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Background: The Veterans Health Administration (VHA) is the largest integrated health care system in the United States (US). Among VHA patients, the rate of use of concurrent chemoradiation therapy (CCRT) among those with unresectable, stage III non-small cell lung cancer (NSCLC) is unknown. The objective was to report recent CCRT treatment patterns in VHA patients and identify characteristics associated with receipt of CCRT.Methods: Using Department of Veteran Affairs (VA) Cancer Registry System data linked to VA electronic medical records, we determined rates of CCRT, sequential CRT (SCRT), radiation therapy (RT) only, chemotherapy (CT) only, and neither treatment.Results: Among 4054 VHA patients who met study criteria, CCRT rates slightly increased from 44 to 50% between 2013 and 2017. Factors associated with decreased odds of CCRT receipt compared to any other treatment included increasing age (adjusted odds ratio [aOR] per 10 years = 0.67; 95% CI: 0.60-0.76) and Charlson-Deyo comorbidity score (aOR = 0.94; 95% CI: 0.91-0.97). White race was associated with increased odds of CCRT receipt (aOR = 1.24; 95% CI: 1.004-1.53). In a chart review sample of 200 patients, less than half (n = 85) had a documented reason for not receiving CCRT. Among these, 29% declined treatment, and 71% did not receive CCRT due to "not being a candidate" for reasons related to frailty or lung nodules being too far apart for radiation therapy.Conclusions: CCRT rates among VHA patients with unresectable, stage III NSCLC slightly increased from 2013 to 2017; however in 2017, only half were receiving CCRT. Older patients and those with multiple comorbidities were less likely to receive CCRT and even when controlling for these factors, non-white patients were less likely to receive CCRT. [ABSTRACT FROM AUTHOR]

PURPOSE: Advances in precision oncology, including RAS testing to predict response to epidermal growth factor receptor monoclonal antibodies (EGFR mAbs) in colorectal cancer (CRC), can extend patients' lives. We evaluated uptake and clinical use of KRAS molecular testing, guideline recommended since 2010, in the Veterans Affairs Healthcare System (VA). MATERIALS AND METHODS: We conducted a retrospective cohort study of patients with stage IV CRC diagnosed in the VA 2006-2015. We gathered clinical, demographic, molecular, and treatment data from the VA Corporate Data Warehouse and 29 commercial laboratories. We performed multivariable analyses of associations between patient characteristics, KRAS testing, and EGFR mAb treatment. RESULTS: Among 5,943 patients diagnosed with stage IV CRC, only 1,053 (17.7%) had KRAS testing. Testing rates increased from 2.3% in 2006 to 28.4% in 2013. In multivariable regression, older patients (odds ratio, 0.17; 95% CI, 0.09 to 0.32 for ≥ age 85 v < 45 years) and those treated in the Northeast and South regions were less likely, and those treated at high-volume CRC centers were more likely to have KRAS testing (odds ratio, 2.32; 95% CI, 1.48 to 3.63). Rates of potentially guideline discordant care were high: 64.3% (321/499) of KRAS wild-type (WT) went untreated with EGFR mAb and 8.8% (401/4,570) with no KRAS testing received EGFR mAb. Among KRAS -WT patients, survival was better for patients who received EGFR mAb treatment (29.6 v 18.8 months; P <.001). CONCLUSION: We found underuse of KRAS testing in advanced CRC, especially among older patients and those treated at lower-volume CRC centers. We found high rates of potentially guideline discordant underuse of EGFR mAb in patients with KRAS -WT tumors. Efforts to understand barriers to precision oncology are needed to maximize patient benefit. [ABSTRACT FROM AUTHOR]

Background: Transportation barriers limit access to cancer care services and contribute to suboptimal clinical outcomes. Our objectives were to describe the frequency of Veterans reporting and the factors associated with transportation barriers to or from colorectal cancer (CRC) care visits.Methods: Between November 2015 and September 2016, Veterans with incident stage I, II, or III CRC completed a mailed survey to assess perceived barriers to recommended care. Participants who reported difficulty with transportation to or from CRC care appointments were categorized as experiencing transportation barriers. We assessed pairwise correlations between transportation barriers, transportation-related factors (e.g., mode of travel), and chaotic lifestyle (e.g., predictability of schedules), and used logistic regression to examine the association between the reporting of transportation difficulties, distance traveled to the nearest Veterans Affairs (VA) facility, and life chaos.Results: Of the 115 Veterans included in this analysis, 18% reported experiencing transportation barriers. Distance to the VA was not strongly correlated with the reporting of transportation barriers (Spearman's ρ = 0.12, p = 0.19), but chaotic lifestyle was both positively and significantly correlated with experiencing transportation barriers (Spearman's ρ = 0.22, p = 0.02). Results from the logistic regression model modestly supported the findings from the pairwise correlations, but were not statistically significant.Conclusions: Transportation is an important barrier to or from CRC care visits, especially among Veterans who experience greater life chaos. Identifying Veterans who experience chaotic lifestyles would allow for timely engagement in behavioral interventions (e.g., organizational skills training) and with support services (e.g., patient navigation). [ABSTRACT FROM AUTHOR]

Background: To support the rising need for testing and to standardize tumor DNA sequencing practices within the U.S. Department of Veterans Affairs (VA)'s Veterans Health Administration (VHA), the National Precision Oncology Program (NPOP) was launched in 2016. We sought to assess oncologists' practices, concerns, and perceptions regarding Next-Generation Sequencing (NGS) and the NPOP. Materials and methods: Using a purposive total sampling approach, oncologists who had previously ordered NGS for at least one tumor sample through the NPOP were invited to participate in semi-structured interviews. Questions assessed the following: expectations for the NPOP, procedural requirements, applicability of testing results, and the summative utility of the NPOP. Interviews were assessed using an open coding approach. Thematic analysis was conducted to evaluate the completed codebook. Themes were defined deductively by reviewing the direct responses to interview questions as well as inductively by identifying emerging patterns of data. Results: Of the 105 medical oncologists who were invited to participate, 20 (19%) were interviewed from 19 different VA medical centers in 14 states. Five recurrent themes were observed: (1) Educational Efforts Regarding Tumor DNA Sequencing Should be Undertaken, (2) Pathology Departments Share a Critical Role in Facilitating Test Completion, (3) Tumor DNA Sequencing via NGS Serves as the Most Comprehensive Testing Modality within Precision Oncology, (4) The Availability of the NPOP Has Expanded Options for Select Patients, and (5) The Completion of Tumor DNA Sequencing through the NPOP Could Help Improve Research Efforts within VHA Oncology Practices. Conclusion: Medical oncologists believe that the availability of tumor DNA sequencing through the NPOP could potentially lead to an improvement in outcomes for veterans with metastatic solid tumors. Efforts should be directed toward improving oncologists' understanding of sequencing, strengthening collaborative relationships between oncologists and pathologists, and assessing the role of comprehensive NGS panels within the battery of precision tests. [ABSTRACT FROM AUTHOR]

PURPOSE: Next-generation sequencing (NGS) multigene panel testing has become widespread, including the Veterans Affairs (VA), through the VA National Precision Oncology Program (NPOP). The interpretation of genomic alterations remains a bottleneck for realizing precision medicine. We sought to examine the concordance for pathogenicity determination and clinical actionability of annotation services in NPOP. METHODS: Unique gene variants were generated from NGS gene panel results using two sequencing services. For each unique gene variant, annotations were provided through N-of-One (NoO), IBM Watson for Genomics (WfG), and OncoKB. Annotations for pathogenicity (all three sources) and actionability (WfG and OncoKB) were examined for concordance. Cohen's kappa statistic was calculated to measure agreement between annotation services. RESULTS: Among 1,227 NGS results obtained between 2015 and 2017, 1,388 unique variants were identified in 117 genes. The genes with the largest number of variants included TP53 (270), STK11 (92), and CDKN2A (81). The most common cancer type was lung adenocarcinoma (440), followed by colon adenocarcinoma (113). For pathogenic and likely pathogenic variants, there was 30% agreement between WfG and NoO (kappa, −0.26), 76% agreement between WfG and OncoKB (kappa, 0.22), and 42% agreement between NoO and OncoKB (kappa, −0.07). For level 1 drug actionability of gene variant–diagnosis combinations, there was moderate agreement between WfG and OncoKB (96.9%; kappa, 0.44), with 27 combinations identified as level 1 by both services, 58 by WfG alone, and 6 variants by OncoKB alone. CONCLUSION: There is substantial variability in pathogenicity assessment of NGS variants in solid tumors by annotation services. In addition, there was only moderate agreement in level 1 therapeutic actionability recommendations between WfG and OncoKB. Improvement in the precision of NGS multigene panel annotation is needed. [ABSTRACT FROM AUTHOR]

PURPOSE: The Veterans Health Administration (VHA) is the largest cancer care provider in the United States, with the added challenge of serving more than twice the percentage of patients with cancer in rural areas than the national average. The VHA established the National Precision Oncology Program in 2016 to implement and standardize the practice of precision oncology across the diverse VHA system. METHODS: Tumor or peripheral blood specimens from veterans with advanced solid tumors who were eligible for treatment were submitted for next-generation sequencing (NGS) at two commercial laboratories. Annotated results were generated by the laboratories and independently using IBM Watson for Genomics. Levels-of-evidence treatment recommendations were based on OncoKB criteria. RESULTS: From July 2016 to June 2018, 3,698 samples from 72 VHA facilities were submitted for NGS testing, of which 3,182 samples (86%) were successfully sequenced. Most samples came from men with lung, prostate, and colorectal cancers. Thirty-four percent of samples were from patients who lived in a rural area. TP53 , ATM , and KRAS were among the most commonly mutated genes. Approximately 70% of samples had at least one actionable mutation, with clinical trials identified as the recommended option in more than 50%. Mutations in genes associated with a neuroendocrine prostate cancer phenotype were expressed at increased frequency among veterans than in the general population. The most frequent therapies prescribed in response to NGS testing were immune checkpoint inhibitors, EGFR kinase inhibitors, and PARP inhibitors. CONCLUSION: Clinical implementation of precision oncology is feasible across the VHA health care system, including rural sites. Veterans have unique occupational exposures that might inform the nature of the mutational signatures identified here. Importantly, these results underscore the importance of increasing clinical trial availability to veterans. [ABSTRACT FROM AUTHOR]

Purpose: Standard therapy for locally advanced rectal cancer includes neoadjuvant chemoradiation and surgery. Complete response (CR) rates after chemoradiation can be as high as 29%, suggesting that nonoperative management (NOM) may be reasonable with appropriately selected patients. We sought to identify potential NOM candidates.Methods and Materials: Using the Veterans Administration Central Cancer Registry, patients with stage II to III rectal cancer receiving chemoradiation with or without subsequent surgery were identified. Clinical CR (cCR) was assessed by physical examination, endoscopy, or imaging. Kaplan-Meier and log-rank tests were used to assess survival; multivariate analysis was performed using Cox proportional hazards.Results: A total of 1313 patients were identified. Of these, 313 received chemoradiation alone (CRT cohort); 1000 received chemoradiation followed by surgery (CRT + S cohort). Median follow-up was 67.2 months. Median overall survival (OS) was 68.5 months. Median OS was 30.6 months for CRT and 89.3 months for CRT + S (P < .001). Median disease-specific survival (DSS) was 44.8 months for CRT and not reached (NR) for CRT + S (P < .001). Sixty-five CRT patients (20.8%) had a cCR. Median OS for CRT cCR patients was 73.5 months (P = .128 vs CRT + S); median DSS was NR (P = .161 vs CRT + S). One hundred thirty-seven (10.5%) CRT + S patients had a pathologic CR (pCR). Median OS with pCR was 133.7 months (P < .001 vs CRT cCR), and median DSS was NR (P = .276 vs CRT cCR).Conclusions: CRT patients with cCR had similar OS and DSS versus CRT + S patients and similar DSS versus CRT + S patients with a pCR. This suggests that patients with locally advanced rectal cancer with a cCR to CRT have an excellent prognosis and may be candidates for organ preservation. [ABSTRACT FROM AUTHOR]

Background: The Veterans Affairs (VA) healthcare system is a high-volume provider of cancer care. Women are the fastest growing patient population using VA healthcare services. Quantifying the types of cancers diagnosed among women in the VA is a critical step toward identifying needed healthcare resources for women Veterans with cancer. Materials and Methods: We obtained data from the VA Central Cancer Registry for cancers newly diagnosed in calendar year 2010. Our analysis was limited to women diagnosed with invasive cancers (e.g., stages I-IV) between January 1, 2010, and December 31, 2010, in the VA healthcare system. We evaluated frequency distributions of incident cancer diagnoses by primary anatomical site, race, and geographic region. For commonly occurring cancers, we reported distribution by stage. Results: We identified 1,330 women diagnosed with invasive cancer in the VA healthcare system in 2010. The most commonly diagnosed cancer among women Veterans was breast (30%), followed by cancers of the respiratory (16%), gastrointestinal (12%), and gynecological systems (12%). The most commonly diagnosed cancers were similar for white and minority women, except white women were significantly more likely to be diagnosed with respiratory cancers (p < 0.01) and minority women were significantly more likely to be diagnosed with gastrointestinal cancers (p = 0.03). Conclusions: Understanding cancer incidence among women Veterans is important for healthcare resource planning. While cancer incidence among women using the VA healthcare system is similar to U.S civilian women, the geographic dispersion and small incidence relative to male cancers raise challenges for high quality, well-coordinated cancer care within the VA. [ABSTRACT FROM AUTHOR]

Colorectal cancer (CRC) accounts for ~9% of all cancers in the Veteran population, a fact which has focused a great deal of the attention of the VA's research and development efforts. A field-based meeting of CRC experts was convened to discuss both challenges and opportunities in precision medicine for CRC. This group, designated as the VA Colorectal Cancer Cell-genomics Consortium (VA4C), discussed advances in CRC biology, biomarkers, and imaging for early detection and prevention. There was also a discussion of precision treatment involving fluorescence-guided surgery, targeted chemotherapies and immunotherapies, and personalized cancer treatment approaches. The overarching goal was to identify modalities that might ultimately lead to personalized cancer diagnosis and treatment. This review summarizes the findings of this VA field-based meeting, in which much of the current knowledge on CRC prescreening and treatment was discussed. It was concluded that there is a need and an opportunity to identify new targets for both the prevention of CRC and the development of effective therapies for advanced disease. Also, developing methods integrating genomic testing with tumoroid-based clinical drug response might lead to more accurate diagnosis and prognostication and more effective personalized treatment of CRC. [ABSTRACT FROM AUTHOR]

Introduction: Nearly 50,000 incident cancer cases are reported in Veterans Affairs (VA) Central Cancer Registry (VACCR) annually. This article provides an updated report of cancer incidence recorded in VACCR.Materials and Methods: Data were obtained from VACCR for incident cancers diagnosed in the VA health care system, focusing on 2010 data. Cancer incidence among VA patients is described by anatomical site, sex, race, stage, and geographic location, and was compared to the general U.S. cancer population.Results: In 2010, among 46,170 invasive cancers, 97% were diagnosed among men. Approximately 80% of newly diagnosed patients were white, 19% black, and less than 2% were other minority races. Median age at diagnosis was 65 years. The three most frequently diagnosed cancers among VA were prostate (29%), lung/bronchus (18%), and colon/rectum (8%). Melanoma and kidney/renal pelvis tied for fourth (4%), and urinary bladder tied for sixth with liver and intrahepatic bile duct (3.4%). Approximately 23% of prostate, 21% of lung/bronchus, and 31% of colon/rectum cancers were diagnosed with Stage I disease. The overall invasive cancer incidence rate among VA users was 505.8 per 100,000 person-years.Conclusions: Although the composition of the VA population is shifting and includes a larger number of women, registry data indicate that incident cancers in VA in 2010 were most similar to those observed among U.S. men. Consistent reporting of VACCR data is important to provide accurate estimates of VA cancer incidence. This information can be used to plan efforts to improve quality of cancer care and access to services. [ABSTRACT FROM AUTHOR]

Background: Current clinical guidelines recommend epidermal growth factor receptor (EGFR) mutational testing in patients with metastatic non-small cell lung cancer (NSCLC) to predict the benefit of the tyrosine kinase inhibitor erlotinib as first-line treatment. Proteomic (VeriStrat) testing is recommended for patients with EGFR negative or unknown status when erlotinib is being considered. Departure from this clinical algorithm can increase costs and may result in worse outcomes. We examined EGFR and proteomic testing among patients with NSCLC within the Department of Veterans Affairs (VA). We explored adherence to guidelines and the impact of test results on treatment decisions and cost of care.Methods: Proteomic and EGFR test results from 2013 to 2015 were merged with VA electronic health records and pharmacy data. Chart reviews were conducted. Cases were categorized based on the appropriateness of testing and treatment.Results: Of the 69 patients with NSCLC who underwent proteomic testing, 33 (48%) were EGFR-negative and 36 (52%) did not have documented EGFR status. We analyzed 138 clinical decisions surrounding EGFR/proteomic testing and erlotinib treatment. Most decisions (105, or 76%) were concordant with clinical practice guidelines. However, for 24 (17%) decisions documentation of testing or justification of treatment was inadequate, and 9 (7%) decisions represented clear departures from guidelines.Conclusion: EGFR testing, the least expensive clinical intervention analyzed in this study, was significantly underutilized or undocumented. The records of more than half of the patients lacked information on EGFR status. Our analysis illustrated several clinical scenarios where the timing of proteomic testing and erlotinib diverged from the recommended algorithm, resulting in excessive costs of care with no documented improvements in health outcomes. [ABSTRACT FROM AUTHOR]

BACKGROUND Adjuvant chemotherapy after surgical resection improves outcomes for patients with early-stage non-small cell lung cancer (NSCLC). To the authors' knowledge, there are no published prospective trials to date of adjuvant chemotherapy after surgical resection administered exclusively in older patients. In the current study, the authors sought to evaluate the efficacy of adjuvant chemotherapy in older patients in a Veterans Health Administration cohort. METHODS Patients who underwent surgical resection for American Joint Committee on Cancer stages IB to III NSCLC between 2001 and 2011 were analyzed. Data regarding patient demographics and comorbidities, tumor characteristics, and primary treatment were collected. Patients were divided into 2 groups based on age at diagnosis: those aged <70 years and those aged ≥70 years. The primary exposure was use of adjuvant chemotherapy. A Cox proportional hazards model was used to estimate the significance of patient characteristics. Survival curves were estimated using the Kaplan-Meier method and group comparisons were performed using the log-rank test. RESULTS The analysis included 7593 patients who underwent surgical resection for stage IB to stage III NSCLC. Among these, 2897 patients (38%) were aged ≥70 years. The percentage of older patients who received adjuvant chemotherapy was approximately one-half that of younger patients who did so (15.3% vs 31.6%; P<.0001). Carboplatin-based doublets were used most often in all patients (64.6%). Both younger patients (hazard ratio, 0.79; 95% confidence interval, 0.72-0.86) and older patients (hazard ratio, 0.81; 95% confidence interval, 0.71-0.92) were found to have a lower risk of death with receipt of adjuvant chemotherapy. CONCLUSIONS Older patients derive a similar magnitude of benefit from adjuvant chemotherapy as younger patients and therefore adjuvant chemotherapy should not be withheld based on age alone. Cancer 2015;121:2578-2585. © 2015 American Cancer Society. [ABSTRACT FROM AUTHOR]

BACKGROUND Despite clinical trials demonstrating improved survival with adjuvant chemotherapy (AC) for patients with American Joint Committee on Cancer stages I to III non-small cell lung cancer (NSCLC), it is unclear whether this survival benefit extends to broader populations. The current study evaluated patterns of AC use and examined the impact of AC on survival. METHODS A retrospective analysis was conducted of patients in the Veterans Affairs Central Cancer Registry diagnosed with stages IB to IIIA NSCLC between 2001 and 2008. Descriptive statistics were used to examine patterns of AC use over an 8-year time period. Cox proportional hazards regression analyses were used to estimate hazards ratios (HR) and 95% confidence intervals (95% CIs) to compare mortality risk among patients treated with and without AC. RESULTS Among 14,306 patients with stages IB to IIIA NSCLC, 4929 underwent surgery and 22% of these received AC. The percentages of patients diagnosed in 2001 through 2003, 2004 through 2005, and 2006 through 2008 receiving AC were 7.0%, 29.8%, and 29.5%, respectively. There was no survival benefit with AC noted for patients diagnosed between 2001 and 2003, but AC was associated with improved survival for the period between 2004 and 2005 (HR, 0.78; 95% CI, 0.67-0.91) and 2006 through 2008 (HR, 0.79; 95% CI, 0.69-0.91). Of those patients receiving AC, 89% received platinum-doublet chemotherapy. Carboplatin remained the most common agent, although cisplatin use reached 43% in the period between 2006 and 2008. The HR for cisplatin relative to carboplatin was 0.96 (95% CI, 0.80-1.15). CONCLUSIONS There was a significant increase in the use of AC between 2001 and 2008 and AC was associated with an improvement in overall survival. Cancer 2014;120:1939-1947. © 2014 American Cancer Society. [ABSTRACT FROM AUTHOR]

Objective: Approximately 40,000 incident cancer cases are reported in the Veterans Affairs Central Cancer Registry (VACCR) annually (approximately 3% of U.S. cancer cases). Our objective was to provide the first comprehensive description of cancer incidence as reported in VACCR.Methods: Data were obtained from VACCR for incident cancers diagnosed in VA. Analyses focused on 2007 data. Cancer incidence among VA patients was compared to the general U.S. cancer population.Results: In 2007, 97.5% of VA cancers were diagnosed among men. Approximately 78.5% of newly diagnosed patients were White, 19.0% Black, and 2.5% were another race. Median age at diagnosis was 66 years. The geographic distribution of cancer patients in VA aligns that of VA users. The most commonly diagnosed cancers were similar between VA and the U.S. male cancer population. The five most frequently diagnosed cancers among VA cancer patients were: prostate (31.8%), lung/bronchus (18.8%), colon/rectum (8.6%), urinary bladder (3.6%), and skin melanomas (3.4%). VA patients were diagnosed at an earlier stage of disease for the three most commonly diagnosed cancers--lung/bronchus, colon/rectum, and prostate--compared to the U.S. male cancer population.Conclusions: Registry data indicate that incident cancers in VA in 2007 approximately mirrored those observed among U.S. men. [ABSTRACT FROM AUTHOR]

We have generated 3 mouse lines, each with a different mutation in the nonmuscle myosin II-A gene, Myh9 (R702C, D1424N, and E1841K). Each line develops MYH9-related disease similar to that found in human patients. R702C mutant human cDNA fused with green fluorescent protein was introduced into the first coding exon of Myh9, and D1424N and E1841K mutations were introduced directly into the corresponding exons. Homozygous R702C mice die at embryonic day 10.5-11.5, whereas homozygous D1424N and E1841K mice are viable. All heterozygous and homozygous mutant mice show macrothrombocytopenia with prolonged bleeding times, a defect in clot retraction, and increased extramedullary megakaryocytes. Studies of cultured megakaryocytes and live-cell imaging of megakaryocytes in the BM show that heterozygous R702C megakaryocytes form fewer and shorter proplatelets with less branching and larger buds. The results indicate that disrupted proplatelet formation contributes to the macrothrombocytopenia in mice and most probably in humans. We also observed premature cataract formation, kidney abnormalities, including albuminuria, focal segmental glomerulosclerosis and progressive kidney disease, and mild hearing loss. Our results show that heterozygous mice with mutations in the myosin motor or filament-forming domain manifest similar hematologic, eye, and kidney phenotypes to humans with MYH9-related disease. [ABSTRACT FROM AUTHOR]

Abstract: As superconducting niobium radio-frequency (SRF) cavities approach fundamental material limits, there is increased interest in understanding the details of topographical influences on realized performance limitations. Micro- and nano-roughness are implicated in both direct geometrical field enhancements as well as complications of the composition of the 50nm surface layer in which the super-currents typically flow. Interior surface chemical treatments such as buffered chemical polishing (BCP) and electropolishing (EP) used to remove mechanical damage leave surface topography, including pits and protrusions of varying sharpness. These may promote RF magnetic field entry, locally quenching superconductivity, so as to degrade cavity performance. A more incisive analysis of surface topography than the widely used average roughness is needed. In this study, a power spectral density (PSD) approach based on Fourier analysis of surface topography data acquired by both stylus profilometry and atomic force microscopy (AFM) is introduced to distinguish the scale-dependent smoothing effects, resulting in a novel qualitative and quantitative description of Nb surface topography. The topographical evolution of the Nb surface as a function of different steps of well-controlled EP is discussed. This study will greatly help to identify optimum EP parameter sets for controlled and reproducible surface levelling of Nb for cavity production. [Copyright &y& Elsevier]

Despite efforts for patient stabilization before radiologic procedures, cardiopulmonary arrests still occur. The purpose of our study was to define the incidence, patient characteristics, and outcomes of patients having cardiopulmonary arrest in a radiology department. We retrospectively reviewed patients sustaining cardiopulmonary arrest in the radiology department from 2002 to 2007. Patient characteristics and outcomes were documented. Descriptive statistics were calculated. Over the 6 years of the study, 1,480,578 radiographic procedures were performed, and 27 patients sustained a cardiopulmonary arrest in the radiology department for an incidence rate of 0.002 per cent. The average patient age was 66 years (range, 35 to 88 years); 12 were male (44%) Radiological procedures were diagnostic in 15 cases and therapeutic in 12 cases. The most common locations for arrest were in the CT area (9 patients) and the vascular procedures area (8 patients). The most common preprocedural patient locations were the hospital wards (11 patients [41%]), the emergency department/trauma bay (5 patients [19%]), the intensive care unit (4 patients [15%]), and an outpatient setting (four patients [15%]). Nineteen patients (70%) survived the initial code, 14 patients (52%) survived 24 hours, and 9 patients (33%) survived until discharge. Survival to discharge was significantly impacted by body mass index (P = 0.005 and type of radiologic procedure (P = 0.04) but not by the preprocedure patient location. Cardiopulmonary arrest occurring in the radiology department is a rare but potentially lethal occurrence. Patients undergoing vascular access procedures may be an at-risk group. Further study is needed to evaluate potential risk factors for cardiopulmonary arrest occurring in the radiology department. [ABSTRACT FROM AUTHOR]

Immortal tumor cell lines are an important model system for cancer research, however,misidentification and cross-contamination of cell lines are a common problem. Seven chordoma cell lines are reported in the literature, but none has been characterized in detail. We analyzed gene expression patterns and genomic copy number variations in five putative chordoma cell lines (U-CH1, CCL3, CCL4, GB60, and CM319). We also created a new chordoma cell line, U-CH2, and provided genotypes for cell lines for identity confirmation. Our analyses revealed that CCL3, CCL4, and GB60 are not chordoma cell lines, and that CM319 is a cancer cell line possibly derived from chordoma, but lacking expression of key chordoma biomarkers. U-CH1 and U-CH2 both have gene expression profiles, copy number aberrations, and morphology consistent with chordoma tumors. These cell lines also harbor genetic changes, such as loss of p16, MTAP, or PTEN, that make them potentially useful models for studying mechanisms of chordoma pathogenesis and for evaluating targeted therapies. [ABSTRACT FROM AUTHOR]

Tumors contain oxygenated and hypoxic regions, so the tumor cell population is heterogeneous. Hypoxic tumor cells primarily use glucose for glycolytic energy production and release lactic acid, creating a lactate gradient that mirrors the oxygen gradient in the tumor. By contrast, oxygenated tumor cells have been thought to primarily use glucose for oxidative energy production. Although lactate is generally considered a waste product, we now show that it is a prominent substrate that fuels the oxidative metabolism of oxygenated tumor cells. There is therefore a symbiosis in which glycolytic and oxidative tumor cells mutually regulate their access to energy metabolites. We identified monocarboxylate transporter 1 (MCT1) as the prominent path for lactate uptake by a human cervix squamous carcinoma cell line that preferentially utilized lactate for oxidative metabolism. Inhibiting MCT1 with alpha-cyano-4-hydroxycinnamate (CHC) or siRNA in these cells induced a switch from lactate-fueled respiration to glycolysis. A similar switch from lactate-fueled respiration to glycolysis by oxygenated tumor cells in both a mouse model of lung carcinoma and xenotransplanted human colorectal adenocarcinoma cells was observed after administration of CHC. This retarded tumor growth, as the hypoxic/glycolytic tumor cells died from glucose starvation, and rendered the remaining cells sensitive to irradiation. As MCT1 was found to be expressed by an array of primary human tumors, we suggest that MCT1 inhibition has clinical antitumor potential. [ABSTRACT FROM AUTHOR]

Summary: Endogenous hypoxia markers have been studied as prognostic indicators because they appear to be associated with tumor aggressiveness. This study was undertaken to compare the expression of two endogenous hypoxia markers, Hypoxia-inducible factor-1α (HIF-1α) and carbonic anhydrase IX (CA IX), with regard to their prognostic significance. We also compared spatial distribution of HIF-1α and CA IX and examined their relationship with expression of vascular endothelial growth factor (VEGF) and matrix metalloproteinase (MMP)-9, which may be regulated by hypoxia. We studied 74 resected stage I/II non-small cell lung cancers (NSCLCs) for expression of HIF-1α, CA IX, VEGF, and MMP-9 by immunohistochemistry, and the extent of tumor necrosis. Univariate and multivariate analyses were performed to assess prognostic implications of these markers for disease free survival. HIF-1α expression was strongly correlated with CA IX (r =0.667, p &#60;0.001) and was co-localized with CA IX in corresponding areas. HIF-1α and CA IX expression were higher in areas with moderate to severe tumor necrosis relative to areas with minimal necrosis, suggesting their relationship with hypoxia. VEGF expression also showed a modest relationship with HIF-1α (p =0.07); however, there was no relationship between HIF-1α and MMP-9 expression (p >0.99). Expression of HIF-1α and CA IX above the median value was significantly associated with shorter disease free survival in univariate analysis (p &#60;0.05). However, only high CA IX expression and pathologic stage were independent prognostic indicators in a multivariate analysis. Of the markers considered in this study, CA IX expression status was the most reliable hypoxia marker for predicting tumor aggressiveness. [Copyright &y& Elsevier]

Examines the implication of nonmuscle myosin MYH9 mutation for human nonsyndromic hereditary deafness DFNA17. Localization of MYH9 expression in the cochlea; Effect of the amino acid residues alteration on the ATPase activity in myosin II; Mechanism of R705H mutation.

Using high-resolution array-CGH, we identified unique duplications of a region on 6q27 in four multiplex families with at least three cases of chordoma, a cancer of presumed notochordal origin. The duplicated region contains only the T (brachyury) gene, which is important in notochord development and is expressed in most sporadic chordomas. Our findings highlight the value of screening for complex genomic rearrangements in searches for cancer-susceptibility genes. [ABSTRACT FROM AUTHOR]

Purpose: National guidelines recommend next generation sequencing (NGS) of tumors in patients diagnosed with metastatic prostate cancer (mPCa) to identify potential actionable alterations. We sought to describe the spectrum and frequency of alterations in PCa-related genes and pathways, as well as associations with self-identified race/ethnicity, and overall survival in US Veterans., Patients and Methods: This retrospective cohort study included Non-Hispanic Black (NHB) and Non-Hispanic white (NHW) Veterans with mPCa who obtained NGS through the Veterans Affairs National Precision Oncology Program. 45 genes in seven canonical or targetable mPCa pathways were evaluated in addition to TMB and MSI status. Multivariable logistic regression evaluated associations between race/ethnicity and genomic alteration frequencies. Cox proportional hazards models were used to determine associations between race/ethnicity, specific gene/pathway alteration, and overall survival., Results: 5,015 Veterans with mPCa who had NGS conducted were included (1,784 NHB, 3,231 NHW). NHB Veterans were younger, had higher PSA at diagnosis, were less likely to report Agent Orange exposure, and resided in more deprived neighborhoods compared to NHW Veterans. Nine of the top ten most commonly altered genes were the same in NHB v NHW Veterans; however, the frequencies of alterations varied by race/ethnicity. NHB race/ethnicity was associated with higher odds of genomic alterations in SPOP (OR 1.7 [1.2-2.6]) as well as immunotherapy targets (OR 1.7 [1.1-2.7]) including MSI high status (OR 3.1 [1.1-9.4]). Furthermore, NHB race/ethnicity was significantly associated with lower odds of genomic alterations in the AKT/PI3K pathway (OR 0.6 [0.4-0.7]), AR axis (OR 0.7 [0.5-0.9]), and tumor suppressor genes (OR 0.7 [0.5-0.8]). Cox proportional hazards modelling stratified by race/ethnicity demonstrated alterations in tumor suppressor genes including TP53 were associated with shorter OS in both NHB (HR 1.54 [1.13-2.11] and NHW individuals (HR 1.52 [1.25-1.85])., Conclusion: In the equal access VA healthcare setting, Veterans undergoing NGS for mPCa exhibited differences in alteration frequencies in both actionable and non-actionable pathways that may be associated with survival. This analysis affirms the utility of genomic testing for identifying candidates irrespective of race/ethnicity for precision oncology treatments, which could contribute to equitable outcomes in patients with mPCa., Competing Interests: Conflict of Interest Disclosures: Dr. Valle reported receiving funding from The Bristol Myers Squibb Foundation, Mike Slive Foundation for Prostate Cancer Research, the Parker Institute for Cancer Immunotherapy, and the Jonsson Comprehensive Cancer Center. Dr Rettig reported receiving grants from the Prostate Cancer Foundation during the conduct of the study; receiving personal fees from Bayer, Janssen, Inmune Bio, and Myovant; grants from Merck, Progenics, Clovis, ORIC, Pfizer, Novartis, and Amgen; and nonfinancial support from Merck, Lantheus, Clovis, ORIC, Novartis, and Amgen outside the submitted work; and holding a patent, issued, for Inhibitors of the N-terminal Domain of the Androgen Receptor. Dr. Chatwal reported being on the Merck advisory board. Dr. Kelley reported receiving research funding from Regeneron, and Bristol Myers Squibb. Dr Nickols reported receiving grants from the Prostate Cancer Foundation during the conduct of the study; grants from Janssen, Bayer, and Lantheus outside the submitted work; and consulting fee from PrimeFour outside the submitted work. Dr. Garraway reported receiving research funding from the Prostate Cancer Foundation, Jean Perkins Foundation, and STOP Cancer Foundation. Dr. Yamoah reported receiving research funding from the Prostate Cancer Foundation. Dr. Maxwell reported receiving research funding from Prostate Cancer Foundation, Burroughs Welcome Foundation and the Basser Center for BRCA at the University of Pennsylvania. No other disclosures were reported.

Women are the fastest growing population among Veterans and have substantial risk factors that increase their likelihood for developing cancer. To ensure that the Department of Veterans Affairs Veterans Health Administration (VHA) offers the best possible cancer care to women Veterans, it established the Breast and Gynecologic Oncology System of Excellence (BGSoE) in 2021. The BGSoE offers telehealth oncology services and a comprehensive cancer navigation program. Veterans are identified through physician referral or through the BGSoE dashboard which integrates ICD-10 codes and text mining from VA electronic health records to identify eligible Veterans with breast or gynecological cancers. Descriptive statistics, including Veteran demographics and geographical location, were derived from BGSoE dashboard data. From January 1, 2021 to March 15, 2024, the BGSoE identified a total of 7,187 incident cases of breast or gynecological cancer among living Veterans. Most cancers were breast (78%) versus gynecological cancers (22%) and 10% of Veterans with breast cancer were identified as male. The average age at diagnosis was 59 for Veterans with breast cancer and 56 for those Veterans with gynecological cancers. Among Veterans in the BGSoE, 28% identified as Black and 6% identified as Hispanic. As the prevalence of women Veterans requiring cancer-related care continues to rise, it will be essential for VHA to evaluate the equitable reach, quality, and acceptability of women-focused cancer health services. The BGSoE focuses on providing high-quality and coordinated clinical cancer care. Veterans Health Administration also established the Center for Oncology Outcomes Review and Gender (COURAGE) to evaluate the BGSoE and continue to strengthen cancer care services in VHA. Initial evaluation objectives include establishing an evidence base regarding Veterans with breast and gynecological cancers, including their experiences with cancer care in the VHA. Eventually, COURAGE will provide ongoing monitoring and evaluation to continue to grow and improve cancer care in the VHA., (Published by Oxford University Press on behalf of the Association of Military Surgeons of the United States 2024. This work is written by (a) US Government employee(s) and is in the public domain in the US.)

Background: An 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., Objective: To 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 Participants: An 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 Analysis: Mortality (all cause, non-PCM, and PCM) was evaluated. Accuracy was assessed using calibration curves and C statistic in the development, validation, and combined sets; overall; and by age (<65 and 65+ yr), race (White and Black), Hispanic ethnicity, and treatment groups., Results and Limitations: Among 107 370 individuals, we observed 24 977 deaths (86% non-PCM). The median age was 65 yr, 4947 were Black, and 5010 were Hispanic. Compared with CCI and age alone (C statistic 0.67, 95% confidence interval [CI] 0.67-0.68), VACS-CCI demonstrated improved validated discrimination (C statistic 0.75, 95% CI 0.74-0.75 for non-PCM). The prostate cancer mortality tool also discriminated well in validation (C statistic 0.81, 95% CI 0.78-0.83). Both were well calibrated overall and within subgroups. Owing to missing data, 18 009/125 379 (14%) were excluded, and VACS-CCI should be validated outside the VA prior to outside application., Conclusions: VACS-CCI is ready for implementation within the VA. Electronic health record-assisted calculation is feasible, improves accuracy over age and CCI alone, and could mitigate inaccuracy and bias in provider estimation., Patient Summary: Veterans Aging Cohort Study Charlson Comorbidity Index is ready for application within the Veterans Health Administration. Electronic health record-assisted calculation is feasible, improves accuracy over age and Charlson Comorbidity Index alone, and might help mitigate inaccuracy and bias in provider estimation of the risk of non-prostate cancer mortality., (Published by Elsevier B.V.)

Women are the largest growing population of Veterans within the U.S. Department of Veterans Affairs (VA) Health Care System. Among women Veterans, breast cancer is the most common malignancy (30% of all cancers), yet little is known about the unique needs of women Veterans with cancer and how to provide them with high quality care. The VA health care system has initiated multiple system-wide systemic efforts, including launching the Breast and Gynecologic Cancer System of Excellence (BGSOE) to address this knowledge gap. This report summarizes the outcomes of the inaugural 2023 VA Women's Cancer Research Conference, which assembled 37 multidisciplinary clinicians, scientists, the VA and civilian partners with a shared goal of advancing VA breast cancer research. Conference objectives were to build a collective vision for improving: (1) referral patterns for breast cancer treatment and patient-level outcomes and (2) molecular and genetic testing patterns across the breast cancer continuum among women Veterans. The meeting hosted 15 speakers at the Houston VA Medical Center. Future research priorities for women Veterans with cancer were identified from discussions and a post-conference survey. We then administered a 13-question post-conference survey to conference attendees. Respondents ranked the research priorities. The survey results show that the cross-cutting cancer research priorities designed to transform cancer care for women Veterans at the VA fit into 5 broad areas of study, including (1) care quality for treatment, (2) improving treatment, (3) care quality of molecular and genetic testing, (4) risk reduction through risk assessment and germline genetic testing, and (5) establishing strategic partnerships. Our data elucidate areas for further investigation to improve the delivery of cancer care., (© The Association of Military Surgeons of the United States 2024. All rights reserved. For commercial re-use, please contact reprints@oup.com for reprints and translation rights for reprints. All other permissions can be obtained through our RightsLink service via the Permissions link on the article page on our site–for further information please contact journals.permissions@oup.com.)

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., (© The Author(s) 2024. Published by Oxford University Press. All rights reserved. For permissions, please email: journals.permissions@oup.com.)

The Veterans Health Administration (VHA) has pioneered teleoncology to address access challenges faced by Veterans requiring cancer care. This ASCO Educational Book highlights the development of teleoncology programs within the VHA: the local VA Pittsburgh Healthcare System (VAPHS) Virtual Cancer Care Center, the National TeleOncology Program (NTO), and the regional Clinical Resource Hub (CRH) Oncology Program. These initiatives provide oncology care using a hub-and-spoke model, which centralizes expertise at hub sites and reaches Veterans at distant spoke sites through synchronous and asynchronous care. The deployment of these teleoncology programs has resulted in significant benefits, such as decreased travel for Veterans, high levels of patient satisfaction, and improved access to specialized treatments. Despite these advancements, disparities in teleoncology utilization and access to clinical trials persist. This educational manuscript highlights the successes and challenges of tele-oncology within the VHA, underscoring the critical role of telehealth in overcoming access barriers.

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 geographically separated from trial site., Results: There were 141 surveys analyzed (5.1% response rate). Ninety percent of respondents had been Principal Investigators, 98% practiced in a norural site. Most respondents had enrolled patients in phase I (82%) and phase II/III trials (99%). Across all phases and trial components, there was a higher frequency of researcher comfort compared to experience. Regarding remote care in treatment trials, 75% reported using TM, RPM, or both. Among these individuals, 62% had never provided remote care to trial patients before the pandemic., Conclusion: COVID-19 spurred the rise of TM/RPM in cancer treatment trials, and some TM/RPM use continues in this context. Among oncology researchers, higher levels of comfort compared with real-world experience with TM/RPM reveal opportunities for expanding TM/RPM policies and guidelines in oncology research., (© The Author(s) 2023. Published by Oxford University Press.)

Introduction: The KRAS G12C inhibitor sotorasib was approved for treating advanced NSCLC in the second line or later on the basis of the CodeBreaK100 trial. Nevertheless, data on the real-world efficacy and safety of sotorasib, and to its optimal dose, remain limited., Methods: Patients treated with sotorasib for NSCLC through the Veterans Health Administration were retrospectively identified from the Corporate Data Warehouse. Survival, response, and toxicity data were obtained from chart review., Results: Among the 128 patients treated with sotorasib through the Veterans Health Administration, objective response rate was 34%, progression-free survival (PFS) six months, and overall survival 12 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, whereas sotorasib discontinuation for toxicity occurred in 25%. Notably, sotorasib dose reduction was associated with substantially improved PFS and OS., Conclusions: In this real-world study, the observed efficacy of sotorasib was similar to the results of CodeBreaK100. Patients who received frontline sotorasib had similar PFS to our overall cohort, suggesting that first-line sotorasib monotherapy may benefit patients who are not eligible for chemotherapy. Toxicities leading to sotorasib interruption, dose reduction, or discontinuation were common. Sotorasib dose reduction was associated with improved survival, suggesting that sotorasib dose reduction may not compromise efficacy., Competing Interests: Dr. Lin reported serving as a consultant for Rigel and on the advisory board of Autolus. Dr. Dowell participated in advisory boards for Mirati, Astra Zeneca, Catalyst, and Takeda. Dr. Kelley reported research funding (paid to his institution) from 10.13039/100004336Novartis, 10.13039/100002491Bristol-Myers Squibb, 10.13039/100009857Regeneron, and Mirati Therapeutics. The remaining authors declare no conflict of interest.

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 hemorrhage occurred in 9.6% and 2.0% of patients, respectively. One SNP (rs1478947; HR 6.26; 95% CI 3.19-12.28; P = 9.40 × 10 -8 ) surpassed Bonferroni-corrected significance. Grade 2 or higher gastrointestinal hemorrhage rate was 33.3% and 6.2% in bevacizumab-treated patients with the AA/AG and GG genotypes, versus 2.9% and 1.9% in the placebo arm, respectively. Prospective validation of these findings and functional analyses are needed to better understand the genetic contribution to treatment-related gastrointestinal hemorrhage., (© 2024. The Author(s).)

Objectives: The Veterans Health Administration (VHA) is a leader in generating transformational research across the cancer care continuum. Given the extensive body of cancer-related literature utilizing VHA data, our objectives are to: (1) describe the VHA data sources available for conducting cancer-related research, and (2) discuss examples of published cancer research using each data source., Methods: We identified commonly used data sources within the VHA and reviewed previously published cancer-related research that utilized these data sources. In addition, we reviewed VHA clinical and health services research web pages and consulted with a multidisciplinary group of cancer researchers that included hematologist/oncologists, health services researchers, and epidemiologists., Results: Commonly used VHA cancer data sources include the Veterans Affairs (VA) Cancer Registry System, the VA Central Cancer Registry (VACCR), the Corporate Data Warehouse (CDW)-Oncology Raw Domain (subset of data within the CDW), and the VA Cancer Care Cube (Cube). While no reference standard exists for cancer case ascertainment, the VACCR provides a systematic approach to ensure the complete capture of clinical history, cancer diagnosis, and treatment. Like many population-based cancer registries, a significant time lag exists due to constrained resources, which may make it best suited for historical epidemiologic studies. The CDW-Oncology Raw Domain and the Cube contain national information on incident cancers which may be useful for case ascertainment and prospective recruitment; however, additional resources may be needed for data cleaning., Conclusions: The VHA has a wealth of data sources available for cancer-related research. It is imperative that researchers recognize the advantages and disadvantages of each data source to ensure their research questions are addressed appropriately., (© 2024 National Cancer Registrars Association.)

Purpose: Telegenetics 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., Methods: We 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., Results: A total of 238 Veterans, including 108 (45%) seen on site, were identified for cancer genetics services during the study period, with the majority referred for a personal (65%) or family (26%) history of cancer. In the subcohort of new consults, 121 Veterans (54% self-identified race/ethnicity [SIRE]-Black), including 60 (50%) seen on site, were included in the analysis of germline genetic testing completion. In a univariate analysis, patients who were seen by the on-site genetics service had 3.2-fold higher likelihood of completing GT (relative risk, 3.22; 95% CI, 1.89 to 5.48) compared with the telegenetics service. In multivariable regression analysis, the on-site genetics service was associated with higher likelihood of GT completion, but this association was only statistically significant in SIRE-Black compared with SIRE-White Veterans (adjusted RR, 4.78; 95% CI, 1.53 to 14.96; P < .001; P -interaction of race × genetics service = .016)., Conclusion: An on-site nurse-led cancer genetics service embedded in a VAMC Oncology practice was associated with higher likelihood of germline genetic testing completion than a telegenetics service among self-identified Black Veterans.

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 checkpoint inhibitor administration events. We identified baseline annual VHA spending for these drugs of approximately $537 million. Combining weight-based dosing, dose rounding, and pharmacy-level vial sharing would generate expected annual VHA health system savings of $74 million (13.7 percent). We conclude that adoption of pharmacologically justified immune checkpoint inhibitor stewardship measures would generate sizable reductions in spending for these drugs. Combining these operational innovations with value-based drug price negotiation enabled by recent policy changes may improve the long-term financial viability of cancer care in the US.

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 alteration rates were higher in White Veterans (12.0% vs. 6.1%, P < .0001). Racial disparities in outcome are unlikely attributable to acquired somatic alterations in actionable pathways., (Published by Oxford University Press 2023.)

Purpose: 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: 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: 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: 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.

Purpose: Genetic tests have become widely available. We sought to understand the use of genetic tests in the practice of frontline clinicians within the United States Department of Veterans Affairs (VA)., Methods: We administered a web-based survey to clinicians at 20 VA facilities. Physicians, nurse practitioners, physician assistants, and pharmacists were eligible. We excluded genetics providers and clinicians not seeing patients. We used multiple logistic regression to evaluate the associations between clinician characteristics and experience with genetics., Results: The response rate was 11.3% (1207/10,680) and of these, 909 respondents were eligible. Only 20.8% of the respondents reported feeling prepared to use genetic tests and 13.0% of the respondents were currently ordering genetic tests; although, it was usually only 1 or 2 a year. Delivery of genetic tests without involving genetics providers was preferred by only 7.9% of the respondents. Characteristics positively associated with currently ordering genetic tests included practice in clinical and research settings, believing improving genetics knowledge could alter their practice, feeling prepared to use genetic tests, and referral of at least 1 patient to genetics in the past year., Conclusion: Most VA clinicians don't feel prepared to use genetic tests. Those with genetic testing experience are more likely to consult genetics providers. The demand for genetics providers should increase as frontline clinicians use genetic tests in their practice., Competing Interests: Conflict of Interest The authors declare no conflicts of interest., (Published by Elsevier Inc.)

Importance: Extended-interval dosing of pembrolizumab (400 mg every 6 weeks) was approved by US Food and Drug Administration (FDA) in April 2020 as an alternative to standard-interval dosing (200 mg every 3 weeks). Extended-interval dosing may enhance access, alleviate patient and health system financial toxicity, and improve patient quality of life, particularly during the COVID-19 pandemic. Neither adoption nor effectiveness of extended interval in the US has been adequately described., Objective: To describe adoption of extended-interval dosing of pembrolizumab since its FDA approval and to measure its preliminary real-world effectiveness compared with standard-interval dosing., Design, Setting, and Participants: This was a retrospective cohort study that used data from the Veterans Health Administration (VHA), a US-based, nationwide single-payer health system. Participants were veterans who were prescribed single-agent pembrolizumab within the VHA between April 1, 2020, and July 1, 2021. Patients receiving combinations of pembrolizumab and cytotoxic chemotherapy or tyrosine kinase inhibitors were excluded. A subcohort of veterans with non-small cell lung cancer (NSCLC) was also identified using claims-based codes., Exposures: Single-agent pembrolizumab at extended or standard intervals., Main Outcomes and Measures: The number and proportion of single-agent pembrolizumab prescriptions that were extended compared with standard interval. Effectiveness was described in terms of time-to-treatment discontinuation (TTD) and extended- to standard-interval pembrolizumab prescriptions were compared using Cox proportional hazards regression., Results: A total of 835 veterans (mean age [SD], 70.9 [8.7] years; 809 [96.9%] men) began single-agent pembrolizumab during the study period (all-diseases cohort), and of these, 234 (mean [SD] age, 71.6 [7.3] years; 225 [96.2%] men) had NSCLC (NSCLC cohort). Extended-interval adoption reached its steady state plateau of approximately 35% by January 2021; 65% of participants who began standard-interval single-agent pembrolizumab received only standard-interval dosing during the treatment course. In analysis consistent with the intention-to-treat principle, no differences in TTD were observed between standard- and extended-interval dosing in either the all-diseases cohort (HR, 1.00; 95% CI, 1.00-1.00) or the NSCLC cohort (HR, 1.00; 95% CI, 1.00-1.00)., Conclusions and Relevance: This retrospective cohort study found that extended-interval dosing comprised a minority of single-agent pembrolizumab prescriptions despite the FDA approval and its potential health system and public health benefits. The findings support the TTD equivalence of standard- and extended-interval pembrolizumab across indications, complementing clinical pharmacology and single-arm clinical trial data in melanoma. This study provides further support for extended-interval pembrolizumab dosing.

Purpose: Increased access and utilization of tumor profiling of cancers in our veteran population uncovered a modest number of potentially pathogenic germline variants (PPGVs) that require genetics referral for follow-up evaluation and germline sequencing. Challenges identified specific to the veteran population include paucity of genetics providers, either at a veteran's VA facility or nearby non-VA facilities. We sought to investigate the number of veterans who would benefit from having such resources at both local and national levels., Methods: Annotated clinical reports of mutations identified by tumor-only profiling and medical records of veterans with solid tumors at the Veterans Administration Ann Arbor Healthcare System (VA AAHS) between 2015 and 2020 were reviewed. PPGVs were identified according to society recommendations (such as ESMO and American Board of Medical Genetics and Genomics), expert review, and/or previously published criteria. After the analysis of our local VA population, these same criteria were then applied to veterans in the National Precision Oncology Program (NPOP)., Results: Two hundred eight veterans underwent tumor profiling at the VA AAHS over the defined time period. This included 20 different primary tumor sites with over half (n = 130) being advanced cancer at diagnosis. Of these, 18 veterans (8.5%) had mutations suggestive of a PPGV. Applying these criteria to the larger NPOP database (n = 20,014), a similar percentage (6%) of PPGVs were identified., Conclusion: These results indicate a PPGV frequency (6%-9% of veterans) consistent with the prevalence of inherited cancer predisposition syndromes in the general population, underscoring the need for medical genetics as part of standard oncologic care for veterans. We explore current and future care delivery models to optimize incorporation of medical genetics and genetic counseling to best serve veterans needing such services., Competing Interests: Arathi MohanStock and Other Ownership Interests: Johnson and Johnson, Pfizer, Viatris, EI Dupont Michael J. KelleyResearch Funding: Novartis (Inst), AstraZeneca (Inst), Bristol Myers Squibb (Inst), Regeneron (Inst), Genentech (Inst)Other Relationship: IBM (Inst)Open Payments Link: https://openpaymentsdata.cms.gov/physician/827136 Nithya RamnathResearch Funding: Merck (Inst), Clovis Oncology (Inst), Clovis Oncology (Inst)No other potential conflicts of interest were reported.

Lung cancer is the leading cause of cancer mortality in men and women. Genomic sequencing of non-small cell lung cancer (NSCLC) is critical for the optimal treatment of NSCLC. In this study we sought to describe the frequencies of highly actionable driver mutations in lung adenocarcinoma (LUAD), squamous cell (LUSQ) and other NSCLC histologies (LUOT) in Veterans tested through the VA's National Precision Oncology Program (NPOP) and compare these frequencies to other published datasets from highly specialized academic cancer centers. The NPOP cohort included 3,376 unique Veterans with a diagnosis of lung carcinoma tested between February 2019 and January 2021 including 1892 with LUAD, 940 with LUSQ, and 549 with LUOT. Among patients with LUAD, 27.5% had highly actionable genetic variants. The frequency of targetable mutations was as follows: ALK rearrangement 0.8%, BRAF V600E 2.1%, EGFR exon 20 insertion mutation 0.48%, EGFR sensitizing mutations 6.6%, ERBB2 small variants 1.2%, KRAS G12C 14.0%, MET exon 14 skipping mutation 1.5%, NTRK rearrangement 0.1%, RET rearrangement 0.4%, and ROS1 rearrangement 0.3%. The frequency of EGFR mutations, RET rearrangement, MET exon 14 and ERBB2 small variants frequencies were significantly lower in NPOP compared to other published reports while MET amplification was more common in NPOP. Combined rates of highly actionable genetic variants were 2.7% and 13.4% in LUSQ and LUOT, respectively. In this study, 27.5% of Veterans with lung adenocarcinoma have actionable genetic alterations eligible for FDA approved targeted therapies, a frequency only slightly lower than other published datasets despite higher smoking rates in Veterans. Genomic sequencing should be performed in all Veterans with advanced LUAD and LUOT., (Published by Elsevier Inc.)

One year of durvalumab following concurrent chemoradiotherapy improves progression-free (PFS) and overall survival (OS) for patients with stage III non-small cell lung cancer (NSCLC). However, the real-world efficacy of durvalumab has not been determined. We conducted a multi-center observational cohort study across the Veterans Health Administration, including patients with stage III NSCLC who received concurrent chemoradiotherapy and durvalumab, compared to patients who received concurrent chemoradiotherapy alone. Kaplan-Meier and Cox regression approaches were used to identify factors associated with PFS and OS. We calculated a hazard ratio and efficacy-effectiveness factor to compare OS of veterans to the referenced clinical trial population. A total of 1006 patients with stage III NSCLC who received concurrent chemoradiotherapy and at least one dose of durvalumab from November 2017 to April 2021 were compared to 989 patients who received concurrent chemoradiotherapy alone from January 2015 to December 2016. Adjuvant durvalumab was associated with higher PFS (HR 0.62, 95% CI 0.55-0.70, p < 0.001) and OS (HR 0.57, 95% CI 0.50-0.66, p < 0.001). OS was shorter in veterans compared to PACIFIC (HR 1.24, 95% CI 1.03-1.48, p = 0.02: EE gap 0.73). OS of veterans with stage III NSCLC treated with adjuvant durvalumab is improved compared to a modern comparator but is reduced compared to the PACIFIC population.

Aim: The first Plan-Do-Study-Act cycle for the Veterans Affairs Pharmacogenomic Testing for Veterans pharmacogenomic clinical testing program is described. Materials & methods: Surveys evaluating implementation resources and processes were distributed to implementation teams, providers, laboratory and health informatics staff. Survey responses were mapped to the Consolidated Framework for Implementation Research constructs to identify implementation barriers. The Expert Recommendation for Implementing Change strategies were used to address implementation barriers. Results: Survey response rate was 23-73% across personnel groups at six Veterans Affairs sites. Nine Consolidated Framework for Implementation Research constructs were most salient implementation barriers. Program revisions addressed these barriers using the Expert Recommendation for Implementing Change strategies related to three domains. Conclusion: Beyond providing free pharmacogenomic testing, additional implementation barriers need to be addressed for improved program uptake.

Purpose: Next-generation sequencing (NGS) gene panels are frequently completed for patients with advanced non-small-cell lung cancer (NSCLC). Patients with highly actionable gene variants have improved outcomes and reduced toxicities with the use of corresponding targeted agents. We sought to identify barriers to targeted agent use within the Veterans Health Affairs' National Precision Oncology Program (NPOP)., Methods: A retrospective evaluation of patients with NSCLC who underwent NGS multigene panels through NPOP between July 2015 and February 2019 was conducted. Patients who were assigned level 1 or 2A evidence for oncogenic gene variants by an artificial intelligence offering (IBM Watson for Genomics [WfG]) and NPOP staff were selected. Antineoplastic drug prescriptions and provider notes were reviewed. Reasons for withholding targeted treatments were categorized., Results: Of 1,749 patients with NSCLC who successfully underwent NGS gene panel testing, 112 (6.4%) patients were assigned level 1 and/or 2A evidence for available targeted treatments by WfG and NPOP staff. All highly actionable gene variants were within ALK , BRAF , EGFR , ERBB2 , MET , RET , and ROS1 . Of these, 36 (32.1%) patients were not prescribed targeted agents. The three most common reasons were (1) patient did not carry a diagnosis of metastatic disease (33.3%), (2) treating provider did not comment on the NGS results (25.0%), and (3) provider felt that patient could not tolerate therapy (19.4%). No patients were denied access to level 1 or 2A targeted drugs because of rejection of a nonformulary drug request., Conclusion: A substantial minority of patients with NSCLC bearing highly actionable gene variants are not prescribed targeted agents. Further provider- and pathologist-directed educational efforts and implementation of health informatics systems to provide real-time decision support for test ordering and interpretation are needed., Competing Interests: Vishal VashisthaEmployment: UnitedHealthcare (I)Research Funding: IBM Watson HealthOther Relationship: IBMUncompensated Relationships: IBM Watson Health Pradeep J. PoonnenHonoraria: M3, Sermo Jane L. SnowdonEmployment: IBMStock and Other Ownership Interests: IBM Dilhan WeeraratneEmployment: IBM David BrotmanEmployment: IBM Gretchen P. JacksonEmployment: IBM, Vanderbilt University Medical CenterLeadership: IBM, American Medical Informatics AssociationStock and Other Ownership Interests: IBMSpeakers' Bureau: IBMResearch Funding: IBMTravel, Accommodations, Expenses: IBM Michael J. KelleyConsulting or Advisory Role: IBMResearch Funding: Novartis, AstraZeneca, Bristol-Myers Squibb, Regeneron, GenentechOther Relationship: IBMOpen Payments Link: https://openpaymentsdata.cms.gov/physician/827136No other potential conflicts of interest were reported.