Faculty Bibliography

OBJECTIVE:To define oncologic outcomes in Veterans in the modern era using a multi-institutional cohort designed to support development and validation of prognostic and predictive biomarkers for oropharyngeal squamous cell carcinoma (OPSCC). METHODS:A retrospective analysis was conducted including adult OPSCC patients treated at one of nine Veterans Affairs Medical Centers between 2000 and 2024; inclusive of 597 HPV-associated and 197 HPV-independent tumors. All patients were treated with curative intent external beam radiotherapy (100%) with (90%) or without concurrent chemotherapy. RESULTS:A total of 894 adult patients (mean age, 64 years; 881 (99.5%) male) were included in the study; 22% of patients self-identified as Black. The estimated 2- and 5-year OS rates for the entire cohort were 71% and 54%, respectively and lagged substantially behind locoregional control (LRC) and distant metastatic control (DMC). For Veterans with HPV-associated OPSCC, LRC and DMC at 5 years were 87% and 87% respectively. The strongest drivers of OS and LRC were T-classification and chemotherapy choice on univariate and multivariate analysis. CONCLUSIONS:Although LRC and DMC rates among Veterans track well with recently completed clinical trial outcomes, OS rates lag substantially suggestive of higher rates of non-cancer-specific mortality. Together, these data suggest that predictive biomarker strategies focused on treatment effectiveness should be predicated on LRC and DMC rather than OS. This multicenter study is the first step in providing a robust dataset capable of developing and optimizing artificial intelligence (AI)-informed prognostic and predictive strategies essential to a precision oncology approach to OPSCC.

PURPOSE/OBJECTIVE:This study evaluated how frequently patients with early onset colorectal cancer received fertility counseling and whether patient characteristics affected the likelihood of receiving such counseling. METHODS:We conducted a single-center retrospective review of all new patients seen by medical oncology for colorectal cancer who were age 55 years or younger for men and 50 years or younger for women. Associations between patient demographics and clinical characteristics with receipt of fertility counseling were explored using univariate analyses and multivariable logistical regression analyses. RESULTS:A total of 194 patients were included, of whom 15.5% received fertility counseling. Using multivariate analysis, we found that age < 40 (OR 15.587, p < 0.0001, 95% CI 4.841-50.191) and female sex (OR 3.979, p = 0.0292, 95% CI 1.150-13.770) were correlated with increased likelihood of fertility counseling. Patients living in areas of higher household income were more likely to receive fertility counseling, with a statistically significant difference between the 3rd and 1st quartiles of income (p = 0.0369, 95% CI 1.161-115.940). CONCLUSION/CONCLUSIONS:A majority of patients with EOCRC did not receive fertility counseling despite the known toxicities of CRC treatment modalities on fertility. Older age, male sex, and residence in areas of lower income were associated with decreased likelihood of receiving fertility counseling.

BACKGROUND/UNASSIGNED:Management of precision oncology testing imposes a substantial burden on pathology departments. As the number of tests continue to grow, developing more efficient processes will become even more important. OBSERVATIONS/UNASSIGNED:A consult process for anatomic pathology molecular testing offers a way to maximize efficiency. While use of such a consult has been reported, detailed descriptions of the steps involved to facilitate adoption and adaptation at prospective sites is lacking. This article describes a consult process that was implemented at the Kansas City Veterans Affairs Medical Center in 2021. Areas of inefficiency are identified and a target process map is presented. CONCLUSIONS/UNASSIGNED:The proposed consult process increases test utilization, ensures appropriateness of orders, standardizes reporting, and improves efficiency. Laboratory understaffing and growing demand for testing necessitate more efficient processes for pathology to manage the workload and maintain the highest quality of cancer care.

BACKGROUND:5-Fluorouracil (5-FU) is a major component of gastrointestinal cancer treatments. In multidrug regimens such as FOLFOX, FOLFIRI, and FOLFIRINOX, 5-FU is commonly administered as a bolus followed by an infusion. However, the pharmacologic rationale for incorporating the 5-FU bolus in these regimens is unclear, and there are other effective regimens for gastrointestinal cancers that do not include the bolus. The purpose of this study was to determine whether omission of the 5-FU bolus was associated with a difference in survival and toxicity. METHODS:A real-world database from Flatiron Health was queried for patients with advanced colorectal, gastroesophageal, and pancreatic cancers who received first-line FOLFOX, FOLFIRI, and FOLFIRINOX regimens. Cox proportional hazards and Kaplan-Meier analyses were performed to compare survival outcomes between patients who received the 5-FU bolus and those who did not. Inverse probability of treatment weighted (IPTW) analysis was performed to adjust for treatment selection bias. RESULTS:This study included 11,765 patients with advanced colorectal (n=8,670), gastroesophageal (n=1,481), and pancreatic (n=1,614) cancers. Among all first-line 5-FU multidrug regimens, 10,148 (86.3%) patients received a 5-FU bolus and 1,617 (13.7%) did not. After IPTW analysis, we found that omitting the bolus was not associated with a decrease in overall survival (hazard ratio, 0.99; 95% CI, 0.91-1.07; P=.74). However, omitting the bolus was associated with reductions in neutropenia (10.7% vs 22.7%; P<.01), thrombocytopenia (11.2% vs 16.1%; P<.01), and use of granulocyte colony-stimulating factors after treatment (19.6% vs 29.1%; P<.01). CONCLUSIONS:After adjusting for baseline clinical factors, we found that omission of the 5-FU bolus from FOLFOX, FOLFIRI, and FOLFIRINOX regimens was not associated with decreased survival, but resulted in decreased toxicity and possible health care savings.

BACKGROUND:In recent years the US health-care system has witnessed a substantial increase in telehealth use. Telehealth enhances health-care access and quality and may reduce costs. However, there is a concern that the shift from in-person to telehealth care delivery may differentially improve cancer care access and quality in certain clinical settings and for specific patient populations while potentially exacerbating disparities in care for others. Our National Cancer Institute-funded center, called Telehealth Research and Innovation for Veterans with Cancer (THRIVE), is focused on health equity for telehealth-delivered cancer care. We seek to understand how social determinants of telehealth-particularly race and ethnicity, poverty, and rurality-affect the use of telehealth. METHODS:THRIVE draws from the Health Disparities Research Framework and the Consolidated Framework for Implementation Research. THRIVE consists of multiple cores that work synergistically to assess and understand health equity for telehealth-delivered cancer care. These include the Administrative Core, Research and Methods Core, Clinical Practice Network, and Pragmatic Trial. RESULTS:As of October 2023, we identified and trained 5 THRIVE scholars, who are junior faculty beginning a research career. We have reviewed 20 potential pilot studies, funding 6. Additionally, in communication with our funders and advisory boards, we have adjusted our study design and analytic approach, ensuring feasibility while addressing our operational partners' needs. CONCLUSIONS:THRIVE has several key strengths. First, the Veterans Health Administration's health-care system is large and diverse regarding health-care setting type and patient population. Second, we have access to longitudinal data, predating the COVID-19 pandemic, about telehealth use. Finally, equitable access to high-quality care for all veterans is a major tenet of the Veterans Health Administration health-care mission. As a result of these advantages, THRIVE can focus on isolating and evaluating the impact of social determinants of telehealth on equity in cancer care.

PURPOSE/OBJECTIVE:Previous studies document underuse of next-generation sequencing (NGS). We examined the impact to oncology care for veterans of incorporating NGS ordering into the Veterans Affairs (VA) electronic medical record (EMR) at two New York City VA Medical Centers. METHODS:We identified patients with non-small cell lung cancer and prostate cancer with oncology clinic visits and NGS testing indications between January and December 2021. Patients were divided into external ordering (EO) with visits before we implemented an EMR ordering system for NGS in July 2021, and internal ordering (IO) with visits after this date. The primary outcome was proportion of NGS testing performed in EO versus IO groups. Secondary outcomes were time between metastatic disease diagnosis to receipt of test by vendor, time of metastatic diagnosis to result, and proportion of testing by race. RESULTS:= .03). The proportion of tissue received by the vendor was not significantly different between the two groups. There were no significant differences in testing according to self-reported race. CONCLUSION/CONCLUSIONS:Integration of NGS ordering in the EMR led to increased proportion and speed of testing for a vulnerable patient population served by the country's largest health system.

The Veterans Health Administration is chartered "to serve as the primary backup for any health care services needed…in the event of war or national emergency" according to a 1982 Congressional Act. This mission was invoked during the COVID-19 pandemic to divert clinical and research resources. We used an electronic mixed-methods questionnaire constructed using the Theoretical Domains Framework (TDF) and the Capability, Opportunity, and Motivation (COM-B) model for behavior change to study the effects of the pandemic on VHA researchers. The questionnaire was distributed electronically to 118 cancer researchers participating in national VHA collaborations. The questionnaire received 42 responses (36%). Only 36% did not feel that their research focus changed during the pandemic. Only 26% reported prior experience with infectious disease research, and 74% agreed that they gained new research skills. When asked to describe helpful support structures, 29% mentioned local supervisors, mentors, and research staff, 15% cited larger VHA organizations and 18% mentioned remote work. Lack of timely communication and remote work, particularly for individuals with caregiving responsibilities, were limiting factors. Fewer than half felt professionally rewarded for pursuing research related to COVID. This study demonstrated the tremendous effects of the COVID-19 pandemic on research activities of VHA investigators. We identified perceptions of insufficient recognition and lack of professional advancement related to pandemic-era research, yet most reported gaining new research skills. Individualizing the structure of remote work and ensuring clear and timely team communication represent high yield areas for improvement.

BACKGROUND:Evading immune surveillance is a hallmark for the development of multiple cancer types. Whether immune evasion contributes to the pathogenesis of high-grade prostate cancer (HGPCa) remains an area of active inquiry. METHODS:Through single-cell RNA sequencing and multicolor flow cytometry of freshly isolated prostatectomy specimens and matched peripheral blood, we aimed to characterize the tumor immune microenvironment (TME) of localized prostate cancer (PCa), including HGPCa and low-grade prostate cancer (LGPCa). RESULTS: TILs. The PCa TME was infiltrated by macrophages but these did not clearly cluster by M1 and M2 markers. CONCLUSIONS:T cell exhaustion in localized PCa, a finding enriched in HGPCa relative to LGPCa. These studies suggest a possible link between the clinical-pathologic risk of PCa and the associated TME. Our results have implications for our understanding of the immunologic mechanisms of PCa pathogenesis and the implementation of immunotherapy for localized PCa.

PURPOSE/UNASSIGNED:As the largest integrated health care system in the United States, the Veterans Health Administration (VA) is a leader in telehealth-delivered care. All 10 million Veterans cared for within the VA are eligible for telehealth. The VA cares for approximately 46,000 Veteran patients with newly diagnosed cancer and an estimated 400,000 prevalent cases annually. With nearly 38% of VA health care system users residing in rural areas and only 44% of rural counties having an oncologist, many Veterans lack local access to specialized cancer services. METHODS/UNASSIGNED:We describe the VA's National TeleOncology (NTO) Service. NTO was established to provide Veterans with the opportunity for specialized treatment regardless of geographical location. Designed as a hub-and-spoke model, VA oncologists from across the country can provide care to patients at spoke sites. Spoke sites are smaller and rural VA medical centers that are less able to independently provide the full range of services available at larger facilities. In addition to smaller rural spoke sites, NTO also provides subspecialized oncology care to Veterans located in larger VA medical facilities that do not have subspecialties available or that have limited capacity. RESULTS/UNASSIGNED:As of fiscal year 2021, 23 clinics are served by or engaged in planning for delivery of NTO and there are 24 physicians providing care through the NTO virtual hub. Most NTO physicians continue to provide patient care in separate traditional in-person clinics. Approximately 4,300 unique Veterans have used NTO services. Approximately half (52%) of Veterans using NTO lived in rural areas. Most of these Veterans had more than one remote visit through NTO. CONCLUSION/UNASSIGNED:NTO is a state-of-the-art model that has the potential to revolutionize the way cancer care is delivered, which should improve the experience of Veterans receiving cancer care.

Emerging evidence suggests that STK11 alterations, frequently found in non-small-cell lung cancers, may be prognostic and/or predictive of response to therapy, particularly immunotherapy. STK11 affects multiple important cellular pathways, and mutations lead to tumor growth by creating an immunosuppressive and altered metabolic environment through changes in AMPK, STING, and vascular endothelial growth factor pathways. We illustrate the questions surrounding STK11 genomic alteration in NSCLC with a case series comprising six United States Veterans from a single institution. We discuss the history of STK11, review studies on its clinical impact, and describe putative mechanisms of how loss of STK11 might engender resistance to immunotherapy or other therapies. While the exact impact of STK11 alteration in non-small-cell lung cancer remain to be fully elucidated, future research and ongoing clinical trials will help us better understand its role in cancer development and devise more effective treatment strategies.