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Ketorolac may reduce breast cancer recurrence risk, particularly in overweight patients
Ketorolac administered during primary tumor surgery may cut risk of distant recurrences in patients with breast cancer, results of a retrospective study show.
Overweight patients appeared most likely to benefit from interoperative treatment with this nonsteroidal anti-inflammatory drug, study investigators reported.
“This approach could be extremely appealing for parts of the globe where obesity has been strongly increasing during the last decade and where resources for cancer treatment are scarce,” they wrote. The report was published in the Journal of the National Cancer Institute.
Ketorolac inhibits enzymes upregulated by leptin, a hormone abnormally secreted in the setting of overweight or obesity, which might explain the concentration of benefit in high–body mass index individuals, noted Christine Desmedt, PhD, of the Breast Cancer Translational Research Laboratory, Institut Jules Bordet, Brussels, and her coauthors.
Indeed, the study also showed no benefit to intraoperative administration of another NSAID, diclofenac, which does not appear to have the same enzyme-inhibitory effects as ketorolac, the investigators said.
This recently published analysis by Dr. Desmedt and her colleagues was based on two retrospective series of patients: one evaluating intraoperative ketorolac in 529 patients versus 298 patients who received no ketorolac, and one evaluating intraoperative diclofenac in 787 patients, versus 220 who did not receive that NSAID.
The investigators found a significant association between ketorolac given during surgery and decreased incidence of distant metastasis (adjusted hazard ratio [aHR], 0.59, 95% confidence interval, 0.37-0.96, P = .03). Reduced recurrence was most evident in patients with high BMI (aHR, 0.55; 95% CI, 0.31-0.96; P = .04).
Further evaluation revealed that the benefit of ketorolac was “clearly associated” with a reduction in early metastases, both overall and in the high-BMI subgroup, the investigators said.
By contrast, intraoperative diclofenac was not associated with a decrease in distant recurrences, overall (adjusted HR, 1.04; 95% CI, 0.58-1.87, P = .88) or in BMI subgroup analysis, investigators said.
While some might be surprised that a single dose of ketorolac could reduce distant recurrence, it might be explained by the timing of NSAID delivery, they noted. In previous studies, primary tumor removal has been shown to disturb disease homeostasis, and thus might trigger early recurrences.
“Complex system dynamics are exquisitely sensitive on initial conditions, and, therefore, changes occurring in critical early times may be able to cause major changes in system evolution,” the investigators wrote in a discussion of the results.
The finding is also not without precedent. The authors cited one Scandinavian randomized trial in which a single course of perioperative cyclophosphamide significantly improved disease-free survival at more than 17 years of follow-up; by contrast, giving the treatment 2-4 weeks after mastectomy provided no such benefit.
In addition, ketorolac’s potential perioperative benefit has been shown in other tumor types, including improved disease-free survival in one institutional series of lung cancer patients, and reduced disease-specific mortality in a retrospective study of ovarian cancer patients.
The present breast cancer study is limited because it is retrospective, and does not address questions regarding optimal timing or duration of dose. However, “it suggests a potentially important repositioning of ketorolac in the intraoperative treatment of breast cancer patients with elevated BMI, and points to the need for a prospective confirmatory randomized trial,” the authors said.
Dr. Desmedt and her colleagues reported no conflicts of interest related to the study.
SOURCE: Desmedt C et al. J Natl Cancer Inst. 2018 Apr 30. doi: 10.1093/jnci/djy042.
Ketorolac administered during primary tumor surgery may cut risk of distant recurrences in patients with breast cancer, results of a retrospective study show.
Overweight patients appeared most likely to benefit from interoperative treatment with this nonsteroidal anti-inflammatory drug, study investigators reported.
“This approach could be extremely appealing for parts of the globe where obesity has been strongly increasing during the last decade and where resources for cancer treatment are scarce,” they wrote. The report was published in the Journal of the National Cancer Institute.
Ketorolac inhibits enzymes upregulated by leptin, a hormone abnormally secreted in the setting of overweight or obesity, which might explain the concentration of benefit in high–body mass index individuals, noted Christine Desmedt, PhD, of the Breast Cancer Translational Research Laboratory, Institut Jules Bordet, Brussels, and her coauthors.
Indeed, the study also showed no benefit to intraoperative administration of another NSAID, diclofenac, which does not appear to have the same enzyme-inhibitory effects as ketorolac, the investigators said.
This recently published analysis by Dr. Desmedt and her colleagues was based on two retrospective series of patients: one evaluating intraoperative ketorolac in 529 patients versus 298 patients who received no ketorolac, and one evaluating intraoperative diclofenac in 787 patients, versus 220 who did not receive that NSAID.
The investigators found a significant association between ketorolac given during surgery and decreased incidence of distant metastasis (adjusted hazard ratio [aHR], 0.59, 95% confidence interval, 0.37-0.96, P = .03). Reduced recurrence was most evident in patients with high BMI (aHR, 0.55; 95% CI, 0.31-0.96; P = .04).
Further evaluation revealed that the benefit of ketorolac was “clearly associated” with a reduction in early metastases, both overall and in the high-BMI subgroup, the investigators said.
By contrast, intraoperative diclofenac was not associated with a decrease in distant recurrences, overall (adjusted HR, 1.04; 95% CI, 0.58-1.87, P = .88) or in BMI subgroup analysis, investigators said.
While some might be surprised that a single dose of ketorolac could reduce distant recurrence, it might be explained by the timing of NSAID delivery, they noted. In previous studies, primary tumor removal has been shown to disturb disease homeostasis, and thus might trigger early recurrences.
“Complex system dynamics are exquisitely sensitive on initial conditions, and, therefore, changes occurring in critical early times may be able to cause major changes in system evolution,” the investigators wrote in a discussion of the results.
The finding is also not without precedent. The authors cited one Scandinavian randomized trial in which a single course of perioperative cyclophosphamide significantly improved disease-free survival at more than 17 years of follow-up; by contrast, giving the treatment 2-4 weeks after mastectomy provided no such benefit.
In addition, ketorolac’s potential perioperative benefit has been shown in other tumor types, including improved disease-free survival in one institutional series of lung cancer patients, and reduced disease-specific mortality in a retrospective study of ovarian cancer patients.
The present breast cancer study is limited because it is retrospective, and does not address questions regarding optimal timing or duration of dose. However, “it suggests a potentially important repositioning of ketorolac in the intraoperative treatment of breast cancer patients with elevated BMI, and points to the need for a prospective confirmatory randomized trial,” the authors said.
Dr. Desmedt and her colleagues reported no conflicts of interest related to the study.
SOURCE: Desmedt C et al. J Natl Cancer Inst. 2018 Apr 30. doi: 10.1093/jnci/djy042.
Ketorolac administered during primary tumor surgery may cut risk of distant recurrences in patients with breast cancer, results of a retrospective study show.
Overweight patients appeared most likely to benefit from interoperative treatment with this nonsteroidal anti-inflammatory drug, study investigators reported.
“This approach could be extremely appealing for parts of the globe where obesity has been strongly increasing during the last decade and where resources for cancer treatment are scarce,” they wrote. The report was published in the Journal of the National Cancer Institute.
Ketorolac inhibits enzymes upregulated by leptin, a hormone abnormally secreted in the setting of overweight or obesity, which might explain the concentration of benefit in high–body mass index individuals, noted Christine Desmedt, PhD, of the Breast Cancer Translational Research Laboratory, Institut Jules Bordet, Brussels, and her coauthors.
Indeed, the study also showed no benefit to intraoperative administration of another NSAID, diclofenac, which does not appear to have the same enzyme-inhibitory effects as ketorolac, the investigators said.
This recently published analysis by Dr. Desmedt and her colleagues was based on two retrospective series of patients: one evaluating intraoperative ketorolac in 529 patients versus 298 patients who received no ketorolac, and one evaluating intraoperative diclofenac in 787 patients, versus 220 who did not receive that NSAID.
The investigators found a significant association between ketorolac given during surgery and decreased incidence of distant metastasis (adjusted hazard ratio [aHR], 0.59, 95% confidence interval, 0.37-0.96, P = .03). Reduced recurrence was most evident in patients with high BMI (aHR, 0.55; 95% CI, 0.31-0.96; P = .04).
Further evaluation revealed that the benefit of ketorolac was “clearly associated” with a reduction in early metastases, both overall and in the high-BMI subgroup, the investigators said.
By contrast, intraoperative diclofenac was not associated with a decrease in distant recurrences, overall (adjusted HR, 1.04; 95% CI, 0.58-1.87, P = .88) or in BMI subgroup analysis, investigators said.
While some might be surprised that a single dose of ketorolac could reduce distant recurrence, it might be explained by the timing of NSAID delivery, they noted. In previous studies, primary tumor removal has been shown to disturb disease homeostasis, and thus might trigger early recurrences.
“Complex system dynamics are exquisitely sensitive on initial conditions, and, therefore, changes occurring in critical early times may be able to cause major changes in system evolution,” the investigators wrote in a discussion of the results.
The finding is also not without precedent. The authors cited one Scandinavian randomized trial in which a single course of perioperative cyclophosphamide significantly improved disease-free survival at more than 17 years of follow-up; by contrast, giving the treatment 2-4 weeks after mastectomy provided no such benefit.
In addition, ketorolac’s potential perioperative benefit has been shown in other tumor types, including improved disease-free survival in one institutional series of lung cancer patients, and reduced disease-specific mortality in a retrospective study of ovarian cancer patients.
The present breast cancer study is limited because it is retrospective, and does not address questions regarding optimal timing or duration of dose. However, “it suggests a potentially important repositioning of ketorolac in the intraoperative treatment of breast cancer patients with elevated BMI, and points to the need for a prospective confirmatory randomized trial,” the authors said.
Dr. Desmedt and her colleagues reported no conflicts of interest related to the study.
SOURCE: Desmedt C et al. J Natl Cancer Inst. 2018 Apr 30. doi: 10.1093/jnci/djy042.
FROM THE JOURNAL OF THE NATIONAL CANCER INSTITUTE
Key clinical point: Administration of ketorolac during primary tumor surgery was associated with a reduction of distant recurrences, particularly in overweight patients.
Major finding: Reduced recurrence was most evident in patients with high BMI (adjusted hazard ratio, 0.55; 95% CI, 0.31-0.96; P = .04).
Study details: Analysis of two retrospective series, including a total of 1,834 patients with breast cancer, evaluating intraoperative administration of ketorolac or diclofenac.
Disclosures: The authors declared no conflicts of interest.
Source: Desmedt C et al. J Natl Cancer Inst. 2018 Apr 30. doi: 10.1093/jnci/djy042.
Oral diabetes drugs linked to lower levels of bone formation marker
in a Danish clinical trial.
Procollagen type 1 N-terminal peptide (P1NP) plasma concentrations were lower in patients who received either metformin or metformin plus rosiglitazone, Tore Bjerregaard Stage, PhD, a specialist in clinical pharmacology and pharmacy at the University of Southern Denmark, Odense, and his coauthors wrote in Bone.
By contrast, insulin did not appear to influence markers of bone turnover.
Improving glycemic control was associated with increased plasma concentrations of C-terminal telopeptide of collagen (CTx), a marker of bone resorption. However, this finding might reflect “normalization, rather than an abnormal increase in bone resorption,” Dr. Stage and his colleagues wrote.
These findings come from an analysis of the South Danish Diabetes Study, a 2-year, multicenter, randomized, controlled trial including 371 patients with type 2 diabetes. Patients were first randomized to receive short- or long-acting human insulin, then further randomized to metformin plus rosiglitazone, metformin plus placebo, rosiglitazone plus placebo, or two placebos.
Bone turnover markers were assessed at baseline and at 3-, 12-, and 24-month follow-ups.
Dr. Stage and his coinvestigators hoped the analysis would provide insights into how antidiabetic medication might influence bone turnover, potentially helping explain the increased risk of fracture found in patients with type 2 diabetes. “Alterations in bone metabolism due to antidiabetic medication may influence bone metabolism both directly, e.g., by insulin promoting bone formation, and indirectly by improvement of glycemic control,” they wrote.
Overall, levels of both bone turnover markers increased over time in the study. However, investigators found that concentrations of the bone formation marker P1NP were 13% lower in patients randomized to metformin alone, and 21% lower in patients randomized to metformin and rosiglitazone; no such association was found between P1NP concentrations and treatment with rosiglitazone alone. By contrast, the type of oral antidiabetic drug treatment had no effect on concentrations of CTx concentrations, the investigators said.
Type of insulin treatment received in the trial did not appear to have an impact on concentrations of either bone turnover marker, they added.
HbA1c had no influence on concentrations of P1NP; but it was inversely correlated with levels of CTx, a finding that the investigators said merits more study.
“Further clinical trials investigating the effects of improved glycemic control on bone remodeling including other biochemical markers of bone turnover are needed to confirm if lowering of glucose levels solely changes bone resorption and not formation,” Dr. Stage and his coauthors wrote.
This study was funded with grants from the Danish Council for Independent Research and the Region of Southern Denmark. Dr. Stage and coauthors reported no conflicts of interest related to the report.
SOURCE: Stage TB et al. Bone. 2018 Apr 12;112:35-41.
in a Danish clinical trial.
Procollagen type 1 N-terminal peptide (P1NP) plasma concentrations were lower in patients who received either metformin or metformin plus rosiglitazone, Tore Bjerregaard Stage, PhD, a specialist in clinical pharmacology and pharmacy at the University of Southern Denmark, Odense, and his coauthors wrote in Bone.
By contrast, insulin did not appear to influence markers of bone turnover.
Improving glycemic control was associated with increased plasma concentrations of C-terminal telopeptide of collagen (CTx), a marker of bone resorption. However, this finding might reflect “normalization, rather than an abnormal increase in bone resorption,” Dr. Stage and his colleagues wrote.
These findings come from an analysis of the South Danish Diabetes Study, a 2-year, multicenter, randomized, controlled trial including 371 patients with type 2 diabetes. Patients were first randomized to receive short- or long-acting human insulin, then further randomized to metformin plus rosiglitazone, metformin plus placebo, rosiglitazone plus placebo, or two placebos.
Bone turnover markers were assessed at baseline and at 3-, 12-, and 24-month follow-ups.
Dr. Stage and his coinvestigators hoped the analysis would provide insights into how antidiabetic medication might influence bone turnover, potentially helping explain the increased risk of fracture found in patients with type 2 diabetes. “Alterations in bone metabolism due to antidiabetic medication may influence bone metabolism both directly, e.g., by insulin promoting bone formation, and indirectly by improvement of glycemic control,” they wrote.
Overall, levels of both bone turnover markers increased over time in the study. However, investigators found that concentrations of the bone formation marker P1NP were 13% lower in patients randomized to metformin alone, and 21% lower in patients randomized to metformin and rosiglitazone; no such association was found between P1NP concentrations and treatment with rosiglitazone alone. By contrast, the type of oral antidiabetic drug treatment had no effect on concentrations of CTx concentrations, the investigators said.
Type of insulin treatment received in the trial did not appear to have an impact on concentrations of either bone turnover marker, they added.
HbA1c had no influence on concentrations of P1NP; but it was inversely correlated with levels of CTx, a finding that the investigators said merits more study.
“Further clinical trials investigating the effects of improved glycemic control on bone remodeling including other biochemical markers of bone turnover are needed to confirm if lowering of glucose levels solely changes bone resorption and not formation,” Dr. Stage and his coauthors wrote.
This study was funded with grants from the Danish Council for Independent Research and the Region of Southern Denmark. Dr. Stage and coauthors reported no conflicts of interest related to the report.
SOURCE: Stage TB et al. Bone. 2018 Apr 12;112:35-41.
in a Danish clinical trial.
Procollagen type 1 N-terminal peptide (P1NP) plasma concentrations were lower in patients who received either metformin or metformin plus rosiglitazone, Tore Bjerregaard Stage, PhD, a specialist in clinical pharmacology and pharmacy at the University of Southern Denmark, Odense, and his coauthors wrote in Bone.
By contrast, insulin did not appear to influence markers of bone turnover.
Improving glycemic control was associated with increased plasma concentrations of C-terminal telopeptide of collagen (CTx), a marker of bone resorption. However, this finding might reflect “normalization, rather than an abnormal increase in bone resorption,” Dr. Stage and his colleagues wrote.
These findings come from an analysis of the South Danish Diabetes Study, a 2-year, multicenter, randomized, controlled trial including 371 patients with type 2 diabetes. Patients were first randomized to receive short- or long-acting human insulin, then further randomized to metformin plus rosiglitazone, metformin plus placebo, rosiglitazone plus placebo, or two placebos.
Bone turnover markers were assessed at baseline and at 3-, 12-, and 24-month follow-ups.
Dr. Stage and his coinvestigators hoped the analysis would provide insights into how antidiabetic medication might influence bone turnover, potentially helping explain the increased risk of fracture found in patients with type 2 diabetes. “Alterations in bone metabolism due to antidiabetic medication may influence bone metabolism both directly, e.g., by insulin promoting bone formation, and indirectly by improvement of glycemic control,” they wrote.
Overall, levels of both bone turnover markers increased over time in the study. However, investigators found that concentrations of the bone formation marker P1NP were 13% lower in patients randomized to metformin alone, and 21% lower in patients randomized to metformin and rosiglitazone; no such association was found between P1NP concentrations and treatment with rosiglitazone alone. By contrast, the type of oral antidiabetic drug treatment had no effect on concentrations of CTx concentrations, the investigators said.
Type of insulin treatment received in the trial did not appear to have an impact on concentrations of either bone turnover marker, they added.
HbA1c had no influence on concentrations of P1NP; but it was inversely correlated with levels of CTx, a finding that the investigators said merits more study.
“Further clinical trials investigating the effects of improved glycemic control on bone remodeling including other biochemical markers of bone turnover are needed to confirm if lowering of glucose levels solely changes bone resorption and not formation,” Dr. Stage and his coauthors wrote.
This study was funded with grants from the Danish Council for Independent Research and the Region of Southern Denmark. Dr. Stage and coauthors reported no conflicts of interest related to the report.
SOURCE: Stage TB et al. Bone. 2018 Apr 12;112:35-41.
FROM BONE
Key clinical point: Treatment with oral antidiabetic drugs was associated with reductions in levels of P1NP, a marker of bone formation.
Major finding: Concentrations of P1NP were 13% lower in patients randomized to metformin and 21% lower in patients randomized to metformin and rosiglitazone.
Study details: An analysis of the South Danish Diabetes Study, a 2-year, multicenter, randomized, controlled trial of 371 patients with type 2 diabetes.
Disclosures: The authors reported no conflicts of interest related to the study.
Source: Stage TB et al. Bone. 2018 Apr 12;112:35-41.
Screening for brain mets could improve quality of life for some with breast cancer
Despite having more extensive metastases at presentation, breast cancer patients had outcomes after brain-directed therapy similar to those of lung cancer patients, results of a retrospective, single-center study show.
The breast cancer patients had larger and more numerous brain metastases compared with the non-small-cell lung cancer (NSCLC) patients, according to study results published in JAMA Oncology.
However, median survival was not statistically different between groups, at 1.45 years for the breast cancer patients and 1.09 years for NSCLC patients (P = .06), wrote Daniel N. Cagney, MD, of Dana-Farber/Brigham and Women’s Cancer Center, Harvard Medical School, Boston, and his coauthors.
“This finding suggests that intracranial disease in patients with breast cancer was not more aggressive or resistant to treatment, but rather was diagnosed at a later stage,” noted Dr. Cagney and his colleagues.
They described a retrospective analysis of 349 patients with breast cancer and 659 patients with NSCLC, all treated between 2000 and 2015 at Dana-Farber/Brigham and Women’s Cancer Center.
Median metastasis diameter at presentation was 17 mm for the breast cancer patients, compared with 14 mm for the lung cancer patients (P less than .001). Breast cancer patients were significantly more likely to be symptomatic, have seizures, harbor brainstem involvement, and have leptomeningeal disease at the time of diagnosis, the researchers wrote.
“After initial brain-directed therapy, no significant differences in recurrence or treatment-based intracranial outcomes were found between the two groups,” they noted. However, neurological death was seen in 37.3% of the breast cancer group versus 19.9% of the lung cancer group (P less than .001).
Dr. Cagney and his coauthors said they conducted the study to identify the potential value of brain-directed MRI screening in breast cancer, which they said is “important given the impact of neurological compromise on quality of life.”
Brain metastases are common in some subsets of breast cancer patients, yet National Comprehensive Cancer Network guidelines do not recommend brain-directed screening in breast cancer, “a recommendation that is based only on expert consensus given the lack of definitive or prospective studies on this issue,” they wrote.
In light of their findings, the investigators suggest that brain-directed MRI screening is important for breast cancer patients who present with potential for intracranial involvement.
“Early identification of intracranial disease facilitates less invasive or less toxic approaches, such as stereotactic radiosurgery or careful use of promising systemic agents, rather than [whole brain radiation therapy] or neurosurgical resection.” they wrote.
In this study, whole brain radiation therapy was more common in the breast cancer group (59.9% versus 42.9% for the lung cancer group; P less than .001), the investigators noted.
Dr. Cagney and colleagues had no conflicts of interest to report.
SOURCE: Cagney DN et al. JAMA Oncol. 2018 May 17. doi: 10.1001/jamaoncol.2018.0813.
Despite having more extensive metastases at presentation, breast cancer patients had outcomes after brain-directed therapy similar to those of lung cancer patients, results of a retrospective, single-center study show.
The breast cancer patients had larger and more numerous brain metastases compared with the non-small-cell lung cancer (NSCLC) patients, according to study results published in JAMA Oncology.
However, median survival was not statistically different between groups, at 1.45 years for the breast cancer patients and 1.09 years for NSCLC patients (P = .06), wrote Daniel N. Cagney, MD, of Dana-Farber/Brigham and Women’s Cancer Center, Harvard Medical School, Boston, and his coauthors.
“This finding suggests that intracranial disease in patients with breast cancer was not more aggressive or resistant to treatment, but rather was diagnosed at a later stage,” noted Dr. Cagney and his colleagues.
They described a retrospective analysis of 349 patients with breast cancer and 659 patients with NSCLC, all treated between 2000 and 2015 at Dana-Farber/Brigham and Women’s Cancer Center.
Median metastasis diameter at presentation was 17 mm for the breast cancer patients, compared with 14 mm for the lung cancer patients (P less than .001). Breast cancer patients were significantly more likely to be symptomatic, have seizures, harbor brainstem involvement, and have leptomeningeal disease at the time of diagnosis, the researchers wrote.
“After initial brain-directed therapy, no significant differences in recurrence or treatment-based intracranial outcomes were found between the two groups,” they noted. However, neurological death was seen in 37.3% of the breast cancer group versus 19.9% of the lung cancer group (P less than .001).
Dr. Cagney and his coauthors said they conducted the study to identify the potential value of brain-directed MRI screening in breast cancer, which they said is “important given the impact of neurological compromise on quality of life.”
Brain metastases are common in some subsets of breast cancer patients, yet National Comprehensive Cancer Network guidelines do not recommend brain-directed screening in breast cancer, “a recommendation that is based only on expert consensus given the lack of definitive or prospective studies on this issue,” they wrote.
In light of their findings, the investigators suggest that brain-directed MRI screening is important for breast cancer patients who present with potential for intracranial involvement.
“Early identification of intracranial disease facilitates less invasive or less toxic approaches, such as stereotactic radiosurgery or careful use of promising systemic agents, rather than [whole brain radiation therapy] or neurosurgical resection.” they wrote.
In this study, whole brain radiation therapy was more common in the breast cancer group (59.9% versus 42.9% for the lung cancer group; P less than .001), the investigators noted.
Dr. Cagney and colleagues had no conflicts of interest to report.
SOURCE: Cagney DN et al. JAMA Oncol. 2018 May 17. doi: 10.1001/jamaoncol.2018.0813.
Despite having more extensive metastases at presentation, breast cancer patients had outcomes after brain-directed therapy similar to those of lung cancer patients, results of a retrospective, single-center study show.
The breast cancer patients had larger and more numerous brain metastases compared with the non-small-cell lung cancer (NSCLC) patients, according to study results published in JAMA Oncology.
However, median survival was not statistically different between groups, at 1.45 years for the breast cancer patients and 1.09 years for NSCLC patients (P = .06), wrote Daniel N. Cagney, MD, of Dana-Farber/Brigham and Women’s Cancer Center, Harvard Medical School, Boston, and his coauthors.
“This finding suggests that intracranial disease in patients with breast cancer was not more aggressive or resistant to treatment, but rather was diagnosed at a later stage,” noted Dr. Cagney and his colleagues.
They described a retrospective analysis of 349 patients with breast cancer and 659 patients with NSCLC, all treated between 2000 and 2015 at Dana-Farber/Brigham and Women’s Cancer Center.
Median metastasis diameter at presentation was 17 mm for the breast cancer patients, compared with 14 mm for the lung cancer patients (P less than .001). Breast cancer patients were significantly more likely to be symptomatic, have seizures, harbor brainstem involvement, and have leptomeningeal disease at the time of diagnosis, the researchers wrote.
“After initial brain-directed therapy, no significant differences in recurrence or treatment-based intracranial outcomes were found between the two groups,” they noted. However, neurological death was seen in 37.3% of the breast cancer group versus 19.9% of the lung cancer group (P less than .001).
Dr. Cagney and his coauthors said they conducted the study to identify the potential value of brain-directed MRI screening in breast cancer, which they said is “important given the impact of neurological compromise on quality of life.”
Brain metastases are common in some subsets of breast cancer patients, yet National Comprehensive Cancer Network guidelines do not recommend brain-directed screening in breast cancer, “a recommendation that is based only on expert consensus given the lack of definitive or prospective studies on this issue,” they wrote.
In light of their findings, the investigators suggest that brain-directed MRI screening is important for breast cancer patients who present with potential for intracranial involvement.
“Early identification of intracranial disease facilitates less invasive or less toxic approaches, such as stereotactic radiosurgery or careful use of promising systemic agents, rather than [whole brain radiation therapy] or neurosurgical resection.” they wrote.
In this study, whole brain radiation therapy was more common in the breast cancer group (59.9% versus 42.9% for the lung cancer group; P less than .001), the investigators noted.
Dr. Cagney and colleagues had no conflicts of interest to report.
SOURCE: Cagney DN et al. JAMA Oncol. 2018 May 17. doi: 10.1001/jamaoncol.2018.0813.
FROM JAMA ONCOLOGY
Key clinical point: Breast cancer patients presented with larger and more numerous brain metastases compared with non–small-cell lung cancer patients, but after brain-directed therapy, there were no differences in outcomes between groups.
Major finding: Median survival was 1.45 years for breast cancer patients and 1.09 for NSCLC patients.
Study details: A retrospective analysis of 349 patients with breast cancer and 659 patients with NSCLC treated between 2000 and 2015 at Dana-Farber/Brigham and Women’s Cancer Center.
Disclosures: The authors reported no conflicts of interest.
Source: Cagney DN et al. JAMA Oncol. 2018 May 17. doi: 10.1001/jamaoncol.2018.0813.
Recent studies of microbiota offer insights into digestive disease management
LAS VEGAS – Recent studies of human microbiota are yielding new insights that could improve the diagnosis, evaluation, and treatment of digestive diseases, according to Eamonn M. Quigley, MD.
There are “many possibilities” for new therapeutics that focus on the assemblage of bacteria and other microorganisms present in the human body, said Dr. Quigley, director of the Lynda K. and David M. Underwood Center for Digestive Disorders, Houston Methodist.
The role of the microbiota has already been well established, for example, in cases of Helicobacter pylori infection and Clostridium difficile–associated disease. “They’re the classics,” Dr. Quigley told attendees. “They’re the templates for studies in other diseases.”
Dr. Quigley shared results of one recent treatment-related study that he said could have important implications for sepsis prevention in infants. The randomized trial showed that administration of a particular synbiotic – a probiotic plus a prebiotic substance – may have reduced sepsis incidence among infants in rural India.
The study comprised 4,556 infants with no signs of sepsis who were given an oral synbiotic preparation of Lactobacillus plantarum plus fructooligosaccharide. The composite outcome of sepsis and death was reduced in the treatment arm of the study (risk ratio, 0.60; 95% confidence interval, 0.48-0.74).
Based on that outcome, investigators said in their report that the preparation could prevent a “large proportion” of neonatal sepsis in developing countries.
“This is a very dramatic result for a very simple and cheap intervention in a high-risk population,” Dr. Quigley said in his presentation at the meeting.
He also provided a short list of studies showing “exciting recent data” regarding the predictive role of microbiota.
In one such study, investigators showed that the oral microbiota associated with colorectal cancer is distinctive, raising the possibility that analyzing microbiota could help identify patients at risk for development of colon cancer or offer an alternative cancer screening method.
In other studies, Dr. Quigley said, microbiota have been associated with response to metformin, and to the immune checkpoint inhibitors that have become important in the treatment of cancers.
In addition, microbiota have been associated with predicting response to low fermentable, oligosaccharide, disaccharide, monosaccharide, and polyol (FODMAP) diets in irritable bowel syndrome patients, and predicting metabolic response to high-fiber diets, he added.
Diagnostics is another area where microbiota could soon become important: “In diseases like [inflammatory bowel disease and irritable bowel syndrome] where we have a very heterogeneous population, looking at the microbiota might allow us to define new disease categories,” Dr. Quigley said.
Despite the promise, much research is still needed to confirm many of the findings of experimental studies.
“I think it’s clear that the microbiota is important in health and disease,” Dr. Quigley said. “However, host/microbiome interactions in [humans] are complex and far from completely understood, and unfortunately, some of the elegant work in animal models has not quite translated into man.”
Global Academy for Medical Education and this news organization are owned by the same parent company.
Dr. Quigley reported disclosures related to Alimentary Health, Almirall, Biocodex, 4D Pharma, Menarini, Pharmasierra, Salix, Synergy, and Vibrant.
LAS VEGAS – Recent studies of human microbiota are yielding new insights that could improve the diagnosis, evaluation, and treatment of digestive diseases, according to Eamonn M. Quigley, MD.
There are “many possibilities” for new therapeutics that focus on the assemblage of bacteria and other microorganisms present in the human body, said Dr. Quigley, director of the Lynda K. and David M. Underwood Center for Digestive Disorders, Houston Methodist.
The role of the microbiota has already been well established, for example, in cases of Helicobacter pylori infection and Clostridium difficile–associated disease. “They’re the classics,” Dr. Quigley told attendees. “They’re the templates for studies in other diseases.”
Dr. Quigley shared results of one recent treatment-related study that he said could have important implications for sepsis prevention in infants. The randomized trial showed that administration of a particular synbiotic – a probiotic plus a prebiotic substance – may have reduced sepsis incidence among infants in rural India.
The study comprised 4,556 infants with no signs of sepsis who were given an oral synbiotic preparation of Lactobacillus plantarum plus fructooligosaccharide. The composite outcome of sepsis and death was reduced in the treatment arm of the study (risk ratio, 0.60; 95% confidence interval, 0.48-0.74).
Based on that outcome, investigators said in their report that the preparation could prevent a “large proportion” of neonatal sepsis in developing countries.
“This is a very dramatic result for a very simple and cheap intervention in a high-risk population,” Dr. Quigley said in his presentation at the meeting.
He also provided a short list of studies showing “exciting recent data” regarding the predictive role of microbiota.
In one such study, investigators showed that the oral microbiota associated with colorectal cancer is distinctive, raising the possibility that analyzing microbiota could help identify patients at risk for development of colon cancer or offer an alternative cancer screening method.
In other studies, Dr. Quigley said, microbiota have been associated with response to metformin, and to the immune checkpoint inhibitors that have become important in the treatment of cancers.
In addition, microbiota have been associated with predicting response to low fermentable, oligosaccharide, disaccharide, monosaccharide, and polyol (FODMAP) diets in irritable bowel syndrome patients, and predicting metabolic response to high-fiber diets, he added.
Diagnostics is another area where microbiota could soon become important: “In diseases like [inflammatory bowel disease and irritable bowel syndrome] where we have a very heterogeneous population, looking at the microbiota might allow us to define new disease categories,” Dr. Quigley said.
Despite the promise, much research is still needed to confirm many of the findings of experimental studies.
“I think it’s clear that the microbiota is important in health and disease,” Dr. Quigley said. “However, host/microbiome interactions in [humans] are complex and far from completely understood, and unfortunately, some of the elegant work in animal models has not quite translated into man.”
Global Academy for Medical Education and this news organization are owned by the same parent company.
Dr. Quigley reported disclosures related to Alimentary Health, Almirall, Biocodex, 4D Pharma, Menarini, Pharmasierra, Salix, Synergy, and Vibrant.
LAS VEGAS – Recent studies of human microbiota are yielding new insights that could improve the diagnosis, evaluation, and treatment of digestive diseases, according to Eamonn M. Quigley, MD.
There are “many possibilities” for new therapeutics that focus on the assemblage of bacteria and other microorganisms present in the human body, said Dr. Quigley, director of the Lynda K. and David M. Underwood Center for Digestive Disorders, Houston Methodist.
The role of the microbiota has already been well established, for example, in cases of Helicobacter pylori infection and Clostridium difficile–associated disease. “They’re the classics,” Dr. Quigley told attendees. “They’re the templates for studies in other diseases.”
Dr. Quigley shared results of one recent treatment-related study that he said could have important implications for sepsis prevention in infants. The randomized trial showed that administration of a particular synbiotic – a probiotic plus a prebiotic substance – may have reduced sepsis incidence among infants in rural India.
The study comprised 4,556 infants with no signs of sepsis who were given an oral synbiotic preparation of Lactobacillus plantarum plus fructooligosaccharide. The composite outcome of sepsis and death was reduced in the treatment arm of the study (risk ratio, 0.60; 95% confidence interval, 0.48-0.74).
Based on that outcome, investigators said in their report that the preparation could prevent a “large proportion” of neonatal sepsis in developing countries.
“This is a very dramatic result for a very simple and cheap intervention in a high-risk population,” Dr. Quigley said in his presentation at the meeting.
He also provided a short list of studies showing “exciting recent data” regarding the predictive role of microbiota.
In one such study, investigators showed that the oral microbiota associated with colorectal cancer is distinctive, raising the possibility that analyzing microbiota could help identify patients at risk for development of colon cancer or offer an alternative cancer screening method.
In other studies, Dr. Quigley said, microbiota have been associated with response to metformin, and to the immune checkpoint inhibitors that have become important in the treatment of cancers.
In addition, microbiota have been associated with predicting response to low fermentable, oligosaccharide, disaccharide, monosaccharide, and polyol (FODMAP) diets in irritable bowel syndrome patients, and predicting metabolic response to high-fiber diets, he added.
Diagnostics is another area where microbiota could soon become important: “In diseases like [inflammatory bowel disease and irritable bowel syndrome] where we have a very heterogeneous population, looking at the microbiota might allow us to define new disease categories,” Dr. Quigley said.
Despite the promise, much research is still needed to confirm many of the findings of experimental studies.
“I think it’s clear that the microbiota is important in health and disease,” Dr. Quigley said. “However, host/microbiome interactions in [humans] are complex and far from completely understood, and unfortunately, some of the elegant work in animal models has not quite translated into man.”
Global Academy for Medical Education and this news organization are owned by the same parent company.
Dr. Quigley reported disclosures related to Alimentary Health, Almirall, Biocodex, 4D Pharma, Menarini, Pharmasierra, Salix, Synergy, and Vibrant.
REPORTING FROM PERSPECTIVES IN DIGESTIVE DISEASES
CRC recurrence surveillance studies: No benefit to high-intensity strategy
More frequent follow-up with computed tomography of the thorax and abdomen and serum carcinoembyronic antigen (CEA) testing does not significantly improve mortality rates or improve time to detection of recurrence, results of two studies published in JAMA have suggested.*
In COLOFOL, a randomized clinical trial including more than 2,500 patients with stage II or III colorectal cancer, more frequent follow-up with CT of the thorax and abdomen and serum CEA did not significantly improve 5-year overall mortality or colorectal cancer–specific mortality rates.
In the second study, a retrospective cohort analysis of the National Cancer Database (NCDB) including more than 8,500 patients with stage I-III colorectal cancer, investigators found no significant association between the surveillance testing frequency and time to detection of disease recurrence.
Taken together, these findings suggest a need to revisit clinical practice guidelines, Hanna K. Sanoff, MD, of the University of North Carolina at Chapel Hill said in a related editorial (for details, see “Views on the News”).
The COLOFOL randomized trial, reported by Henrik T. Sørensen, DMSc, head of the department of clinical epidemiology at Aarhus (Denmark) University Hospital, and his colleagues, included 2,509 patients with stage II or III colorectal cancer.
“The question of appropriate follow-up intervals has been controversial, and varying intensity of follow-up has been used within and among countries,” Dr. Sørensen and his coauthors said.
Patients were randomized either to a high-frequency group, in which CT and CEA testing were conducted at 6, 12, 18, 24, and 36 months after surgery, or to a low-frequency group that received testing only at 12 and 36 months after surgery.
Results of COLOFOL showed that the 5-year colorectal cancer–specific mortality rate was similar: 10.6% for the high-frequency follow-up group versus 11.4% for the low frequency group (risk difference, 0.8%; 95%confidence interval, –1.7% to 3.3%; P = .52).
Likewise, 5-year overall mortality was 13.0% for the high-frequency group and 14.1% for the low-frequency follow-up groups (risk difference, 1.1%; 95% CI, –1.6% to 3.8%; P = .43
High-intensity testing did result in recurrences being detected earlier; nevertheless, this did not translate into a reduced mortality rate, investigators said.
The retrospective NCDB analysis, reported by George J. Chang, MD, of University of Texas MD Anderson Cancer Center, Houston, and his coauthors, included 8,529 patients with stage I-III colorectal cancer treated at 1,175 facilities.
Facilities designated as high intensity for imaging performed a mean of 2.87 imaging tests over 3 years, compared with 1.63 for facilities designated as low intensity. Median time to detection of recurrence was similar between arms, at 15.1 months for patients treated at centers with high-intensity surveillance versus 16.0 months for those treated at low-intensity surveillance centers (hazard ratio, 0.99; 95% CI, 0.90-1.09).
High-intensity CEA testing facilities performed a mean of 4.31 tests within 3 years versus 1.63 for low-intensity facilities. Again, investigators found similar median time to detection of recurrence for high- and low-intensity facilities (15.9 months versus 15.3 months, respectively; hazard ratio, 1.00; 95% CI, 0.90-1.11)
Previously, the Follow-up After Colorectal Surgery (FACS) study, a randomized controlled trial, showed no survival benefit to more frequent testing, Dr. Chang and his colleagues noted.
“Based on these data and the recent FACS trial, current National Comprehensive Cancer Network (NCCN) guideline recommendations could be considered overtesting given the absence of improvement in recurrence detection or survival,” they wrote, noting that the NCCN guidelines have suggested CT testing every 6 months for 3 years.
Disclosures for the COLOFOL trial included one investigator who reported potential conflicts of interest with Janssen-Cilag and Merck Serono. For the NCDB study, one coauthor reported a potential conflict of interest related to Johnson & Johnson. No other disclosures were reported.
SOURCES: Sørensen HT et al. JAMA Oncol. 2018 May 22. doi: 10.1001/jama.2018.5623; Chang GJ et al. JAMA Oncol. 2018 May 22. doi; 10.1001/jama.2018.5816.
Correction, 6/8/18: An earlier version of this article misstated the name of the journal in which this study was published.
Clinical practice guidelines should be reevaluated in light of the findings of these two studies, according to Hanna K. Sanoff, MD.
While the studies both have methodological limitations, the need to revisit recommendations is important given the potential harms associated with more frequent testing, Dr. Sanoff said in an accompanying editorial.
“Because of their designs, results of the COLOFOL trial and the NCDB study should not be considered precise estimates of the effect of surveillance on survival,” she wrote. “However, as gold standard randomized controlled trial evidence is unlikely to become available, decisions must be made on the basis of these imperfect, although methodologically sound, reports.”
Both studies found that a high-intensity surveillance strategy offered no significant differences in key outcomes versus a low-intensity strategy. However, the NCDB study was a retrospective cohort analysis, so the results should be viewed in light of the inherent limitations of that study approach.
Similarly, although the COLOFOL study is randomized, it should be viewed as a pragmatic study, according to Dr. Sanoff, since investigators made several practical design decisions to ensure that patients would be enrolled and the study completed. For example, the eligibility criteria were not stringent with regard to confirming metastatic disease at entry.
Even so, the results of the trial are corroborated by another pragmatic randomized controlled trial, the Follow-up After Colorectal Surgery (FACS) study, which also showed no benefit to more frequent testing.
“There is now a considerable body of evidence that imaging and CEA testing more often than every year does little to improve survival in a meaningful way,” Dr. Sanoff said in her editorial.
Hanna K. Sanoff, MD, is with the division of hematology/oncology at the University of North Carolina at Chapel Hill. These comments are derived from her editorial in JAMA Oncology. Dr. Sanoff reported no conflicts of interest relevant to her work on the editorial.
Clinical practice guidelines should be reevaluated in light of the findings of these two studies, according to Hanna K. Sanoff, MD.
While the studies both have methodological limitations, the need to revisit recommendations is important given the potential harms associated with more frequent testing, Dr. Sanoff said in an accompanying editorial.
“Because of their designs, results of the COLOFOL trial and the NCDB study should not be considered precise estimates of the effect of surveillance on survival,” she wrote. “However, as gold standard randomized controlled trial evidence is unlikely to become available, decisions must be made on the basis of these imperfect, although methodologically sound, reports.”
Both studies found that a high-intensity surveillance strategy offered no significant differences in key outcomes versus a low-intensity strategy. However, the NCDB study was a retrospective cohort analysis, so the results should be viewed in light of the inherent limitations of that study approach.
Similarly, although the COLOFOL study is randomized, it should be viewed as a pragmatic study, according to Dr. Sanoff, since investigators made several practical design decisions to ensure that patients would be enrolled and the study completed. For example, the eligibility criteria were not stringent with regard to confirming metastatic disease at entry.
Even so, the results of the trial are corroborated by another pragmatic randomized controlled trial, the Follow-up After Colorectal Surgery (FACS) study, which also showed no benefit to more frequent testing.
“There is now a considerable body of evidence that imaging and CEA testing more often than every year does little to improve survival in a meaningful way,” Dr. Sanoff said in her editorial.
Hanna K. Sanoff, MD, is with the division of hematology/oncology at the University of North Carolina at Chapel Hill. These comments are derived from her editorial in JAMA Oncology. Dr. Sanoff reported no conflicts of interest relevant to her work on the editorial.
Clinical practice guidelines should be reevaluated in light of the findings of these two studies, according to Hanna K. Sanoff, MD.
While the studies both have methodological limitations, the need to revisit recommendations is important given the potential harms associated with more frequent testing, Dr. Sanoff said in an accompanying editorial.
“Because of their designs, results of the COLOFOL trial and the NCDB study should not be considered precise estimates of the effect of surveillance on survival,” she wrote. “However, as gold standard randomized controlled trial evidence is unlikely to become available, decisions must be made on the basis of these imperfect, although methodologically sound, reports.”
Both studies found that a high-intensity surveillance strategy offered no significant differences in key outcomes versus a low-intensity strategy. However, the NCDB study was a retrospective cohort analysis, so the results should be viewed in light of the inherent limitations of that study approach.
Similarly, although the COLOFOL study is randomized, it should be viewed as a pragmatic study, according to Dr. Sanoff, since investigators made several practical design decisions to ensure that patients would be enrolled and the study completed. For example, the eligibility criteria were not stringent with regard to confirming metastatic disease at entry.
Even so, the results of the trial are corroborated by another pragmatic randomized controlled trial, the Follow-up After Colorectal Surgery (FACS) study, which also showed no benefit to more frequent testing.
“There is now a considerable body of evidence that imaging and CEA testing more often than every year does little to improve survival in a meaningful way,” Dr. Sanoff said in her editorial.
Hanna K. Sanoff, MD, is with the division of hematology/oncology at the University of North Carolina at Chapel Hill. These comments are derived from her editorial in JAMA Oncology. Dr. Sanoff reported no conflicts of interest relevant to her work on the editorial.
More frequent follow-up with computed tomography of the thorax and abdomen and serum carcinoembyronic antigen (CEA) testing does not significantly improve mortality rates or improve time to detection of recurrence, results of two studies published in JAMA have suggested.*
In COLOFOL, a randomized clinical trial including more than 2,500 patients with stage II or III colorectal cancer, more frequent follow-up with CT of the thorax and abdomen and serum CEA did not significantly improve 5-year overall mortality or colorectal cancer–specific mortality rates.
In the second study, a retrospective cohort analysis of the National Cancer Database (NCDB) including more than 8,500 patients with stage I-III colorectal cancer, investigators found no significant association between the surveillance testing frequency and time to detection of disease recurrence.
Taken together, these findings suggest a need to revisit clinical practice guidelines, Hanna K. Sanoff, MD, of the University of North Carolina at Chapel Hill said in a related editorial (for details, see “Views on the News”).
The COLOFOL randomized trial, reported by Henrik T. Sørensen, DMSc, head of the department of clinical epidemiology at Aarhus (Denmark) University Hospital, and his colleagues, included 2,509 patients with stage II or III colorectal cancer.
“The question of appropriate follow-up intervals has been controversial, and varying intensity of follow-up has been used within and among countries,” Dr. Sørensen and his coauthors said.
Patients were randomized either to a high-frequency group, in which CT and CEA testing were conducted at 6, 12, 18, 24, and 36 months after surgery, or to a low-frequency group that received testing only at 12 and 36 months after surgery.
Results of COLOFOL showed that the 5-year colorectal cancer–specific mortality rate was similar: 10.6% for the high-frequency follow-up group versus 11.4% for the low frequency group (risk difference, 0.8%; 95%confidence interval, –1.7% to 3.3%; P = .52).
Likewise, 5-year overall mortality was 13.0% for the high-frequency group and 14.1% for the low-frequency follow-up groups (risk difference, 1.1%; 95% CI, –1.6% to 3.8%; P = .43
High-intensity testing did result in recurrences being detected earlier; nevertheless, this did not translate into a reduced mortality rate, investigators said.
The retrospective NCDB analysis, reported by George J. Chang, MD, of University of Texas MD Anderson Cancer Center, Houston, and his coauthors, included 8,529 patients with stage I-III colorectal cancer treated at 1,175 facilities.
Facilities designated as high intensity for imaging performed a mean of 2.87 imaging tests over 3 years, compared with 1.63 for facilities designated as low intensity. Median time to detection of recurrence was similar between arms, at 15.1 months for patients treated at centers with high-intensity surveillance versus 16.0 months for those treated at low-intensity surveillance centers (hazard ratio, 0.99; 95% CI, 0.90-1.09).
High-intensity CEA testing facilities performed a mean of 4.31 tests within 3 years versus 1.63 for low-intensity facilities. Again, investigators found similar median time to detection of recurrence for high- and low-intensity facilities (15.9 months versus 15.3 months, respectively; hazard ratio, 1.00; 95% CI, 0.90-1.11)
Previously, the Follow-up After Colorectal Surgery (FACS) study, a randomized controlled trial, showed no survival benefit to more frequent testing, Dr. Chang and his colleagues noted.
“Based on these data and the recent FACS trial, current National Comprehensive Cancer Network (NCCN) guideline recommendations could be considered overtesting given the absence of improvement in recurrence detection or survival,” they wrote, noting that the NCCN guidelines have suggested CT testing every 6 months for 3 years.
Disclosures for the COLOFOL trial included one investigator who reported potential conflicts of interest with Janssen-Cilag and Merck Serono. For the NCDB study, one coauthor reported a potential conflict of interest related to Johnson & Johnson. No other disclosures were reported.
SOURCES: Sørensen HT et al. JAMA Oncol. 2018 May 22. doi: 10.1001/jama.2018.5623; Chang GJ et al. JAMA Oncol. 2018 May 22. doi; 10.1001/jama.2018.5816.
Correction, 6/8/18: An earlier version of this article misstated the name of the journal in which this study was published.
More frequent follow-up with computed tomography of the thorax and abdomen and serum carcinoembyronic antigen (CEA) testing does not significantly improve mortality rates or improve time to detection of recurrence, results of two studies published in JAMA have suggested.*
In COLOFOL, a randomized clinical trial including more than 2,500 patients with stage II or III colorectal cancer, more frequent follow-up with CT of the thorax and abdomen and serum CEA did not significantly improve 5-year overall mortality or colorectal cancer–specific mortality rates.
In the second study, a retrospective cohort analysis of the National Cancer Database (NCDB) including more than 8,500 patients with stage I-III colorectal cancer, investigators found no significant association between the surveillance testing frequency and time to detection of disease recurrence.
Taken together, these findings suggest a need to revisit clinical practice guidelines, Hanna K. Sanoff, MD, of the University of North Carolina at Chapel Hill said in a related editorial (for details, see “Views on the News”).
The COLOFOL randomized trial, reported by Henrik T. Sørensen, DMSc, head of the department of clinical epidemiology at Aarhus (Denmark) University Hospital, and his colleagues, included 2,509 patients with stage II or III colorectal cancer.
“The question of appropriate follow-up intervals has been controversial, and varying intensity of follow-up has been used within and among countries,” Dr. Sørensen and his coauthors said.
Patients were randomized either to a high-frequency group, in which CT and CEA testing were conducted at 6, 12, 18, 24, and 36 months after surgery, or to a low-frequency group that received testing only at 12 and 36 months after surgery.
Results of COLOFOL showed that the 5-year colorectal cancer–specific mortality rate was similar: 10.6% for the high-frequency follow-up group versus 11.4% for the low frequency group (risk difference, 0.8%; 95%confidence interval, –1.7% to 3.3%; P = .52).
Likewise, 5-year overall mortality was 13.0% for the high-frequency group and 14.1% for the low-frequency follow-up groups (risk difference, 1.1%; 95% CI, –1.6% to 3.8%; P = .43
High-intensity testing did result in recurrences being detected earlier; nevertheless, this did not translate into a reduced mortality rate, investigators said.
The retrospective NCDB analysis, reported by George J. Chang, MD, of University of Texas MD Anderson Cancer Center, Houston, and his coauthors, included 8,529 patients with stage I-III colorectal cancer treated at 1,175 facilities.
Facilities designated as high intensity for imaging performed a mean of 2.87 imaging tests over 3 years, compared with 1.63 for facilities designated as low intensity. Median time to detection of recurrence was similar between arms, at 15.1 months for patients treated at centers with high-intensity surveillance versus 16.0 months for those treated at low-intensity surveillance centers (hazard ratio, 0.99; 95% CI, 0.90-1.09).
High-intensity CEA testing facilities performed a mean of 4.31 tests within 3 years versus 1.63 for low-intensity facilities. Again, investigators found similar median time to detection of recurrence for high- and low-intensity facilities (15.9 months versus 15.3 months, respectively; hazard ratio, 1.00; 95% CI, 0.90-1.11)
Previously, the Follow-up After Colorectal Surgery (FACS) study, a randomized controlled trial, showed no survival benefit to more frequent testing, Dr. Chang and his colleagues noted.
“Based on these data and the recent FACS trial, current National Comprehensive Cancer Network (NCCN) guideline recommendations could be considered overtesting given the absence of improvement in recurrence detection or survival,” they wrote, noting that the NCCN guidelines have suggested CT testing every 6 months for 3 years.
Disclosures for the COLOFOL trial included one investigator who reported potential conflicts of interest with Janssen-Cilag and Merck Serono. For the NCDB study, one coauthor reported a potential conflict of interest related to Johnson & Johnson. No other disclosures were reported.
SOURCES: Sørensen HT et al. JAMA Oncol. 2018 May 22. doi: 10.1001/jama.2018.5623; Chang GJ et al. JAMA Oncol. 2018 May 22. doi; 10.1001/jama.2018.5816.
Correction, 6/8/18: An earlier version of this article misstated the name of the journal in which this study was published.
FROM JAMA
Key clinical point: In a randomized study, more frequent follow-up with CT of the thorax and abdomen and serum carcinoembryonic antigen (CEA) did not significantly improve mortality rates. In a retrospective study, there was no association found between frequency of testing and time to detection of recurrence.
Major finding: In the randomized trial, the 5-year colorectal cancer–specific mortality rate was 10.6% for high-frequency follow-up versus 11.4% for low frequency (risk difference, 0.8%; 95% confidence interval, –1.7% to 3.3%; P = .52). In the retrospective study, the median time to detection of recurrence was 15.1 months versus 16.0 months, respectively, for patients treated at centers with high- or low-intensity imaging surveillance (difference, –0.95 months; 95% CI, –2.59 to 0.68; hazard ratio, 0.99), with similar results for high- versus low-intensity CEA testing.
Study details: The COLOFOL randomized clinical trial, which included 2,509 patients with stage II or III colorectal cancer, and a retrospective cohort study of the National Cancer Database (NCDB), which included 8,529 patients with stage I-III colorectal cancer.
Disclosures: For the COLOFOL trial, one investigator reported disclosures with Janssen-Cilag and Merck Serono. For the NCDB study, one coauthor reported a disclosure related to Johnson & Johnson. No other disclosures were reported.
Source: Sørensen HT et al. JAMA Oncol. 2018 May 22. doi: 10.1001/jama.2018.5623; Chang GJ et al. JAMA Oncol. 2018 May 22. doi: 10.1001/jama.2018.5816.
CARPREG II fine-tunes assessment of cardiac complication risk in pregnancy
A study of pregnant women with heart disease has yielded a new risk index that improves on its predecessor by integrating general, lesion-specific, and delivery-of-care variables, investigators say.
“Compared with other published risk indices, including the original CARPREG [Cardiac Disease in Pregnancy] score, CARPREG II risk index had the highest discriminative and calibrative accuracy in our study group,” investigators said in a report published in the Journal of the American College of Cardiology.
First author on the report was Candice K. Silversides, MD, division of cardiology, University of Toronto pregnancy and heart disease research program, Mount Sinai Hospital/Sinai Health System.
The widely used, original CARPREG risk index was the first to predict maternal cardiac complications based on general clinical and echocardiographic data from the baseline antepartum visit, the researchers wrote in their report.
The new index developed by Dr. Silversides and her colleagues stems from a study of pregnant women with heart disease receiving care at two large Canadian obstetric centers.
Based on analysis of 1,938 pregnancies progressing beyond 20 weeks of gestation, the investigators found that cardiac complications were overall quite common in pregnant women with heart disease, occurring in 16% of participants. However, maternal cardiac deaths or cardiac arrests were rare, they said, occurring in just 11 (0.6%) of the pregnancies.
Most complications (64%) occurred in the antepartum period, according to the report.
Looking at patient data before or after 2001, investigators found the rates of most complications were consistent over time. However, rates of pulmonary edema decreased in the post-2001 period.
Multivariate analysis of these findings revealed 10 predictors of adverse cardiac events. Those included five general factors, including previous cardiac events or arrhythmia, four lesion-specific variables including pulmonary hypertension and coronary artery disease, and one process of care variable: late pregnancy assessment.
Only 4 of those 10 factors were included in the original CARPREG index, investigators noted.
In CARPREG II, each of the 10 factors is weighted with 1-3 points, depending on risk. For example, history of prior cardiac events was associated with a higher odds ratio, and so was assigned 3 points.
The predicted risk of primary cardiac events ranges from 5% for women with a total of 0-1 points, up to 41% for women with 5 or more points.
The finding that some predictors had higher odds ratios than others reinforces the “foundational role” of clinical assessment, investigators said in the report.
“There may be other factors that affect outcomes,” they wrote. “Risk assessment for the individual patient will need to integrate risk score estimates, known lesion-specific information, and clinical judgment by an experienced physician.”
Dr. Silversides and her coauthors reported that they had no relationships to disclose relevant to the contents of their report on the study.
SOURCE: Silversides CK et al. J Am Coll Cardiol. 2018;71:2419-30.
This update and expansion of the original CARPREG scoring system is a “useful starting point” for prediction of the risk of pregnancy in women with cardiac disease, according to Uri Elkayam, MD.
However, a detailed and lesion specific evaluation is still required for a more precise determination of risk for any given patient, Dr. Elkayam cautioned in an editorial accompanying the article.
Clinicians need to thoroughly understand how the patient’s cardiac condition could be affected by hemodynamic changes during pregnancy, labor, delivery, and the postpartum period, Dr. Elkayam added in his comments.
To fully take advantage of CARPREG II, clinicians need to take into account the limitations of the scoring system, he said, including the fact that it is based on population studies.
“Although the system presented is designed to examine all adverse cardiac events that could have an impact on maternal health, it is less effective for distinguishing between mild and easily manageable events that do not have serious effects on maternal or fetal outcomes and those that may be severe, life-threatening, or require hospitalizations or early delivery,” he wrote.
Dr. Elkayam is with the department of medicine, division of cardiovascular medicine, and the department of obstetrics and gynecology, University of Southern California, Los Angeles. These comments are derived from his editorial in the Journal of the American College of Cardiology . Dr. Elkayam reported he had no relationships relevant to the contents of this paper to disclose.
This update and expansion of the original CARPREG scoring system is a “useful starting point” for prediction of the risk of pregnancy in women with cardiac disease, according to Uri Elkayam, MD.
However, a detailed and lesion specific evaluation is still required for a more precise determination of risk for any given patient, Dr. Elkayam cautioned in an editorial accompanying the article.
Clinicians need to thoroughly understand how the patient’s cardiac condition could be affected by hemodynamic changes during pregnancy, labor, delivery, and the postpartum period, Dr. Elkayam added in his comments.
To fully take advantage of CARPREG II, clinicians need to take into account the limitations of the scoring system, he said, including the fact that it is based on population studies.
“Although the system presented is designed to examine all adverse cardiac events that could have an impact on maternal health, it is less effective for distinguishing between mild and easily manageable events that do not have serious effects on maternal or fetal outcomes and those that may be severe, life-threatening, or require hospitalizations or early delivery,” he wrote.
Dr. Elkayam is with the department of medicine, division of cardiovascular medicine, and the department of obstetrics and gynecology, University of Southern California, Los Angeles. These comments are derived from his editorial in the Journal of the American College of Cardiology . Dr. Elkayam reported he had no relationships relevant to the contents of this paper to disclose.
This update and expansion of the original CARPREG scoring system is a “useful starting point” for prediction of the risk of pregnancy in women with cardiac disease, according to Uri Elkayam, MD.
However, a detailed and lesion specific evaluation is still required for a more precise determination of risk for any given patient, Dr. Elkayam cautioned in an editorial accompanying the article.
Clinicians need to thoroughly understand how the patient’s cardiac condition could be affected by hemodynamic changes during pregnancy, labor, delivery, and the postpartum period, Dr. Elkayam added in his comments.
To fully take advantage of CARPREG II, clinicians need to take into account the limitations of the scoring system, he said, including the fact that it is based on population studies.
“Although the system presented is designed to examine all adverse cardiac events that could have an impact on maternal health, it is less effective for distinguishing between mild and easily manageable events that do not have serious effects on maternal or fetal outcomes and those that may be severe, life-threatening, or require hospitalizations or early delivery,” he wrote.
Dr. Elkayam is with the department of medicine, division of cardiovascular medicine, and the department of obstetrics and gynecology, University of Southern California, Los Angeles. These comments are derived from his editorial in the Journal of the American College of Cardiology . Dr. Elkayam reported he had no relationships relevant to the contents of this paper to disclose.
A study of pregnant women with heart disease has yielded a new risk index that improves on its predecessor by integrating general, lesion-specific, and delivery-of-care variables, investigators say.
“Compared with other published risk indices, including the original CARPREG [Cardiac Disease in Pregnancy] score, CARPREG II risk index had the highest discriminative and calibrative accuracy in our study group,” investigators said in a report published in the Journal of the American College of Cardiology.
First author on the report was Candice K. Silversides, MD, division of cardiology, University of Toronto pregnancy and heart disease research program, Mount Sinai Hospital/Sinai Health System.
The widely used, original CARPREG risk index was the first to predict maternal cardiac complications based on general clinical and echocardiographic data from the baseline antepartum visit, the researchers wrote in their report.
The new index developed by Dr. Silversides and her colleagues stems from a study of pregnant women with heart disease receiving care at two large Canadian obstetric centers.
Based on analysis of 1,938 pregnancies progressing beyond 20 weeks of gestation, the investigators found that cardiac complications were overall quite common in pregnant women with heart disease, occurring in 16% of participants. However, maternal cardiac deaths or cardiac arrests were rare, they said, occurring in just 11 (0.6%) of the pregnancies.
Most complications (64%) occurred in the antepartum period, according to the report.
Looking at patient data before or after 2001, investigators found the rates of most complications were consistent over time. However, rates of pulmonary edema decreased in the post-2001 period.
Multivariate analysis of these findings revealed 10 predictors of adverse cardiac events. Those included five general factors, including previous cardiac events or arrhythmia, four lesion-specific variables including pulmonary hypertension and coronary artery disease, and one process of care variable: late pregnancy assessment.
Only 4 of those 10 factors were included in the original CARPREG index, investigators noted.
In CARPREG II, each of the 10 factors is weighted with 1-3 points, depending on risk. For example, history of prior cardiac events was associated with a higher odds ratio, and so was assigned 3 points.
The predicted risk of primary cardiac events ranges from 5% for women with a total of 0-1 points, up to 41% for women with 5 or more points.
The finding that some predictors had higher odds ratios than others reinforces the “foundational role” of clinical assessment, investigators said in the report.
“There may be other factors that affect outcomes,” they wrote. “Risk assessment for the individual patient will need to integrate risk score estimates, known lesion-specific information, and clinical judgment by an experienced physician.”
Dr. Silversides and her coauthors reported that they had no relationships to disclose relevant to the contents of their report on the study.
SOURCE: Silversides CK et al. J Am Coll Cardiol. 2018;71:2419-30.
A study of pregnant women with heart disease has yielded a new risk index that improves on its predecessor by integrating general, lesion-specific, and delivery-of-care variables, investigators say.
“Compared with other published risk indices, including the original CARPREG [Cardiac Disease in Pregnancy] score, CARPREG II risk index had the highest discriminative and calibrative accuracy in our study group,” investigators said in a report published in the Journal of the American College of Cardiology.
First author on the report was Candice K. Silversides, MD, division of cardiology, University of Toronto pregnancy and heart disease research program, Mount Sinai Hospital/Sinai Health System.
The widely used, original CARPREG risk index was the first to predict maternal cardiac complications based on general clinical and echocardiographic data from the baseline antepartum visit, the researchers wrote in their report.
The new index developed by Dr. Silversides and her colleagues stems from a study of pregnant women with heart disease receiving care at two large Canadian obstetric centers.
Based on analysis of 1,938 pregnancies progressing beyond 20 weeks of gestation, the investigators found that cardiac complications were overall quite common in pregnant women with heart disease, occurring in 16% of participants. However, maternal cardiac deaths or cardiac arrests were rare, they said, occurring in just 11 (0.6%) of the pregnancies.
Most complications (64%) occurred in the antepartum period, according to the report.
Looking at patient data before or after 2001, investigators found the rates of most complications were consistent over time. However, rates of pulmonary edema decreased in the post-2001 period.
Multivariate analysis of these findings revealed 10 predictors of adverse cardiac events. Those included five general factors, including previous cardiac events or arrhythmia, four lesion-specific variables including pulmonary hypertension and coronary artery disease, and one process of care variable: late pregnancy assessment.
Only 4 of those 10 factors were included in the original CARPREG index, investigators noted.
In CARPREG II, each of the 10 factors is weighted with 1-3 points, depending on risk. For example, history of prior cardiac events was associated with a higher odds ratio, and so was assigned 3 points.
The predicted risk of primary cardiac events ranges from 5% for women with a total of 0-1 points, up to 41% for women with 5 or more points.
The finding that some predictors had higher odds ratios than others reinforces the “foundational role” of clinical assessment, investigators said in the report.
“There may be other factors that affect outcomes,” they wrote. “Risk assessment for the individual patient will need to integrate risk score estimates, known lesion-specific information, and clinical judgment by an experienced physician.”
Dr. Silversides and her coauthors reported that they had no relationships to disclose relevant to the contents of their report on the study.
SOURCE: Silversides CK et al. J Am Coll Cardiol. 2018;71:2419-30.
FROM THE JOURNAL OF THE AMERICAN COLLEGE OF CARDIOLOGY
Key clinical point: A newly developed risk index enhances the ability to predict maternal cardiac complications by combining general, lesion-specific, and delivery-of-care variables.
Major finding: Investigators developed the CARPREG II risk index based on 10 predictors of maternal cardiac complications (5 general, 4 lesion-specific, and 1 related to delivery of care).
Study details: The CARPREG II Study, which included more than 2,000 prospectively enrolled consecutive pregnant women with heart disease seen at one of two large Canadian obstetric centers.
Disclosures: Authors reported that they had no relationships to disclose relevant to the contents of their report on the study.
Source: Silversides CK et al. J Am Coll Cardiol. 2018;71:2419-30.
Automated bone scan index predicts survival in metastatic castration-resistant prostate cancer patients
A system that automatically evaluates bone scans produces a measure that is prognostic for overall survival (OS) in patients with metastatic prostate cancer, investigators are reporting.
The automated bone scan index (BSI) produced by the artificial intelligence–based system provides prognostic discrimination beyond other established risk markers, investigators reported in JAMA Oncology.
The automated BSI also provides significantly greater discriminative ability compared with the current standard, which is manual assessment by counting metastatic lesion numbers, according to Andrew J. Armstrong, MD, of Duke University, Durham, N.C. and his coauthors.
“Incorporating the aBSI into clinical practice to supplement nuclear medicine reports may permit a more objective analysis of bone scan changes over time and their clinical relevance to patient care,” Dr. Armstrong and colleagues said.
The BSI represents tumor burden as a percentage of total skeletal weight. The system used in this study automates BSI methods by using artificial neural networks to detect metastatic hot spots and classify them as malignant or benign.
The automated system was evaluated in a preplanned secondary analysis of a randomized clinical trial of imiquimod in men with chemotherapy-naive metastatic castration-resistant prostate cancer. Evaluable bone scans were available for 721 out of 1,245 total enrollees from 241 sites in 37 countries.
In the secondary analysis, investigators found that baseline aBSI was significantly associated with OS. Risk of death increased by 20% for every doubling of the aBSI score (hazard ratio, 1.20; 95% confidence interval, 1.14-1.26; P less than .001).
The association remained significant in a multivariable model adjusting for five variables associated with OS: albumin, lactate dehydrogenase, C-reactive protein, serum prostate-specific antigen, and Eastern European geographic region.
In addition, the automated BSI had a better discriminating ability in prognosticating OS as compared to manual lesion counting (C-index of 0.63 and 0.60, respectively; P = .03), investigators said.
Secondary analyses showed the automated BSI was also associated with time to symptomatic progression, prostate cancer specific survival, and time to opiate use for cancer pain.
“These data support the clinical utility of the automated BSI, given its association with clinically relevant outcomes that are critically important in patient care,” wrote Dr. Armstrong and his colleagues.
The study was funded by EXINI Diagnostics AB, a subsidiary of Progenics Pharmaceuticals. The researchers reported disclosures related to EXINI Diagnostics AB and Active Biotech.
SOURCE: Armstrong AJ et al. JAMA Oncol. 2018 May 17. doi: 10.1001/jamaoncol.2018.1093.
This study prospectively validates the potential usefulness and establishes the prognostic value of an automated system for evaluating bone metastases, according to Fred Saad, MD.
The automated bone scan index (aBSI) was predictive of overall survival in univariate analysis, and remained significant in multivariate analysis, Dr. Saad noted in an editorial accompanying the study.
Despite some limitations, the system provides an encouraging framework to build on, he noted.
“With ongoing and future work in validating aBSI, this technology could eventually be introduced in clinical practice and research settings for improved stratification,” he wrote in the editorial.
Now, researchers are integrating Prostate Cancer Working Group progression criteria into the aBSI framework, which could be useful for evaluating response and resistance to treatment, if validated.
“This is extremely important for anyone who realizes the time and effort required for comparing bone scans to determine whether or not patients are progressing on clinical trials,” Dr. Saad wrote.
Dr. Saad is the University of Montreal Endowed Chair in Prostate Cancer, Surgery, University of Montreal Hospital Center. These comments are derived from his editorial in JAMA Oncology . Dr. Saad had no reported conflict of interest related to the editorial.
This study prospectively validates the potential usefulness and establishes the prognostic value of an automated system for evaluating bone metastases, according to Fred Saad, MD.
The automated bone scan index (aBSI) was predictive of overall survival in univariate analysis, and remained significant in multivariate analysis, Dr. Saad noted in an editorial accompanying the study.
Despite some limitations, the system provides an encouraging framework to build on, he noted.
“With ongoing and future work in validating aBSI, this technology could eventually be introduced in clinical practice and research settings for improved stratification,” he wrote in the editorial.
Now, researchers are integrating Prostate Cancer Working Group progression criteria into the aBSI framework, which could be useful for evaluating response and resistance to treatment, if validated.
“This is extremely important for anyone who realizes the time and effort required for comparing bone scans to determine whether or not patients are progressing on clinical trials,” Dr. Saad wrote.
Dr. Saad is the University of Montreal Endowed Chair in Prostate Cancer, Surgery, University of Montreal Hospital Center. These comments are derived from his editorial in JAMA Oncology . Dr. Saad had no reported conflict of interest related to the editorial.
This study prospectively validates the potential usefulness and establishes the prognostic value of an automated system for evaluating bone metastases, according to Fred Saad, MD.
The automated bone scan index (aBSI) was predictive of overall survival in univariate analysis, and remained significant in multivariate analysis, Dr. Saad noted in an editorial accompanying the study.
Despite some limitations, the system provides an encouraging framework to build on, he noted.
“With ongoing and future work in validating aBSI, this technology could eventually be introduced in clinical practice and research settings for improved stratification,” he wrote in the editorial.
Now, researchers are integrating Prostate Cancer Working Group progression criteria into the aBSI framework, which could be useful for evaluating response and resistance to treatment, if validated.
“This is extremely important for anyone who realizes the time and effort required for comparing bone scans to determine whether or not patients are progressing on clinical trials,” Dr. Saad wrote.
Dr. Saad is the University of Montreal Endowed Chair in Prostate Cancer, Surgery, University of Montreal Hospital Center. These comments are derived from his editorial in JAMA Oncology . Dr. Saad had no reported conflict of interest related to the editorial.
A system that automatically evaluates bone scans produces a measure that is prognostic for overall survival (OS) in patients with metastatic prostate cancer, investigators are reporting.
The automated bone scan index (BSI) produced by the artificial intelligence–based system provides prognostic discrimination beyond other established risk markers, investigators reported in JAMA Oncology.
The automated BSI also provides significantly greater discriminative ability compared with the current standard, which is manual assessment by counting metastatic lesion numbers, according to Andrew J. Armstrong, MD, of Duke University, Durham, N.C. and his coauthors.
“Incorporating the aBSI into clinical practice to supplement nuclear medicine reports may permit a more objective analysis of bone scan changes over time and their clinical relevance to patient care,” Dr. Armstrong and colleagues said.
The BSI represents tumor burden as a percentage of total skeletal weight. The system used in this study automates BSI methods by using artificial neural networks to detect metastatic hot spots and classify them as malignant or benign.
The automated system was evaluated in a preplanned secondary analysis of a randomized clinical trial of imiquimod in men with chemotherapy-naive metastatic castration-resistant prostate cancer. Evaluable bone scans were available for 721 out of 1,245 total enrollees from 241 sites in 37 countries.
In the secondary analysis, investigators found that baseline aBSI was significantly associated with OS. Risk of death increased by 20% for every doubling of the aBSI score (hazard ratio, 1.20; 95% confidence interval, 1.14-1.26; P less than .001).
The association remained significant in a multivariable model adjusting for five variables associated with OS: albumin, lactate dehydrogenase, C-reactive protein, serum prostate-specific antigen, and Eastern European geographic region.
In addition, the automated BSI had a better discriminating ability in prognosticating OS as compared to manual lesion counting (C-index of 0.63 and 0.60, respectively; P = .03), investigators said.
Secondary analyses showed the automated BSI was also associated with time to symptomatic progression, prostate cancer specific survival, and time to opiate use for cancer pain.
“These data support the clinical utility of the automated BSI, given its association with clinically relevant outcomes that are critically important in patient care,” wrote Dr. Armstrong and his colleagues.
The study was funded by EXINI Diagnostics AB, a subsidiary of Progenics Pharmaceuticals. The researchers reported disclosures related to EXINI Diagnostics AB and Active Biotech.
SOURCE: Armstrong AJ et al. JAMA Oncol. 2018 May 17. doi: 10.1001/jamaoncol.2018.1093.
A system that automatically evaluates bone scans produces a measure that is prognostic for overall survival (OS) in patients with metastatic prostate cancer, investigators are reporting.
The automated bone scan index (BSI) produced by the artificial intelligence–based system provides prognostic discrimination beyond other established risk markers, investigators reported in JAMA Oncology.
The automated BSI also provides significantly greater discriminative ability compared with the current standard, which is manual assessment by counting metastatic lesion numbers, according to Andrew J. Armstrong, MD, of Duke University, Durham, N.C. and his coauthors.
“Incorporating the aBSI into clinical practice to supplement nuclear medicine reports may permit a more objective analysis of bone scan changes over time and their clinical relevance to patient care,” Dr. Armstrong and colleagues said.
The BSI represents tumor burden as a percentage of total skeletal weight. The system used in this study automates BSI methods by using artificial neural networks to detect metastatic hot spots and classify them as malignant or benign.
The automated system was evaluated in a preplanned secondary analysis of a randomized clinical trial of imiquimod in men with chemotherapy-naive metastatic castration-resistant prostate cancer. Evaluable bone scans were available for 721 out of 1,245 total enrollees from 241 sites in 37 countries.
In the secondary analysis, investigators found that baseline aBSI was significantly associated with OS. Risk of death increased by 20% for every doubling of the aBSI score (hazard ratio, 1.20; 95% confidence interval, 1.14-1.26; P less than .001).
The association remained significant in a multivariable model adjusting for five variables associated with OS: albumin, lactate dehydrogenase, C-reactive protein, serum prostate-specific antigen, and Eastern European geographic region.
In addition, the automated BSI had a better discriminating ability in prognosticating OS as compared to manual lesion counting (C-index of 0.63 and 0.60, respectively; P = .03), investigators said.
Secondary analyses showed the automated BSI was also associated with time to symptomatic progression, prostate cancer specific survival, and time to opiate use for cancer pain.
“These data support the clinical utility of the automated BSI, given its association with clinically relevant outcomes that are critically important in patient care,” wrote Dr. Armstrong and his colleagues.
The study was funded by EXINI Diagnostics AB, a subsidiary of Progenics Pharmaceuticals. The researchers reported disclosures related to EXINI Diagnostics AB and Active Biotech.
SOURCE: Armstrong AJ et al. JAMA Oncol. 2018 May 17. doi: 10.1001/jamaoncol.2018.1093.
FROM JAMA Oncology
Key clinical point: For patients with metastatic castration-resistant prostate cancer, an automated bone scan index (BSI) system predicted overall survival even after adjustment for other known prognostic factors.
Major finding: In multivariate analysis, higher automated BSI values remained independently associated with overall survival (hazard ratio, 1.06; 95% CI, 1.01-1.11; P = .03).
Study details: Preplanned secondary analysis of automated BSI in 721 men with bone metastatic, chemotherapy-naive castration-resistant prostate cancer who were enrolled in 10TASQ10, a randomized phase 3 clinical trial of tasquinimod.
Disclosures: The study was funded by EXINI Diagnostics AB, a subsidiary of Progenics Pharmaceuticals. The researchers reported disclosures related to EXINI Diagnostics AB and Active Biotech.
Source: Armstrong AJ et al. JAMA Oncol. 2018 May 17. doi: 10.1001/jamaoncol.2018.1093.
Canagliflozin linked to lower HbA1c levels in younger patients
BOSTON – The effects of canagliflozin on hemoglobin A1c levels were greater in participants under age 65 years in randomized clinical trials of the SGLT2 inhibitor, according to results of a prespecified subgroup analysis.
Some cardiovascular, renal, and mortality outcomes also varied by age group, according to the analysis of participants in the CANVAS (Canagliflozin Cardiovascular Assessment Study) program. Despite those differences, the effect of canagliflozin was generally consistent on other outcomes, such as body weight and blood pressure, in patient grouped into those aged less than 65 years and those aged 65 years and older, investigators reported at the annual meeting of the American Association of Clinical Endocrinologists.
Nonfatal MI, nonfatal stroke, and the composite of doubling of serum creatine, end-stage renal disease, or renal death were lower in study participants aged 65 and older on canagliflozin. Lower risks of cardiovascular death and all-cause mortality were seen in participants under age 65 years who were taking canagliflozin. However, “these results should be interpreted with caution given the large number of subgroup analyses performed,” wrote Fernando Ovalle, MD, director of the multidisciplinary comprehensive diabetes clinic at the University of Alabama at Birmingham, and his colleagues.
Canagliflozin was found to reduce risk of the composite endpoint of cardiovascular death, nonfatal myocardial infarction, or nonfatal stroke versus placebo in previously published results of the CANVAS study, which included individuals with type 2 diabetes mellitus who either had or were at high risk for having cardiovascular disease.
The two multicenter, randomized, controlled trials, CANVAS and CANVAS-R, included more than 10,000 patients. The subgroup analysis presented here at the AACE meeting included 5,578 patients aged less than 65 years (55%) and 4,564 patients aged 65 years or older (45%).
The subgroup analysis found that placebo-subtracted differences in HbA1c were greater in patients under 65 years than those in patients 65 or older (–0.7% and –0.5%, respectively; P less than .0001). However, there were no significant differences by age group in body weight changes, systolic blood pressure, or diastolic blood pressure.
Patients aged 65 years or older at baseline had a lower risk of nonfatal MI and nonfatal stroke with canagliflozin versus placebo (P for heterogeneity, .02 and.01, respectively), according to investigators. Older patients also had lower risk of the composite of serum creatinine doubling, end-stage kidney disease, or renal death with canagliflozin versus placebo (P = .01).
Patients aged less than 65 years at baseline had lower risk of cardiovascular death (P = .01) and all cause mortality (P = .01) for canagliflozin versus placebo.
Dr. Ovalle reported disclosures related to Merck, AstraZeneca, Sanofi Pasteur, Novo Nordisk, GlaxoSmithKline, Janssen, Eli Lilly, Medtronic, Pfizer, and GI Dynamics, along with the National Institutes of Health and Juvenile Diabetes Research Foundation.
SOURCE: Ovalle F et al. AACE 2018, Abstract 233.
BOSTON – The effects of canagliflozin on hemoglobin A1c levels were greater in participants under age 65 years in randomized clinical trials of the SGLT2 inhibitor, according to results of a prespecified subgroup analysis.
Some cardiovascular, renal, and mortality outcomes also varied by age group, according to the analysis of participants in the CANVAS (Canagliflozin Cardiovascular Assessment Study) program. Despite those differences, the effect of canagliflozin was generally consistent on other outcomes, such as body weight and blood pressure, in patient grouped into those aged less than 65 years and those aged 65 years and older, investigators reported at the annual meeting of the American Association of Clinical Endocrinologists.
Nonfatal MI, nonfatal stroke, and the composite of doubling of serum creatine, end-stage renal disease, or renal death were lower in study participants aged 65 and older on canagliflozin. Lower risks of cardiovascular death and all-cause mortality were seen in participants under age 65 years who were taking canagliflozin. However, “these results should be interpreted with caution given the large number of subgroup analyses performed,” wrote Fernando Ovalle, MD, director of the multidisciplinary comprehensive diabetes clinic at the University of Alabama at Birmingham, and his colleagues.
Canagliflozin was found to reduce risk of the composite endpoint of cardiovascular death, nonfatal myocardial infarction, or nonfatal stroke versus placebo in previously published results of the CANVAS study, which included individuals with type 2 diabetes mellitus who either had or were at high risk for having cardiovascular disease.
The two multicenter, randomized, controlled trials, CANVAS and CANVAS-R, included more than 10,000 patients. The subgroup analysis presented here at the AACE meeting included 5,578 patients aged less than 65 years (55%) and 4,564 patients aged 65 years or older (45%).
The subgroup analysis found that placebo-subtracted differences in HbA1c were greater in patients under 65 years than those in patients 65 or older (–0.7% and –0.5%, respectively; P less than .0001). However, there were no significant differences by age group in body weight changes, systolic blood pressure, or diastolic blood pressure.
Patients aged 65 years or older at baseline had a lower risk of nonfatal MI and nonfatal stroke with canagliflozin versus placebo (P for heterogeneity, .02 and.01, respectively), according to investigators. Older patients also had lower risk of the composite of serum creatinine doubling, end-stage kidney disease, or renal death with canagliflozin versus placebo (P = .01).
Patients aged less than 65 years at baseline had lower risk of cardiovascular death (P = .01) and all cause mortality (P = .01) for canagliflozin versus placebo.
Dr. Ovalle reported disclosures related to Merck, AstraZeneca, Sanofi Pasteur, Novo Nordisk, GlaxoSmithKline, Janssen, Eli Lilly, Medtronic, Pfizer, and GI Dynamics, along with the National Institutes of Health and Juvenile Diabetes Research Foundation.
SOURCE: Ovalle F et al. AACE 2018, Abstract 233.
BOSTON – The effects of canagliflozin on hemoglobin A1c levels were greater in participants under age 65 years in randomized clinical trials of the SGLT2 inhibitor, according to results of a prespecified subgroup analysis.
Some cardiovascular, renal, and mortality outcomes also varied by age group, according to the analysis of participants in the CANVAS (Canagliflozin Cardiovascular Assessment Study) program. Despite those differences, the effect of canagliflozin was generally consistent on other outcomes, such as body weight and blood pressure, in patient grouped into those aged less than 65 years and those aged 65 years and older, investigators reported at the annual meeting of the American Association of Clinical Endocrinologists.
Nonfatal MI, nonfatal stroke, and the composite of doubling of serum creatine, end-stage renal disease, or renal death were lower in study participants aged 65 and older on canagliflozin. Lower risks of cardiovascular death and all-cause mortality were seen in participants under age 65 years who were taking canagliflozin. However, “these results should be interpreted with caution given the large number of subgroup analyses performed,” wrote Fernando Ovalle, MD, director of the multidisciplinary comprehensive diabetes clinic at the University of Alabama at Birmingham, and his colleagues.
Canagliflozin was found to reduce risk of the composite endpoint of cardiovascular death, nonfatal myocardial infarction, or nonfatal stroke versus placebo in previously published results of the CANVAS study, which included individuals with type 2 diabetes mellitus who either had or were at high risk for having cardiovascular disease.
The two multicenter, randomized, controlled trials, CANVAS and CANVAS-R, included more than 10,000 patients. The subgroup analysis presented here at the AACE meeting included 5,578 patients aged less than 65 years (55%) and 4,564 patients aged 65 years or older (45%).
The subgroup analysis found that placebo-subtracted differences in HbA1c were greater in patients under 65 years than those in patients 65 or older (–0.7% and –0.5%, respectively; P less than .0001). However, there were no significant differences by age group in body weight changes, systolic blood pressure, or diastolic blood pressure.
Patients aged 65 years or older at baseline had a lower risk of nonfatal MI and nonfatal stroke with canagliflozin versus placebo (P for heterogeneity, .02 and.01, respectively), according to investigators. Older patients also had lower risk of the composite of serum creatinine doubling, end-stage kidney disease, or renal death with canagliflozin versus placebo (P = .01).
Patients aged less than 65 years at baseline had lower risk of cardiovascular death (P = .01) and all cause mortality (P = .01) for canagliflozin versus placebo.
Dr. Ovalle reported disclosures related to Merck, AstraZeneca, Sanofi Pasteur, Novo Nordisk, GlaxoSmithKline, Janssen, Eli Lilly, Medtronic, Pfizer, and GI Dynamics, along with the National Institutes of Health and Juvenile Diabetes Research Foundation.
SOURCE: Ovalle F et al. AACE 2018, Abstract 233.
REPORTING FROM AACE 2018
Key clinical point: Placebo-subtracted differences in HbA1c were greater in patients under age 65 years versus patients age 65 years and older, while some cardiovascular, renal, and mortality outcomes varied by age group.
Major finding: Placebo-subtracted differences in HbA1c were greater in patients under 65 years versus patients 65 or older (-0.7% and -0.5%, respectively; P less than 0.0001).
Study details: A prespecified subset analysis of the 2 multicenter randomized controlled trials in the CANVAS Program (CANVAS and CANVAS-R studies) including more than 10,000 individuals with type 2 diabetes mellitus and either established CV disease or high risk for CV disease.
Disclosures: Dr. Ovalle reported disclosures related to Merck, AstraZeneca, Sanofi Pasteur, Novo Nordisk, GlaxoSmithKline, Janssen, Eli Lilly, Medtronic, Pfizer, and GI Dynamics, along with the National Institutes of Health and Juvenile Diabetes Research Foundation.
Source: Ovalle F, et al. AACE 2018, Abstract 233
VIDEO: Canagliflozin’s HbA1c effect muted over time by placebo group effects
BOSTON – In a large, long-term study of canagliflozin versus placebo, an excess of discontinuations in the placebo group contributed to a dampening in the magnitude of improvement in hemoglobin A1c.
That’s according to investigators who reported the findings at the annual meeting of the American Association of Clinical Endocrinologists.
A higher rate of starting new antihyperglycemic agents in the placebo arm also likely contributed to the decrease in the difference in HbA1c after 52 weeks in CANVAS (Canagliflozin Cardiovascular Assessment Study), according to investigator Carol Wysham, MD, of the University of Washington, Spokane.
As previously reported, the two randomized trials in the CANVAS program showed that canagliflozin reduced risk of cardiovascular events in patients with type 2 diabetes at elevated risk of cardiovascular disease.
While the CANVAS program was not designed to assess glucose lowering – and, in fact, allowed adjustment of background antihyperglycemic agents at any time – canagliflozin patients were more likely than placebo-treated patients to achieve HbA1c less than 7.0%.
However, the mean placebo-subtracted reduction in HbA1c peaked at –0.64% at week 26 but shrank to –0.24% by week 338, the end of the study.
“In this case, [the analysis] is helping to understand why we might have seen a deterioration in A1c control over a very long period of time,” Dr. Wysham explained.
The analysis showed that, after week 52 of the study, more patients discontinued placebo, compared with those taking canagliflozin. Over the entire CANVAS program, investigators said, the rate of discontinuation was 118.0 per 1,000 patient-years in the placebo group and 94.1 per 1,000 patient-years for canagliflozin.
In addition, while the concomitant use of antihyperglycemic agents was well balanced at baseline, the number of participants initiating new antihyperglycemic agents over the course of the study was 27% for the placebo-treated patients and 17.8% for the canagliflozin-treated patients, investigators found.
All together, the CANVAS program has provided the longest-term experience to date regarding glycemic control with canagliflozin, demonstrating greater reductions in HbA1c, versus placebo, over about 6.5 years, Dr. Wysham and her coinvestigators said in their poster presentation.
The new analysis provides better clarity on why the durability in HbA1c benefit seemed somewhat attenuated over time, according to Dr. Wysham.
“Most of us think that, if you start an SGLT2 inhibitor, especially starting it relatively early in diagnosis of diabetes, it gives you better durability than what you might see with other agents,” she said. “In fact, that’s been seen in many of the clinical trials, compared to sulphonylurea or DPP-4 inhibitor.”
Dr. Wysham reported disclosures related to AstraZeneca, Boehringer Ingelheim, Eli Lilly, Insulet, Janssen Scientific Affairs, Novo Nordisk, and Sanofi Pasteur.
SOURCE: Wysham C et al. AACE 2018, Abstract 262.
BOSTON – In a large, long-term study of canagliflozin versus placebo, an excess of discontinuations in the placebo group contributed to a dampening in the magnitude of improvement in hemoglobin A1c.
That’s according to investigators who reported the findings at the annual meeting of the American Association of Clinical Endocrinologists.
A higher rate of starting new antihyperglycemic agents in the placebo arm also likely contributed to the decrease in the difference in HbA1c after 52 weeks in CANVAS (Canagliflozin Cardiovascular Assessment Study), according to investigator Carol Wysham, MD, of the University of Washington, Spokane.
As previously reported, the two randomized trials in the CANVAS program showed that canagliflozin reduced risk of cardiovascular events in patients with type 2 diabetes at elevated risk of cardiovascular disease.
While the CANVAS program was not designed to assess glucose lowering – and, in fact, allowed adjustment of background antihyperglycemic agents at any time – canagliflozin patients were more likely than placebo-treated patients to achieve HbA1c less than 7.0%.
However, the mean placebo-subtracted reduction in HbA1c peaked at –0.64% at week 26 but shrank to –0.24% by week 338, the end of the study.
“In this case, [the analysis] is helping to understand why we might have seen a deterioration in A1c control over a very long period of time,” Dr. Wysham explained.
The analysis showed that, after week 52 of the study, more patients discontinued placebo, compared with those taking canagliflozin. Over the entire CANVAS program, investigators said, the rate of discontinuation was 118.0 per 1,000 patient-years in the placebo group and 94.1 per 1,000 patient-years for canagliflozin.
In addition, while the concomitant use of antihyperglycemic agents was well balanced at baseline, the number of participants initiating new antihyperglycemic agents over the course of the study was 27% for the placebo-treated patients and 17.8% for the canagliflozin-treated patients, investigators found.
All together, the CANVAS program has provided the longest-term experience to date regarding glycemic control with canagliflozin, demonstrating greater reductions in HbA1c, versus placebo, over about 6.5 years, Dr. Wysham and her coinvestigators said in their poster presentation.
The new analysis provides better clarity on why the durability in HbA1c benefit seemed somewhat attenuated over time, according to Dr. Wysham.
“Most of us think that, if you start an SGLT2 inhibitor, especially starting it relatively early in diagnosis of diabetes, it gives you better durability than what you might see with other agents,” she said. “In fact, that’s been seen in many of the clinical trials, compared to sulphonylurea or DPP-4 inhibitor.”
Dr. Wysham reported disclosures related to AstraZeneca, Boehringer Ingelheim, Eli Lilly, Insulet, Janssen Scientific Affairs, Novo Nordisk, and Sanofi Pasteur.
SOURCE: Wysham C et al. AACE 2018, Abstract 262.
BOSTON – In a large, long-term study of canagliflozin versus placebo, an excess of discontinuations in the placebo group contributed to a dampening in the magnitude of improvement in hemoglobin A1c.
That’s according to investigators who reported the findings at the annual meeting of the American Association of Clinical Endocrinologists.
A higher rate of starting new antihyperglycemic agents in the placebo arm also likely contributed to the decrease in the difference in HbA1c after 52 weeks in CANVAS (Canagliflozin Cardiovascular Assessment Study), according to investigator Carol Wysham, MD, of the University of Washington, Spokane.
As previously reported, the two randomized trials in the CANVAS program showed that canagliflozin reduced risk of cardiovascular events in patients with type 2 diabetes at elevated risk of cardiovascular disease.
While the CANVAS program was not designed to assess glucose lowering – and, in fact, allowed adjustment of background antihyperglycemic agents at any time – canagliflozin patients were more likely than placebo-treated patients to achieve HbA1c less than 7.0%.
However, the mean placebo-subtracted reduction in HbA1c peaked at –0.64% at week 26 but shrank to –0.24% by week 338, the end of the study.
“In this case, [the analysis] is helping to understand why we might have seen a deterioration in A1c control over a very long period of time,” Dr. Wysham explained.
The analysis showed that, after week 52 of the study, more patients discontinued placebo, compared with those taking canagliflozin. Over the entire CANVAS program, investigators said, the rate of discontinuation was 118.0 per 1,000 patient-years in the placebo group and 94.1 per 1,000 patient-years for canagliflozin.
In addition, while the concomitant use of antihyperglycemic agents was well balanced at baseline, the number of participants initiating new antihyperglycemic agents over the course of the study was 27% for the placebo-treated patients and 17.8% for the canagliflozin-treated patients, investigators found.
All together, the CANVAS program has provided the longest-term experience to date regarding glycemic control with canagliflozin, demonstrating greater reductions in HbA1c, versus placebo, over about 6.5 years, Dr. Wysham and her coinvestigators said in their poster presentation.
The new analysis provides better clarity on why the durability in HbA1c benefit seemed somewhat attenuated over time, according to Dr. Wysham.
“Most of us think that, if you start an SGLT2 inhibitor, especially starting it relatively early in diagnosis of diabetes, it gives you better durability than what you might see with other agents,” she said. “In fact, that’s been seen in many of the clinical trials, compared to sulphonylurea or DPP-4 inhibitor.”
Dr. Wysham reported disclosures related to AstraZeneca, Boehringer Ingelheim, Eli Lilly, Insulet, Janssen Scientific Affairs, Novo Nordisk, and Sanofi Pasteur.
SOURCE: Wysham C et al. AACE 2018, Abstract 262.
REPORTING FROM AACE 2018
Key clinical point: and a higher rate of starting new antihyperglycemic agents in the placebo arm.
Major finding: After week 52 of the study, more patients discontinued placebo versus canagliflozin. The number of participants initiating new antihyperglycemic agents over the course of the study was 17.8% for the canagliflozin arm and 27% for placebo.
Study details: An analysis of the effects of canagliflozin on HbA1c and changes in use of antihyperglycemic agents in the CANVAS study.
Disclosures: Dr. Wysham reported disclosures related to AstraZeneca, Boehringer Ingelheim, Eli Lilly, Insulet, Janssen Scientific Affairs, Novo Nordisk, and Sanofi Pasteur.
Source: Wysham C et al. AACE 2018, Abstract 262.
VIDEO: Acromegaly study reveals gender-specific differences
BOSTON – , according to study results presented at the annual meeting of the American Association of Clinical Endocrinologists.
The study was based on data for 112 patients (54 male, 58 female) operated on by one neurosurgeon between 1994 and 2016. The mean age at surgery was 43.6 years in men and 48.7 in women (P = .04), according to Talin Handa, Emory University, Atlanta, who presented the retrospective analysis.
The video associated with this article is no longer available on this site. Please view all of our videos on the MDedge YouTube channel
Men had higher mean IGF-1 levels (874 ng/mL vs. 716 ng/mL for women; P less than .01), and were more likely to have hypopituitarism.
Adjuvant treatment for acromegaly was needed in 57% of men and 49% of women. Following adjuvant treatment, 72% of men maintained surgical remission or achieved normal IGF-1 levels, compared with 89% of women (P = .03). Mean follow-up was shorter in men, 3.6 years, versus 5.2 years for women (P = .02), the researchers reported.
Six-year event-free survival was higher in women (P less than .01), according to the researchers.
For more study findings, watch our video interview.
SOURCE: Handa T et al. AACE 2018. Abstract #824.
BOSTON – , according to study results presented at the annual meeting of the American Association of Clinical Endocrinologists.
The study was based on data for 112 patients (54 male, 58 female) operated on by one neurosurgeon between 1994 and 2016. The mean age at surgery was 43.6 years in men and 48.7 in women (P = .04), according to Talin Handa, Emory University, Atlanta, who presented the retrospective analysis.
The video associated with this article is no longer available on this site. Please view all of our videos on the MDedge YouTube channel
Men had higher mean IGF-1 levels (874 ng/mL vs. 716 ng/mL for women; P less than .01), and were more likely to have hypopituitarism.
Adjuvant treatment for acromegaly was needed in 57% of men and 49% of women. Following adjuvant treatment, 72% of men maintained surgical remission or achieved normal IGF-1 levels, compared with 89% of women (P = .03). Mean follow-up was shorter in men, 3.6 years, versus 5.2 years for women (P = .02), the researchers reported.
Six-year event-free survival was higher in women (P less than .01), according to the researchers.
For more study findings, watch our video interview.
SOURCE: Handa T et al. AACE 2018. Abstract #824.
BOSTON – , according to study results presented at the annual meeting of the American Association of Clinical Endocrinologists.
The study was based on data for 112 patients (54 male, 58 female) operated on by one neurosurgeon between 1994 and 2016. The mean age at surgery was 43.6 years in men and 48.7 in women (P = .04), according to Talin Handa, Emory University, Atlanta, who presented the retrospective analysis.
The video associated with this article is no longer available on this site. Please view all of our videos on the MDedge YouTube channel
Men had higher mean IGF-1 levels (874 ng/mL vs. 716 ng/mL for women; P less than .01), and were more likely to have hypopituitarism.
Adjuvant treatment for acromegaly was needed in 57% of men and 49% of women. Following adjuvant treatment, 72% of men maintained surgical remission or achieved normal IGF-1 levels, compared with 89% of women (P = .03). Mean follow-up was shorter in men, 3.6 years, versus 5.2 years for women (P = .02), the researchers reported.
Six-year event-free survival was higher in women (P less than .01), according to the researchers.
For more study findings, watch our video interview.
SOURCE: Handa T et al. AACE 2018. Abstract #824.
REPORTING FROM AACE 2018
Key clinical point: Men with acromegaly present at a younger age, have higher IGF-1 levels, and achieve lower biochemical control rates than do women with the disorder.
Major finding: Men were less likely than women to have surgical remissions or normal IGF-1 levels after adjuvant treatment (72% for men and 89% for women; P = .03).
Study details: A retrospective analysis of 112 patients (54 male, 58 female) operated on by one neurosurgeon during 1994-2016.
Disclosures: The presenter had no disclosures related to the presentation.
Source: Handa T et al. AACE 2018. Abstract #824.