tbuckley/cabot-search huggingface dataset:
A novel predictive model using changes in clinical and serum biomarkers and automated quantitative imaging for mCRPC patients treated with AR-directed therapy.
Authors: Michael J. Morris, Jessica Flynn, Binsheng Zhao, Aseem Anand, Karl Sjöstrand, Steven M. Larson, Howard I. Scher, Ashley M. Regazzi, Gary V. Borzillo, Autumn Park, Lawrence Howard Schwartz, Glenn Heller
Journal: Journal of Clinical Oncology (2025)

264 Background: In mCRPC, standard risk models use baseline clinical and blood-based biomarkers, excluding imaging. This study developed a new predictive model incorporating baseline and early on-treatment clinical, blood, and imaging biomarkers to inform overall survival (OS). The training set was derived from COU-AA-302 and validated using Alliance 031201 (A031201). Eligibility required patients to have at least two CT and bone scans within 6 months of randomization (COU-AA-302: n = 785; A031201: n = 582). Methods: Conventional biomarker data included PSA, albumin, alkaline phosphatase, hemoglobin, and ECOG status. Imaging data included &gt; 1000 radiomic features and the automated Bone Scan Index (aBSI). Six-month biomarker trajectories were summarized using the intercept and slope from a random effects model, yielding over 2000 risk biomarkers. Due to the high dimensionality, an elastic net proportional hazards model was applied. Predictive concordance probability, which evaluates the ability to distinguish between long-term and short-term survivors, and R-square, a calibration measure that indicates how accurately the model predicts actual survival time were determined. Results: 46 biomarkers were selected from over 2000, including 9 blood-based, 4 from aBSI, 1 tumor volume measure, and the remaining from radiomic features. In contrast, the non-imaging risk model contained 10 risk factors. Risk scores from these models were categorized into low, moderate, and high-risk groups. The median survival per group revealed significant separation, with a difference of over 30 months between low and high-risk groups. This separation was observed regardless of whether imaging was included in the model. Conclusions: This is the first model for mCRPC to integrate pre-treatment and early on-treatment serum, imaging, and clinical data from two large phase 3 trials, with external validation. While both imaging and non-imaging models showed good predictive accuracy, imaging did not significantly improve the discrimination of long-term from short-term survivors or enhance the precision of the model-based survival predictions. Clinical + Serum biomarkers with imaging Clinical + Serum biomarkers without imaging Total # of risk factors 46 10 # of clinical/serum factors 9 10 # of radiomics factors 32 0 # of aBSI factors 4 0 # of tumor volume factors 1 0 Median Survival (mos) Low risk group 55 54 Moderate risk group 38 39 High risk group 20 21 Predictive Concordance Probability 0.74 0.73 R-square Measure of Calibration 0.37 0.39
<i>NECTIN4</i> RNA expression and clinical outcomes with first-line (1L) platinum-based chemotherapy (PBC) and avelumab 1L maintenance in locally advanced or metastatic urothelial carcinoma (la/mUC): Exploratory analyses from JAVELIN Bladder 100.
Authors: Niklas Klümper, Markus Eckstein, Petros Grivas, Enrique Grande, Johannes Brägelmann, Jason Hoffman, Parantu K. Shah, Olga Bogatyrova, Viktor Grünwald
Journal: Journal of Clinical Oncology (2025)

827 Background: Nectin-4 is widely expressed in UC tumors, although protein expression levels vary between patients. Prior analyses have suggested that low overall Nectin-4 expression based on immunohistochemistry may be associated with worse outcomes in patients with advanced UC irrespective of treatment. We report exploratory biomarker analyses from the JAVELIN Bladder 100 phase 3 trial evaluating response to 1L PBC and survival outcomes with avelumab administered as 1L switch-maintenance treatment in subgroups defined by tumor NECTIN4 RNA expression. Methods: In JAVELIN Bladder 100 (NCT02603432), patients with unresectable la/mUC without progression after 4-6 cycles of 1L PBC were randomized to receive avelumab 1L maintenance + best supportive care (BSC) or BSC alone. Whole-transcriptome profiles in tumor samples (primary tumors in ≈75%) were generated using RNA sequencing, and transcript levels were quantified using Personalis ACE technology. NECTIN4 RNA expression was assessed as a continuous variable for subgroups defined by response to 1L PBC, and as a dichotomous variable (median split) for survival analyses. Results: In biomarker-assessable patients enrolled in JAVELIN Bladder 100, no significant differences were observed in tumor NECTIN4 RNA expression in patients who had complete response (n=149), partial response (n=261), or stable disease (n=150) to 1L PBC (Kruskal-Wallis p=0.192). In subgroups with high or low NECTIN4 RNA expression, overall survival (OS) and progression-free survival (PFS) improvements with avelumab + BSC vs BSC alone were consistent with improvements observed in the overall study population (Table). No significant differences in OS and PFS were observed between subgroups with high or low NECTIN4 RNA expression within the avelumab + BSC (p=0.26 and 0.89) and BSC alone (p=0.34 and 0.94) arms. Limitations include ad hoc exploratory analysis and potential selection bias. Conclusions: Exploratory analyses from JAVELIN Bladder 100 suggest that NECTIN4 RNA expression was not prognostic or predictive of level of response to 1L PBC or survival with avelumab 1L maintenance treatment in patients with la/mUC without progression after 1L PBC. Clinical trial information: NCT02603432 . Avelumab + BSC BSC alone High NECTIN4 RNA expression n=139 n=140 Median OS (95% CI), months 22.0 (18.2-30.9) 14.8 (12.9-19.4) Median PFS (95% CI), months 5.65 (4.60-9.00) 3.29 (1.97-3.75) Low NECTIN4 RNA expression n=145 n=136 Median OS (95% CI), months 30.0 (21.4-35.2) 18.7 (13.7-25.5) Median PFS (95% CI), months 5.65 (3.81-9.95) 2.20 (1.91-3.71)
Efficacy and safety of tislelizumab (T) combined with gemcitabine and cisplatin (GC) for patients with localized muscle-invasive bladder cancer (MIBC) after radical transurethral resection of bladder tumor/partial cystectomy: A prospective, phase II study.
Authors: Ming Cao, Dongdong Xiao, Wei Xue
Journal: Journal of Clinical Oncology (2025)

784 Background: Transurethral resection of bladder tumor (TURBT) combined with concurrent chemoradiotherapy is the standard treatment for bladder preservation in MIBC. TURBT alone and partial cystectomy are only suitable for selected patients with solitary tumors, T2, and tumors in the bladder diverticulum while patients could have tumor recurrence after surgery. This prospective phase II study aims to explore the efficacy and safety of T combined with GC after radical TURBT or partial cystectomy as bladder preservation therapy in patients with PD-L1 positive MIBC. Methods: Eligible patients had clinical stage T2-T3N0M0, histologically confirmed PD-L1 positive urothelial carcinoma, no prior systemic treatment, and no residual tumor after radical TURBT or partial cystectomy. Patients received T combined with GC within 8 weeks of local treatment (G 1000mg/m2, d1, d8; C 70mg/m2, d1, IV, q3w, for a total of 6 cycles. T 200mg, d8, IV, q3w, for a total of 8 cycles). The primary endpoint was 1-year bladder intact disease-free survival rate. Secondary endpoints included 2-year bladder intact disease-free survival rate, metastasis-free survival, time to salvage cystectomy, overall survival, and safety. Results: From August 2022 to October 2024, a total of 13 patients were enrolled in the study. Median age was 70 years (65-75). Twelve patients were staged as pT2 and 1 patient had pT3. Twelve patients were evaluable for efficacy and 1 patient withdrew the consent. Seven patients underwent TURBT and 5 patients underwent partial cystectomy. Median follow-up time was 8.0 months. One patient had non-muscle-invasive bladder cancer recurrence and receive intravesical BCG instillation while the remains had no recurrence of disease. 1-year bladder-intact disease-free survival rate was 100%. Grade 3 or higher adverse events occurred in 33.3% of patients. No new safety signals were observed. Conclusions: The study demonstrated that combination of T and GC after complete resection of tumor seemed promising as bladder preservation strategy in selected patients. Further recruitment is ongoing. Clinical trial information: NCT05401279 .
Enfortumab vedotin-related skin toxicities in patients with urothelial carcinoma: A systematic review and meta-analysis.
Authors: Gabriela Gazzoni, Maysa Vilbert, João Pedro Oliveira, Maria Inez Dacoregio, Isabella Michelon, Pedro Reis, Marcelo Braga, Clara Simões, Lilia Oliveira, Ana Paula Garcia Cardoso
Journal: Journal of Clinical Oncology (2025)

761 Background: Enfortumab vedotin (EV) is an antibody-drug conjugate that binds nectin-4, a cell-adhesion molecule highly expressed in urothelial carcinoma (UC) and epidermal keratinocytes. Dermatologic events have become important EV-related toxicities in clinical trials (CT) and observational studies. We conducted a systematic review and meta-analysis on skin toxicity in UC patients treated with EV. Methods: We systematically searched Pubmed, Cochrane, and Embase for published CT and observational studies reporting EV-related skin toxicities in UC patients. We investigated treatment-related adverse events (TRAE) and severe cutaneous adverse reactions (SCAR) in UC patients of all-grade and ≥ 3. The outcomes were presented as overall incidence rates and 95% confidence intervals (95% CI). Statistical analyses were performed using R software. Results: Ten studies comprising 1,061 participants were included. Median age ranged from 66 to 76 years, and 74% (783) were male. 72% of patients had prior immune checkpoint inhibitors. The median time to onset of skin toxicity varied from two to four weeks. In a pooled analysis, the skin reaction rate for all-grade of UC was 50% (95% CI 38-61), while for grade ≥ 3 was 10% (95% CI 7-15). The incidence of SCAR was 19% (95% CI 16-23) and 8% (95% CI 3-18) for grade ≥ 3. Alopecia was seen in 37% of patients, pruritus in 22% and dry skin in 21%. All-grade rash incidence rate was 29% and the most reported was maculopapular rash 22%, followed by erythematous rash (6%). Important cutaneous reactions included bullous dermatitis in 2.91% of patients (95% CI 1-6), palmar-plantar erythrodysesthesia in 2.46% (95% CI 1-5), Stevens-Johnson syndrome in 1.46% (95% CI 0.4-5), and toxic epidermal necrolysis in 0.95% (95% CI 0.2-4) of patients. Conclusions: This is the first study to characterize EV-related dermatological toxicities. We found a high incidence of all-grade events and a moderate frequency of severe and grade ≥ 3 toxicities. This study intends to highlight the need for close monitoring and adequate treatment for skin toxicities in UC patients receiving EV.
Implementing Indiana regimen salvage high-dose chemotherapy in relapsed germ cell tumors in Slovakia.
Authors: Michal Chovanec, Zuzana Rusinakova, Miriam Ladicka, Jana Obertova, Patrik Palacka, Katarina Rejlekova, Zuzana Sycova-Mila, Zuzana Orszaghova, Peter Lesko, Jozef Mardiak, Andrej Vranovsky, Michal Mego, Lubos Drgona
Journal: Journal of Clinical Oncology (2025)

642 Background: Salvage chemotherapy for relapsed testicular germ cell tumors (GCT) remains controversial, however, large retrospective series show higher cure rates with high-dose chemotherapy (HDCT) and peripheral blood stem cell transplant (PBSCT) compared to conventional dose chemotherapy (CDCT). Successful implementation of HDCT salvage treatment in high-volume centers is an important step towards achieving optimal cure rates in relapsed GCTs. Methods: 22 relapsed GCT patients were treated at National Cancer Institute in Slovakia with first (41%), second (54%) and third line (5%) salvage HDCT between 2014 and 2024. Median age at 1 st HDCT cycle was 33 years (range 21-55). Of the 22 patients, 3 (14%) had pure seminoma, 3 (14%) had primary mediastinal non-seminoma (PMNSGCT), 10 (45%) patients had cisplatin resistant disease, 7 (32%) and 15 (68%) of patients received 1 and 2 cycles of HDCT, respectively, 5 (23%) received maintenance oral etoposide and 6 (27%) had post-HDCT surgery. Indiana regimen consisted of 750mg/m2 etoposide and 700mg/m2 of carboplatin given on days -5,-4,-3 followed by PBSCT on day 0. Of 22 patients, 3 have received single dose CarboPEC (carboplatin, etoposide, cyclophosphamide) regimen in 2014 and 2015. Results: Median time between two cycles was 43 days (range 26-89) showing decreasing trend over the last years. 2-year PFS and OS were 40% (95% CI 0.19-0.61) and 34% (95% CI 0.13-0.55) and 5-year PFS and OS were 32% (95% CI 0.1-0.54) and 27% (0.06-0.48). Kaplan-Meier analysis produced inaccurate outcomes due to small sample size, currently 32% of patients is alive and disease-free. Predictors of unfavorable outcome were non-seminoma, NPMGCT, 1 cycle of HDCT, CarboPEC regimen and platinum resistant disease. Patients who underwent post-HDCT surgical resection had longer OS compared to patients unable to undergo surgery HR 4,85 (95% CI 1,69-13,9), p = 0.01 Patients receiving pre-HDCT bridging CDCT regimens had significantly worse OS compared to patients going directly to HDCT, HR 0 (95% CI 0-0), 5 year OS 19% vs 100%, p = 0.05. 10% of patients with cisplatin resistant disease is surviving beyond 5 years. There was one (4.5%) treatment-related death due to septic shock. Conclusions: HDCT is an effective salvage option in heavily pretreated relapsed GCTs. Our study suffers from weakness associated with small number of patients and selection biases. However, increasing expertise and timely delivery of HDCT results in cures in relapsed GCTs including cisplatin resistant subgroup.
Application of acceptance and commitment therapy in cancer-related fatigue management: insights from clinical trials and future perspectives
Authors: Xiaoyan Chen, Zhi Li
Journal: International Journal of Surgery (2025)

aMedical College of Nanchang Institute of Technology, Nanchang, Jiangxi Province, China bInterventional Cancer Institute of Chinese Integrative Medicine, Putuo Hospital, Shanghai University of Traditional Chinese Medicine, Shanghai, China cHubei Provincial Clinical Research Center for Umbilical Cord Blood Hematopoietic Stem Cells, Taihe Hospital, Hubei University of Medicine, Shiyan, China *Corresponding author. Address: Interventional Cancer Institute of Chinese Integrative Medicine, Putuo Hospital, Shanghai University of Traditional Chinese Medicine, Shanghai 200062, China, E-mail: ([email protected]) (Z. Li). This is an open access article distributed under the Creative Commons Attribution-ShareAlike License 4.0, which allows others to remix, tweak, and build upon the work, even for commercial purposes, as long as the author is credited and the new creations are licensed under the identical terms.
Feasibility of enriched amplicon circulating tumor DNA sequencing to detect minimal residual disease (MRD) after prostatectomy in localized prostate cancer.
Authors: Peter D. Zang, Daniel Lama, Ziyi Huang, Salvador Jaime-Casas, Tania Contente-Cuomo, Mojca Stampar, Adriana Marshall, Devin Dinwiddie, Michael E. Berens, Stephanie Pond, Jeffrey M. Trent, Bertram Yuh, Clayton S. Lau, Muhammed Murtaza, Yun Rose Li, Tanya B. Dorff
Journal: Journal of Clinical Oncology (2025)

402 Background: Nearly one third of men with prostate cancer experience relapse after radical prostatectomy, often despite achieving undetectable PSA nadir. An assay to detect minimal residual disease would be valuable to identify patients who could benefit from adjuvant therapy. Methods: Eligible patients had biopsy proven prostate cancer and planned to undergo prostatectomy for definitive therapy. Blood was drawn at pre-specified timepoints (TP) including prior to prostatectomy (TP1), on the day after surgery or at the 1-week post-op catheter removal visit (TP2), and at 1-month post-op with no interval treatment (TP3). We performed tumor-guided plasma DNA analysis using a novel method based on single-stranded adapter ligation, incorporation of unique molecular identifiers (UMIs), targeted PCR, normalization of amplicons using hybrid-capture, and targeted sequencing. Using tumor and germline exome sequencing, we designed and validated multiplexed assays to target somatic founder mutations. We prepared targeted sequencing libraries using a median of 6.7 ng input plasma DNA. Results: 11 patients were enrolled after IRB approval. 1 (9.09%) had grade group 2, 1 (9.09%) grade group 3, 5 (45.45%) grade group 4, 4 (36.36%) grade group 5 disease. Median PSA pre-op was 9.3 ng/mL (range: 1.7 – 21.47). Tumor DNA sequencing was successful and targeted assays were generated for all patients (11/11). Median number of targets tested was 20 (range 4 to 88). We analyzed 31 plasma DNA samples obtained from 11 patients. Median on-target rate in plasma DNA was 90.5% (range 76.0% to 96.3%). Prior to surgery (TP1), 5/11 (45%) patients had detectable ctDNA at a median tumor fraction of 0.077% (range: 0.006% to 3.4%). At post-op TP (TP2), the ctDNA was detectable in 7/11 patients (64%) at a median tumor fraction of 0.024% (range: 0.004% to 3.1%). Detectable ctDNA was observed at 1 month (TP3) in 5/8 patients (62.5%) at a median tumor fraction of 0.022% (range 0.010% to 0.037%). For an exploratory analysis, we examined whether persistent ctDNA detection at the 1 month TP3 was associated with later relapse. Of the 5 patients with PSA relapse, 3 (60%) of patients had detectable residual ctDNA at TP3 with median follow up time of 61.75 months. Conclusions: Localized prostate cancer has been noted to have low tumor shed, limiting meaningful ctDNA detection rates with prior assays (Hennigan 2019). Our results show promising feasibility of a novel tumor-informed ctDNA assay in this setting. In addition, there was preliminary evidence of residual ctDNA detection predicting relapse.
Mevrometostat (PF-06821497) in combination with enzalutamide for androgen receptor pathway inhibitor (ARPI)-naïve patients with metastatic castration-resistant prostate cancer (mCRPC): The phase 3, randomized MEVPRO-2 trial.
Authors: Michael Thomas Schweizer, Jayeta Chakrabarti, Sujata Narayanan, Stella Lin
Journal: Journal of Clinical Oncology (2025)

TPS287 Background: Mevrometostat (PF-06821497) is a potent, selective inhibitor of the histone methyltransferase enhancer of zeste 2 (EZH2), which is canonically involved in epigenetic repression of target genes. In prostate cancer, EZH2 overexpression is associated with poor prognosis, contributing to disease progression through transcriptional repression of tumor suppressor genes and androgen receptor (AR) activation, co-regulation of AR-mediated transcriptional programs, and cell cycle deregulation through methylation of non-histone targets. Given the associations between EZH2 and the AR, the addition of an EZH2 inhibitor to ARPI is hypothesized to extend the duration of clinical response and delay antiandrogen resistance compared with ARPI alone. In a nonrandomized, phase 1 dose-escalation study, objective responses to mevrometostat with enzalutamide were observed in patients with CRPC and prior abiraterone or enzalutamide treatment (NCT03460977; Schweizer MT, et al. J Clin Oncol . 2024;42(16_suppl):5061). Despite guideline recommendations of treatment intensification with ARPIs or chemotherapy for metastatic castration-sensitive prostate cancer (mCSPC), many patients do not receive ARPIs at the mCSPC stage. MEVPRO-2 (NCT06629779) will evaluate mevrometostat plus enzalutamide compared with enzalutamide alone in ARPI-naïve patients with mCRPC. Methods: MEVPRO-2 is a global, double-blind, randomized, phase 3 trial. Key inclusion criteria are males, ≥18 years, with progressive mCRPC, castrate testosterone of ≤50 ng/dL, Eastern Cooperative Oncology Group performance status of 0 or 1, and life expectancy of ≥12 months. Patients with systemic treatments for mCRPC (except androgen deprivation therapy and first-generation antiandrogens) are excluded. Approximately 900 patients will be randomized 1:1 to receive mevrometostat (875 mg, twice daily) with enzalutamide (160 mg, once daily) or placebo with enzalutamide. The primary endpoint is blinded independent central review-assessed radiographic progression-free survival per Response Evaluation Criteria in Solid Tumours 1.1 (soft tissue) or Prostate Cancer Working Group 3 (bone). Key secondary endpoints are overall survival and time to pain progression (Brief Pain Inventory – Short Form question 3 or opioid use). Hazard ratios and 95% confidence intervals will be estimated using a Cox proportional hazard model, stratified by prior docetaxel and presence of hepatic metastases. P-values will be provided using a stratified log-rank test. Safety and tolerability will also be assessed. Clinical trial information: NCT06629779 .
Association between proto-oncogene N-RAS transcript level and overall survival in node-negative muscle-invasive urothelial bladder carcinoma.
Authors: Donghyun Kim, Bilal G. Rahim
Journal: Journal of Clinical Oncology (2025)

820 Background: Prognostication of urothelial bladder carcinoma relies on clinicopathologic factors including histology, TNM stage and genomic profiles. The prognostic value of tumor subtyping based on gene expression signature clustering has been proposed, but their clinical value remains uncertain. Here, we retrospectively review node-negative muscle-invasive urothelial bladder carcinoma RNA-Seq data and demonstrate that “low” mRNA expression of proto-oncogene N-RAS is associated with significantly superior overall survival (OS). Methods: The Cancer Genome Atlas (TCGA) Pan-Cancer project batch-corrected primary tumor RNA-Seq expression profiles of 114 urothelial bladder carcinoma cases (pT2-4a pN0 M0, n=97; any pT pN1 M0, n=17) and their associated clinical data were retrieved from the cBioPortal. Cohort median was used as a reference to determine “high” vs. “low” transcript levels of N-RAS gene. Log-rank Kaplan-Meier was performed for survival analysis. Two-tailed Mann-Whitney test was performed for group comparison. Results: In node-negative disease group, “low” N-RAS expression (n=58) was associated with significantly superior 5-year OS compared to patients with “high” N-RAS expression (n=39) with hazard ratio (HR) for death at 0.41 (95% CI 0.19-0.86, p=0.007). N-RAS expression-associated differential OS was independent from age group (≥67 vs. &lt;67), gender, T stage (T2 vs. T3-4a), cisplatin-based chemotherapy exposure or underlying TP53, RB1, FGFR3, RAS mutation. However, in patients with “low” N-RAS expression the 5-year OS of those who received cisplatin-based chemotherapy (n=5) was significantly superior compared to those who did not (n=53) with HR for death at 0.26 (95% CI 0.07-0.98, p=0.047). “High” N-RAS expression group was associated with higher CD274 (PD-L1) mRNA expression (x3.9 higher median value, p&lt;0.0001) and larger portion of patients with ≥10 mut/Mb tumor mutational burden (40% vs. 23%) compared to “low” N-RAS expression group. In node-positive disease group, N-RAS expression-dependent differential OS was not present. Conclusions: In node-negative muscle-invasive urothelial bladder carcinoma, “low” N-RAS expression was associated with superior OS which was most pronounced in patients who received cisplatin-based chemotherapy. “High” N-RAS expression was associated with higher PD-L1 mRNA expression and tumor mutational burden. We speculate that N-RAS transcript level might be a novel biomarker for prognostication and treatment response as an adjunct to TNM stage. Further investigation is warranted.