tbuckley/cabot-search huggingface dataset:
Individualized neoantigen vaccine with nivolumab plus cabozantinib for translocation renal cell carcinoma: Single patient investigational new drug.
Authors: Adam McLain Kase, Winston Tan, John A. Copland, Michael Gustafson, Yan W. Asmann, Brian Necela, Keith L. Knutson
Journal: Journal of Clinical Oncology (2025)

537 Background: Translocation renal cell carcinoma (tRCC) is a rare renal cell carcinoma subtype found in about 1-4% of adult patients with RCC and 40% of pediatric RCC cases. Management of advanced tRCC has been guided by clear cell RCC therapy and retrospective reviews which include tRCC cohorts. Novel therapeutic strategies are needed to improve outcomes. This study assessed an individualized neoantigen vaccine with nivolumab plus cabozantinib in a patient with metastatic TFE3-tRCC. Methods: Patient was consented (IRB# 20-011945) for a single-patient investigational new drug (IND#27755). In-house neoantigen prediction bioinformatics pipeline (REAL-neo v2.0) was performed to identify and prioritize neoantigen candidates. Patient underwent lymphodepletion with cyclophosphamide followed by vaccine administration on days 1, 4, 8, 11, 20, 40, week 12, and week 20. Patient was also treated with concurrent nivolumab 480 mg every 4 weeks and cabozantinib 40 mg daily. Objective response rate (ORR) and progression-free survival (PFS) were measured. Results: Patient was diagnosed with TFE3-tRCC and underwent nephrectomy prior to developing metastatic disease. He was treated with multiple liver surgeries, ablations, and radiation therapy without systemic therapy. This controlled his disease for 7 years before he required systemic therapy with ipilimumab plus nivolumab. After 4 cycles, imaging showed progression and was started on cabozantinib which controlled his disease for 1 year. Patient was consented for the neoantigen vaccine. Cycle 1 was administered in April 2022. Three liver lesions and 1 periportal lymph node were monitored. After 4 months of therapy, imaging showed partial response with 34% decrease in sum of target lesions. In June 2023, partial response was ongoing with a 57.4% decrease. A 2 nd vaccine series was administered in June 2023 and had stable disease until progression in June 2024 when patient held his cabozantinib for at least 4 weeks. Neoantigen combination therapy achieved a progression-free survival of 26 months and was well tolerated without significant vaccine-related adverse events. Conclusions: Individualized neoantigen vaccine plus nivolumab and cabozantinib achieved a durable partial response with prolonged progression-free survival. A randomized clinical trial is warranted to further evaluate the efficacy of this combination therapy.
Real-world treatment patterns and outcomes of novel androgen receptor axis-targeted agents in non-metastatic castration-resistant prostate cancer: A multi-institutional retrospective study.
Authors: Naoki Fujita, Fumiya Yoneyama, Yohei Kawashima, Ryuma Tanaka, Takuya Oishi, Hikari Miura, Kazutaka Okita, Chikara Ohyama, Shingo Hatakeyama
Journal: Journal of Clinical Oncology (2025)

368 Background: Recently, three phase III trials have demonstrated that novel androgen receptor axis-targeted agents (ARATs) significantly improved metastasis-free survival (MFS) and overall survival (OS) compared to placebo in patients with non-metastatic castration-resistant prostate cancer (nmCRPC). However, the treatment patterns and outcomes of novel ARATs in real-world settings remain unclear. Methods: This multi-institutional retrospective study included 245 patients with nmCRPC treated between September 2003 and April 2024. Trends in the use of novel ARATs were evaluated. Patients were divided into two groups: those who were treated with any novel ARATs, including apalutamide, enzalutamide, darolutamide, and abiraterone acetate, during any line of nmCRPC treatment (novel ARATs group) and those who were not (control group). Multivariable Cox proportional hazards regression analyses were performed to evaluate the effects of novel ARATs on MFS and OS. Adverse events (AEs) associated with novel ARATs were evaluated using the Common Terminology Criteria for Adverse Events version 5.0. Results: The median age and follow-up period after nmCRPC diagnosis were 77 years and 45 months, respectively. Of the 245 patients, 175 (71%) were treated with novel ARATs after nmCRPC diagnosis. Novel ARATs use in first line and any line was gradually increased from 2014 to 2023 (0% to 85% and 38% to 92%, respectively). The MFS and OS in the novel ARATs group were significantly longer than those in the control group ( P &lt; 0.001 and P = 0.001, respectively). In multivariable analyses, a prostate-specific antigen doubling time (PSADT) and novel ARATs were independently and significantly associated with MFS and OS (Table). The rate of grade 3 AEs and discontinuation due to AEs were 1.1% and 6.0%, respectively. Conclusions: The use of novel ARATs for the treatment of nmCRPC increased over time. Novel ARATs use was safe and associated with improved oncological outcomes in a real-world setting. Multivariable analyses for MFS and OS. MFS Factor P value Hazard ratio 95% CI Age Continuous 0.003 0.956 0.928–0.984 Time of nmCRPC diagnosis Before 2014 0.706 0.917 0.584–1.439 PSADT &lt;2.5 months &lt;0.001 2.040 1.339–3.107 Novel ARATs Positive &lt;0.001 0.364 0.238–0.557 OS Factor P value Hazard ratio 95% CI Age Continuous 0.418 1.014 0.980–1.049 Time of nmCRPC diagnosis Before 2014 0.626 0.883 0.537–1.454 PSADT &lt;2.5 months &lt;0.001 2.138 1.360–3.360 Novel ARATs Positive 0.001 0.479 0.306–0.748
Timely BRCA mutation testing in patients with metastatic prostate cancer: A comparative analysis between Medicare Advantage and traditional Medicare.
Authors: Jonathan Wenbin Ji, Chuan Angel Lu, Baqir Jafry, Raj Bhanvadia, Qian Qin, Joseph Vento, Kevin Dale Courtney, Jue Wang, Waddah Arafat, Daniel X. Yang, Suzanne Cole, Tian Zhang, Changchuan Jiang
Journal: Journal of Clinical Oncology (2025)

319 Background: BRCA mutations have emerged as critical biomarkers for guiding the use of PARP inhibitors in metastatic prostate cancer. Timely access to BRCA testing remains a challenge, especially for those enrolled in Medicare Advantage (MA) plans, which cover more than half of Medicare beneficiaries but often impose greater restrictions than Traditional Medicare (TM). This study compares the timeliness of BRCA testing in patients with metastatic prostate cancer (mPCa) across these two insurance types. Methods: A retrospective cohort study was conducted using the Flatiron Health deidentified Database, including electronic health record-derived data from ~280 cancer practices across the US. Our study population consisted of patients aged 65 or older, diagnosed with mPCa since 2018, and enrolled in either TM or MA. TM and MA were defined as patients enrolled in TM or MA health plans, respectively, either prior to or within 90 days following their mPCa diagnosis. BRCA testing was defined as either germline or somatic testing. We compared the rates of BRCA testing within 45, 90, and 180 days of diagnosis between TM and MA. Given the lack of clinical consensus, we defined timely BRCA testing using three-time windows—45-, 90-, and 180-days post-mPCa diagnosis. Multivariate logistic regression with inverse probability of treatment weighting was used, adjusting for demographics, year of mPCa diagnosis, practice setting, and baseline ECOG performance status. Results: Among the 1,582 MA patients (mean age: 75.9 ± 5.8) and 2,749 TM patients (mean age: 75.4 ± 5.8), significant proportions were from community practice (MA: 78%, TM: 80%) and were characterized by being White (MA: 59%, TM: 65%), aged 75 to 85 (MA: 54%, TM: 57%), having better socioeconomic status (SES 4 or 5: MA: 40.3%, TM: 47.5%), presenting with de-novo mPCa (MA: 53%, TM: 54%), and having better baseline functional performance (ECOG 0 or 1: MA: 70%, TM: 69%). Since 2018, 25.0%, 29.4%, 33.2% of MA patients and 25.9%, 29.1%, 31.9% of TM patients received BRCA testing at 45, 90 and 180 days, respectively. After adjusting for covariates, MA was associated with a 15.2% (OR=0.84, 95%CI 0.73-0.98), 11% (OR=0.89, 95%CI 0.77-1.02), 7.9% (OR=0.92 95%CI 0.80-1.06) lower chance to receive timely BRCA testing within 45 days, 90 days and 180 days, respectively. Conclusions: This study suggests that, compared to TM, mPCa patients enrolled in MA are less likely to receive timely BRCA testing. These findings highlight the needs for further investigation into how Medicare Advantage plans impact cancer care delivery and patient outcomes.
Long-term outcomes of neoadjuvant chemotherapy (NAC) before bladder-sparing chemoradiotherapy (CRT) for patients with nonmetastatic muscle-invasive bladder cancer (MIBC).
Authors: Meghan Elizabeth Mahoney, Nely Meija, Eshetu G. Atenafu, Peter W. M. Chung, Alex Zlotta, Nimira S. Alimohamed, Neil Fleshner, Gregory Lo, Girish S. Kulkarni, Alejandro Berlin, Robert G. Bristow, Maria Jiang, Srikala S. Sridhar
Journal: Journal of Clinical Oncology (2025)

819 Background: Neoadjuvant cisplatin-based combination chemotherapy followed by concurrent chemoradiation is an emerging approach in carefully selected MIBC patients who opt for bladder sparing however, long-term data on its efficacy and tolerability remains lacking. We evaluated long-term outcomes in MIBC patients treated with this approach. Methods: We conducted a retrospective chart review of patients treated with NAC followed by CRT bladder sparing approaches between 2008 and 2017 at the Princess Margaret Cancer Centre and Lakeridge Health Cancer Centers. We initially published the feasibility of this approach and early outcome data in 2018. In this analysis, we updated long-term disease free survival (DFS), bladder intact disease free survival (BI-DFS) and overall survival (OS). Results: In total 57 patients were treated with NAC + CRT. Most were male with a median age of 72 (range 45-87), and an Eastern Cooperative Oncology Group performance status of 0 (60%) or 1 (40%). Patients with stage II (65%), and stage III disease (25%), as well as regional nodal metastases (11%), carcinoma in situ (28%) and hydronephrosis (25%) were included. The majority of patients completed planned NAC (95%). All patients completed external-beam radiotherapy, and 84% completed at least 60% of the planned concurrent weekly cisplatin doses. Median follow up for this population was 74.4 months (9.7-142.1). At the time of this updated analysis, 23/57 (40%) recurred, local recurrence occurred in 11/57 patients (19%), and 9/57 patients (16%) required salvage cystectomy. Distant recurrence occurred in 12/57 (21%) patients, all of whom died as a result of bladder cancer. The median DFS for the study population was 56.7 months (95% CI 25.3-99.1), and 5-year DFS rate was 49%. The median BI-DFS was 40.1 months (95% CI 23.3-85.4) and 5-year BI-DFS rate was 45%. The median OS was 104.9 months (95% CI 60.8-119.2) with a 5-year OS rate of 65% (95% CI 50.7-75.5). Conclusions: NAC+CRT is a safe and effective approach for selected patients with MIBC with encouraging long-term outcomes. This data supports evaluating neoadjuvant and adjuvant systemic therapies along with bladder preservation strategies in prospective clinical trials.
First preliminary results of artificial intelligence-generated, explainable treatment recommendations for renal cell cancer based on multidisciplinary cancer conferences.
Authors: Gregor Duwe, Dominique Mercier, Verena Kauth, Kerstin Moench, Markus Junker, Andreas Dengel, Axel Haferkamp, Thomas Höfner
Journal: Journal of Clinical Oncology (2025)

465 Background: The expert panel in multidisciplinary cancer conferences (MCC) decides on the best available treatment for the individual cancer patient. To support these complex evidence-based decisions, an artificial intelligence (AI) was developed to generate treatment recommendations for renal cell cancer (RCC) patients to support decision-making in MCC. Methods: We have transformed comprehensive patient data (99 individual machine-readable features) of 880 MCC recommendations for RCC from the years 2015 - 2022 into representations that can be used in software development. We developed a two-step process in order to train classifiers to mimic MMC recommendations. First, we identified superordinate categories of the recommendations. Afterwards, we specified the detailed recommendation. For this purpose, we used different machine learning (CatBoost, XGBoost, Random Forest) and deep learning (SoftOrdering-1d-CNN) approaches with 787 training cases and 93 test set cases. Accuracy weights are determined by F1-Score. Results: The KITTU-AI is able to generate fully automated treatment recommendations for patients with histologically confirmed RCC in MCC. First, the AI can decide which kind of superordinate recommendation should be applied, e.g. surgery or anticancer-drugs (Table). Second, our AI system is able to suggest the specific surgical treatment as well as the correct drugs (Table). The AI-generated recommendation is presented explainable based on the clinical features and their importance score. Conclusions: To our knowledge, we present the first time data for fully automated AI-based treatment recommendations for MMC in RCC with promising accuracy rates.Our selected AI architecture is able to learn and to generate medically comprehensible and explainable treatment recommendations. Small numbers of recommended therapies hamper AI training but this will improve with increasing numbers over time. Next, clinical trial data will be implemented to enable a higher level of explainability. Meanwhile, the first prospective validation is ongoing. Accuracy rates for AI-generated treatment recommendations of renal cell cancer based on F1-scores (test set of 93 cases). Task (number) F1-Score ↑ #Classes Class (number) F1-Score High Level Prediction (93) 0.76 (CatBoost) 5 Surgery (10)Medication (45)Aftercare (22)Best supportive care (4)Radiotherapy (12) 0.450.920.880.000.47 Low Level Surgical Prediction (10) 0.81(Soft Ordering) 3 Primary tumor resection (4)Resection of recurrent tumor (1)Metastases resection (5) 0.670.000.73 Low LevelDrug Prediction (45) 0.73 (XGBoost) 8 Sunitinib (8)Nivolumab (7)Cabozantinib (6)Pembrolizumab/Axitinib (5)Nivolumab/Ipilimumab (4)Pazopanib (3)Pembrolizumab (3)Other (9) 0.520.780.400.890.601.001.000.67
Evaluating clinical and pathologic predictors for pathologic lymph node positivity (pN+) in patients with clinical T1-4N0M0 bladder cancer undergoing cystectomy.
Authors: Salvador Jaime-Casas, Regina Barragan-Carrillo, Miguel Zugman, Peter D. Zang, Hedyeh Ebrahimi, Daniela V. Castro, Benjamin Mercier, Xiaochen Li, Nazli Dizman, Nicholas Salgia, Joann Hsu, Charles B Nguyen, Wesley Yip, Alex Chehrazi-Raffle, Zeynep Busra Zengin, Luis A Meza, Sumanta Kumar Pal, Abhishek Tripathi
Journal: Journal of Clinical Oncology (2025)

877 Background: Occult pathological lymph node involvement at radical cystectomy (RC) in patients with clinical (cN0) bladder cancer (BC) remains a diagnostic and therapeutic challenge. We sought to evaluate clinical and pathological predictors of lymph node positivity (pN+) and its correlation with outcomes in patients with cT1-4N0M0 BC at RC. Methods: The study included patients with cT1-4N0M0 BC undergoing RC and pelvic lymph node dissection between 2004 and 2020. Patients were grouped as pN+ vs. pN0 at surgery. Baseline characteristics like age at surgery, sex, ethnicity, body mass index, concomitant carcinoma in situ (CIS) on TURBT, and lymphovascular invasion (LVI) were summarized using descriptive statistics. We performed logistic, univariable, and multivariable Cox regression models to identify independent predictors for pN+ at surgery. Kaplan Meier analysis and multivariable Cox proportional hazards model were used to analyze recurrence-free survival (RFS) and overall survival (OS). Results: 440 patients with T1-4N0M0 bladder cancer undergoing RC were evaluated, of which 359 (81.6%) were pN0 and 74 (16.8%) were pN+. Seven patients (1.6%) had incomplete information and were not included in the final analysis. Most patients were male (79.8%), White (87.7%), and had a median age of 71 years at surgery. Most patients had T2 (54.5%) disease, followed by T1 (24.8%) and T3 (5.7%) disease. On multivariable analysis, LVI [HR 3.02 (95% CI 1.21-7.54); p = 0.018] and positive surgical margins [HR 15.38 (95% CI 4.69-50.41); p &lt; 0.001] at RC were independent predictors for lymph node positivity at surgery. Interestingly, pN+ was not significantly associated with concomitant CIS, preoperative hydronephrosis, and preoperative renal function on multivariable analysis. pN+ demonstrated significantly worse RFS [HR 7.48 (95% CI 4.89-11.42); p &lt; 0.001] and OS (HR 7.86 (95% CI 5.20-11.89); p &lt; 0.001]. Preoperative hydronephrosis [HR 1.76 (95% CI 1.16-2.69); p = 0.008] was an independent predictor for RFS. Preoperative hydronephrosis [HR 1.60 (95% CI 1.19-2.15); p = 0.002] and positive surgical margins [HR 2.31 (95% CI 1.26-4.25); p = 0.007] were independent predictors for OS. Conclusions: LVI and positive surgical margins were significant predictors for pN+ at surgery in patients with cT1-4N0M0 BC. These features could inform perioperative therapy considerations and bladder preservation approaches in cN0 BC.
Transdermal oestradiol (tE2) patches as androgen deprivation therapy (ADT): Efficacy and safety of combining with androgen receptor pathway inhibitors (ARPIs) in metastatic (M1) prostate cancer—Randomised comparison from the STAMPEDE trial platform.
Authors: Nicholas David James, Hannah Rush, Matthew Guy Nankivell, Jyoti Sehjal, Stephen A Mangar, Neil McPhail, Simon Brown, Jacob S Tanguay, Joanna Gale, Wael Mohamed, Simon Crabb, Omar Khan, John Russell, William Cross, Claire Murphy, John Deighan, Noel W Clarke, Mahesh K. B. Parmar, Duncan C. Gilbert, Ruth Langley
Journal: Journal of Clinical Oncology (2025)

21 Background: Recent phase III data (n=1360) has shown that starting ADT with tE2 patches is non-inferior in terms of metastasis-free survival (with similar overall survival) to luteinising hormone releasing hormone analogues (LHRHa) for locally advanced (M0) prostate cancer. For both M0 and M1 patients, tE2 has advantages in terms of reported quality of life, bone mineral density, hot flushes and metabolic outcomes compared to LHRHa, with no excess of thromboembolic events. However, there is currently no data on the use of androgen receptor pathway inhibitors (ARPIs) (abiraterone, enzalutamide or apalutamide) with tE2. Methods: STAMPEDE [NCT00268476] is a multi-arm, multi-stage platform trial. This embedded phase 2 randomised study assessed efficacy and toxicity in participants (pts) randomly allocated (1:1) to tE2 patches (releasing 100mcg/24hrs, 3 patches changed twice weekly once testosterone ≤1.7ng/ml) or LHRHa (standard doses) and scheduled to receive ARPIs. Primary outcome measure was the proportion of pts reaching a PSA nadir of ≤0.2ng/ml during the first 6 months. Other PSA parameters, testosterone ≤1.7ng/ml at 12 weeks with tE2, and adverse events within the first 12 months (including hypertension, hot flushes and gynaecomastia) were assessed. Results: Between Oct-2020 and Mar-2023, 79 pts with histologically confirmed M1 prostate cancer (median (IQR) age 69 (65-75), median (IQR) baseline PSA 43.3 (11.5-296.2)) received either LHRHa+ARPI (n=41) or tE2+ARPI (n=38). Baseline characteristics were similar between the 2 groups. The proportion of pts achieving PSA ≤0.2ng/ml was LHRHa+ARPI 25/41 (61%) and tE2+ARPI 23/38 (61%). LHRHa v tE2: PSA90 (93% v 95%) and PSA50 (100% v 100%). 31/34 (91%) men treated with tE2 had testosterone ≤1.7ng/ml at 12 weeks. Hot flushes: LHRHa (grade 1: 32%, grade 2: 20%) v tE2 (grade 1: 24%, grade 2: 5%). Gynaecomastia: LHRHa (grade 1: 10%, grade 2: 0%) v tE2 (grade 1: 35%, grade 2: 8%) and any grade hypertension LHRHa v tE2 17% versus 5%. Conclusions: PSA responses were similar in pts treated with tE2+ARPI or LHRHa+ARPI further supporting the use of tE2 patches for ADT in prostate cancer management. tE2 patches provide patients with ADT choices about expected toxicity profiles, including reduced hot flushes (and subsequent impact on quality of life), and mode of administration. Clinical trial information: NCT00268476 .
Implementation and preliminary validity of the Functional Assessment of Cancer Therapy – Radionuclide Therapy (FACT-RNT) in patients receiving radionuclide therapy for prostate cancer.
Authors: Lisa Marie Gudenkauf, Tugce Telli, Astrid Delker, Danielle F. Simon, Heather S.L. Jim, Laura B. Oswald, Xiaoyin Li, Aasha Hoogland, Adam P. Dicker, Scott T. Tagawa, David Cella, Michael S. Hofman, Johannes Czernin, Jeremie Calais, Lena Unterrainer, Wolfgang Peter Fendler, Ken Herrmann, Ghassan El-Haddad, Brian D. Gonzalez
Journal: Journal of Clinical Oncology (2025)

118 Background: The Functional Assessment of Cancer Therapy-Radionuclide Therapy (FACT-RNT) is used in trials and clinical practice to monitor patient-reported RNT-relevant symptoms and toxicities in advanced metastatic castrate-resistant prostate cancer (mCRPC) patients receiving RNT. This study examined FACT-RNT feasibility and preliminary validity for U.S. patients receiving RNT. Methods: Patients scheduled to start 177Lu-PSMA-617 for advanced mCRPC at Moffitt Cancer Center from October 2023 – March 2024 completed patient-reported outcome (PRO) measures before each cycle. PROs included previously validated measures of prostate cancer specific-symptoms (NFPSI-17) and physical function (Scored Patient-Generated Subjective Global Assessment; PG-SGA) and the FACT-RNT, a 15-item measure of symptoms/toxicities with higher total scores (range: 0-60) indicating less symptom burden. Correlations between the FACT-RNT and other PROs were calculated. Results: Patients (N=17) were, on average, 69 years old (SD=11, range=43-90) at RNT cycle 1 and mostly non-Hispanic (76%) and White (82%). Gleason scores at diagnosis were 7-8 (30%) or 9-10 (71%). Patients had previously undergone surgery (35%), chemotherapy (94%), radiation (71%), hormone therapy (94%), targeted therapy (88%), and immunotherapy (29%). Fifteen patients (88%) received ≥2 RNT infusions; of these, 1 (6%) died and 1 (6%) discontinued RNT prior to cycle 2. Thirteen (87% of those with ≥2 infusions) completed the FACT-RNT at ≥2 cycles. Cycle 1 FACT-RNT total scores ranged from 31-58 (M=46.5, SD=8). The FACT-RNT was positively associated with symptoms as assessed by NFPSI-17 at cycles 1-3 ( p s≤.03) and negatively associated with physical function at cycles 1-2 ( p s≤.05). Conclusions: Preliminary results support FACT-RNT validity due to associations with validated PRO measures and the feasibility of FACT-RNT implementation in the U.S. The FACT-RNT may be helpful in clinical management and decision-making with RNT recipients. Future research will replicate and extend these findings in a larger longitudinal sample and examine validity with clinician-rated outcomes and RNT dosimetry.