tbuckley/cabot-search huggingface dataset:
A phase II single arm prospective study of high dose testosterone in combination with carboplatin chemotherapy in late line metastatic castrate-resistant prostate cancer (HIGH-TeCH study).
Authors: Megan Crumbaker, Samantha Shekar, Mitchell G. Lawrence, Leonard D Goldstein, Andrew O. Yam, Teesha Downton, Stephen Begbie, Rob Zielinski, William Fox, Nicole Araiza, Jacob Yousif, Lalith Ratnayake, Emmanuel S. Antonarakis, Samuel R. Denmeade, Anthony M. Joshua
Journal: Journal of Clinical Oncology (2025)

218 Background: Bipolar androgen therapy (BAT) is a safe and well-tolerated treatment paradigm in metastatic castrate resistant prostate cancer (mCRPC) but response rates and duration are modest. Preclinical data suggests supraphysiologic androgens interrupt DNA relicensing and increase double-stranded DNA breaks, suggesting a potential synergy with the addition of carboplatin chemotherapy. We assessed the safety and efficacy of this treatment combination in Arm B of the HIGH-TeCH trial. Methods: Men with refractory mCRPC after at least one line of taxane based chemotherapy and androgen signaling inhibitor received four weekly testosterone enanthate (500mg IM) with Carboplatin (AUC 5) and androgen deprivation therapy. Five (24%) PSA50 responses were achieved at planned interim analysis of the first 21 patients, meeting threshold for study expansion to a total of 40 participants. Results: Currently, 37 of a target total 40 patients have been recruited. Median follow up was 14.8 months as of 1st October 2024. Median age 72. Median prior lines of treatment 3; 51% of patients had prior 177-Lutetium. 27 patients discontinued treatment for disease progression (PSA, radiological, clinical), 1 discontinued due to a serious adverse event (CVA) and 9 patients remain on trial. Median of 5 cycles of BAT with Carboplatin were administered. Seven (19%) patients had a PSA response ≥ 50%. Fourteen (38%) patients had clinical benefit (&gt; 6 months duration on study). Median progression-free survival was 6.6 months (95% CI, 5.5 – 9.9). Median overall survival was 20.4 months (95% CI, 15.5 – not reached). Thirty-one (84%) patients experienced a treatment–related adverse event (TRAE); of which, 94% were grade 1 – 2. Highest rates of TRAEs were fatigue (52%), nausea (39%), musculoskeletal pain (23%), constipation (23%). There was no grade 4 TRAEs or deaths. Conclusions: BAT with carboplatin has an acceptable safety profile and demonstrated clinical benefit in heavily pre-treated mCRPC patients. Accrual will be completed imminently with final analysis to be presented. Translational studies to identify predictive biomarkers and quality of life analyses are underway. Clinical trial information: NCT00309985 .
Bacillus Calmette-Guérin (BCG) treatment patterns and real-world outcomes in high-risk (HR) non-muscle-invasive bladder cancer (NMIBC): A systematic literature review (SLR).
Authors: Anthony Eccleston, Abin Koshy, Mihaela Georgiana Musat, Cristiana Tzonev, Julia Brinkmann, Jane Chang
Journal: Journal of Clinical Oncology (2025)

730 Background: Transurethral resection followed by induction and maintenance intravesical BCG is currently standard of care for patients with HR NMIBC. HR is generally defined as stage T1, high grade (HG), carcinoma in situ, tumors &gt;3 cm, variant histology, BCG failure in HG tumor, or lymphovascular invasion. Considering the variability in HR definitions and BCG maintenance schedules, we analyzed the evidence on maintenance utilization and outcomes in patients with HR NMIBC. Methods: We conducted an SLR of English-language real-world evidence (RWE) studies published 01/01/2011–06/12/2024 reporting efficacy or safety outcomes with BCG in patients with HR NMIBC using MEDLINE, Embase, and Cochrane supplemented by manual searches of relevant conference proceedings 2021–2024. Studies reporting treatment patterns or progression-/recurrence-related outcomes were analyzed. Results: Among 244 RWE studies identified, 86 reported data on HR populations, which was defined by commonly accepted definitions such as T1 high grade (HG) or any HG, with 37.2% using AUA/EAU guidelines. Across studies reporting BCG maintenance patterns in the HR population, 40.7% of patients (6,795/16,712; 16 studies) received some form of maintenance. Details on maintenance duration were reported in 11 studies; among them, 27.9% of patients (1,154/4,142) completed ≥1 year of maintenance. Details on adequate BCG treatment were reported in 8 studies, defined as receipt of ≥5/6 induction instillations and ≥2/3 maintenance instillations. Across these eight studies, 59.5% of patients (10,122/17,007) did not receive adequate BCG treatment. While comparisons across studies should be interpreted with caution due to heterogeneity in study populations. Median 2-year recurrence-free survival (RFS), 5-year RFS, and 2-year progression-free survival (PFS) across studies was numerically longer with maintenance versus induction alone (table). However, median 5-year PFS across studies appeared similar with or without maintenance. Conclusions: Less than 50% of HR patients who started BCG treatment received some form of maintenance; however, studies were highly heterogenous in reporting patterns of BCG treatment and definitions of HR NMIBC. Although maintenance duration was underreported, ~30% of patients completed ≥1 year of maintenance. In patients with HR NMIBC, RWE suggests improved outcomes with maintenance versus induction alone. More studies are needed to confirm the benefit of different maintenance schedules and durations. Real-world efficacy outcomes: HR NMIBC population. Induction, median (range) [n studies], % Induction + maintenance, median (range) [n studies], % 2-year PFS 85.7 (81–95) [3] 92.0 (89–98) [8] 2-year RFS 66.7 (53–81) [2] 77.1 (62–85) [7] 5-year PFS 82.6 (72–89) [4] 84.0 (53–98) [13] 5-year RFS 53.0 (31–75) [6] 64.7 (27–78) [10]
Coronary Vasospasm and Heart Rhythm Disorders: A Case Report
Authors: Luca Rodella
Journal: Clinical Cardiology and Cardiovascular Interventions (2025)

Vasospastic angina (VSA), also known as variant angina, is a condition characterized by recurrent episodes of chest pain, frequently during the night or in the early hours in the morning, due to spasm and contraction of the muscular tonaca of the coronary arteries, differentiating therefore from classic angina. The real physiopatological mechanisms of VSA are still a field of considerable research, although it is now clear that inflammation plays an important role in the genesis of the spasm. Pharmacological therapy, based today primarily on the use of nitrates and calcium channel blockers, is also an area of study to guarantee a bassetter prognosis for these patients.
Efficacy and safety of immune checkpoint inhibitors (ICI) for the treatment of metastatic penile squamous cell carcinoma (mPSCC).
Authors: Tiewei Cheng, Timothy J. Schieber, Anna Clennon, Katie Bertken, Sunny Shengyuan Cai, Elizabeth Marie Wulff-Burchfield, Saqib Abbasi, Rahul Atul Parikh, Haoran Li
Journal: Journal of Clinical Oncology (2025)

4 Background: Metastatic penile squamous cell carcinoma (mPSCC) is a rare and aggressive malignancy with limited treatment options. Standard systemic therapies include paclitaxel, ifosfamide, cisplatin (TIP), fluorouracil and cisplatin (5-FU + cis), paclitaxel monotherapy and cetuximab. These regimens were evaluated as small single-arm studies. The HERCULES trial, a single-arm phase 2 clinical study, demonstrated the safety and efficacy of combining immunotherapy with chemotherapy, signaling a potential benefit of immunotherapy. Our retrospective analysis evaluates the safety and efficacy of single-agent immunotherapy at the University of Kansas and Aurora St. Luke’s Medical Center. Methods: We conducted a multicenter retrospective, IRB-approved study of mPSCC patients treated with single-agent immunotherapy from 2015 to 2023. Objective response rates were assessed per RECIST version 1.1, and progression-free survival (PFS) and overall survival (OS) were estimated using the Kaplan-Meier method. Adverse events were graded per CTCAE version 5.0, with only grade 3+ immune-related adverse events being recorded. Results: Nine patients with mPSCC were included, with a median age of 75 years (range, 50-92). Over half (n=5) had an Eastern Cooperative Oncology Group performance status (ECOG PS) of 2 or more, and most (n=8) had visceral metastasis. Single-agent immunotherapy was administered as first-line (n=3), second-line (n=4), and third-line or beyond (n=2). Pembrolizumab was used in six patients, with two receiving nivolumab and one cemiplimab. The objective response rate was 33.3% (n=3), including one complete response. Median PFS was 2.82 months (range, 1.0-14.3), and median OS was 4.3 months (range, 1.0-24.9). Patients who responded had PFS exceeding 12 months, with two still ongoing at data cutoff. No grade 3 or higher treatment-related adverse event has been observed during the treatment period. Additional analyses to correlate the response with HPV positivity are ongoing. Conclusions: Our findings suggest that single-agent immunotherapy can yield favorable response rates and durations in older and/or frail mPSCC patients. While our sample size is small and retrospective, response rates are comparable to those in the HERCULES trial (33.3% vs. 39.4% with chemoimmunotherapy). Notably, grade 3+ treatment-related adverse events were lower in our study compared to 51.4% of HERCULES patients. This underscores the potential of single-agent immunotherapy as a safe and effective option for this rare malignancy. Further prospective studies are needed to optimize treatment strategies for mPSCC.
Global spatiotemporal trends in prostate cancer burden and its socioeconomic disparities: An observational study from 1990 to 2021.
Authors: Xianghong Zhou, Qiang Wei
Journal: Journal of Clinical Oncology (2025)

325 Background: Prostate cancer is the second most common cancer in men globally, posing significant health challenges. Conflicting findings on its global burden and trends necessitate updated analyses. This study provides recent estimates of prostate cancer's global, regional, and national burden from 1990 to 2021, analyzes temporal trends, and offers epidemiological insights for clinicians, researchers, and policymakers. Methods: We analyzed data from the Global Burden of Disease Study 2021 on prostate cancer cases, deaths, and disability-adjusted life years (DALYs) from 1990 to 2021, including age-standardized rates (ASRs) for incidence, mortality, and DALYs. Trend analyses utilized average annual percent change (AAPC) calculations and joinpoint regression models. Age-period-cohort analysis assessed the effects of age, period, and cohort on incidence and mortality trends. Pearson correlation evaluated associations between ASRs and the Socio-demographic Index (SDI) to explore socioeconomic impacts. Results: From 1990 to 2021, global prostate cancer cases, deaths, and DALYs increased, reflecting aging populations. The age-standardized incidence rate (ASIR) showed a slight global increase (AAPC = 0.15, 95% CI: 0.05–0.25), while the age-standardized mortality rate (ASMR) and age-standardized DALY rate (ASDR) decreased (ASMR AAPC = -0.83, 95% CI: -0.92 to -0.74; ASDR AAPC = -0.75, 95% CI: -0.82 to -0.68), indicating improved survival. High-SDI regions had decreasing ASMR and ASDR despite high ASIRs due to better detection and treatment. Low-SDI regions saw increases in ASIR, ASMR, and ASDR, with the highest mortality and DALY rates, indicating rising burden and potential healthcare access issues. Joinpoint regression showed initial increases then decreases in ASIR, ASMR, and ASDR, with regional differences in timing. Age-period-cohort analysis revealed age effects with rising incidence and mortality risks, declining incidence risk in the oldest age groups. Period effects showed incidence risk increasing until 2011–2017, then declining; mortality risk decreased over time. Cohort effects showed stable then increasing incidence risk in younger cohorts, while mortality risk decreased across cohorts, reflecting healthcare improvements. Conclusions: The global absolute burden of prostate cancer has increased, but age-standardized mortality and DALY rates have decreased, especially in high-SDI regions due to advancements in detection and treatment. Low-SDI regions face rising incidence and mortality, highlighting growing disparities. Targeted interventions and resource allocation in low-SDI regions are needed to address the increasing burden and reduce global health inequalities.
Safety evaluation of stereotactic body radiation therapy (SBRT) during lutetium-177-PSMA-617 (177Lu-PSMA-617) treatment for patients with metastatic prostate cancer.
Authors: Adam Kessel, Miguel Muniz, Jamie T O'Byrne, Ryan Phillips, Sean Sunghun Park, Brian Davis, Brad J. Stish, Chunhee Richard Choo, Kenneth Merrell, Eugene D. Kwon, Geoffrey Johnson, Fernando Quevedo, Jacob Orme, Daniel S Childs, Jessica M Wilson
Journal: Journal of Clinical Oncology (2025)

129 Background: Few studies have explored the use of focal therapies to address select sites of resistant disease in men receiving 177-Lu-PSMA-617 for metastatic castrate resistant prostate cancer (mCRPC). Our institutional practice is to offer SBRT for patients with up to 5 sites of oligoprogression or non-responding lesions while undergoing 177Lu-PSMA-617 (every 6 weeks for 6 cycles total). This is determined by PSMA or choline PET imaging during the course of 177Lu-PSMA-617. Herein, we evaluated the safety of adding target SBRT during treatment with 177Lu-PSMA-617. Methods: This retrospective single institution analysis was conducted via systematic chart review to evaluate for adverse events during or after treatment. Grading of treatment-related adverse events was conducted using Common Terminology Criteria for Adverse Events Version 5.0 (CTCAE v5). Results: Thirty-one patients receiving 177Lu-PSMA-617 with 51 sites of oligoprogressive or non-responding metastatic disease were treated with SBRT. The median number of sites treated was 1 (range 1-4). Most patients received SBRT immediately after cycle 6 (32%) or after cycle 3 or 4 (42%). Bone was the most commonly treated site of disease (90%) with the majority (54%) of bone sites being spine or sacrum, followed by lymph nodes (10%). Ultimately, 84% of patients completed all 6 cycles of 177Lu-PSMA-617 (range 4-6). The median follow-up time was 19.1 months (IQR 15.5-22.4) after 177Lu-PSMA-617 therapy start. A total of 2 patients experienced a pathologic fracture within the SBRT treatment field that could possibly be related to radiotherapy. One patient experienced a grade 2 neuropathy which may have been related to radiation therapy. Other potential adverse events are listed (Table). Conclusions: Our data demonstrates a low rate of significant toxicity with the use SBRT during treatment with 177Lu-PSMA-617. Further study is indicated to determine the oncologic efficacy and potential late side effects of this treatment strategy. Adverse events. Event All Grades Grade &gt; 3 Any Adverse Event 104 2 Anemia 29 (94%) 0 Low Platelets 11 (35.5%) 1 (3.2%) Any Pathologic Fracture 7 (22.5%) 1 (3.2%) Possible SBRT-related Pathologic Fracture 2 (6.5%) 1 (3.2%) Bone Pain Flare 3 (9.6%) 0 Neuropathy 1 (3.2%) 0
Enfortumab vedotin plus pembrolizumab in metastatic urothelial carcinoma: First results on outcomes and safety in a German multicenter real-world patient cohort (GUARDIANS).
Authors: Stefanie Zschaebitz, Jozefina Casuscelli, Thomas Büttner, Christopher Darr, Anna-Lisa Volk, Martin Hennig, Nina Holzwarth, Friedemann Zengerling, Muammar Dib, Katrin Schlack, Pia Paffenholz, Julia Heinzelbecker, Subhajit Mandal, Frederik Wessels, Daniel Seidl, Eva Erne, Susan Foller, Alexander Höllein, Viktor Grünwald, Marco Julius Schnabel
Journal: Journal of Clinical Oncology (2025)

715 Background: The prospective phase 3 study EV-302 demonstrated superiority regarding efficacy of Enfortumab vedotin plus Pembrolizumab (EVP) compared to platinum-based chemotherapy in patients (pts) that received first-line (1L) therapy for metastatic urothelial carcinoma (mUC). Since presentation of the data in September 2023 EVP was considered a new standard of care (SOC) however only approved in Europe in August 2024. We analyzed efficacy and safety outcomes of pts treated with EVP outside of clinical trials. Methods: Retrospective data were collected from 19 German academic and community hospitals for pts with metastatic UC who received EVP as off-label therapy when reimbursed by their insurance company before European Medicines Agency (EMA) approval, or as SOC treatment after EMA approval. Imaging and therapy management were in accordance with local standards. Adverse events (AEs) were reported according to Common Terminology Criteria for Adverse Events (CTCAE) version 5.0 criteria. Median progression-free survival (mPFS) and overall survival (mOS) were estimated using the Kaplan-Meier method by local investigators. Results: We identified 215 pts for the safety cohort (all pts who received EVP at least once) and 164 pts for the efficacy cohort (all pts who received at least one staging or died prior to first planned imaging).The median age for the eligible patients was 71 yr (range 25-89). The Eastern Cooperative Oncology Group performance status (ECOG PS) was 0/1/2/3-4/unknown for 46.0/31.6/17.2/4.7/0.5% of patients. The overall response rate was 60.7% (partial response 51.0%, complete response 9.7%). mOS was not reached and mPFS was 13 mo (95% confidence interval 4.5-21.5). Any-grade AEs were observed in 73.0% and CTCAE grade ≥3 AEs in 30.2%. Any-grade immune-related AEs were observed in 37.7% and CTCAE grade ≥3 AEs in 16.7%. The most common AEs were peripheral sensory neuropathy (all grade: 30.2%) and skin toxicity (all grade:24.2%). No treatment-related fatal event occurred. Limitations include the retrospective design and short follow-up. Conclusions: Administration of EVP in a real-world patient population showed promising effectiveness and an acceptable toxicity profile. No new safety signals were reported. Our results support the use of EVP in 1L in pts with mUC. Updated data with longer follow-up will be presented at the meeting.
AI-driven prediction of prostate cancer risk: A comparative analysis with C the Signs in the Mayo Clinic data platform.
Authors: Bea Bakshi, Sana Raoof, Tufia C. Haddad, Tushar Patel, Charles J. Ryan, Irbaz Bin Riaz, Seema Dadhania, Brian Herrick, Miles Payling
Journal: Journal of Clinical Oncology (2025)

371 Background: Prostate cancer is the most common malignancy in men globally and remains among the top five leading causes of cancer-related deaths. Emerging evidence suggests that early identification of symptoms can detect localized disease thus enabling opportunities for curative intent treatments. This study evaluates the use of the AI-powered prediction model, C the Signs, to passively screen for prostate cancer by leveraging data from electronic medical records (EMRs), offering a novel pathway for identifying high-risk individuals. Methods: A retrospective analysis was conducted using the Mayo Data Platform, encompassing 418,477 male patient records, of which 16,835 were diagnosed with prostate cancer. C the Signs identified patients at risk based solely on their EMR data, utilizing AI-driven pattern recognition. Sensitivity and specificity analyses were performed to assess the prediction model’s accuracy. Additionally, we examined the time-to-diagnosis advantage for patients flagged by the model compared to traditional physician clinical diagnoses. Results: C the Signs demonstrated a sensitivity of 83.3% and a specificity of 52.5% for identifying patients at risk of prostate cancer. Notably, 31.8% of prostate cancer cases were identified at risk up to five years earlier by the model compared to traditional physician clinical diagnosis. Conclusions: The integration of AI-driven prediction models like C the Signs into prostate cancer screening pathways provides an opportunity to enhance early detection, particularly in symptomatic individuals. Compared to prostate-specific antigen (PSA) testing, the model achieved equivalent sensitivity and 38% higher specificity, positioning it as a valuable companion tool for improving patient outcomes.
Adherence to clinical surveillance guidelines in von Hippel-Lindau (vHL) disease: Evaluating the impact of a coordinated care centre implementation in Canada.
Authors: Dawson Born, Anna Pasco, Maryam Soleimani
Journal: Journal of Clinical Oncology (2025)

460 Background: VHL is a rare hereditary cancer syndrome, predisposing to the development of multiorgan tumour growth, including bilateral and recurrent clear cell renal cell carcinoma. While guidelines for the screening and management of these patients exist, adherence to guidelines is variable. The development of coordinated clinical care centres with multidisciplinary expertise in rare diseases has been demonstrated to improve outcomes. Methods: In this study, we reviewed adherence to surveillance guidelines prior to and after development of a Canadian provincial vHL clinic at our institution, British Columbia (BC) Cancer. Care in this clinic is provided both in-person and through telehealth. We sought to evaluate whether patient geographic distance from the clinic impacted time to being seen for consultation, and whether there was a change in management plan after being seen in the clinic. Results: Between June 2022, and April 2024, 57 patients were seen in the vHL clinic (median age 34, 58% female, and 42% male). Of these, 13 lived within 50km from the clinic, 7 within 50-100km, 8 within 100-500km, and 29 lived more than 500km away. We found significant improvement in adherence to nearly all surveillance guidelines after the development of the vHL Clinic (table). 10.5% of patients had never had germline confirmation of vHL and were referred for expedited testing after being seen. We did not find any difference in time from referral to consultation based on patient geographic proximity to the clinic, F(3,53)=1.10, p =0.35 nor the modality of initial consultation (t(55)=1.07, p =0.29; in person vs telehealth). Finally, after initial consultation, 87% of patients had a change in their management plans, most commonly involving referral for further subspecialty evaluation (n=41) or initiation of pharmaceutical treatment (n=24). Conclusions: Our results add to existing evidence that coordinated care centres with multidisciplinary expertise in vHL are feasible in the Canadian public healthcare system and can result in improvements in quality of care. Our clinic model has a robust multidisciplinary care team that utilizes technology to reach patients for equitable access to care. Future work will evaluate potential cost savings to the healthcare system with this model, as well as patient satisfaction with their care pre and post participation in the vHL clinic. Adherence to clinical screening guidelines for patients with vHL before and after consultation with the BC cancer provincial vHL clinic. Screening Guideline Parameter Pre connection with vHL clinic Post connection with vHL clinic Central nervous system imaging 51.8% 100%* Abdomen/Pelvis imaging 44.6% 100%* Metanephrines 8.9% 64.3%* Ophthalmologic 75.0% 85.7% Audiology 21.4% 85.7%* *Statistically significant difference ( p &lt;0.05).