Studies address DPYD pharmacogenomics, lung cancer eligibility criteria, advance care planning, prostate cancer genomics, fatigue treatment, and more.
CHICAGO — VA researchers had a strong presence at the 2026 American Society of Clinical Oncology Annual Meeting in Chicago, with dozens of abstracts and posters selected for publication spanning cancer prevention, treatment, survivorship, and health systems science.
Studies presented at the annual meeting, which ended early last month, were drawn from VA health records, cancer registries, and clinical programs addressed questions ranging from how to identify more veterans at risk for lung cancer to whether pharmacogenomic testing can reduce treatment toxicity across the largest integrated healthcare system in the country.
DPYD Testing Enters VA Standard of Care
Among the most consequential findings for everyday oncology practice was a presentation describing how the VA has moved pretreatment DPYD testing from an aspirational goal to an embedded clinical standard across its national oncology pathways.
Fluoropyrimidine chemotherapies, including 5-fluorouracil and capecitabine, are cornerstones of treatment for colorectal, breast, head and neck, and esophageal cancers. Patients with variants in the DPYD gene, which encodes the enzyme responsible for metabolizing flouropyrimidines, face substantially elevated risk of severe and potentially fatal toxicity at standard doses. Despite longstanding evidence supporting pretreatment testing, uptake has been uneven across healthcare systems.
Jeremy D. Kratz, MD, of the William S. Middleton Memorial Veterans Hospital and the University of Wisconsin School of Medicine and Public Health, described how the VA’s National Pharmacogenomics Program has expanded to 162 sites since its full launch in 2023 that built on testing that began in 2019. Today, the program includes trained clinical pharmacist practitioners available at 165 facilities. As of March 2025, more than 100,000 veterans had received pharmacogenomic testing, and the proportion of sites online grew from 83% in fiscal year 2024 to the current 93% of VA facilities.
The program’s impact has been measurable. The rate of identified drug-gene interactions fell from 8.4% to 4.4% following implementation, and 16% of veterans received a different prescription than originally planned as a direct result of testing results. Oncology accounts for 5% of providers ordering the testing, with the remainder distributed across primary care, mental health, cardiology, and pharmacy, a breadth that Kratz attributed to the utility of panel-based testing beyond any single disease.
DPYD testing has now been formally incorporated into VA clinical pathways for gastrointestinal, breast, head and neck, and esophageal cancers, placing it alongside established molecular markers such as KRAS and BRAF in the standard pre-treatment workup.
Kratz emphasized that dose adjustments must be paired with ongoing clinical judgment. “If the patient tolerates their initial dose of 5-fluorouracil, we need to go back to the drawing board and say, ‘we’re still working for cure,’” he said, underscoring that initial dose reductions in intermediate metabolizers should not be interpreted as a ceiling.
The program uses a Microsoft Power BI application integrated within VA systems to track testing implementation in real time across VISNs, enabling the identification of access gaps and sites where additional pharmacist training may be needed.1
Smoking Duration Outperforms Pack-Years for Lung Cancer Screening
A study of nearly one million veterans argues that current national lung cancer screening criteria leave too many high-risk smokers undetected and that a simpler metric, smoking duration, can close much of that gap while improving equity.
Current U.S. Preventive Services Task Force guidelines use tobacco pack-years as the primary eligibility criterion for low-dose CT screening, requiring at least 20 pack-years and cessation within the past 15 years. Pack-year calculations require patients to accurately recall average daily cigarette consumption over decades, a figure that tends to vary and is frequently miscalculated by both patients and providers.
Brendan Heiden, of the Division of Cardiothoracic Surgery at Washington University School of Medicine in St. Louis and the VA St. Louis Healthcare System and co-investigators at VA St. Louis and VA facilities in Los Angeles examined whether replacing pack-years with a more straightforward 20-year smoking duration threshold would better identify veterans at elevated lung cancer risk. Their retrospective cohort study drew on the VA’s National Lung Cancer Screening program, which prospectively collects smoking histories. Of the 960,770 veterans included in the study, 340,312 (35.4%) currently smoke, 304,589 (31.7%) formerly smoked, and 315,869 (32.9%) never smoked.
The results were striking. Under 2021 USPSTF criteria, 65% of veterans with smoking histories qualified for screening; under a 20-year duration threshold, 80% qualified, an expansion of nearly 30%.
Critically, the proportion of lung cancers occurring in screening-ineligible individuals, used as a proxy for missed diagnoses, fell from 17.1% under current guidelines to 7.5% under duration-based criteria, a reduction of more than 70% in potentially missed cancers. The five-year lung cancer incidence among those meeting duration criteria was 1.48%, more than 11 times the 0.13% rate observed in never-smokers, indicating that expanded eligibility does not meaningfully reduce screening efficiency.
The equity implications were equally significant. Under current USPSTF criteria, Black and female veterans are approximately 20% less likely to qualify for screening than their white male counterparts. Under duration-based criteria, that disparity largely disappeared, with more than 80% of Black veterans with a smoking history and more than 80% of female veterans who have smoked qualifying. “Smoking duration is a simpler, more sensitive, and more equitable metric for screening eligibility,” Heiden said, adding that the National Comprehensive Cancer Network (NCCN) adopted duration-based criteria in 2025 and that the findings support ongoing USPSTF consideration of a similar shift.2
Community Health Workers Improve Advance Care Planning at Scale
Cancer patients frequently reach the end of life without documented goals-of-care preferences, a gap driven by clinician time constraints, workforce shortages in palliative care, and inadequate reimbursement for advance care planning conversations. A randomized trial conducted at a VA medical center tested whether trained community health workers leading small-group education sessions could address that gap more efficiently than one-on-one approaches.
Olivia Viruet Quintero, BS, a health educator at the Palo Alto VA Medical Center and graduate student at Stanford University, presented results from a prospective randomized clinical trial enrolling veterans newly diagnosed with solid tumor malignancies at one VA facility. Sixty patients were randomized 1:1 to either two 90-minute community health worker-led group sessions over one month, covering advance care planning, surrogate decision-maker designation, and communication strategies, or to usual care. The median participant age was 79 years; 88.3% had stage III or IV cancer; and the cohort was racially diverse, with 20% identifying as Black and 5% as American Indian.
At six-month follow-up, the results favored the intervention across multiple endpoints. All 30 intervention participants (100%) had completed advance care planning documentation, compared with 12 of 30 controls (40%). Satisfaction with care, measured as strongly agreeing that care matched personal preferences, was higher in the intervention group (90% versus 66.7%). Hospice use was substantially greater in the intervention arm (55.6% versus 10.0%), with no difference in palliative care utilization between groups.
There were no withdrawals and no participants lost to follow-up, an unusual retention rate Quintero attributed in part to the group format’s social engagement. Scheduling coordination for groups of four to five veterans and technology access for those preferring virtual sessions were identified as practical barriers to scaling the approach. “Group community health worker interventions can be a really effective way to increase advanced care planning documentation, as well as hospice use and satisfaction with care,” Quintero said.3
Multiple Primary Cancers: Non-Random Patterns in the VA Registry
As cancer survival improves, a growing number of veterans live long enough to develop second and subsequent primary malignancies and a large registry analysis presented at the ASCO meeting found that those occurrences follow consistent, non-random patterns with direct implications for survivorship surveillance.
Thomas George, MBBS, of Boston University Chobanian & Avedisian School of Medicine and Boston Medical Center, analyzed the VA Cancer Registry from 2003 to 2023, identifying 822,564 veterans with cancer, of whom 11.1% developed two or more primary cancers. Three etiologic patterns emerged. Exposure-related cancers clustered as expected: lung cancer was the most common second and third primary malignancy after bladder and oral cavity cancers, consistent with shared tobacco exposure.
Therapy-related cancers increased markedly, with rates of acute myeloid leukemia rising from 0.02 per standard rate as a first cancer to 39.01 as a second, reflecting treatment-related myeloid toxicity. Genetically predisposed cancers did not cluster, likely reflecting the cohort’s older age at first diagnosis. Notably, intervals between successive cancers shortened with each subsequent malignancy, suggesting that prior cancer alters the biological milieu in ways that accelerate subsequent oncogenesis. The findings, George argued, support risk-adapted long-term surveillance programs rather than assuming that second cancers arise by chance.4
Bupropion Reduces Cancer-Related Fatigue, Especially in Women
A nationwide phase III randomized trial found that bupropion, a norepinephrine-dopamine reuptake inhibitor already approved for depression and smoking cessation, produced statistically significant reductions in cancer-related fatigue compared with placebo, with the benefit concentrated among women.
Cancer-related fatigue affects 80% to 90% of patients during treatment, and roughly 40% continue to experience moderate-to-severe fatigue after therapy ends. Existing pharmacologic options are limited: methylphenidate offers modest benefit with tolerability concerns, and SSRIs, modafinil, and armodafinil have each failed to outperform placebo in large trials.
Luke Peppone, of the University of Rochester Medical Center and co-investigators at the James Haley VA Hospital in Tampa among others, enrolled 428 patients with moderate-to-severe fatigue across 26 community oncology sites. Participants had completed surgery, radiation, or intravenous anticancer therapy at least two months prior to enrollment. They were randomized to bupropion 300 mg daily or matched placebo for 12 weeks.
The trial met its primary endpoint. At 12 weeks, bupropion produced a statistically significant improvement in the FACIT-Fatigue subscale score compared with placebo (effect size 0.23, p=0.03). In pre-specified moderator analyses, the benefit was driven by reduced fatigue in women, among whom the effect size reached 0.33 and the group difference of 2.83 points met the pre-established minimal clinically important difference (p=0.006).
Among the 73 men enrolled, no significant benefit was detected, though the small sample size limits interpretation. Notably, bupropion, a norepinephrine-dopamine reuptake inhibitor often used to treat depression, did not preferentially benefit patients with baseline depressive symptoms, suggesting a mechanism beyond simple antidepressant activity. Exploratory cytokine analyses found no significant anti-inflammatory effect, pointing instead toward hypothalamic-pituitary-adrenal axis modulation and cortisol rhythm restoration as likely drivers. Tolerability was favorable, with no significant group differences in adverse events, insomnia, or dose reduction rates.
“Bupropion should be considered as a potential treatment option for cancer-related fatigue, particularly in women survivors, while applying appropriate screening,” Peppone concluded, noting that contraindications including seizure risk and drug interactions require clinical review before prescribing.5
VA Prostate and Hematologic Cancer Research
Several additional VA presentations addressed treatment outcomes and precision oncology in prostate cancer and hematologic malignancies.
Martin Schoen, MD, MPH, of the VA St. Louis Healthcare System, discussed a real-world subgroup analysis of veterans with de novo metastatic castration-sensitive prostate cancer who were elderly, frail, or had high comorbidity, populations systematically underrepresented in clinical trials. Among 1,629 veterans, those receiving enzalutamide plus androgen deprivation therapy (ADT) had a median overall survival of 36.1 months compared with 23.4 months for ADT alone (adjusted hazard ratio 0.70; 95% CI: 0.60–0.83; p<0.001). In the high-volume disease subgroup, any androgen-receptor pathway inhibitor combination was associated with a median survival of 29.1 months versus 18.8 months for ADT alone (adjusted hazard ratio 0.73; 95% CI: 0.65–0.83; p<0.001).6
Omar Yaghi, MD, MPH, of George Washington University with co-investigators utilizing the VA Informatics and Computing Infrastructure evaluated asciminib, a third-generation BCR-ABL inhibitor approved in 2021, in 110 veterans with chronic myeloid leukemia who had failed first- and second-generation tyrosine kinase inhibitors. By six months, median BCR-ABL levels fell from 1.03% at baseline to 0.05%, consistent with major molecular response. Restricted mean survival time over five years was 3.3 years, with low rates of thrombocytopenia (10%) and neutropenia (3%), supporting a favorable safety profile in a heavily pretreated population.7
Researchers also presented VA-based research on PARP inhibitor use and sequencing in metastatic castration-resistant prostate cancer, the cardiovascular safety of darolutamide versus abiraterone in a national cohort of nearly 12,000 veterans, genomic classification of hormone-sensitive prostate cancer using the STRATOS-P system, and a large language model approach to extracting cytogenetic risk data from unstructured myeloma records in the VA registry.
Beyond prostate cancer and hematology, VA researchers presented on topics reflected the scale and diversity of VA oncology research. Topics included financial vulnerability among veteran cancer survivors, chemo-immunotherapy outcomes in veterans with brain metastases, cachexia in metastatic NSCLC, opioid prescribing trends across two decades of VA data, rare melanoma risk factors, clinical trial enrollment barriers in veterans with aerodigestive cancers, and germline genetic testing conformance under the VA’s mainstream testing model, among many others.
- Kratz JD. Changing the standard of care by recommending pretreatment DPYD testing in Veterans Affairs oncology clinical pathways. 2026 ASCO Annual Meeting; May 30–June 3, 2026; Chicago, IL.
- Heiden B, Eaton DB Jr, Puri V, et al. Redefining lung cancer screening eligibility: smoking duration vs. pack-years in a national VA cohort of nearly 1 million patients. J Clin Oncol. 2026;44(suppl 16):abstr 8004. doi:10.1200/JCO.2026.44.16_suppl.8004
- Viruet Quintero O. Effect of group community health worker–led advance care planning education on advance care planning documentation, satisfaction, palliative care, and hospice: results from a randomized clinical trial. J Clin Oncol. 2026;44(suppl 16):abstr 1521. doi:10.1200/JCO.2026.44.16_suppl.1521
- George T. Non-random patterns of multiple primary malignancies in the era of cancer survival. J Clin Oncol. 2026;44(suppl 16):abstr 10584. doi:10.1200/JCO.2026.44.16_suppl.10584
- Peppone L, Guido JJ, Li C-S, et al. Nationwide randomized, phase III, placebo-controlled trial of bupropion for cancer-related fatigue: primary outcome results. J Clin Oncol. 2026;44(suppl 17):abstr LBA12003. doi:10.1200/JCO.2026.44.17_suppl.LBA12003
- Schoen M. Outcomes with androgen-deprivation therapy plus androgen receptor pathway inhibitors in veterans with de novo metastatic castration-sensitive prostate cancer who were elderly, frail, or had high comorbidity. J Clin Oncol. 2026;44(suppl 16):abstr 5094. doi:10.1200/JCO.2026.44.16_suppl.5094
- Yaghi OS, Gill P, Rose J, Liu S, Diao G. Safety and efficacy of asciminib in veterans with chronic myeloid leukemia. J Clin Oncol. 2026;44(suppl 16):abstr 6591. doi:10.1200/JCO.2026.44.16_suppl.6591