12%) patients received 60 Gy in 3 fractions, and another 3 (12%) patients received 48 Gy in 4 fractions. Clinical response was evaluated using RECIST 1.1 criteria. The primary endpoints included assessment of overall survival (OS), disease free survival (DFS), local control (LC), regional failure (RF), and distant failure (DF) rates.
Results: The median follow-up was 37 months and the median OS and DFS rates were 50 months and 45.3 months, respectively. The three-year OS, DFS, LC, RF, and DF rates were 68.2%, 64.7%, 78.6%, 35.3%, and 8.3%, respectively. Eleven (44%) patients failed. Two (8%) with LF alone, 4 (16%) with RF, and 3 (12%) patients had LR, RF and DF. Of the 5 LFs, 2 of the patients failed within the planning target volume (PTV), while 3 patients had failures outside the PTV. There were a total of 12 deaths at last follow-up. Three patients died due to the malignancy, while 1 patient died from complications with radiation-related pneumonitis.
Conclusions: Our results were comparable to several larger reported series. While LC is excellent, failure within the same lobe is a problem with SBRT. Strategies such as tighter constraints of normal structures need to be applied, as about a third of these patients will require retreatment of a new lesion in the same lobe that was outside the previously irradiated field.
Pulmonary metastasectomy may be useful for soft-tissue sarcoma spread
The rate of soft-tissue sarcoma has nearly doubled over the past two decades, and up to 50% of patients with tissue sarcoma develop lung metastasis. A single-center study of 539 patients who had treatment for soft-tissue sarcoma has revealed disease and treatment characteristics that may aid patient selection and help predict overall and disease-free survival after diagnosis and treatment.
“Histologic subtype and size of the primary tumor were significantly associated with overall survival,” said lead author Neel P. Chudgar, MD, and his coauthors in the July issue of the Journal of Thoracic and Cardiovascular Surgery (2017;154:319-30).
“Patients who underwent pulmonary metastasectomy [PM] for pleomorphic sarcoma/malignant fibrous histocytoma had the shortest median overall survival (23.6 months), whereas those who underwent PM for leiomyosarcoma had a median overall survival of 42 months,” he said.
The study subjects had pulmonary metastasectomies at Memorial Sloan Kettering Cancer Center, New York, during September 1991–June 2014. The median overall survival was 33.2 months, and median disease-free survival was 6.8 months for the entire cohort.
Among the disease characteristics associated with a lower hazard ratio of death shown by multivariable analyses were leiomyosarcoma histologic subtype (HR, 0.57), primary tumor size of 10 cm or less (HR, 1.00 vs. HR, 1.37 for those greater than 10 cm), increasing time from primary tumor resection to development of metastases (HR, 0.4 at less than 24 months vs. 1.0 at less than 6 months), solitary lung metastasis (HR, 1.0 vs. 1.8 for one year or more), and minimally invasive resection (HR, 0.71), all of which were statistically significant differences. Disease-free interval of more than one year and one pulmonary metastasis were significantly associated with lower hazard of disease recurrence.
Of patients, 70% had pulmonary metastasectomy as their primary treatment. The remainder had induction chemotherapy. In addition, 71% had open procedures over the 23-year study period, but minimally invasive operations became more common with time, increasing more than fourfold from the first half of the study period, vs. the last. They accounted for more than half of all procedures in the last five years of the study.
With regard to tumor type, fibrosarcoma was associated with longest median overall survival (65.2 months). Dr. Chudgar and his colleagues noted that 43% of these patients had low-grade primary tumors. Patients with low-grade tumors of all types had a median overall survival of 71.8 months, vs. 30.8 months for those with high-grade tumors.
“Our results indicate that therapeutic-intent pulmonary metastasectomy for soft-tissue sarcoma can be associated with prolonged survival,” Dr. Chudgar and his coauthors said. “The median survivals in our study are comparable with those in previous studies.” However, their analysis went beyond previous studies because they identified positive prognostic factors.
Dr. Chudgar and his coauthors acknowledge that various studies have drawn conflicting conclusions about the validity of histologic subtype as a prognostic factor, but their study differs from previous studies because it is a single-center cohort, “which increases the power to potentially identify significant differences, and we focused on soft-tissue sarcoma exclusively to enhance the homogeneity of the study population.”
Nonetheless, the researchers noted some limitations of their study, namely their collective analysis of the various soft-tissue sarcoma subtypes and the lack of a control group. Soft tissue sarcoma, because of its heterogeneous nature, challenges the adoption of precision medicine for this cancer type, but, until clinicians better understand the underlying mechanism of metastasis in these tumor types, Dr. Chudgar and his coauthors said, pulmonary metastasectomy “remains the best available treatment for soft tissue sarcoma pulmonary metastases.”
Dr. Chudgar and his coauthors had no financial relationships to disclose.
The findings that surgery for pulmonary metastases achieves “relatively good median survival” that Dr. Chudgar and coauthors reported are “especially impressive when considering that more than 25% of these patients with metastatic cancer had five or more pulmonary lesions,” said Mark F. Berry, MD, MHS, of Stanford University in his invited commentary (J Thorac Cardiovasc Surg. 2017;154:117-8).
Dr. Berry also said, however, that surgeons still must consider these results cautiously for several reasons. One, the study is retrospective and uncontrolled. Two, the study does not address whether the researchers selected healthy patients “with favorable disease characteristics” for pulmonary metastasectomy. “The sobering reality is that most patients still had recurrence relatively soon after complete pulmonary resection,” Dr. Berry said.
The study does support the current practice of pulmonary metastasectomy, which many patients may prefer for its invasive nature, compared with systemic chemotherapy treatment, he said. “Overall, surgeons can use this study to aid patient selection [and] to support the clinical decision to pursue resection of soft-tissue sarcoma pulmonary metastases for patients judged to be appropriate surgical candidates,” Dr. Berry concluded.
Dr. Berry had reported no financial disclosures.
The findings that surgery for pulmonary metastases achieves “relatively good median survival” that Dr. Chudgar and coauthors reported are “especially impressive when considering that more than 25% of these patients with metastatic cancer had five or more pulmonary lesions,” said Mark F. Berry, MD, MHS, of Stanford University in his invited commentary (J Thorac Cardiovasc Surg. 2017;154:117-8).
Dr. Berry also said, however, that surgeons still must consider these results cautiously for several reasons. One, the study is retrospective and uncontrolled. Two, the study does not address whether the researchers selected healthy patients “with favorable disease characteristics” for pulmonary metastasectomy. “The sobering reality is that most patients still had recurrence relatively soon after complete pulmonary resection,” Dr. Berry said.
The study does support the current practice of pulmonary metastasectomy, which many patients may prefer for its invasive nature, compared with systemic chemotherapy treatment, he said. “Overall, surgeons can use this study to aid patient selection [and] to support the clinical decision to pursue resection of soft-tissue sarcoma pulmonary metastases for patients judged to be appropriate surgical candidates,” Dr. Berry concluded.
Dr. Berry had reported no financial disclosures.
The findings that surgery for pulmonary metastases achieves “relatively good median survival” that Dr. Chudgar and coauthors reported are “especially impressive when considering that more than 25% of these patients with metastatic cancer had five or more pulmonary lesions,” said Mark F. Berry, MD, MHS, of Stanford University in his invited commentary (J Thorac Cardiovasc Surg. 2017;154:117-8).
Dr. Berry also said, however, that surgeons still must consider these results cautiously for several reasons. One, the study is retrospective and uncontrolled. Two, the study does not address whether the researchers selected healthy patients “with favorable disease characteristics” for pulmonary metastasectomy. “The sobering reality is that most patients still had recurrence relatively soon after complete pulmonary resection,” Dr. Berry said.
The study does support the current practice of pulmonary metastasectomy, which many patients may prefer for its invasive nature, compared with systemic chemotherapy treatment, he said. “Overall, surgeons can use this study to aid patient selection [and] to support the clinical decision to pursue resection of soft-tissue sarcoma pulmonary metastases for patients judged to be appropriate surgical candidates,” Dr. Berry concluded.
Dr. Berry had reported no financial disclosures.
The rate of soft-tissue sarcoma has nearly doubled over the past two decades, and up to 50% of patients with tissue sarcoma develop lung metastasis. A single-center study of 539 patients who had treatment for soft-tissue sarcoma has revealed disease and treatment characteristics that may aid patient selection and help predict overall and disease-free survival after diagnosis and treatment.
“Histologic subtype and size of the primary tumor were significantly associated with overall survival,” said lead author Neel P. Chudgar, MD, and his coauthors in the July issue of the Journal of Thoracic and Cardiovascular Surgery (2017;154:319-30).
“Patients who underwent pulmonary metastasectomy [PM] for pleomorphic sarcoma/malignant fibrous histocytoma had the shortest median overall survival (23.6 months), whereas those who underwent PM for leiomyosarcoma had a median overall survival of 42 months,” he said.
The study subjects had pulmonary metastasectomies at Memorial Sloan Kettering Cancer Center, New York, during September 1991–June 2014. The median overall survival was 33.2 months, and median disease-free survival was 6.8 months for the entire cohort.
Among the disease characteristics associated with a lower hazard ratio of death shown by multivariable analyses were leiomyosarcoma histologic subtype (HR, 0.57), primary tumor size of 10 cm or less (HR, 1.00 vs. HR, 1.37 for those greater than 10 cm), increasing time from primary tumor resection to development of metastases (HR, 0.4 at less than 24 months vs. 1.0 at less than 6 months), solitary lung metastasis (HR, 1.0 vs. 1.8 for one year or more), and minimally invasive resection (HR, 0.71), all of which were statistically significant differences. Disease-free interval of more than one year and one pulmonary metastasis were significantly associated with lower hazard of disease recurrence.
Of patients, 70% had pulmonary metastasectomy as their primary treatment. The remainder had induction chemotherapy. In addition, 71% had open procedures over the 23-year study period, but minimally invasive operations became more common with time, increasing more than fourfold from the first half of the study period, vs. the last. They accounted for more than half of all procedures in the last five years of the study.
With regard to tumor type, fibrosarcoma was associated with longest median overall survival (65.2 months). Dr. Chudgar and his colleagues noted that 43% of these patients had low-grade primary tumors. Patients with low-grade tumors of all types had a median overall survival of 71.8 months, vs. 30.8 months for those with high-grade tumors.
“Our results indicate that therapeutic-intent pulmonary metastasectomy for soft-tissue sarcoma can be associated with prolonged survival,” Dr. Chudgar and his coauthors said. “The median survivals in our study are comparable with those in previous studies.” However, their analysis went beyond previous studies because they identified positive prognostic factors.
Dr. Chudgar and his coauthors acknowledge that various studies have drawn conflicting conclusions about the validity of histologic subtype as a prognostic factor, but their study differs from previous studies because it is a single-center cohort, “which increases the power to potentially identify significant differences, and we focused on soft-tissue sarcoma exclusively to enhance the homogeneity of the study population.”
Nonetheless, the researchers noted some limitations of their study, namely their collective analysis of the various soft-tissue sarcoma subtypes and the lack of a control group. Soft tissue sarcoma, because of its heterogeneous nature, challenges the adoption of precision medicine for this cancer type, but, until clinicians better understand the underlying mechanism of metastasis in these tumor types, Dr. Chudgar and his coauthors said, pulmonary metastasectomy “remains the best available treatment for soft tissue sarcoma pulmonary metastases.”
Dr. Chudgar and his coauthors had no financial relationships to disclose.
The rate of soft-tissue sarcoma has nearly doubled over the past two decades, and up to 50% of patients with tissue sarcoma develop lung metastasis. A single-center study of 539 patients who had treatment for soft-tissue sarcoma has revealed disease and treatment characteristics that may aid patient selection and help predict overall and disease-free survival after diagnosis and treatment.
“Histologic subtype and size of the primary tumor were significantly associated with overall survival,” said lead author Neel P. Chudgar, MD, and his coauthors in the July issue of the Journal of Thoracic and Cardiovascular Surgery (2017;154:319-30).
“Patients who underwent pulmonary metastasectomy [PM] for pleomorphic sarcoma/malignant fibrous histocytoma had the shortest median overall survival (23.6 months), whereas those who underwent PM for leiomyosarcoma had a median overall survival of 42 months,” he said.
The study subjects had pulmonary metastasectomies at Memorial Sloan Kettering Cancer Center, New York, during September 1991–June 2014. The median overall survival was 33.2 months, and median disease-free survival was 6.8 months for the entire cohort.
Among the disease characteristics associated with a lower hazard ratio of death shown by multivariable analyses were leiomyosarcoma histologic subtype (HR, 0.57), primary tumor size of 10 cm or less (HR, 1.00 vs. HR, 1.37 for those greater than 10 cm), increasing time from primary tumor resection to development of metastases (HR, 0.4 at less than 24 months vs. 1.0 at less than 6 months), solitary lung metastasis (HR, 1.0 vs. 1.8 for one year or more), and minimally invasive resection (HR, 0.71), all of which were statistically significant differences. Disease-free interval of more than one year and one pulmonary metastasis were significantly associated with lower hazard of disease recurrence.
Of patients, 70% had pulmonary metastasectomy as their primary treatment. The remainder had induction chemotherapy. In addition, 71% had open procedures over the 23-year study period, but minimally invasive operations became more common with time, increasing more than fourfold from the first half of the study period, vs. the last. They accounted for more than half of all procedures in the last five years of the study.
With regard to tumor type, fibrosarcoma was associated with longest median overall survival (65.2 months). Dr. Chudgar and his colleagues noted that 43% of these patients had low-grade primary tumors. Patients with low-grade tumors of all types had a median overall survival of 71.8 months, vs. 30.8 months for those with high-grade tumors.
“Our results indicate that therapeutic-intent pulmonary metastasectomy for soft-tissue sarcoma can be associated with prolonged survival,” Dr. Chudgar and his coauthors said. “The median survivals in our study are comparable with those in previous studies.” However, their analysis went beyond previous studies because they identified positive prognostic factors.
Dr. Chudgar and his coauthors acknowledge that various studies have drawn conflicting conclusions about the validity of histologic subtype as a prognostic factor, but their study differs from previous studies because it is a single-center cohort, “which increases the power to potentially identify significant differences, and we focused on soft-tissue sarcoma exclusively to enhance the homogeneity of the study population.”
Nonetheless, the researchers noted some limitations of their study, namely their collective analysis of the various soft-tissue sarcoma subtypes and the lack of a control group. Soft tissue sarcoma, because of its heterogeneous nature, challenges the adoption of precision medicine for this cancer type, but, until clinicians better understand the underlying mechanism of metastasis in these tumor types, Dr. Chudgar and his coauthors said, pulmonary metastasectomy “remains the best available treatment for soft tissue sarcoma pulmonary metastases.”
Dr. Chudgar and his coauthors had no financial relationships to disclose.
FROM THE JOURNAL OF THORACIC AND CARDIOVASCULAR SURGERY
Key clinical point: Characteristics that determine survival in patients with sarcomatous pulmonary metastases are tumor subtype and size, number of and time to metastases, and minimally invasive surgery.
Major finding: Patients with leiomyosarcoma histologic subtype tumor had a hazard ratio of 0.57 (P = .001), and those with a primary tumor size of 10 cm or less had an HR of 1, vs. an HR of 1.37 for those greater than 10 cm (P = .006)
Data source: A single-institution study of 539 patients who had pulmonary mastectomy for metastatic soft tissue sarcoma from September 1991 to June 2014.
Disclosures: Dr. Chudgar and his coauthors had no financial relationships to disclose.
Immune signature shows good prognostic performance in early-stage NSCLC
A new tumor immune-related gene signature may help take the guesswork out of prognostication in patients with early-stage non–small cell lung cancer (NSCLC), according to a retrospective cohort study.
“Various components of the immune system have been shown to be a determining factor during cancer initiation and progression,” note the investigators, who were led by Bailiang Li, PhD, of Stanford (Calif.) University. “Recent immunotherapies targeting specific immune checkpoints such as programmed death 1 or programmed death ligand 1 have demonstrated a remarkable, durable response in NSCLC. Certain histopathologic patterns, such as intratumoral infiltration by cytotoxic lymphocytes, have also been associated with better prognoses in several cancer types, including NSCLC.”
For the study, the investigators developed and validated an immune-related gene signature using frozen tumors from 2,414 patients with stage I or II nonsquamous NSCLC from 19 public cohorts who underwent resection with negative margins and did not receive any neoadjuvant or adjuvant therapy.
The new signature contained 25 gene pairs consisting of 40 unique immune-related genes, Dr. Li and associates report (JAMA Oncol. 2017 Jul 6. doi: 10.1001/jamaoncol.2017.1609).
Processes such as chemotaxis were enriched among the included genes.
The signature significantly stratified patients into groups that have high and low risks of death during follow-up, both across and within subsets with stage I, IA, IB, or II disease. Relative to counterparts falling into the signature-defined low-risk group, those falling into the signature-defined high-risk group had roughly twice the risk of death after adjustment for clinical and pathologic characteristics, with a hazard ratio range of 1.72 (P less than .001) to 2.36 (P less than .001).
Accuracy of the immune signature exceeded that of two commercialized gene signatures for estimating survival in similar validation cohorts (mean concordance index [C-index], 0.64 vs 0.53 and 0.61).
Moreover, the combination of the immune signature with clinical factors outperformed the signature alone (mean C-index, 0.70 vs 0.63) and another commercialized clinical-molecular combination signature (mean C-index, 0.68 vs 0.65).
“The proposed immune-related gene pair–based signature is a promising prognostic biomarker in nonsquamous NSCLC, including early-stage disease,” concluded the investigators. “Prospective studies are needed to further validate its analytical accuracy for estimating prognoses and to test its clinical utility in individualized management of nonsquamous NSCLC.”
M. Patricia Rivera, MD, FCCP, comments: As lung cancer screening implementation increases, it is expected that the prevalence of early-stage non–small cell lung cancer (NSCLC) will increase.
Currently, adjuvant therapy is reserved for patients with tumors greater than 4 cm or those with N1 disease. Having reliable biomarkers to identify patients at a high risk for recurrence after surgical resection is a significant clinical advantage in order to guide adjuvant therapy. The clinical-immune signature described in this study is an exciting and promising biomarker for estimating overall survival in NSCLC.
M. Patricia Rivera, MD, FCCP, comments: As lung cancer screening implementation increases, it is expected that the prevalence of early-stage non–small cell lung cancer (NSCLC) will increase.
Currently, adjuvant therapy is reserved for patients with tumors greater than 4 cm or those with N1 disease. Having reliable biomarkers to identify patients at a high risk for recurrence after surgical resection is a significant clinical advantage in order to guide adjuvant therapy. The clinical-immune signature described in this study is an exciting and promising biomarker for estimating overall survival in NSCLC.
M. Patricia Rivera, MD, FCCP, comments: As lung cancer screening implementation increases, it is expected that the prevalence of early-stage non–small cell lung cancer (NSCLC) will increase.
Currently, adjuvant therapy is reserved for patients with tumors greater than 4 cm or those with N1 disease. Having reliable biomarkers to identify patients at a high risk for recurrence after surgical resection is a significant clinical advantage in order to guide adjuvant therapy. The clinical-immune signature described in this study is an exciting and promising biomarker for estimating overall survival in NSCLC.
A new tumor immune-related gene signature may help take the guesswork out of prognostication in patients with early-stage non–small cell lung cancer (NSCLC), according to a retrospective cohort study.
“Various components of the immune system have been shown to be a determining factor during cancer initiation and progression,” note the investigators, who were led by Bailiang Li, PhD, of Stanford (Calif.) University. “Recent immunotherapies targeting specific immune checkpoints such as programmed death 1 or programmed death ligand 1 have demonstrated a remarkable, durable response in NSCLC. Certain histopathologic patterns, such as intratumoral infiltration by cytotoxic lymphocytes, have also been associated with better prognoses in several cancer types, including NSCLC.”
For the study, the investigators developed and validated an immune-related gene signature using frozen tumors from 2,414 patients with stage I or II nonsquamous NSCLC from 19 public cohorts who underwent resection with negative margins and did not receive any neoadjuvant or adjuvant therapy.
The new signature contained 25 gene pairs consisting of 40 unique immune-related genes, Dr. Li and associates report (JAMA Oncol. 2017 Jul 6. doi: 10.1001/jamaoncol.2017.1609).
Processes such as chemotaxis were enriched among the included genes.
The signature significantly stratified patients into groups that have high and low risks of death during follow-up, both across and within subsets with stage I, IA, IB, or II disease. Relative to counterparts falling into the signature-defined low-risk group, those falling into the signature-defined high-risk group had roughly twice the risk of death after adjustment for clinical and pathologic characteristics, with a hazard ratio range of 1.72 (P less than .001) to 2.36 (P less than .001).
Accuracy of the immune signature exceeded that of two commercialized gene signatures for estimating survival in similar validation cohorts (mean concordance index [C-index], 0.64 vs 0.53 and 0.61).
Moreover, the combination of the immune signature with clinical factors outperformed the signature alone (mean C-index, 0.70 vs 0.63) and another commercialized clinical-molecular combination signature (mean C-index, 0.68 vs 0.65).
“The proposed immune-related gene pair–based signature is a promising prognostic biomarker in nonsquamous NSCLC, including early-stage disease,” concluded the investigators. “Prospective studies are needed to further validate its analytical accuracy for estimating prognoses and to test its clinical utility in individualized management of nonsquamous NSCLC.”
A new tumor immune-related gene signature may help take the guesswork out of prognostication in patients with early-stage non–small cell lung cancer (NSCLC), according to a retrospective cohort study.
“Various components of the immune system have been shown to be a determining factor during cancer initiation and progression,” note the investigators, who were led by Bailiang Li, PhD, of Stanford (Calif.) University. “Recent immunotherapies targeting specific immune checkpoints such as programmed death 1 or programmed death ligand 1 have demonstrated a remarkable, durable response in NSCLC. Certain histopathologic patterns, such as intratumoral infiltration by cytotoxic lymphocytes, have also been associated with better prognoses in several cancer types, including NSCLC.”
For the study, the investigators developed and validated an immune-related gene signature using frozen tumors from 2,414 patients with stage I or II nonsquamous NSCLC from 19 public cohorts who underwent resection with negative margins and did not receive any neoadjuvant or adjuvant therapy.
The new signature contained 25 gene pairs consisting of 40 unique immune-related genes, Dr. Li and associates report (JAMA Oncol. 2017 Jul 6. doi: 10.1001/jamaoncol.2017.1609).
Processes such as chemotaxis were enriched among the included genes.
The signature significantly stratified patients into groups that have high and low risks of death during follow-up, both across and within subsets with stage I, IA, IB, or II disease. Relative to counterparts falling into the signature-defined low-risk group, those falling into the signature-defined high-risk group had roughly twice the risk of death after adjustment for clinical and pathologic characteristics, with a hazard ratio range of 1.72 (P less than .001) to 2.36 (P less than .001).
Accuracy of the immune signature exceeded that of two commercialized gene signatures for estimating survival in similar validation cohorts (mean concordance index [C-index], 0.64 vs 0.53 and 0.61).
Moreover, the combination of the immune signature with clinical factors outperformed the signature alone (mean C-index, 0.70 vs 0.63) and another commercialized clinical-molecular combination signature (mean C-index, 0.68 vs 0.65).
“The proposed immune-related gene pair–based signature is a promising prognostic biomarker in nonsquamous NSCLC, including early-stage disease,” concluded the investigators. “Prospective studies are needed to further validate its analytical accuracy for estimating prognoses and to test its clinical utility in individualized management of nonsquamous NSCLC.”
FROM JAMA ONCOLOGY
Key clinical point:
Major finding: Compared with peers in the signature-defined low-risk group, patients in the signature-defined high-risk group had roughly twice the adjusted risk of death (hazard ratio range, 1.72-2.36).
Data source: A retrospective cohort study using frozen tumors from 2,414 patients with stage I or II nonsquamous NSCLC who underwent complete resection and did not receive adjuvant or neoadjuvant therapy.
Disclosures: The investigators reported that they had no relevant disclosures. The study was supported in part by the National Institutes of Health.