bluuebunny/crossref_metadata_2025_split huggingface dataset:
Associations between plant-based diets and risk of disease progression in men with prostate cancer.
Authors: Liu Vivian N , Van Blarigan Erin L. , Zhang Li , Graff Rebecca E. , Langlais Crystal , Cowan Janet E. , Carroll Peter , Chan June M. , Kenfield Stacey A. 
Published: March 2023

392 Background: Plant-based diets have been linked to multiple health benefits. For prostate cancer (PC), individual plant foods (e.g., tomatoes with lycopene) appear to reduce PC incidence and mortality. However, less is known about plant-based dietary patterns and PC survivorship. Methods: We examined 2038 men diagnosed with T1-T3a PC who were enrolled in the Cancer of the Prostate Strategic Urologic Research Endeavor (CaPSURE) and had completed a food frequency questionnaire (FFQ) a median of 31.5 months post-diagnosis. “Overall” and “healthy plant-based” dietary indices (PDI and hPDI, respectively,) were calculated from the FFQ. Multivariable Cox proportional hazards models estimated adjusted hazard ratios (HR) and 95% confidence intervals (CI) for associations between plant-based diets and risk of PC progression (recurrence, secondary treatment, bone metastases, or PC death) as the primary outcome, and PC recurrence as a secondary outcome. We also examined whether age, stage, grade, and walking pace modified associations. Results: We observed 204 progression events (169 due to biochemical recurrence) over a median follow up of 7.4 years after the FFQ. Men in the highest quintile of PDI had a 52% lower risk of progression (HR 0.48, 95% CI 0.36-0.65, p-trend<0.001) and a 53% lower risk of recurrence (HR 0.47, 95% CI 0.32-0.68, p-trend<0.001) compared to men in the lowest quintile. Although the hPDI was not associated with PC progression or recurrence overall (p-trend >0.05), men in the higher quintiles had statistically significant reductions in risk of recurrence. Among men >65 years, greater consumption of a healthful plant-based diet was associated with lower risk of PC recurrence (HR 0.41, 95% CI 0.24-0.7, p-trend=0.03). In addition, among those with a brisk/fast walking pace (>3 h/wk), men in the highest PDI quintile had a 56% (HR 0.33, 95% CI 0.26, 0.73) lower risk of PC progression, and a 59% (HR 0.41, 95% CI 0.25, 0.68) decrease in risk of PC recurrence. Grade and stage did not modify associations between either index and PC progression or recurrence. Conclusions: This study indicates that plant-based dietary patterns are associated with lower risk of PC progression and recurrence, particularly among older men and those who reported a higher intensity walking pace. PC survivors may be recommended diet and exercise counseling to improve clinical outcomes after PC diagnosis.
The landscape of prostate cancer research in Canada.
Authors: Fraser Mike , Mohammad Atiqa 
Published: March 2023

394 Background: Prostate cancer (PCa) is the most prevalent malignancy in Canadian men; in 2023, an estimated 24,700 men will be diagnosed while ~4,700 will die of their disease. Lifetime risk of developing PCa is approximately 1-in-8 and approximately 3% of all deaths of Canadian men are caused by the disease. While Canada has a robust, modern health research landscape, with major academic centres located in all provinces and territories, the investment in academic PCa research – and the impact of that investment – has not been systematically quantified. An improved understanding of this landscape is necessary to ensure research funding remains efficient, impactful, and equitable. As such, we evaluated the size, scope, and impact of the investment in academic PCa research in Canada. Methods: We extracted funding records from the Canadian Research Information System (CRIS), the United States Congressionally Directed Medical Research Program database and the United States National Institutes of Health RePORT database for the National Cancer Institute, using keywords ‘prostate’ OR ‘prostatic’ AND ‘cancer’ OR ‘carcinoma’ for 1999-2021. US-sourced records were included when the principal investigator (PI) was based at a Canadian institution at the time the award was granted. Records were validated using data from the Canadian Cancer Research Alliance (CCRA). Intramural and industry-derived funding was unavailable and thus excluded from the analysis. Results: We identified 1,748 unique funding events (FEs) from 33 sources. These FEs involved 1,561 investigators and had an inflation-adjusted value of $682,113,116. The top three funders of PCa research were the Canadian Institutes of Health Research, Movember Canada, and the Canadian Cancer Society. Basic and translational research received ~83% of all funding while psychosocial, health economics, and epidemiology research received only ~7.2%. Strikingly, we found that 30.5% of all funding was held by 1% of investigators. We identified 6,671 dyads ( ie. pairs of collaborating investigators); 85% collaborated only once, while 15% collaborated at least twice (range: 2-19). Female investigators participated in significantly fewer collaborations than males (P: 3.28 x 10-3) and were less likely than expected to serve as PI (P: 8.87 x 10-8). FEs with ≥ one female PI had a significantly lower value than those with only male PIs (P: 1.34 x 10-6) and FEs with only female PIs had a significantly value than those with only male PIs (P: 7.32 x 10-4). Conclusions: While Canadian PCa research has been highly funded over the past 25 years, there remain substantial funding disparities across scientific disciplines, geographic regions, and, in particular, gender. There is also substantial ‘wealth inequality’; a small minority of investigators receive most of the funding. We are currently assessing stakeholder attitudes toward these disparities, to help inform the next phase of PCa research funding in Canada.
Implementing 18F-DCFPyL PET in clinical practice: Prescribing patterns and utilization at a large academic center.
Authors: Hsu Miles , Shan Xinhe , Takvorian Samuel U , Pantel Austin , Narayan Vivek , Shevach Jeffrey , Vapiwala Neha , Vaughn David J. , Haas Naomi B. 
Published: March 2023

42 Background: 18F-DCFPyL imaging was recently approved for initial staging in patients (pts) with prostate cancer and suspected metastasis and for those with biochemical recurrence (BCR). 18F-DCFPyL recently became available at our NCI-Designated Comprehensive Cancer Center comprising 6 teaching hospitals and 2 outpatient facilities. As real-world data on 18F-DCFPyL usage in the US are lacking, our objective was to describe prescription patterns and utilization for 18F-DCFPyL. Methods: We identified 18F-DCFPyL scans performed at our center from 1/1/2022-5/10/2022 and abstracted corresponding clinical data through electronic medical record (EMR) review. Demographic, laboratory, pathological and clinical data and provider-level usage were characterized by review of the EMR and, if necessary and feasible, provider interview. Results: There were 164 18F-DCFPyL scans performed across the study period for 164 unique pts (median age 70 years, 73.8% White, 20.1% Black). Ordering providers belonged to Medical Oncology (54.3%), Radiation Oncology (42.7%), Urology (2.4%), and Nuclear Medicine (1%). The majority of scans were ordered for isolated PSA rise (n=93, 56.7%) and initial staging (n=26, 15.9%), in concordance with FDA-approved indications. Nevertheless, many scans were ordered for alternate indications. Restaging of pts with known refractory or metastatic disease (11.0%), PSA persistence after definitive therapy (8.5%), and PSA rises below the threshold of BCR (4.9%) were common alternate rationales for imaging. A minority of scans had a secondary indication such as RT field planning, distinguishing between two primary cancers, PSA persistence in high-risk disease, possible radioisotope therapy, and, most frequently, clarification of lesions seen on conventional imaging (n = 7). 22 pts were on androgen-deprivation (ADT, n=17) or anti-androgens (AR, n=11) when receiving PSMA imaging, with 5 pts on both; the median testosterone at time of imaging was <20 ng/dL. Indeterminate lesions, defined as tracer avid with uncertain malignant status, were most often found in lymph nodes (n = 22) and focal rib lesions (n = 17), of which 12 were solitary, 3 were multifocal and 2 were superimposed on fractures. Conclusions: Shortly after adoption at a large cancer center, 18F-DCFPyL has been prescribed in various clinical settings outside of FDA approvals. Around 1/8 were performed with pts on ADT/AR, with testosterone at castrate levels. Findings of uncertain malignant etiology included solitary (7%) and multifocal (2%) rib lesions. These data reveal substantial variability in usage and areas of uncertainty in the interpretation of 18F-DCFPyL imaging in real-world clinical settings, underlining the need for further studies on its potential usefulness in expanded indications.
Origin of extragonadal versus gonadal seminomas.
Authors: Tasneem Sara , Chen Jim Zhongning , Johns Andrew , Tu Shi-Ming , Estecio Marcos Roberto 
Published: March 2023

423 Background: There is debate whether a primary seminoma of the anterior mediastinum originates from a stranded germ cell in the midline near the thymus as it migrates from the yolk sac to the gonad1 or from abnormal development of the thymic anlage during embryogenesis.2 We hypothesized that if extragonadal seminoma were to arise from an adult stem cell at an ectopic site rather than from an errant primordial germ cell (PGC), it would display a methylated imprint resembling that of thymic epithelial tumors, such as a thymoma, rather than that of a gonadal seminoma. Methods: We performed reduced representation bisulfite sequencing (RRBS) of FFPE DNA of testicular seminoma, anterior mediastinal seminoma, thymomas, atypical thymomas, and thymic carcinomas. Results: RRBS of testicular seminoma (n=1), anterior mediastinal seminoma (n=1), thymomas (n=2), atypical thymomas (n=2), and thymic carcinomas (n=2) showed that the methylated genetic imprint of an extragonadal seminoma clustered more closely to that of an atypical thymoma than that of testicular seminoma. Conclusions: Our preliminary RRBS results suggest that extragonadal seminoma may have a thymic rather than PGC origin. We plan to confirm these results by evaluating certain PGC-specific genetic biomarkers and epigenetic signatures in additional cases. References: 1. Dixon FJ, Moore RA. Testicular tumors: a clinicopathological study. Cancer 1953;6:427. 2. Schlumberger HG. Teratoma of the anterior mediastinum in the group of military age: a study of sixteen cases, and a review of theories of genesis. Arch Pathol 1946;41:398.
Refining the serum miR-371a-3p test for viable germ cell tumor detection: Identification and definition of an indeterminate range.
Authors: Bagrodia Aditya , Lafin John T. , Scarpini Cinzia , Konneh Bendu , Gerald Thomas , Nuno Michelle , Piao Jin , Savelyeva Anna , Jia Liwei , Murray Sarah , Cheng Yun , Margulis Vitaly , Woldu Solomon L. , Coleman Nicholas , Amatruda James F. , Frazier Lindsay Lindsay , Murray Matthew 
Published: March 2023

425 Background: Existing conventional serum tumor markers (STMs) exhibit moderate performance for the detection of germ cell tumors (GCTs). Circulating miR-371a-3p has excellent performance in the detection of viable (non-teratoma) GCT pre-orchiectomy; however, its ability to detect occult disease is understudied. We refine the serum miR-371a-3p assay and expand upon our previous experience in this setting. Methods: We compared performance of raw (Cq) and normalized (∆Cq, RQ) values from prior assays (n=93), and validated interlaboratory concordance by aliquot swapping. Revised assay performance was determined in a cohort of 32 patients suspected of occult retroperitoneal disease. Assay superiority was determined by comparing resulting receiver-operator characteristic (ROC) curves using the Delong method. Pairwise t-tests were used to test for interlaboratory concordance. We defined an indeterminate range as the mean of the low Cq peak from controls ± 2 SDs. Results: Performance was comparable when thresholding based on raw Cq vs. normalized values. Calculated sensitivity and specificity were both greater than 0.9 in all cases and did not change appreciably across any of the metrics tested. Interlaboratory concordance of miR-371a-3p was high, but reference genes miR-30b-5p and cel-miR-39-3p were discordant. We identified for the 1st time an indeterminate range; Introduction of an indeterminate range of Cq 28-35 with a repeat run for any indeterminate improved assay accuracy from 0.84 to 0.92 in a group of patients suspected of occult GCT. Conclusions: We recommend that serum miR-371a-3p test protocols are updated to a) utilize threshold-based approaches using raw Cq values, b) continue to include an endogenous (e.g., miR-30b-5p) and exogenous non-human spike-in (e.g., cel-miR-39-3p) microRNA for quality control, and c) to re-run any sample with an indeterminate result.
Bilateral germ cell tumor of the testis (TGCT): Implications for a stem cell versus genetic origin of cancers.
Authors: Sanchez Darren , Chen Jim Zhongning , Ebare Kingsley , Joon Aron , Estecio Marcos Roberto , Zhang Miao , Adriazola Ana Cecilia , Shah Amishi Yogesh , Singh Sunny R , Ward John Francis , Pisters Louis L. , Tu Shi-Ming , Zacharias Niki Marie 
Published: March 2023

428 Background: Bilateral TGCT offers a unique opportunity to elucidate a stem cell versus genetic origin of cancer (Coffey, 2008). Comparison of the epigenetics and genetics of disparate tumors in either synchronous or metachronous bilateral TGCT from the same patients is feasible and may be informative. Methods: We examined the clinical characteristics and natural history of 37 patients with bilateral TGCT. We performed reduced representation bisulfite sequencing (RRBS) of FFPE DNA and whole exon sequencing (WES) of 5 of those patients whose tumor samples were available for the study. Results: We identified 37 patients with bilateral TGCT, who underwent their first orchiectomy between January 1984 and April 2022 and the second between August 1997 and April 2022. Thirty-five (95%) of these patients are still alive. Seven patients had synchronous, while 30 had metachronous bilateral TGCT. There were 13 bilateral seminomas, 14 bilateral nonseminomas, and 10 bilateral seminoma and nonseminoma. For those patients with metachronous bilateral TGCT, the median time between the two TGCT was 59 months (range 6-400). WES revealed a mutation in 189 (<1%) out of about 20,000 genes in the 10 paired samples from 5 patients. A total of 2 genes were mutated in more than 1 sample: KIT (n=4), and KRAS (n=2). Although one patient with synchronous bilateral seminomas shared KIT mutation, another did not with KIT and KRAS mutations (Table). RRBS showed a similar methylation profile in the 2 metachronous nonseminomas, which did not share any genetic mutations in the WES study. Conclusions: The clinical course of our patients with synchronous and metachronous bilateral TGCT and the results of our RRBS and WES reaffirmed that a preponderance of TGCT was curable and alluded to whether its epigenetic vs genetic origins might be causative or contributory to its general curability vs potential lethality. Coffey J et al. Somatic KIT mutations occur predominantly in seminoma germ cell tumors and are not predictive of bilateral disease: report of 220 tumors and review of literature. Genes Chromosomes Cancer 2008;47:34-42. [Table: see text]
Molecular features and actionable targets for testicular germ cell tumors in a real-world setting.
Authors: Morales-Grimany Rafael , Delgado Cesar , Baky Fady , Amini Armon , Gerald Thomas , Badia Rohit R , Taylor Jacob , Wang Luke , Javier-Desloges Juan , Margulis Vitaly , Woldu Solomon L. , Salmasi Amir , Millard Fred , McKay Rana R. , Bagrodia Aditya 
Published: March 2023

430 Background: Molecular features of testicular germ cell tumors (GCT) in various clinical states (pre- vs post-chemotherapy, localized versus metastatic) may inform treatment options for patients with recurrence after definitive therapy. In his study, we describe molecular features and potential therapeutic targets in a cohort of patients with testicular GCT. Methods: We retrospectively examined clinicopathologic and next-generation sequencing (NGS) data from 27 patients with GCT. Tumors were sequenced using the Tempus|xT solid tumor assay, which includes DNA sequencing of 595-648 genes at 500x coverage and RNA sequencing for all human coding genes. Tumor mutational burden (TMB) was measured for all tumors and PD-L1 levels were assessed qualitatively by 22C3 pharmDx immunohistochemistry assay in 8 patients. All genetic variants detected were quantified and analyzed to identify potentially actionable targets. Results: We identified 13 (48%) stage I GCT, 11 (41%) stage II, and 3 (11%) stage III. There were 7 seminomas and 20 nonseminomas. 12 tumor specimen resections were obtained from orchiectomy, and 15 from retroperitoneal lymph node dissection (RPLND), of which, 8 were chemotherapy-naïve and 7 were post-chemotherapy. Chemo-naïve RPLND histology showed a combination of teratoma, seminoma, and mixed GCT, while post-chemo histology revealed 6 teratomas and 9 benign pathologies. The median TMB for the cohort was 0.75 mutations/megabase. Somatic mutations were identified in 55% of patients and most commonly within: KRAS (25.9%), KIT (11.1%), and PIK3CB (7.4%). PD-L1 expression was observed in 75% of the tumors measured (60% positivity at stage I and 100% positivity at stage III). Microsatellite stability was stable in 18 tumors tested. DNA alterations- [single base pair substitutions, insertions, and deletions]- in KRAS (GTPase) proto-oncogenes were detected in 7 tumors and tyrosine kinase receptor gene variants (KIT, P1K3CB) were found at similar frequencies across disease stages. Whole transcriptome NGS RNA expression assays were performed on 21 untreated specimens revealing overexpression of MTOR (33%), MAPK1(14%), and MET (8.0%). Actionable targets with FDA-approved therapies in other organ tissues were detected in 11 patients (40.7%). Incidental germline mutations, including MSH6, RB1, and MSH2, were identified in 9 patients though all were variants of unknown significance. Conclusions: In our study, a significant proportion of patients had potentially actionable molecular targets across the disease spectrum. The identified genetic alterations provide a genomic landscape for risk stratification, future therapies, and molecularly informed treatment paradigms for GCT patients.
Biomarkers of response to enfortumab vedotin (EV) in patients (pts) with advanced urothelial carcinoma (aUC): Analysis of the UNITE study.
Authors: Jindal Tanya , Kilari Deepak , Alhalabi Omar , Nizam Amanda , Khaki Ali Raza , Basu Arnab , Barata Pedro C. , Bilen Mehmet Asim , Shah Sumit , Zakharia Yousef , Milowsky Matthew I. , Bellmunt Joaquim , Emamekhoo Hamid , Davis Nancy B. , Grivas Petros , Gupta Shilpa , Hoimes Christopher J. , Campbell Matthew T , Alva Ajjai Shivaram , Koshkin Vadim S 
Published: March 2023

450 Background: EV, an antibody-drug conjugate (ADC) targeting Nectin-4, is used widely in treatment-refractory aUC, but limited data are available on biomarkers predictive of EV outcomes. We investigated potential biomarkers of response to EV in a pt cohort in the UNITE dataset. Methods: We included the retrospective UNITE study pts from 16 sites, with available next generation sequencing using institutional or commercial platforms, treated with EV alone outside clinical trials. Observed response (ORR) was determined by investigators for evaluable pts with scans after ≥1 dose of EV. Assessed molecular biomarkers included tumor mutation burden (TMB), PD-L1 status, somatic alterations (alts) in ≥ 10% of pts ( TERTp, TP53, ARID1A, CDKN2A, CDKN2B, FGFR3, ERBB2, CCND1, KDM6A, MTAP, PIK3CA, RB1, TSC1) and presence of ≥1 DNA damage response mutations ( ATM, BARD1, BRCA1, BRCA2, CDK12, CHEK2, PALB2, PPP2R2A, or RAD51B). ORRs were compared using Chi-squared test, while median progression-free and overall survival (mPFS, mOS) from EV start were compared with log-rank test and Cox proportional hazards in pts with and without biomarker presence. Results: A total of 170 pts had outcomes and NGS data available. Median age was 70, 133 (78%) were men, 144 (85%) Caucasian, 110 (65%) with pure urothelial histology, 118 (69%) with primary bladder tumor, and 116 (68%) had ≥ 2 lines of therapy before EV. For all pts, ORR 47%, mPFS 6 mos, mOS 12 mos. ORRs were higher in pts with ERBB2 (67% vs 44%; p = 0.05) and TSC1 (68% vs 25%; p=0.04) alts vs wild-type. Shorter mPFS was noted in pts with CDKN2A, CDKN2B, and MTAP alts, and longer mOS in pts with high TMB (table). Conclusions: This large, multi-site, retrospective cohort of pts with aUC identified several potential biomarkers associated with differential outcomes to EV. These findings, upon external validation, may help inform clinical decision making and potential therapy sequencing with available ADCs. Limitations include retrospective nature, pt selection, and confounding biases. [Table: see text]
Facility-level disparities in the delivery of guideline-based treatment across genitourinary cancers.
Authors: Szymaniak Julie A. , Zhang Li , Porten Sima P. , Meng Maxwell , Cooperberg Matthew R. , Carroll Peter , Washington Samuel L. 
Published: March 2023

456 Background: Disparities in guideline-based treatment (GBT) for genitourinary cancers are commonly presented individually, impeding comprehensive examinations of institutional drivers. While patient-level factors impacting disparities in treatment have been well documented, our understanding of how race-based disparities in treatment exist at the institution level remains relatively limited. In this study, we aim to characterize the prevalence of disparities in GBT for prostate (PCa), bladder (BCa), and kidney (KCa) cancer within the same facility to evaluate whether disparities cluster at the institutional level. Methods: Patients diagnosed with clinically localized (cT2-4aNX-1MX-0) bladder, (cT2b-4NX-0MX-0) prostate, or (cT2a-3cNX-1MX-0) kidney cancer between 2004-2017 within each National Cancer Database dataset were included. We collected clinicodemographics, treatment received, and facility data. GBT was defined according to NCCN Guidelines by TNM staging. We calculated rates of GBT by cancer type and race and compared rates between White, Black, Hispanic, and Asian patients using Chi-squared tests. Pairwise correlations in GBT rates between PCa, BCa, and KCa treated across and within facilities were estimated using Pearson correlation coefficients, where facilities with <10 cases of each cancer were excluded. Results: We identified 91904 BCa, 73,050 KCa, and 252,403 PCa cases. Overall, unadjusted GBT rates for BCa (41%, SD 18%) were significantly lower than for KCa (72%, SD 17%) and PCa (77%, SD 16%), all p<0.001. Correlation coefficients at academic medical centers were highest among the four facility types, though still low (r=0.31 prostate-bladder, 0.39 prostate-kidney, 0.39 bladder-kidney). BCa GBT was highest for White and Asian patients (50.5% and 48.6%, respectively) versus 42.2% for Black patients. KCa GBT rates were equivalent for White, Hispanic, and Asian patients (~76%) but lowest for Black patients (74.8%). In PCa, the highest GBT rate was 80.8% (White patients) and lowest was 76.5% (Black patients). After controlling for confounding variables and matching based on cohort size, intra-facility odds of receipt of GBT by Black patients (compared to White counterparts) correlated poorly across cancer types for all comparisons. This was true even when restricting analysis to higher-volume facilities (>200 patients), with r=0.1 for bladder-kidney, 0 for bladder-prostate, and 0.12 for kidney-prostate; p-value >0.05. Conclusions: Our findings show that, overall, there is little correlation between racial disparities in GBT across GU cancers treated in the same facility. As we push further for interventions to combat racial inequities in healthcare, we must continue to explore their prevalence within the context of a multi-disease and multi-level paradigm to identify systems-level factors that perpetuate their existence.