tbuckley/cabot-search huggingface dataset:
Patient and caregiver preferences for the treatment of locally advanced or metastatic urothelial carcinoma (la/mUC): Results of a targeted literature review (TLR).
Authors: Mairead Kearney, Rosanne Janssens, Matt Quaife, Myrto Trapali, Caitlin Thomas
Journal: Journal of Clinical Oncology (2025)

755 Background: The treatment landscape for la/mUC has evolved with multiple care options available. As new therapies are adopted, decision-making among physicians, patients, and their caregivers becomes more complex and challenging. This study summarizes the existing literature on preferences of patients and caregivers about aspects of treatment following a diagnosis of la/mUC. Methods: A TLR of English-language conference abstracts and full-text manuscripts published from 2015 was conducted using Embase and PubMed, to identify qualitative and quantitative studies on the treatment preferences of patients with la/mUC and caregivers of people with la/mUC. Literature was independently screened against predefined eligibility criteria by two researchers, with a third researcher resolving disagreements. Results: Data from 13 publications were extracted (n=10 [77%] qualitative, n=3 [23%] quantitative); of these, 6 (46%) were full-text manuscripts and 7 (54%) were conference abstracts/posters. When specified, most studies (6/10 [60%]) were conducted in the US. Six studies (46%) assessed preferences among both patients and caregivers. The quantitative preference studies assessed varied efficacy endpoints, including overall survival (n=2), overall response rate (ORR; n=1), and progression-free survival (n=1). Treatment efficacy was the most important consideration in 2 quantitative studies, while 1 study found adverse events (AEs), combined with number and duration of medicines, to be more important to patients. Across publications, attributes related to treatment AEs significantly impacted preferences. Unmet needs related to symptoms and AEs were identified. The symptoms/AEs reported most frequently across all 13 studies were fatigue (n=7 [53%]), cancer-related pain (n=6 [46%]), peripheral neuropathy (PN; n=3 [23%]), blood in urine (n=3 [23%]), and nausea (n=3 [23%]). In 1 quantitative study, cancer-related pain was ranked as the second most important treatment attribute after ORR. Patients in this study also indicated that they would accept a 7.8% reduction in ORR to reduce the risk of developing PN by 10%. Of 3 studies that compared differences between patient and caregiver preferences, 2 quantitative studies found that caregivers placed a higher importance on avoiding side effects than patients. Conclusions: Despite heterogeneity in study designs and outcomes reported, patients and caregivers often prioritized treatment efficacy over tolerability. However, in quantitative studies, patients and caregivers were willing to accept lower efficacy for a more tolerable treatment, although the magnitude of trade-offs varied by AE. Such insights highlight the importance of incorporating patient and caregiver preferences in shared decision-making and personalizing treatment according to individual patient goals.
Analysis of gene expression signatures in prostate cancer prior to liver metastases.
Authors: Joshua Watson, Sungyong You, Neil Bhowmick, Edwin Melencio Posadas
Journal: Journal of Clinical Oncology (2025)

206 Background: It has been recognized that as a prostate cancer (PCa) metastasizes to bone, it begins to express bone-specific proteins such as osteopontin, bone sialoprotein, and osteocalcin. This process is known as osteomimicry. Liver metastases (LM) are associated with the poorest clinical outcomes and affect 25% of PCa patients at autopsy. We hypothesized that PCa that metastasize to the liver express liver-specific genes prior to liver metastasis – a process we have named “hepatomimicry”. Methods: We have curated a list of 23 putative genes that are both primarily expressed in the liver and found in RNA-seq data from over 3000 PCa samples. Initial sources included the PCa transcription atlas (n = 2115), West Coast/SU2C Dream Team (n = 210), neuroendocrine PCa from cBioPortal (n = 49), and TEMPUS RNA-seq data generated specifically for Cedars-Sinai (n = 88). In each dataset, for the 23 hepatomimicry genes, we used recursive feature elimination and a t-test to discriminate between PCa LM and non-liver visceral metastases. In datasets with count-level data, we performed differential gene expression analysis with DeSeq2 and gene set enrichment analysis (GSEA) on identified differentially expressed genes. Results: In three different datasets, MAT1A, ELF3, and WEE1 were found to be either optimal genes for discriminating between these two groups or significantly different by t-test and were more highly expressed in LM. 270 genes were downregulated and 437 genes were upregulated in liver metastases (FDR q-value &lt; 0.05, log2 fold change &gt; 1 for upregulated and &lt; -1 for downregulated). Subsequent GSEA found that liver-specific gene sets are highly enriched in the genes upregulated in LM, and endothelial cell genes are strongly downregulated. Conclusions: The initial results indicate that a three-gene subpanel of our initial set have predictive power for LM against other visceral metastases in PCa.While hepatocyte infiltration may impact the characterization of these samples by yielding a strong signal for liver-specific gene expression signature, confirmation of this finding remains important. Ongoing work is directed at confirming this signature in single-cell RNA-seq from PCa LM. Our work may be adaptable to developing diagnostic technologies such as liquid biopsies that may enhance the identification of patients who may have occult LM or that may develop LM as part of their natural history so that interventions may be enacted in a more timely manner.
A multicenter, open-label phase 1/2 study of TYRA-300 in advanced urothelial carcinoma and other solid tumors with activating FGFR3 alterations (SURF301).
Authors: Aaron Richard Hansen, Alison Yan Zhang, Valentina Boni, Charlene Mantia, Evan Y. Yu, Andrew James Weickhardt, Marie Robert, Shilpa Gupta, Rafael Morales-Barrera, Christopher J. Hoimes, Jordan Berlin, Gopa Iyer, Michael Millward, Christine Francis Lihou, Yohan Loriot, Damien Pouessel, Kriti Mittal, Andrew Graham Hill, Fabricio Racca, Ben Tran
Journal: Journal of Clinical Oncology (2025)

TPS904 Background: Activating FGFR3 gene alterations have been identified in up to 20% of advanced/metastatic urothelial cancers (mUC). The pan-FGFR inhibitor erdafitinib (erda) is approved for the treatment of mUC with susceptible FGFR3 genetic alterations whose disease has progressed on or after at least one line of prior systemic therapy. Since pan-FGFR inhibitors target all four isoforms of FGFR (1-4), their lack of FGFR isoform specificity can lead to off-target toxicity (e.g., hyperphosphatemia, stomatitis, ocular toxicity, skin and nail toxicity) and loss of activity due to development of on-target resistance mutations (e.g., V555M/L gatekeeper). TYRA-300 has been designed to be more selective for FGFR3 over FGFR1/2/4 to minimize off-target toxicity and to avoid interactions with known FGFR3 gatekeeper mutations. TYRA-300 is in development for the treatment of FGFR3 + mUC and other solid tumors (SURF301 - NCT05544552). Methods: SURF301 is a first-in-human, open-label, Phase 1/2 global study in several parts: dose escalation in participants with advanced malignancies, with/without FGFR3 alterations (Phase 1, Part A); dose expansion in participants with FGFR3 -activating mutations or fusions (Phase 1, Part B); and select tumor expansion cohorts with FGFR3 activating mutations or fusions (Phase 2). The purpose of Phase 1 is to evaluate the safety, tolerability, pharmacokinetics (PK), preliminary antitumor activity of TYRA-300, and identify the recommended Phase 2 dose (RP2D). Phase 2 will enroll participants in FGFR3 + mUC and other tumor types to further explore the anti-tumor activity and safety of TYRA-300. SURF301 study began enrolling patients in November 2022 and is ongoing in Australia, the United States, France, and Spain. Clinical trial information: NCT05544552 .
Efficacy and safety of organoid-based drug sensitivity screening to guide the treatment of mCRPC patients progressed after first-line treatment.
Authors: Diwei Zhao, Junliang Zhao, Yuanwei Li, Xinyang Cai, Zhenyu Yang, Meiting Chen, Liru He, Yang Liu, Fangjian Zhou, Yonghong Li, Jun Wang
Journal: Journal of Clinical Oncology (2025)

TPS278 Background: Treatment for metastatic castration-resistant prostate cancer (mCRPC) patients progress after first-line therapy remains challenging due to limited options and heterogeneous response. Organoid-based drug sensitivity screening offers an innovative approach by simulating the tumor microenvironment in vitro, potentially allowing for personalized treatment strategies based on individual tumor responses to various drugs. This study aims to assess the efficacy and safety of using organoid-based drug sensitivity screening to guide treatment decisions in mCRPC patients. Methods: This is a prospective, open-label, single-arm observational study designed to recruit 30 mCRPC patients with bone metastases who have progressed after first-line therapy. Residual tissue from biopsies of bone metastatic lesions will be used to culture organoids for drug sensitivity screening. Screening regimens include at least Olaparib, Docetaxel or platinum-based chemotherapy, and Abiraterone plus Niraparib, as recommended by current guidelines. Additionally, 141 other drugs from a previously established library are available for screening, based on investigator and patient preferences. The treatment regimen will be selected based on the agent that demonstrates the highest sensitivity in the screening process. The primary endpoint is PSA response rate, defined as a 50% decrease in PSA levels from baseline. Secondary endpoints include radiologic progression-free survival (rPFS), objective response rate (ORR), duration of response (DOR), and overall survival (OS). Patient recruitment is ongoing at Sun Yat-sen University Cancer Center, with 5 patients (5/30, 16.7%) enrolled as of September 3, 2024. Data analysis is expected to begin in 2025, following the completion of recruitment. Clinical trial information: NCT06529549 .
Adrenal androgens and overall survival (OS) in men with castration-resistant prostate cancer (CRPC) treated with enzalutamide without (ENZ) or with abiraterone and prednisone (ENZ/AAP) (Alliance).
Authors: Nima Sharifi, Hyotae Kim, Mohammad Alyamani, Robert Diaz, Himisha Beltran, Andrew J. Armstrong, Michael J. Morris, Susan Halabi, Charles J. Ryan
Journal: Journal of Clinical Oncology (2025)

230 Background: DHEA, testosterone (T) and androstenedione (AD) are adrenal androgens that can drive CRPC. HSD3B1 encodes for 3β-hydroxysteroid dehydrogenase-1 (3βHSD1) and has 2 common missense-encoding germline variants: the more active adrenal-permissive allele and the less active adrenal-restrictive allele that are associated with greater and lesser non-gonadal androgen biosynthesis from DHEA. A single adrenal-permissive HSD3B1 (1245C) allele is sufficient to confer more rapid development of CRPC and homozygous inheritance (about 7-10% of men) is the most common monogenic link to prostate cancer mortality. Alliance A031201 (NCT01949337) is a phase 3 trial of ENZ versus ENZ/AAP for metastatic CRPC. This analysis combines clinical outcomes associated with adrenal androgens and HSD3B1 as the gene encoding the enzyme that uses dehydroepiandrosterone (DHEA). Methods: Germline DNA was genotyped for HSD3B1 in 929 men from A031201 (469 ENZ and 460 ENZ/AAP). Baseline DHEA, T and AD were assessed in 922 men (464 ENZ and 458 ENZ/AAP) using mass spectrometry. The Cox proportional hazards model was used to determine the prognostic significance of DHEA, T and AD categorized as tertiles in predicting OS. Results: In the combined treatment arms, median (95% CI) OS for men in low, medium and high DHEA tertiles was 27 (25, 31), 36 (33, 42) and 39 (37, 47) months (Table). In the ENZ arm, men with inheritance of 0, 1 and 2 adrenal-permissive alleles had median OS of 34 (30, 39), 34 (29, 39) and 28 (23, 37) months. Conclusions: DHEA is the most informative adrenal androgen. Men with the lowest tertile for this substrate of 3βHSD1 have the shortest OS. These data are consistent with prior analyses demonstrating poor prognosis for men with low adrenal androgens. Outcomes for men homozygous for the adrenal-permissive HSD3B1 allele treated with ENZ are consistent with prior retrospective studies. Overall survival and adrenal androgens. Serum Androgen Median OS in months (95% CI) Multivariable Hazard Ratio (95% CI) DHEA 1 st Tertile (Low) DHEA 2 nd Tertile (Medium) DHEA 3 rd Tertile (High) 27 (25, 31)36 (33, 42)39 (37, 47) AC vs. AA 0.97 (0.82,1.14)CC vs. AA 1.08 (0.81,1.44)DHEA: Med vs High 1.17 (0.97,1.42)DHEA: Low vs. High 1.65 (1.37,2.00) AD 1 st Tertile (Low) AD 2 nd Tertile (Medium) AD 3 rd Tertile (High) 32 (27, 36)36 (34,43)34 (31, 39) AC vs. AA 0.96 (0.82,1.13)CC vs. AA 1.08 (0.81, 1.44)AD: Med. vs. High 0.89 (0.73,1.07)AD: Low vs. High 1.16 (0.97,1.40) T 1 st Tertile (Low) T 2 nd Terile (Medium) T 3 rd Tertile (High) 28 (26, 35)37 (34, 41)36 (32, 41) AC vs. AA 0.95 (0.81,1.12)CC vs. AA 1.07(0.80,1.43)T: Med vs. High 1.01 (0.83,1.22)T: Low vs. High 1.28 (1.06,1.54)
Evaluation of circulating kidney injury marker-1 (KIM-1) as a prognostic and predictive biomarker in advanced renal cell carcinoma (aRCC): Post-hoc analysis of CheckMate 214.
Authors: Wenxin Xu, Sai Vikram Vemula, Robert J. Motzer, Aparna Chhibber, Deepthi Chowbene, Nahuel Perrot, Xiaowen Liu, Joseph Bonventre, Toni K. Choueiri, David F. McDermott, Saurabh Gupta, Rupal Satish Bhatt
Journal: Journal of Clinical Oncology (2025)

437 Background: CheckMate 214 established nivolumab and ipilimumab (NIVO+IPI) as a first line standard of care regimen with superior survival and durable response versus sunitinib (SUN) in advanced RCC. Previous studies have shown that high levels of circulating KIM-1 are associated with worse prognosis and reduction in KIM-1 levels is associated with benefit from adjuvant immunotherapy. In this post-hoc analysis we evaluated whether KIM-1 levels at baseline and after 1 cycle of NIVO+IPI or SUN are associated with treatment outcomes in CheckMate 214. Methods: Patients with advanced RCC were randomized to NIVO+IPI or SUN as previously described. Serum KIM-1 was measured at baseline and 3 wks after first treatment dose using an enzyme based electrochemiluminescence assay. The association between KIM-1 levels and clinical outcomes was evaluated using Kaplan-Meier and Cox proportional hazards analyses. Results: We analyzed serum from 821 patients (75% of the CM 214 ITT population). Median KIM-1 at baseline was 660.4 pg/mL. Across both arms, higher KIM-1 levels were associated with shorter overall survival (OS) independent of IMDC risk group, nephrectomy status, and tumor burden. Benefit for NIVO+IPI versus SUN was seen across KIM-1 tertiles. Decrease in KIM-1 from baseline to C2D1 was strongly associated with progression free survival (PFS) and OS among patients treated with NIVO+IPI (Median PFS 70.8 months vs 4.2 months for patients with &gt;30% decrease vs &gt;30% increase in KIM-1, with median OS 85.4 vs 26.6 months, overall response rate (ORR) 69.3 % vs 13.9%), but not in patients treated with SUN. Conclusions: In CheckMate 214, increased levels of baseline circulating KIM-1 were associated with worse clinical outcomes both in NIVO+IPI and SUN arms. The extent of reduction in serum KIM-1 just 3 wks after single cycle of NIVO+IPI was associated with long term efficacy of this IO doublet. Circulating KIM-1 may be a useful minimally invasive biomarker for monitoring patients on RCC immunotherapy. KIM-1 change at 3 weeks (prior to second dose of NIVO+IPI) and association with outcomes (NIVO+IPI arm). 3 week KIM-1 change N (%) ORR, % (95% CI) mPFS, months (95% CI) mOS, months (95% CI) &gt;30% Decrease 140 (31.7) 69.29 (60.94-76.80) 70.80 (17.84- NA) 85.36 (63.08- NA) &gt;10-30% Decrease 87 (19.7) 36.78 (26.69-47.80) 11.43 (6.28-18.20) 66.14 (40.44-80.10) &lt;10% Change 86 (19.5) 30.23 (20.79-41.08) 15.41 (10.32-20.73) 52.70 (30.26-70.67) &gt;10-30% Increase 56 (12.7) 23.21 (12.98-36.42) 7.13 (4.17-16.79) 40.34 (23.82-58.41) &gt;30% Increase 72 (16.3) 13.89 (6.87-24.06) 4.17 (3.02-8.08) 26.61 (18.79-38.44)
Understanding metastatic squamous cell carcinoma patients receiving pelvic exenteration vs radical cystectomy: A nationwide context.
Authors: Christopher Reese Bine, Alec Czaplicki, Peter T. Silberstein
Journal: Journal of Clinical Oncology (2025)

681 Background: Squamous Cell Carcinoma (SCC) is a rare subtype of bladder cancers, consisting of 2-5% of all bladder cancers. SCC is associated with chronic bladder inflammation often due to catheters, kidney stones, and bladder outlet obstruction. While gold standard treatment for SCC is radical cystectomy (RC), many patients receive more extensive surgery such as pelvic exenteration (PE). PE involves removing all organs from a person’s pelvic cavity whereas RC involves removing the bladder and nearby tissue. This study will examine the characteristics of metastatic SCC patients receiving PE vs RC to better understand why some patients may not receive RC. Methods: The National Cancer Database (NCDB) was used to identify patients diagnosed with bladder squamous cell carcinoma from 2004 to 2020 using the histology codes 8050, 8070-8076, 8084 and NCDB analytic stage code IV as assigned by the Commission on Cancer Accreditation program. Kaplan-Meier, ANOVA Chi-Square, and Cox Proportional Hazards tests were performed. Data was analyzed using SPSS version 27 and statistical significance was set at α = 0.05. Results: Of the 561 patients in the sample, 211 (37.6%) received PE and 350 (62.4%) received RC. Patients receiving PE survived 32.8 months and patients receiving RC survived 35.8 months (p&gt;0.05). Patients receiving PE were more likely to receive adjuvant radiation or chemoradiation, have no residual tumor or microscopic residual tumor after surgery, receive care from an academic facility, and to have lymph vascular invasion (p&lt;0.05). These patients were also more likely to present at a younger age (62.86 vs 65.37 years) yet interestingly were more likely to have fewer regional lymph nodes positive (9.27 vs 14.90) (p&lt;0.05). There were no significant differences between income level, race, the number of comorbid conditions (Charlson-Deyo Score), insurance status, tumor size, or time to surgery (p&gt;0.05) between the two groups. Conclusions: 37.6% of patients in this sample received PE over RC, the gold standard. PE patients had disease that more greatly invaded the lymphatics and had better surgical margins, yet PE offered no significant survival benefit. More research is needed to better understand why some patients receive more extensive surgical intervention.
Hydroxychloroquine effects on tumor suppressor PAR-4 levels in patients with oligometastatic prostate cancer: Results from a phase-2 trial.
Authors: Joon Kyung Kim, Andrew Callaway James, Ravshan Burikhanov, Zhengyan Huang, Zin Myint, Don Cohen, Donglin Yan, Akosua Adu, Leigh Anne Faul, Ning Li, Peng Wang, Stephen Strup, William H St. Clair, Vivek Rangnekar, Patrick J. Hensley
Journal: Journal of Clinical Oncology (2025)

233 Background: In oligometastatic prostate cancer (OMPC), delaying time to initiation of androgen deprivation therapy (ADT) may have oncologic and quality of life benefits. Additionally, there is an emerging role for metastatic/primary tumor site-directed therapy for patients with OMPC. Prostate apoptosis response-4 (PAR-4) is a potent tumor suppressor, facilitating apoptosis in prostate cancer cells. Hydroxychloroquine (HCQ) has been identified to be a potent inducer of PAR-4 secretion and downstream tumor inhibition in preclinical models and Phase I trials. We present a single institution Phase II trial assessing induction of PAR-4 levels in the plasma of patients in response to HCQ administration in combination with radiation therapy (RT) for OMPC. Methods: Men with OMPC (≤5 synchronous metastatic lesions) following primary tumor treatment were eligible. Patients received 400 mg HCQ daily for 2 weeks prior to metastatic site-directed RT and 400 mg HCQ daily for 90 days post-radiation. Plasma samples were collected on Day 0, 14, 30, 60, and 90. The primary endpoint was induction of ≥50% serum PAR-4 expression above baseline level within 90 days of treatment initiation. We hypothesized that over half of patients would exhibit ≥50% induction of serum PAR-4 expression. Results: Nineteen participants met inclusion criteria and were treated with 90 days of HCQ and RT to oligometastatic lesions. Median age was 68 years (range 55-77), the majority of patients were Caucasian (94%) and the median baseline PSA was 6.30 ng/ml (range 0.99 to 27.80). Prior primary tumor treatment included radiation therapy in 26%, radical prostatectomy in 32%, and radical prostatectomy with radiation in 42%. Eleven patients (58%) showed ≥50% increase in plasma PAR-4 above baseline levels (p=0.0006). This was associated with a concomitant PSA decline at 6-months (mean -0.98 ng/ml, 95% CI -6.61 to 4.65) and 12-months (mean -7.21 ng/ml, 95% CI -12.45 to -1.97). At 12-month follow-up, seven patients (37%) were free from ADT and median progression-free survival was 9.3 months (95% CI 6.4 to N/A). Twelve patients (63%) reported at least one adverse event, with 2 patients (11%) experiencing grade 3 toxicity. Conclusions: Oral administration of HCQ is well tolerated and effectively induces plasma expression of the potent tumor suppressor PAR-4 in patients with OMPC. Given the promising findings, further investigation into possible radiosensitizing and anti-tumor benefits of HQC in a larger cohort of OMPC is necessary. Clinical trial information: NCT04011410 .