Michael J Kelley

Purpose: The Veterans Health Administration (VA) created National TeleOncology (NTO) service in 2019 to provide telehealth cancer care to Veterans and to augment care provided at VA facilities through a hub and spoke model. More recently, VA established a Decentralized Clinical Trials (DCTs) infrastructure to support clinical trials (CTs) that rely on telehealth, where research staff are at different locations, and/or where a single IRB provides oversight even when subjects are at different locations. Brief Description: Research support and infrastructure is variable across VA facilities resulting in uneven access to cancer CTs in the VA system. Veterans often live in rural areas or have transportation challenges, which are barriers to participate in CTs. The COVID-19 pandemic resulted in increased telehealth use in clinical care and in CTs, providing the rationale for a focused effort in DCTs. DCTs have the potential to …

The objective of this study was to discover clinical and pharmacogenetic factors associated with bevacizumab-related gastrointestinal hemorrhage in Cancer and Leukemia Group B (Alliance) 90401. Patients with metastatic castration-resistant prostate cancer received docetaxel and prednisone±bevacizumab. Patients were genotyped using Illumina HumanHap610-Quad and assessed using cause-specific risk for association between single nucleotide polymorphisms (SNPs) and gastrointestinal hemorrhage. In 1008 patients, grade 2 or higher gastrointestinal hemorrhage occurred in 9.5% and 3.8% of bevacizumab (n= 503) and placebo (n= 505) treated patients, respectively. Bevacizumab (P< 0.001) and age (P= 0.002) were associated with gastrointestinal hemorrhage. In 616 genetically estimated Europeans (n= 314 bevacizumab and n= 302 placebo treated patients), grade 2 or higher gastrointestinal …

BackgroundAn electronic health record–based tool could improve accuracy and eliminate bias in provider estimation of the risk of death from other causes among men with nonmetastatic cancer.ObjectiveTo recalibrate and validate the Veterans Aging Cohort Study Charlson Comorbidity Index (VACS-CCI) to predict non–prostate cancer mortality (non-PCM) and to compare it with a tool predicting prostate cancer mortality (PCM).Design, setting, and participantsAn observational cohort of men with biopsy-confirmed nonmetastatic prostate cancer, enrolled from 2001 to 2018 in the national US Veterans Health Administration (VA), was divided by the year of diagnosis into the development (2001–2006 and 2008–2018) and validation (2007) sets.Outcome measurements and statistical analysisMortality (all cause, non-PCM, and PCM) was evaluated. Accuracy was assessed using calibration curves and C statistic in the …

PurposeThe National TeleOncology Service (NTO) is a clinical service that enables VA oncologists, from across the country, to provide services via telehealth to Veterans with cancer. We sought to understand the early experiences of medical oncologists, Veterans, and clinical staff to inform the national NTO scale–out.Materials and methodsWe recruited clinicians who provided and/or Veterans who received care from three early adopting NTO sites. We purposively sampled Veteran participants who were: (1) diagnosed and/or treated December 2016 – March 2021 with prostate, non-small cell lung, non-Hodgkin's lymphoma, or colorectal cancer as confirmed by ICD–10 codes, and (2) obtained NTO-delivered care in October 2016 through July 2022 at one of the included NTO sites. We used rapid qualitative analysis.ResultsWe conducted 3 provider focus groups and interviewed 15 Veterans. Participants noted the …

MethodsWe conducted an observational study to evaluate uptake of germline testing for patients with advanced prostate cancer after the launch of the prostate cancer OCP. Patients with advanced prostate cancer were identified using VA’s Corporate Data Warehouse. Inclusion criteria included living as of 5/2/2021 with at least one VA oncology or urology visit in the year prior (prevalent cases) or diagnosed during the observation period (5/3/2021-11/2/2022)(incident cases). All patients were followed for germline test orders through 5/2/2023. Contracted reference laboratories provided reports about germline test orders. We estimated associations between patient (age, self-reported race/ethnicity, vital status, marital status, rurality, area deprivation index), clinical (tumor testing ordered, oncology or urology visit), and facility (hospital complexity, region, Prostate Cancer Foundation Center of Excellence) characteristics …

Background Since the onset of COVID-19, oncology practices across the US have integrated telemedicine (TM) and remote patient monitoring (RPM) into routine care and clinical trials. The extent of provider experience and comfort with TM/RPM in treatment trials, however, is unknown. We surveyed oncology researchers to assess experience and comfort with TM/RPM. Methods Between April 10 and June 1, 2022, we distributed email surveys to US-based members of the American Society of Clinical Oncology (ASCO) whose member records indicated interest or specialization in clinical research. We collected respondent demographic data, clinical trial experience, workplace characteristics, and comfort and experience with TM/RPM use across trial components in phase I and phase II/III trials. TM/RPM was defined as clinical trial-related healthcare and monitoring for patients …

BackgroundThe KRAS G12C inhibitor sotorasib was approved for the treatment of advanced NSCLC in the second line or later based on the CodeBreaK100 trial. However, data on the real-world efficacy and safety of sotorasib, as well as its optimal dose, remain limited.MethodsPatients treated with sotorasib for NSCLC through the Veterans Health Administration (VHA) were retrospectively identified from the Corporate Data Warehouse. Survival, response, and toxicity data were obtained from chart review.ResultsAmong the 128 patients treated with sotorasib through the VHA, objective response rate was 34%, progression-free survival (PFS) 6.0 months, and overall survival (OS) 12.0 months. Similar PFS was observed among the 16 patients who received frontline sotorasib without any prior systemic therapy for NSCLC. Toxicity leading to sotorasib interruption or dose reduction occurred in 37% of patients, while …

Background Until recently, multi-agent chemotherapy (CT) was the standard of care for patients with advanced non-small cell lung cancer (NSCLC). Clinical trials have confirmed benefits in overall survival (OS) and progression-free survival with immunotherapy (IO) compared to CT. This study compares real-world treatment patterns and outcomes between CT and IO administrations in second-line (2L) settings for patients with stage IV NSCLC. Materials and methods This retrospective study included patients in the United States Department of Veterans Affairs healthcare system diagnosed with stage IV NSCLC during 2012–2017 and receiving IO or CT in the 2L. Patient demographics and clinical characteristics, healthcare resource utilization (HCRU), and adverse events (AEs) were compared between treatment groups. Logistic regression was used to examine differences in baseline characteristics between groups, and inverse probability weighting multivariable Cox proportional hazard regression was used to analyze OS. Results Among 4,609 Veterans who received first-line (1L) therapy for stage IV NSCLC, 96% received 1L CT alone. A total of 1,630 (35%) were administered 2L systemic therapy, with 695 (43%) receiving IO and 935 (57%) receiving CT. Median age was 67 years (IO group) and 65 years (CT group); most patients were male (97%) and white (76–77%). Patients administered 2L IO had a higher Charlson Comorbidity Index than those administered CT (p = 0.0002). 2L IO was associated with significantly longer OS compared with CT (hazard ratio 0.84, 95% CI 0.75–0.94). IO was more frequently prescribed during the study …

Black Veterans have higher a incidence of localized and metastatic prostate cancer compared to White Veterans yet are underrepresented in reports of frequencies of somatic and germline alterations. This retrospective analysis of somatic and putative germline alterations was conducted in a large cohort of Veterans with prostate cancer (N = 835 Black, 1613 White) who underwent next generation sequencing through the VA Precision Oncology Program, which facilitates molecular testing for Veterans with metastatic cancer. No differences were observed in gene alterations for FDA approved targetable therapies (13.5% in Black Veterans vs. 15.5% in White Veterans, P = .21), nor in any potentially actionable alterations (25.5% vs. 28.7%, P =.1). Black Veterans had higher rates of BRAF (5.5% vs. 2.6%, P < .001) alterations, White Veterans TMPRSS2 fusions (27.2% vs. 11.7%, P < .0001). Putative germline …

3602Background: Colorectal cancer is the fourth most common cancer among Veterans and the third leading cause of cancer-related death in the USA. Use of comprehensive genomic profiling (CGP) to guide administration of FDA-approved biomarker directed therapies can improve outcomes among metastatic CRC (mCRC) patients. We sought to compute the rates of actionable biomarkers and prescriptions of associated FDA-approved therapies among Veterans in NPOP. Methods: The NPOP database was queried to identify mCRC patients who had undergone CGP via tissue or liquid biopsy between February 2019 and July 2022 and had one of the following 5 actionable biomarker profiles: NRAS/KRAS/BRAF wildtype, BRAF V600E, MSI-H, TMB-H, or NTRK fusion or rearrangement. The VA’s Corporate Data Warehouse (CDW) was queried to extract prescription data for seven FDA-approved biomarker …

PURPOSETelegenetics services can expand access to guideline-recommended cancer genetic testing. However, access is often not distributed equitably to all races and ethnicities. We evaluated the impact of an on-site nurse-led cancer genetics service in a diverse Veterans Affairs Medical Center (VAMC) oncology clinic on likelihood of germline testing (GT) completion.METHODSWe conducted an observational retrospective cohort study of patients who were referred for cancer genetics services at the Philadelphia VAMC between October 1, 2020, and February 28, 2022. We evaluated the association between genetics service (on-site v telegenetics) and likelihood of GT completion in a subcohort of new consults, excluding patients with prior consults and those referred for known history of germline mutations.RESULTSA total of 238 Veterans, including 108 (45%) seen on site, were identified for cancer genetics …

PURPOSEImmune checkpoint inhibitors (ICIs) are used for an increasing number of indications across various tumor types, as well as several tumor-agnostic indications in patients with advanced cancer. Although many patients benefit from ICI therapy, others do not, highlighting a need for better predictive biomarkers. Tumor mutational burden (TMB) reflects the global number of mutations within a tumor and has been widely explored as a predictive biomarker of ICI response. The current tumor type–agnostic US Food and Drug Administration approval of pembrolizumab for metastatic solid tumors defines high TMB (TMB-H) as ≥10 mut/Mb as measured by FoundationOne CDx. This fixed cutoff may not be the ideal value across all solid tumors.METHODSWe performed a retrospective analysis of the association of survival outcomes with TMB in patients treated with ICI for five major cancer types, using real-world …

PURPOSEIncreasing utilization of comprehensive genomic profiling (CGP) and a growing number of targeted agents (TAs) have led to substantial improvements in outcomes among patients with cancer with actionable mutations. We sought to evaluate real-world experience with off-label TAs among Veterans who underwent CGP.METHODSThe National Precision Oncology Program database and VA Corporate Data Warehouse were queried to identify patients who underwent CGP between February 2019 and December 2021 and were prescribed 1 of 73 TAs for malignancy. OncoKB annotations were used to select patients who received off-label TAs based upon CGP results. Chart abstraction was performed to review response, toxicities, and time to progression.RESULTSOf 18,686 patients who underwent CGP, 2,107 (11%) were prescribed a TA and 169 (0.9%) were prescribed a total of 183 regimens …

INTRODUCTION AND OBJECTIVEAgent Orange has been posited as an environmental risk factor for prostate cancer among United States Veterans. Prior studies have shown that Veterans with Agent Orange exposure are diagnosed at a younger age and at more advanced clinical stages. It is unknown if there are differences in somatic alterations among Veterans exposed to Agent Orange.METHODSGenomic alterations were identified from clinical tumor testing conducted from 2019–2022 in a large cohort of Veterans with metastatic prostate cancer diagnosed from 2001–2022. Primary prostate and metastatic carcinoma tissue specimens were submitted for Foundation Medicine tumor-only sequencing. Baseline demographics, clinical, and genomic alterations data were stratified by Veteran self-reported exposure to Agent Orange in accordance with an Institutional Review Board approved protocol.RESULTSOf …

e13567Background: Liquid biopsies using cell-free DNA (cfDNA) can be used in prostate cancer (PrCa) patients when tissue is unavailable and repeat biopsy is not feasible. Given the older age of PrCa patients, liquid biopsy may detect alterations related to clonal hematopoiesis of indeterminate potential (CHIP), generating uncertainty in the clinical utility of the results. We sought to identify clinical predictors of successful cfDNA biopsy, where the reported alterations are more likely to reflect the individual’s prostate cancer cfDNA instead of CHIP in a large cohort of United States Veterans with PrCa. Methods: Next-generation sequencing of cfDNA biopsy specimens was performed through the VA National Precision Oncology Program (NPOP) from February 2019 to November 2022. Successful identification of PrCa cfDNA testing was defined as the identification of an alteration in one or more PrCa-related genes …

Immune checkpoint inhibitors, a class of drugs used in approximately forty unique cancer indications, are a sizable component of the economic burden of cancer care in the US. Instead of personalized weight-based dosing, immune checkpoint inhibitors are most commonly administered at “one-size-fits-all” flat doses that are higher than necessary for the vast majority of patients. We hypothesized that personalized weight-based dosing along with common stewardship efforts at the pharmacy level, such as dose rounding and vial sharing, would lead to reductions in immune checkpoint inhibitor use and lower spending. Using data from the Veterans Health Administration (VHA) and Medicare drug prices, we estimated reductions in immune checkpoint inhibitor use and spending that would be associated with pharmacy-level stewardship strategies, in a case-control simulation study of individual patient–level immune …

BACKGROUND Dexamethasone is commonly used to manage peritumoral edema and alleviate neurologic symptoms in patients with intracranial tumors. The optimal dexamethasone dose for brain metastases is unknown and widely variable. Recent literature reports the most common regimen is 4 mg four times daily. However, the half-life of dexamethasone is 35-54 hours, suggesting that such frequent dosing may be unnecessary. We explored the dose-effect relationship of dexamethasone on brain metastases patient outcomes to improve quality of care. METHODS We retrospectively identified 100 patients (1/1/2016 – 12/31/2022) with brain metastases who were treated with dexamethasone and had adequate follow-up. All patients received standard oncologic care including chemotherapy, radiotherapy, and/or surgical intervention. We evaluated the association between …

Background Cancer diagnoses are associated with an increased risk for suicide. The aim of this study was to evaluate this association among Veterans receiving Veterans Health Administration (VHA) care, a population that has an especially high suicide risk. Methods Among 4,926,373 Veterans with VHA use in 2011 and in 2012 or 2013, and without VHA cancer diagnoses in 2011, we assessed suicide risk following incident cancer diagnoses. Risk time was from initial VHA use in 2012–2013 to 12/31/2018 or death, whichever came first. Cox proportional hazards regression models evaluated associations between new cancer diagnoses and suicide risk, adjusting for age, sex, VHA regional network, and mental health comorbidities. Suicide rates were calculated among Veterans with new cancer diagnoses through 84 months following diagnosis. Results A new cancer diagnosis corresponded to a 47% higher …

PURPOSEAs 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.METHODSWe 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 …

1519Background: Diagnosing and treating more than 43,000 Veterans annually, the Veterans Affairs (VA) National Oncology Program (NOP) oversees the largest integrated providers of hematology/oncology services in the US. Within the VA, parenteral therapies are primarily offered at VA Medical Centers (VAMC) in urban areas, often inaccessible to rural patients. Travel distance, parking, time, and caregiver support can prevent patients from adhering to treatment regimens. To resolve these challenges, NOP launched the Close to Me (CTM) infusion service. The service seeks to reduce travel time for patients, improve VA care continuity, and increase access points to patient-centric care by administering treatments utilizing the network of VA Community Based Outpatient Clinics (CBOC). Methods: In the CTM CBOC infusion service select medications are compounded at the main VAMC, then transported via a …