AVAHO

TOPLINE: In 75,453 veterans with head and neck squamous cell carcinoma (HNSCC), 36.4% live in rural or highly rural areas and 32.0% have a national area deprivation index (ADI) ≥ 75. The average drive time to the nearest tertiary or complex US Department of Veterans Affairs (VA) facility is 94 minutes, highlighting potential access and equity barriers related to rurality, deprivation, and distance.

METHODOLOGY:

• A retrospective descriptive study using nationwide VA data from fiscal years 2012 to 2022 identified 75,453 veterans with head and neck squamous cell carcinoma (HNSCC) by International Classification of Diseases, Ninth Revision and International Classification of Diseases, Tenth Revision codes.

• Patients were grouped into 5 primary tumor subsites: oral cavity, oropharynx, hypopharynx, larynx, and nasopharynx.

• Rurality was classified using Rural-Urban Commuting Area-derived urban, rural, and highly rural scores; socioeconomic disadvantage was measured with national ADI scores.

• Travel burden was assessed using time and distance to the nearest primary, secondary, and tertiary VA facilities.

TAKEAWAY:

• Oropharyngeal cancer (OPC) cases among veterans increased from 26.3% in 2012 to 46.0% in 2022, while laryngeal cancers decreased from 41.2% to 29.3%.

• HNSCCs locations included 35.6% in the larynx, 34.4% in the oropharynx, 22.6% in the oral cavity 3.7% in the hypopharynx, and 3.7% in the nasopharynx.

• Veterans with OPC were younger than non-OPC patients and more likely to be White; > 70% were current or former smokers.

IN PRACTICE: “Understanding the geographic and socioeconomic landscape of veterans with HNSCC will allow us to tease out the factors associated with poor outcomes and ultimately design interventions that target high-risk veteran populations to improve overall health outcomes,” the authors argued.

SOURCE: The study was led by researchers at the Veterans Affairs Pittsburgh Healthcare System. It was published online in Head & Neck.

LIMITATIONS: The inability to extract accurate data from a large dataset, challenges in obtaining tumor stage information due to varying documentation practices across physicians and treatment courses, and the inability to assess HPV or p16 data for the cohort represents significant limitations that may have impacted interpretation of results. Clinical outcome measures and cause of death assessment were limited in this national database, affecting the ability to draw conclusions regarding the impact of rurality, area deprivation, and travel time on outcomes.

DISCLOSURES: Chad Brenner reported holding several patents related to the development and use of circulating tumor DNA tests in patients with HNSCC. Jose P. Zevallos disclosed being the founder, equity shareholder, and board member of Droplet Biosciences and Echogenesis Therapeutics, serving as chief scientific advisor and shareholder of Vine Medical, and acting as a consultant for Merck and Johnson & Johnson. Matthew E. Spector reported serving as a consultant for Hologic. Kristen L. Zayan, Jennifer L. McCoy, Monique Y. Boudreaux-Kelly, Zachary Hahn, John Hotchkiss, and Jessica H. Maxwell declared no 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.

TOPLINE: In 75,453 veterans with head and neck squamous cell carcinoma (HNSCC), 36.4% live in rural or highly rural areas and 32.0% have a national area deprivation index (ADI) ≥ 75. The average drive time to the nearest tertiary or complex US Department of Veterans Affairs (VA) facility is 94 minutes, highlighting potential access and equity barriers related to rurality, deprivation, and distance.

METHODOLOGY:

• A retrospective descriptive study using nationwide VA data from fiscal years 2012 to 2022 identified 75,453 veterans with head and neck squamous cell carcinoma (HNSCC) by International Classification of Diseases, Ninth Revision and International Classification of Diseases, Tenth Revision codes.

• Patients were grouped into 5 primary tumor subsites: oral cavity, oropharynx, hypopharynx, larynx, and nasopharynx.

• Rurality was classified using Rural-Urban Commuting Area-derived urban, rural, and highly rural scores; socioeconomic disadvantage was measured with national ADI scores.

• Travel burden was assessed using time and distance to the nearest primary, secondary, and tertiary VA facilities.

TAKEAWAY:

• Oropharyngeal cancer (OPC) cases among veterans increased from 26.3% in 2012 to 46.0% in 2022, while laryngeal cancers decreased from 41.2% to 29.3%.

• HNSCCs locations included 35.6% in the larynx, 34.4% in the oropharynx, 22.6% in the oral cavity 3.7% in the hypopharynx, and 3.7% in the nasopharynx.

• Veterans with OPC were younger than non-OPC patients and more likely to be White; > 70% were current or former smokers.

IN PRACTICE: “Understanding the geographic and socioeconomic landscape of veterans with HNSCC will allow us to tease out the factors associated with poor outcomes and ultimately design interventions that target high-risk veteran populations to improve overall health outcomes,” the authors argued.

SOURCE: The study was led by researchers at the Veterans Affairs Pittsburgh Healthcare System. It was published online in Head & Neck.

LIMITATIONS: The inability to extract accurate data from a large dataset, challenges in obtaining tumor stage information due to varying documentation practices across physicians and treatment courses, and the inability to assess HPV or p16 data for the cohort represents significant limitations that may have impacted interpretation of results. Clinical outcome measures and cause of death assessment were limited in this national database, affecting the ability to draw conclusions regarding the impact of rurality, area deprivation, and travel time on outcomes.

DISCLOSURES: Chad Brenner reported holding several patents related to the development and use of circulating tumor DNA tests in patients with HNSCC. Jose P. Zevallos disclosed being the founder, equity shareholder, and board member of Droplet Biosciences and Echogenesis Therapeutics, serving as chief scientific advisor and shareholder of Vine Medical, and acting as a consultant for Merck and Johnson & Johnson. Matthew E. Spector reported serving as a consultant for Hologic. Kristen L. Zayan, Jennifer L. McCoy, Monique Y. Boudreaux-Kelly, Zachary Hahn, John Hotchkiss, and Jessica H. Maxwell declared no 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.

TOPLINE: In 75,453 veterans with head and neck squamous cell carcinoma (HNSCC), 36.4% live in rural or highly rural areas and 32.0% have a national area deprivation index (ADI) ≥ 75. The average drive time to the nearest tertiary or complex US Department of Veterans Affairs (VA) facility is 94 minutes, highlighting potential access and equity barriers related to rurality, deprivation, and distance.

METHODOLOGY:

• A retrospective descriptive study using nationwide VA data from fiscal years 2012 to 2022 identified 75,453 veterans with head and neck squamous cell carcinoma (HNSCC) by International Classification of Diseases, Ninth Revision and International Classification of Diseases, Tenth Revision codes.

• Patients were grouped into 5 primary tumor subsites: oral cavity, oropharynx, hypopharynx, larynx, and nasopharynx.

• Rurality was classified using Rural-Urban Commuting Area-derived urban, rural, and highly rural scores; socioeconomic disadvantage was measured with national ADI scores.

• Travel burden was assessed using time and distance to the nearest primary, secondary, and tertiary VA facilities.

TAKEAWAY:

• Oropharyngeal cancer (OPC) cases among veterans increased from 26.3% in 2012 to 46.0% in 2022, while laryngeal cancers decreased from 41.2% to 29.3%.

• HNSCCs locations included 35.6% in the larynx, 34.4% in the oropharynx, 22.6% in the oral cavity 3.7% in the hypopharynx, and 3.7% in the nasopharynx.

• Veterans with OPC were younger than non-OPC patients and more likely to be White; > 70% were current or former smokers.

IN PRACTICE: “Understanding the geographic and socioeconomic landscape of veterans with HNSCC will allow us to tease out the factors associated with poor outcomes and ultimately design interventions that target high-risk veteran populations to improve overall health outcomes,” the authors argued.

SOURCE: The study was led by researchers at the Veterans Affairs Pittsburgh Healthcare System. It was published online in Head & Neck.

LIMITATIONS: The inability to extract accurate data from a large dataset, challenges in obtaining tumor stage information due to varying documentation practices across physicians and treatment courses, and the inability to assess HPV or p16 data for the cohort represents significant limitations that may have impacted interpretation of results. Clinical outcome measures and cause of death assessment were limited in this national database, affecting the ability to draw conclusions regarding the impact of rurality, area deprivation, and travel time on outcomes.

DISCLOSURES: Chad Brenner reported holding several patents related to the development and use of circulating tumor DNA tests in patients with HNSCC. Jose P. Zevallos disclosed being the founder, equity shareholder, and board member of Droplet Biosciences and Echogenesis Therapeutics, serving as chief scientific advisor and shareholder of Vine Medical, and acting as a consultant for Merck and Johnson & Johnson. Matthew E. Spector reported serving as a consultant for Hologic. Kristen L. Zayan, Jennifer L. McCoy, Monique Y. Boudreaux-Kelly, Zachary Hahn, John Hotchkiss, and Jessica H. Maxwell declared no 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.

Adults who have never been married had a higher cancer risk than their married or previously married peers, with patterns observed across many major cancer types and particularly strong for cancers linked to infections, smoking, and reproductive factors, new data suggest.

The findings are based on a large, population-based cancer registry analysis of more than 4 million cases, making it the largest study of its kind in the US.

First author Paulo Pinheiro, PhD, cautioned, however, that the study does not suggest that marriage itself is protective.

"As with any observational study, we cannot establish causation, and unmeasured factors may contribute to the associations,” said Pinheiro, with Sylvester Comprehensive Cancer Center, University of Miami Health System, in Miami.

Marital status may, however, help identify groups with different patterns of cancer risk, which likely reflect social and lifestyle behaviors rather than a direct causal effect, Pinheiro explained.

Married individuals, for instance, are less likely to smoke — a known cancer risk factor — and more likely to have children and undergo cancer screening, which can influence cancer incidence through reproductive effects and screening, including earlier detection and removal of precancerous lesions.

"Marital status is therefore best understood as a marker of those accumulated factors," Pinheiro said.

The study was published online on April 8 in Cancer Research Communications.

Filling a Data Gap

Marriage has consistently been associated with earlier cancer diagnosis and improved survival among those with cancer, but its relationship to cancer incidence remains less clear.

To address that gap, researchers analyzed data from 12 US states that included demographic and cancer information for more than 4.2 million cancer cases diagnosed between 2015 and 2022.

The analysis included more than 500 million person-years at risk in adults 30 years or older, representing an annual population of more than 62 million. The never-married group comprised about 19% of the total population — 22% were men and 17% were women.

Compared with ever-married individuals, never-married men and women had higher cancer incidence across many major cancer types, racial and ethnic groups, and age groups.

Overall, cancer rates were about 68% higher in never-married men and 85% higher in never-married women compared with their ever-married counterparts (incidence rate ratios [IRRs], 1.68 and 1.85, respectively).

Never-married Black men had the highest overall cancer rates (1600 per 100,000), whereas married Black men had significantly lower rates than married White men (752.6 vs 836.2 per 100,000), suggesting complex interactions between marital status and structural factors, the researchers noted.

Site-specific patterns revealed clues to potential mechanisms linking marital status and cancer.

Compared with ever-married individuals, never-married people had the highest excess risks for human papillomavirus-related cancers — about five times higher for anal cancer in men (IRR, 5.04) and approaching three times higher for cervical cancer in women (IRR, 2.64).

Other strong associations between never-married individuals and cancer risk were observed for smoking-related cancers, including lung (IRR, 2.1 for both men and women) and esophageal cancers (IRR, 2.4 in men and 2.7 in women), and malignancies including liver (IRR, 2.3 for both men and women), bladder (IRR, 2.3 women only), and colorectal (IRR, 2.1 women only) cancers.

Among women, the higher incidence of ovarian and uterine cancers (IRR, 2.4 for both) among the never-married group supports the influence of reproductive mechanisms, such as giving birth, on cancer risk.

The association between marital status and cancer risk was weaker for breast, prostate, and thyroid cancers (with IRRs < 2), suggesting potentially less modifiable etiologies.

Overall, “methodologically, it is quite robust, particularly in its clear framing of ever- vs never-married individuals and the use of standardized incidence rates and regression modeling,” Pinheiro said.

The analysis did not adjust for individual-level risk factors such as smoking, diet, physical activity, or alcohol use — factors that may partly explain the observed associations.

Adjusting for these lifestyle and health behavior factors at the individual level would require detailed information on these behaviors, and “data at that level simply do not exist at a national scale,” Pinheiro said. It would also “obscure the real-world pattern we are trying to measure.”

Gilbert Welch, MD, noted that adjusting for these individual-level cancer risk factors “would certainly attenuate the associations.”

“That said, it wouldn’t be crazy to suggest marriage drives some of these risk factors,” said Welch, general internist and senior investigator at the Center for Surgery and Public Health, Brigham and Women’s Hospital, Boston. Married couples benefit from combined incomes and shared expenses, and “may well help support individuals in making healthy choices (like not smoking).”

But, he added, “it would be crazy to suggest that the reason to get married is to lower cancer risk.”

The authors flagged a study limitation — the fact that ever-married status lumps together people who are currently married, divorced, and widowed, and these groups may have different risk profiles. Additionally, “individuals in strained or abusive marriages may not experience protective social benefits,” while those in long-term cohabiting relationships classified as never-married may experience high levels of support, the authors wrote.

Overall, though, Pinheiro clarified that the main finding is “not about marriage as a causal agent, but about identifying a large population group, the never-married, with a consistently higher cancer burden that has been largely overlooked in public health practice and cancer prevention efforts.”

Linda Waite, professor, Department of Sociology, University of Chicago, who wasn’t involved in the study, wasn’t surprised by the findings. For men, not having a spouse may “disadvantage” them in ways that might increase cancer risk.

Unmarried men are more likely to drink and smoke heavily, which increase cancer risk, she said. A spouse may also influence health awareness and decisions, such as noticing suspicious symptoms, pushing their partner to see a doctor, or helping manage their partner’s care.

Plus, “for both men and women, having a spouse may improve medical care by giving each partner a companion for medical appointments and another person to help manage risks of disease,” Waite said.

The study had no commercial funding. Pinheiro and Waite had no relevant disclosures.

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

Adults who have never been married had a higher cancer risk than their married or previously married peers, with patterns observed across many major cancer types and particularly strong for cancers linked to infections, smoking, and reproductive factors, new data suggest.

The findings are based on a large, population-based cancer registry analysis of more than 4 million cases, making it the largest study of its kind in the US.

First author Paulo Pinheiro, PhD, cautioned, however, that the study does not suggest that marriage itself is protective.

"As with any observational study, we cannot establish causation, and unmeasured factors may contribute to the associations,” said Pinheiro, with Sylvester Comprehensive Cancer Center, University of Miami Health System, in Miami.

Marital status may, however, help identify groups with different patterns of cancer risk, which likely reflect social and lifestyle behaviors rather than a direct causal effect, Pinheiro explained.

Married individuals, for instance, are less likely to smoke — a known cancer risk factor — and more likely to have children and undergo cancer screening, which can influence cancer incidence through reproductive effects and screening, including earlier detection and removal of precancerous lesions.

"Marital status is therefore best understood as a marker of those accumulated factors," Pinheiro said.

The study was published online on April 8 in Cancer Research Communications.

Filling a Data Gap

Marriage has consistently been associated with earlier cancer diagnosis and improved survival among those with cancer, but its relationship to cancer incidence remains less clear.

To address that gap, researchers analyzed data from 12 US states that included demographic and cancer information for more than 4.2 million cancer cases diagnosed between 2015 and 2022.

The analysis included more than 500 million person-years at risk in adults 30 years or older, representing an annual population of more than 62 million. The never-married group comprised about 19% of the total population — 22% were men and 17% were women.

Compared with ever-married individuals, never-married men and women had higher cancer incidence across many major cancer types, racial and ethnic groups, and age groups.

Overall, cancer rates were about 68% higher in never-married men and 85% higher in never-married women compared with their ever-married counterparts (incidence rate ratios [IRRs], 1.68 and 1.85, respectively).

Never-married Black men had the highest overall cancer rates (1600 per 100,000), whereas married Black men had significantly lower rates than married White men (752.6 vs 836.2 per 100,000), suggesting complex interactions between marital status and structural factors, the researchers noted.

Site-specific patterns revealed clues to potential mechanisms linking marital status and cancer.

Compared with ever-married individuals, never-married people had the highest excess risks for human papillomavirus-related cancers — about five times higher for anal cancer in men (IRR, 5.04) and approaching three times higher for cervical cancer in women (IRR, 2.64).

Other strong associations between never-married individuals and cancer risk were observed for smoking-related cancers, including lung (IRR, 2.1 for both men and women) and esophageal cancers (IRR, 2.4 in men and 2.7 in women), and malignancies including liver (IRR, 2.3 for both men and women), bladder (IRR, 2.3 women only), and colorectal (IRR, 2.1 women only) cancers.

Among women, the higher incidence of ovarian and uterine cancers (IRR, 2.4 for both) among the never-married group supports the influence of reproductive mechanisms, such as giving birth, on cancer risk.

The association between marital status and cancer risk was weaker for breast, prostate, and thyroid cancers (with IRRs < 2), suggesting potentially less modifiable etiologies.

Overall, “methodologically, it is quite robust, particularly in its clear framing of ever- vs never-married individuals and the use of standardized incidence rates and regression modeling,” Pinheiro said.

The analysis did not adjust for individual-level risk factors such as smoking, diet, physical activity, or alcohol use — factors that may partly explain the observed associations.

Adjusting for these lifestyle and health behavior factors at the individual level would require detailed information on these behaviors, and “data at that level simply do not exist at a national scale,” Pinheiro said. It would also “obscure the real-world pattern we are trying to measure.”

Gilbert Welch, MD, noted that adjusting for these individual-level cancer risk factors “would certainly attenuate the associations.”

“That said, it wouldn’t be crazy to suggest marriage drives some of these risk factors,” said Welch, general internist and senior investigator at the Center for Surgery and Public Health, Brigham and Women’s Hospital, Boston. Married couples benefit from combined incomes and shared expenses, and “may well help support individuals in making healthy choices (like not smoking).”

But, he added, “it would be crazy to suggest that the reason to get married is to lower cancer risk.”

The authors flagged a study limitation — the fact that ever-married status lumps together people who are currently married, divorced, and widowed, and these groups may have different risk profiles. Additionally, “individuals in strained or abusive marriages may not experience protective social benefits,” while those in long-term cohabiting relationships classified as never-married may experience high levels of support, the authors wrote.

Overall, though, Pinheiro clarified that the main finding is “not about marriage as a causal agent, but about identifying a large population group, the never-married, with a consistently higher cancer burden that has been largely overlooked in public health practice and cancer prevention efforts.”

Linda Waite, professor, Department of Sociology, University of Chicago, who wasn’t involved in the study, wasn’t surprised by the findings. For men, not having a spouse may “disadvantage” them in ways that might increase cancer risk.

Unmarried men are more likely to drink and smoke heavily, which increase cancer risk, she said. A spouse may also influence health awareness and decisions, such as noticing suspicious symptoms, pushing their partner to see a doctor, or helping manage their partner’s care.

Plus, “for both men and women, having a spouse may improve medical care by giving each partner a companion for medical appointments and another person to help manage risks of disease,” Waite said.

The study had no commercial funding. Pinheiro and Waite had no relevant disclosures.

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

Adults who have never been married had a higher cancer risk than their married or previously married peers, with patterns observed across many major cancer types and particularly strong for cancers linked to infections, smoking, and reproductive factors, new data suggest.

The findings are based on a large, population-based cancer registry analysis of more than 4 million cases, making it the largest study of its kind in the US.

First author Paulo Pinheiro, PhD, cautioned, however, that the study does not suggest that marriage itself is protective.

"As with any observational study, we cannot establish causation, and unmeasured factors may contribute to the associations,” said Pinheiro, with Sylvester Comprehensive Cancer Center, University of Miami Health System, in Miami.

Marital status may, however, help identify groups with different patterns of cancer risk, which likely reflect social and lifestyle behaviors rather than a direct causal effect, Pinheiro explained.

Married individuals, for instance, are less likely to smoke — a known cancer risk factor — and more likely to have children and undergo cancer screening, which can influence cancer incidence through reproductive effects and screening, including earlier detection and removal of precancerous lesions.

"Marital status is therefore best understood as a marker of those accumulated factors," Pinheiro said.

The study was published online on April 8 in Cancer Research Communications.

Filling a Data Gap

Marriage has consistently been associated with earlier cancer diagnosis and improved survival among those with cancer, but its relationship to cancer incidence remains less clear.

To address that gap, researchers analyzed data from 12 US states that included demographic and cancer information for more than 4.2 million cancer cases diagnosed between 2015 and 2022.

The analysis included more than 500 million person-years at risk in adults 30 years or older, representing an annual population of more than 62 million. The never-married group comprised about 19% of the total population — 22% were men and 17% were women.

Compared with ever-married individuals, never-married men and women had higher cancer incidence across many major cancer types, racial and ethnic groups, and age groups.

Overall, cancer rates were about 68% higher in never-married men and 85% higher in never-married women compared with their ever-married counterparts (incidence rate ratios [IRRs], 1.68 and 1.85, respectively).

Never-married Black men had the highest overall cancer rates (1600 per 100,000), whereas married Black men had significantly lower rates than married White men (752.6 vs 836.2 per 100,000), suggesting complex interactions between marital status and structural factors, the researchers noted.

Site-specific patterns revealed clues to potential mechanisms linking marital status and cancer.

Compared with ever-married individuals, never-married people had the highest excess risks for human papillomavirus-related cancers — about five times higher for anal cancer in men (IRR, 5.04) and approaching three times higher for cervical cancer in women (IRR, 2.64).

Other strong associations between never-married individuals and cancer risk were observed for smoking-related cancers, including lung (IRR, 2.1 for both men and women) and esophageal cancers (IRR, 2.4 in men and 2.7 in women), and malignancies including liver (IRR, 2.3 for both men and women), bladder (IRR, 2.3 women only), and colorectal (IRR, 2.1 women only) cancers.

Among women, the higher incidence of ovarian and uterine cancers (IRR, 2.4 for both) among the never-married group supports the influence of reproductive mechanisms, such as giving birth, on cancer risk.

The association between marital status and cancer risk was weaker for breast, prostate, and thyroid cancers (with IRRs < 2), suggesting potentially less modifiable etiologies.

Overall, “methodologically, it is quite robust, particularly in its clear framing of ever- vs never-married individuals and the use of standardized incidence rates and regression modeling,” Pinheiro said.

The analysis did not adjust for individual-level risk factors such as smoking, diet, physical activity, or alcohol use — factors that may partly explain the observed associations.

Adjusting for these lifestyle and health behavior factors at the individual level would require detailed information on these behaviors, and “data at that level simply do not exist at a national scale,” Pinheiro said. It would also “obscure the real-world pattern we are trying to measure.”

Gilbert Welch, MD, noted that adjusting for these individual-level cancer risk factors “would certainly attenuate the associations.”

“That said, it wouldn’t be crazy to suggest marriage drives some of these risk factors,” said Welch, general internist and senior investigator at the Center for Surgery and Public Health, Brigham and Women’s Hospital, Boston. Married couples benefit from combined incomes and shared expenses, and “may well help support individuals in making healthy choices (like not smoking).”

But, he added, “it would be crazy to suggest that the reason to get married is to lower cancer risk.”

The authors flagged a study limitation — the fact that ever-married status lumps together people who are currently married, divorced, and widowed, and these groups may have different risk profiles. Additionally, “individuals in strained or abusive marriages may not experience protective social benefits,” while those in long-term cohabiting relationships classified as never-married may experience high levels of support, the authors wrote.

Overall, though, Pinheiro clarified that the main finding is “not about marriage as a causal agent, but about identifying a large population group, the never-married, with a consistently higher cancer burden that has been largely overlooked in public health practice and cancer prevention efforts.”

Linda Waite, professor, Department of Sociology, University of Chicago, who wasn’t involved in the study, wasn’t surprised by the findings. For men, not having a spouse may “disadvantage” them in ways that might increase cancer risk.

Unmarried men are more likely to drink and smoke heavily, which increase cancer risk, she said. A spouse may also influence health awareness and decisions, such as noticing suspicious symptoms, pushing their partner to see a doctor, or helping manage their partner’s care.

Plus, “for both men and women, having a spouse may improve medical care by giving each partner a companion for medical appointments and another person to help manage risks of disease,” Waite said.

The study had no commercial funding. Pinheiro and Waite had no relevant disclosures.

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

SAN FRANCISCO – Treatment for follicular lymphoma (FL) continues to evolve, according to a US Department of Veterans Affairs (VA) hematologist-oncologist, as second-line regimens emerge but the withdrawal of a recently approved agent complicates the picture.

“The future for our understanding and treatment of follicular lymphoma remains bright,” said Gerald Hsu, MD, PhD, of the University of California at San Francisco and the San Francisco VA Health Care System, during a presentation at the March Association of VA Hematology/Oncology (AVAHO) regional meeting on lymphoma.

By the Numbers

About 16,500 people in the US are diagnosed with FL each year. The median age of diagnosis is 64 years, and the 5-year survival rate from 2015-2021 was 89.0%, according to the National Cancer Institute. 

FL is slow-growing and indolent, Hsu said.

“[That] means that we tend to see patients who are older when they are diagnosed,” he added. “They tend to live a long time, and they’re not usually curable.”

A better understanding of the biology of FL has allowed for the development of new markers and ways of measuring residual disease, Hsu said. Additional insight may allow clinicians to identify which patients could benefit most from specific therapies.

Frontline Options

Hsu highlighted the VA Oncology Clinical Pathway for FL, which offers step-by-step guidance regarding therapy and was updated in March 2026. “It walks you through the pathway, but it’s not something that you are beholden to,” he said.

If the patient has classic FL grades 1-3A, is not at risk of transformation to aggressive lymphoma, is not in stage 1 or continuous stage lymphoma, and is indicated for therapy, the guideline recommends lenalidomide plus rituximab (R² or R-Len) or rituximab-bendamustine (R-Benda). 

“There’s a lot of data to support R-Benda,” Hsu said, pointing to a pair of studies with large numbers of patients with FL. The 2013 StiL trial tracked > 500 patients with indolent or mantle cell lymphoma (46% high risk). Those on R-Benda displayed better progression-free survival (PFS) than those taking the combination rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisone (R-CHOP; hazard ratio [HR], 0.61).

In a 5-year update of the BRIGHT trial, which enrolled > 500 patients with indolent or mantle cell lymphoma (9% high risk), the R-Benda group had better PFS than patients on R-CHOP or rituximab plus cyclophosphamide, vincristine, and prednisone (HR, 0.61).

R² is a somewhat newer regimen, Hsu said. Data from the 2018 RELEVANCE study (> 1000 patients) found R² to be nonsuperior to 3 rituximab-plus-chemotherapy regimens but with a lower rate of grade 3-4 neutropenia (32% vs 50% for the other regimens). 

However, R² is “not an FDA-approved regimen in the frontline because it did not demonstrate superiority” over other treatments, Hsu said. 

Selecting the Right Therapy

Which therapy is best? It’s a bit of a wash, Hsu said. 

He noted that R², R-Benda, and another therapy that’s not yet in the VA pathway (R-CHOP) appear to be noninferior to one another, although R-Benda has the edge. R² is better regarding neutropenia risk, although it lacks FDA approval.

“I think about these 3 regimens as appropriate and good,” Hsu said. “It’s nice having 3 wonderful regimens.”

Hsu highlighted the importance of complete remission (CR) as a goal. He pointed to a 2022 analysis of > 5,200 patients that showed progression within 24 months greatly boosted the risk of death vs no-progression (HR, 3.03). Progression within 24 months also lowered estimated 5-year overall survival to 71%.

“Timing really does matter,” Hsu said. “We often worry about transformation to diffuse large B-cell in patients who relapse, particularly this early.”

Second-Line Therapy Options

Two regimens have recently achieved National Comprehensive Cancer Network Category 1 preferred status in the second-line setting, Hsu said, although neither appears in the VA pathway. 

One is tafasitamab plus R², which was shown to extend median PFS to 22.4 months vs 13.9 months for R² alone in the 2026 inMIND study (HR, 0.43), but without an overall survival benefit. 

The other therapy is epcoritamab plus R²: Data from the 2026 EPCORE FL-1 study showed an overall response rate (ORR) of 95% for the combination vs 79% for R² alone and an estimated 16-month PFS of 85.5% for the combination vs 40.2% for R².

Hsu cautioned about the adverse event profile for community infusion centers. The combination carried higher rates of grade ≥ 3 infections (33% vs 16%) and neutropenia (69% vs 42%) compared with R² alone. However, grade ≥ 3 cytokine release syndrome was absent. 

“Stay alert to higher risk for infections and neutropenia here,” Hsu said.

Beyond Second Line: Biospecifics and CAR-T

The biospecifics mosunetuzumab and epcoritamab are now FDA-approved for patients who have relapsed ≥ 2 times. Mosunetuzumab showed ORR of 78% and CR rate of 60% in a 2025 study, while epcoritamab monotherapy showed ORR of 82% and CR of 63% in a 2024 study.

Mosunetuzumab had a 2.2% rate of cytokine release syndrome and a 4.4% rate of immune effector cell-associated neurotoxicity syndrome; epcoritamab had 0% rates of both.

“Think of these 2 options as getting you to the same place, potentially, but maybe with slightly different rates of toxicity,” Hsu said. 

Meanwhile, CAR-T therapy has shown “impressive results for the right patient,” Hsu said. 

Tazemetostat Withdrawn

Hsu noted that tazemetostat, an EZH2 inhibitor that was FDA-approved for relapsed/refractory FL with EZH2 mutations and patients with FL and no satisfactory alternative options, was withdrawn from the market by Eisai in March 2026. The cause of withdrawal was increased rates of secondary hematologic malignancies. 

Meanwhile, patients enrolled in the ongoing SYMPHONY-1 trial will be switched to R².

The withdrawal was “unfortunate,” Hsu said, “but the concept is important. Identifying new targets for therapy and developing those is how we make progress.”

SAN FRANCISCO – Treatment for follicular lymphoma (FL) continues to evolve, according to a US Department of Veterans Affairs (VA) hematologist-oncologist, as second-line regimens emerge but the withdrawal of a recently approved agent complicates the picture.

“The future for our understanding and treatment of follicular lymphoma remains bright,” said Gerald Hsu, MD, PhD, of the University of California at San Francisco and the San Francisco VA Health Care System, during a presentation at the March Association of VA Hematology/Oncology (AVAHO) regional meeting on lymphoma.

By the Numbers

About 16,500 people in the US are diagnosed with FL each year. The median age of diagnosis is 64 years, and the 5-year survival rate from 2015-2021 was 89.0%, according to the National Cancer Institute. 

FL is slow-growing and indolent, Hsu said.

“[That] means that we tend to see patients who are older when they are diagnosed,” he added. “They tend to live a long time, and they’re not usually curable.”

A better understanding of the biology of FL has allowed for the development of new markers and ways of measuring residual disease, Hsu said. Additional insight may allow clinicians to identify which patients could benefit most from specific therapies.

Frontline Options

Hsu highlighted the VA Oncology Clinical Pathway for FL, which offers step-by-step guidance regarding therapy and was updated in March 2026. “It walks you through the pathway, but it’s not something that you are beholden to,” he said.

If the patient has classic FL grades 1-3A, is not at risk of transformation to aggressive lymphoma, is not in stage 1 or continuous stage lymphoma, and is indicated for therapy, the guideline recommends lenalidomide plus rituximab (R² or R-Len) or rituximab-bendamustine (R-Benda). 

“There’s a lot of data to support R-Benda,” Hsu said, pointing to a pair of studies with large numbers of patients with FL. The 2013 StiL trial tracked > 500 patients with indolent or mantle cell lymphoma (46% high risk). Those on R-Benda displayed better progression-free survival (PFS) than those taking the combination rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisone (R-CHOP; hazard ratio [HR], 0.61).

In a 5-year update of the BRIGHT trial, which enrolled > 500 patients with indolent or mantle cell lymphoma (9% high risk), the R-Benda group had better PFS than patients on R-CHOP or rituximab plus cyclophosphamide, vincristine, and prednisone (HR, 0.61).

R² is a somewhat newer regimen, Hsu said. Data from the 2018 RELEVANCE study (> 1000 patients) found R² to be nonsuperior to 3 rituximab-plus-chemotherapy regimens but with a lower rate of grade 3-4 neutropenia (32% vs 50% for the other regimens). 

However, R² is “not an FDA-approved regimen in the frontline because it did not demonstrate superiority” over other treatments, Hsu said. 

Selecting the Right Therapy

Which therapy is best? It’s a bit of a wash, Hsu said. 

He noted that R², R-Benda, and another therapy that’s not yet in the VA pathway (R-CHOP) appear to be noninferior to one another, although R-Benda has the edge. R² is better regarding neutropenia risk, although it lacks FDA approval.

“I think about these 3 regimens as appropriate and good,” Hsu said. “It’s nice having 3 wonderful regimens.”

Hsu highlighted the importance of complete remission (CR) as a goal. He pointed to a 2022 analysis of > 5,200 patients that showed progression within 24 months greatly boosted the risk of death vs no-progression (HR, 3.03). Progression within 24 months also lowered estimated 5-year overall survival to 71%.

“Timing really does matter,” Hsu said. “We often worry about transformation to diffuse large B-cell in patients who relapse, particularly this early.”

Second-Line Therapy Options

Two regimens have recently achieved National Comprehensive Cancer Network Category 1 preferred status in the second-line setting, Hsu said, although neither appears in the VA pathway. 

One is tafasitamab plus R², which was shown to extend median PFS to 22.4 months vs 13.9 months for R² alone in the 2026 inMIND study (HR, 0.43), but without an overall survival benefit. 

The other therapy is epcoritamab plus R²: Data from the 2026 EPCORE FL-1 study showed an overall response rate (ORR) of 95% for the combination vs 79% for R² alone and an estimated 16-month PFS of 85.5% for the combination vs 40.2% for R².

Hsu cautioned about the adverse event profile for community infusion centers. The combination carried higher rates of grade ≥ 3 infections (33% vs 16%) and neutropenia (69% vs 42%) compared with R² alone. However, grade ≥ 3 cytokine release syndrome was absent. 

“Stay alert to higher risk for infections and neutropenia here,” Hsu said.

Beyond Second Line: Biospecifics and CAR-T

The biospecifics mosunetuzumab and epcoritamab are now FDA-approved for patients who have relapsed ≥ 2 times. Mosunetuzumab showed ORR of 78% and CR rate of 60% in a 2025 study, while epcoritamab monotherapy showed ORR of 82% and CR of 63% in a 2024 study.

Mosunetuzumab had a 2.2% rate of cytokine release syndrome and a 4.4% rate of immune effector cell-associated neurotoxicity syndrome; epcoritamab had 0% rates of both.

“Think of these 2 options as getting you to the same place, potentially, but maybe with slightly different rates of toxicity,” Hsu said. 

Meanwhile, CAR-T therapy has shown “impressive results for the right patient,” Hsu said. 

Tazemetostat Withdrawn

Hsu noted that tazemetostat, an EZH2 inhibitor that was FDA-approved for relapsed/refractory FL with EZH2 mutations and patients with FL and no satisfactory alternative options, was withdrawn from the market by Eisai in March 2026. The cause of withdrawal was increased rates of secondary hematologic malignancies. 

Meanwhile, patients enrolled in the ongoing SYMPHONY-1 trial will be switched to R².

The withdrawal was “unfortunate,” Hsu said, “but the concept is important. Identifying new targets for therapy and developing those is how we make progress.”

SAN FRANCISCO – Treatment for follicular lymphoma (FL) continues to evolve, according to a US Department of Veterans Affairs (VA) hematologist-oncologist, as second-line regimens emerge but the withdrawal of a recently approved agent complicates the picture.

“The future for our understanding and treatment of follicular lymphoma remains bright,” said Gerald Hsu, MD, PhD, of the University of California at San Francisco and the San Francisco VA Health Care System, during a presentation at the March Association of VA Hematology/Oncology (AVAHO) regional meeting on lymphoma.

By the Numbers

About 16,500 people in the US are diagnosed with FL each year. The median age of diagnosis is 64 years, and the 5-year survival rate from 2015-2021 was 89.0%, according to the National Cancer Institute. 

FL is slow-growing and indolent, Hsu said.

“[That] means that we tend to see patients who are older when they are diagnosed,” he added. “They tend to live a long time, and they’re not usually curable.”

A better understanding of the biology of FL has allowed for the development of new markers and ways of measuring residual disease, Hsu said. Additional insight may allow clinicians to identify which patients could benefit most from specific therapies.

Frontline Options

Hsu highlighted the VA Oncology Clinical Pathway for FL, which offers step-by-step guidance regarding therapy and was updated in March 2026. “It walks you through the pathway, but it’s not something that you are beholden to,” he said.

If the patient has classic FL grades 1-3A, is not at risk of transformation to aggressive lymphoma, is not in stage 1 or continuous stage lymphoma, and is indicated for therapy, the guideline recommends lenalidomide plus rituximab (R² or R-Len) or rituximab-bendamustine (R-Benda). 

“There’s a lot of data to support R-Benda,” Hsu said, pointing to a pair of studies with large numbers of patients with FL. The 2013 StiL trial tracked > 500 patients with indolent or mantle cell lymphoma (46% high risk). Those on R-Benda displayed better progression-free survival (PFS) than those taking the combination rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisone (R-CHOP; hazard ratio [HR], 0.61).

In a 5-year update of the BRIGHT trial, which enrolled > 500 patients with indolent or mantle cell lymphoma (9% high risk), the R-Benda group had better PFS than patients on R-CHOP or rituximab plus cyclophosphamide, vincristine, and prednisone (HR, 0.61).

R² is a somewhat newer regimen, Hsu said. Data from the 2018 RELEVANCE study (> 1000 patients) found R² to be nonsuperior to 3 rituximab-plus-chemotherapy regimens but with a lower rate of grade 3-4 neutropenia (32% vs 50% for the other regimens). 

However, R² is “not an FDA-approved regimen in the frontline because it did not demonstrate superiority” over other treatments, Hsu said. 

Selecting the Right Therapy

Which therapy is best? It’s a bit of a wash, Hsu said. 

He noted that R², R-Benda, and another therapy that’s not yet in the VA pathway (R-CHOP) appear to be noninferior to one another, although R-Benda has the edge. R² is better regarding neutropenia risk, although it lacks FDA approval.

“I think about these 3 regimens as appropriate and good,” Hsu said. “It’s nice having 3 wonderful regimens.”

Hsu highlighted the importance of complete remission (CR) as a goal. He pointed to a 2022 analysis of > 5,200 patients that showed progression within 24 months greatly boosted the risk of death vs no-progression (HR, 3.03). Progression within 24 months also lowered estimated 5-year overall survival to 71%.

“Timing really does matter,” Hsu said. “We often worry about transformation to diffuse large B-cell in patients who relapse, particularly this early.”

Second-Line Therapy Options

Two regimens have recently achieved National Comprehensive Cancer Network Category 1 preferred status in the second-line setting, Hsu said, although neither appears in the VA pathway. 

One is tafasitamab plus R², which was shown to extend median PFS to 22.4 months vs 13.9 months for R² alone in the 2026 inMIND study (HR, 0.43), but without an overall survival benefit. 

The other therapy is epcoritamab plus R²: Data from the 2026 EPCORE FL-1 study showed an overall response rate (ORR) of 95% for the combination vs 79% for R² alone and an estimated 16-month PFS of 85.5% for the combination vs 40.2% for R².

Hsu cautioned about the adverse event profile for community infusion centers. The combination carried higher rates of grade ≥ 3 infections (33% vs 16%) and neutropenia (69% vs 42%) compared with R² alone. However, grade ≥ 3 cytokine release syndrome was absent. 

“Stay alert to higher risk for infections and neutropenia here,” Hsu said.

Beyond Second Line: Biospecifics and CAR-T

The biospecifics mosunetuzumab and epcoritamab are now FDA-approved for patients who have relapsed ≥ 2 times. Mosunetuzumab showed ORR of 78% and CR rate of 60% in a 2025 study, while epcoritamab monotherapy showed ORR of 82% and CR of 63% in a 2024 study.

Mosunetuzumab had a 2.2% rate of cytokine release syndrome and a 4.4% rate of immune effector cell-associated neurotoxicity syndrome; epcoritamab had 0% rates of both.

“Think of these 2 options as getting you to the same place, potentially, but maybe with slightly different rates of toxicity,” Hsu said. 

Meanwhile, CAR-T therapy has shown “impressive results for the right patient,” Hsu said. 

Tazemetostat Withdrawn

Hsu noted that tazemetostat, an EZH2 inhibitor that was FDA-approved for relapsed/refractory FL with EZH2 mutations and patients with FL and no satisfactory alternative options, was withdrawn from the market by Eisai in March 2026. The cause of withdrawal was increased rates of secondary hematologic malignancies. 

Meanwhile, patients enrolled in the ongoing SYMPHONY-1 trial will be switched to R².

The withdrawal was “unfortunate,” Hsu said, “but the concept is important. Identifying new targets for therapy and developing those is how we make progress.”

SAN FRANCISCO – The treatment of early-stage diffuse large B-cell lymphoma (DLBCL) is evolving after decades of failed attempts to improve on the standard treatment of R-CHOP (rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisone), a hematologist-oncologist said at the Association of Veterans Affairs (VA) Hematology/Oncology regional meeting on lymphoma on March 21.

A combination therapy known as pola-R-CHP is now the preferred option for many patients but has limited additional benefit, said Solomon A. Graf, MD, of the University of Washington and VA Puget Sound Health Care System. Pola-R-CHP is a modified regimen of R-CHOP that replaced vincristine in R-CHOP with polatuzumab vedotin.

The keys to treatment, Graf said, include consideration of disease variations that can affect therapy efficacy and understanding the special needs of older patients.

Understanding DLBCL

DLBCL is the most common non-Hodgkin lymphoma in the US with about 30,000 new cases per year; the median age at diagnosis is 67 years, Graf said.

“The overall incidence of DLBCL has been relatively stable over the last decades,” he said. “But gratifyingly, the rate of death from this disease has steadily been declining since about the turn of the century.”

Pola-R-CHP: A New Standard, Significant Limitations

From 2002-2022, “many attempts to improve on first-line DLBCL therapy did not pan out,” Graf said, as more than a dozen large phase 3 trials failed to dethrone R-CHOP as the standard. Most of the trials attempted to add an agent to R-CHOP but showed no additional benefit.

Then, in 2021, the landmark POLARIX study was published. The double-blind, randomized trial on the new regime showed a progression-free survival benefit (PFS) vs R-CHOP (76.7% vs 70.2% at 2 years, respectively). Safety profiles were similar between the 2 combination therapies.

However, overall survival (OS) did not differ.

"Pola-R-CHP is now considered a preferred standard, despite no overall survival benefit and despite increased upfront cost,” Graf said. (A 2023 analysis found that pola-R-CHP is more cost-effective than R-CHOP in DLBCL.)

Pola-R-CHP or Not Pola-R-CHP?

Pola-R-CHP is not for all patients with DLBCL. In advanced cases, Graf said, genomic analyses provide important information that helps clinicians understand whether patients will fare better with R-CHOP. Cell-of-origin classifications include germinal center B-cell like (GCB), activated B-cell like (ABC), and unclassifiable.

“If it’s GCB type, there's no clear benefit for Pola-R-CHP,” Graf said. “On the other hand, the ABC subtype does much better when treated with Pola-R-CHP.”

Graf highlighted the recently updated VA Oncology Clinical Pathway for DLBCL, which recommends cell-of-origin testing by the Hans algorithm for certain advanced-stage patients. The guidelines suggest R-CHOP for GCB-type patients and Pola-R-CHP for non–GCB-type patients. However, he cautioned that the Hans algorithm comes with an increased risk of misclassification.

Early-Stage Disease: Radiation or No Radiation?

About 25% to 30% of patients have stage I or II disease, and the landmark 1998 SWOG trial initially suggested that 3 cycles of CHOP plus radiation had superior PFS and OS compared with 8 cycles of CHOP alone, Graf said. This trial was conducted prior to the R-CHOP era. However, follow-up revealed that the benefit vanished over time and the risk of secondary cancers grew. “Both strategies are perfectly viable, but there isn’t as much of a preference anymore,” Graf said.

A pair of recent trials – a 2019 European study and a 2020 US study – support eliminating radiation and lowering the number of cycles of therapy in certain patients, he said.

Managing Older Patients

Patients with DLBCL tend to be older, Graf said, and many have comorbidities and other limitations. A standard course of 6 cycles of therapy may be too much for them, he said. Graf highlighted the Elderly Prognostic Index, a tool created by an Italian group that allows clinicians to predict outcomes based on patient fitness levels.

Graf offered additional guidance for this population:

• Consider corticosteroids in the prephase setting, which can be “very valuable” and improve a patient’s ECOG performance status, “giving you better confidence about proceeding with more standard therapy.”
• Include anthracycline-based therapies such as R-CHOP if appropriate, such as in patients who are focused on living longer, since they “are really crucial to achieving cure in patients with DLBCL.” Graf noted that he has “a low threshold to involve cardiology if there’s anthracycline use and some underlying cardiac comorbidity.”
• Adjust dosage as appropriate: “You can adjust in the middle, be rather flexible and creative about these doses and dosing levels as you get going with your patient and see just what they can tolerate,” he said. “Sometimes you can ramp it up over the course, and sometimes you have to ramp it down to respond to toxicities.”
• Be aware that older patients are at much higher risk of suffering from toxicities due to the vincristine component of R-CHOP. These include neurotoxicities and constipation.

Graf highlighted the phase 3 Polar Bear study, which may offer more insight into therapy options in patients aged ≥ 75 years who are frail or those aged ≥ 80 years. The trial is scheduled to end in early 2027.

Graf discloses relationships with Janssen, TG Therapeutics, BeOne, AstraZeneca, Genentech, Incyte, Eli Lilly, and Pfizer.

SAN FRANCISCO – The treatment of early-stage diffuse large B-cell lymphoma (DLBCL) is evolving after decades of failed attempts to improve on the standard treatment of R-CHOP (rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisone), a hematologist-oncologist said at the Association of Veterans Affairs (VA) Hematology/Oncology regional meeting on lymphoma on March 21.

A combination therapy known as pola-R-CHP is now the preferred option for many patients but has limited additional benefit, said Solomon A. Graf, MD, of the University of Washington and VA Puget Sound Health Care System. Pola-R-CHP is a modified regimen of R-CHOP that replaced vincristine in R-CHOP with polatuzumab vedotin.

The keys to treatment, Graf said, include consideration of disease variations that can affect therapy efficacy and understanding the special needs of older patients.

Understanding DLBCL

DLBCL is the most common non-Hodgkin lymphoma in the US with about 30,000 new cases per year; the median age at diagnosis is 67 years, Graf said.

“The overall incidence of DLBCL has been relatively stable over the last decades,” he said. “But gratifyingly, the rate of death from this disease has steadily been declining since about the turn of the century.”

Pola-R-CHP: A New Standard, Significant Limitations

From 2002-2022, “many attempts to improve on first-line DLBCL therapy did not pan out,” Graf said, as more than a dozen large phase 3 trials failed to dethrone R-CHOP as the standard. Most of the trials attempted to add an agent to R-CHOP but showed no additional benefit.

Then, in 2021, the landmark POLARIX study was published. The double-blind, randomized trial on the new regime showed a progression-free survival benefit (PFS) vs R-CHOP (76.7% vs 70.2% at 2 years, respectively). Safety profiles were similar between the 2 combination therapies.

However, overall survival (OS) did not differ.

"Pola-R-CHP is now considered a preferred standard, despite no overall survival benefit and despite increased upfront cost,” Graf said. (A 2023 analysis found that pola-R-CHP is more cost-effective than R-CHOP in DLBCL.)

Pola-R-CHP or Not Pola-R-CHP?

Pola-R-CHP is not for all patients with DLBCL. In advanced cases, Graf said, genomic analyses provide important information that helps clinicians understand whether patients will fare better with R-CHOP. Cell-of-origin classifications include germinal center B-cell like (GCB), activated B-cell like (ABC), and unclassifiable.

“If it’s GCB type, there's no clear benefit for Pola-R-CHP,” Graf said. “On the other hand, the ABC subtype does much better when treated with Pola-R-CHP.”

Graf highlighted the recently updated VA Oncology Clinical Pathway for DLBCL, which recommends cell-of-origin testing by the Hans algorithm for certain advanced-stage patients. The guidelines suggest R-CHOP for GCB-type patients and Pola-R-CHP for non–GCB-type patients. However, he cautioned that the Hans algorithm comes with an increased risk of misclassification.

Early-Stage Disease: Radiation or No Radiation?

About 25% to 30% of patients have stage I or II disease, and the landmark 1998 SWOG trial initially suggested that 3 cycles of CHOP plus radiation had superior PFS and OS compared with 8 cycles of CHOP alone, Graf said. This trial was conducted prior to the R-CHOP era. However, follow-up revealed that the benefit vanished over time and the risk of secondary cancers grew. “Both strategies are perfectly viable, but there isn’t as much of a preference anymore,” Graf said.

A pair of recent trials – a 2019 European study and a 2020 US study – support eliminating radiation and lowering the number of cycles of therapy in certain patients, he said.

Managing Older Patients

Patients with DLBCL tend to be older, Graf said, and many have comorbidities and other limitations. A standard course of 6 cycles of therapy may be too much for them, he said. Graf highlighted the Elderly Prognostic Index, a tool created by an Italian group that allows clinicians to predict outcomes based on patient fitness levels.

Graf offered additional guidance for this population:

• Consider corticosteroids in the prephase setting, which can be “very valuable” and improve a patient’s ECOG performance status, “giving you better confidence about proceeding with more standard therapy.”
• Include anthracycline-based therapies such as R-CHOP if appropriate, such as in patients who are focused on living longer, since they “are really crucial to achieving cure in patients with DLBCL.” Graf noted that he has “a low threshold to involve cardiology if there’s anthracycline use and some underlying cardiac comorbidity.”
• Adjust dosage as appropriate: “You can adjust in the middle, be rather flexible and creative about these doses and dosing levels as you get going with your patient and see just what they can tolerate,” he said. “Sometimes you can ramp it up over the course, and sometimes you have to ramp it down to respond to toxicities.”
• Be aware that older patients are at much higher risk of suffering from toxicities due to the vincristine component of R-CHOP. These include neurotoxicities and constipation.

Graf highlighted the phase 3 Polar Bear study, which may offer more insight into therapy options in patients aged ≥ 75 years who are frail or those aged ≥ 80 years. The trial is scheduled to end in early 2027.

Graf discloses relationships with Janssen, TG Therapeutics, BeOne, AstraZeneca, Genentech, Incyte, Eli Lilly, and Pfizer.

SAN FRANCISCO – The treatment of early-stage diffuse large B-cell lymphoma (DLBCL) is evolving after decades of failed attempts to improve on the standard treatment of R-CHOP (rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisone), a hematologist-oncologist said at the Association of Veterans Affairs (VA) Hematology/Oncology regional meeting on lymphoma on March 21.

A combination therapy known as pola-R-CHP is now the preferred option for many patients but has limited additional benefit, said Solomon A. Graf, MD, of the University of Washington and VA Puget Sound Health Care System. Pola-R-CHP is a modified regimen of R-CHOP that replaced vincristine in R-CHOP with polatuzumab vedotin.

The keys to treatment, Graf said, include consideration of disease variations that can affect therapy efficacy and understanding the special needs of older patients.

Understanding DLBCL

DLBCL is the most common non-Hodgkin lymphoma in the US with about 30,000 new cases per year; the median age at diagnosis is 67 years, Graf said.

“The overall incidence of DLBCL has been relatively stable over the last decades,” he said. “But gratifyingly, the rate of death from this disease has steadily been declining since about the turn of the century.”

Pola-R-CHP: A New Standard, Significant Limitations

From 2002-2022, “many attempts to improve on first-line DLBCL therapy did not pan out,” Graf said, as more than a dozen large phase 3 trials failed to dethrone R-CHOP as the standard. Most of the trials attempted to add an agent to R-CHOP but showed no additional benefit.

Then, in 2021, the landmark POLARIX study was published. The double-blind, randomized trial on the new regime showed a progression-free survival benefit (PFS) vs R-CHOP (76.7% vs 70.2% at 2 years, respectively). Safety profiles were similar between the 2 combination therapies.

However, overall survival (OS) did not differ.

"Pola-R-CHP is now considered a preferred standard, despite no overall survival benefit and despite increased upfront cost,” Graf said. (A 2023 analysis found that pola-R-CHP is more cost-effective than R-CHOP in DLBCL.)

Pola-R-CHP or Not Pola-R-CHP?

Pola-R-CHP is not for all patients with DLBCL. In advanced cases, Graf said, genomic analyses provide important information that helps clinicians understand whether patients will fare better with R-CHOP. Cell-of-origin classifications include germinal center B-cell like (GCB), activated B-cell like (ABC), and unclassifiable.

“If it’s GCB type, there's no clear benefit for Pola-R-CHP,” Graf said. “On the other hand, the ABC subtype does much better when treated with Pola-R-CHP.”

Graf highlighted the recently updated VA Oncology Clinical Pathway for DLBCL, which recommends cell-of-origin testing by the Hans algorithm for certain advanced-stage patients. The guidelines suggest R-CHOP for GCB-type patients and Pola-R-CHP for non–GCB-type patients. However, he cautioned that the Hans algorithm comes with an increased risk of misclassification.

Early-Stage Disease: Radiation or No Radiation?

About 25% to 30% of patients have stage I or II disease, and the landmark 1998 SWOG trial initially suggested that 3 cycles of CHOP plus radiation had superior PFS and OS compared with 8 cycles of CHOP alone, Graf said. This trial was conducted prior to the R-CHOP era. However, follow-up revealed that the benefit vanished over time and the risk of secondary cancers grew. “Both strategies are perfectly viable, but there isn’t as much of a preference anymore,” Graf said.

A pair of recent trials – a 2019 European study and a 2020 US study – support eliminating radiation and lowering the number of cycles of therapy in certain patients, he said.

Managing Older Patients

Patients with DLBCL tend to be older, Graf said, and many have comorbidities and other limitations. A standard course of 6 cycles of therapy may be too much for them, he said. Graf highlighted the Elderly Prognostic Index, a tool created by an Italian group that allows clinicians to predict outcomes based on patient fitness levels.

Graf offered additional guidance for this population:

• Consider corticosteroids in the prephase setting, which can be “very valuable” and improve a patient’s ECOG performance status, “giving you better confidence about proceeding with more standard therapy.”
• Include anthracycline-based therapies such as R-CHOP if appropriate, such as in patients who are focused on living longer, since they “are really crucial to achieving cure in patients with DLBCL.” Graf noted that he has “a low threshold to involve cardiology if there’s anthracycline use and some underlying cardiac comorbidity.”
• Adjust dosage as appropriate: “You can adjust in the middle, be rather flexible and creative about these doses and dosing levels as you get going with your patient and see just what they can tolerate,” he said. “Sometimes you can ramp it up over the course, and sometimes you have to ramp it down to respond to toxicities.”
• Be aware that older patients are at much higher risk of suffering from toxicities due to the vincristine component of R-CHOP. These include neurotoxicities and constipation.

Graf highlighted the phase 3 Polar Bear study, which may offer more insight into therapy options in patients aged ≥ 75 years who are frail or those aged ≥ 80 years. The trial is scheduled to end in early 2027.

Graf discloses relationships with Janssen, TG Therapeutics, BeOne, AstraZeneca, Genentech, Incyte, Eli Lilly, and Pfizer.

TOPLINE:

Among 1.3 million male veterans treated for prostate cancer, 11,327 (0.86%) developed breast cancer an average of 5.4 years after initial diagnosis. Younger age at prostate cancer diagnosis, metastatic disease, androgen deprivation therapy (ADT), radiation treatment, and prolonged use of certain cardiovascular disease (CVD) medications were associated with increased risk for breast cancer.

METHODOLOGY:

• Researchers used a retrospective cohort design in Veterans Health Administration (VHA) care, pulling data from the Veterans Affairs (VA) Prostate Cancer Data Core at the VA Corporate Data Warehouse.
• Participants included 1,314,492 male veterans with prostate cancer treated at VHA facilities from January 1, 2000, to March 12, 2024.
• Exposure definitions included prostate cancer treatments (ADT, anti-androgen treatment, radiation-brachytherapy, and platinum chemotherapy) and CVD medications (furosemide, spironolactone, digoxin) captured via inpatient/outpatient/fee-based pharmacy and Current Procedural Terminology codes.
• Analysis measured time from prostate cancer diagnosis to breast cancer diagnosis, death, or March 12, 2024, applying Cox proportional hazards and Fine-Gray competing risk methods, with a sensitivity analysis adding body mass index (BMI) after excluding 71,718 missing values.

TAKEAWAY:

• Metastatic prostate cancer at diagnosis more than doubled the risk for breast cancer compared to nonmetastatic disease (hazard ratio [HR], 2.03; 95% CI, 1.90-2.17; P < .0001; subdistribution hazard ratio [SHR], 1.68; 95% CI, 1.57-1.81; P < .0001).
• Younger age at prostate cancer diagnosis was associated with increased risk for breast cancer (HR, 0.97; 95% CI, 0.97-0.98; P < .0001; SHR, 0.957; 95% CI, 0.955-0.959; P < .0001), indicating that for each additional year of age at diagnosis, the risk decreased.
• Continuation of CVD medications after prostate cancer diagnosis was associated with increased risk for breast cancer: furosemide (HR, 1.51; 95% CI, 1.39-1.63; P < .0001; SHR, 1.21; 95% CI, 1.12-1.31; P < .0001), spironolactone (HR, 1.36; 95% CI, 1.15-1.61; P = .0004; SHR, 1.23; 95% CI, 1.04-1.47; P = .0174), and digoxin (HR, 1.49; 95% CI, 1.29-1.72; P < .0001; SHR, 1.26; 95% CI, 1.10-1.46; P = .0015).
• Radiation therapy and ADT were associated with increased risk for breast cancer (radiation: HR, 1.06; 95% CI, 1.02-1.11; P = .0088; SHR, 1.10; 95% CI, 1.05-1.15; P < .0001; ADT: HR, 1.24; 95% CI, 1.17-1.32; P < .0001; SHR, 1.28; 95% CI, 1.20-1.37; P < .0001), while abiraterone was associated with decreased risk (HR, 0.36; 95% CI, 0.31-0.42; P < .0001; SHR, 0.39; 95% CI, 0.34-0.45; P < .0001).

IN PRACTICE:

"While there is a lack of data, male veterans with previous prostate cancer are at an elevated risk of breast cancer (0.87%), than their civilian counterparts (0.14%),” the authors wrote. “To address the current gap in knowledge and data, this study leveraged an existing large cohort of male veterans with prostate cancer and examined factors associated with increased risk of male breast cancer."

SOURCE:

The study was led by Erum Z. Whyne, VA North Texas Health Care System in Dallas, and Haekyung Jeon-Slaughter, University of Texas Southwestern Medical Center in Dallas. It was published online in The Prostate.

LIMITATIONS:

Though the study findings are based on large, representative data from male veterans with previously diagnosed prostate cancer, the results might not be generalizable to the overall male breast cancer population. As a retrospective cohort study, results may be biased and causality is difficult to establish. The study did not examine other known risk factors for male breast cancer incidence, such as family history, BRCA2 mutations, and military environmental exposure due to lack of data. BMI had missingness of 5.46% (n = 71,718) and was not included as a covariate in the final model, though sensitivity analysis showed it was not significantly associated with increased risk for male breast cancer.

DISCLOSURES:

The research was supported using resources and facilities of the VA Informatics and Computing Infrastructure (VINCI), VA HSR RES 13-457. The VA North Texas Health Care System Institutional Review Board approved the study and waived informed consent. No conflicts of interest were disclosed by the authors.

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

TOPLINE:

Among 1.3 million male veterans treated for prostate cancer, 11,327 (0.86%) developed breast cancer an average of 5.4 years after initial diagnosis. Younger age at prostate cancer diagnosis, metastatic disease, androgen deprivation therapy (ADT), radiation treatment, and prolonged use of certain cardiovascular disease (CVD) medications were associated with increased risk for breast cancer.

METHODOLOGY:

• Researchers used a retrospective cohort design in Veterans Health Administration (VHA) care, pulling data from the Veterans Affairs (VA) Prostate Cancer Data Core at the VA Corporate Data Warehouse.
• Participants included 1,314,492 male veterans with prostate cancer treated at VHA facilities from January 1, 2000, to March 12, 2024.
• Exposure definitions included prostate cancer treatments (ADT, anti-androgen treatment, radiation-brachytherapy, and platinum chemotherapy) and CVD medications (furosemide, spironolactone, digoxin) captured via inpatient/outpatient/fee-based pharmacy and Current Procedural Terminology codes.
• Analysis measured time from prostate cancer diagnosis to breast cancer diagnosis, death, or March 12, 2024, applying Cox proportional hazards and Fine-Gray competing risk methods, with a sensitivity analysis adding body mass index (BMI) after excluding 71,718 missing values.

TAKEAWAY:

• Metastatic prostate cancer at diagnosis more than doubled the risk for breast cancer compared to nonmetastatic disease (hazard ratio [HR], 2.03; 95% CI, 1.90-2.17; P < .0001; subdistribution hazard ratio [SHR], 1.68; 95% CI, 1.57-1.81; P < .0001).
• Younger age at prostate cancer diagnosis was associated with increased risk for breast cancer (HR, 0.97; 95% CI, 0.97-0.98; P < .0001; SHR, 0.957; 95% CI, 0.955-0.959; P < .0001), indicating that for each additional year of age at diagnosis, the risk decreased.
• Continuation of CVD medications after prostate cancer diagnosis was associated with increased risk for breast cancer: furosemide (HR, 1.51; 95% CI, 1.39-1.63; P < .0001; SHR, 1.21; 95% CI, 1.12-1.31; P < .0001), spironolactone (HR, 1.36; 95% CI, 1.15-1.61; P = .0004; SHR, 1.23; 95% CI, 1.04-1.47; P = .0174), and digoxin (HR, 1.49; 95% CI, 1.29-1.72; P < .0001; SHR, 1.26; 95% CI, 1.10-1.46; P = .0015).
• Radiation therapy and ADT were associated with increased risk for breast cancer (radiation: HR, 1.06; 95% CI, 1.02-1.11; P = .0088; SHR, 1.10; 95% CI, 1.05-1.15; P < .0001; ADT: HR, 1.24; 95% CI, 1.17-1.32; P < .0001; SHR, 1.28; 95% CI, 1.20-1.37; P < .0001), while abiraterone was associated with decreased risk (HR, 0.36; 95% CI, 0.31-0.42; P < .0001; SHR, 0.39; 95% CI, 0.34-0.45; P < .0001).

IN PRACTICE:

"While there is a lack of data, male veterans with previous prostate cancer are at an elevated risk of breast cancer (0.87%), than their civilian counterparts (0.14%),” the authors wrote. “To address the current gap in knowledge and data, this study leveraged an existing large cohort of male veterans with prostate cancer and examined factors associated with increased risk of male breast cancer."

SOURCE:

The study was led by Erum Z. Whyne, VA North Texas Health Care System in Dallas, and Haekyung Jeon-Slaughter, University of Texas Southwestern Medical Center in Dallas. It was published online in The Prostate.

LIMITATIONS:

Though the study findings are based on large, representative data from male veterans with previously diagnosed prostate cancer, the results might not be generalizable to the overall male breast cancer population. As a retrospective cohort study, results may be biased and causality is difficult to establish. The study did not examine other known risk factors for male breast cancer incidence, such as family history, BRCA2 mutations, and military environmental exposure due to lack of data. BMI had missingness of 5.46% (n = 71,718) and was not included as a covariate in the final model, though sensitivity analysis showed it was not significantly associated with increased risk for male breast cancer.

DISCLOSURES:

The research was supported using resources and facilities of the VA Informatics and Computing Infrastructure (VINCI), VA HSR RES 13-457. The VA North Texas Health Care System Institutional Review Board approved the study and waived informed consent. No conflicts of interest were disclosed by the authors.

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

TOPLINE:

Among 1.3 million male veterans treated for prostate cancer, 11,327 (0.86%) developed breast cancer an average of 5.4 years after initial diagnosis. Younger age at prostate cancer diagnosis, metastatic disease, androgen deprivation therapy (ADT), radiation treatment, and prolonged use of certain cardiovascular disease (CVD) medications were associated with increased risk for breast cancer.

METHODOLOGY:

• Researchers used a retrospective cohort design in Veterans Health Administration (VHA) care, pulling data from the Veterans Affairs (VA) Prostate Cancer Data Core at the VA Corporate Data Warehouse.
• Participants included 1,314,492 male veterans with prostate cancer treated at VHA facilities from January 1, 2000, to March 12, 2024.
• Exposure definitions included prostate cancer treatments (ADT, anti-androgen treatment, radiation-brachytherapy, and platinum chemotherapy) and CVD medications (furosemide, spironolactone, digoxin) captured via inpatient/outpatient/fee-based pharmacy and Current Procedural Terminology codes.
• Analysis measured time from prostate cancer diagnosis to breast cancer diagnosis, death, or March 12, 2024, applying Cox proportional hazards and Fine-Gray competing risk methods, with a sensitivity analysis adding body mass index (BMI) after excluding 71,718 missing values.

TAKEAWAY:

• Metastatic prostate cancer at diagnosis more than doubled the risk for breast cancer compared to nonmetastatic disease (hazard ratio [HR], 2.03; 95% CI, 1.90-2.17; P < .0001; subdistribution hazard ratio [SHR], 1.68; 95% CI, 1.57-1.81; P < .0001).
• Younger age at prostate cancer diagnosis was associated with increased risk for breast cancer (HR, 0.97; 95% CI, 0.97-0.98; P < .0001; SHR, 0.957; 95% CI, 0.955-0.959; P < .0001), indicating that for each additional year of age at diagnosis, the risk decreased.
• Continuation of CVD medications after prostate cancer diagnosis was associated with increased risk for breast cancer: furosemide (HR, 1.51; 95% CI, 1.39-1.63; P < .0001; SHR, 1.21; 95% CI, 1.12-1.31; P < .0001), spironolactone (HR, 1.36; 95% CI, 1.15-1.61; P = .0004; SHR, 1.23; 95% CI, 1.04-1.47; P = .0174), and digoxin (HR, 1.49; 95% CI, 1.29-1.72; P < .0001; SHR, 1.26; 95% CI, 1.10-1.46; P = .0015).
• Radiation therapy and ADT were associated with increased risk for breast cancer (radiation: HR, 1.06; 95% CI, 1.02-1.11; P = .0088; SHR, 1.10; 95% CI, 1.05-1.15; P < .0001; ADT: HR, 1.24; 95% CI, 1.17-1.32; P < .0001; SHR, 1.28; 95% CI, 1.20-1.37; P < .0001), while abiraterone was associated with decreased risk (HR, 0.36; 95% CI, 0.31-0.42; P < .0001; SHR, 0.39; 95% CI, 0.34-0.45; P < .0001).

IN PRACTICE:

"While there is a lack of data, male veterans with previous prostate cancer are at an elevated risk of breast cancer (0.87%), than their civilian counterparts (0.14%),” the authors wrote. “To address the current gap in knowledge and data, this study leveraged an existing large cohort of male veterans with prostate cancer and examined factors associated with increased risk of male breast cancer."

SOURCE:

The study was led by Erum Z. Whyne, VA North Texas Health Care System in Dallas, and Haekyung Jeon-Slaughter, University of Texas Southwestern Medical Center in Dallas. It was published online in The Prostate.

LIMITATIONS:

Though the study findings are based on large, representative data from male veterans with previously diagnosed prostate cancer, the results might not be generalizable to the overall male breast cancer population. As a retrospective cohort study, results may be biased and causality is difficult to establish. The study did not examine other known risk factors for male breast cancer incidence, such as family history, BRCA2 mutations, and military environmental exposure due to lack of data. BMI had missingness of 5.46% (n = 71,718) and was not included as a covariate in the final model, though sensitivity analysis showed it was not significantly associated with increased risk for male breast cancer.

DISCLOSURES:

The research was supported using resources and facilities of the VA Informatics and Computing Infrastructure (VINCI), VA HSR RES 13-457. The VA North Texas Health Care System Institutional Review Board approved the study and waived informed consent. No conflicts of interest were disclosed by the authors.

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

Mostly it is loss that teaches us about the worth of things.
Arthur Schopenhauer¹

One of the leaders I most respected in my US Department of Veterans Affairs (VA) career was a man who had worked his way up through the ranks to become a medical center director. Usually calm, cool, and collected, he would wax poetic when discussing the hero of the VA Health Care System revolution, Ken Kizer, MD, MPH.

In this issue of Federal Practitioner, journalist Randy Dotinga interviews Kizer about the current challenges facing the VA. Though many readers will have participated in or at least know about Kizer’s unprecedented overhaul of the agency, many others, especially those new to VA, may not. It seemed a fitting time to offer an outline of the immense and positive accomplishments that occurred in the agency during his tenure, especially as, under the current administration, many of his most forward-thinking initiatives seem to be moving backward.²

When President Clinton nominated Kizer to serve as the Under Secretary for Health for the Veterans Health Administration in 1994, the poor quality care the agency delivered was castigated in popular movies like Born on the Fourth of July. Veterans who were seen in that era, and who eventually returned to a far better, kinder VA thanks to Kizer, would often tell me, “Doc, the VA was really bad then, and I was afraid to come back.” The critique of VA health care in the mid-1990s sounds like a bureaucratic déjà vu of many of the concerns Kizer raised in his interview, including fragmentation of care, access barriers, and poor coordination of treatment.³

If anyone was prepared and qualified to take on this seeming mission impossible, it was Kizer. A US Navy veteran with 6 board certifications, he came to the VA following a brave and innovative stint as the top health official in California, where he successfully took on the tobacco lobby and dramatically reduced the state’s rates of smoking and related diseases.⁴

Long before it was the subject of reality TV shows, Kizer dubbed his major renovation of the VA’s antiquated structure an “extreme makeover.”³ Though this description is an oversimplification of Kizer’s monumental efforts, the makeover can be considered in 4 to 6 buckets, depending on how various health policy experts parse the re-engineering efforts.^5-7

Decentralization. Kizer instituted the Veterans Integrated Service Network (VISN) system to coordinate the management and operations of all the hospitals, clinics, and other VA health care entities in what is roughly a region. The locus of decision-making shifted from the VA Central Office to the VISNs, intended to promote more efficient, economical, and streamlined health care delivery.

Capitation. Accompanying this restructuring was a shift to a capitated system focused on preventive care. The Veterans Equitable Resource Allocation system was designed to logically link workload and funding. This was a major shift away from VA’s previous emphasis on inpatient and specialty care and resulted in the closing of multiple hospitals.⁴

Information Systems. I can still remember the first time I sat down at a prehistoric computer to use the Computerized Patient Record System (CPRS). Though now much maligned, then it was like something out of Star Trek, at a time when almost every other health care institution was buried in paper charts. With CPRS, VA suddenly had a pioneering and much-envied electronic medical record that facilitated continuity of care, communication between professionals, and accuracy and completeness of documentation.

Data Driven Performance Improvement. The VISNs and information systems inaugurated a new era of data-driven quality improvement. The assembly and analysis of data enabled VISNs to have real-time input about comparative facility performance.

Performance Measures. The data enabled evidence-based performance measures to be developed and monitored. Though these have now become the bane of many Federal Practitioner readers’ existence, they were originally intended for VISN directors and members of the senior executive service at VA central office. These were tied to incentives that, though recently the subject of watchdog investigation, were intended to motivate and reward high-quality care.⁶

Even this cursory look at Kizer’s accomplishments is more than enough to demonstrate the magnitude of the makeover, and when the time frame of the achievements is factored in, the transformation is the equivalent of a planet changing its orbit at light speed. Rhetoric aside, there are now hundreds of research articles published in top medical and health policy journals, many of them authored by Kizer,^7,8 that have amply demonstrated that when he departed the VA in 1999, it had become “the best care anywhere.” ⁹ For example, a 2000 New England Journal of Medicine article found that from 1994 to 2000, the percentage of veterans whose care met ≥ 90% of 9 of 17 quality standards was > 70% for 13 of the measures, outperforming fee-for-service Medicare.¹⁰

There had been uncertainty about whether Kizer would seek a second term as Under Secretary when he announced that he was leaving. With concise modesty, Kizer said he had met his charge to, “re-engineer the veterans’ health care system so that it could effectively function in the 21^st century.”¹¹

Despite openly and critically discussing the many difficulties the VA currently confronts, Kizer ends his interview on a note of hope. Since he likely knows more about VA than any person alive, we need to trust his judgment that his legacy, which currently seems more in jeopardy than ever before, will somehow prevail. Perhaps I am too melancholic, but I believe it will take a professional of the stature of Dr. Kizer to take us back to that future, and I fear we will not see his likes again.

Mostly it is loss that teaches us about the worth of things.
Arthur Schopenhauer¹

One of the leaders I most respected in my US Department of Veterans Affairs (VA) career was a man who had worked his way up through the ranks to become a medical center director. Usually calm, cool, and collected, he would wax poetic when discussing the hero of the VA Health Care System revolution, Ken Kizer, MD, MPH.

In this issue of Federal Practitioner, journalist Randy Dotinga interviews Kizer about the current challenges facing the VA. Though many readers will have participated in or at least know about Kizer’s unprecedented overhaul of the agency, many others, especially those new to VA, may not. It seemed a fitting time to offer an outline of the immense and positive accomplishments that occurred in the agency during his tenure, especially as, under the current administration, many of his most forward-thinking initiatives seem to be moving backward.²

When President Clinton nominated Kizer to serve as the Under Secretary for Health for the Veterans Health Administration in 1994, the poor quality care the agency delivered was castigated in popular movies like Born on the Fourth of July. Veterans who were seen in that era, and who eventually returned to a far better, kinder VA thanks to Kizer, would often tell me, “Doc, the VA was really bad then, and I was afraid to come back.” The critique of VA health care in the mid-1990s sounds like a bureaucratic déjà vu of many of the concerns Kizer raised in his interview, including fragmentation of care, access barriers, and poor coordination of treatment.³

If anyone was prepared and qualified to take on this seeming mission impossible, it was Kizer. A US Navy veteran with 6 board certifications, he came to the VA following a brave and innovative stint as the top health official in California, where he successfully took on the tobacco lobby and dramatically reduced the state’s rates of smoking and related diseases.⁴

Long before it was the subject of reality TV shows, Kizer dubbed his major renovation of the VA’s antiquated structure an “extreme makeover.”³ Though this description is an oversimplification of Kizer’s monumental efforts, the makeover can be considered in 4 to 6 buckets, depending on how various health policy experts parse the re-engineering efforts.^5-7

Decentralization. Kizer instituted the Veterans Integrated Service Network (VISN) system to coordinate the management and operations of all the hospitals, clinics, and other VA health care entities in what is roughly a region. The locus of decision-making shifted from the VA Central Office to the VISNs, intended to promote more efficient, economical, and streamlined health care delivery.

Capitation. Accompanying this restructuring was a shift to a capitated system focused on preventive care. The Veterans Equitable Resource Allocation system was designed to logically link workload and funding. This was a major shift away from VA’s previous emphasis on inpatient and specialty care and resulted in the closing of multiple hospitals.⁴

Information Systems. I can still remember the first time I sat down at a prehistoric computer to use the Computerized Patient Record System (CPRS). Though now much maligned, then it was like something out of Star Trek, at a time when almost every other health care institution was buried in paper charts. With CPRS, VA suddenly had a pioneering and much-envied electronic medical record that facilitated continuity of care, communication between professionals, and accuracy and completeness of documentation.

Data Driven Performance Improvement. The VISNs and information systems inaugurated a new era of data-driven quality improvement. The assembly and analysis of data enabled VISNs to have real-time input about comparative facility performance.

Performance Measures. The data enabled evidence-based performance measures to be developed and monitored. Though these have now become the bane of many Federal Practitioner readers’ existence, they were originally intended for VISN directors and members of the senior executive service at VA central office. These were tied to incentives that, though recently the subject of watchdog investigation, were intended to motivate and reward high-quality care.⁶

Even this cursory look at Kizer’s accomplishments is more than enough to demonstrate the magnitude of the makeover, and when the time frame of the achievements is factored in, the transformation is the equivalent of a planet changing its orbit at light speed. Rhetoric aside, there are now hundreds of research articles published in top medical and health policy journals, many of them authored by Kizer,^7,8 that have amply demonstrated that when he departed the VA in 1999, it had become “the best care anywhere.” ⁹ For example, a 2000 New England Journal of Medicine article found that from 1994 to 2000, the percentage of veterans whose care met ≥ 90% of 9 of 17 quality standards was > 70% for 13 of the measures, outperforming fee-for-service Medicare.¹⁰

There had been uncertainty about whether Kizer would seek a second term as Under Secretary when he announced that he was leaving. With concise modesty, Kizer said he had met his charge to, “re-engineer the veterans’ health care system so that it could effectively function in the 21^st century.”¹¹

Despite openly and critically discussing the many difficulties the VA currently confronts, Kizer ends his interview on a note of hope. Since he likely knows more about VA than any person alive, we need to trust his judgment that his legacy, which currently seems more in jeopardy than ever before, will somehow prevail. Perhaps I am too melancholic, but I believe it will take a professional of the stature of Dr. Kizer to take us back to that future, and I fear we will not see his likes again.

Mostly it is loss that teaches us about the worth of things.
Arthur Schopenhauer¹

One of the leaders I most respected in my US Department of Veterans Affairs (VA) career was a man who had worked his way up through the ranks to become a medical center director. Usually calm, cool, and collected, he would wax poetic when discussing the hero of the VA Health Care System revolution, Ken Kizer, MD, MPH.

In this issue of Federal Practitioner, journalist Randy Dotinga interviews Kizer about the current challenges facing the VA. Though many readers will have participated in or at least know about Kizer’s unprecedented overhaul of the agency, many others, especially those new to VA, may not. It seemed a fitting time to offer an outline of the immense and positive accomplishments that occurred in the agency during his tenure, especially as, under the current administration, many of his most forward-thinking initiatives seem to be moving backward.²

When President Clinton nominated Kizer to serve as the Under Secretary for Health for the Veterans Health Administration in 1994, the poor quality care the agency delivered was castigated in popular movies like Born on the Fourth of July. Veterans who were seen in that era, and who eventually returned to a far better, kinder VA thanks to Kizer, would often tell me, “Doc, the VA was really bad then, and I was afraid to come back.” The critique of VA health care in the mid-1990s sounds like a bureaucratic déjà vu of many of the concerns Kizer raised in his interview, including fragmentation of care, access barriers, and poor coordination of treatment.³

If anyone was prepared and qualified to take on this seeming mission impossible, it was Kizer. A US Navy veteran with 6 board certifications, he came to the VA following a brave and innovative stint as the top health official in California, where he successfully took on the tobacco lobby and dramatically reduced the state’s rates of smoking and related diseases.⁴

Long before it was the subject of reality TV shows, Kizer dubbed his major renovation of the VA’s antiquated structure an “extreme makeover.”³ Though this description is an oversimplification of Kizer’s monumental efforts, the makeover can be considered in 4 to 6 buckets, depending on how various health policy experts parse the re-engineering efforts.^5-7

Decentralization. Kizer instituted the Veterans Integrated Service Network (VISN) system to coordinate the management and operations of all the hospitals, clinics, and other VA health care entities in what is roughly a region. The locus of decision-making shifted from the VA Central Office to the VISNs, intended to promote more efficient, economical, and streamlined health care delivery.

Capitation. Accompanying this restructuring was a shift to a capitated system focused on preventive care. The Veterans Equitable Resource Allocation system was designed to logically link workload and funding. This was a major shift away from VA’s previous emphasis on inpatient and specialty care and resulted in the closing of multiple hospitals.⁴

Information Systems. I can still remember the first time I sat down at a prehistoric computer to use the Computerized Patient Record System (CPRS). Though now much maligned, then it was like something out of Star Trek, at a time when almost every other health care institution was buried in paper charts. With CPRS, VA suddenly had a pioneering and much-envied electronic medical record that facilitated continuity of care, communication between professionals, and accuracy and completeness of documentation.

Data Driven Performance Improvement. The VISNs and information systems inaugurated a new era of data-driven quality improvement. The assembly and analysis of data enabled VISNs to have real-time input about comparative facility performance.

Performance Measures. The data enabled evidence-based performance measures to be developed and monitored. Though these have now become the bane of many Federal Practitioner readers’ existence, they were originally intended for VISN directors and members of the senior executive service at VA central office. These were tied to incentives that, though recently the subject of watchdog investigation, were intended to motivate and reward high-quality care.⁶

Even this cursory look at Kizer’s accomplishments is more than enough to demonstrate the magnitude of the makeover, and when the time frame of the achievements is factored in, the transformation is the equivalent of a planet changing its orbit at light speed. Rhetoric aside, there are now hundreds of research articles published in top medical and health policy journals, many of them authored by Kizer,^7,8 that have amply demonstrated that when he departed the VA in 1999, it had become “the best care anywhere.” ⁹ For example, a 2000 New England Journal of Medicine article found that from 1994 to 2000, the percentage of veterans whose care met ≥ 90% of 9 of 17 quality standards was > 70% for 13 of the measures, outperforming fee-for-service Medicare.¹⁰

There had been uncertainty about whether Kizer would seek a second term as Under Secretary when he announced that he was leaving. With concise modesty, Kizer said he had met his charge to, “re-engineer the veterans’ health care system so that it could effectively function in the 21^st century.”¹¹

Despite openly and critically discussing the many difficulties the VA currently confronts, Kizer ends his interview on a note of hope. Since he likely knows more about VA than any person alive, we need to trust his judgment that his legacy, which currently seems more in jeopardy than ever before, will somehow prevail. Perhaps I am too melancholic, but I believe it will take a professional of the stature of Dr. Kizer to take us back to that future, and I fear we will not see his likes again.

TOPLINE:

Among adults with obesity, nonsurgical weight loss was significantly associated with reduced odds for developing obesity-related and other cancers at 3 and 5 years, a study of real-world data found.

METHODOLOGY:

• Although weight loss after bariatric surgery is linked to a reduced risk for cancer, the effect of nonsurgical weight loss on cancer risk remains unclear.
• Researchers conducted a retrospective observational study using electronic health record data from a US health system to assess the association between nonsurgical weight loss and the risk for cancer among adults with obesity.
• The inclusion criteria were age of ≥ 20 years, BMI > 30, and at least seven health system visits over 3 years. Patients with a history of alcohol or substance abuse, amputations, HIV infection, organ transplant, thyroid problems, or those who underwent bariatric surgery were excluded.
• The 143,630 patients who met inclusion criteria (7703 cancer cases and 135,927 controls) were divided into 3 cohorts based on weight change over time intervals of 3 years (115,942 patients), 5 years (105,472 patients), and 10 years (59,112 patients).
• Primary endpoints included obesity-related cancers (esophageal cancer, liver cancer, gallbladder cancer, pancreatic cancer, colorectal cancer, renal cell carcinoma, endometrial cancer, multiple myeloma, and postmenopausal breast cancer), and secondary endpoints included all malignant neoplasms.

TAKEAWAY:

• Each 1% reduction in BMI was associated with reduced odds of obesity-related cancers at 3 years and 5 years (odds ratio [OR], 0.99 and 0.989, respectively; P < .001 for both). These results translate to 5% weight loss corresponding to 4.9% and 5.4% reductions in obesity-related cancer odds at 3 and 5 years, respectively.
• Weight loss was associated with reduced odds of endometrial cancer at 3, 5, and 10 years (OR, 0.978; P < .05), of renal cell carcinoma at 3 and 5 years (OR, 0.983; P < .05), and of multiple myeloma at 10 years (OR, 0.969; P = .004).
• Weight loss was also associated with reduced odds of developing any malignancy at 3 years (OR, 0.992), 5 years (OR, 0.994), and 10 years (OR, 0.991; P = .001 for all). These results translate into a 5% weight loss corresponding to 3.9%, 3%, and 4.4% lower odds of any malignancy at 3, 5, and 10 years, respectively.

IN PRACTICE:

"Real-world weight loss was associated with a decreased risk of developing obesity-related cancers and all other cancers. Our study serves as a call for action and a strong public health message to healthcare stakeholders to intensify efforts and resources to treat obesity as a chronic disease to help reduce the risk of developing cancer," the author wrote.

SOURCE:

This study, led by endocrinologist Kenda Alkwatli, MD, Starling Physicians, Wethersfield, Connecticut, was published online in Obesity.

LIMITATIONS:

The study included only individuals with sufficient longitudinal health records, which may have introduced selection bias. It could not distinguish between intentional and unintentional weight loss or differentiate between fat and lean mass. Due to its observational nature, the study could not assess whether weight loss preceding cancer diagnosis was related to delay in diagnosis.

DISCLOSURES:

The study was funded in part by the Cleveland Clinic Center for Quantitative Metabolic Research. Three authors reported receiving research funding, consulting fees, honoraria, grants, or research support and holding patent applications, license agreements, leadership roles, or equity in healthcare and biotechnology companies.

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:

Among adults with obesity, nonsurgical weight loss was significantly associated with reduced odds for developing obesity-related and other cancers at 3 and 5 years, a study of real-world data found.

METHODOLOGY:

• Although weight loss after bariatric surgery is linked to a reduced risk for cancer, the effect of nonsurgical weight loss on cancer risk remains unclear.
• Researchers conducted a retrospective observational study using electronic health record data from a US health system to assess the association between nonsurgical weight loss and the risk for cancer among adults with obesity.
• The inclusion criteria were age of ≥ 20 years, BMI > 30, and at least seven health system visits over 3 years. Patients with a history of alcohol or substance abuse, amputations, HIV infection, organ transplant, thyroid problems, or those who underwent bariatric surgery were excluded.
• The 143,630 patients who met inclusion criteria (7703 cancer cases and 135,927 controls) were divided into 3 cohorts based on weight change over time intervals of 3 years (115,942 patients), 5 years (105,472 patients), and 10 years (59,112 patients).
• Primary endpoints included obesity-related cancers (esophageal cancer, liver cancer, gallbladder cancer, pancreatic cancer, colorectal cancer, renal cell carcinoma, endometrial cancer, multiple myeloma, and postmenopausal breast cancer), and secondary endpoints included all malignant neoplasms.

TAKEAWAY:

• Each 1% reduction in BMI was associated with reduced odds of obesity-related cancers at 3 years and 5 years (odds ratio [OR], 0.99 and 0.989, respectively; P < .001 for both). These results translate to 5% weight loss corresponding to 4.9% and 5.4% reductions in obesity-related cancer odds at 3 and 5 years, respectively.
• Weight loss was associated with reduced odds of endometrial cancer at 3, 5, and 10 years (OR, 0.978; P < .05), of renal cell carcinoma at 3 and 5 years (OR, 0.983; P < .05), and of multiple myeloma at 10 years (OR, 0.969; P = .004).
• Weight loss was also associated with reduced odds of developing any malignancy at 3 years (OR, 0.992), 5 years (OR, 0.994), and 10 years (OR, 0.991; P = .001 for all). These results translate into a 5% weight loss corresponding to 3.9%, 3%, and 4.4% lower odds of any malignancy at 3, 5, and 10 years, respectively.

IN PRACTICE:

"Real-world weight loss was associated with a decreased risk of developing obesity-related cancers and all other cancers. Our study serves as a call for action and a strong public health message to healthcare stakeholders to intensify efforts and resources to treat obesity as a chronic disease to help reduce the risk of developing cancer," the author wrote.

SOURCE:

This study, led by endocrinologist Kenda Alkwatli, MD, Starling Physicians, Wethersfield, Connecticut, was published online in Obesity.

LIMITATIONS:

The study included only individuals with sufficient longitudinal health records, which may have introduced selection bias. It could not distinguish between intentional and unintentional weight loss or differentiate between fat and lean mass. Due to its observational nature, the study could not assess whether weight loss preceding cancer diagnosis was related to delay in diagnosis.

DISCLOSURES:

The study was funded in part by the Cleveland Clinic Center for Quantitative Metabolic Research. Three authors reported receiving research funding, consulting fees, honoraria, grants, or research support and holding patent applications, license agreements, leadership roles, or equity in healthcare and biotechnology companies.

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:

Among adults with obesity, nonsurgical weight loss was significantly associated with reduced odds for developing obesity-related and other cancers at 3 and 5 years, a study of real-world data found.

METHODOLOGY:

• Although weight loss after bariatric surgery is linked to a reduced risk for cancer, the effect of nonsurgical weight loss on cancer risk remains unclear.
• Researchers conducted a retrospective observational study using electronic health record data from a US health system to assess the association between nonsurgical weight loss and the risk for cancer among adults with obesity.
• The inclusion criteria were age of ≥ 20 years, BMI > 30, and at least seven health system visits over 3 years. Patients with a history of alcohol or substance abuse, amputations, HIV infection, organ transplant, thyroid problems, or those who underwent bariatric surgery were excluded.
• The 143,630 patients who met inclusion criteria (7703 cancer cases and 135,927 controls) were divided into 3 cohorts based on weight change over time intervals of 3 years (115,942 patients), 5 years (105,472 patients), and 10 years (59,112 patients).
• Primary endpoints included obesity-related cancers (esophageal cancer, liver cancer, gallbladder cancer, pancreatic cancer, colorectal cancer, renal cell carcinoma, endometrial cancer, multiple myeloma, and postmenopausal breast cancer), and secondary endpoints included all malignant neoplasms.

TAKEAWAY:

• Each 1% reduction in BMI was associated with reduced odds of obesity-related cancers at 3 years and 5 years (odds ratio [OR], 0.99 and 0.989, respectively; P < .001 for both). These results translate to 5% weight loss corresponding to 4.9% and 5.4% reductions in obesity-related cancer odds at 3 and 5 years, respectively.
• Weight loss was associated with reduced odds of endometrial cancer at 3, 5, and 10 years (OR, 0.978; P < .05), of renal cell carcinoma at 3 and 5 years (OR, 0.983; P < .05), and of multiple myeloma at 10 years (OR, 0.969; P = .004).
• Weight loss was also associated with reduced odds of developing any malignancy at 3 years (OR, 0.992), 5 years (OR, 0.994), and 10 years (OR, 0.991; P = .001 for all). These results translate into a 5% weight loss corresponding to 3.9%, 3%, and 4.4% lower odds of any malignancy at 3, 5, and 10 years, respectively.

IN PRACTICE:

"Real-world weight loss was associated with a decreased risk of developing obesity-related cancers and all other cancers. Our study serves as a call for action and a strong public health message to healthcare stakeholders to intensify efforts and resources to treat obesity as a chronic disease to help reduce the risk of developing cancer," the author wrote.

SOURCE:

This study, led by endocrinologist Kenda Alkwatli, MD, Starling Physicians, Wethersfield, Connecticut, was published online in Obesity.

LIMITATIONS:

The study included only individuals with sufficient longitudinal health records, which may have introduced selection bias. It could not distinguish between intentional and unintentional weight loss or differentiate between fat and lean mass. Due to its observational nature, the study could not assess whether weight loss preceding cancer diagnosis was related to delay in diagnosis.

DISCLOSURES:

The study was funded in part by the Cleveland Clinic Center for Quantitative Metabolic Research. Three authors reported receiving research funding, consulting fees, honoraria, grants, or research support and holding patent applications, license agreements, leadership roles, or equity in healthcare and biotechnology companies.

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.

Recent research has revealed potential links between Agent Orange (AO) exposure and risk of acral melanoma (AM) among Vietnam War-era veterans, providing strong evidence of a relationship between the chemical and this type of cancer.

Localized to the palms, soles, and nail units, AM is a melanoma subtype less associated with UV radiation. From 1962 to 1971, the US military sprayed an estimated 18 million gallons of herbicides, including AO, over the fields and forests of Vietnam. Those herbicides have since been connected to numerous health issues, including cancer, though evidence of a relationship between AO and skin cancers has been weak. 

Vietnam War-era veterans have a higher melanoma burden than the general population, with the disease being the fourth-most common cancer among those who served. AM, however, is rare, representing about 2% to 3% of all melanomas. 

In a nested case-control study, Hwang et al used US Department of Veterans Affairs (VA) health care system data, including the VA Cancer Registry. The authors compared 1292 patients with AM and 2 pair-matched control groups: a group matched 4:1 to nonacral cutaneous melanoma controls, and a group without a melanoma diagnosis. 

Hwang et al found AO exposure was associated with increased odds of AM compared with each control group. In an accompanying editorial, Andrew Olshan, PhD, from Department of Epidemiology at the University of North Carolina Gillings School of Global Public Health, wrote, “The magnitude of the effects was modest (about 30%) but noteworthy.” 

A limitation of the study was that presumptive AOE status was based on whether the veteran filed a disability claim with evidence of officially recognized service in a period and place where Agent Orange was used—not on an assessment of the veteran’s individual AOE potential, including level of exposure. Because melanoma has never been included on the VA list of cancers presumed to be related to AO exposure, veterans do not automatically gain benefits by filing AOE claims after diagnosis. Even so, Olshan says, the reported study findings may underestimate the true effect of AO exposure on the risk of AM. 

Given the rarity of AM, the association (if causal) would translate to 0.4 to 0.8 new annual cases of AM per 1,000,000 veterans, according to the study. Narrowed down to Vietnam War-era veterans—who are dwindling in number—the attributable cases would be scarce.

Nevertheless, the search for a better understanding of a potential link between AOE and melanomas among Vietnam War-era veterans is important, Olshan wrote.

“The Hwang et al study provides a strong impetus to further these research goals and contribute to the investigation of the legacy of the Vietnam War and honor a commitment to the veterans community.”

Recent research has revealed potential links between Agent Orange (AO) exposure and risk of acral melanoma (AM) among Vietnam War-era veterans, providing strong evidence of a relationship between the chemical and this type of cancer.

Localized to the palms, soles, and nail units, AM is a melanoma subtype less associated with UV radiation. From 1962 to 1971, the US military sprayed an estimated 18 million gallons of herbicides, including AO, over the fields and forests of Vietnam. Those herbicides have since been connected to numerous health issues, including cancer, though evidence of a relationship between AO and skin cancers has been weak. 

Vietnam War-era veterans have a higher melanoma burden than the general population, with the disease being the fourth-most common cancer among those who served. AM, however, is rare, representing about 2% to 3% of all melanomas. 

In a nested case-control study, Hwang et al used US Department of Veterans Affairs (VA) health care system data, including the VA Cancer Registry. The authors compared 1292 patients with AM and 2 pair-matched control groups: a group matched 4:1 to nonacral cutaneous melanoma controls, and a group without a melanoma diagnosis. 

Hwang et al found AO exposure was associated with increased odds of AM compared with each control group. In an accompanying editorial, Andrew Olshan, PhD, from Department of Epidemiology at the University of North Carolina Gillings School of Global Public Health, wrote, “The magnitude of the effects was modest (about 30%) but noteworthy.” 

A limitation of the study was that presumptive AOE status was based on whether the veteran filed a disability claim with evidence of officially recognized service in a period and place where Agent Orange was used—not on an assessment of the veteran’s individual AOE potential, including level of exposure. Because melanoma has never been included on the VA list of cancers presumed to be related to AO exposure, veterans do not automatically gain benefits by filing AOE claims after diagnosis. Even so, Olshan says, the reported study findings may underestimate the true effect of AO exposure on the risk of AM. 

Given the rarity of AM, the association (if causal) would translate to 0.4 to 0.8 new annual cases of AM per 1,000,000 veterans, according to the study. Narrowed down to Vietnam War-era veterans—who are dwindling in number—the attributable cases would be scarce.

Nevertheless, the search for a better understanding of a potential link between AOE and melanomas among Vietnam War-era veterans is important, Olshan wrote.

“The Hwang et al study provides a strong impetus to further these research goals and contribute to the investigation of the legacy of the Vietnam War and honor a commitment to the veterans community.”

Recent research has revealed potential links between Agent Orange (AO) exposure and risk of acral melanoma (AM) among Vietnam War-era veterans, providing strong evidence of a relationship between the chemical and this type of cancer.

Localized to the palms, soles, and nail units, AM is a melanoma subtype less associated with UV radiation. From 1962 to 1971, the US military sprayed an estimated 18 million gallons of herbicides, including AO, over the fields and forests of Vietnam. Those herbicides have since been connected to numerous health issues, including cancer, though evidence of a relationship between AO and skin cancers has been weak. 

Vietnam War-era veterans have a higher melanoma burden than the general population, with the disease being the fourth-most common cancer among those who served. AM, however, is rare, representing about 2% to 3% of all melanomas. 

In a nested case-control study, Hwang et al used US Department of Veterans Affairs (VA) health care system data, including the VA Cancer Registry. The authors compared 1292 patients with AM and 2 pair-matched control groups: a group matched 4:1 to nonacral cutaneous melanoma controls, and a group without a melanoma diagnosis. 

Hwang et al found AO exposure was associated with increased odds of AM compared with each control group. In an accompanying editorial, Andrew Olshan, PhD, from Department of Epidemiology at the University of North Carolina Gillings School of Global Public Health, wrote, “The magnitude of the effects was modest (about 30%) but noteworthy.” 

A limitation of the study was that presumptive AOE status was based on whether the veteran filed a disability claim with evidence of officially recognized service in a period and place where Agent Orange was used—not on an assessment of the veteran’s individual AOE potential, including level of exposure. Because melanoma has never been included on the VA list of cancers presumed to be related to AO exposure, veterans do not automatically gain benefits by filing AOE claims after diagnosis. Even so, Olshan says, the reported study findings may underestimate the true effect of AO exposure on the risk of AM. 

Given the rarity of AM, the association (if causal) would translate to 0.4 to 0.8 new annual cases of AM per 1,000,000 veterans, according to the study. Narrowed down to Vietnam War-era veterans—who are dwindling in number—the attributable cases would be scarce.

Nevertheless, the search for a better understanding of a potential link between AOE and melanomas among Vietnam War-era veterans is important, Olshan wrote.

“The Hwang et al study provides a strong impetus to further these research goals and contribute to the investigation of the legacy of the Vietnam War and honor a commitment to the veterans community.”

SAN FRANCISCO – Peripheral T-cell lymphoma (PTCL) accounts for 4% of mature non-Hodgkin lymphoma cases in the US, or only about 4000 cases a year. While the number of patients is small, however, treatment for PTCL is complex due to wide variations in subtypes and survival rates, a hematologist-oncologist said at the March 21 Association of VA Hematology/Oncology (AVAHO) regional meeting on lymphoma.

Weiyun Ai, MD, PhD, a clinical professor of medicine at University of California, San Francisco who specializes in lymphoma, explained that there are multiple subtypes of PTCL based on their location within the body. Ai discussed a 2008 analysis of North American cases of PTCL and natural killer/T-cell lymphoma from 1990-2002, of which:

• 34% were PTCL, not otherwise specified;

• 16% were angioimmunoblastic T-cell lymphoma (AITL);

• 16% were anaplastic large cell lymphoma (ALCL), anaplastic lymphoma kinase (ALK)-positive;

• 7.8% were ALCL, ALK-negative;

• 5.8% were enteropathy-type;

• 5.4% were primary cutaneous ALCL; and

• 5.1% were extranodal natural killer/T-cell lymphoma, nasal type.

The remaining cases were adult T-cell leukemia/lymphoma, hepatosplenic, subcutaneous panniculitis-like, and unclassified. 

International Prognostic Index Predicts Outcomes

“The subtype with the best outcome is ALCL, ALK-positive with a 5-year overall survival rate of 70% followed by ALK-negative ALCL at 50%, and all the other common subtypes at 30%,” Ai said. 

Ai outlined the International Prognostic Index (IPI), a tool to predict clinical outcomes in patients with aggressive non-Hodgkin lymphoma based on risk factors. IPI assigns worse scores to patients aged > 60 years; patients who have higher (worse) performance scores, higher lactate dehydrogenase (LDH) levels, and more extranodal sites; and patients at stages III-IV.

First-Line Therapy: Consider Subtypes and CD30 Levels

Subtypes and CD30 expression levels are important factors in choosing therapy, Ai said, and 2019’s landmark ECHELON-2 study (updated in 2022) defines the standard. 

Newly diagnosed patients who strongly express CD30 (ie, those with both types of ALCL) are recommended to be treated with A+CHP (brentuximab vedotin [BV] plus cyclophosphamide, doxorubicin, and prednisone). 

Combination therapy of cyclophosphamide, doxorubicin, hydroxydaunorubicin, vincristine, and prednisone (CHOP) was the prior standard of care until the ECHELON-2 study, Ai said. 

That trial, which randomized 452 patients with untreated PTCL (CD30 ≥ 10%) to A+CHP or CHOP, found that 5-year progression-free rates were 51.4% vs 43.0%, respectively (hazard ratio [HR], 0.70; 95% CI, 0.53-0.91). Five-year overall survival rates were 70.1% vs. 61.0%, respectively (HR, 0.72; 95% CI, 0.53-0.99).

The threshold CD30 level at which to turn to A+CHP—1%, 5%, or 10%—“is kind of a dealer’s choice,” Ai said. Her own cutoff is 1%.

“If they're < 1%, I tend not to do it,” Ai said. “It's usually much more expensive, as you can imagine.”

If CD30 < 1%, Ai recommends CHOP or, in younger patients, CHOP plus etoposide (CHOEP).

Follow-up treatments include autologous stem cell transplant (ASCT) and observation/maintenance, depending on factors such as subtype, fitness, and remission.

Transplant: Still Relevant

When ECHELON-2 was released, some clinicians wondered if ASCT was still warranted, Ai said. A posthoc exploratory analysis found a 62% reduction in relative risk for progression in patients who underwent transplants after reaching complete remission with A+CHP. 

The findings provide support for transplant, she said. 

For transplant-ineligible patients, a small analysis of BV and CHP followed by BV maintenance showed a progression-free survival curve that appeared to plateau after 18-24 months.

“You don't see this kind of curve very often. I was quite impressed,” Ai said. “If the patient is willing and able, I will give them BV cycles.”

Ai discloses relationships with ADC, AbbVie, Acrotech, Kite, and Kyowa Kirin.

SAN FRANCISCO – Peripheral T-cell lymphoma (PTCL) accounts for 4% of mature non-Hodgkin lymphoma cases in the US, or only about 4000 cases a year. While the number of patients is small, however, treatment for PTCL is complex due to wide variations in subtypes and survival rates, a hematologist-oncologist said at the March 21 Association of VA Hematology/Oncology (AVAHO) regional meeting on lymphoma.

Weiyun Ai, MD, PhD, a clinical professor of medicine at University of California, San Francisco who specializes in lymphoma, explained that there are multiple subtypes of PTCL based on their location within the body. Ai discussed a 2008 analysis of North American cases of PTCL and natural killer/T-cell lymphoma from 1990-2002, of which:

• 34% were PTCL, not otherwise specified;

• 16% were angioimmunoblastic T-cell lymphoma (AITL);

• 16% were anaplastic large cell lymphoma (ALCL), anaplastic lymphoma kinase (ALK)-positive;

• 7.8% were ALCL, ALK-negative;

• 5.8% were enteropathy-type;

• 5.4% were primary cutaneous ALCL; and

• 5.1% were extranodal natural killer/T-cell lymphoma, nasal type.

The remaining cases were adult T-cell leukemia/lymphoma, hepatosplenic, subcutaneous panniculitis-like, and unclassified. 

International Prognostic Index Predicts Outcomes

“The subtype with the best outcome is ALCL, ALK-positive with a 5-year overall survival rate of 70% followed by ALK-negative ALCL at 50%, and all the other common subtypes at 30%,” Ai said. 

Ai outlined the International Prognostic Index (IPI), a tool to predict clinical outcomes in patients with aggressive non-Hodgkin lymphoma based on risk factors. IPI assigns worse scores to patients aged > 60 years; patients who have higher (worse) performance scores, higher lactate dehydrogenase (LDH) levels, and more extranodal sites; and patients at stages III-IV.

First-Line Therapy: Consider Subtypes and CD30 Levels

Subtypes and CD30 expression levels are important factors in choosing therapy, Ai said, and 2019’s landmark ECHELON-2 study (updated in 2022) defines the standard. 

Newly diagnosed patients who strongly express CD30 (ie, those with both types of ALCL) are recommended to be treated with A+CHP (brentuximab vedotin [BV] plus cyclophosphamide, doxorubicin, and prednisone). 

Combination therapy of cyclophosphamide, doxorubicin, hydroxydaunorubicin, vincristine, and prednisone (CHOP) was the prior standard of care until the ECHELON-2 study, Ai said. 

That trial, which randomized 452 patients with untreated PTCL (CD30 ≥ 10%) to A+CHP or CHOP, found that 5-year progression-free rates were 51.4% vs 43.0%, respectively (hazard ratio [HR], 0.70; 95% CI, 0.53-0.91). Five-year overall survival rates were 70.1% vs. 61.0%, respectively (HR, 0.72; 95% CI, 0.53-0.99).

The threshold CD30 level at which to turn to A+CHP—1%, 5%, or 10%—“is kind of a dealer’s choice,” Ai said. Her own cutoff is 1%.

“If they're < 1%, I tend not to do it,” Ai said. “It's usually much more expensive, as you can imagine.”

If CD30 < 1%, Ai recommends CHOP or, in younger patients, CHOP plus etoposide (CHOEP).

Follow-up treatments include autologous stem cell transplant (ASCT) and observation/maintenance, depending on factors such as subtype, fitness, and remission.

Transplant: Still Relevant

When ECHELON-2 was released, some clinicians wondered if ASCT was still warranted, Ai said. A posthoc exploratory analysis found a 62% reduction in relative risk for progression in patients who underwent transplants after reaching complete remission with A+CHP. 

The findings provide support for transplant, she said. 

For transplant-ineligible patients, a small analysis of BV and CHP followed by BV maintenance showed a progression-free survival curve that appeared to plateau after 18-24 months.

“You don't see this kind of curve very often. I was quite impressed,” Ai said. “If the patient is willing and able, I will give them BV cycles.”

Ai discloses relationships with ADC, AbbVie, Acrotech, Kite, and Kyowa Kirin.

SAN FRANCISCO – Peripheral T-cell lymphoma (PTCL) accounts for 4% of mature non-Hodgkin lymphoma cases in the US, or only about 4000 cases a year. While the number of patients is small, however, treatment for PTCL is complex due to wide variations in subtypes and survival rates, a hematologist-oncologist said at the March 21 Association of VA Hematology/Oncology (AVAHO) regional meeting on lymphoma.

Weiyun Ai, MD, PhD, a clinical professor of medicine at University of California, San Francisco who specializes in lymphoma, explained that there are multiple subtypes of PTCL based on their location within the body. Ai discussed a 2008 analysis of North American cases of PTCL and natural killer/T-cell lymphoma from 1990-2002, of which:

• 34% were PTCL, not otherwise specified;

• 16% were angioimmunoblastic T-cell lymphoma (AITL);

• 16% were anaplastic large cell lymphoma (ALCL), anaplastic lymphoma kinase (ALK)-positive;

• 7.8% were ALCL, ALK-negative;

• 5.8% were enteropathy-type;

• 5.4% were primary cutaneous ALCL; and

• 5.1% were extranodal natural killer/T-cell lymphoma, nasal type.

The remaining cases were adult T-cell leukemia/lymphoma, hepatosplenic, subcutaneous panniculitis-like, and unclassified. 

International Prognostic Index Predicts Outcomes

“The subtype with the best outcome is ALCL, ALK-positive with a 5-year overall survival rate of 70% followed by ALK-negative ALCL at 50%, and all the other common subtypes at 30%,” Ai said. 

Ai outlined the International Prognostic Index (IPI), a tool to predict clinical outcomes in patients with aggressive non-Hodgkin lymphoma based on risk factors. IPI assigns worse scores to patients aged > 60 years; patients who have higher (worse) performance scores, higher lactate dehydrogenase (LDH) levels, and more extranodal sites; and patients at stages III-IV.

First-Line Therapy: Consider Subtypes and CD30 Levels

Subtypes and CD30 expression levels are important factors in choosing therapy, Ai said, and 2019’s landmark ECHELON-2 study (updated in 2022) defines the standard. 

Newly diagnosed patients who strongly express CD30 (ie, those with both types of ALCL) are recommended to be treated with A+CHP (brentuximab vedotin [BV] plus cyclophosphamide, doxorubicin, and prednisone). 

Combination therapy of cyclophosphamide, doxorubicin, hydroxydaunorubicin, vincristine, and prednisone (CHOP) was the prior standard of care until the ECHELON-2 study, Ai said. 

That trial, which randomized 452 patients with untreated PTCL (CD30 ≥ 10%) to A+CHP or CHOP, found that 5-year progression-free rates were 51.4% vs 43.0%, respectively (hazard ratio [HR], 0.70; 95% CI, 0.53-0.91). Five-year overall survival rates were 70.1% vs. 61.0%, respectively (HR, 0.72; 95% CI, 0.53-0.99).

The threshold CD30 level at which to turn to A+CHP—1%, 5%, or 10%—“is kind of a dealer’s choice,” Ai said. Her own cutoff is 1%.

“If they're < 1%, I tend not to do it,” Ai said. “It's usually much more expensive, as you can imagine.”

If CD30 < 1%, Ai recommends CHOP or, in younger patients, CHOP plus etoposide (CHOEP).

Follow-up treatments include autologous stem cell transplant (ASCT) and observation/maintenance, depending on factors such as subtype, fitness, and remission.

Transplant: Still Relevant

When ECHELON-2 was released, some clinicians wondered if ASCT was still warranted, Ai said. A posthoc exploratory analysis found a 62% reduction in relative risk for progression in patients who underwent transplants after reaching complete remission with A+CHP. 

The findings provide support for transplant, she said. 

For transplant-ineligible patients, a small analysis of BV and CHP followed by BV maintenance showed a progression-free survival curve that appeared to plateau after 18-24 months.

“You don't see this kind of curve very often. I was quite impressed,” Ai said. “If the patient is willing and able, I will give them BV cycles.”

Ai discloses relationships with ADC, AbbVie, Acrotech, Kite, and Kyowa Kirin.

TOPLINE:

More than 1 in 8 colorectal cancer (CRC) cases among veterans occur outside the standard screening age of 50-75 years or those with high-risk personal or family history. High-risk patients face > 6 times the risk for CRC compared with average-risk patients aged 50-75 years who are up to date with screening, while Black patients have > 50% higher risk compared with White patients.

METHODOLOGY:

• Researchers conducted a case-control analysis using Veterans Health Administration (VHA) Corporate Data Warehouse data from 2012-2018 at 2 sites: Veterans Affairs (VA) New York Harbor Health Care System and VA Puget Sound Health Care System.

• Participants included 3714 cases among veterans with CRC matched to 14,856 controls (4:1), with matching on age (± 3 years), sex, and facility site; each control was used once.

• Screening categories included 5 groups by age (50-75 years vs < 50 years or > 75 years), screening up-to-date status, and high-risk status (inflammatory bowel disease, hereditary cancer syndromes, or family history).

• CRC screening was considered up to date if US Preventive Services Task Force-recommended tests were completed on time (colonoscopy ≤ 10 years; guaiac-based fecal occult blood test or fecal immunochemical test ≤ 1 year).

TAKEAWAY:

• Compared with category 1 (age 50-75 years and up-to-date with screening), CRC was associated with category 4 (age < 50 years or > 75 years and not up to date) (odds ratio [OR], 1.40; 95% CI, 1.11-1.78), and category 5 (high risk) (OR, 6.23; 95% CI, 5.06-7.66).

• Race and comorbidity associations included higher CRC risk for Black vs White patients (OR, 1.54; 95% CI, 1.37-1.73), and higher CRC risk with diabetes (OR, 1.65; 95% CI, 1.51-1.81) and alcohol use disorder (OR, 1.53; 95% CI, 1.35-1.73).

• Among 3714 CRC cases, 71.1% occurred in individuals aged 50-75 years not up to date with screening.

• A total of 12.5% of CRC cases occurred in people outside age 50-75 or with high-risk personal or family history, suggesting that conventional screening-adherence metrics may miss a clinically relevant minority.

IN PRACTICE:

“The conventional measure of CRC screening, focused on average-risk individuals aged 50 to 75, does not reflect screening status in an important minority of CRC patients," the authors wrote.

SOURCE:

The study was led by researchers at NYU Grossman School of Medicine and Veterans Affairs New York Harbor Health Care System, and published online July 9, 2026 in Medicine.

LIMITATIONS:

The study population consisted predominantly of male veterans (97.1%), who tend to be older and have more comorbidities compared with the US population, which may limit the generalizability of findings to other populations. Researchers defined screening status cross-sectionally relative to a single point in time rather than assessing longitudinal screening adherence, which may not fully capture the consistency of screening over time that is likely important for defining CRC risk. Veterans may receive screening at non-VA medical facilities, potentially leading to incomplete documentation of screening status and important covariates such as race, ethnicity, and comorbidities. The possibility of residual confounding cannot be excluded despite adjustment for multiple risk factors in the analysis.

DISCLOSURES:

This study received support from NIH grant K08 CA230162 and the AGA Caroline Craig Augustyn & Damian Augustyn Award in Digestive Cancer, both awarded to Peter S. Liang. Liang disclosed receiving research support from Freenome and serving on the advisory boards for Guardant Health and Natera. The remaining authors reported no funding or conflicts of interest to disclose.

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

TOPLINE:

More than 1 in 8 colorectal cancer (CRC) cases among veterans occur outside the standard screening age of 50-75 years or those with high-risk personal or family history. High-risk patients face > 6 times the risk for CRC compared with average-risk patients aged 50-75 years who are up to date with screening, while Black patients have > 50% higher risk compared with White patients.

METHODOLOGY:

• Researchers conducted a case-control analysis using Veterans Health Administration (VHA) Corporate Data Warehouse data from 2012-2018 at 2 sites: Veterans Affairs (VA) New York Harbor Health Care System and VA Puget Sound Health Care System.

• Participants included 3714 cases among veterans with CRC matched to 14,856 controls (4:1), with matching on age (± 3 years), sex, and facility site; each control was used once.

• Screening categories included 5 groups by age (50-75 years vs < 50 years or > 75 years), screening up-to-date status, and high-risk status (inflammatory bowel disease, hereditary cancer syndromes, or family history).

• CRC screening was considered up to date if US Preventive Services Task Force-recommended tests were completed on time (colonoscopy ≤ 10 years; guaiac-based fecal occult blood test or fecal immunochemical test ≤ 1 year).

TAKEAWAY:

• Compared with category 1 (age 50-75 years and up-to-date with screening), CRC was associated with category 4 (age < 50 years or > 75 years and not up to date) (odds ratio [OR], 1.40; 95% CI, 1.11-1.78), and category 5 (high risk) (OR, 6.23; 95% CI, 5.06-7.66).

• Race and comorbidity associations included higher CRC risk for Black vs White patients (OR, 1.54; 95% CI, 1.37-1.73), and higher CRC risk with diabetes (OR, 1.65; 95% CI, 1.51-1.81) and alcohol use disorder (OR, 1.53; 95% CI, 1.35-1.73).

• Among 3714 CRC cases, 71.1% occurred in individuals aged 50-75 years not up to date with screening.

• A total of 12.5% of CRC cases occurred in people outside age 50-75 or with high-risk personal or family history, suggesting that conventional screening-adherence metrics may miss a clinically relevant minority.

IN PRACTICE:

“The conventional measure of CRC screening, focused on average-risk individuals aged 50 to 75, does not reflect screening status in an important minority of CRC patients," the authors wrote.

SOURCE:

The study was led by researchers at NYU Grossman School of Medicine and Veterans Affairs New York Harbor Health Care System, and published online July 9, 2026 in Medicine.

LIMITATIONS:

The study population consisted predominantly of male veterans (97.1%), who tend to be older and have more comorbidities compared with the US population, which may limit the generalizability of findings to other populations. Researchers defined screening status cross-sectionally relative to a single point in time rather than assessing longitudinal screening adherence, which may not fully capture the consistency of screening over time that is likely important for defining CRC risk. Veterans may receive screening at non-VA medical facilities, potentially leading to incomplete documentation of screening status and important covariates such as race, ethnicity, and comorbidities. The possibility of residual confounding cannot be excluded despite adjustment for multiple risk factors in the analysis.

DISCLOSURES:

This study received support from NIH grant K08 CA230162 and the AGA Caroline Craig Augustyn & Damian Augustyn Award in Digestive Cancer, both awarded to Peter S. Liang. Liang disclosed receiving research support from Freenome and serving on the advisory boards for Guardant Health and Natera. The remaining authors reported no funding or conflicts of interest to disclose.

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

TOPLINE:

More than 1 in 8 colorectal cancer (CRC) cases among veterans occur outside the standard screening age of 50-75 years or those with high-risk personal or family history. High-risk patients face > 6 times the risk for CRC compared with average-risk patients aged 50-75 years who are up to date with screening, while Black patients have > 50% higher risk compared with White patients.

METHODOLOGY:

• Researchers conducted a case-control analysis using Veterans Health Administration (VHA) Corporate Data Warehouse data from 2012-2018 at 2 sites: Veterans Affairs (VA) New York Harbor Health Care System and VA Puget Sound Health Care System.

• Participants included 3714 cases among veterans with CRC matched to 14,856 controls (4:1), with matching on age (± 3 years), sex, and facility site; each control was used once.

• Screening categories included 5 groups by age (50-75 years vs < 50 years or > 75 years), screening up-to-date status, and high-risk status (inflammatory bowel disease, hereditary cancer syndromes, or family history).

• CRC screening was considered up to date if US Preventive Services Task Force-recommended tests were completed on time (colonoscopy ≤ 10 years; guaiac-based fecal occult blood test or fecal immunochemical test ≤ 1 year).

TAKEAWAY:

• Compared with category 1 (age 50-75 years and up-to-date with screening), CRC was associated with category 4 (age < 50 years or > 75 years and not up to date) (odds ratio [OR], 1.40; 95% CI, 1.11-1.78), and category 5 (high risk) (OR, 6.23; 95% CI, 5.06-7.66).

• Race and comorbidity associations included higher CRC risk for Black vs White patients (OR, 1.54; 95% CI, 1.37-1.73), and higher CRC risk with diabetes (OR, 1.65; 95% CI, 1.51-1.81) and alcohol use disorder (OR, 1.53; 95% CI, 1.35-1.73).

• Among 3714 CRC cases, 71.1% occurred in individuals aged 50-75 years not up to date with screening.

• A total of 12.5% of CRC cases occurred in people outside age 50-75 or with high-risk personal or family history, suggesting that conventional screening-adherence metrics may miss a clinically relevant minority.

IN PRACTICE:

“The conventional measure of CRC screening, focused on average-risk individuals aged 50 to 75, does not reflect screening status in an important minority of CRC patients," the authors wrote.

SOURCE:

The study was led by researchers at NYU Grossman School of Medicine and Veterans Affairs New York Harbor Health Care System, and published online July 9, 2026 in Medicine.

LIMITATIONS:

The study population consisted predominantly of male veterans (97.1%), who tend to be older and have more comorbidities compared with the US population, which may limit the generalizability of findings to other populations. Researchers defined screening status cross-sectionally relative to a single point in time rather than assessing longitudinal screening adherence, which may not fully capture the consistency of screening over time that is likely important for defining CRC risk. Veterans may receive screening at non-VA medical facilities, potentially leading to incomplete documentation of screening status and important covariates such as race, ethnicity, and comorbidities. The possibility of residual confounding cannot be excluded despite adjustment for multiple risk factors in the analysis.

DISCLOSURES:

This study received support from NIH grant K08 CA230162 and the AGA Caroline Craig Augustyn & Damian Augustyn Award in Digestive Cancer, both awarded to Peter S. Liang. Liang disclosed receiving research support from Freenome and serving on the advisory boards for Guardant Health and Natera. The remaining authors reported no funding or conflicts of interest to disclose.

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