tbuckley/cabot-search huggingface dataset:
Experiences of patients with bladder cancer: A comparison of urban and rural areas.
Authors: Lydia Makaroff, Alex Filicevas, Patrick J. Hensley, Ashish M. Kamat
Journal: Journal of Clinical Oncology (2024)

568 Background: Bladder cancer patients encounter unique challenges and advantages in urban and rural environments, significantly influencing their path from diagnosis to treatment. While numerous studies explore bladder cancer from clinical and therapeutic perspectives, there is a noticeable gap in research addressing patients' experiences based on geographical locale. This study aims to bridge this gap by offering a comparative analysis of urban versus rural experiences. Methods: The World Bladder Cancer Patient Coalition and IQVIA formulated an online survey, designed to capture the multifaceted experiences of bladder cancer patients. Available in various languages, the survey was accessible from October 2021 to February 2022. Responses underwent systematic analysis, with parameters including gender, time since diagnosis, age, region, and disease stage, forming the sub-analytical categories. Results: We received a total of 1,198 responses from 45 countries. Key findings are summarized in the table, highlighting the comparative experiences of urban and rural patients. Conclusions: Significant disparities emerge between urban and rural bladder cancer patients. Rural patients particularly face prolonged diagnosis times, less clear communication from healthcare providers, and experience greater challenges in accessing treatment. These findings underscore the need for a re-evaluation of communication strategies and healthcare infrastructure, especially in rural areas. This research serves as a stepping stone for further investigations aimed at fostering a more patient-centric approach to bladder cancer care. Limitations to consider involve the inherent biases of online survey distribution and the possibility of certain regions being underrepresented. [Table: see text]
Exploring the utility of prostate-derived extracellular vesicles as a urine biomarker for clinically significant prostate cancer.
Authors: Ekamjit Singh Deol, Cameron J Britton, Jack R. Andrews, Edlira Horjeti, Yohan J Kim, Vidhu B. Joshi, Mohamed E. Ahmed, R. Jeffrey Karnes, Fabrice Lucien
Journal: Journal of Clinical Oncology (2024)

334 Background: Prostate cancer (PCa) screening has relied on prostate-specific antigen (PSA) levels to screen patients for biopsy. However, the limited specificity of serum PSA leads to high rates of negative biopsies and detection of clinically insignificant cancers. Tumor-derived extracellular vesicles, microscopic particles released by tumor cells and ubiquitously found in all bodily fluids, have emerged as novel biomarkers for a diverse set of malignancies. This study explored the utility of urine prostate-specific extracellular vesicles (ProsEVs) identified by unique surface protein markers with novel flow cytometry-based techniques as biomarkers for PCa screening. Methods: This prospective study recruited at a tertiary care center between Oct 2019 and Mar 2022. Patients with PSA≥2 ng/ml underwent prebiopsy mpMRI followed by transperineal prostate biopsy (PI-RADS 1-2) or combined MRI-guided biopsy (PI-RADS ≥ 3). Patients with metastatic PCa or prior systemic therapy were excluded. Urine samples were collected at MRI using Colli-Pee. ProsEVs were labeled using monoclonal antibodies for PSMA and STEAP1 and ProsEV concentrations were determined using nanoscale flow cytometry. EV densities were calculated by normalizing EV counts to prostate volume. Multivariable logistic regression models were constructed and model performance was compared used ROC curve analysis. Results: This study had a total of 179 patients prospectively recruited, 95 were diagnosed with Gleason score (GS) ≥ 7 prostate cancer (csPCa), while the remaining had GS &lt;7 or benign disease. Analysis of urinary ProsEV densities revealed a significant dose-response relationship between benign, GS &lt;7 PCa and GS ≥ 7 PCa groups and ProsEV densities (p=0.01 for PSMA, and &lt;0.001 for STEAP1). The log sum of the PSMA and STEAP1 EV densities exhibited the strongest correlation with other ProsEV variables and was selected for model development. ROC curve analysis showed that the final model including Log Sum ProsEVs, PSA, and PI-RADS outperformed one including PSA and PI-RADS (0.733 vs 0.651, p=0.02). Specificity for detecting csPCa at a sensitivity of 90% was 39.5% in the final model compared to 37% for PSA and PI-RADS (Table). Conclusions: This study highlights the potential of urine ProsEVs as novel biomarkers for improving screening specificity for csPCa detection. Future works should explore analysis of intra-ProsEV content to further improve specificity and advance liquid biopsy techniques. [Table: see text]
Deep learning (DL) algorithms to predict prostate cancer progression on low/intermediate-risk needle core biopsies.
Authors: Chien-Kuang Cornelia Ding, Thiago Vidotto, Eric Erak, Lia De Paula Oliveira, Saikiran Bonthu, Chaith Kondragunta, Uttara Joshi, Nitin Singhal, Angelo M De Marzo, Tamara L. Lotan
Journal: Journal of Clinical Oncology (2024)

335 Background: Gleason Grade Group (GG) remains the standard of care to guide disease management in prostate cancer. Deep Learning (DL) algorithms assessing GG on whole slide images (WSI) have been largely validated by comparison to pathologist-determined GG. However, few studies have assessed DL grading of needle biopsies for predicting relevant clinical end-points. Methods: WSI of biopsies from two previously published cohorts (PMID 30279579, 27693448) were analyzed by a modified DL system for Gleason grading (PMID 35233002). In the Active Surveillance (AS) cohort (case-control design), all patients (n=137) had an initial biopsy with GG1 disease. Cases (63/137) had grade reclassification to GG2+ on repeat biopsies, or GG3+ or non-organ-confined disease by radical prostatectomy (RP), while the controls (74/137) continued on AS for &gt;8 years without grade reclassification. For the Grade Group 2 (GG2) cohort, all patients (n=285) had GG2 disease on biopsy followed by RP, and progression was defined as biochemical recurrence (38/285). One representative H&amp;E slide containing up to two biopsy cores from the diagnostic or confirmatory biopsy in both cohorts was graded by the DL system, and evaluated by 2-3 blinded uropathologists to provide consensus Gleason grading. Results: The agreement of GG between uropathologists and the modified DL system (κ quad ) was 0.32 for the AS cohort and 0.37 for the GG2 cohort. In the AS cohort, upgrading of the initial GG1 biopsy to GG2+ by the uropathologists occurred in 10% of cases compared to 7% of controls (p = 0.78). Upgrading by the DL system to GG2+ occurred in 33% of cases compared to 8% of controls (p=0.0005). In the GG2 cohort, biochemical recurrent after RP was not significantly associated with upgrading of the original biopsy to GG3+ by the uropathologists (HR= 0.55; 95% CI: 0.21-14.88; p=0.58) but significantly associated with upgrading by the DL system (HR=4.47; 95% CI: 1.32-15.09; p=0.01) in multivariable models including pre-operative PSA, clinical stage and fraction cores involved by tumor. Conclusions: In low or intermediate risk needle biopsies (GG1 and GG2), the agreement of grading between uropathologists and modified DL system is lower than that seen in analyses on a broader range of grade groups (PMID 35233002). Nevertheless, the DL system grading outperformed uropathologist consensus in predicting progression in patients with low/intermediate grade prostate cancer receiving active surveillance or radical prostatectomy.
Detection of sarcomatoid renal cell carcinoma using plasma cell-free DNA methylation.
Authors: Karl Semaan, Talal El Zarif, Ji-Heui Seo, Marc Eid, John Canniff, Brad Fortunato, Hunter Savignano, Matthew P. Davidsohn, Gitanjali Lakshminarayanan, Eddy Saad, Renee Maria Saliby, Ziad Bakouny, Sayed Matar, Pier Vitale Nuzzo, Jacob E Berchuck, Sabina Signoretti, David A. Braun, Matthew Freedman, Sylvan Baca, Toni K. Choueiri
Journal: Journal of Clinical Oncology (2024)

449 Background: Sarcomatoid differentiation (SD) in renal cell carcinoma (RCC) is associated with poor survival and heightened response to immune checkpoint blockade. Detection of SD can be challenging due to spatial heterogeneity and sampling error. Herein, we introduce a novel tissue–informed epigenomic approach to noninvasively identify sarcomatoid differentiation in patients with RCC from cell-free DNA (cfDNA) using &lt;1mL of plasma. Methods: Methylated immunoprecipitation and high-throughput sequencing (MeDIP-seq) was performed on pathologically reviewed clear cell RCC frozen tissue samples with and without SD (sarcomatoid-RCC and epithelioid-RCC, resp.) collected at the Dana-Farber Cancer Institute. Differentially methylated regions (DMRs) between sarcomatoid and epithelioid subtypes were identified using DESeq2 (false discovery rate of q &lt; 0.01). Then, MeDIP-seq was performed on cell-free DNA (cfMeDIP-seq) from patients with sarc-RCC and epi-RCC. A Sarcomatoid Methylation Score (SMS) was derived for each sample by aggregating the methylated cfDNA signal at tissue-derived sarcomatoid-enriched DMRs (sarc-DMRs), while normalizing to signal at epithelioid-enriched DMRs (epi-DMRs). Scores were compared between the two groups using a Wilcoxon rank-sum test. A classifier was built to distinguish sarc-RCC from epi-RCC based on SMS and its performance was evaluated using the area under the receiver operating characteristic (AUROC) curve. Results: We identified 32,086 DMRs between 9 sarc-RCC and 10 epi-RCC tissue samples at a false discovery rate of q &lt; 0.01, among which We selected 16,083 DMRs that are enriched in sarcomatoid vs. epithelioid. We generated high-quality cfMeDIP-seq profiles from plasma of 46 patients, 13 with sarc-RCC and 33 with epi-RCC. SMS were significantly higher in sarc-RCC vs. epi-RCC plasma samples (p = 6.7×10 -8 ). These scores achieved an AUROC curve of 0.95 for classifying patients with sarc-RCC from patients with epi-RCC. Conclusions: We present the first proof of concept study for the detection of sarcomatoid differentiation in RCC based on tissue-informed assessment of DNA methylation signals in cfDNA using &lt;1mL of plasma. This approach could overcome the challenges of spatial heterogeneity and sampling error that make identification of sarc-RCC difficult. More generally, it establishes a paradigm for identifying histologic subtypes of cancer based on their epigenomic correlates from cfDNA, with possible therapeutic implications in real-time.
Significance of CD73/adenosine receptor 2 (A2aR) and immune microenvironmental status in renal cell carcinoma with sarcomatoid changes and rhabdoid features.
Authors: Dai Takamatsu, Masatoshi Eto
Journal: Journal of Clinical Oncology (2024)

447 Background: One of the most aggressive forms among the kidney cancer is sarcomatoid and rhabdoid (S/R) renal cell carcinoma (RCC). There is still no effective treatment, and new therapies are needed. In this study, we focused on CD73 and A2aR, which regulate Treg involved in immune escape, and examined them clinicopathologically. Methods: We reviewed a total 1390 formalin-fixed, paraffin-embedded specimens of surgically resected RCC between 1989 and 2016. We detected 60 cases of RCC with sarcomatoid changes and rhabdoid features. We performed immunohistochemistry of CD73, A2aR, PD-L1, and CD8. We attempted to examine clinicopathological significance of CD73- and A2aR- positive RCC with S/R RCCs. The relationship between clinical and pathological features was evaluated using Wilcoxon’s rank sum and Fisher’s exact tests. A Cox proportional hazards regression model was used for multivariate analysis. Both PFS and OS were analyzed by using the Kaplan-Meier method and compared by the Wilcoxon’s rank test. All statistically signiﬁcances were defined as P&lt;0.05. Results: High-grade components were sarcomatoid changes (31 cases, 51.7%), rhabdoid features (16 cases, 21.7%), and both sarcomatoid and rhabdoid (13 cases, 21.7%). CD73 expression in the high-grade component was observed in 41 cases (68.3%), and A2aR expression was observed in 27 cases (45%). Significant differences among cMstage and high-grade components, sarcomatoid and rhabdoid, are detected in A2aR positive cases, respectively (p=0.0368, 0.0396, 0.0187). The univariate analysis showed a significantly poorer OS for patients whose tumors expressed CD73 and A2aR ( P = 0.0109 and P &lt; .0001). To validate this finding further, a multivariate analysis was performed using the Cox proportional hazards model). The results indicated that A2aR expression ( P = 0.0206) and pTstage ( P = 0.0433) were independent markers for unfavorable prognosis in S/R RCCs. CD73 and A2aR expressions were significantly related to poor PFS ( P = 0.0395, P = 0.0043, respectively). CD73 and A2aR expressions were significantly related to poor OS ( P = 0.0188, P &lt; .0001, respectively). Conclusions: CD73 and A2aR expression correlated with the poorest prognosis group among S/R RCCs, indicating that the use of inhibitors against them in combination with conventional therapies may improve prognosis.
Effect of body mass index (BMI) on efficacy of immune checkpoint inhibitors (ICIs) in patients with metastatic urothelial carcinoma (mUC) in a real-world setting.
Authors: David Lynn, Charbel Hobeika, Ubenthira Patgunarajah, Scott Dawsey, Nikhil Pramod, Wei Wei, Monica Nair, Kimberly Maroli, Allison Martin, Moshe Chaim Ornstein, Christopher Eing Wee, Timothy D. Gilligan, Amanda Nizam, Amanda Bonham, Omar Y. Mian, Paul G. Pavicic, C. Marcela Diaz-Montero, Shilpa Gupta
Journal: Journal of Clinical Oncology (2024)

571 Background: There is emerging data on the role of BMI and outcomes of ICIs in various solid tumors, with underweight pts having worse outcomes to ICIs. The effect of BMI on efficacy of ICIs in pts with mUC is not clear. Methods: We identified 335 adult pts with mUC at the Cleveland Clinic treated who received &gt;/= 2 cycles of ICI with pembrolizumab (P) or atezolizumab (A) between 2015 and 2023. Patient characteristics including age, sex, race, primary site (bladder vs upper tract UC (UTUC)), tumor histology and pre-ICI treatment NLR values were collected. BMI was calculated and values were collected and compared to assess impact on overall (OS) and progression free survival (PFS) after ICI start date. BMI was broken down into four categories: underweight (BMI less than 18.5 kg/m2), normal weight (BMI between 18.5 and 24.9 kg/m2), obese (BMI 30 kg/m2 or greater) and overweight (BMI between 25 and 29.9 kg/m2). OS and PFS were estimated by Kaplan Meier method and compared using log rank test. Results: Median age of pts was 73 yrs (35-95) and 254 (76%) pts were males. 247 (74%) received P, 88 (26%) received A. We found that underweight pts had significantly worse OS compared to normal or higher BMI (2.32 vs 13.08 mos; p=0.001) as well a significantly worse PFS (1.61 vs 4.75 mos; p=0.02) (Table). Conclusions: In our large real-world cohort of pts with mUC receiving ICI, we report for the first time the effect of BMI on outcomes with ICI. Further prospective studies are warranted. [Table: see text]
Evaluation of provider preferences in first-line metastatic cisplatin-ineligible urothelial carcinoma in the setting of platinum shortages.
Authors: Michael Seth Weinfeld, Priyanka Vinod Chablani, Natalie Marie Reizine, Walter Michael Stadler, Karine Tawagi
Journal: Journal of Clinical Oncology (2024)

576 Background: Standard of care for patients with metastatic urothelial carcinoma (mUC) who are ineligible to receive cisplatin has been gemcitabine and carboplatin (gem/carbo), and more recently followed by maintenance therapy with avelumab. Combination pembrolizumab (pembro) and the antibody-drug conjugate enfortumab vedotin (EV) has shown very promising results and is now approved for first-line therapy in cisplatin-ineligible patients based on the phase Ib/II EV-103 trial. We were interested in assessing providers’ decision-making between gem/carbo and EV/pembro based on perceived comparative response rates and toxicity profiles, as well as the nationwide platinum chemotherapy shortage in 2023. Methods: We sent a 10-question encrypted electronic survey centered on a scenario of a mUC case to 150 oncologists via email listservs and social media. Results: We received 45 responses: 7 oncologists (15.6%) chose gem/carbo, 15 (33.3%) chose EV/pembro, and a majority, 23 (51.5%) chose to discuss both options with patients. 40 (88.9%) were academic or disease focused and 5 (11.1%) described their practice as general oncology. Of oncologists who chose gem/carbo, the most common reasons were: gem/carbo has more long-term data (86.6%) and lack of phase 3 data for EV/pembro (71.4%). Of oncologists who chose EV/pembro, the most common reasons were: higher response rates (86.7%) followed by the carboplatin shortage (40%). Only 6.7% chose the carboplatin shortage as the main reason while 73.3% chose higher response rates as the main reason. Of oncologists who chose to discuss both, the most common reasons why they would consider EV/pembro were: higher response rates (82.6%), followed by patient preference (56.5%), followed by the carboplatin shortage (43.5%). 60.9% chose higher response rates as the main reason why they would consider EV/pembro. Conclusions: This questionnaire-based study of predominantly academic genitourinary oncologists suggests that the majority would consider EV/pembro as a first-line treatment for cisplatin-ineligible patients with mUC. The primary reason for this choice was the belief that it has higher response rates, as opposed to the national shortage of carboplatin or concerns regarding toxicity. We anticipate that the awaited results of the EV-302 trial in the coming months will also change the treatment landscape of mUC. However, similar issues may be relevant in the future for other treatment decisions in which incomplete information is available or with ongoing chemotherapy shortages.
Survival outcomes of metastatic prostate adenocarcinoma by primary metastatic site: A Surveillance, Epidemiology, and End Results (SEER) database study.
Authors: Shannon Bagot, Veronica Rasmusen, Sarah Kim, Amir A. Rahnemai-Azar
Journal: Journal of Clinical Oncology (2024)

200 Background: Prostatic adenocarcinoma (PAC) is the second leading cause of cancer-related death in men in the United States. The aim of this study is to investigate the effect of different sites of primary metastasis on overall survival (OS) of patients with metastatic PAC as well as identify risk factors that may impact prognosis. Methods: From the Surveillance, Epidemiology, and End Results (SEER) database, 26,085 patients diagnosed with metastatic PAC between 2010 and 2020 were analyzed to assess OS. Primary metastatic sites included in the study were bone, brain, liver, or lung and patients with multiple metastatic sites were excluded. Kaplan-Meier curves and Univariate Cox Regression analyses were used to determine the effect of various primary metastatic sites on OS. Results: Of all PAC primary metastatic sites, bone was the largest group (n=25,421, 97.5%), followed by lung (n=423, 1.6%), liver (n=194, 0.7%), and brain (n=47, 0.2%). Cox Regression analysis of PAC patients found that primary liver metastasis was associated with worst OS (Hazard Ratio (HR) 1.785, p&lt;.001) while primary lung metastasis had better OS (HR 0.738, p&lt;.001) when compared to patients with primary bone metastasis. Further analysis of the bone metastasis group with Univariate Cox Regression models was performed to evaluate the impact of age, treatment type, and race on OS. Factors found to significantly decrease OS included diagnosis at or after age 70 (HR 1.536, p&lt;.001) and treatment with transurethral resection of the prostate (TURP) (HR 1.239, p&lt;.001). Factors that significantly improved OS included treatment with radical prostatectomy (HR 0.222, p&lt;.001) and radiation therapy (HR 0.872, p=.002). No significant improvement in OS was seen with systemic therapy. Regarding race, OS was observed to be higher among Hispanic (HR 0.911, p&lt;.001) and Asian/Pacific Islander (API) (HR 0.773, p&lt;.001) populations when compared to Non-Hispanic Whites (NHW). No statistically significant difference in OS was found between NHW, Black, or American Indian and Alaska Native (AIAN) populations. Conclusions: Results of this study differ from previous publications that found no improvement in OS with radiation therapy and that identified AIAN race as a protective factor in PAC. These findings may inform future treatment of patients based on the site of primary metastasis and increase consideration of risk factors that can contribute to decreased survival.
Evaluating outcomes of sacituzumab govitecan (SG) in patients with urothelial cancer (UC), previously treated with enfortumab vedotin (EV).
Authors: Evangelia Vlachou, Burles Avner Johnson, Noah M. Hahn, Kelli Rourke, David James McConkey, Jean H. Hoffman-Censits
Journal: Journal of Clinical Oncology (2024)

567 Background: SG is an antibody drug conjugate (ADC) FDA approved for treatment refractory UC with Response Rate (RR) of 27%. Many patients (pts) receive SG after disease progression (PD) on EV, another ADC commonly used in earlier lines of therapy. In the TROPHY study, 10/113 pts treated with SG received prior EV and RR was similar to that of the entire cohort. We present a real-world experience in pts treated with SG after EV. Methods: In this retrospective analysis, pts with aUC treated with SG following EV at Johns Hopkins were identified. Demographic and treatment details were extracted by chart review. RR [Complete Response (CR) + Partial Response (PR)] with 95% Confidence Interval (95%CI) were compared between pts who did and did not have response to EV and between subgroups of interest using the χ 2 test. Response to EV was defined as physician-assessed CR or PR. Cox proportional hazard model analysis was used for comparing progression free (PFS) and overall (OS) survival for SG between groups. Results: 23 pts were identified, including 10 (43.5%) females and 19 (82.6%) white. Median age was 71.8 years (range: 46.3, 85.4). Primary tumor location was upper tract for 11 (47.8%) pts, lower tract for 11 (47.8%) and 1 pt had tumor in both sites. 11 (47.8%) pts had liver metastasis present at SG initiation. SG was 3rd line treatment for 5 (21.7%) pts and ≥ 4th line for 18 (78.3%). 4 (17.4%) pts had tumors with variant histology. RR for the entire cohort was 17.4%. Reason for discontinuation was PD in 16 (69.6%) pts and toxicity/functional decline in 7 (30.4%). The table summarizes RR in different subgroups. Median PFS for SG was 2.63 months among EV responders and 1.35 months for non-responders [Hazard Ratio (HR): 0.31, 95%CI: 0.12, 0.83, P = 0.02]. Median OS for SG was 5.36 months in EV responders and 5.78 months in non-responders (HR: 0.82, 95%CI: 0.27, 2.46, P= 0.7). No PFS or OS difference was found between subgroups: Upper vs lower tract primary tumor, liver metastasis presence vs absence, variant histology vs pure UC, estimated glomerular filtration rate (eGFR) ≥ 30 mL/min vs &lt; 30. The small sample precluded multivariable analysis. Conclusions: To our knowledge this is the largest real-world cohort of pts with UC treated with SG post EV. A trend towards improved RR and PFS for SG was noted among EV responders. In our analysis clinical outcomes remained consistently similar across all subgroups, including pts with known poor prognosis risk factors. [Table: see text]