tbuckley/cabot-search huggingface dataset:
Evaluation of ctDNA alterations in lethal mCRPC.
Authors: Minqi Huang, Nicholas Habibian, Tivoli Nguyen, Akerele Opeoluwa, Olivia Pocha, Priya Bhandari, Courtney Johnson, Alexandra Lieberman, Jennifer Schwartz, Jodi Lyn Layton, Brian E. Lewis, Alton Oliver Sartor, Elisa Marie Ledet
Journal: Journal of Clinical Oncology (2025)

245 Background: Circulating tumor DNA (ctDNA) can be used as a prognostic biomarker in mCRPC patients, with changes in ctDNA providing insight into patient survival. In this study, we evaluate the ctDNA landscape of patients with mCRPC prior to their death. Methods: A retrospective clinical data review, 2015-2024, was conducted at Tulane Cancer Center to identify mCRPC patients who underwent ctDNA testing prior to death. All ctDNA data were obtained through a multi-gene cancer panel via the Guardant 360 assay (70-83 genes). Lethal mCRPC was defined as patients who underwent ctDNA testing ≤3 months prior to death. A matched control group (CTRL) was defined as mCRPC patients with ctDNA collection ≥2 years prior to death or most recent follow-up. Statistical analyses were performed using Pearson Chi-Square Test or Fisher Exact Test whenever appropriate. Furthermore, survival analysis was conducted using the Kaplan-Meier method. Results: There were 70 patients in lethal mCRPC group and 157 patients in CTRL group. Compared to the CTRL group, in lethal mCRPC, somatic mutations and/or amplifications in BRAF(OR=2.1549, 95% C.I. [1.1136,4.1523], p=0.0298), CCND2 (OR=3.7925, 95% C.I.[1.1937,13.3380], p=0.03326), MYC (OR=2.6332, 95%C.I. [1.4158, 4.9120], p=0.0029), PDGFRA (OR=2.5235, 95% C.I. [1.1438, 5.5793], p=0.0291), and PIK3CA (OR=2.0328, 95% C.I. [1.1098, 3.7166], p=0.02846) were significantly more frequent. Additionally, lethal mCRPC patients were more likely to have missense (OR=4.3194, 95% C.I. [1.443456,19.3338], p=0.01687) and nonsense (OR=1.9364, 95% C.I. [1.06091,3.5250], p=0.04112) mutations at the end-of-life. Patients with a higher allelic fraction (≥0.6%) of TP53 alterations had a shorter median survival (p-value= 0.034). Conclusions: ctDNA mutations and/or amplifications in BRAF, CCND2, MYC, PDGFRA, and PIK3CA were more frequently detected in lethal mCRPC compared to matched CTRLs. Additionally, mCRPC patients with a lethal phenotype were more likely to have missense and nonsense mutations compared to the CTRL group. CtDNA assessment of copy number alterations was limited to amplifications only; additionally, with this assay, distinguishing between gene level and large scale chromosomal amplification is not assessable. Though this study is limited to a single-institution with retrospective analyses of clinical testing, understanding the somatic landscape of lethal mCRPC is critical for development of new biomarkers, strategies and ultimately druggable targets.
Evaluating the impact of single vs. combination therapy on survival outcomes in mHSPC patients stratified by BMI.
Authors: Luke Rohde, Rohan Agarwal, Martin W. Schoen
Journal: Journal of Clinical Oncology (2025)

187 Background: Metastatic hormone sensitive prostate cancer (mHSPC) is a heterogenous disease with a variety of treatment options. De novo mHSPC can be treated with androgen deprivation therapy (ADT) monotherapy or combinations including docetaxel or androgen receptor pathway inhibitors. Body mass index (BMI) is known to be associated with survival, but there is little data to show the effectiveness of treatment intensity (single or combination therapy) based on BMI. Methods: Patients treated for mHSPC within the Veterans Health Affairs from 2017-2023 were included. BMI was assessed using height and weight at diagnosis and treatment intensity was determined by treatments within 4 months of start of ADT. Additional baseline characteristics for each group included age, prostate specific antigen (PSA), and Charlson Comorbidity Index (CCI). Survival was estimated using the Kaplan-Meier method and Cox proportion hazard modeling was used to account for known covariates. Results: There were 4184 veterans identified with 33.5% BMI &lt;25, 35% BMI 25-30, and 31.5% with BMI &gt;30. The BMI 25-30 group had longer survival compared to BMI of &lt;25 (37.3 vs. 30.7 months, HR 0.78 95% CI 0.71-0.86) and the BMI &gt;30 had longer survival compared to BMI 25-30 (42.5 vs. 37.3 months, HR 0.87 95% CI 0.79-0.96). In patients with BMI of &lt;25 combination therapy was associated with longer survival (HR 0.73 (0.63-0.83)) and in patients with BMI of 25-30, combination therapy was also associated with longer survival 0.76 (0.67-0.88). However, in patients with BMI &gt;30, there was no difference in overall survival based on combination or monotherapy (HR 0.97 (0.83-1.13)). In a multivariable model including age, PSA, CCI, and treatment intensity, BMI &gt;30 and BMI 25-30 was associated with decreased risk of death compared to BMI &lt;25, aHR 0.80 (95% CI 0.72-0.89) and aHR 0.89 (95% CI 0.81-0.98) respectively. Conclusions: In patients with mHSPC, higher BMI is associated with longer survival compared to lower BMI. In all patients, combination therapy was associated with longer survival, however, there was no difference in survival with combination therapy compared to monotherapy in patients with BMI &gt;30. Future studies could investigate the reason why combination therapy is only associated with benefit in patients with BMI &lt;30. BMI (kg/m 2 ) &lt;25 n=1403 25-30 n=1465 &gt;30 n=1316 P value (ANOVA) Age (mean years) 76.2 74.4 71.8 p&lt;0.001 PSA (median ng/mL) 177 91.6 61.25 p&lt;0.001 Overall Survival (median months) 30.7 37.3 42.5 p&lt;0.001 ADT monotherapy 26.9 (n=736) 33.1 (n=683) 42.5 (n=582) Combination therapy 36.3 (n=667) 41.5 (n=782) 42.6 (n=734) HR (95% CI) 0.73 (0.63-0.83) 0.76 (0.67-0.88) 0.97 (0.83-1.13)
ABLE-32: A randomized, controlled, phase 3b clinical trial of nadofaragene firadenovec-vncg versus observation in patients with intermediate-risk non–muscle-invasive bladder cancer.
Authors: Neal D. Shore, Rian J. Dickstein, Mark Tyson, Vikram M. Narayan, Gautum Agarwal, Evan R. Goldfischer, Michael Brandon Williams, Corine Baayen, Kristian Juul, Per Sandstrom, Trinity Bivalacqua
Journal: Journal of Clinical Oncology (2025)

TPS888 Background: There is currently no Food and Drug Administration (FDA)-approved treatment for intermediate-risk non–muscle-invasive bladder cancer (IR NMIBC), defined by the AUA as recurrence of low-grade (LG) Ta within 1 year, solitary LG Ta &gt;3 cm, multifocal LG Ta, high-grade (HG) Ta (≤3 cm), and/or LG T1. Nadofaragene firadenovec-vncg is the first FDA-approved intravesical nonreplicating gene therapy for the treatment of adult patients with high-risk Bacillus Calmette Guérin (BCG)-unresponsive NMIBC with carcinoma in situ (CIS) with or without papillary tumors. In a nonrandomized, multicenter, open-label, repeat-dose, phase 3 study, 53.4% of participants (55/103) with CIS ± HG Ta/T1 achieved complete response 3 months after the first instillation. Nadofaragene firadenovec was well tolerated, with no grade 4/5 study drug-related AEs. Because maintenance treatment with nadofaragene firadenovec following tumor resection may improve clinical outcomes in patients with IR NMIBC, the ABLE-32 open-label randomized study is being conducted to evaluate the efficacy of nadofaragene firadenovec administered every 3 months versus observation in participants with IR NMIBC. Methods: This phase 3 study includes approximately 100 global sites with 454 anticipated participants. Adults diagnosed with new or recurrent IR NMIBC and having undergone transurethral resection of bladder tumor within 60 days prior to randomization are eligible. Participants will be randomly assigned 1:1 to receive nadofaragene firadenovec or continue observation. The nadofaragene firadenovec group will receive quarterly doses unless disease recurs or progresses. The observation group will be followed quarterly and may receive nadofaragene firadenovec if IR NMIBC recurs within 24 months. All participants will be evaluated for recurrence and progression using cytology, cystoscopy, and for-cause biopsy for up to 5 years. The primary endpoint is recurrence-free survival (RFS), from randomization to first documented recurrence, progression, or death. Secondary endpoints include RFS at 12 and 24 months and safety. Exploratory endpoints include effect on potential biomarkers and health-related quality of life. Final results are expected in 2031. Clinical trial information: NCT06510374 .
Validation of navigator-assisted hypofractionation (NAVAH) program surveys in African-American prostate cancer patients.
Authors: Erica Fleming Hall, Ursula Burnette, Tamika Smith, Abizairie Sanchez Feliciano, Maya J Stephens, Louisa Onyewadume, Chesley Cheatham, Daniel Eidelberg Spratt, Angela Y Jia, Shearwood McClelland
Journal: Journal of Clinical Oncology (2025)

313 Background: Prostate cancer is a leading cause of malignancy and death in men. African-Americans have the highest overall cancer death rate and shortest survival time of any racial or ethnic group in the United States, with African-American prostate cancer patients having a morality rate 80% higher than White patients. The disparities in access to radiation therapy (RT), mortality rates, and treatment outcomes among African-American prostate cancer patients compared to other populations highlight the urgent need for targeted interventions. The Navigator-Assisted Hypofractionation (NAVAH) program, with its innovative patient navigation approach and culturally sensitive survey, aims to better identify the specific barriers faced by African-American patients with prostate cancer. This study is a report of the NAVAH program experience piloting a culturally sensitive survey in African -American prostate cancer patients. Methods: African-American patients with established prostate cancer having seen a Radiation Oncologist and consented to receive RT were recruited to participate in our ongoing Phase I trial (clinicaltrials.gov, NCT05978232); those enrolling on trial were administered surveys prior to receipt of RT. Survey information was assessed by topic category and survey responses were combined into a representative score for each category (outstanding, excellent, good, average, below average). Survey categories include availability (access to a medical center, coordinating care, and overall quality of care), accessibility (transportation, distance to care, and healthcare literacy), affordability (financial considerations, employment, and level of education), accommodation (access to internet, navigating transportation), acceptability (comfort and prejudice among interactions with the system), and cancer screening/cancer treatment. Results: Mean scores noted good availability (32 responses), excellent accessibility (20 responses), excellent affordability (22 responses), excellent accommodation (18 responses), average acceptability (44 responses), and average cancer screening/cancer treatment (40 responses). Patients noted neutral to positive interactions with doctors and nurses, but distrust of following the advice given to them at hospitals, and that the time interval from their first abnormal test to being informed of a cancer diagnosis was too long. Conclusions: Our findings indicate that this novel survey design is feasible in the African-American prostate cancer population. As more patients enroll in our ongoing Phase I trial, implementation of this survey will provide more definitive and comprehensive answers regarding additional topics, including financial challenges during treatment, access to accommodations, and perception of treatment during cancer care.
Outcomes with multi parametric MRI (mpMRI) compared to diagnostic transurethral resection of bladder tumor (TURBT) in patients (pts) with suspected muscle-invasive bladder cancer (MIBC): A pilot study.
Authors: Nataliya Mar, Amanda Macaraeg, Ali Raad, Dalia Kaakour, Arash Rezazadeh, Michael A Daneshvar
Journal: Journal of Clinical Oncology (2025)

TPS881 Background: TURBT is a standard diagnostic procedure to determine the depth of bladder tumor invasion into the bladder wall, particularly whether the muscularis propria layer is involved by tumor. This is crucial in order to distinguish between non-MIBC and MIBC, providing accurate tumor staging and determining appropriate therapy. However, TURBT may be associated with multiple complications such as pain, infection, need for Foley catheters, blood loss requiring transfusions, hospitalization, and a small mortality risk. A proportion of pts end up with a superficial resection out of concern for bladder perforation, where the muscularis propria layer is absent from the surgical specimen, and require a repeat TURBT that is typically performed 4-6 weeks following the initial procedure. Further, TURBT scheduling requires coordination with urology and operating room availability. These factors may cause delays in initiation of cancer-directed therapy. Recent data suggests that mpMRI may accurately predict the degree of invasiveness of bladder tumors by generating a Vesical Imaging-Reporting and Data System (VI-RADS) score. mpMRI is not commonly associated with complications and can be performed quickly by radiology. Methods: This is an IRB-approved, single-institution, prospective, single-arm, phase 2 pilot study, which aims to compare two diagnostic modalities for bladder cancer - TURBT versus mpMRI. Pts are identified based on tumor appearance during initial routine cystoscopy, if MIBC is suspected. If eligible for the study, pts then proceed with an mpMRI and a diagnostic TURBT. Primary study endpoint is incidence of concordance between VI-RADS score 4 and 5 bladder tumors on mpMRI, which represent “likely” and "very likely" muscularis propria invasion, and pathologic muscularis propria invasion on TURBT. Secondary study endpoints include time from initial cystoscopy to performing each diagnostic test, time from performing each diagnostic test to initiation of cancer-directed therapy, incidence of repeat TURBT, patient-assessed quality of life with each diagnostic test, incidence of adverse events related to each diagnostic test, progression free survival, and financial toxicity of each diagnostic test. Based on prior literature, the rate of detecting muscularis propria invasion with TURBT is about 90%. We hypothesized that diagnostic accuracy of mpMRI would be non-inferior to TURBT, within a 10% difference. Power calculations for this study were based on a one-sided, one-proportion exact test, with a power of 80% at a significance level of 0.05 using a non-inferiority design. Out of 30 anticipated pts, 11 have been enrolled to date. Clinical trial information: NCT06335667 .
The impact of micropapillary histology and clinical staging on overall survival in bladder cancer: A retrospective analysis.
Authors: Muhammad Hassan Alkazemi, Syed Muneeb Alam, Ao Zhang, Eugene J. Pietzak, S. Machele Donat, Harry W. Herr, Bernard H. Bochner, Jie-Fu Chen, Hikmat Al-Ahmadie
Journal: Journal of Clinical Oncology (2025)

744 Background: Micropapillary variant bladder cancer (MPC) is a rare subtype of urothelial carcinoma, representing 0.01–2.2% of cases, with a higher stage at diagnosis and increased metastatic potential. The prognostic role of MPC remains uncertain, and previous studies have been limited by small cohort sizes, with only a few larges studies. This study analyzed the prognostic impact of MPC on clinical stage and survival outcomes in the largest single-institution cohort of patients with MPC who underwent radical cystectomy (RC). Methods: This retrospective study included 130 patients who underwent RC at Memorial Sloan Kettering Cancer Center for MPC between June 21, 1995, and April 14, 2023. Data included demographic, histologic, and clinical variables, as well as overall survival (OS) outcomes. Cystectomy specimens were reviewed by genitourinary pathologists to determine the proportion of the MPC component (MPC%) in each tumor. For OS comparison, a separate cohort of 430 patients with urothelial carcinoma not otherwise specified (UC NOS) who also underwent RC was used. Patients with MPC were further stratified by stage at diagnostic transurethral resection of bladder tumor (TURBT) as either non-muscle-invasive bladder cancer (NMIBC) or muscle-invasive bladder cancer (MIBC). Additional stratifications included MPC% ( &lt; 50% vs. ≥50%, &lt; 20% vs. &gt; 80%) and receipt of neoadjuvant chemotherapy (NAC). Results: MPC was associated with a significantly shorter OS compared to UC NOS patients (p = 0.011). The MPC cohort had a mean OS of 83.8 months (95% CI: 62.2–105.4) and a median OS of 36.8 months (95% CI: 22.3–51.3), whereas the UC NOS cohort had a mean OS of 72.1 months (95% CI: 66.6–77.6) and a median OS of 84.4 months (95% CI: 64.5–104.2). Within the MPC cohort, patients with MIBC at initial TURBT had significantly worse OS compared to those with NMIBC (p = 0.0005). MPC% did not impact OS, with no differences between patients with &lt; 50% versus ≥50% MPC (p = 0.59) or &lt; 20% versus &gt; 80% MPC (p = 0.57). Additionally, NAC did not affect OS within the MPC cohort (p = 0.055). N stage at cystectomy (N0 vs. N1+) was also not predictive of OS (p = 0.16). Conclusions: The presence of MPC, regardless of its proportion or the use of NAC, predicts poor outcomes. Clinical stage—particularly the presence of muscle invasion—remains the key predictor of survival. These findings emphasize the importance of clinical staging in guiding treatment decisions and prognostic assessments in the management of this disease.
Real-world treatment patterns in patients diagnosed with metastatic castration-resistant prostate cancer in the US, 2018-2023.
Authors: Eleni Efstathiou, Weiyan Li, James Roose, Brendan T Kerr, Chinelo Orji, Nina Yeh, Stephen Corson, Kumar Mukherjee
Journal: Journal of Clinical Oncology (2025)

74 Background: The treatment landscape in patients with metastatic castration-resistant prostate cancer (mCRPC) has evolved in recent years. This real-world study evaluates treatment patterns among a large contemporary cohort of patients with mCRPC in the US. Methods: This retrospective cohort study included patients with a confirmed mCRPC diagnosis from 1/1/2018 to 12/31/2023 in the US nationwide Flatiron Health electronic health record-derived deidentified database. Treatment patterns were evaluated by disease setting (metastatic hormone-sensitive prostate cancer [mHSPC], nonmetastatic castration-resistant prostate cancer [nmCRPC], mCRPC) and by use of androgen receptor pathway inhibitors (ARPI; abiraterone, enzalutamide, apalutamide, darolutamide) before mCRPC diagnosis. Patients were considered ARPI-experienced if they received at least 1 line of therapy (LOT) containing an ARPI before progressing to mCRPC. Patients were considered ARPI-naive otherwise. Results: Of 6301 patients with mCRPC (mean age, 75 years), 4915 (78%) received ≥1 LOT in the mCRPC setting. Among those with ≥1 LOT, 48% received second-line (2L) therapy. The most common first-line (1L) and 2L therapies in mCRPC were ARPI (1L, 75%; 2L, 55%) and chemotherapy (1L,16%; 2L, 33%). Most patients (4491, 71%) were ARPI-naive before mCRPC diagnosis. Among the 1810 (29%) patients who were ARPI-experienced before their mCRPC diagnosis, the median treatment duration with ARPI was 23 months. Use of ARPI in the mHSPC setting increased from 11% to 39% in patients diagnosed with mCRPC in 2018 and 2022, respectively. Similarly, in the nmCRPC setting, this figure rose from 20% to 39%. Consecutive use of ARPI in the mCRPC setting, with variations based on the year of mCRPC diagnosis, was observed in 54% to 65% of ARPI-naive patients and 31% to 48% of ARPI-experienced patients who received 1L ARPI and any 2L therapy. Use of chemotherapy increased from 13% to 19% in 1L and 29% to 40% in 2L in the mCRPC setting but decreased from 11% to 7% in mHSPC setting. Conclusions: In this community practice-based study, ARPI was the most common 1L and 2L therapy, followed by chemotherapy, in patients diagnosed with mCRPC from 2018 to 2023. Although ARPI use before mCRPC diagnosis has increased, more than two-thirds of patients overall remain ARPI-naive at mCRPC diagnosis. Despite not being recommended by guidelines, consecutive use of ARPI in the mCRPC setting was common in patients regardless of ARPI use before mCRPC diagnosis.
A phase 1, first-in-human, open label, dose escalating study of B440, an oral cancer vaccine using a WT1-expressing <i>Bifidobacterium</i> , in patients with advanced urothelial cancer.
Authors: Toshiro Shirakawa, Junya Furukawa, Yasumasa Kakei, Hideto Ueki, Takuto Hara, Jun Teishima, Nobuyuki Hinata, Hideaki Miyake, Masato Fujisawa
Journal: Journal of Clinical Oncology (2025)

TPS883 Background: B440, an oral cancer therapeutic vaccine, is based on an innovative oral vaccine platform utilizing gut microbiota ( B. longum; Bifidobacterium longum ) that can efficiently deliver the heterogeneous antigen protein to dendritic cells (DCs) in Peyer's patches in gut-associated lymphoid tissue (GALT). B440 is a lyophilized powder of inactivated B. longum 440, a recombinant B. longum expressing a partially modified human WT1 tumor-associated antigen protein (amino acids 117-419 with a single amino acid substitution at 236 from M to Y to enhance immunogenicity). In preclinical studies, B440 showed superior anti-tumor activity to the WT1 peptide vaccine (WT1 126-134 peptide, human HLA-A02 or mouse H-2Db restricted CD8 epitope) due to the large length of the WT1 117-419 protein, including multiple CD8 and CD4 epitopes without HLA restriction, and its ability to internalize into DCs (1, 2). Furthermore, our extensive preclinical studies showed that B440 alone or as an adjunct to an anti-PD1 antibody can induce potent WT1-specific cellular immunity and anti-tumor activity in several mouse syngeneic tumor models (urothelial cancer (3), prostate cancer (4), and renal cell carcinoma (5)). Methods: This first-in-human, multicenter, open-label, single-arm, investigator-initiated phase 1 study will evaluate the safety and initial efficacy of B440 monotherapy in patients with advanced urothelial cancer who are refractory to all standard therapies, including chemotherapeutic agents, PD-1/PD-L1 inhibitors and antibody-drug conjugates (ADCs). A total of 12 patients will receive B440 orally once daily for 5 consecutive days followed by a 2-day rest for a total of 20 doses for 4 weeks. The study consists of 2 escalating doses of 6 patients each; the low dose group will receive 800 mg (4 capsules) per dose and the high dose group will receive 1,600 mg (8 capsules) per dose. One enteric capsule contains 200 mg of B440, equivalent to 2X10 10 colony forming units (cfu) of B. longum 440. The primary endpoint is the determination of dose-limiting toxicity (DLT) with an assessment period of 4 weeks during treatment. Secondary endpoints are safety as assessed by adverse events (AEs) using CTCAE 5.0 and efficacy as assessed by best overall response and progression-free survival (PFS) using RECIST ver1.1. In addition, the immunological response to B440 will be evaluated by enzyme-linked immunosorbent assay (ELISPOT). The study was registered with the Japan Registry of Clinical Trials under the number jRCT2051220143 on December 27, 2022. Patient enrollment was completed in September 2024. Research Sponsor: Immunorock Co., Ltd., Grant: the Japan Agency for Medical Research and Development (AMED); 23ym0126081h0002. Clinical trial information: jRCT2051220143 .