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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.

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.

Two studies published in March by researchers at the Veterans Affairs Saint Louis Healthcare System highlight the clinical significance of glucagon-like peptide 1 receptor agonists (GLP-1s) and their impact on reducing substance use disorder (SUD) risks. The studies also explore the impact of GLP-1 discontinuation or interruption on their effectiveness in protection against the cardiovascular events.

In one study, Al-Aly et al assigned 606,434 veterans with type 2 diabetes to 1 of 2 protocols, comparing GLP-1s with sodium-glucose cotransporter-2 (SGLT-2) inhibitors, and followed the patients for up to 3 years. Al-Aly et al found that GLP-1s were “consistently associated” with a lower risk of developing SUDs, including those involving alcohol, cannabis, cocaine, nicotine, and opioids. The findings suggested “potential preventive effects across a broad range of addictive substances.”

In participants with pre-existing SUDs, GLP-1s were also associated with reduced risks of SUD-related emergency department visits, hospital admissions, and mortality, in addition to drug overdoses and suicidal behaviors. A study published in 2025 from the same research group reported that GLP-1s could have a variety of health benefits, including reducing the risk of incident alcohol and cannabis disorders, neurocognitive disorders (such as Alzheimer's disease and dementia), coagulation disorders, cardiometabolic disorders, infectious illnesses and several respiratory conditions, but less was known about the potential for preventing development of opioid use disorder and other SUDs. 

GLP-1s target the brain’s reward pathways and have recently made attention-grabbing headlines regarding celebrity weight loss, with social media boosting public interest. One study, for example, found 100 videos on TikTok with the #Ozempic viewed nearly 70 million times.

Al-Aly et al used SGLT-2 inhibitors as active comparators because “they have no established direct actions on mesolimbic reward circuits in the brain, whereas GLP-1 receptors are present in areas of the brain involved in impulse control and reward signaling.”

The second study found that quitting or pausing GLP-1 treatment for 6 months could have a rebound effect and possibly reverse any progress. Discontinuing GLP-1 treatment is common, with rates ranging from 36% to 81% in the first year. Stopping or interrupting the treatment is often followed by weight regain and a rebound in inflammation, both major drivers in cardiovascular disease risk. 

The study followed 132,551 VA patients using GLP-1s and 201,136 using sulfonylureas from 2017 through 2023. About two-thirds of participants took semaglutide, prescribed as Ozempic to treat diabetes and Wegovy to reduce obesity. A total of 26% of the participants stopped GLP-1 treatment during the follow-up period, with 64% occurring during the first year. Most (67%) treatment interruptions also came in the first year.

Compared with incident use of sulfonylureas, incident use of GLP-1s was associated with a reduced risk of heart attack, stroke, or death. Patients who took the GLP-1s without interruption > 3 years experienced an 18% lower risk for heart attack or stroke.  

Cardiovascular benefits accumulated with continuous use over 3 years, but even brief periods of discontinuations or interruptions could progressively erode and ultimately reverse this protection, the researchers found. Discontinuing treatment for half a year was associated with an increased risk of major adverse cardiovascular events (incidence risk ratio [IRR], 1.04), while longer gaps were progressively associated with a higher risk of disease (IRR, 1.12 for 1 year; IRR, 1.16 for 2 years of interrupted use, respectively).

Dr. Ziyad Al-Aly, a study author and Chief of the Research and Education Service at the Veterans Affairs Saint Louis Healthcare System, called it “metabolic whiplash.” In an interview, he said it was important to caution patients that these medications “need to be taken for the long haul. This is not something (patients) can take for a month or 2 or 3 and get off of it. It's not going to work like that.”

Two studies published in March by researchers at the Veterans Affairs Saint Louis Healthcare System highlight the clinical significance of glucagon-like peptide 1 receptor agonists (GLP-1s) and their impact on reducing substance use disorder (SUD) risks. The studies also explore the impact of GLP-1 discontinuation or interruption on their effectiveness in protection against the cardiovascular events.

In one study, Al-Aly et al assigned 606,434 veterans with type 2 diabetes to 1 of 2 protocols, comparing GLP-1s with sodium-glucose cotransporter-2 (SGLT-2) inhibitors, and followed the patients for up to 3 years. Al-Aly et al found that GLP-1s were “consistently associated” with a lower risk of developing SUDs, including those involving alcohol, cannabis, cocaine, nicotine, and opioids. The findings suggested “potential preventive effects across a broad range of addictive substances.”

In participants with pre-existing SUDs, GLP-1s were also associated with reduced risks of SUD-related emergency department visits, hospital admissions, and mortality, in addition to drug overdoses and suicidal behaviors. A study published in 2025 from the same research group reported that GLP-1s could have a variety of health benefits, including reducing the risk of incident alcohol and cannabis disorders, neurocognitive disorders (such as Alzheimer's disease and dementia), coagulation disorders, cardiometabolic disorders, infectious illnesses and several respiratory conditions, but less was known about the potential for preventing development of opioid use disorder and other SUDs. 

GLP-1s target the brain’s reward pathways and have recently made attention-grabbing headlines regarding celebrity weight loss, with social media boosting public interest. One study, for example, found 100 videos on TikTok with the #Ozempic viewed nearly 70 million times.

Al-Aly et al used SGLT-2 inhibitors as active comparators because “they have no established direct actions on mesolimbic reward circuits in the brain, whereas GLP-1 receptors are present in areas of the brain involved in impulse control and reward signaling.”

The second study found that quitting or pausing GLP-1 treatment for 6 months could have a rebound effect and possibly reverse any progress. Discontinuing GLP-1 treatment is common, with rates ranging from 36% to 81% in the first year. Stopping or interrupting the treatment is often followed by weight regain and a rebound in inflammation, both major drivers in cardiovascular disease risk. 

The study followed 132,551 VA patients using GLP-1s and 201,136 using sulfonylureas from 2017 through 2023. About two-thirds of participants took semaglutide, prescribed as Ozempic to treat diabetes and Wegovy to reduce obesity. A total of 26% of the participants stopped GLP-1 treatment during the follow-up period, with 64% occurring during the first year. Most (67%) treatment interruptions also came in the first year.

Compared with incident use of sulfonylureas, incident use of GLP-1s was associated with a reduced risk of heart attack, stroke, or death. Patients who took the GLP-1s without interruption > 3 years experienced an 18% lower risk for heart attack or stroke.  

Cardiovascular benefits accumulated with continuous use over 3 years, but even brief periods of discontinuations or interruptions could progressively erode and ultimately reverse this protection, the researchers found. Discontinuing treatment for half a year was associated with an increased risk of major adverse cardiovascular events (incidence risk ratio [IRR], 1.04), while longer gaps were progressively associated with a higher risk of disease (IRR, 1.12 for 1 year; IRR, 1.16 for 2 years of interrupted use, respectively).

Dr. Ziyad Al-Aly, a study author and Chief of the Research and Education Service at the Veterans Affairs Saint Louis Healthcare System, called it “metabolic whiplash.” In an interview, he said it was important to caution patients that these medications “need to be taken for the long haul. This is not something (patients) can take for a month or 2 or 3 and get off of it. It's not going to work like that.”

Two studies published in March by researchers at the Veterans Affairs Saint Louis Healthcare System highlight the clinical significance of glucagon-like peptide 1 receptor agonists (GLP-1s) and their impact on reducing substance use disorder (SUD) risks. The studies also explore the impact of GLP-1 discontinuation or interruption on their effectiveness in protection against the cardiovascular events.

In one study, Al-Aly et al assigned 606,434 veterans with type 2 diabetes to 1 of 2 protocols, comparing GLP-1s with sodium-glucose cotransporter-2 (SGLT-2) inhibitors, and followed the patients for up to 3 years. Al-Aly et al found that GLP-1s were “consistently associated” with a lower risk of developing SUDs, including those involving alcohol, cannabis, cocaine, nicotine, and opioids. The findings suggested “potential preventive effects across a broad range of addictive substances.”

In participants with pre-existing SUDs, GLP-1s were also associated with reduced risks of SUD-related emergency department visits, hospital admissions, and mortality, in addition to drug overdoses and suicidal behaviors. A study published in 2025 from the same research group reported that GLP-1s could have a variety of health benefits, including reducing the risk of incident alcohol and cannabis disorders, neurocognitive disorders (such as Alzheimer's disease and dementia), coagulation disorders, cardiometabolic disorders, infectious illnesses and several respiratory conditions, but less was known about the potential for preventing development of opioid use disorder and other SUDs. 

GLP-1s target the brain’s reward pathways and have recently made attention-grabbing headlines regarding celebrity weight loss, with social media boosting public interest. One study, for example, found 100 videos on TikTok with the #Ozempic viewed nearly 70 million times.

Al-Aly et al used SGLT-2 inhibitors as active comparators because “they have no established direct actions on mesolimbic reward circuits in the brain, whereas GLP-1 receptors are present in areas of the brain involved in impulse control and reward signaling.”

The second study found that quitting or pausing GLP-1 treatment for 6 months could have a rebound effect and possibly reverse any progress. Discontinuing GLP-1 treatment is common, with rates ranging from 36% to 81% in the first year. Stopping or interrupting the treatment is often followed by weight regain and a rebound in inflammation, both major drivers in cardiovascular disease risk. 

The study followed 132,551 VA patients using GLP-1s and 201,136 using sulfonylureas from 2017 through 2023. About two-thirds of participants took semaglutide, prescribed as Ozempic to treat diabetes and Wegovy to reduce obesity. A total of 26% of the participants stopped GLP-1 treatment during the follow-up period, with 64% occurring during the first year. Most (67%) treatment interruptions also came in the first year.

Compared with incident use of sulfonylureas, incident use of GLP-1s was associated with a reduced risk of heart attack, stroke, or death. Patients who took the GLP-1s without interruption > 3 years experienced an 18% lower risk for heart attack or stroke.  

Cardiovascular benefits accumulated with continuous use over 3 years, but even brief periods of discontinuations or interruptions could progressively erode and ultimately reverse this protection, the researchers found. Discontinuing treatment for half a year was associated with an increased risk of major adverse cardiovascular events (incidence risk ratio [IRR], 1.04), while longer gaps were progressively associated with a higher risk of disease (IRR, 1.12 for 1 year; IRR, 1.16 for 2 years of interrupted use, respectively).

Dr. Ziyad Al-Aly, a study author and Chief of the Research and Education Service at the Veterans Affairs Saint Louis Healthcare System, called it “metabolic whiplash.” In an interview, he said it was important to caution patients that these medications “need to be taken for the long haul. This is not something (patients) can take for a month or 2 or 3 and get off of it. It's not going to work like that.”

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.

Seeking to modernize treatment for traumatic brain injury (TBI), Reps. Jack Bergman (R-MI) and Sarah Elfreth (D-MD) introduced the bipartisan BEACON Act to Congress on January 9. The legislation aims to expand access to innovative, evidence-based, nonpharmacological therapies to treat TBI beyond medication-centered approaches that do not always address the long-term and individualized needs of these veterans. These current methods leave “gaps in recovery, wellness, and post-service outcomes,” Bergman and Elfreth argued.

During a March 5 House Committee on Veterans’ Affairs Subcommittee on Health hearing, discussion centered on the proposed BEACON Act, as well as the additional challenges Neurology Centers of Excellence (CoEs) face to address TBI in veterans.

The act proposes awarding $60 million in grants over 3 years to private entities for TBI treatment and research and establishing 2 US Department of Veterans Affairs (VA) grant programs. The TBI Innovation Grant Program would support clinical studies and partnerships between community health care institutions, academic institutions, and the VA. The Independent Research Grant Program would advance third-party research and “implementation of proven alternative treatments,” with oversight by an independent entity modeled after the VA National Center for PTSD.

The proposed legislation has drawn criticism. “I do not disagree that veterans may need support from several different avenues to support their recovery journeys and I don't discount the role that nonprofits and academic affiliates play in facilitating and supporting that care,” said Ranking Member Rep. Julia Brownley (D-CA) said. “However, I need to draw the line at legislation that will take money from existing VA programs and redirect it to outside organizations and providers to do essentially the very same thing VA is already doing.” 

Russell Gore, MD, a neurologist and chief medical officer of Avalon Action Alliance, called VA TBI care fragmented and said the BEACON Act offers an opportunity to enhance it.

“This legislation is designed to evaluate effective treatments and leverage civilian and academic TBI expertise that is aligned with the VA’s mission,” he said. “This is not an attempt to privatize care, but to complement VA research and clinical capacity… With smart, coordinated partnerships and targeted investment, we can reach more veterans earlier, treat them more effectively.”

The VA has 5 polytrauma rehabilitation centers, 23 polytrauma network sites, and numerous clinics supporting > 110 TBI teams. It also has 42 CoEs related to neurology. 

In a prepared statement, Glenn Graham, MD, PhD, retired Executive Director of the VA’s Neurology Clinical Programs representing the Association of VA Neurology Services cited the CoEs’ contribution to standardization of care. “Without systemwide coordination, practice patterns can vary. A veteran in a rural facility should receive the same standard of neurological assessment and management as a veteran treated in one of our flagship medical centers,” he said, before highlighting the capabilities of tele-neurology, electronic consultation, and remote interpretation of diagnostic studies to reduce travel burdens and promote equity in access. 

Graham cautioned, though, that the CoEs face challenges with budgeting and recent VA reductions in force. The proposed legislation, Graham said, would use VA appropriations to fund extramural research and “could drain vital resources from ongoing research, training and clinical programs, diverting funds to institutions with uncertain track records and limited experience working with the veteran population.” 

Several people highlighted the world-renowned research coming out of the VA, efforts that both veterans and the general public endorse.

Russell Lemle, former chief psychologist for the San Francisco VA Healthcare System and a senior policy analyst at the Veterans Healthcare Policy Institute, wrote with Jasper Craven: “The private sector has nothing commensurate with this level of care. And yet this bill would push TBI treatment out to private grantees, part of the accelerating movement to privatize the entire VA—even its signature, best-in-class programs.

“The act aims to divert resources from the VA’s world-class TBI and PTSD programs by creating a parallel treatment framework.”

Gore, however, said the Avalon Action Alliance supports a “fill-the-void” approach of “capacity augmentation, not privatization.”

“The intent is to complement VA by partnering with high-performing programs capable of delivering comprehensive assessment, interdisciplinary treatment, and structured follow-up for veterans who are not effectively reached (or not successfully retained) within traditional pathways,” he said.

Seeking to modernize treatment for traumatic brain injury (TBI), Reps. Jack Bergman (R-MI) and Sarah Elfreth (D-MD) introduced the bipartisan BEACON Act to Congress on January 9. The legislation aims to expand access to innovative, evidence-based, nonpharmacological therapies to treat TBI beyond medication-centered approaches that do not always address the long-term and individualized needs of these veterans. These current methods leave “gaps in recovery, wellness, and post-service outcomes,” Bergman and Elfreth argued.

During a March 5 House Committee on Veterans’ Affairs Subcommittee on Health hearing, discussion centered on the proposed BEACON Act, as well as the additional challenges Neurology Centers of Excellence (CoEs) face to address TBI in veterans.

The act proposes awarding $60 million in grants over 3 years to private entities for TBI treatment and research and establishing 2 US Department of Veterans Affairs (VA) grant programs. The TBI Innovation Grant Program would support clinical studies and partnerships between community health care institutions, academic institutions, and the VA. The Independent Research Grant Program would advance third-party research and “implementation of proven alternative treatments,” with oversight by an independent entity modeled after the VA National Center for PTSD.

The proposed legislation has drawn criticism. “I do not disagree that veterans may need support from several different avenues to support their recovery journeys and I don't discount the role that nonprofits and academic affiliates play in facilitating and supporting that care,” said Ranking Member Rep. Julia Brownley (D-CA) said. “However, I need to draw the line at legislation that will take money from existing VA programs and redirect it to outside organizations and providers to do essentially the very same thing VA is already doing.” 

Russell Gore, MD, a neurologist and chief medical officer of Avalon Action Alliance, called VA TBI care fragmented and said the BEACON Act offers an opportunity to enhance it.

“This legislation is designed to evaluate effective treatments and leverage civilian and academic TBI expertise that is aligned with the VA’s mission,” he said. “This is not an attempt to privatize care, but to complement VA research and clinical capacity… With smart, coordinated partnerships and targeted investment, we can reach more veterans earlier, treat them more effectively.”

The VA has 5 polytrauma rehabilitation centers, 23 polytrauma network sites, and numerous clinics supporting > 110 TBI teams. It also has 42 CoEs related to neurology. 

In a prepared statement, Glenn Graham, MD, PhD, retired Executive Director of the VA’s Neurology Clinical Programs representing the Association of VA Neurology Services cited the CoEs’ contribution to standardization of care. “Without systemwide coordination, practice patterns can vary. A veteran in a rural facility should receive the same standard of neurological assessment and management as a veteran treated in one of our flagship medical centers,” he said, before highlighting the capabilities of tele-neurology, electronic consultation, and remote interpretation of diagnostic studies to reduce travel burdens and promote equity in access. 

Graham cautioned, though, that the CoEs face challenges with budgeting and recent VA reductions in force. The proposed legislation, Graham said, would use VA appropriations to fund extramural research and “could drain vital resources from ongoing research, training and clinical programs, diverting funds to institutions with uncertain track records and limited experience working with the veteran population.” 

Several people highlighted the world-renowned research coming out of the VA, efforts that both veterans and the general public endorse.

Russell Lemle, former chief psychologist for the San Francisco VA Healthcare System and a senior policy analyst at the Veterans Healthcare Policy Institute, wrote with Jasper Craven: “The private sector has nothing commensurate with this level of care. And yet this bill would push TBI treatment out to private grantees, part of the accelerating movement to privatize the entire VA—even its signature, best-in-class programs.

“The act aims to divert resources from the VA’s world-class TBI and PTSD programs by creating a parallel treatment framework.”

Gore, however, said the Avalon Action Alliance supports a “fill-the-void” approach of “capacity augmentation, not privatization.”

“The intent is to complement VA by partnering with high-performing programs capable of delivering comprehensive assessment, interdisciplinary treatment, and structured follow-up for veterans who are not effectively reached (or not successfully retained) within traditional pathways,” he said.

Seeking to modernize treatment for traumatic brain injury (TBI), Reps. Jack Bergman (R-MI) and Sarah Elfreth (D-MD) introduced the bipartisan BEACON Act to Congress on January 9. The legislation aims to expand access to innovative, evidence-based, nonpharmacological therapies to treat TBI beyond medication-centered approaches that do not always address the long-term and individualized needs of these veterans. These current methods leave “gaps in recovery, wellness, and post-service outcomes,” Bergman and Elfreth argued.

During a March 5 House Committee on Veterans’ Affairs Subcommittee on Health hearing, discussion centered on the proposed BEACON Act, as well as the additional challenges Neurology Centers of Excellence (CoEs) face to address TBI in veterans.

The act proposes awarding $60 million in grants over 3 years to private entities for TBI treatment and research and establishing 2 US Department of Veterans Affairs (VA) grant programs. The TBI Innovation Grant Program would support clinical studies and partnerships between community health care institutions, academic institutions, and the VA. The Independent Research Grant Program would advance third-party research and “implementation of proven alternative treatments,” with oversight by an independent entity modeled after the VA National Center for PTSD.

The proposed legislation has drawn criticism. “I do not disagree that veterans may need support from several different avenues to support their recovery journeys and I don't discount the role that nonprofits and academic affiliates play in facilitating and supporting that care,” said Ranking Member Rep. Julia Brownley (D-CA) said. “However, I need to draw the line at legislation that will take money from existing VA programs and redirect it to outside organizations and providers to do essentially the very same thing VA is already doing.” 

Russell Gore, MD, a neurologist and chief medical officer of Avalon Action Alliance, called VA TBI care fragmented and said the BEACON Act offers an opportunity to enhance it.

“This legislation is designed to evaluate effective treatments and leverage civilian and academic TBI expertise that is aligned with the VA’s mission,” he said. “This is not an attempt to privatize care, but to complement VA research and clinical capacity… With smart, coordinated partnerships and targeted investment, we can reach more veterans earlier, treat them more effectively.”

The VA has 5 polytrauma rehabilitation centers, 23 polytrauma network sites, and numerous clinics supporting > 110 TBI teams. It also has 42 CoEs related to neurology. 

In a prepared statement, Glenn Graham, MD, PhD, retired Executive Director of the VA’s Neurology Clinical Programs representing the Association of VA Neurology Services cited the CoEs’ contribution to standardization of care. “Without systemwide coordination, practice patterns can vary. A veteran in a rural facility should receive the same standard of neurological assessment and management as a veteran treated in one of our flagship medical centers,” he said, before highlighting the capabilities of tele-neurology, electronic consultation, and remote interpretation of diagnostic studies to reduce travel burdens and promote equity in access. 

Graham cautioned, though, that the CoEs face challenges with budgeting and recent VA reductions in force. The proposed legislation, Graham said, would use VA appropriations to fund extramural research and “could drain vital resources from ongoing research, training and clinical programs, diverting funds to institutions with uncertain track records and limited experience working with the veteran population.” 

Several people highlighted the world-renowned research coming out of the VA, efforts that both veterans and the general public endorse.

Russell Lemle, former chief psychologist for the San Francisco VA Healthcare System and a senior policy analyst at the Veterans Healthcare Policy Institute, wrote with Jasper Craven: “The private sector has nothing commensurate with this level of care. And yet this bill would push TBI treatment out to private grantees, part of the accelerating movement to privatize the entire VA—even its signature, best-in-class programs.

“The act aims to divert resources from the VA’s world-class TBI and PTSD programs by creating a parallel treatment framework.”

Gore, however, said the Avalon Action Alliance supports a “fill-the-void” approach of “capacity augmentation, not privatization.”

“The intent is to complement VA by partnering with high-performing programs capable of delivering comprehensive assessment, interdisciplinary treatment, and structured follow-up for veterans who are not effectively reached (or not successfully retained) within traditional pathways,” he said.

Simple exercises performed during chemotherapy may significantly reduce treatment-related cognitive impairment, according to findings from a phase 3 randomized controlled trial.

Among patients with cancer receiving 2-week cycles of chemotherapy, a structured and individualized exercise “prescription” combining walking and resistance band training significantly reduced cognitive impairment and mental fatigue compared with usual care.

The results are “practice-changing,” colead author Karen Mustian, PhD, MPH, with the Wilmot Cancer Institute, University of Rochester Medical Center, Rochester, New York, told Medscape Medical News. “Cancer care providers should consider incorporating structured, home-based exercise programs, such as walking and resistance band exercises, into routine chemotherapy care.”

The findings, published online in the Journal of the National Comprehensive Cancer Network (NCCN), reinforce recommendations by the NCCN that survivors with cancer-related cognitive dysfunction engage in routine physical activity.

“Many patients who need chemotherapy worry that they’ll experience ‘chemo brain,’” Lindsay L. Peterson, MD, medical oncologist at Washington University School of Medicine in St. Louis, who was not involved in this research, added in a statement.

This study offers “encouraging news” — exercise may be something patients can do to reduce their risk for cognitive impairment during chemotherapy, Peterson said.

Less Brain Fog, Mental Fatigue

Up to three-fourth of patients experience cancer-related cognitive impairment during treatment, which often occurs alongside mental fatigue. Research assessing the effects of exercise on cancer-related cognitive impairment during treatment is limited. To investigate, Mustian and colleagues enrolled 687 chemotherapy-naive adults with various cancers as well as Karnofsky performance status scores of at least 70 and no physical limitations, who were scheduled to start chemotherapy with cycles of 2, 3, or 4 weeks. Participants were randomly assigned to either the Exercise for Cancer Patients (EXCAP) intervention or usual care while undergoing chemotherapy. Developed by Mustian and colleagues, EXCAP is a 6-week, home-based, individually tailored walking and resistance band exercise program, introduced during a single in-person training session and reinforced through follow-up calls.

Before chemotherapy began, participants in both groups averaged roughly 2 miles of walking daily. After 6 weeks, patients in the EXCAP group largely maintained their activity levels, while those receiving usual care reduced their daily steps by about half. The exercise group also added resistance-band training three times per week for about 25 minutes per session, while the usual care group did no resistance exercises.

Cognitive function was measured using the Functional Assessment of Cancer Therapy-Cognitive Function questionnaire, and mental fatigue was assessed using the Multidimensional Fatigue Symptom Inventory. Blood samples were collected to measure key inflammatory markers.

Overall, across the study population, cognitive function declined and mental fatigue worsened during chemotherapy, but outcomes differed by treatment group and chemotherapy schedule.

Patients assigned to EXCAP and receiving chemotherapy on 2-week cycles fared best. More specifically, compared with usual care, EXCAP participants undergoing 2-week chemotherapy cycles reported less overall cognitive impairment (mean difference, 7.0; P = .04) and lower perceived cognitive impairment (mean difference, 4.1; P = .05). The exercisers also received fewer perceived comments from others about cognitive difficulties (mean difference, 0.6; P = .02) and reported less mental fatigue (-1.6; P < .01).

These benefits, however, were not observed in patients receiving 3- and 4-week chemotherapy cycles. In the 3-week cohort, there were no significant differences between groups in cognitive impairment (mean difference, 0.5; P = .85) or mental fatigue (mean difference, -0.2; P = .60).

“This was surprising,” Mustian said. “We really don’t know why the patients receiving chemo every 2 weeks were the ones to benefit the most. We do not have the capacity in our current data to answer that question for sure.”

However, Mustian speculated that it’s possible patients who receive their chemotherapy on differing weekly schedules receive different chemotherapy agents that have different toxicity and adverse-effect profiles.

For instance, chemotherapy among patients on a 2-week cycle may come with less severe acute adverse effects, which in turn may allow patients to remain more active throughout their treatments. On the other hand, chemotherapy among patients on a 3-week cycle may come with more severe acute adverse effects, which prevent them from staying as active.

“Once a person starts to lower their activity levels, it is more difficult to get back to their baseline levels and maintain them, and definitely harder to add anything additional to their activity routines,” Mustian said.

Immune Benefits?

Mustian and her team also assessed ties between exercise, cognitive impairment, and inflammation during chemotherapy. Previous work from the team showed that patients who received the EXCAP intervention exhibited higher immunocompetence.

In the current study, the researchers observed that a “healthy inflammatory response” — reflecting balanced increases in both proinflammatory and anti-inflammatory cytokines — was associated with better cognitive outcomes, suggesting that immune regulation may play a role in chemotherapy-related cognitive symptoms.

While chemotherapy may contribute to cognitive impairment by disrupting the body’s inflammatory and immune responses, “exercise may help keep these body systems working more normally, which could explain why patients who exercised had better thinking and less mental fatigue,” Mustian said.

Role for Exercise Oncology

Mustian suggested that oncologists consider referring patients receiving chemotherapy to exercise oncology specialists who can tailor programs for individual capabilities.

There are now > 2000 exercise oncology programs across the US. “Many of them provide both in-person and remote online opportunities for patients to access highly qualified exercise oncology professionals,” Mustian said.

Taking time to learn about community resources, developing a referral method of referral, or even providing patients with simple handouts on credible exercise programs and NCCN guidelines can help, Mustian added.

Peterson noted that, for many patients, maintaining the ability to think clearly, remember details, and stay mentally engaged during treatment is essential to preserving independence, continuing to work and care for their families, and sustaining overall quality of life.

“Interventions that are accessible and low cost, such as structured physical activity, give us a powerful opportunity not only to support long-term survivorship, but to help patients remain as cognitively sharp and mentally resilient as possible throughout treatment,” Peterson said in a statement.

This study was supported by the National Cancer Institute. Mustian and Peterson reported having no relevant disclosures.

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

Simple exercises performed during chemotherapy may significantly reduce treatment-related cognitive impairment, according to findings from a phase 3 randomized controlled trial.

Among patients with cancer receiving 2-week cycles of chemotherapy, a structured and individualized exercise “prescription” combining walking and resistance band training significantly reduced cognitive impairment and mental fatigue compared with usual care.

The results are “practice-changing,” colead author Karen Mustian, PhD, MPH, with the Wilmot Cancer Institute, University of Rochester Medical Center, Rochester, New York, told Medscape Medical News. “Cancer care providers should consider incorporating structured, home-based exercise programs, such as walking and resistance band exercises, into routine chemotherapy care.”

The findings, published online in the Journal of the National Comprehensive Cancer Network (NCCN), reinforce recommendations by the NCCN that survivors with cancer-related cognitive dysfunction engage in routine physical activity.

“Many patients who need chemotherapy worry that they’ll experience ‘chemo brain,’” Lindsay L. Peterson, MD, medical oncologist at Washington University School of Medicine in St. Louis, who was not involved in this research, added in a statement.

This study offers “encouraging news” — exercise may be something patients can do to reduce their risk for cognitive impairment during chemotherapy, Peterson said.

Less Brain Fog, Mental Fatigue

Up to three-fourth of patients experience cancer-related cognitive impairment during treatment, which often occurs alongside mental fatigue. Research assessing the effects of exercise on cancer-related cognitive impairment during treatment is limited. To investigate, Mustian and colleagues enrolled 687 chemotherapy-naive adults with various cancers as well as Karnofsky performance status scores of at least 70 and no physical limitations, who were scheduled to start chemotherapy with cycles of 2, 3, or 4 weeks. Participants were randomly assigned to either the Exercise for Cancer Patients (EXCAP) intervention or usual care while undergoing chemotherapy. Developed by Mustian and colleagues, EXCAP is a 6-week, home-based, individually tailored walking and resistance band exercise program, introduced during a single in-person training session and reinforced through follow-up calls.

Before chemotherapy began, participants in both groups averaged roughly 2 miles of walking daily. After 6 weeks, patients in the EXCAP group largely maintained their activity levels, while those receiving usual care reduced their daily steps by about half. The exercise group also added resistance-band training three times per week for about 25 minutes per session, while the usual care group did no resistance exercises.

Cognitive function was measured using the Functional Assessment of Cancer Therapy-Cognitive Function questionnaire, and mental fatigue was assessed using the Multidimensional Fatigue Symptom Inventory. Blood samples were collected to measure key inflammatory markers.

Overall, across the study population, cognitive function declined and mental fatigue worsened during chemotherapy, but outcomes differed by treatment group and chemotherapy schedule.

Patients assigned to EXCAP and receiving chemotherapy on 2-week cycles fared best. More specifically, compared with usual care, EXCAP participants undergoing 2-week chemotherapy cycles reported less overall cognitive impairment (mean difference, 7.0; P = .04) and lower perceived cognitive impairment (mean difference, 4.1; P = .05). The exercisers also received fewer perceived comments from others about cognitive difficulties (mean difference, 0.6; P = .02) and reported less mental fatigue (-1.6; P < .01).

These benefits, however, were not observed in patients receiving 3- and 4-week chemotherapy cycles. In the 3-week cohort, there were no significant differences between groups in cognitive impairment (mean difference, 0.5; P = .85) or mental fatigue (mean difference, -0.2; P = .60).

“This was surprising,” Mustian said. “We really don’t know why the patients receiving chemo every 2 weeks were the ones to benefit the most. We do not have the capacity in our current data to answer that question for sure.”

However, Mustian speculated that it’s possible patients who receive their chemotherapy on differing weekly schedules receive different chemotherapy agents that have different toxicity and adverse-effect profiles.

For instance, chemotherapy among patients on a 2-week cycle may come with less severe acute adverse effects, which in turn may allow patients to remain more active throughout their treatments. On the other hand, chemotherapy among patients on a 3-week cycle may come with more severe acute adverse effects, which prevent them from staying as active.

“Once a person starts to lower their activity levels, it is more difficult to get back to their baseline levels and maintain them, and definitely harder to add anything additional to their activity routines,” Mustian said.

Immune Benefits?

Mustian and her team also assessed ties between exercise, cognitive impairment, and inflammation during chemotherapy. Previous work from the team showed that patients who received the EXCAP intervention exhibited higher immunocompetence.

In the current study, the researchers observed that a “healthy inflammatory response” — reflecting balanced increases in both proinflammatory and anti-inflammatory cytokines — was associated with better cognitive outcomes, suggesting that immune regulation may play a role in chemotherapy-related cognitive symptoms.

While chemotherapy may contribute to cognitive impairment by disrupting the body’s inflammatory and immune responses, “exercise may help keep these body systems working more normally, which could explain why patients who exercised had better thinking and less mental fatigue,” Mustian said.

Role for Exercise Oncology

Mustian suggested that oncologists consider referring patients receiving chemotherapy to exercise oncology specialists who can tailor programs for individual capabilities.

There are now > 2000 exercise oncology programs across the US. “Many of them provide both in-person and remote online opportunities for patients to access highly qualified exercise oncology professionals,” Mustian said.

Taking time to learn about community resources, developing a referral method of referral, or even providing patients with simple handouts on credible exercise programs and NCCN guidelines can help, Mustian added.

Peterson noted that, for many patients, maintaining the ability to think clearly, remember details, and stay mentally engaged during treatment is essential to preserving independence, continuing to work and care for their families, and sustaining overall quality of life.

“Interventions that are accessible and low cost, such as structured physical activity, give us a powerful opportunity not only to support long-term survivorship, but to help patients remain as cognitively sharp and mentally resilient as possible throughout treatment,” Peterson said in a statement.

This study was supported by the National Cancer Institute. Mustian and Peterson reported having no relevant disclosures.

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

Simple exercises performed during chemotherapy may significantly reduce treatment-related cognitive impairment, according to findings from a phase 3 randomized controlled trial.

Among patients with cancer receiving 2-week cycles of chemotherapy, a structured and individualized exercise “prescription” combining walking and resistance band training significantly reduced cognitive impairment and mental fatigue compared with usual care.

The results are “practice-changing,” colead author Karen Mustian, PhD, MPH, with the Wilmot Cancer Institute, University of Rochester Medical Center, Rochester, New York, told Medscape Medical News. “Cancer care providers should consider incorporating structured, home-based exercise programs, such as walking and resistance band exercises, into routine chemotherapy care.”

The findings, published online in the Journal of the National Comprehensive Cancer Network (NCCN), reinforce recommendations by the NCCN that survivors with cancer-related cognitive dysfunction engage in routine physical activity.

“Many patients who need chemotherapy worry that they’ll experience ‘chemo brain,’” Lindsay L. Peterson, MD, medical oncologist at Washington University School of Medicine in St. Louis, who was not involved in this research, added in a statement.

This study offers “encouraging news” — exercise may be something patients can do to reduce their risk for cognitive impairment during chemotherapy, Peterson said.

Less Brain Fog, Mental Fatigue

Up to three-fourth of patients experience cancer-related cognitive impairment during treatment, which often occurs alongside mental fatigue. Research assessing the effects of exercise on cancer-related cognitive impairment during treatment is limited. To investigate, Mustian and colleagues enrolled 687 chemotherapy-naive adults with various cancers as well as Karnofsky performance status scores of at least 70 and no physical limitations, who were scheduled to start chemotherapy with cycles of 2, 3, or 4 weeks. Participants were randomly assigned to either the Exercise for Cancer Patients (EXCAP) intervention or usual care while undergoing chemotherapy. Developed by Mustian and colleagues, EXCAP is a 6-week, home-based, individually tailored walking and resistance band exercise program, introduced during a single in-person training session and reinforced through follow-up calls.

Before chemotherapy began, participants in both groups averaged roughly 2 miles of walking daily. After 6 weeks, patients in the EXCAP group largely maintained their activity levels, while those receiving usual care reduced their daily steps by about half. The exercise group also added resistance-band training three times per week for about 25 minutes per session, while the usual care group did no resistance exercises.

Cognitive function was measured using the Functional Assessment of Cancer Therapy-Cognitive Function questionnaire, and mental fatigue was assessed using the Multidimensional Fatigue Symptom Inventory. Blood samples were collected to measure key inflammatory markers.

Overall, across the study population, cognitive function declined and mental fatigue worsened during chemotherapy, but outcomes differed by treatment group and chemotherapy schedule.

Patients assigned to EXCAP and receiving chemotherapy on 2-week cycles fared best. More specifically, compared with usual care, EXCAP participants undergoing 2-week chemotherapy cycles reported less overall cognitive impairment (mean difference, 7.0; P = .04) and lower perceived cognitive impairment (mean difference, 4.1; P = .05). The exercisers also received fewer perceived comments from others about cognitive difficulties (mean difference, 0.6; P = .02) and reported less mental fatigue (-1.6; P < .01).

These benefits, however, were not observed in patients receiving 3- and 4-week chemotherapy cycles. In the 3-week cohort, there were no significant differences between groups in cognitive impairment (mean difference, 0.5; P = .85) or mental fatigue (mean difference, -0.2; P = .60).

“This was surprising,” Mustian said. “We really don’t know why the patients receiving chemo every 2 weeks were the ones to benefit the most. We do not have the capacity in our current data to answer that question for sure.”

However, Mustian speculated that it’s possible patients who receive their chemotherapy on differing weekly schedules receive different chemotherapy agents that have different toxicity and adverse-effect profiles.

For instance, chemotherapy among patients on a 2-week cycle may come with less severe acute adverse effects, which in turn may allow patients to remain more active throughout their treatments. On the other hand, chemotherapy among patients on a 3-week cycle may come with more severe acute adverse effects, which prevent them from staying as active.

“Once a person starts to lower their activity levels, it is more difficult to get back to their baseline levels and maintain them, and definitely harder to add anything additional to their activity routines,” Mustian said.

Immune Benefits?

Mustian and her team also assessed ties between exercise, cognitive impairment, and inflammation during chemotherapy. Previous work from the team showed that patients who received the EXCAP intervention exhibited higher immunocompetence.

In the current study, the researchers observed that a “healthy inflammatory response” — reflecting balanced increases in both proinflammatory and anti-inflammatory cytokines — was associated with better cognitive outcomes, suggesting that immune regulation may play a role in chemotherapy-related cognitive symptoms.

While chemotherapy may contribute to cognitive impairment by disrupting the body’s inflammatory and immune responses, “exercise may help keep these body systems working more normally, which could explain why patients who exercised had better thinking and less mental fatigue,” Mustian said.

Role for Exercise Oncology

Mustian suggested that oncologists consider referring patients receiving chemotherapy to exercise oncology specialists who can tailor programs for individual capabilities.

There are now > 2000 exercise oncology programs across the US. “Many of them provide both in-person and remote online opportunities for patients to access highly qualified exercise oncology professionals,” Mustian said.

Taking time to learn about community resources, developing a referral method of referral, or even providing patients with simple handouts on credible exercise programs and NCCN guidelines can help, Mustian added.

Peterson noted that, for many patients, maintaining the ability to think clearly, remember details, and stay mentally engaged during treatment is essential to preserving independence, continuing to work and care for their families, and sustaining overall quality of life.

“Interventions that are accessible and low cost, such as structured physical activity, give us a powerful opportunity not only to support long-term survivorship, but to help patients remain as cognitively sharp and mentally resilient as possible throughout treatment,” Peterson said in a statement.

This study was supported by the National Cancer Institute. Mustian and Peterson reported having no relevant disclosures.

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