tbuckley/cabot-search huggingface dataset:
Marijuana use may be associated with reduced prevalence of prostate cancer: A cross-sectional study using the national survey on drug use and health database.
Authors: Turab J Mohammed, James Yu, Yong Qiao, Youngchul Kim, Helen Swede, Zhao Wu, Eric Mortensen, Jingsong Zhang
Journal: Journal of Clinical Oncology (2024)

101 Background: Preclinical data from cell lines and animal xenograft models support the anti-tumor effects of cannabinoids in prostate cancer (PC). Methods: We performed a cross-sectional study to investigate this association using National Survey on Drug Use and Health (NSDUH) data consisting of 2503 participants accrued from 2002 to 2020. Key independent variable was defined as current, former, and never users of marijuana (MJ). Dependent variable was self-reported PC (yes, no). Other MJ-related variables evaluated: age at first use, number of days used in the past 30 days, use of medical MJ, legality of MJ use in state of residence. Demographic variables assessed as potential confounders or covariates were: age, sex, race/ethnicity, education, marital status, total family income, insurance status, sexual identity, residence status, served in armed forces, cigarette smoking, and alcohol consumption. Multivariate (MV) logistic regression was employed to calculate odds ratios (OR) and 95th percentile confidence intervals (CI) to quantify relationship with MJ use in relation to PC status. Results: Prevalence of PC was significantly lower among current MJ users (46/145, 31.7%), and former users (323/1021, 31.6%) in comparison to non-users (534/1337, 39.9%, p &lt; 0.001). Older MJ users (≥ 65) had significantly lower prevalence of PC compared to nonusers (36.4% vs. 42.4%, p = 0.016). A similar significant reduction was documented among non-Hispanic white (NHW) MJ users when compared to nonusers (28.9% vs. 38.3%, p &lt; 0.001). There were no significant differences in the prevalence of PC between MJ users and non-users among the young (50-64) or other race/ethnicity. In MV logistic regression analyses, former MJ use was associated with a lower prevalence of PC compared to never use (OR = 0.74, 95% CI 0.62 - 0.90, p=0.001). Current MJ use also was suggestive of reduced prevalence but did not reach statistical significance (OR=0.77, 95% CI 0.52 – 1.14, p=0.198) possibly due to low sample size. Conclusions: Our findings provide additional data to link MJ use with low prevalence of PC, particularly in NHW. Future prospective studies using regulatory approved medical MJ are warranted. [Table: see text]
The effect of radiotherapy on the course of disease in prostatic cancer with high metastatic burden.
Authors: Tal Falick, Philip Blumenfeld, Antoni Skripai, Marc R. Wygoda
Journal: Journal of Clinical Oncology (2024)

112 Background: Many retrospective studies suggest that local RT for the prostate in the metastatic setting improves overall survival, however the question of whether metastatic burden is an independent factor influencing the results of localized treatment was not directly addressed. Moreover, results are conflicting with the outcomes from prospective trials on the subject. Thus overall, there is a limited, conflicting and insufficient data on the effect of radiotherapy on prostate cancer patients with a significant metastatic burden. Here we show that RT treatment in prostate cancer patients with a significant metastatic burden (four or more bone metastases with one or more outside the vertebral bodies or pelvis or a visceral metastases) is beneficial and extends overall survival while reducing symptoms. Methods: We conducted a retrospective study examining 100 high metastatic burden prostate cancer patients treated in Hadassah Ein Karem Medical Center between the years of 2004-2022. Data was collected from the medical records of the hospital. Variables that were recorded include basic demographics, time and durations of hospitalization, cancer staging, treatment course, RT course, imaging after RT, vital status, clinical symptoms and PSA levels. Tumors could be of any grade (Gleason score 6–10) and T or N stage (T1-T4; N0-N1; M1). Prostate RT included external EBRT to the prostate with/ without pelvis. Radiotherapy dosage between 30-60 gy using conventional fractionation. Results: Overall Survival was higher in the RT group when compared to NRT group (P &lt; 0.046). Progression free survival (PFS) was not significantly higher in the RT group as compared to the NRT group (P &lt; 0.153). However, a trend towards better PFS was noted. Biochemical progression free survival was higher in the RT group when compared to NRT group (P &lt; 0.033). Time without symptom worsening as defined by time since treatment beginning until worsening of a symptom or appearance of a new symptom reported by the patient included urinary incontinence, urinary urgency, and increased frequency, need for catheter or urinary obstruction. Time without symptom worsening was higher in the RT group as compared to NRT group (P &lt; 0.017). The amount of hospitalization wasn’t significantly higher in the RT group when compared to NRT group (P &lt; 0.460). The duration of hospitalization was significantly higher in the NRT group when compared to the RT group (P &lt; 0.038). Conclusions: Here we show for the first time an increase of overall survival specifically in the high metastatic burden group when adding the RT to a standard treatment of choice (ADT with or without chemotherapy). We also demonstrate an improvement in QOL of our patients.
Estimating median overall survival of apalutamide compared to placebo in metastatic hormone-sensitive prostate cancer (mHSPC) populations: Statistical extrapolations of the TITAN study.
Authors: Neeraj Agarwal, Anders Bjartell, Álvaro Juárez, Ronja Kerßenboom, Nolen Perualila, Peter Wigfield, Kim N. Chi
Journal: Journal of Clinical Oncology (2024)

223 Background: Apalutamide plus ADT (APA) demonstrated significantly improved overall survival (OS) compared to placebo plus ADT (PBO) for patients with mHSPC in the TITAN study (HR, 0.65; 95% CI, 0.53 to 0.79; P &lt; .0001). At the time of final analysis, the median OS was not reached in the APA arm or subgroups after a median follow up of 44 months. This work aimed to estimate OS medians for APA and PBO arms beyond the TITAN follow-up by fitting validated survival models. Methods: OS was predicted for the overall population treated with APA or PBO, with or without Inverse probability of censoring weighting (IPCW) crossover adjustment, and for the low and high-volume (LVD, HVD), HVD synchronous and HVD metachronous subgroups. General population mortality adjusted TITAN patient-level data was fitted to six parametric models (Weibull, exponential, log-normal, log-logistic, generalized gamma, and Gompertz) using the individual fits approach. Best fit was determined by statistical and visual fits, along with the Akaike Information Criterion (AIC)/Bayesian Information Criterion (BIC) ranking, according to the recommendations of the National Institute for Health and Care Excellence Decision Support Unit 14. Results: Best fit extrapolation estimated median OS of 71.8 months for the overall mHSPC population treated with APA (Table), leading to an estimated median improvement of up to 32 months versus PBO. Median OS values predicted by the other five models ranged from 62.4 to 78.1 months. Across subgroups, best fit models estimated median OS of 113.7 months for APA in LVD and a consistent median OS of 52 months for HVD subgroups. Conclusions: While results of this extrapolation study should not be equated to those of a clinical trial, this analysis meets an evidence gap by predicting median OS in the APA arm of the TITAN study for the overall mHSPC population as well as for various subgroups of this heterogeneous population, strengthening the evidence supporting early treatment with APA across the broad mHSPC population. [Table: see text]
Toxicity-benefit analysis of advanced prostate cancer trials using weighted toxicity scoring.
Authors: Jaspreet Kaur Gill, Rubens Copia Sperandio, Tuan Hoang Nguyen, Urban Emmenegger
Journal: Journal of Clinical Oncology (2024)

110 Background: The weighted toxicity score (WTS) is a metric suitable for comparing the toxicity burden in experimental versus control arms of randomized controlled trials (RCTs). When compared against clinical endpoints, the WTS can be used to evaluate the cost versus benefit of anti-cancer agents. This study sought to apply the WTS to prostate cancer (PC) clinical trials. Methods: Select phase 3 PC RCTs with reported adverse event (AE) data were compiled. The WTS was computed for each trial arm and compared to reported hazard ratios (HRs) of primary and/or secondary endpoints (i.e., overall survival (OS) and progression-free survival (PFS)). Average WTSs for the experimental versus control arms were used to calculate the toxicity differential between treatment arms. Average HRs for OS and PFS were used to compare efficacy. Results: Sixteen RCTs were analyzed (investigational agents: androgen-receptor signaling inhibitors (ARSi) [n = 4], poly (ADP-ribose) polymerase inhibitors (PARPi) monotherapy [n = 3], ARSi + PARPi as well as ARSi + ARSi combination therapies [n = 3 each], and triple therapy [n=3]). The median number of distinct reported AEs across all studies was 18 (range, 9-61). Overall, toxicity and efficacy were greater among experimental than control arms (6.62 versus 4.00 median WTS; median HR for OS 0.71, median HR for PFS 0.61). The triple therapy studies observed the lowest increase in toxicity by adding an ARSi to control therapy (10.4%), associated with 52% lower risk of progression, and 29% lower risk of death. Comparably, the ARSi + PARPi trials noted the highest increase in toxicity (79.7%), with 32% lower risk of progression and 12% lower risk of death. The PARPi monotherapy, ARSi monotherapy, and ARSi + ARSi combination therapy studies reported increased toxicity due to experimental therapy in descending order (Table). Conclusions: The WTS enables toxicity versus benefit assessment for anti-cancer regimens. Clinical application of this metric may facilitate individualized treatment planning in advanced PC management. [Table: see text]
Days spent with healthcare contact by patients with metastatic castrate-resistant prostate cancer in the last year of life.
Authors: Daniel Sentana Lledo, Amelia Barnett, David Johnson Einstein, Arjun Gupta, Alicia K. Morgans
Journal: Journal of Clinical Oncology (2024)

100 Background: Days spent with healthcare contact while pursuing cancer treatment (i.e., “time toxicity”) may be particularly relevant when life expectancy is most limited. Patients with metastatic castrate resistant prostate cancer (mCRPC) ultimately choose whether to pursue further cancer directed therapies or receive supportive care and reduce expected healthcare contact. We sought to define the evolution of time toxicity over the last year of life in patients with mCRPC. Methods: Contact days, defined as any day with healthcare contact outside the home, were retrospectively assessed and categorized (e.g., infusion, ER visit) in 96 patients at an academic cancer center. The primary objective was to compare contact days in the 90-day period between 12 and 9 months prior to date of death (“first quarter”) and the 90-day period prior to death (“last quarter”) using the Wilcoxon signed rank test. Additional exploratory analyses were performed evaluating the association between clinicodemographic variables and systemic treatments received. Results: There were higher median [IQR] total contact days in the last quarter (6 [2,17]) compared to the first quarter (4 [3,6], p &lt; 0.01), driven by ER visits and hospitalizations. Compared to patients off treatment/supportive care (4 [3,4]) in the first quarter, chemotherapy (5 [4,6], p = 0.02) and radiotherapeutics (5 [4,9], p = 0.03) were associated with greater contact days, but androgen signaling inhibitors were not (3 [2,5], p = 0.20). However, there were no significant differences in contact days between any treatment vs non-treatment in the last quarter. Non-White patients (n = 27) and those without higher education (n = 30) had more contact days in the last quarter (9 [2,19], p &lt; 0.01 for both). Patients who enrolled on hospice 7 days (n = 11) or 30 days (n = 39) before date of death had more contact days in the last quarter than those with earlier enrollment (23 [7,28], p &lt; 0.01; 13 [4,24], p &lt; 0.01 respectively). Conclusions: Healthcare contact was higher in the last 3 months of life due to increased number of days with inpatient level of care. Further studies to define healthcare exposure and time toxicity of mCRPC treatments are warranted to inform patient expectations towards the end-of-life. [Table: see text]
Cost-effectiveness of triplet therapies in metastatic hormone-sensitive prostate cancer used in PEACE-1 and ARASENS.
Authors: Nataniel Hernan Lester-Coll, David Joseph Benjamin, Hélène Ribault, Stéphanie Foulon, Karim Fizazi, Arash Rezazadeh
Journal: Journal of Clinical Oncology (2024)

222 Background: Recent findings from the PEACE-1 and ARASENS trials have demonstrated survival benefits in men with newly diagnosed metastatic hormone-sensitive prostate cancer using different triplet therapies, including Abiraterone and Darolutamide added to Androgen Deprivation Therapy and Docetaxel. Given the rising costs of cancer care, this study aimed to assess the cost-effectiveness of these treatment regimens. Methods: Drug prices were obtained from drugs.com and assurance-maladie.ameli.fr at wholesale prices to evaluate both United States (US) and France payer perspectives. Survival and progression data were sourced from Kaplan-Meier curves of the PEACE-1 and ARASENS trials and fitted to Weibull distribution models in R. The parameters were imported into TreeAge Pro 2023 for partitioned survival analysis. Health states were classified as "Pre-Progression," "Post-Progression," and "Death," each assigned specific health utility values and costs. Outcomes including total costs, quality-adjusted life years (QALYs), and incremental cost-effectiveness ratios (ICERs) were calculated. Uncertainty was addressed through one-way and probabilistic sensitivity analyses. The baseline willingness-to-pay (WTP) threshold was $100,000 per QALY. Euros were converted to US Dollars. Results: At the baseline WTP of 100,000, generic Abiraterone (US, France) in PEACE-1 and Darolutamide in ARASENS from the French perspective were cost-effective. Generic Abiraterone was dominant, associated with lower net costs (-1,347 to -333) and higher QALYs (0.16) and Darolutamide had an ICER of .7,001 per QALY. In contrast, other triplet therapies increased both net costs and QALYs. Abiraterone yielded ICERs of 408,074 (US) and 114,995 (France) per QALY. Darolutamide in the US had an ICER of $383,732 per QALY. On one-way sensitivity analyses, most drugs would need to be priced at less than ~4,000 a month to be cost-effective at WTP of 100,000 per QALY. On probabilistic sensitivity analyses, with WTP of 100,000 per QALY, generic Abiraterone (US) was the cost-effective drug (88% of simulations), while brand Abiraterone and Darolutamide (US) were the least cost-effective (0% of simulations). Conclusions: Cost-effectiveness of therapies in metastatic hormone-sensitive prostate cancer vary significantly based on pricing and country payer perspective. At a WTP threshold of $100,000, only generic Abiraterone (US, FRA) and Darolutamide (France) were cost-effective. [Table: see text]
Trop-2: A promising new therapeutic target in penile squamous cell carcinoma.
Authors: Richard Weiten, Carolina Kessler, Hanna Elisa Spohn, Enno Storz, David A. Pfister, Tim Nestler, Yuri Tolkach, Ralph M. Wirtz, Melanie von Brandenstein, Philipp Krausewitz, Axel Heidenreich
Journal: Journal of Clinical Oncology (2024)

12 Background: Penile squamous cell carcinoma (PSCC) is an infrequent yet progressively prevalent malignancy. Despite ongoing advancements in personalized and immunotherapeutic approaches, patients grappling with the diagnosis of locally advanced or metastasized PSCC still confront a limited therapeutic arsenal, leading to an unfavorable prognosis. Consequently, an imperative mandate arises to explore alternative therapeutic modalities, particularly antibody-drug-conjugates (ADCs), which have demonstrated significant clinical efficacy in the context of metastatic solid tumor pathologies. Our aim was to ascertain the potential utility of ADCs targeting Trop-2 in both localized PSCC (PRIM) and patient-matched distant metastases (MET). Methods: Immunohistochemical analysis of Trop-2 expression was conducted in PRIM ( N=40) and their corresponding METs ( N=9, including lymph node and lung metastases). We assessed overall survival (OS) by stratifying patients into subgroups based on Trop-2 expression: weak (H-score 15-99) versus moderate/strong (H-score 100-300). Additionally, we explored the relationship between Trop-2 and HPV-dependency. Furthermore, Trop-2 mRNA expression levels were quantified via qRT-PCR, and an enzyme-linked immunosorbent assay was employed to measure Trop-2 in serum samples derived from PRIM ( N=40) and a healthy control group ( N=10). Results: We found a statistically significant increase in Trop-2 mRNA expression levels in individuals afflicted with PSCC compared to healthy controls ( p&lt;0.0001). Moreover, a notable elevation in Trop-2 protein expression was observed in the serum specimens obtained from PSCC patients ( p&lt;0.01). The majority of patients exhibited moderate to strong Trop-2 expression, indicative of a robust median H-score of 280 (interquartile range: 210-300). Subgroup analysis revealed a correlation between Trop-2 expression and HPV status ( p&lt;0.01), demonstrating discernible associations with more favorable clinical outcomes, as evidenced by the log-rank (Mantel-Cox) test ( p&lt;0.05). Conclusions: Trop-2 protein expression in PSCC holds prognostic significance. Furthermore, the elevated Trop-2 levels in both PRIM and PSCC metastases suggest that the Trop-2-targeted ADC, Sacituzumab govitecan, may emerge as a promising novel therapeutic intervention for these patients.
Prostate extracellular vesicles and prediction of clinically significant prostate cancer: A prospective single-institution pilot study.
Authors: Cameron J Britton, Jack R. Andrews, Ali Arafa, Yohan J Kim, Laureano J Rangel, Phillip J. Schulte, Vidhu B. Joshi, Mohamed E. Ahmed, R. Jeffrey Karnes, Fabrice Lucien
Journal: Journal of Clinical Oncology (2024)

337 Background: Prostate cancer remains the most common solid organ malignancy among males in the United States. Commercial biomarkers and multiparametric MRI have been utilized to better triage men with elevated PSA and determine patients most likely to have clinically significant prostate cancer (csPCa) upon prostate biopsy. We studied the combination of MRI with PSA-based and novel extracellular vesicle (EV)-based biomarkers to determine the optimal pre-biopsy testing to reduce the number of unnecessary biopsies. Methods: Men presenting to our clinic with elevated PSA (≥ 2 ng/ml) were prospectively enrolled from October 2019 to March 2022. All men underwent multiparametric MRI and blood draws to determine prostate health index (PHI) scoring, EV density, and PSA density. MRI-fusion biopsy was performed with both systematic and targeted prostate sampling, with clinicians blinded to prior blood testing results. Blood concentrations of prostate EV (ProsEVs) were measured by nanoscale flow cytometry using antibodies against PSMA and STEAP1. Sensitivity, specificity, positive predictive value, and negative predictive value were calculated, and receiver operator characteristic (ROC) curves were constructed separately for all patients, those without prior diagnosis of PCa, and biopsy-naïve patients. Bootstrapping analysis was performed to provide more accurate assessment of the predictive ability of all combinations. Results: Ultimately, 175 men enrolled and underwent MRI, blood testing, and prostate biopsy. Among the 175 patients included, 101 (58%) had never undergone biopsy, 38 (22%) had a previous negative biopsy, and 36 (21%) were on active surveillance (AS) for GS6 disease. AUC of mpMRI (PI-RADS≥3) to predict clinically significant PCa was 0.66 with a sensitivity, specificity, NPV and PPV of 95.2%, 37.6%, 76.0% and 79.26%. MRI combined with STEAP1-EV density had an AUC of 0.77 with a sensitivity, specificity, NPV and PPV of 90.1%, 46.7%, 64.4% and 80.9%. A multivariable model including MRI, STEAP1-EV density, PSA density and PHI density outperformed other combinations with an AUC, sensitivity, specificity, NPV and PPV of 0.90, 89.2%, 68.7%, 72.8% and 88.1%. Conclusions: Combination of mpMRI with ProsEV and PSA derivatives demonstrated better predictive ability for csPCa on biopsy compared to imaging or serum testing alone. Inclusion of prostate volume with biomarkers further increased predictive ability which could lead to a decrease in number of unnecessary biopsies for men with benign conditions and indolent cancer.
Clinicopathological features and transcriptomic profiles of MED15-TFE3-rearranged renal cell carcinoma: A retrospective study of 14 cases.
Authors: Sike He, Haoyang Liu, Xu Hu, Guangxi Sun, Zhenhua Liu, Pengfei Shen, Hao Zeng
Journal: Journal of Clinical Oncology (2024)

462 Background: TFE3-rearranged renal cell carcinoma (TFE3-rRCC) is a rare type of RCCs with various fusion types and heterogeneous clinicopathological features. MED15-TFE3 is a fusion that usually present as an extensive cystic mass with low malignant potential. We sought to summarize the clinicopathological, transcriptomic characteristics and survival outcome in MED15-TFE3-rRCC patients. Methods: All 14 cases were collected retrospectively fromSichuan University West China Hospital from 8/2011 to now. Diagnosis of MED15-TFE3 fusion was confirmed by fluorescence in situ hybridization and RNA sequencing. The clinicopathological features and follow-up data were collected for further analysis. The tumor transcriptomic profiles were analyzed by Gene Set Enrichment Analysis (GSEA), Gene Ontology (GO) analysis, Kyoto Encyclopedia of Genes and Genomes (KEGG) analysis via R tool. Results: The median age was 43.5 years (range, 22 to 70). Majority of the cases were female (10/14). 8 patients (57.1%) underwent radical nephrectomy, 1 patient received cytoreductive surgery, and 5 patients (35.7%) received partial nephrectomy. At initial diagnosis, most cases (10/14) were localized disease, while 2 patients had regional lymph nodes metastasis, and 1 patient had distant metastasis (bone). For the patients without distant metastasis (n=13), 2 patients developed metastasis (liver, lung, abdominal, in situ) with disease-free survival of 11.4 and 29.0 months. As for the pathological features, 10 (71.4%) of thesamples presentedcystic morphologically, and other 4 (28.6%) were papillary. 10 (71.4%) were in G2 by ISUP score. For metastatic patients, 3 received first-line therapy (1 axitinib, 1 axitinib + sintilimab, 1 sunitinib), 2 received second-line therapy (1 axitinib + sintilimab, 1 axitinib + toripalimab), 1 received third-line therapy (axitinib + toripalimab + everolimus). They are still under follow-up. GSEA analysis illustrated that compared to paraneoplastic tissue, apical surface, bile acid metabolism, KRAS signaling, Xenobiotic Metabolism, and estrogen response were upregulated in tumor. For the patients with distant metastases, the transcriptomic analysis revealed that organelle fission, nuclear division, mitotic nuclear division, and chromosome segregation were significantly upregulated, which may be associated with tumor metastasis. The overall immune cell infiltration was comparable in metastatic patients and non-metastatic patients. However, the expression level of type 17 T helper cell, B cells, plasmacytoid dendritic cell, and activated dendritic cell were significantly different. Conclusions: MED15-TFE3 rRCC mainly present low-grade cystic renal neoplasm with favorable prognosis. For metastatic MED15-TFE3 rRCC, there is no standard therapy. And the transcriptomic evidence may provide insights for future research.