Cancer

TOPLINE:

A history of tuberculosis (TB) and a history of chronic bronchitis were associated with an increased risk for lung cancer in individuals who had never smoked, whereas asthma had a positive, nonsignificant association overall and a significant association in women.

METHODOLOGY:

• Researchers conducted a systematic review and meta-analysis of clinical databases from inception to July 2025, to assess the association between asthma, TB, and/or chronic bronchitis and the risk for lung cancer among participants aged 18 years or older who had never smoked.
• They included data from 20 case-control studies involving 54,135 participants and five cohort studies involving 377,983 participants.
• The primary outcome was the risk for lung cancer among participants with a history of TB, asthma, or chronic bronchitis.
• Participants were labeled as “never smokers” if they were explicitly described in the manuscripts as having “never smoked” or reported smoking < 100 cigarettes in their lifetime.

TAKEAWAY:

• In case-control studies, TB (16 studies) and chronic bronchitis (9 studies) were significantly associated with an increased risk for lung cancer (odds ratio [OR], 1.76; P < .001 and OR, 1.36; P = .012, respectively).
• In four case-cohort studies, TB was associated with an increased but nonsignificant risk for lung cancer (hazard ratio, 1.64).
• Eleven case-control studies demonstrated a positive but nonsignificant association between asthma and the risk for lung cancer (OR, 1.34). However, a significant association emerged when analyses were limited to women (five studies; OR, 1.61; P < .01).

IN PRACTICE:

History of TB was especially associated with increased LC [lung cancer] risk, meriting particular attention for prospective CT screening studies,” the authors of the study wrote.

SOURCE:

This study was led by Nishwant Swami, MD, Hospital of the University of Pennsylvania, Philadelphia. It was published online on January 11, 2026, in Chest.

LIMITATIONS:

Most studies lacked uniform adjustment for key confounders, increasing the risk for residual confounding. The inclusion of few cohort studies in the analysis may have limited the assessment of temporality and precision. Additionally, differences in covariate adjustment, variable definitions, and language restrictions may have limited comparability and generalizability.

DISCLOSURES:

No specific funding was reported for this study. One author reported serving as a consultant or advisor for various companies, including AstraZeneca, Merck, and Pfizer. Another author reported receiving funding, in part, through the Prostate Cancer Foundation Young Investigator Award and through the Cancer Center Support Grant 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:

A history of tuberculosis (TB) and a history of chronic bronchitis were associated with an increased risk for lung cancer in individuals who had never smoked, whereas asthma had a positive, nonsignificant association overall and a significant association in women.

METHODOLOGY:

• Researchers conducted a systematic review and meta-analysis of clinical databases from inception to July 2025, to assess the association between asthma, TB, and/or chronic bronchitis and the risk for lung cancer among participants aged 18 years or older who had never smoked.
• They included data from 20 case-control studies involving 54,135 participants and five cohort studies involving 377,983 participants.
• The primary outcome was the risk for lung cancer among participants with a history of TB, asthma, or chronic bronchitis.
• Participants were labeled as “never smokers” if they were explicitly described in the manuscripts as having “never smoked” or reported smoking < 100 cigarettes in their lifetime.

TAKEAWAY:

• In case-control studies, TB (16 studies) and chronic bronchitis (9 studies) were significantly associated with an increased risk for lung cancer (odds ratio [OR], 1.76; P < .001 and OR, 1.36; P = .012, respectively).
• In four case-cohort studies, TB was associated with an increased but nonsignificant risk for lung cancer (hazard ratio, 1.64).
• Eleven case-control studies demonstrated a positive but nonsignificant association between asthma and the risk for lung cancer (OR, 1.34). However, a significant association emerged when analyses were limited to women (five studies; OR, 1.61; P < .01).

IN PRACTICE:

History of TB was especially associated with increased LC [lung cancer] risk, meriting particular attention for prospective CT screening studies,” the authors of the study wrote.

SOURCE:

This study was led by Nishwant Swami, MD, Hospital of the University of Pennsylvania, Philadelphia. It was published online on January 11, 2026, in Chest.

LIMITATIONS:

Most studies lacked uniform adjustment for key confounders, increasing the risk for residual confounding. The inclusion of few cohort studies in the analysis may have limited the assessment of temporality and precision. Additionally, differences in covariate adjustment, variable definitions, and language restrictions may have limited comparability and generalizability.

DISCLOSURES:

No specific funding was reported for this study. One author reported serving as a consultant or advisor for various companies, including AstraZeneca, Merck, and Pfizer. Another author reported receiving funding, in part, through the Prostate Cancer Foundation Young Investigator Award and through the Cancer Center Support Grant 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:

A history of tuberculosis (TB) and a history of chronic bronchitis were associated with an increased risk for lung cancer in individuals who had never smoked, whereas asthma had a positive, nonsignificant association overall and a significant association in women.

METHODOLOGY:

• Researchers conducted a systematic review and meta-analysis of clinical databases from inception to July 2025, to assess the association between asthma, TB, and/or chronic bronchitis and the risk for lung cancer among participants aged 18 years or older who had never smoked.
• They included data from 20 case-control studies involving 54,135 participants and five cohort studies involving 377,983 participants.
• The primary outcome was the risk for lung cancer among participants with a history of TB, asthma, or chronic bronchitis.
• Participants were labeled as “never smokers” if they were explicitly described in the manuscripts as having “never smoked” or reported smoking < 100 cigarettes in their lifetime.

TAKEAWAY:

• In case-control studies, TB (16 studies) and chronic bronchitis (9 studies) were significantly associated with an increased risk for lung cancer (odds ratio [OR], 1.76; P < .001 and OR, 1.36; P = .012, respectively).
• In four case-cohort studies, TB was associated with an increased but nonsignificant risk for lung cancer (hazard ratio, 1.64).
• Eleven case-control studies demonstrated a positive but nonsignificant association between asthma and the risk for lung cancer (OR, 1.34). However, a significant association emerged when analyses were limited to women (five studies; OR, 1.61; P < .01).

IN PRACTICE:

History of TB was especially associated with increased LC [lung cancer] risk, meriting particular attention for prospective CT screening studies,” the authors of the study wrote.

SOURCE:

This study was led by Nishwant Swami, MD, Hospital of the University of Pennsylvania, Philadelphia. It was published online on January 11, 2026, in Chest.

LIMITATIONS:

Most studies lacked uniform adjustment for key confounders, increasing the risk for residual confounding. The inclusion of few cohort studies in the analysis may have limited the assessment of temporality and precision. Additionally, differences in covariate adjustment, variable definitions, and language restrictions may have limited comparability and generalizability.

DISCLOSURES:

No specific funding was reported for this study. One author reported serving as a consultant or advisor for various companies, including AstraZeneca, Merck, and Pfizer. Another author reported receiving funding, in part, through the Prostate Cancer Foundation Young Investigator Award and through the Cancer Center Support Grant 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:

Healthy donor fecal microbiota transplantation (FMT) combined with immune checkpoint inhibitors (ICI) in metastatic renal cell carcinoma demonstrated safety with a 50% objective response rate and no grade 4-5 toxicities. Successful engraftment of diverse, anti-inflammatory microbiota correlated with improved clinical response and reduced immune-related adverse events.

METHODOLOGY:

• Many patients with metastatic renal cell carcinoma who take ICI experience immune-related adverse events that may require treatment interruption. Recent studies have provided proof of concept for microbiome modulation as a therapeutic adjunct in metastatic renal cell carcinoma, with FMT showing efficacy in resolving TKI-induced toxicities. However, the safety and clinical activity of healthy donor FMT in metastatic renal cell carcinoma remained unexplored, and its mechanism of action was unclear prior to this study.
• The new phase 1 trial enrolled 20 treatment-naive patients with metastatic renal cell carcinoma classified as intermediate-risk or poor-risk disease, who received encapsulated healthy donor FMT (LND101) combined with ipilimumab plus nivolumab (n = 16), pembrolizumab plus axitinib (n = 3), or pembrolizumab plus lenvatinib (n = 1).
• Participants underwent polyethylene glycol bowel preparation before receiving one full dose (36-40 capsules containing 80-100 g of stool) and two half-doses (20-25 capsules each containing 50-60 g of stool) of FMT from rigorously screened healthy donors.
• The primary endpoint was safety assessed through incidence and severity of immune-related adverse events, while secondary endpoints included objective response rate by response evaluation criteria in solid tumors version 1.1, gut microbiome changes, immune correlates, and quality of life.
• Analysis included longitudinal monitoring of stool and blood samples at five timepoints: baseline, week 1 post-FMT, week 4, week 7, and week 10, with a median follow-up of 21.9 months.

TAKEAWAY:

• The safety endpoint was met, with half (10 of 20) of patients experiencing grade 3 immune-related adverse events and no serious FMT-related toxicities or grade 4-5 immune-related adverse events. One patient (5%) reported experiencing an FMT-related grade 1 gastrointestinal event.
• Among evaluable patients (n = 18), the objective response rate was 50% (9 of 18), including two complete responses (11%; 2 of 18), while 67% (12 of 18) achieved clinical benefit defined as complete response, partial response, or stable disease for at least 6 months.
• Higher alpha diversity and greater functional engraftment of short-chain fatty acid-producing and anti-inflammatory taxa correlated with protection from severe immune-related adverse events (P = .041) and improved therapeutic response (P = .006).
• Expansion of Segatella copri above 10 counts per million at 10 weeks post-FMT predicted severe toxicity in patients receiving ipilimumab plus nivolumab, regardless of donor or recipient microbiota origin.

IN PRACTICE:

These findings demonstrate the safety and potential for functional microbiome engraftment to optimize response and minimize toxicity in ICI-treated [metastatic renal cell carcinoma]. Together, our results underscore the importance of functional donor screening and targeted modulation of the microbiome in optimizing the safety and efficacy of next-generation immune-based therapies,” wrote the authors of the study.

SOURCE:

The study was led by Ricardo Fernandes, Behnam Jabbarizadeh, and Adnan Rajeh, London Health Sciences Centre, London, Ontario, Canada. It was published online on January 28 in Nature Medicine.

LIMITATIONS:

According to the authors, the study’s primary limitation was its small sample size, which was not powered to define the ideal donor microbiome composition for enhancing immunotherapy efficacy without additional toxicities. The single-center design and highly selected patient population may limit external generalizability, requiring validation in larger, multicenter trials to refine donor selection criteria and clarify microbiome-immunity mechanisms.

DISCLOSURES:

The clinical trial was primarily funded through philanthropic donations to co-authors Saman Maleki Vareki and Fernandes through the London Health Sciences Foundation clinical trials program. Vareki and Michael Silverman, another co-author, reported having US Patent application no. 63/913,940 related to FMT donor screening. Vareki reported receiving grants from the Lotte and John Hecht Memorial Foundation, the Weston Family Foundation, and the Canadian Institutes of Health Research. 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:

Healthy donor fecal microbiota transplantation (FMT) combined with immune checkpoint inhibitors (ICI) in metastatic renal cell carcinoma demonstrated safety with a 50% objective response rate and no grade 4-5 toxicities. Successful engraftment of diverse, anti-inflammatory microbiota correlated with improved clinical response and reduced immune-related adverse events.

METHODOLOGY:

• Many patients with metastatic renal cell carcinoma who take ICI experience immune-related adverse events that may require treatment interruption. Recent studies have provided proof of concept for microbiome modulation as a therapeutic adjunct in metastatic renal cell carcinoma, with FMT showing efficacy in resolving TKI-induced toxicities. However, the safety and clinical activity of healthy donor FMT in metastatic renal cell carcinoma remained unexplored, and its mechanism of action was unclear prior to this study.
• The new phase 1 trial enrolled 20 treatment-naive patients with metastatic renal cell carcinoma classified as intermediate-risk or poor-risk disease, who received encapsulated healthy donor FMT (LND101) combined with ipilimumab plus nivolumab (n = 16), pembrolizumab plus axitinib (n = 3), or pembrolizumab plus lenvatinib (n = 1).
• Participants underwent polyethylene glycol bowel preparation before receiving one full dose (36-40 capsules containing 80-100 g of stool) and two half-doses (20-25 capsules each containing 50-60 g of stool) of FMT from rigorously screened healthy donors.
• The primary endpoint was safety assessed through incidence and severity of immune-related adverse events, while secondary endpoints included objective response rate by response evaluation criteria in solid tumors version 1.1, gut microbiome changes, immune correlates, and quality of life.
• Analysis included longitudinal monitoring of stool and blood samples at five timepoints: baseline, week 1 post-FMT, week 4, week 7, and week 10, with a median follow-up of 21.9 months.

TAKEAWAY:

• The safety endpoint was met, with half (10 of 20) of patients experiencing grade 3 immune-related adverse events and no serious FMT-related toxicities or grade 4-5 immune-related adverse events. One patient (5%) reported experiencing an FMT-related grade 1 gastrointestinal event.
• Among evaluable patients (n = 18), the objective response rate was 50% (9 of 18), including two complete responses (11%; 2 of 18), while 67% (12 of 18) achieved clinical benefit defined as complete response, partial response, or stable disease for at least 6 months.
• Higher alpha diversity and greater functional engraftment of short-chain fatty acid-producing and anti-inflammatory taxa correlated with protection from severe immune-related adverse events (P = .041) and improved therapeutic response (P = .006).
• Expansion of Segatella copri above 10 counts per million at 10 weeks post-FMT predicted severe toxicity in patients receiving ipilimumab plus nivolumab, regardless of donor or recipient microbiota origin.

IN PRACTICE:

These findings demonstrate the safety and potential for functional microbiome engraftment to optimize response and minimize toxicity in ICI-treated [metastatic renal cell carcinoma]. Together, our results underscore the importance of functional donor screening and targeted modulation of the microbiome in optimizing the safety and efficacy of next-generation immune-based therapies,” wrote the authors of the study.

SOURCE:

The study was led by Ricardo Fernandes, Behnam Jabbarizadeh, and Adnan Rajeh, London Health Sciences Centre, London, Ontario, Canada. It was published online on January 28 in Nature Medicine.

LIMITATIONS:

According to the authors, the study’s primary limitation was its small sample size, which was not powered to define the ideal donor microbiome composition for enhancing immunotherapy efficacy without additional toxicities. The single-center design and highly selected patient population may limit external generalizability, requiring validation in larger, multicenter trials to refine donor selection criteria and clarify microbiome-immunity mechanisms.

DISCLOSURES:

The clinical trial was primarily funded through philanthropic donations to co-authors Saman Maleki Vareki and Fernandes through the London Health Sciences Foundation clinical trials program. Vareki and Michael Silverman, another co-author, reported having US Patent application no. 63/913,940 related to FMT donor screening. Vareki reported receiving grants from the Lotte and John Hecht Memorial Foundation, the Weston Family Foundation, and the Canadian Institutes of Health Research. 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:

Healthy donor fecal microbiota transplantation (FMT) combined with immune checkpoint inhibitors (ICI) in metastatic renal cell carcinoma demonstrated safety with a 50% objective response rate and no grade 4-5 toxicities. Successful engraftment of diverse, anti-inflammatory microbiota correlated with improved clinical response and reduced immune-related adverse events.

METHODOLOGY:

• Many patients with metastatic renal cell carcinoma who take ICI experience immune-related adverse events that may require treatment interruption. Recent studies have provided proof of concept for microbiome modulation as a therapeutic adjunct in metastatic renal cell carcinoma, with FMT showing efficacy in resolving TKI-induced toxicities. However, the safety and clinical activity of healthy donor FMT in metastatic renal cell carcinoma remained unexplored, and its mechanism of action was unclear prior to this study.
• The new phase 1 trial enrolled 20 treatment-naive patients with metastatic renal cell carcinoma classified as intermediate-risk or poor-risk disease, who received encapsulated healthy donor FMT (LND101) combined with ipilimumab plus nivolumab (n = 16), pembrolizumab plus axitinib (n = 3), or pembrolizumab plus lenvatinib (n = 1).
• Participants underwent polyethylene glycol bowel preparation before receiving one full dose (36-40 capsules containing 80-100 g of stool) and two half-doses (20-25 capsules each containing 50-60 g of stool) of FMT from rigorously screened healthy donors.
• The primary endpoint was safety assessed through incidence and severity of immune-related adverse events, while secondary endpoints included objective response rate by response evaluation criteria in solid tumors version 1.1, gut microbiome changes, immune correlates, and quality of life.
• Analysis included longitudinal monitoring of stool and blood samples at five timepoints: baseline, week 1 post-FMT, week 4, week 7, and week 10, with a median follow-up of 21.9 months.

TAKEAWAY:

• The safety endpoint was met, with half (10 of 20) of patients experiencing grade 3 immune-related adverse events and no serious FMT-related toxicities or grade 4-5 immune-related adverse events. One patient (5%) reported experiencing an FMT-related grade 1 gastrointestinal event.
• Among evaluable patients (n = 18), the objective response rate was 50% (9 of 18), including two complete responses (11%; 2 of 18), while 67% (12 of 18) achieved clinical benefit defined as complete response, partial response, or stable disease for at least 6 months.
• Higher alpha diversity and greater functional engraftment of short-chain fatty acid-producing and anti-inflammatory taxa correlated with protection from severe immune-related adverse events (P = .041) and improved therapeutic response (P = .006).
• Expansion of Segatella copri above 10 counts per million at 10 weeks post-FMT predicted severe toxicity in patients receiving ipilimumab plus nivolumab, regardless of donor or recipient microbiota origin.

IN PRACTICE:

These findings demonstrate the safety and potential for functional microbiome engraftment to optimize response and minimize toxicity in ICI-treated [metastatic renal cell carcinoma]. Together, our results underscore the importance of functional donor screening and targeted modulation of the microbiome in optimizing the safety and efficacy of next-generation immune-based therapies,” wrote the authors of the study.

SOURCE:

The study was led by Ricardo Fernandes, Behnam Jabbarizadeh, and Adnan Rajeh, London Health Sciences Centre, London, Ontario, Canada. It was published online on January 28 in Nature Medicine.

LIMITATIONS:

According to the authors, the study’s primary limitation was its small sample size, which was not powered to define the ideal donor microbiome composition for enhancing immunotherapy efficacy without additional toxicities. The single-center design and highly selected patient population may limit external generalizability, requiring validation in larger, multicenter trials to refine donor selection criteria and clarify microbiome-immunity mechanisms.

DISCLOSURES:

The clinical trial was primarily funded through philanthropic donations to co-authors Saman Maleki Vareki and Fernandes through the London Health Sciences Foundation clinical trials program. Vareki and Michael Silverman, another co-author, reported having US Patent application no. 63/913,940 related to FMT donor screening. Vareki reported receiving grants from the Lotte and John Hecht Memorial Foundation, the Weston Family Foundation, and the Canadian Institutes of Health Research. 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:

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.