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TOPLINE:

A new analysis found that high-deductible health plans were associated with worse overall survival and cancer-specific survival among cancer survivors. High-deductible plans, however, were not associated with worse overall survival among adults without a history of cancer.

METHODOLOGY:

• Previous studies have linked high-deductible health plans with decreased or delayed health utilization among cancer survivors and higher out-of-pocket costs. However, it’s not clear whether these plans influence cancer outcomes.
• In a cross-sectional study, researchers analyzed data from 147,254 respondents (aged 18 to 84 years) in the National Health Interview Survey from 2011 to 2018 and identified individuals with high-deductible plans — 2331 cancer survivors and 37,473 people without a history of cancer.
• The researchers acquired linked mortality files from the National Death Index, which included data on mortality events through the end of 2019.
• High-deductible health plans were identified through survey responses and defined as plans with yearly deductibles of at least $1200-$1350 for individuals or at least $2400-$2700 for families.
• The primary endpoints included overall survival and cancer-specific survival. Researchers adjusted for insurance status, marital status, sex, comorbidities, education, household income, geographic region, cancer site, and time since diagnosis.

TAKEAWAY:

• Among cancer survivors, having a high-deductible health plan was associated with worse overall survival (hazard ratio [HR], 1.46) and cancer-specific survival (HR, 1.34). However, sensitivity analyses incorporating time since diagnosis slightly attenuated the cancer-specific survival association (HR, 1.20; 95% CI, 0.92-1.55).
• Among adults without a history of cancer, having a high-deductible health plan was not associated with significantly worse overall survival (HR, 1.08; 95% CI, 0.96-1.21).
• General concerns over finances, worry about medical bills, cost-related delays, or forgone care, as well as cost-related underuse of medications were significant mediators of the associations between high-deductible health plan status and mortality outcomes among cancer survivors.
• High-deductible health plan status was also associated with worse cancer-specific survival among cancer survivors with incomes at least 400% of the federal poverty level (HR, 1.65; P for interaction = .03).

IN PRACTICE:

“These data suggest that insurance coverage that financially discourages medical care may financially discourage necessary care and ultimately worsen cancer outcomes,” the study authors wrote. “This danger appears to be unique to cancer survivors, as [high-deductible health plans] were not associated with survival among adults without a cancer history.”

SOURCE:

The study, led by Justin M. Barnes, MD, MS, Department of Radiation Oncology, Mayo Clinic in Rochester, Minnesota, was published online on January 29 in JAMA Network Open.

LIMITATIONS:

High-deductible health plan status was self-reported and may have been inaccurate for some individuals, with more than half of consumers being unsure about their annual deductible amount. The study lacked specific plan details and exact deductible amounts, and high-deductible health plan status was based on a single time point during survey participation. Additionally, researchers lacked information about cancer stage, cancer-directed therapies, recurrences, or complications, and cancer mortality could be from cancers diagnosed after survey participation.

DISCLOSURES:

Meera Ragavan, MD, MPH, disclosed receiving personal fees from Trial Library and AstraZeneca and grants from Merck, outside the submitted work. Other authors reported receiving personal fees from Costs of Care during the study. Additional disclosures are noted in the original article.

This article was created using several editorial tools, including AI, as part of the process. Human editors reviewed this content before publication.

A version of this article first appeared on Medscape.com.

TOPLINE:

A new analysis found that high-deductible health plans were associated with worse overall survival and cancer-specific survival among cancer survivors. High-deductible plans, however, were not associated with worse overall survival among adults without a history of cancer.

METHODOLOGY:

• Previous studies have linked high-deductible health plans with decreased or delayed health utilization among cancer survivors and higher out-of-pocket costs. However, it’s not clear whether these plans influence cancer outcomes.
• In a cross-sectional study, researchers analyzed data from 147,254 respondents (aged 18 to 84 years) in the National Health Interview Survey from 2011 to 2018 and identified individuals with high-deductible plans — 2331 cancer survivors and 37,473 people without a history of cancer.
• The researchers acquired linked mortality files from the National Death Index, which included data on mortality events through the end of 2019.
• High-deductible health plans were identified through survey responses and defined as plans with yearly deductibles of at least $1200-$1350 for individuals or at least $2400-$2700 for families.
• The primary endpoints included overall survival and cancer-specific survival. Researchers adjusted for insurance status, marital status, sex, comorbidities, education, household income, geographic region, cancer site, and time since diagnosis.

TAKEAWAY:

• Among cancer survivors, having a high-deductible health plan was associated with worse overall survival (hazard ratio [HR], 1.46) and cancer-specific survival (HR, 1.34). However, sensitivity analyses incorporating time since diagnosis slightly attenuated the cancer-specific survival association (HR, 1.20; 95% CI, 0.92-1.55).
• Among adults without a history of cancer, having a high-deductible health plan was not associated with significantly worse overall survival (HR, 1.08; 95% CI, 0.96-1.21).
• General concerns over finances, worry about medical bills, cost-related delays, or forgone care, as well as cost-related underuse of medications were significant mediators of the associations between high-deductible health plan status and mortality outcomes among cancer survivors.
• High-deductible health plan status was also associated with worse cancer-specific survival among cancer survivors with incomes at least 400% of the federal poverty level (HR, 1.65; P for interaction = .03).

IN PRACTICE:

“These data suggest that insurance coverage that financially discourages medical care may financially discourage necessary care and ultimately worsen cancer outcomes,” the study authors wrote. “This danger appears to be unique to cancer survivors, as [high-deductible health plans] were not associated with survival among adults without a cancer history.”

SOURCE:

The study, led by Justin M. Barnes, MD, MS, Department of Radiation Oncology, Mayo Clinic in Rochester, Minnesota, was published online on January 29 in JAMA Network Open.

LIMITATIONS:

High-deductible health plan status was self-reported and may have been inaccurate for some individuals, with more than half of consumers being unsure about their annual deductible amount. The study lacked specific plan details and exact deductible amounts, and high-deductible health plan status was based on a single time point during survey participation. Additionally, researchers lacked information about cancer stage, cancer-directed therapies, recurrences, or complications, and cancer mortality could be from cancers diagnosed after survey participation.

DISCLOSURES:

Meera Ragavan, MD, MPH, disclosed receiving personal fees from Trial Library and AstraZeneca and grants from Merck, outside the submitted work. Other authors reported receiving personal fees from Costs of Care during the study. Additional disclosures are noted in the original article.

This article was created using several editorial tools, including AI, as part of the process. Human editors reviewed this content before publication.

A version of this article first appeared on Medscape.com.

TOPLINE:

A new analysis found that high-deductible health plans were associated with worse overall survival and cancer-specific survival among cancer survivors. High-deductible plans, however, were not associated with worse overall survival among adults without a history of cancer.

METHODOLOGY:

• Previous studies have linked high-deductible health plans with decreased or delayed health utilization among cancer survivors and higher out-of-pocket costs. However, it’s not clear whether these plans influence cancer outcomes.
• In a cross-sectional study, researchers analyzed data from 147,254 respondents (aged 18 to 84 years) in the National Health Interview Survey from 2011 to 2018 and identified individuals with high-deductible plans — 2331 cancer survivors and 37,473 people without a history of cancer.
• The researchers acquired linked mortality files from the National Death Index, which included data on mortality events through the end of 2019.
• High-deductible health plans were identified through survey responses and defined as plans with yearly deductibles of at least $1200-$1350 for individuals or at least $2400-$2700 for families.
• The primary endpoints included overall survival and cancer-specific survival. Researchers adjusted for insurance status, marital status, sex, comorbidities, education, household income, geographic region, cancer site, and time since diagnosis.

TAKEAWAY:

• Among cancer survivors, having a high-deductible health plan was associated with worse overall survival (hazard ratio [HR], 1.46) and cancer-specific survival (HR, 1.34). However, sensitivity analyses incorporating time since diagnosis slightly attenuated the cancer-specific survival association (HR, 1.20; 95% CI, 0.92-1.55).
• Among adults without a history of cancer, having a high-deductible health plan was not associated with significantly worse overall survival (HR, 1.08; 95% CI, 0.96-1.21).
• General concerns over finances, worry about medical bills, cost-related delays, or forgone care, as well as cost-related underuse of medications were significant mediators of the associations between high-deductible health plan status and mortality outcomes among cancer survivors.
• High-deductible health plan status was also associated with worse cancer-specific survival among cancer survivors with incomes at least 400% of the federal poverty level (HR, 1.65; P for interaction = .03).

IN PRACTICE:

“These data suggest that insurance coverage that financially discourages medical care may financially discourage necessary care and ultimately worsen cancer outcomes,” the study authors wrote. “This danger appears to be unique to cancer survivors, as [high-deductible health plans] were not associated with survival among adults without a cancer history.”

SOURCE:

The study, led by Justin M. Barnes, MD, MS, Department of Radiation Oncology, Mayo Clinic in Rochester, Minnesota, was published online on January 29 in JAMA Network Open.

LIMITATIONS:

High-deductible health plan status was self-reported and may have been inaccurate for some individuals, with more than half of consumers being unsure about their annual deductible amount. The study lacked specific plan details and exact deductible amounts, and high-deductible health plan status was based on a single time point during survey participation. Additionally, researchers lacked information about cancer stage, cancer-directed therapies, recurrences, or complications, and cancer mortality could be from cancers diagnosed after survey participation.

DISCLOSURES:

Meera Ragavan, MD, MPH, disclosed receiving personal fees from Trial Library and AstraZeneca and grants from Merck, outside the submitted work. Other authors reported receiving personal fees from Costs of Care during the study. Additional disclosures are noted in the original article.

This article was created using several editorial tools, including AI, as part of the process. Human editors reviewed this content before publication.

A version of this article first appeared on Medscape.com.

TOPLINE:

Adding aminopeptidase N and polymeric immunoglobin receptor to a plasma biomarker panel of carbohydrate antigen 19-9 (CA19-9) and thrombospondin 2 (THBS2) enhanced the detection of early-stage pancreatic ductal adenocarcinoma (PDAC). At 95% specificity, the four-marker panel achieved more than 87% sensitivity for early-stage and more than 91% sensitivity for disease at any stage in two independent phase II studies. But prospective validation is required to ascertain clinical applicability.

METHODOLOGY:

• PDAC is associated with high mortality, but markedly improved survival is observed with early detection. Biomarkers such as CA19-9 are widely used to monitor PDAC treatment response but lack sensitivity and specificity for early-stage disease and can be influenced by patients’ genetics. A phase 2 study found THBS2 complements CA19‑9, with higher THBS2 levels linked to poorer prognosis in late-stage disease. This study uses phase 1 and 2 analyses to identify additional plasma biomarkers to improve early detection of PDAC.
• In phase 1 discovery, researchers used pooled plasma from 2 centers (University of Pennsylvania [Penn] and Mayo Clinic [Mayo]) to create representative samples for healthy control, chronic pancreatitis, early-stage PDAC (stage I/II), mid-stage PDAC (stage III), and late-stage PDAC.
• Plasma pools underwent abundant-protein depletion and were analyzed by two complementary mass spectrometry workflows; proteins consistently elevated in early PDAC (aminopeptidase N and polymeric immunoglobin receptor) were prioritized.
• Phase 2 validation measured CA19-9, THBS2, aminopeptidase N, and polymeric immunoglobin receptor levels by enzyme-linked immunosorbent assay in two blinded retrospective cohorts (Penn, n = 135; Mayo, n = 537). Overall, the Penn cohort included 59 patients with PDAC, 47 healthy control individuals, and 29 control patients with diseases (chronic pancreatitis, pancreatic cysts, pancreatic intraepithelial neoplasia, and intraductal papillary mucinous neoplasms). The Mayo cohort included 197 patients with PDAC, 140 healthy control individuals, and 200 control patients with diseases (intraductal papillary mucinous neoplasms, pancreatic neuroendocrine tumors, and chronic pancreatitis).
• Investigators developed univariate and multivariable logistic regression models to evaluate each marker alone and in combinations (2-, 3-, and 4-marker panels) for discriminating patients with PDAC from healthy control individuals and from control patients with diseases. Model performance was assessed using receiver-operating characteristic (ROC) curves and area under the ROC curve (AUC), and bootstrap methods were used to estimate 95% CIs.

TAKEAWAY:

• Comparing the performances of single markers for patients with stage I/II PDAC vs healthy control individuals, no single marker could outperform CA19-9 alone (AUC = 0.90 in both Penn and Mayo cohorts). Two-marker models (CA19-9 plus one marker) vs CA19-9 alone improved AUCs for both early- and all-stage PDACs in both cohorts.
• Looking at multivariable panels for patients with stage I/II PDAC vs healthy control individuals, the 3-marker panel of CA19-9/THBS2/ aminopeptidase N outperformed the other three-marker models, with AUCs of 0.96 (Penn) and 0.97 (Mayo). The 4-marker panel of CA19-9/THBS2/aminopeptidase N /polymeric immunoglobin receptor was the strongest performing panel with AUCs of 0.96 (Penn) and 0.97 (Mayo).
• In the Mayo cohort, the 4-marker panel (CA19-9/THBS2/aminopeptidase N/polymeric immunoglobin receptor) achieved AUCs of 0.87 and 0.91 for patients with stage I/II PDAC vs control patients with diseases and patients with stages I-IV PDAC vs control patients with diseases, respectively.
• At a specificity of 95%, “a plasma biomarker panel composed of CA19-9 (≥ 35 U/mL), THBS2 (≥ 42 ng/mL), aminopeptidase N (≥ 2995 ng/mL), and polymeric immunoglobin receptor (≥ 1800 ng/mL) yielded a sensitivity of 91.94% for all stages and 87.53% for early stage I/II PDAC detection,” the authors wrote.

IN PRACTICE:

“A panel composed of CA19-9/THBS2/aminopeptidase N/polymeric immunoglobin receptor may be suitable for early detection of PDAC based on results showing a high sensitivity and specificity in the larger Mayo phase II cohort but would require prediagnostic cohorts for verification,” the authors of the study wrote.

SOURCE:

The study, led by Brianna M. Krusen, Institute for Regenerative Medicine, Perelman School of Medicine at Penn, Philadelphia, was published online in Clinical Cancer Research.

LIMITATIONS:

The biomarker panel was evaluated on samples drawn at the time of diagnosis and has not yet been assessed in prediagnostic or high‑risk surveillance cohorts, which are necessary to establish its clinical performance.

DISCLOSURES:

The study was supported by the Penn Pancreatic Cancer Research Center, A Love for Life, and National Institutes of Health (NIH) Grant. Several authors reported receiving grants and other support from the NIH and various other sources.

This article was created using several editorial tools, including AI, as part of the process. Human editors reviewed this content before publication.

A version of this article first appeared on Medscape.com.

TOPLINE:

Adding aminopeptidase N and polymeric immunoglobin receptor to a plasma biomarker panel of carbohydrate antigen 19-9 (CA19-9) and thrombospondin 2 (THBS2) enhanced the detection of early-stage pancreatic ductal adenocarcinoma (PDAC). At 95% specificity, the four-marker panel achieved more than 87% sensitivity for early-stage and more than 91% sensitivity for disease at any stage in two independent phase II studies. But prospective validation is required to ascertain clinical applicability.

METHODOLOGY:

• PDAC is associated with high mortality, but markedly improved survival is observed with early detection. Biomarkers such as CA19-9 are widely used to monitor PDAC treatment response but lack sensitivity and specificity for early-stage disease and can be influenced by patients’ genetics. A phase 2 study found THBS2 complements CA19‑9, with higher THBS2 levels linked to poorer prognosis in late-stage disease. This study uses phase 1 and 2 analyses to identify additional plasma biomarkers to improve early detection of PDAC.
• In phase 1 discovery, researchers used pooled plasma from 2 centers (University of Pennsylvania [Penn] and Mayo Clinic [Mayo]) to create representative samples for healthy control, chronic pancreatitis, early-stage PDAC (stage I/II), mid-stage PDAC (stage III), and late-stage PDAC.
• Plasma pools underwent abundant-protein depletion and were analyzed by two complementary mass spectrometry workflows; proteins consistently elevated in early PDAC (aminopeptidase N and polymeric immunoglobin receptor) were prioritized.
• Phase 2 validation measured CA19-9, THBS2, aminopeptidase N, and polymeric immunoglobin receptor levels by enzyme-linked immunosorbent assay in two blinded retrospective cohorts (Penn, n = 135; Mayo, n = 537). Overall, the Penn cohort included 59 patients with PDAC, 47 healthy control individuals, and 29 control patients with diseases (chronic pancreatitis, pancreatic cysts, pancreatic intraepithelial neoplasia, and intraductal papillary mucinous neoplasms). The Mayo cohort included 197 patients with PDAC, 140 healthy control individuals, and 200 control patients with diseases (intraductal papillary mucinous neoplasms, pancreatic neuroendocrine tumors, and chronic pancreatitis).
• Investigators developed univariate and multivariable logistic regression models to evaluate each marker alone and in combinations (2-, 3-, and 4-marker panels) for discriminating patients with PDAC from healthy control individuals and from control patients with diseases. Model performance was assessed using receiver-operating characteristic (ROC) curves and area under the ROC curve (AUC), and bootstrap methods were used to estimate 95% CIs.

TAKEAWAY:

• Comparing the performances of single markers for patients with stage I/II PDAC vs healthy control individuals, no single marker could outperform CA19-9 alone (AUC = 0.90 in both Penn and Mayo cohorts). Two-marker models (CA19-9 plus one marker) vs CA19-9 alone improved AUCs for both early- and all-stage PDACs in both cohorts.
• Looking at multivariable panels for patients with stage I/II PDAC vs healthy control individuals, the 3-marker panel of CA19-9/THBS2/ aminopeptidase N outperformed the other three-marker models, with AUCs of 0.96 (Penn) and 0.97 (Mayo). The 4-marker panel of CA19-9/THBS2/aminopeptidase N /polymeric immunoglobin receptor was the strongest performing panel with AUCs of 0.96 (Penn) and 0.97 (Mayo).
• In the Mayo cohort, the 4-marker panel (CA19-9/THBS2/aminopeptidase N/polymeric immunoglobin receptor) achieved AUCs of 0.87 and 0.91 for patients with stage I/II PDAC vs control patients with diseases and patients with stages I-IV PDAC vs control patients with diseases, respectively.
• At a specificity of 95%, “a plasma biomarker panel composed of CA19-9 (≥ 35 U/mL), THBS2 (≥ 42 ng/mL), aminopeptidase N (≥ 2995 ng/mL), and polymeric immunoglobin receptor (≥ 1800 ng/mL) yielded a sensitivity of 91.94% for all stages and 87.53% for early stage I/II PDAC detection,” the authors wrote.

IN PRACTICE:

“A panel composed of CA19-9/THBS2/aminopeptidase N/polymeric immunoglobin receptor may be suitable for early detection of PDAC based on results showing a high sensitivity and specificity in the larger Mayo phase II cohort but would require prediagnostic cohorts for verification,” the authors of the study wrote.

SOURCE:

The study, led by Brianna M. Krusen, Institute for Regenerative Medicine, Perelman School of Medicine at Penn, Philadelphia, was published online in Clinical Cancer Research.

LIMITATIONS:

The biomarker panel was evaluated on samples drawn at the time of diagnosis and has not yet been assessed in prediagnostic or high‑risk surveillance cohorts, which are necessary to establish its clinical performance.

DISCLOSURES:

The study was supported by the Penn Pancreatic Cancer Research Center, A Love for Life, and National Institutes of Health (NIH) Grant. Several authors reported receiving grants and other support from the NIH and various other sources.

This article was created using several editorial tools, including AI, as part of the process. Human editors reviewed this content before publication.

A version of this article first appeared on Medscape.com.

TOPLINE:

Adding aminopeptidase N and polymeric immunoglobin receptor to a plasma biomarker panel of carbohydrate antigen 19-9 (CA19-9) and thrombospondin 2 (THBS2) enhanced the detection of early-stage pancreatic ductal adenocarcinoma (PDAC). At 95% specificity, the four-marker panel achieved more than 87% sensitivity for early-stage and more than 91% sensitivity for disease at any stage in two independent phase II studies. But prospective validation is required to ascertain clinical applicability.

METHODOLOGY:

• PDAC is associated with high mortality, but markedly improved survival is observed with early detection. Biomarkers such as CA19-9 are widely used to monitor PDAC treatment response but lack sensitivity and specificity for early-stage disease and can be influenced by patients’ genetics. A phase 2 study found THBS2 complements CA19‑9, with higher THBS2 levels linked to poorer prognosis in late-stage disease. This study uses phase 1 and 2 analyses to identify additional plasma biomarkers to improve early detection of PDAC.
• In phase 1 discovery, researchers used pooled plasma from 2 centers (University of Pennsylvania [Penn] and Mayo Clinic [Mayo]) to create representative samples for healthy control, chronic pancreatitis, early-stage PDAC (stage I/II), mid-stage PDAC (stage III), and late-stage PDAC.
• Plasma pools underwent abundant-protein depletion and were analyzed by two complementary mass spectrometry workflows; proteins consistently elevated in early PDAC (aminopeptidase N and polymeric immunoglobin receptor) were prioritized.
• Phase 2 validation measured CA19-9, THBS2, aminopeptidase N, and polymeric immunoglobin receptor levels by enzyme-linked immunosorbent assay in two blinded retrospective cohorts (Penn, n = 135; Mayo, n = 537). Overall, the Penn cohort included 59 patients with PDAC, 47 healthy control individuals, and 29 control patients with diseases (chronic pancreatitis, pancreatic cysts, pancreatic intraepithelial neoplasia, and intraductal papillary mucinous neoplasms). The Mayo cohort included 197 patients with PDAC, 140 healthy control individuals, and 200 control patients with diseases (intraductal papillary mucinous neoplasms, pancreatic neuroendocrine tumors, and chronic pancreatitis).
• Investigators developed univariate and multivariable logistic regression models to evaluate each marker alone and in combinations (2-, 3-, and 4-marker panels) for discriminating patients with PDAC from healthy control individuals and from control patients with diseases. Model performance was assessed using receiver-operating characteristic (ROC) curves and area under the ROC curve (AUC), and bootstrap methods were used to estimate 95% CIs.

TAKEAWAY:

• Comparing the performances of single markers for patients with stage I/II PDAC vs healthy control individuals, no single marker could outperform CA19-9 alone (AUC = 0.90 in both Penn and Mayo cohorts). Two-marker models (CA19-9 plus one marker) vs CA19-9 alone improved AUCs for both early- and all-stage PDACs in both cohorts.
• Looking at multivariable panels for patients with stage I/II PDAC vs healthy control individuals, the 3-marker panel of CA19-9/THBS2/ aminopeptidase N outperformed the other three-marker models, with AUCs of 0.96 (Penn) and 0.97 (Mayo). The 4-marker panel of CA19-9/THBS2/aminopeptidase N /polymeric immunoglobin receptor was the strongest performing panel with AUCs of 0.96 (Penn) and 0.97 (Mayo).
• In the Mayo cohort, the 4-marker panel (CA19-9/THBS2/aminopeptidase N/polymeric immunoglobin receptor) achieved AUCs of 0.87 and 0.91 for patients with stage I/II PDAC vs control patients with diseases and patients with stages I-IV PDAC vs control patients with diseases, respectively.
• At a specificity of 95%, “a plasma biomarker panel composed of CA19-9 (≥ 35 U/mL), THBS2 (≥ 42 ng/mL), aminopeptidase N (≥ 2995 ng/mL), and polymeric immunoglobin receptor (≥ 1800 ng/mL) yielded a sensitivity of 91.94% for all stages and 87.53% for early stage I/II PDAC detection,” the authors wrote.

IN PRACTICE:

“A panel composed of CA19-9/THBS2/aminopeptidase N/polymeric immunoglobin receptor may be suitable for early detection of PDAC based on results showing a high sensitivity and specificity in the larger Mayo phase II cohort but would require prediagnostic cohorts for verification,” the authors of the study wrote.

SOURCE:

The study, led by Brianna M. Krusen, Institute for Regenerative Medicine, Perelman School of Medicine at Penn, Philadelphia, was published online in Clinical Cancer Research.

LIMITATIONS:

The biomarker panel was evaluated on samples drawn at the time of diagnosis and has not yet been assessed in prediagnostic or high‑risk surveillance cohorts, which are necessary to establish its clinical performance.

DISCLOSURES:

The study was supported by the Penn Pancreatic Cancer Research Center, A Love for Life, and National Institutes of Health (NIH) Grant. Several authors reported receiving grants and other support from the NIH and various other sources.

This article was created using several editorial tools, including AI, as part of the process. Human editors reviewed this content before publication.

A version of this article first appeared on Medscape.com.

New research sheds light on how chronic heavy alcohol use may contribute to colorectal cancer (CRC) development and how quitting may lower the risk for precancerous colorectal adenomas.

In a large US cancer screening trial, current heavy drinkers — with an average lifetime alcohol intake of 14 or more drinks per week — had a 25% higher risk for CRC and an almost twofold higher risk for rectal cancer than light drinkers averaging less than one drink per week.

When the research team further considered drinking consistency, steady heavy drinking throughout adulthood was associated with a 91% higher risk for CRC than consistent light drinking. 

Additionally, no increased risk for CRC was found among former drinkers, and former drinkers were less likely than light drinkers to develop nonadvanced colorectal adenomas.

This analysis “adds to the growing amount of concerning literature showing that chronic heavy alcohol use can potentially contribute to colorectal cancer development,” Benjamin H. Levy III, MD, gastroenterologist and clinical associate of medicine at UChicago Medicine in Chicago, who wasn’t involved in the study, told Medscape Medical News.

The study’s co-senior author, Erikka Loftfield, PhD, MPH, also noted that the study “provides new evidence indicating that drinking cessation, compared to consistent light drinking, may lower adenoma risk.”

Current cancer prevention guidelines recommend limiting alcohol intake or ideally not drinking at all, and “our findings do not change this advice,” said Loftfield, with the National Cancer Institute (NCI) in Bethesda, Maryland. 

The study was published online on January 26 in the journal Cancer.

Addressing a Data Gap

Alcoholic beverages are classified as carcinogenic to humans and are causally associated with CRC, Loftfield told Medscape Medical News. However, much of the evidence for this comes from cohort studies that only measure recent drinking patterns, generally among older adults, at study baseline. Fewer studies have looked at how drinking over a person’s lifetime and alcohol consumption patterns relate to colorectal adenoma and CRC risk, she explained.

To address these gaps, Loftfield and colleagues leveraged data on alcohol intake gathered as part of the NCI’s Prostate, Long, Colorectal, and Ovarian Cancer Screening Trial.

Average lifetime alcohol intake was calculated as drinks per week from age 18 through study baseline, and drinking patterns were further classified based on consistency and intensity over time. 

During 20 years of follow-up, 1679 incident CRC cases occurred among 88,092 study participants. In multivariable-adjusted analyses, current heavy drinkers had a higher risk for CRC than those averaging less than one drink per week (hazard ratio [HR], 1.25), with the strongest association observed for rectal cancer (HR, 1.95).

“The increase in rectal cancer risk for heavy drinkers seen in this 20-year observational study was especially concerning,” Levy told Medscape Medical News.

What About Moderate Drinking?

Perhaps counterintuitively, moderate current drinkers (those consuming an average of 7 to less than 14 drinks per week) had a lower risk for CRC (HR, 0.79), especially distal colon cancer (HR, 0.64), than light drinkers.

Loftfield said that research in rodents suggests moderate alcohol intake may reduce inflammation and lower DNA damage, but it’s possible that the observed inverse association is due to residual confounding by unmeasured or poorly measured confounders, such as socioeconomic status.

She said it’s also important to note that the inverse association of moderate alcohol intake was strongest for distal colon cancer and in the screening arm of the trial. Those in the screening arm who screened positive with flexible sigmoidoscopy had polyps removed and were referred for colonoscopy during the trial period, making screening a potential intervention as well.

“Screening with flexible sigmoidoscopy has previously been found to decrease CRC incidence, specifically distal colon cancer, in this population. Thus, it is possible that better adherence to screening among moderate drinkers over the course of follow-up contributed to this finding,” Loftfield explained.

When looking at consistency of drinking, her team found that current drinkers who were consistent heavy drinkers throughout adulthood had a higher risk for CRC than consistent light drinkers (HR, 1.91).

Separate analyses of incident colorectal adenomas were directionally consistent with the CRC findings. These analyses included 12,327 participants with a negative baseline sigmoidoscopy, among whom 812 adenomas were detected on repeat screening.

Compared with current light drinkers, former drinkers had significantly lower odds of nonadvanced adenomas (odds ratio [OR], 0.58), but no significant association was observed for advanced adenomas (OR, 1.08; 95% CI, 0.62-1.90). The authors cautioned, however, that overall adenoma case numbers were limited, and estimates for advanced lesions were imprecise.

Educating Patients

Reached for comment, William Dahut, chief scientific officer for the American Cancer Society, told Medscape Medical News that this “very well done, large perspective study clearly demonstrates the significant increased risk of colorectal cancer for those that are heavy drinkers.”

He noted that the nearly twofold increased risk for rectal cancer among heavy drinkers “makes biological sense because the rectum is the area of the body where the toxins produced by alcohol potentially spend the most period of time.” 

Heavy drinkers are at the highest risk, Dahut said, and “for them, screenings are particularly important.”

Even with this growing body of evidence, Levy noted that many patients in America and worldwide “have not been educated yet about the potential carcinogenic dangers of chronic alcohol use.”

Levy recommended that physicians get “accurate social histories about alcohol use” and “spend several minutes educating patients about their increased risk of cancer and liver problems from heavy alcohol use.”

Dahut encouraged health providers to tell patients that the risk for CRC from alcohol is also based on one’s lifetime alcohol consumption, “not simply what they had last weekend.”

Overall, this important research study, along with the Surgeon General’s recent publication about Alcohol and Cancer Risk, will hopefully “encourage physicians to have important conversations about alcohol reduction with their patients,” Levy said. 

The study had no commercial funding. Loftfield, Dahult, and Levy reported no relevant disclosures.

A version of this article first appeared on Medscape.com.

New research sheds light on how chronic heavy alcohol use may contribute to colorectal cancer (CRC) development and how quitting may lower the risk for precancerous colorectal adenomas.

In a large US cancer screening trial, current heavy drinkers — with an average lifetime alcohol intake of 14 or more drinks per week — had a 25% higher risk for CRC and an almost twofold higher risk for rectal cancer than light drinkers averaging less than one drink per week.

When the research team further considered drinking consistency, steady heavy drinking throughout adulthood was associated with a 91% higher risk for CRC than consistent light drinking. 

Additionally, no increased risk for CRC was found among former drinkers, and former drinkers were less likely than light drinkers to develop nonadvanced colorectal adenomas.

This analysis “adds to the growing amount of concerning literature showing that chronic heavy alcohol use can potentially contribute to colorectal cancer development,” Benjamin H. Levy III, MD, gastroenterologist and clinical associate of medicine at UChicago Medicine in Chicago, who wasn’t involved in the study, told Medscape Medical News.

The study’s co-senior author, Erikka Loftfield, PhD, MPH, also noted that the study “provides new evidence indicating that drinking cessation, compared to consistent light drinking, may lower adenoma risk.”

Current cancer prevention guidelines recommend limiting alcohol intake or ideally not drinking at all, and “our findings do not change this advice,” said Loftfield, with the National Cancer Institute (NCI) in Bethesda, Maryland. 

The study was published online on January 26 in the journal Cancer.

Addressing a Data Gap

Alcoholic beverages are classified as carcinogenic to humans and are causally associated with CRC, Loftfield told Medscape Medical News. However, much of the evidence for this comes from cohort studies that only measure recent drinking patterns, generally among older adults, at study baseline. Fewer studies have looked at how drinking over a person’s lifetime and alcohol consumption patterns relate to colorectal adenoma and CRC risk, she explained.

To address these gaps, Loftfield and colleagues leveraged data on alcohol intake gathered as part of the NCI’s Prostate, Long, Colorectal, and Ovarian Cancer Screening Trial.

Average lifetime alcohol intake was calculated as drinks per week from age 18 through study baseline, and drinking patterns were further classified based on consistency and intensity over time. 

During 20 years of follow-up, 1679 incident CRC cases occurred among 88,092 study participants. In multivariable-adjusted analyses, current heavy drinkers had a higher risk for CRC than those averaging less than one drink per week (hazard ratio [HR], 1.25), with the strongest association observed for rectal cancer (HR, 1.95).

“The increase in rectal cancer risk for heavy drinkers seen in this 20-year observational study was especially concerning,” Levy told Medscape Medical News.

What About Moderate Drinking?

Perhaps counterintuitively, moderate current drinkers (those consuming an average of 7 to less than 14 drinks per week) had a lower risk for CRC (HR, 0.79), especially distal colon cancer (HR, 0.64), than light drinkers.

Loftfield said that research in rodents suggests moderate alcohol intake may reduce inflammation and lower DNA damage, but it’s possible that the observed inverse association is due to residual confounding by unmeasured or poorly measured confounders, such as socioeconomic status.

She said it’s also important to note that the inverse association of moderate alcohol intake was strongest for distal colon cancer and in the screening arm of the trial. Those in the screening arm who screened positive with flexible sigmoidoscopy had polyps removed and were referred for colonoscopy during the trial period, making screening a potential intervention as well.

“Screening with flexible sigmoidoscopy has previously been found to decrease CRC incidence, specifically distal colon cancer, in this population. Thus, it is possible that better adherence to screening among moderate drinkers over the course of follow-up contributed to this finding,” Loftfield explained.

When looking at consistency of drinking, her team found that current drinkers who were consistent heavy drinkers throughout adulthood had a higher risk for CRC than consistent light drinkers (HR, 1.91).

Separate analyses of incident colorectal adenomas were directionally consistent with the CRC findings. These analyses included 12,327 participants with a negative baseline sigmoidoscopy, among whom 812 adenomas were detected on repeat screening.

Compared with current light drinkers, former drinkers had significantly lower odds of nonadvanced adenomas (odds ratio [OR], 0.58), but no significant association was observed for advanced adenomas (OR, 1.08; 95% CI, 0.62-1.90). The authors cautioned, however, that overall adenoma case numbers were limited, and estimates for advanced lesions were imprecise.

Educating Patients

Reached for comment, William Dahut, chief scientific officer for the American Cancer Society, told Medscape Medical News that this “very well done, large perspective study clearly demonstrates the significant increased risk of colorectal cancer for those that are heavy drinkers.”

He noted that the nearly twofold increased risk for rectal cancer among heavy drinkers “makes biological sense because the rectum is the area of the body where the toxins produced by alcohol potentially spend the most period of time.” 

Heavy drinkers are at the highest risk, Dahut said, and “for them, screenings are particularly important.”

Even with this growing body of evidence, Levy noted that many patients in America and worldwide “have not been educated yet about the potential carcinogenic dangers of chronic alcohol use.”

Levy recommended that physicians get “accurate social histories about alcohol use” and “spend several minutes educating patients about their increased risk of cancer and liver problems from heavy alcohol use.”

Dahut encouraged health providers to tell patients that the risk for CRC from alcohol is also based on one’s lifetime alcohol consumption, “not simply what they had last weekend.”

Overall, this important research study, along with the Surgeon General’s recent publication about Alcohol and Cancer Risk, will hopefully “encourage physicians to have important conversations about alcohol reduction with their patients,” Levy said. 

The study had no commercial funding. Loftfield, Dahult, and Levy reported no relevant disclosures.

A version of this article first appeared on Medscape.com.

New research sheds light on how chronic heavy alcohol use may contribute to colorectal cancer (CRC) development and how quitting may lower the risk for precancerous colorectal adenomas.

In a large US cancer screening trial, current heavy drinkers — with an average lifetime alcohol intake of 14 or more drinks per week — had a 25% higher risk for CRC and an almost twofold higher risk for rectal cancer than light drinkers averaging less than one drink per week.

When the research team further considered drinking consistency, steady heavy drinking throughout adulthood was associated with a 91% higher risk for CRC than consistent light drinking. 

Additionally, no increased risk for CRC was found among former drinkers, and former drinkers were less likely than light drinkers to develop nonadvanced colorectal adenomas.

This analysis “adds to the growing amount of concerning literature showing that chronic heavy alcohol use can potentially contribute to colorectal cancer development,” Benjamin H. Levy III, MD, gastroenterologist and clinical associate of medicine at UChicago Medicine in Chicago, who wasn’t involved in the study, told Medscape Medical News.

The study’s co-senior author, Erikka Loftfield, PhD, MPH, also noted that the study “provides new evidence indicating that drinking cessation, compared to consistent light drinking, may lower adenoma risk.”

Current cancer prevention guidelines recommend limiting alcohol intake or ideally not drinking at all, and “our findings do not change this advice,” said Loftfield, with the National Cancer Institute (NCI) in Bethesda, Maryland. 

The study was published online on January 26 in the journal Cancer.

Addressing a Data Gap

Alcoholic beverages are classified as carcinogenic to humans and are causally associated with CRC, Loftfield told Medscape Medical News. However, much of the evidence for this comes from cohort studies that only measure recent drinking patterns, generally among older adults, at study baseline. Fewer studies have looked at how drinking over a person’s lifetime and alcohol consumption patterns relate to colorectal adenoma and CRC risk, she explained.

To address these gaps, Loftfield and colleagues leveraged data on alcohol intake gathered as part of the NCI’s Prostate, Long, Colorectal, and Ovarian Cancer Screening Trial.

Average lifetime alcohol intake was calculated as drinks per week from age 18 through study baseline, and drinking patterns were further classified based on consistency and intensity over time. 

During 20 years of follow-up, 1679 incident CRC cases occurred among 88,092 study participants. In multivariable-adjusted analyses, current heavy drinkers had a higher risk for CRC than those averaging less than one drink per week (hazard ratio [HR], 1.25), with the strongest association observed for rectal cancer (HR, 1.95).

“The increase in rectal cancer risk for heavy drinkers seen in this 20-year observational study was especially concerning,” Levy told Medscape Medical News.

What About Moderate Drinking?

Perhaps counterintuitively, moderate current drinkers (those consuming an average of 7 to less than 14 drinks per week) had a lower risk for CRC (HR, 0.79), especially distal colon cancer (HR, 0.64), than light drinkers.

Loftfield said that research in rodents suggests moderate alcohol intake may reduce inflammation and lower DNA damage, but it’s possible that the observed inverse association is due to residual confounding by unmeasured or poorly measured confounders, such as socioeconomic status.

She said it’s also important to note that the inverse association of moderate alcohol intake was strongest for distal colon cancer and in the screening arm of the trial. Those in the screening arm who screened positive with flexible sigmoidoscopy had polyps removed and were referred for colonoscopy during the trial period, making screening a potential intervention as well.

“Screening with flexible sigmoidoscopy has previously been found to decrease CRC incidence, specifically distal colon cancer, in this population. Thus, it is possible that better adherence to screening among moderate drinkers over the course of follow-up contributed to this finding,” Loftfield explained.

When looking at consistency of drinking, her team found that current drinkers who were consistent heavy drinkers throughout adulthood had a higher risk for CRC than consistent light drinkers (HR, 1.91).

Separate analyses of incident colorectal adenomas were directionally consistent with the CRC findings. These analyses included 12,327 participants with a negative baseline sigmoidoscopy, among whom 812 adenomas were detected on repeat screening.

Compared with current light drinkers, former drinkers had significantly lower odds of nonadvanced adenomas (odds ratio [OR], 0.58), but no significant association was observed for advanced adenomas (OR, 1.08; 95% CI, 0.62-1.90). The authors cautioned, however, that overall adenoma case numbers were limited, and estimates for advanced lesions were imprecise.

Educating Patients

Reached for comment, William Dahut, chief scientific officer for the American Cancer Society, told Medscape Medical News that this “very well done, large perspective study clearly demonstrates the significant increased risk of colorectal cancer for those that are heavy drinkers.”

He noted that the nearly twofold increased risk for rectal cancer among heavy drinkers “makes biological sense because the rectum is the area of the body where the toxins produced by alcohol potentially spend the most period of time.” 

Heavy drinkers are at the highest risk, Dahut said, and “for them, screenings are particularly important.”

Even with this growing body of evidence, Levy noted that many patients in America and worldwide “have not been educated yet about the potential carcinogenic dangers of chronic alcohol use.”

Levy recommended that physicians get “accurate social histories about alcohol use” and “spend several minutes educating patients about their increased risk of cancer and liver problems from heavy alcohol use.”

Dahut encouraged health providers to tell patients that the risk for CRC from alcohol is also based on one’s lifetime alcohol consumption, “not simply what they had last weekend.”

Overall, this important research study, along with the Surgeon General’s recent publication about Alcohol and Cancer Risk, will hopefully “encourage physicians to have important conversations about alcohol reduction with their patients,” Levy said. 

The study had no commercial funding. Loftfield, Dahult, and Levy reported no relevant disclosures.

A version of this article first appeared on Medscape.com.

TOPLINE:

New research examining recreational physical activity’s relationship with breast tissue composition, oxidative stress, and inflammation in adolescent girls revealed potential pathways for cancer risk reduction.

METHODOLOGY:

• Recent research shows 12-22% lower risk for breast cancer among highly active women, but the biological mechanisms explaining this remain unclear. Breast tissue composition, particularly mammographic density, is one of the strongest predictors of breast cancer risk, and breast tissue composition tracks across the life course.
• Researchers analyzed data from a population-based urban cohort of 191 Black/African American and Hispanic (Dominican) adolescent girls aged 11-20 years.
• Participants reported organized and unorganized recreational physical activity in the past week, categorized as none, < 2 hours, or ≥ 2 hours.
• Optical spectroscopy measured breast tissue composition through chromophores that are positively (percent water content and percent collagen content) or negatively (percent lipid content) correlated with mammographic breast density.
• Analysis included urinary concentrations of 15-F2-isoprostane for oxidative stress and blood biomarkers of inflammation including TNF-alpha, interleukin-6, and high-sensitivity C-reactive protein.

TAKEAWAY:

• Fifty-one percent of adolescent girls reported no past-week engagement in any type of recreational physical activity, with 73% reporting no participation in organized activities and 66% reporting no participation in unorganized activities.
• Girls engaging in at least 2 hours of organized recreational physical activity vs none showed lower percent water content in breast tissue (beta coefficient, -0.41; 95% CI, -0.77 to -0.05) and lower urinary concentrations of 15-F2-isoprostane (beta coefficient, -0.50; 95% CI, -0.95 to -0.05).
• Higher urinary concentrations of 15-F2-isoprostane were associated with higher percent collagen content in breast tissue (beta coefficient, 0.15; 95% CI, 0.00-0.31).
• No associations were found between recreational physical activity and inflammatory biomarkers, and these biomarkers showed no association with breast tissue composition after adjusting for percent body fat.

IN PRACTICE:

“These findings support that recreational physical activity is associated with breast tissue composition and oxidative stress in adolescent girls, independent of body fat. Additional longitudinal research is needed to understand the implications of these findings regarding subsequent breast cancer risk,” the authors of the study wrote.

SOURCE:

The study was led by Rebecca D. Kehm, PhD, Department of Epidemiology, Mailman School of Public Health, Columbia University, New York City. It was published online in Breast Cancer Research.

LIMITATIONS:

Recreational physical activity was assessed using self-reported data capturing only a 1-week timeframe, which may not fully reflect habitual patterns and is susceptible to measurement error. The cross-sectional nature of the analysis prevented establishing temporal relationships or causal inferences. The relatively small sample size limited statistical power, though researchers were able to detect modest associations. The findings may not be generalizable to populations with different demographics or higher levels of physical activity because recreational physical activity was notably low in this cohort. Additionally, while several validated biomarkers were examined, other mechanisms such as hormonal regulation and insulin sensitivity may also be important for understanding the relationship between adolescent physical activity and breast cancer risk.

DISCLOSURES:

The study received support from the National Institute of Environmental Health Sciences through grants U01ES026122 and P30ES009089, as well as grant ROICA263024 from the National Cancer Institute.

This article was created using several editorial tools, including AI, as part of the process. Human editors reviewed this content before publication.

A version of this article first appeared on Medscape.com.

TOPLINE:

New research examining recreational physical activity’s relationship with breast tissue composition, oxidative stress, and inflammation in adolescent girls revealed potential pathways for cancer risk reduction.

METHODOLOGY:

• Recent research shows 12-22% lower risk for breast cancer among highly active women, but the biological mechanisms explaining this remain unclear. Breast tissue composition, particularly mammographic density, is one of the strongest predictors of breast cancer risk, and breast tissue composition tracks across the life course.
• Researchers analyzed data from a population-based urban cohort of 191 Black/African American and Hispanic (Dominican) adolescent girls aged 11-20 years.
• Participants reported organized and unorganized recreational physical activity in the past week, categorized as none, < 2 hours, or ≥ 2 hours.
• Optical spectroscopy measured breast tissue composition through chromophores that are positively (percent water content and percent collagen content) or negatively (percent lipid content) correlated with mammographic breast density.
• Analysis included urinary concentrations of 15-F2-isoprostane for oxidative stress and blood biomarkers of inflammation including TNF-alpha, interleukin-6, and high-sensitivity C-reactive protein.

TAKEAWAY:

• Fifty-one percent of adolescent girls reported no past-week engagement in any type of recreational physical activity, with 73% reporting no participation in organized activities and 66% reporting no participation in unorganized activities.
• Girls engaging in at least 2 hours of organized recreational physical activity vs none showed lower percent water content in breast tissue (beta coefficient, -0.41; 95% CI, -0.77 to -0.05) and lower urinary concentrations of 15-F2-isoprostane (beta coefficient, -0.50; 95% CI, -0.95 to -0.05).
• Higher urinary concentrations of 15-F2-isoprostane were associated with higher percent collagen content in breast tissue (beta coefficient, 0.15; 95% CI, 0.00-0.31).
• No associations were found between recreational physical activity and inflammatory biomarkers, and these biomarkers showed no association with breast tissue composition after adjusting for percent body fat.

IN PRACTICE:

“These findings support that recreational physical activity is associated with breast tissue composition and oxidative stress in adolescent girls, independent of body fat. Additional longitudinal research is needed to understand the implications of these findings regarding subsequent breast cancer risk,” the authors of the study wrote.

SOURCE:

The study was led by Rebecca D. Kehm, PhD, Department of Epidemiology, Mailman School of Public Health, Columbia University, New York City. It was published online in Breast Cancer Research.

LIMITATIONS:

Recreational physical activity was assessed using self-reported data capturing only a 1-week timeframe, which may not fully reflect habitual patterns and is susceptible to measurement error. The cross-sectional nature of the analysis prevented establishing temporal relationships or causal inferences. The relatively small sample size limited statistical power, though researchers were able to detect modest associations. The findings may not be generalizable to populations with different demographics or higher levels of physical activity because recreational physical activity was notably low in this cohort. Additionally, while several validated biomarkers were examined, other mechanisms such as hormonal regulation and insulin sensitivity may also be important for understanding the relationship between adolescent physical activity and breast cancer risk.

DISCLOSURES:

The study received support from the National Institute of Environmental Health Sciences through grants U01ES026122 and P30ES009089, as well as grant ROICA263024 from the National Cancer Institute.

This article was created using several editorial tools, including AI, as part of the process. Human editors reviewed this content before publication.

A version of this article first appeared on Medscape.com.

TOPLINE:

New research examining recreational physical activity’s relationship with breast tissue composition, oxidative stress, and inflammation in adolescent girls revealed potential pathways for cancer risk reduction.

METHODOLOGY:

• Recent research shows 12-22% lower risk for breast cancer among highly active women, but the biological mechanisms explaining this remain unclear. Breast tissue composition, particularly mammographic density, is one of the strongest predictors of breast cancer risk, and breast tissue composition tracks across the life course.
• Researchers analyzed data from a population-based urban cohort of 191 Black/African American and Hispanic (Dominican) adolescent girls aged 11-20 years.
• Participants reported organized and unorganized recreational physical activity in the past week, categorized as none, < 2 hours, or ≥ 2 hours.
• Optical spectroscopy measured breast tissue composition through chromophores that are positively (percent water content and percent collagen content) or negatively (percent lipid content) correlated with mammographic breast density.
• Analysis included urinary concentrations of 15-F2-isoprostane for oxidative stress and blood biomarkers of inflammation including TNF-alpha, interleukin-6, and high-sensitivity C-reactive protein.

TAKEAWAY:

• Fifty-one percent of adolescent girls reported no past-week engagement in any type of recreational physical activity, with 73% reporting no participation in organized activities and 66% reporting no participation in unorganized activities.
• Girls engaging in at least 2 hours of organized recreational physical activity vs none showed lower percent water content in breast tissue (beta coefficient, -0.41; 95% CI, -0.77 to -0.05) and lower urinary concentrations of 15-F2-isoprostane (beta coefficient, -0.50; 95% CI, -0.95 to -0.05).
• Higher urinary concentrations of 15-F2-isoprostane were associated with higher percent collagen content in breast tissue (beta coefficient, 0.15; 95% CI, 0.00-0.31).
• No associations were found between recreational physical activity and inflammatory biomarkers, and these biomarkers showed no association with breast tissue composition after adjusting for percent body fat.

IN PRACTICE:

“These findings support that recreational physical activity is associated with breast tissue composition and oxidative stress in adolescent girls, independent of body fat. Additional longitudinal research is needed to understand the implications of these findings regarding subsequent breast cancer risk,” the authors of the study wrote.

SOURCE:

The study was led by Rebecca D. Kehm, PhD, Department of Epidemiology, Mailman School of Public Health, Columbia University, New York City. It was published online in Breast Cancer Research.

LIMITATIONS:

Recreational physical activity was assessed using self-reported data capturing only a 1-week timeframe, which may not fully reflect habitual patterns and is susceptible to measurement error. The cross-sectional nature of the analysis prevented establishing temporal relationships or causal inferences. The relatively small sample size limited statistical power, though researchers were able to detect modest associations. The findings may not be generalizable to populations with different demographics or higher levels of physical activity because recreational physical activity was notably low in this cohort. Additionally, while several validated biomarkers were examined, other mechanisms such as hormonal regulation and insulin sensitivity may also be important for understanding the relationship between adolescent physical activity and breast cancer risk.

DISCLOSURES:

The study received support from the National Institute of Environmental Health Sciences through grants U01ES026122 and P30ES009089, as well as grant ROICA263024 from the National Cancer Institute.

This article was created using several editorial tools, including AI, as part of the process. Human editors reviewed this content before publication.

A version of this article first appeared on Medscape.com.

Insights from phase 3 trials presented at the 2025 American Society of Hematology Annual Meeting may expand treatment options for veterans with chronic lymphocytic leukemia (CLL), as discussed by Dr Nicholas Burwick from University of Washington, Seattle.

Dr Burwick begins with the CLL17 trial examining continuous treatment vs fixed-duration therapy in previously untreated patients. The fixed-duration therapy showed noninferior results. Research pertaining to the veterans population in the phase 2 Benefit VA study may offer further insight on these results.

He next discusses the first study comparing the noncovalent BTKi pirtobrutinib to covalent ibrutinib in both treatment-naive patients and those with relapsed/refractory CLL. Pirtobrutinib demonstrated noninferiority in each subgroup. 

Pirtobrutinib was compared to bendamustine plus rituximab in the treatment-naive setting in the next study, showing favorable progression-free survival and a notable trend in overall survival. These two trials could lead to use of a noncovalent BTKi as frontline therapy.

Dr Burwick then turns to 6-year follow-up in the SEQUOIA trial, in which zanubrutinib showed sustained superiority over bendamustine and rituximab. He notes that acalabrutinib is currently the preferred BTKi therapy for veterans with CLL.

Finally, he discusses a study examining combination acalabrutinib and venetoclax, to which obinutuzumab was added either early or late. The rate of infections was significantly higher in the early group, an issue of particular concern in the veterans population.

--

Nicholas R. Burwick, MD, VA Puget Sound Health Care System; Associate Professor, Department of Medicine, Division of Hematology, University of Washington, Seattle; President, AVAHO - Association of VA Hematology/Oncology

Nicholas R. Burwick, MD, has disclosed no relevant financial relationships.

Insights from phase 3 trials presented at the 2025 American Society of Hematology Annual Meeting may expand treatment options for veterans with chronic lymphocytic leukemia (CLL), as discussed by Dr Nicholas Burwick from University of Washington, Seattle.

Dr Burwick begins with the CLL17 trial examining continuous treatment vs fixed-duration therapy in previously untreated patients. The fixed-duration therapy showed noninferior results. Research pertaining to the veterans population in the phase 2 Benefit VA study may offer further insight on these results.

He next discusses the first study comparing the noncovalent BTKi pirtobrutinib to covalent ibrutinib in both treatment-naive patients and those with relapsed/refractory CLL. Pirtobrutinib demonstrated noninferiority in each subgroup. 

Pirtobrutinib was compared to bendamustine plus rituximab in the treatment-naive setting in the next study, showing favorable progression-free survival and a notable trend in overall survival. These two trials could lead to use of a noncovalent BTKi as frontline therapy.

Dr Burwick then turns to 6-year follow-up in the SEQUOIA trial, in which zanubrutinib showed sustained superiority over bendamustine and rituximab. He notes that acalabrutinib is currently the preferred BTKi therapy for veterans with CLL.

Finally, he discusses a study examining combination acalabrutinib and venetoclax, to which obinutuzumab was added either early or late. The rate of infections was significantly higher in the early group, an issue of particular concern in the veterans population.

--

Nicholas R. Burwick, MD, VA Puget Sound Health Care System; Associate Professor, Department of Medicine, Division of Hematology, University of Washington, Seattle; President, AVAHO - Association of VA Hematology/Oncology

Nicholas R. Burwick, MD, has disclosed no relevant financial relationships.

Insights from phase 3 trials presented at the 2025 American Society of Hematology Annual Meeting may expand treatment options for veterans with chronic lymphocytic leukemia (CLL), as discussed by Dr Nicholas Burwick from University of Washington, Seattle.

Dr Burwick begins with the CLL17 trial examining continuous treatment vs fixed-duration therapy in previously untreated patients. The fixed-duration therapy showed noninferior results. Research pertaining to the veterans population in the phase 2 Benefit VA study may offer further insight on these results.

He next discusses the first study comparing the noncovalent BTKi pirtobrutinib to covalent ibrutinib in both treatment-naive patients and those with relapsed/refractory CLL. Pirtobrutinib demonstrated noninferiority in each subgroup. 

Pirtobrutinib was compared to bendamustine plus rituximab in the treatment-naive setting in the next study, showing favorable progression-free survival and a notable trend in overall survival. These two trials could lead to use of a noncovalent BTKi as frontline therapy.

Dr Burwick then turns to 6-year follow-up in the SEQUOIA trial, in which zanubrutinib showed sustained superiority over bendamustine and rituximab. He notes that acalabrutinib is currently the preferred BTKi therapy for veterans with CLL.

Finally, he discusses a study examining combination acalabrutinib and venetoclax, to which obinutuzumab was added either early or late. The rate of infections was significantly higher in the early group, an issue of particular concern in the veterans population.

--

Nicholas R. Burwick, MD, VA Puget Sound Health Care System; Associate Professor, Department of Medicine, Division of Hematology, University of Washington, Seattle; President, AVAHO - Association of VA Hematology/Oncology

Nicholas R. Burwick, MD, has disclosed no relevant financial relationships.

TOPLINE:

A systematic review of 69 economic evaluations revealed that adjuvant immunotherapy was cost-effective in 58% of studies, with higher Quality-Adjusted Life-Year gains reported in 91% of cases. Cost-effectiveness varied significantly by cancer type, treatment strategy, and healthcare system context, with industry-funded studies more likely to report favorable outcomes.

METHODOLOGY:

• Multiple phase 3 trials have shown improved survival and reduced recurrence with adjuvant immunotherapy in various cancers. But the high cost of immunotherapy treatments, often exceeding $100,000 per patient, has raised questions about their economic value and affordability across different healthcare systems.
• Researchers conducted a systematic review of 69 economic evaluations published between January 2015 and January 2025, focusing on adjuvant immunotherapy across various cancer types.
• Analysis included studies from PubMed, Embase, Scopus, Web of Science, and Cochrane Library, with most evaluations conducted in the US (26 studies) and China (20 studies).
• Quality assessment utilized the Criteria for Health Economic Quality Evaluation tool, evaluating 48 attributes across methodologic and reporting quality dimensions.
• Markov modeling dominated the analytical approach (46 studies [67%]), with EuroQol Five-Dimensions being the most commonly used health utility instrument (56 studies [81%]).

TAKEAWAY:

• Of 69 studies analyzed, 58% concluded that adjuvant immunotherapy was cost-effective, with stronger evidence in non-small cell lung cancer and melanoma, particularly in early-stage and high-risk populations.
• Industry-funded studies more frequently reported cost-effective outcomes (17 of 20 studies [85%]) than nonindustry funded studies (13 of 28 studies [46%]).
• Higher Quality-Adjusted Life-Year/Life-Year gains were consistently reported in the adjuvant immunotherapy group (63 studies [91%]), especially for non-small cell lung cancer and combination regimens.
• Cost-effectiveness results varied significantly by cancer type, model assumptions, drug pricing, funding organizations, and country-specific willingness-to-pay thresholds.

IN PRACTICE:

“From a policy standpoint, the findings of this systematic review support the use of structured, context-specific health technology assessment frameworks to evaluate adjuvant immunotherapies. For health systems under financial constraints, prioritizing subgroups with the highest absolute benefit may be a viable approach to ensure sustainable access,” the authors of the review wrote.

SOURCE:

The systematic review was led by Rashidul Alam Mahumud, PhD, MCncrSc, MPH, MSc, Health Economics and Health Technology Assessment Unit, National Health and Medical Research Council Clinical Trials Centre, The University of Sydney in Camperdown, Australia. It was published online on January 22 in JAMA Oncology.

LIMITATIONS:

The methodologic heterogeneity across studies presents a significant limitation, with variations in time horizons, discounting methods, survival data extrapolation, and health utility measurements affecting result comparability. Geographic distribution primarily focused on high-income countries, limiting generalizability to low- and middle-income settings. Few evaluations incorporated adaptive pricing schemes or managed entry agreements that increasingly influence clinical reimbursement decisions.

DISCLOSURES:

Mahumud had full access to all study data and takes responsibility for data integrity and analysis accuracy. The authors reported having no relevant conflicts of interest.

This article was created using several editorial tools, including AI, as part of the process. Human editors reviewed this content before publication.

A version of this article first appeared on Medscape.com.

TOPLINE:

A systematic review of 69 economic evaluations revealed that adjuvant immunotherapy was cost-effective in 58% of studies, with higher Quality-Adjusted Life-Year gains reported in 91% of cases. Cost-effectiveness varied significantly by cancer type, treatment strategy, and healthcare system context, with industry-funded studies more likely to report favorable outcomes.

METHODOLOGY:

• Multiple phase 3 trials have shown improved survival and reduced recurrence with adjuvant immunotherapy in various cancers. But the high cost of immunotherapy treatments, often exceeding $100,000 per patient, has raised questions about their economic value and affordability across different healthcare systems.
• Researchers conducted a systematic review of 69 economic evaluations published between January 2015 and January 2025, focusing on adjuvant immunotherapy across various cancer types.
• Analysis included studies from PubMed, Embase, Scopus, Web of Science, and Cochrane Library, with most evaluations conducted in the US (26 studies) and China (20 studies).
• Quality assessment utilized the Criteria for Health Economic Quality Evaluation tool, evaluating 48 attributes across methodologic and reporting quality dimensions.
• Markov modeling dominated the analytical approach (46 studies [67%]), with EuroQol Five-Dimensions being the most commonly used health utility instrument (56 studies [81%]).

TAKEAWAY:

• Of 69 studies analyzed, 58% concluded that adjuvant immunotherapy was cost-effective, with stronger evidence in non-small cell lung cancer and melanoma, particularly in early-stage and high-risk populations.
• Industry-funded studies more frequently reported cost-effective outcomes (17 of 20 studies [85%]) than nonindustry funded studies (13 of 28 studies [46%]).
• Higher Quality-Adjusted Life-Year/Life-Year gains were consistently reported in the adjuvant immunotherapy group (63 studies [91%]), especially for non-small cell lung cancer and combination regimens.
• Cost-effectiveness results varied significantly by cancer type, model assumptions, drug pricing, funding organizations, and country-specific willingness-to-pay thresholds.

IN PRACTICE:

“From a policy standpoint, the findings of this systematic review support the use of structured, context-specific health technology assessment frameworks to evaluate adjuvant immunotherapies. For health systems under financial constraints, prioritizing subgroups with the highest absolute benefit may be a viable approach to ensure sustainable access,” the authors of the review wrote.

SOURCE:

The systematic review was led by Rashidul Alam Mahumud, PhD, MCncrSc, MPH, MSc, Health Economics and Health Technology Assessment Unit, National Health and Medical Research Council Clinical Trials Centre, The University of Sydney in Camperdown, Australia. It was published online on January 22 in JAMA Oncology.

LIMITATIONS:

The methodologic heterogeneity across studies presents a significant limitation, with variations in time horizons, discounting methods, survival data extrapolation, and health utility measurements affecting result comparability. Geographic distribution primarily focused on high-income countries, limiting generalizability to low- and middle-income settings. Few evaluations incorporated adaptive pricing schemes or managed entry agreements that increasingly influence clinical reimbursement decisions.

DISCLOSURES:

Mahumud had full access to all study data and takes responsibility for data integrity and analysis accuracy. The authors reported having no relevant conflicts of interest.

This article was created using several editorial tools, including AI, as part of the process. Human editors reviewed this content before publication.

A version of this article first appeared on Medscape.com.

TOPLINE:

A systematic review of 69 economic evaluations revealed that adjuvant immunotherapy was cost-effective in 58% of studies, with higher Quality-Adjusted Life-Year gains reported in 91% of cases. Cost-effectiveness varied significantly by cancer type, treatment strategy, and healthcare system context, with industry-funded studies more likely to report favorable outcomes.

METHODOLOGY:

• Multiple phase 3 trials have shown improved survival and reduced recurrence with adjuvant immunotherapy in various cancers. But the high cost of immunotherapy treatments, often exceeding $100,000 per patient, has raised questions about their economic value and affordability across different healthcare systems.
• Researchers conducted a systematic review of 69 economic evaluations published between January 2015 and January 2025, focusing on adjuvant immunotherapy across various cancer types.
• Analysis included studies from PubMed, Embase, Scopus, Web of Science, and Cochrane Library, with most evaluations conducted in the US (26 studies) and China (20 studies).
• Quality assessment utilized the Criteria for Health Economic Quality Evaluation tool, evaluating 48 attributes across methodologic and reporting quality dimensions.
• Markov modeling dominated the analytical approach (46 studies [67%]), with EuroQol Five-Dimensions being the most commonly used health utility instrument (56 studies [81%]).

TAKEAWAY:

• Of 69 studies analyzed, 58% concluded that adjuvant immunotherapy was cost-effective, with stronger evidence in non-small cell lung cancer and melanoma, particularly in early-stage and high-risk populations.
• Industry-funded studies more frequently reported cost-effective outcomes (17 of 20 studies [85%]) than nonindustry funded studies (13 of 28 studies [46%]).
• Higher Quality-Adjusted Life-Year/Life-Year gains were consistently reported in the adjuvant immunotherapy group (63 studies [91%]), especially for non-small cell lung cancer and combination regimens.
• Cost-effectiveness results varied significantly by cancer type, model assumptions, drug pricing, funding organizations, and country-specific willingness-to-pay thresholds.

IN PRACTICE:

“From a policy standpoint, the findings of this systematic review support the use of structured, context-specific health technology assessment frameworks to evaluate adjuvant immunotherapies. For health systems under financial constraints, prioritizing subgroups with the highest absolute benefit may be a viable approach to ensure sustainable access,” the authors of the review wrote.

SOURCE:

The systematic review was led by Rashidul Alam Mahumud, PhD, MCncrSc, MPH, MSc, Health Economics and Health Technology Assessment Unit, National Health and Medical Research Council Clinical Trials Centre, The University of Sydney in Camperdown, Australia. It was published online on January 22 in JAMA Oncology.

LIMITATIONS:

The methodologic heterogeneity across studies presents a significant limitation, with variations in time horizons, discounting methods, survival data extrapolation, and health utility measurements affecting result comparability. Geographic distribution primarily focused on high-income countries, limiting generalizability to low- and middle-income settings. Few evaluations incorporated adaptive pricing schemes or managed entry agreements that increasingly influence clinical reimbursement decisions.

DISCLOSURES:

Mahumud had full access to all study data and takes responsibility for data integrity and analysis accuracy. The authors reported having no relevant conflicts of interest.

This article was created using several editorial tools, including AI, as part of the process. Human editors reviewed this content before publication.

A version of this article first appeared on Medscape.com.

The Centenarian Program at the US Department of Veterans Affairs (VA) has expanded to begin honoring veterans for special occasions, such as birthdays, as well as veterans with very limited life expectancy. 

Initially launched in 2020 as a special initiative that awarded commemorative coins to American heroes aged 100 years, the program recognizes each individual’s service to the country. 

“This program symbolizes the commitment that we promise to our veterans,” said Center for Development and Civic Engagement (CDCE) Chief Dennis Montgomery in West Palm Beach, Florida. “They are never forgotten. No matter the years since time of service, the VA will always honor and remind them of the gratitude we proudly hold in our hearts for their bravery and sacrifice.”

Eligible veterans receive a personalized letter from the VA Secretary, a commemorative coin, and public recognition from their local VA facility, which often includes a celebration. To be eligible, veterans must be enrolled and receiving care through the VA health care systems. 

Coins are customized for each veteran with unique attributes, including the veteran’s name, branch of service, military occupational specialty, and years of service.

“I originally learned of the program in 2022, and I explored the possibilities to expand the reach of active engagement from the Center of Development and Civic Engagement and the VA Secretary’s office,” said Saraswathy Battar, MD, a geriatrician at the Thomas H. Corey VA Medical Center (VAMC) Community Living Center in West Palm Beach, who oversaw the program until her retirement in November 2025. The program is currently administered by the office of VA Secretary Douglas Collins.

Between August 2022 and October 15, 2025, 1182 centenarian veterans and 285 special recognition honorees received commemorative coins. 

“As our local veteran population grows within the centenarian coin eligibility criteria,” Montgomery said, “I know this program will continue to grow as well and gain more popularity to honor our veterans as they have earned and deserved.”  

The VA conducts outreach through local health care professionals to identify veterans eligible for the program. This allows for veterans admitted to the VA to be identified, leading to activation of the ceremony process. 

If veterans are in declining health, they become eligible to receive recognition at age 95, Montgomery said. 

The Centenarian Program at the US Department of Veterans Affairs (VA) has expanded to begin honoring veterans for special occasions, such as birthdays, as well as veterans with very limited life expectancy. 

Initially launched in 2020 as a special initiative that awarded commemorative coins to American heroes aged 100 years, the program recognizes each individual’s service to the country. 

“This program symbolizes the commitment that we promise to our veterans,” said Center for Development and Civic Engagement (CDCE) Chief Dennis Montgomery in West Palm Beach, Florida. “They are never forgotten. No matter the years since time of service, the VA will always honor and remind them of the gratitude we proudly hold in our hearts for their bravery and sacrifice.”

Eligible veterans receive a personalized letter from the VA Secretary, a commemorative coin, and public recognition from their local VA facility, which often includes a celebration. To be eligible, veterans must be enrolled and receiving care through the VA health care systems. 

Coins are customized for each veteran with unique attributes, including the veteran’s name, branch of service, military occupational specialty, and years of service.

“I originally learned of the program in 2022, and I explored the possibilities to expand the reach of active engagement from the Center of Development and Civic Engagement and the VA Secretary’s office,” said Saraswathy Battar, MD, a geriatrician at the Thomas H. Corey VA Medical Center (VAMC) Community Living Center in West Palm Beach, who oversaw the program until her retirement in November 2025. The program is currently administered by the office of VA Secretary Douglas Collins.

Between August 2022 and October 15, 2025, 1182 centenarian veterans and 285 special recognition honorees received commemorative coins. 

“As our local veteran population grows within the centenarian coin eligibility criteria,” Montgomery said, “I know this program will continue to grow as well and gain more popularity to honor our veterans as they have earned and deserved.”  

The VA conducts outreach through local health care professionals to identify veterans eligible for the program. This allows for veterans admitted to the VA to be identified, leading to activation of the ceremony process. 

If veterans are in declining health, they become eligible to receive recognition at age 95, Montgomery said. 

The Centenarian Program at the US Department of Veterans Affairs (VA) has expanded to begin honoring veterans for special occasions, such as birthdays, as well as veterans with very limited life expectancy. 

Initially launched in 2020 as a special initiative that awarded commemorative coins to American heroes aged 100 years, the program recognizes each individual’s service to the country. 

“This program symbolizes the commitment that we promise to our veterans,” said Center for Development and Civic Engagement (CDCE) Chief Dennis Montgomery in West Palm Beach, Florida. “They are never forgotten. No matter the years since time of service, the VA will always honor and remind them of the gratitude we proudly hold in our hearts for their bravery and sacrifice.”

Eligible veterans receive a personalized letter from the VA Secretary, a commemorative coin, and public recognition from their local VA facility, which often includes a celebration. To be eligible, veterans must be enrolled and receiving care through the VA health care systems. 

Coins are customized for each veteran with unique attributes, including the veteran’s name, branch of service, military occupational specialty, and years of service.

“I originally learned of the program in 2022, and I explored the possibilities to expand the reach of active engagement from the Center of Development and Civic Engagement and the VA Secretary’s office,” said Saraswathy Battar, MD, a geriatrician at the Thomas H. Corey VA Medical Center (VAMC) Community Living Center in West Palm Beach, who oversaw the program until her retirement in November 2025. The program is currently administered by the office of VA Secretary Douglas Collins.

Between August 2022 and October 15, 2025, 1182 centenarian veterans and 285 special recognition honorees received commemorative coins. 

“As our local veteran population grows within the centenarian coin eligibility criteria,” Montgomery said, “I know this program will continue to grow as well and gain more popularity to honor our veterans as they have earned and deserved.”  

The VA conducts outreach through local health care professionals to identify veterans eligible for the program. This allows for veterans admitted to the VA to be identified, leading to activation of the ceremony process. 

If veterans are in declining health, they become eligible to receive recognition at age 95, Montgomery said. 

TOPLINE:

Spleen volume larger than the 99th percentile was associated with an 11-fold increased risk for hematologic cancer compared with normal volumes, with 5-year risks as high as 46% among men aged 70 years or older. Significant risks for cirrhosis and liver cancer were also seen.

METHODOLOGY:

• Splenomegaly is often detected incidentally during imaging, but guidelines vary as to the threshold that should prompt evaluation — ranging from a spleen length of 120 mm to 150 mm. However, up to 21% of healthy individuals have spleen lengths > 120 mm, which could lead to unnecessary follow-up of low-risk patients.
• Researchers used data from two general population cohorts to evaluate the relative and absolute risks for hematologic cancer and liver disease (two common causes of spleen enlargement) among individuals with incidentally detected splenomegaly. They included 8459 Danish adults (57% female; median age, 61 years) and 38,607 UK adults (51.9% female; median age, 65 years) who underwent CT or MRI scans as part of study procedures.
• Spleen length and volume measurements were available from the Danish cohort, while only spleen volume was available from the UK group.
• Participants were followed for a median of 5 years after imaging to assess the incidence of hematologic cancers (both cohorts) and cirrhosis and liver cancer (UK cohort only). Hazard ratios were adjusted for age, sex, smoking status, alcohol consumption, comorbidities, and C-reactive protein levels.

TAKEAWAY:

• In the Danish cohort, the relative risk for any hematologic cancer was significantly increased among individuals with spleen lengths above the 99th percentile (≥ 135 mm) compared with those with spleen lengths in the 26th-74th percentile (hazard ratio [HR], 5.11; P < .001). Among individuals with a spleen length ≥ 140 mm, absolute 5-year risks reached 23% for men aged 70 years or older and 12% for women in that age group.
• Risks were even more pronounced for Danish adults with a spleen volume above the 99th percentile — > 433 mL. Relative to the 26th-74th percentile, their risk for any hematologic cancer was 11-fold higher (HR, 11.08; P < .001). Among people with a spleen volume ≥ 500 mL, 5-year risks reached 46% for men aged 70 years or older and 27% for women in that age group.
• Findings were similar in the UK cohort. Among individuals with a spleen volume above the 99th percentile (> 386 mL), the risk for hematologic cancer increased nearly 12-fold (HR, 11.82; P < .001). With a spleen volume ≥ 500 mL, 5-year risks reached 21% for men aged 70 years or older and 18% for women in that age group. Relative risks were also elevated — by 1.55-2.94 — among individuals in the 75th-99th percentile (199 mL-386 mL).
• The risks for liver disease began to rise substantially at a spleen volume ≥ 400 mL. Absolute 5-year risks for cirrhosis reached 10.8% for men and 9.3% for women aged 70 years or older with a spleen volume ≥ 500 mL. For liver cancer, 5-year risks reached 3.2% and 1.2% for men and women in that age group with a spleen volume ≥ 400 mL.

IN PRACTICE:

“To our knowledge, no previous studies have examined risk of hematologic cancers by spleen length or volume in incidentally detected splenomegaly,” the authors of the study wrote. “Risk was moderately increased at spleen length of 130-139 mm or spleen volume of 400-499 mL, where diagnostic workup may be considered, and more pronounced at spleen length of 140 mm or greater or spleen volume of 500 mL or greater, supporting that diagnostic workup may likely be relevant.”

They stressed, however, that the study participants were asymptomatic, and the underlying reason for imaging should always be considered.

SOURCE:

The study, led by Jens Helby, MD, PhD, Copenhagen University Hospital – Rigshospitalet, Copenhagen, Denmark, was published online in JAMA Oncology.

DISCLOSURES:

The study was funded by the Danish Cancer Society, the Boserup Foundation, Copenhagen University Hospital – Rigshospitalet, and Sanofi A/S. Helby reported having financial relationships with Sanofi and Disc Medicine. Additional disclosures are available in the full article.

This article was created using several editorial tools, including AI, as part of the process. Human editors reviewed this content before publication.

A version of this article first appeared on Medscape.com.

TOPLINE:

Spleen volume larger than the 99th percentile was associated with an 11-fold increased risk for hematologic cancer compared with normal volumes, with 5-year risks as high as 46% among men aged 70 years or older. Significant risks for cirrhosis and liver cancer were also seen.

METHODOLOGY:

• Splenomegaly is often detected incidentally during imaging, but guidelines vary as to the threshold that should prompt evaluation — ranging from a spleen length of 120 mm to 150 mm. However, up to 21% of healthy individuals have spleen lengths > 120 mm, which could lead to unnecessary follow-up of low-risk patients.
• Researchers used data from two general population cohorts to evaluate the relative and absolute risks for hematologic cancer and liver disease (two common causes of spleen enlargement) among individuals with incidentally detected splenomegaly. They included 8459 Danish adults (57% female; median age, 61 years) and 38,607 UK adults (51.9% female; median age, 65 years) who underwent CT or MRI scans as part of study procedures.
• Spleen length and volume measurements were available from the Danish cohort, while only spleen volume was available from the UK group.
• Participants were followed for a median of 5 years after imaging to assess the incidence of hematologic cancers (both cohorts) and cirrhosis and liver cancer (UK cohort only). Hazard ratios were adjusted for age, sex, smoking status, alcohol consumption, comorbidities, and C-reactive protein levels.

TAKEAWAY:

• In the Danish cohort, the relative risk for any hematologic cancer was significantly increased among individuals with spleen lengths above the 99th percentile (≥ 135 mm) compared with those with spleen lengths in the 26th-74th percentile (hazard ratio [HR], 5.11; P < .001). Among individuals with a spleen length ≥ 140 mm, absolute 5-year risks reached 23% for men aged 70 years or older and 12% for women in that age group.
• Risks were even more pronounced for Danish adults with a spleen volume above the 99th percentile — > 433 mL. Relative to the 26th-74th percentile, their risk for any hematologic cancer was 11-fold higher (HR, 11.08; P < .001). Among people with a spleen volume ≥ 500 mL, 5-year risks reached 46% for men aged 70 years or older and 27% for women in that age group.
• Findings were similar in the UK cohort. Among individuals with a spleen volume above the 99th percentile (> 386 mL), the risk for hematologic cancer increased nearly 12-fold (HR, 11.82; P < .001). With a spleen volume ≥ 500 mL, 5-year risks reached 21% for men aged 70 years or older and 18% for women in that age group. Relative risks were also elevated — by 1.55-2.94 — among individuals in the 75th-99th percentile (199 mL-386 mL).
• The risks for liver disease began to rise substantially at a spleen volume ≥ 400 mL. Absolute 5-year risks for cirrhosis reached 10.8% for men and 9.3% for women aged 70 years or older with a spleen volume ≥ 500 mL. For liver cancer, 5-year risks reached 3.2% and 1.2% for men and women in that age group with a spleen volume ≥ 400 mL.

IN PRACTICE:

“To our knowledge, no previous studies have examined risk of hematologic cancers by spleen length or volume in incidentally detected splenomegaly,” the authors of the study wrote. “Risk was moderately increased at spleen length of 130-139 mm or spleen volume of 400-499 mL, where diagnostic workup may be considered, and more pronounced at spleen length of 140 mm or greater or spleen volume of 500 mL or greater, supporting that diagnostic workup may likely be relevant.”

They stressed, however, that the study participants were asymptomatic, and the underlying reason for imaging should always be considered.

SOURCE:

The study, led by Jens Helby, MD, PhD, Copenhagen University Hospital – Rigshospitalet, Copenhagen, Denmark, was published online in JAMA Oncology.

DISCLOSURES:

The study was funded by the Danish Cancer Society, the Boserup Foundation, Copenhagen University Hospital – Rigshospitalet, and Sanofi A/S. Helby reported having financial relationships with Sanofi and Disc Medicine. Additional disclosures are available in the full article.

This article was created using several editorial tools, including AI, as part of the process. Human editors reviewed this content before publication.

A version of this article first appeared on Medscape.com.

TOPLINE:

Spleen volume larger than the 99th percentile was associated with an 11-fold increased risk for hematologic cancer compared with normal volumes, with 5-year risks as high as 46% among men aged 70 years or older. Significant risks for cirrhosis and liver cancer were also seen.

METHODOLOGY:

• Splenomegaly is often detected incidentally during imaging, but guidelines vary as to the threshold that should prompt evaluation — ranging from a spleen length of 120 mm to 150 mm. However, up to 21% of healthy individuals have spleen lengths > 120 mm, which could lead to unnecessary follow-up of low-risk patients.
• Researchers used data from two general population cohorts to evaluate the relative and absolute risks for hematologic cancer and liver disease (two common causes of spleen enlargement) among individuals with incidentally detected splenomegaly. They included 8459 Danish adults (57% female; median age, 61 years) and 38,607 UK adults (51.9% female; median age, 65 years) who underwent CT or MRI scans as part of study procedures.
• Spleen length and volume measurements were available from the Danish cohort, while only spleen volume was available from the UK group.
• Participants were followed for a median of 5 years after imaging to assess the incidence of hematologic cancers (both cohorts) and cirrhosis and liver cancer (UK cohort only). Hazard ratios were adjusted for age, sex, smoking status, alcohol consumption, comorbidities, and C-reactive protein levels.

TAKEAWAY:

• In the Danish cohort, the relative risk for any hematologic cancer was significantly increased among individuals with spleen lengths above the 99th percentile (≥ 135 mm) compared with those with spleen lengths in the 26th-74th percentile (hazard ratio [HR], 5.11; P < .001). Among individuals with a spleen length ≥ 140 mm, absolute 5-year risks reached 23% for men aged 70 years or older and 12% for women in that age group.
• Risks were even more pronounced for Danish adults with a spleen volume above the 99th percentile — > 433 mL. Relative to the 26th-74th percentile, their risk for any hematologic cancer was 11-fold higher (HR, 11.08; P < .001). Among people with a spleen volume ≥ 500 mL, 5-year risks reached 46% for men aged 70 years or older and 27% for women in that age group.
• Findings were similar in the UK cohort. Among individuals with a spleen volume above the 99th percentile (> 386 mL), the risk for hematologic cancer increased nearly 12-fold (HR, 11.82; P < .001). With a spleen volume ≥ 500 mL, 5-year risks reached 21% for men aged 70 years or older and 18% for women in that age group. Relative risks were also elevated — by 1.55-2.94 — among individuals in the 75th-99th percentile (199 mL-386 mL).
• The risks for liver disease began to rise substantially at a spleen volume ≥ 400 mL. Absolute 5-year risks for cirrhosis reached 10.8% for men and 9.3% for women aged 70 years or older with a spleen volume ≥ 500 mL. For liver cancer, 5-year risks reached 3.2% and 1.2% for men and women in that age group with a spleen volume ≥ 400 mL.

IN PRACTICE:

“To our knowledge, no previous studies have examined risk of hematologic cancers by spleen length or volume in incidentally detected splenomegaly,” the authors of the study wrote. “Risk was moderately increased at spleen length of 130-139 mm or spleen volume of 400-499 mL, where diagnostic workup may be considered, and more pronounced at spleen length of 140 mm or greater or spleen volume of 500 mL or greater, supporting that diagnostic workup may likely be relevant.”

They stressed, however, that the study participants were asymptomatic, and the underlying reason for imaging should always be considered.

SOURCE:

The study, led by Jens Helby, MD, PhD, Copenhagen University Hospital – Rigshospitalet, Copenhagen, Denmark, was published online in JAMA Oncology.

DISCLOSURES:

The study was funded by the Danish Cancer Society, the Boserup Foundation, Copenhagen University Hospital – Rigshospitalet, and Sanofi A/S. Helby reported having financial relationships with Sanofi and Disc Medicine. Additional disclosures are available in the full article.

This article was created using several editorial tools, including AI, as part of the process. Human editors reviewed this content before publication.

A version of this article first appeared on Medscape.com.

Tightened Medicaid eligibility rules under the 2025 Budget Reconciliation Bill could result in more than 1 million missed cancer screenings within 2 years and over 150 avoidable cancer deaths, new findings suggested.

“Clinicians should be genuinely concerned,” corresponding author Adrian Diaz, MD, MPH, a surgical oncology fellow at the University of Chicago, Chicago, told Medscape Medical News. “These projections suggest that Medicaid eligibility restrictions are likely to translate into delayed diagnoses, more advanced disease at presentation, and worse outcomes.”

The new law, which significantly reduces federal Medicaid funding, introduces mandatory work or community-engagement requirements for working-age adults as well as more frequent recertification starting in 2027.

In the study, a Research Letter published online on January 8 in JAMA Oncology, Diaz and Sarah Shubeck, MD, also from the University of Chicago, drew on data from Arkansas to model how these 2025 federal Medicaid eligibility restrictions could lead to loss of Medicaid coverage and consequently missed cancer screenings, especially in states that expanded Medicaid.

Diaz and Shubeck then paired coverage losses with state-level self-reported screening prevalences and estimated incident breast, colorectal, and lung cancers using 2-year risks.

In the first 2 years after implementation, the researchers predicted that 7.5 million adults (range, 5.0-10.8 million) will lose Medicaid coverage due to the new provisions.

This coverage loss will lead to an estimated 405,706 missed mammograms, 679,745 missed colorectal screenings, and 67,213 missed lung cancer screenings.

As a result, 1055 breast cancers, 748 colorectal cancers, and 538 lung cancers will go undetected, with excess deaths totaling 155 — 70 for breast, 50 for colorectal, and 35 for lung cancers.

Predicted missed screenings and related cancer outcomes varied considerably by state, with missed screening rates generally lower in states that didn’t expand Medicaid.

“Importantly, our estimates focus on missed screening and do not account for patients already undergoing cancer treatment whose coverage could be interrupted, meaning the real-world impact is likely larger,” Diaz said.

Farhad Islami, MD, PhD, senior scientific director of Cancer Disparity Research at the American Cancer Society, said the estimated coverage losses are “consistent with the number” — 7.8 million — “estimated by the nonpartisan Congressional Budget Office.”

Islami also stressed that the harm caused by the new restrictions would be “far greater” than what the study reports, with coverage losses leading to delays in care seeking for cancer symptoms of all kinds “and consequently, delayed diagnosis for many more cancer cases.”

“Moreover,” he added, “the restrictions can reduce the utilization of preventive care (eg, counselling and pharmacotherapy for smoking cessation among people who smoke, counselling for reducing weight, and so on) and receipt of guideline-concordant cancer treatments among those who will lose Medicaid coverage.”

In Diaz’ view, clinicians can help mitigate the adverse effects of the new provisions.

“For example, proactively identifying patients at risk of coverage loss, engaging financial counselors and social workers early, and connecting uninsured or underinsured patients to safety-net screening and treatment programs,” he said. “At a systems level, clinicians also have an important role in documenting and communicating these downstream clinical consequences to health systems and policymakers.”

A version of this article first appeared on Medscape.com.

Tightened Medicaid eligibility rules under the 2025 Budget Reconciliation Bill could result in more than 1 million missed cancer screenings within 2 years and over 150 avoidable cancer deaths, new findings suggested.

“Clinicians should be genuinely concerned,” corresponding author Adrian Diaz, MD, MPH, a surgical oncology fellow at the University of Chicago, Chicago, told Medscape Medical News. “These projections suggest that Medicaid eligibility restrictions are likely to translate into delayed diagnoses, more advanced disease at presentation, and worse outcomes.”

The new law, which significantly reduces federal Medicaid funding, introduces mandatory work or community-engagement requirements for working-age adults as well as more frequent recertification starting in 2027.

In the study, a Research Letter published online on January 8 in JAMA Oncology, Diaz and Sarah Shubeck, MD, also from the University of Chicago, drew on data from Arkansas to model how these 2025 federal Medicaid eligibility restrictions could lead to loss of Medicaid coverage and consequently missed cancer screenings, especially in states that expanded Medicaid.

Diaz and Shubeck then paired coverage losses with state-level self-reported screening prevalences and estimated incident breast, colorectal, and lung cancers using 2-year risks.

In the first 2 years after implementation, the researchers predicted that 7.5 million adults (range, 5.0-10.8 million) will lose Medicaid coverage due to the new provisions.

This coverage loss will lead to an estimated 405,706 missed mammograms, 679,745 missed colorectal screenings, and 67,213 missed lung cancer screenings.

As a result, 1055 breast cancers, 748 colorectal cancers, and 538 lung cancers will go undetected, with excess deaths totaling 155 — 70 for breast, 50 for colorectal, and 35 for lung cancers.

Predicted missed screenings and related cancer outcomes varied considerably by state, with missed screening rates generally lower in states that didn’t expand Medicaid.

“Importantly, our estimates focus on missed screening and do not account for patients already undergoing cancer treatment whose coverage could be interrupted, meaning the real-world impact is likely larger,” Diaz said.

Farhad Islami, MD, PhD, senior scientific director of Cancer Disparity Research at the American Cancer Society, said the estimated coverage losses are “consistent with the number” — 7.8 million — “estimated by the nonpartisan Congressional Budget Office.”

Islami also stressed that the harm caused by the new restrictions would be “far greater” than what the study reports, with coverage losses leading to delays in care seeking for cancer symptoms of all kinds “and consequently, delayed diagnosis for many more cancer cases.”

“Moreover,” he added, “the restrictions can reduce the utilization of preventive care (eg, counselling and pharmacotherapy for smoking cessation among people who smoke, counselling for reducing weight, and so on) and receipt of guideline-concordant cancer treatments among those who will lose Medicaid coverage.”

In Diaz’ view, clinicians can help mitigate the adverse effects of the new provisions.

“For example, proactively identifying patients at risk of coverage loss, engaging financial counselors and social workers early, and connecting uninsured or underinsured patients to safety-net screening and treatment programs,” he said. “At a systems level, clinicians also have an important role in documenting and communicating these downstream clinical consequences to health systems and policymakers.”

A version of this article first appeared on Medscape.com.

Tightened Medicaid eligibility rules under the 2025 Budget Reconciliation Bill could result in more than 1 million missed cancer screenings within 2 years and over 150 avoidable cancer deaths, new findings suggested.

“Clinicians should be genuinely concerned,” corresponding author Adrian Diaz, MD, MPH, a surgical oncology fellow at the University of Chicago, Chicago, told Medscape Medical News. “These projections suggest that Medicaid eligibility restrictions are likely to translate into delayed diagnoses, more advanced disease at presentation, and worse outcomes.”

The new law, which significantly reduces federal Medicaid funding, introduces mandatory work or community-engagement requirements for working-age adults as well as more frequent recertification starting in 2027.

In the study, a Research Letter published online on January 8 in JAMA Oncology, Diaz and Sarah Shubeck, MD, also from the University of Chicago, drew on data from Arkansas to model how these 2025 federal Medicaid eligibility restrictions could lead to loss of Medicaid coverage and consequently missed cancer screenings, especially in states that expanded Medicaid.

Diaz and Shubeck then paired coverage losses with state-level self-reported screening prevalences and estimated incident breast, colorectal, and lung cancers using 2-year risks.

In the first 2 years after implementation, the researchers predicted that 7.5 million adults (range, 5.0-10.8 million) will lose Medicaid coverage due to the new provisions.

This coverage loss will lead to an estimated 405,706 missed mammograms, 679,745 missed colorectal screenings, and 67,213 missed lung cancer screenings.

As a result, 1055 breast cancers, 748 colorectal cancers, and 538 lung cancers will go undetected, with excess deaths totaling 155 — 70 for breast, 50 for colorectal, and 35 for lung cancers.

Predicted missed screenings and related cancer outcomes varied considerably by state, with missed screening rates generally lower in states that didn’t expand Medicaid.

“Importantly, our estimates focus on missed screening and do not account for patients already undergoing cancer treatment whose coverage could be interrupted, meaning the real-world impact is likely larger,” Diaz said.

Farhad Islami, MD, PhD, senior scientific director of Cancer Disparity Research at the American Cancer Society, said the estimated coverage losses are “consistent with the number” — 7.8 million — “estimated by the nonpartisan Congressional Budget Office.”

Islami also stressed that the harm caused by the new restrictions would be “far greater” than what the study reports, with coverage losses leading to delays in care seeking for cancer symptoms of all kinds “and consequently, delayed diagnosis for many more cancer cases.”

“Moreover,” he added, “the restrictions can reduce the utilization of preventive care (eg, counselling and pharmacotherapy for smoking cessation among people who smoke, counselling for reducing weight, and so on) and receipt of guideline-concordant cancer treatments among those who will lose Medicaid coverage.”

In Diaz’ view, clinicians can help mitigate the adverse effects of the new provisions.

“For example, proactively identifying patients at risk of coverage loss, engaging financial counselors and social workers early, and connecting uninsured or underinsured patients to safety-net screening and treatment programs,” he said. “At a systems level, clinicians also have an important role in documenting and communicating these downstream clinical consequences to health systems and policymakers.”

A version of this article first appeared on Medscape.com.

The targeted therapy combination of encorafenib and cetuximab with FOLFIRI (leucovorin/5-fluorouracil [FU]/irinotecan) chemotherapy may be a new first-line option for patients with BRAF V600E-mutant metastatic colorectal cancer (CRC), according to new results from the BREAKWATER trial.

After a median follow-up of about 10 months, response rates were significantly better with encorafenib and cetuximab plus FOLFIRI than with FOLFIRI alone — without increasing side effects.

The findings, presented at the ASCO Gastrointestinal Cancers Symposium 2026, point to a potential new option for the 20%-25% of patients with BRAF V600E-mutant metastatic CRC who receive FOLFIRI as their chemotherapy.

Based on previous results from BREAKWATER, the FDA granted accelerated approval to first-line encorafenib (Braftovi) and cetuximab (Erbitux) plus mFOLFOX6 for this patient population. That regimen doubled median overall survival compared with standard chemotherapy with or without bevacizumab.

Cohort 3 of BREAKWATER was designed to address a specific question: Are the benefits with the targeted therapy duo a “FOLFOX-specific phenomenon?” lead investigator Scott Kopetz, MD, PhD, of MD Anderson Cancer Center, Houston, said during a press briefing.

Based on these early results, the answer is no. Instead, Kopetz said, there appears to be a “broader synergy” between the targeted therapies and cytotoxic chemotherapy.

Joel Saltzman, MD, ASCO expert in gastrointestinal cancers based at Taussig Cancer Center, Cleveland Clinic in Cleveland, agreed.

“The additional data from the BREAKWATER trial reveals that it is the targeted therapy backbone that provides the better disease control and response rate in BRAF V600E-mutant colorectal cancers,” he said.

BRAF V600E mutations occur in up to 12% of patients with metastatic CRC and are associated with poor outcomes. While many newly diagnosed patients receive FOLFOX (leucovorin/5-FU/oxaliplatin) in the first line, FOLFIRI is a common alternative — often due to concerns about oxaliplatin-associated peripheral neuropathy, Kopetz noted.

The safety lead-in portion of BREAKWATER showed that encorafenib and cetuximab plus FOLFIRI were tolerable and had promising antitumor activity.

Cohort 3 of the trial included 147 patients (mean age, 62 years; 46% male) with BRAF V600E-mutant metastatic CRC, no prior systemic treatment, and good performance status (Eastern Cooperative Oncology Group PS 0 or 1); 73 patients were randomly allocated to encorafenib and cetuximab plus FOLFIRI and 74 to FOLFIRI with or without bevacizumab. The primary endpoint was objective response rate assessed by blinded independent central review.

After a median follow-up of 10 months, patients in the targeted therapy group had an objective response rate of 64.4% vs 39.2% among patients who received FOLFIRI alone or with bevacizumab (odds ratio, 2.76; P = .001).

Responses to the targeted therapies were “rapid and durable,” Kopetz said. More than half (57.4%) of patients treated with encorafenib and cetuximab and FOLFIRI had a duration of response of 6 months or longer than 34.5% in the control group.

Data on overall survival, a secondary endpoint, were not yet mature, but there was a trend toward improved survival with targeted therapy.

Importantly, Kopetz reported, there were no new safety signals, and serious treatment-emergent adverse events occurred at a similar rate in both treatment groups: 39.4% in the targeted therapy group and 36.8% in the control group.

The most common adverse events in both groups included nausea, diarrhea, vomiting, fatigue, appetite loss, and alopecia. About 10% of patients in the targeted therapy group and 9% of those in the control group discontinued their treatment early, suggesting the severity of side effects was similar between the groups.

Kopetz cautioned that the data are still early and follow-up is ongoing. However, he said, the findings support the targeted drugs plus FOLFIRI as a “potential new standard of care” for this patient population.

“The addition of FOLFIRI chemotherapy in the frontline setting will give oncologists and patients more options when selecting a first-line regimen,” Saltzman said. “To have as many options as possible is certainly something we all hope for.”

The trial was funded by Pfizer. Kopetz reported consulting for Pfizer and several other pharmaceutical companies. Saltzman reported having no disclosures.

A version of this article first appeared on Medscape.com.

The targeted therapy combination of encorafenib and cetuximab with FOLFIRI (leucovorin/5-fluorouracil [FU]/irinotecan) chemotherapy may be a new first-line option for patients with BRAF V600E-mutant metastatic colorectal cancer (CRC), according to new results from the BREAKWATER trial.

After a median follow-up of about 10 months, response rates were significantly better with encorafenib and cetuximab plus FOLFIRI than with FOLFIRI alone — without increasing side effects.

The findings, presented at the ASCO Gastrointestinal Cancers Symposium 2026, point to a potential new option for the 20%-25% of patients with BRAF V600E-mutant metastatic CRC who receive FOLFIRI as their chemotherapy.

Based on previous results from BREAKWATER, the FDA granted accelerated approval to first-line encorafenib (Braftovi) and cetuximab (Erbitux) plus mFOLFOX6 for this patient population. That regimen doubled median overall survival compared with standard chemotherapy with or without bevacizumab.

Cohort 3 of BREAKWATER was designed to address a specific question: Are the benefits with the targeted therapy duo a “FOLFOX-specific phenomenon?” lead investigator Scott Kopetz, MD, PhD, of MD Anderson Cancer Center, Houston, said during a press briefing.

Based on these early results, the answer is no. Instead, Kopetz said, there appears to be a “broader synergy” between the targeted therapies and cytotoxic chemotherapy.

Joel Saltzman, MD, ASCO expert in gastrointestinal cancers based at Taussig Cancer Center, Cleveland Clinic in Cleveland, agreed.

“The additional data from the BREAKWATER trial reveals that it is the targeted therapy backbone that provides the better disease control and response rate in BRAF V600E-mutant colorectal cancers,” he said.

BRAF V600E mutations occur in up to 12% of patients with metastatic CRC and are associated with poor outcomes. While many newly diagnosed patients receive FOLFOX (leucovorin/5-FU/oxaliplatin) in the first line, FOLFIRI is a common alternative — often due to concerns about oxaliplatin-associated peripheral neuropathy, Kopetz noted.

The safety lead-in portion of BREAKWATER showed that encorafenib and cetuximab plus FOLFIRI were tolerable and had promising antitumor activity.

Cohort 3 of the trial included 147 patients (mean age, 62 years; 46% male) with BRAF V600E-mutant metastatic CRC, no prior systemic treatment, and good performance status (Eastern Cooperative Oncology Group PS 0 or 1); 73 patients were randomly allocated to encorafenib and cetuximab plus FOLFIRI and 74 to FOLFIRI with or without bevacizumab. The primary endpoint was objective response rate assessed by blinded independent central review.

After a median follow-up of 10 months, patients in the targeted therapy group had an objective response rate of 64.4% vs 39.2% among patients who received FOLFIRI alone or with bevacizumab (odds ratio, 2.76; P = .001).

Responses to the targeted therapies were “rapid and durable,” Kopetz said. More than half (57.4%) of patients treated with encorafenib and cetuximab and FOLFIRI had a duration of response of 6 months or longer than 34.5% in the control group.

Data on overall survival, a secondary endpoint, were not yet mature, but there was a trend toward improved survival with targeted therapy.

Importantly, Kopetz reported, there were no new safety signals, and serious treatment-emergent adverse events occurred at a similar rate in both treatment groups: 39.4% in the targeted therapy group and 36.8% in the control group.

The most common adverse events in both groups included nausea, diarrhea, vomiting, fatigue, appetite loss, and alopecia. About 10% of patients in the targeted therapy group and 9% of those in the control group discontinued their treatment early, suggesting the severity of side effects was similar between the groups.

Kopetz cautioned that the data are still early and follow-up is ongoing. However, he said, the findings support the targeted drugs plus FOLFIRI as a “potential new standard of care” for this patient population.

“The addition of FOLFIRI chemotherapy in the frontline setting will give oncologists and patients more options when selecting a first-line regimen,” Saltzman said. “To have as many options as possible is certainly something we all hope for.”

The trial was funded by Pfizer. Kopetz reported consulting for Pfizer and several other pharmaceutical companies. Saltzman reported having no disclosures.

A version of this article first appeared on Medscape.com.

The targeted therapy combination of encorafenib and cetuximab with FOLFIRI (leucovorin/5-fluorouracil [FU]/irinotecan) chemotherapy may be a new first-line option for patients with BRAF V600E-mutant metastatic colorectal cancer (CRC), according to new results from the BREAKWATER trial.

After a median follow-up of about 10 months, response rates were significantly better with encorafenib and cetuximab plus FOLFIRI than with FOLFIRI alone — without increasing side effects.

The findings, presented at the ASCO Gastrointestinal Cancers Symposium 2026, point to a potential new option for the 20%-25% of patients with BRAF V600E-mutant metastatic CRC who receive FOLFIRI as their chemotherapy.

Based on previous results from BREAKWATER, the FDA granted accelerated approval to first-line encorafenib (Braftovi) and cetuximab (Erbitux) plus mFOLFOX6 for this patient population. That regimen doubled median overall survival compared with standard chemotherapy with or without bevacizumab.

Cohort 3 of BREAKWATER was designed to address a specific question: Are the benefits with the targeted therapy duo a “FOLFOX-specific phenomenon?” lead investigator Scott Kopetz, MD, PhD, of MD Anderson Cancer Center, Houston, said during a press briefing.

Based on these early results, the answer is no. Instead, Kopetz said, there appears to be a “broader synergy” between the targeted therapies and cytotoxic chemotherapy.

Joel Saltzman, MD, ASCO expert in gastrointestinal cancers based at Taussig Cancer Center, Cleveland Clinic in Cleveland, agreed.

“The additional data from the BREAKWATER trial reveals that it is the targeted therapy backbone that provides the better disease control and response rate in BRAF V600E-mutant colorectal cancers,” he said.

BRAF V600E mutations occur in up to 12% of patients with metastatic CRC and are associated with poor outcomes. While many newly diagnosed patients receive FOLFOX (leucovorin/5-FU/oxaliplatin) in the first line, FOLFIRI is a common alternative — often due to concerns about oxaliplatin-associated peripheral neuropathy, Kopetz noted.

The safety lead-in portion of BREAKWATER showed that encorafenib and cetuximab plus FOLFIRI were tolerable and had promising antitumor activity.

Cohort 3 of the trial included 147 patients (mean age, 62 years; 46% male) with BRAF V600E-mutant metastatic CRC, no prior systemic treatment, and good performance status (Eastern Cooperative Oncology Group PS 0 or 1); 73 patients were randomly allocated to encorafenib and cetuximab plus FOLFIRI and 74 to FOLFIRI with or without bevacizumab. The primary endpoint was objective response rate assessed by blinded independent central review.

After a median follow-up of 10 months, patients in the targeted therapy group had an objective response rate of 64.4% vs 39.2% among patients who received FOLFIRI alone or with bevacizumab (odds ratio, 2.76; P = .001).

Responses to the targeted therapies were “rapid and durable,” Kopetz said. More than half (57.4%) of patients treated with encorafenib and cetuximab and FOLFIRI had a duration of response of 6 months or longer than 34.5% in the control group.

Data on overall survival, a secondary endpoint, were not yet mature, but there was a trend toward improved survival with targeted therapy.

Importantly, Kopetz reported, there were no new safety signals, and serious treatment-emergent adverse events occurred at a similar rate in both treatment groups: 39.4% in the targeted therapy group and 36.8% in the control group.

The most common adverse events in both groups included nausea, diarrhea, vomiting, fatigue, appetite loss, and alopecia. About 10% of patients in the targeted therapy group and 9% of those in the control group discontinued their treatment early, suggesting the severity of side effects was similar between the groups.

Kopetz cautioned that the data are still early and follow-up is ongoing. However, he said, the findings support the targeted drugs plus FOLFIRI as a “potential new standard of care” for this patient population.

“The addition of FOLFIRI chemotherapy in the frontline setting will give oncologists and patients more options when selecting a first-line regimen,” Saltzman said. “To have as many options as possible is certainly something we all hope for.”

The trial was funded by Pfizer. Kopetz reported consulting for Pfizer and several other pharmaceutical companies. Saltzman reported having no disclosures.

A version of this article first appeared on Medscape.com.