tbuckley/cabot-search huggingface dataset:
Associations between protein biomarkers and adverse pathologic features in MRI-mapped prostate cancers: An interim analysis.
Authors: Wesley Hauwei Chou, Solange Bassale, Tao Liu, Tai-Tu Lin, Yuqian Gao, Yi-Ting Wang, Lorenz A Nierves, Athena A Schepmoes, Brianna I Gonzalez, Thomas L Fillmore, Tujin Shi, Patricia S Miller, Andrew N Cowan, Karin Rodland, Fergus V Coakley, Travis L Rice-Stitt, Jen-Jane Liu, Sudhir Isharwal, Christopher L. Amling, Ryan P Kopp
Journal: Journal of Clinical Oncology (2025)

405 Background: While standard mpMRI has shown benefit in increasing detection of clinically significant prostate cancer, it is limited in its ability to detect small lesions, low Gleason scores, and certain tumor architectures. Proteomics may supplement imaging and enhance prediction of clinical outcomes. We investigated associations between MRI-mapped tumors and protein levels obtained from radical prostatectomy (RP) specimens and correlated them to adverse pathology features. Methods: This was an interim analysis of a planned cohort of 124 subjects. Patients underwent routine preoperative mpMRI and whole-mount histopathology after RP, with proteomic analysis performed on tissue from MRI-mapped tumors. A panel previously shown to improve prediction of distant metastasis in RP patients included five proteins: TGFβ-1, SPARC, FOLH1 (PSMA), CAMKK2, and tumor PSA. Protein concentrations were log transformed. Logistic regression assessed protein associations with adverse pathologic features, including extracapsular extension (ECE), seminal vesicle invasion (SVI), lymph node invasion (LNI), Gleason score ≥8, and a composite of these findings. Multivariate analyses were adjusted by patient age, PSA, Gleason Grade Group, and T stage at diagnosis. Results: 61 patients had proteomic data; mean age at diagnosis was 64 years and mean PSA at diagnosis 10 ng/dL. ECE was present in 67%, SVI 20%, LNI 21%, and Gleason score ≥8 26%; 72% had at least one adverse pathologic feature. On initial multivariate analysis of proteins alone, TGFβ-1 significantly correlated with LNI (odds ratio [OR] 24.4 [95% confidence interval (CI) 3.7-160.2], p = 0.0009) and composite adverse pathology (OR 3.1 [95% CI 1.0-9.3], p = 0.05). Even after including clinical characteristics in the model, TGFβ-1 still significantly correlated with LNI (Table). None of the other proteins significantly correlated to these markers of adverse pathology. Conclusions: In this study assessing protein associations with MRI-identified prostate tumors, TGFβ-1 was strongly predictive for LNI. TGFβ signaling has been associated with both prostate cancer suppression and promotion depending on context. Further investigation will assess if the combination of proteins in the panel is more predictive of adverse pathology. Multivariate logistic regression analyzing association between proteins and lymph node invasion. Protein Odds ratio (95% CI) p-value TGFβ-1 235.0 (4.5-N/A) 0.007* SPARC 1.4 (0.3-7.3) 0.7 FOLH1 0.8 (0.3-2.4) 0.7 CAMKK2 2.0 (0.7-5.8) 0.2 PSA 2.0 (0.7-5.6) 0.2 Protein concentrations were log transformed and models included patient age, PSA, Gleason Grade Group, and clinical T-stage at diagnosis.
Early detection of recurrent prostate cancer using 18F-DCFPyL PET/CT PET/CT in patients with minimal PSA levels.
Authors: Ida Sonni, Nicholas George Nickols, Katelyn Niknam, Gholam Reza Berenji, Derace Schaffer, Louis Montagut, Karl Sjöstrand, Aseem Anand, Matthew Rettig
Journal: Journal of Clinical Oncology (2025)

344 Background: PSMA PET imaging is a highly sensitive and specific imaging tool for detecting prostate cancer, especially in biochemical recurrence (BCR). This has led to growing interest in utilizing PSMA PET for patients with minimally detectable PSA levels following definitive treatment as conventional imaging rarely localizes recurrent disease in this range, potentially delaying diagnosis and appropriate management. However, there is limited literature on the detection rate of 18F-DCFPyL at very low PSA levels in the BCR setting. Methods: This is a pooled retrospective analysis of patients from investigator-initiated trials at West Los Angeles Veterans Affairs and the phase III CONDOR trial with minimal PSA levels. Patients included had 18F-DCFPyL PET/CT at minimal PSA values (0.05 to 0.5 ng/ml). BCR was defined as rising PSA and patients were included irrespective of prior conventional imaging findings. The PET/CT scan reads were assisted by the automated Prostate Cancer Molecular Imaging Standardized Evaluation (aPROMISE) platform. The results were verified by an experienced and independent nuclear medicine physician. Primary analysis focused on the detection rate defined as the number of patients with positive PSMA lesions relative to total number of patients with BCR. Results: In total 129 patients were identified, 36 with PSA levels ranging from 0.05 to 0.2 ng/ml, and 93 with PSA levels &gt;0.2 to 0.5 ng/ml. The site of positive findings, the intensity and volume of uptake in the 18F-DCFPyL PET/CT scan are detailed in the table below. Conclusions: 18F-DCFPyL PET/CT demonstrates high detection rate for recurrent prostate cancer even in patients with minimally detectable PSA levels, highlighting its potential as a valuable tool in early identification of metastatic disease. These findings suggest that current thresholds for initiating PSMA PET/CT imaging in BCR patients may need reconsideration to optimize early detection and subsequent clinical management. Further studies are necessary to refine guidelines and assess the cost-effectiveness of incorporating PSMA imaging at very low PSA levels. 0 – 0.2 (N=36) 0.2 – 0.5 (N=93) Total Detection Rate 13 (36%) 47 (51%) Prostate Bed 3 (8%) 4 (4%) Lymph Node Only 5 (14%) 29 (31%) Lymph Node and Bone 12 (33%) 39 (42%) Bone Only 8 (22%) 14 (15%) Visceral (Lung or Liver) 1 (3%) 10 (11%) Total SUVmean 3.8 4.2 Total SUVmax 10.9 12.4 Total disease volume (mean) 4.9 ml 1.9 ml
RadOnc-GPT (gpt-4o) versus human data extraction for prostate cancer clinical research.
Authors: Mohammad Javad Namazi, Mariana Borras Osorio, Jason M Holmes, David M. Routman, Daniel Ebner, Peilong Wang, Wei Liu, Mark Raymond Waddle
Journal: Journal of Clinical Oncology (2025)

425 Background: Prostate cancer (PC) ranks among the most prevalent cancers in men, with incidence rising due to factors like aging populations and enhanced screening techniques. Effective data extraction from clinical records is crucial for advancing research and improving patient care; however, traditional manual methods can be time-consuming and susceptible to mistakes. This study seeks to evaluate RadOnc-GPT against human annotation for extracting essential clinical information from prostate cancer clinical records. Methods: RadOnc-GPT is a retrieval augmented generation (RAG)-based chatbot with access to a variety of patient data including treatment details, radiology reports, and clinical notes. RadOnc-GPT uses Open AI’s gpt-4o model. Patients who received curative intent radiotherapy as initial treatment for PC in our institution between 2014 and 2023 were randomly selected for evaluation. Relevant Clinical factors were extracted by a human expert annotator on our on-site RedCap database. The extraction of the same variables was performed using RadOnc-GPT. A comparison between the ground truth (human annotation) and RadOnc-GPT, to evaluate the performance of the AI system, was carried out including accuracy, recall and F1 score. Results: A total of 382 PC patients were included in the cohort for data extraction. The clinical variables extracted were the treatment intent, NCCN risk category, T and N stage, Gleason score, radiation volume, and Androgen Deprivation therapy (ADT) use. The overall performance of RadOnc-GPT was excellent, with the highest accuracy achieved for treatment intent (99.7%), Gleason score (98.4%), and Treatment Volume (90.1-99.5%). Conclusions: RadOnc-GPT performed excellent at extracting relevant clinical details from the electronic medical record and radiation oncology information systems with dramatic reduction in time and cost compared with manual review. LLMs could be highly useful for large-scale data extraction in PC research, offering a promising solution for automating the accurate data extraction process. Correct (n) Total (n) Accuracy Recall F1 score RT with curative intent 381 382 99.7 99.9 99.9 Prostate Cancer Risk Category 345 382 90.3 90.4 95.1 Primary tumor staging (T) at diagnosis 368 382 96.3 96.3 97.9 Regional nodal status (N) at diagnosis 352 382 92.1 92.2 95.9 Gleason Score Primary Secondary Total 376372376 382382382 98.497.498.4 98.597.498.5 99.298.799.2 Treated Areas Prostate Pelvic Nodes Para-Aortic Nodes Distant Site 380344378372 382382382382 99.590.19997.4 99.490.199.197.4 99.79599.598.7 ADT Use with RT 365 382 95.5 95.7 97.8
Real-world outcomes in metastatic prostate cancer patients with ctDNA-detected <i>SPOP</i> mutations.
Authors: Windy Dean-Colomb, Jayati Saha, Courtney Lewis, Leslie A Bucheit, Clayton Clopton Yates
Journal: Journal of Clinical Oncology (2025)

110 Background: Comprehensive genomic profiling (CGP) is recommended for patients (pts) with metastatic prostate cancer (mPC) to inform therapy. ctDNA analysis provides rapid results with high concordance to tissue-based CGP avoiding the need for invasive biopsy. SPOP mutations ( SPOP+ ) define a novel group of mPC enriched in black pts. Tissue-based data suggests a subset of pts with SPOP+ mPC have improved outcomes with hormonal therapy and may not require intensified treatments. This study examined outcomes for mPC pts following ctDNA-detected SPOP mutations by race. Methods: Real-world (rw) data was sourced from GuardantINFORM from 2014 to September 2024. GuardantINFORM is comprised of aggregated commercial payer health claims and de-identified records from pts with clinical ctDNA testing via Guardant360 (G360). Index date was defined as the first metastatic claim post-mPC diagnosis and baseline period as the six months prior to the index date. Adult mPC pts with &gt;2 mPC claims in the baseline period were analyzed. Demographics and rw first-line outcomes (rw time to next treatment (rwTTNT) and rw overall survival (rwOS), months) in both unmatched and propensity score matched and weighted SPOP + vs. SPOP- were assessed. A subgroup analysis was also conducted by stratifying by the two main racial groups, white and black. Results: SPOP mutations were observed in 2.6% of pts meeting inclusion criteria (346/13283). 346 SPOP+ mPC pts were included as cases, of which 205 (59%) were White, 90 (26%) Black, and 51 (15%) other/unknown race; 43% had prior ADT use (n=151) and the median age was 72 years (range: 45-84). A larger proportion of black pts were in the SPOP + cohort compared to SPOP - (21.8% vs. 14.9%) with other demographics similar between cohorts (age, non-Black race, line of therapy, prior ADT use). In unmatched analyses, SPOP+ had numerically similar median rwTTNT and shortened median rwOS compared to SPOP -, although not significant [rwTTNT: SPOP + 12.7 (10.1-14.3) vs. SPOP - 12.4 (11.8-13.0); p=0.86; rwOS: SPOP + 18.3 (15.2-25.8) vs. SPOP - 21.9 (20.7-22.7); p=0.33]. Upon stratifying by race in matched and weighted cohorts, SPOP + black pts had numerically improved median rwTTNT and median rwOS compared to SPOP + white pts, yet not significant [rwTTNT: Black- SPOP + 13.7 (9.2-NR) vs. White- SPOP + 12.4 (8.3-14.5); p=0.66; rwOS: Black- SPOP + 18.9 (14.7-NR) vs. White- SPOP + 17.1 (13.1-29.1); p=0.38]. Conclusions: This data supports ctDNA use for detecting S POP mutation status in mPC. SPOP + may impact rwTTNT and rwOS among black pts. Further modeling of real-world matched cohorts and additional studies in clinical cohorts are needed to continue to assess the impact of SPOP + on patient outcomes.
Bone metastases and use of bone protective agents (BPA) for metastatic renal cell carcinoma (mRCC): A contemporary national real-world analysis.
Authors: Braden Millan, Sunita Ghosh, Naveen S. Basappa, Lori Wood, Bimal Bhindi, Frederic Pouliot, Rodney H. Breau, Antonio Finelli, Rahul K. Bansal, Jeffrey Graham, Georg A. Bjarnason, Dominick Bosse, Vincent Castonguay, Eric Winquist, Daniel Yick Chin Heng, Christian K. Kollmannsberger, Aly-Khan A. Lalani
Journal: Journal of Clinical Oncology (2025)

490 Background: Bone Metastases (BM) occur in approximately 30% of mRCC patients (pts) with evidence suggesting that they portend a worse prognosis. Systemic therapies such as tyrosine kinase inhibitors (TKIs) and immune checkpoint inhibitors (ICI) are felt to be active in these pts, with radiation therapy (RT) often employed for BM-directed treatment. The evidence for and use of BPAs, such as bisphosphonates and denosumab, is limited in the current ICI era. We investigated the outcomes of mRCC pts with BM and use of BPA in a contemporary real-world cohort. Methods: We analyzed data collected from the prospectively maintained, multi-institutional Canadian Kidney Cancer Information System (CKCis). Patients with clear cell mRCC treated between January 2011-June 2023 were included. Outcomes were compared between BM+ and BM- pts using Cox proportional hazards models. Kaplan-Meier estimates were used to assess time to treatment failure (TTF) and overall survival (OS) adjusted by IMDC criteria. Results: Of 2,307 patients with clear cell mRCC, 893 (39%) had BM+, of whom 691 (77%) underwent RT, and 139 (16%) received a BPA. Median follow-up was longer for BM- patients (34.6 vs 29.1 mos). Significant differences were noted in Karnofsky performance status (&gt; 80%: 84% vs 78%), IMDC risk group (intermediate/poor: 76% versus 82%) use of RT (35% vs 78%), and use of BPAs (2% vs 16%) between BM- vs BM+ pts (all p &lt; 0.05). In our cohort, first-line treatment in BM+ pts was monotherapy TKI (67%), doublet ICI (20%), and combination TKI+ICI (13%). Median TTF was similar in BM- vs BM+ pts: 9.6 vs 8.6 mos (HR 0.92; 95% CI 0.91-1.02). However, median OS was higher in BM- vs BM+ pts: 57.6 vs 35.8 mos (HR 0.67; 0.58-0.76; p&lt;0.0001); this was consistent irrespective of type of systemic therapy. In BM+ pts, those who did not receive BPAs had a lower TTF (7.9 vs 13.4 mos) and OS (34.0 vs 46.0 mos); however, these were not statistically different when adjusted by IMDC criteria (TTF HR 1.2; 0.95-1.51 and OS HR 1.12; 0.85-1.46). There was no significant difference in TTF (HR 0.89; 0.72-1.10) or OS (HR 0.94; 0.73-1.22) in BM+ pts selected to receive RT. Conclusions: BM remain a poor prognostic factor in mRCC in this contemporary cohort of patients. While BPA use was limited, we observed no improvement in TTF or OS in BM+ pts with their use. These data warrant further investigation of BPA in mRCC including assessment of SREs and potential complications.
Receipt of poly(ADP) ribose polymerase inhibitors (PARPi) in patients (pts) with metastatic castration-resistant prostate cancer (mCRPC) harboring <i>BRCA1/2</i> alterations.
Authors: Micah Ostrowski, Yeonjung Jo, Chadi Hage Chehade, Zeynep Irem Ozay, Georges Gebrael, Nicolas Sayegh, Edwin Lin, Ayana Srivastava, Richard Ji, Haoran Li, Vinay Mathew Thomas, Sumati Gupta, Irbaz Bin Riaz, Benjamin L. Maughan, Soumyajit Roy, Umang Swami, Neeraj Agarwal
Journal: Journal of Clinical Oncology (2025)

108 Background: PARPi are approved for the treatment of pts with mCRPC either as single agents or as a combination with an androgen receptor pathway inhibitor (ARPI) [PMID: 37442702]. In a US Food and Drug Administration (FDA) pooled analysis, the benefit from PARPi appeared greatest for pts harboring BRCA1/2 alterations [PMID: 38484203]. However, real-world uptake of PARPi in pts with mCRPC with BRCA1/2 alterations is unknown. Herein, our objective was to assess the usage of PARPi in real-world pts with mCRPC harboring BRCA1/2 alterations. Methods: A de-identified nationwide Flatiron Health electronic health record (EHR)-derived database was used to extract pt-level data. Eligibility criteria: pts with mCRPC harboring alterations in BRCA1 or BRCA2 or both and alive after 8/15/2020 (i.e., 3 months following the approval of the first PARPi, rucaparib, in mCRPC) with available treatment information. The data cutoff date was 5/31/2024. Pts were categorized into two cohorts based on the receipt of any PARPi or not. Baseline characteristics at the time of mCRPC diagnosis, including age, race-ethnicity, and insurance plan, were collected in both cohorts. Results: Of the overall cohort of 24,105 pts with metastatic prostate cancer, 443 pts had mCRPC with BRCA1/2 alterations and were eligible and included in this analysis. 227 (51.2%) received a PARPi, while 216 did not (48.8%). Among the 227 pts who received a PARPi, 166 received it as a single agent (73.1%), 40 received it in combination with an ARPI (17.6%), and 21 received it in combination with other agents (9.3%). The median age was 72 in both cohorts (IQR 65 – 79 in patients receiving a PARPi and 66 – 78 in patients who did not). Other baseline characteristics in both groups are shown (Table). Conclusions: Despite PARPi demonstrating survival improvement in pts with mCRPC with BRCA1/2 alterations, a significant proportion of pts do not receive them. Our findings highlight the need to improve education among clinicians of level 1 evidence and improve access to life-prolonging therapies in pts with mCRPC. Baseline characteristics of pts with mCRPC who received vs. did not receive a PARPi. Characteristic Subgroup Pts who received a PARPiN = 227 Pts who did not receive a PARPiN = 216 Race-ethnicity, n (%) Asian 9 (4) 1 (0.5) Black 22 (9.7) 30 (13.9) Hispanic-Latino 10 (4.4) 10 (4.6) White 149 (65.6) 124 (57.4) Other and unknown 37 (16.3) 51 (23.6) Insurance, n (%) Commercial health plan 192 (84.5) 182 (84.3) Medicare-other government programs 31 (13.7) 18 (8.3) Medicaid 1 (0.4) 3 (1.4) Others and unknown 3 (1.3) 13 (6)
Patterns of next-generation sequencing and associated next-line systemic therapy use in metastatic prostate cancer.
Authors: Julia Shi, Changchuan Jiang, Hamid Ghaderi, James B. Yu, Daniel X. Yang
Journal: Journal of Clinical Oncology (2025)

105 Background: Next-generation sequencing (NGS) testing is used for prognostication and to guide treatment choice in metastatic prostate cancer (mPC). While NGS testing is increasingly available, how its usage has impacted real-world selection of next line therapies including olaparib in mPC is unclear. Methods: We performed a retrospective observational study using the real-world nationwide U.S. Flatiron Health electronic health record-derived de-identified mPC database with patients diagnosed between January 1 st , 2013, and July 30 th , 2024. Due to limitations of follow-up, patients diagnosed with mPC in 2024 were excluded. Rates of patients with documented NGS testing within 6 months of metastatic prostate cancer diagnosis, short-interval changes in systemic therapy defined as initiation of a new therapy within 30 days after NGS testing, and olaparib initiation within 60 days of NGS testing were analysed. Results: A total of 24,222 mPC patients were included, of which 6282 (25.94%)had at least 1 documented NGS test and 1494 (23.78%) of those patients had more than 1 NGS test. NGS test documentation after metastatic diagnosis increased from 0.175% in 2013 to 22.8% in 2023. The median time from metastatic diagnosis to initial NGS testing was 413 days (IQR 76-993). The percentage of NGS tests associated with short-interval initiation of a new line of therapy increased from 14.29% of patients receiving NGS testing in 2014 to 24.19% of patients receiving NGS testing in 2023. The most common therapies initiated within 30 days after NGS testing were abiraterone (37.75%), enzalutamide (13.91%), and docetaxel (10.93%). Among patients with documented NGS testing, the percent who initiated olaparib within 60 days of an NGS test increased from 0.31% in 2015 to 17.34% in 2024, with the greatest year-on-year increase in 2020 corresponding to FDA approval for patients with homologous recombination repair gene alterations. Median time to olaparib initiation after metastatic diagnosis was 798 days (IQR 455-1383). Conclusions: There was a significant increase in rates of documented NGS test for patients diagnosed with mPC over the past decade. Furthermore, systemic therapy change appears to be more frequently influenced by NGS testing, with a significant increase in associated olaparib initiation as next-line therapy.
Association between clonal hematopoiesis and survival after nephrectomy in patients with renal cell carcinoma.
Authors: Yash Khandwala, Neil Ruthen, Ritesh R Kotecha, Paul Russo, Jonathan Coleman, Eduard Reznik, A. Ari Hakimi
Journal: Journal of Clinical Oncology (2025)

589 Background: Clonal hematopoiesis of indeterminate potential (CH) is an age-related phenomenon marked by the clonal expansion of hematopoietic stem cells harboring somatic mutations in the absence of hematologic transformation. These mutations have been linked to worse all-cause mortality from both oncologic and cardiovascular-related risk. Recent pan-cancer studies have also found that CH is common in patients treated for solid tumors and may be associated with survival. We thus sought to characterize CH mutations and their associated clinical impact in patients with localized renal cell carcinoma (RCC) at our institution. Methods: Utilizing a single institutional database of patients who underwent targeted, next-generation sequencing of paired tumor and blood samples (MSK-IMPACT), we identified 311 patients who were diagnosed with localized RCC and underwent nephrectomy. CH mutations were called using a two-tiered filtering schema, requiring a variant allele fraction (VAF) in blood greater than twice that of tumor. Chi-square and Wilcoxon rank-sum tests were used to compare clinical characteristics by CH status. Cox-proportional hazards modeling was used to test the association between CH and survival time following nephrectomy, adjusting for age and presence of diabetes, coronary artery disease (CAD), chronic kidney disease, hypertension, and smoking. We performed separate analyses for patients older and younger than the median age of 56.8 years as these groups had distinct CH, survival, and comorbidity profiles. Results: We assessed variants in 341 genes within the MSK-IMPACT CH database for 311 patients (CH: 79 [25.4%], no CH: 232 [74.6%]) who had localized RCC and underwent a nephrectomy (partial: 114 [36.7%], radical: 197 [63.3%]). DNMT3A (26), PPM1D (7), and TET2 (4) were the most common CH mutations. Patients with CH were older (median age of 64.1 years [IQR: 54.6 to 72.3] vs. 54.8 years [46.1 to 63.5]; p &lt; 0.001) and had higher incidence of CAD (8/48 [16.7%] vs. 12/263 [4.7%], p = 0.004). There was no difference in rates of diabetes, hypertension, or CKD. For patients older than the median age of 57 years, those with CH had a shorter median survival of 86 months [72 to 119] compared to 125 months [96 to NR] (p = 0.02). For patients younger than the median age, age and hypertension were significantly associated with survival time but not CH (p = 0.29). Conclusions: Our study reveals that CH is common in localized RCC patients and may be associated with worse survival especially in older patients. Given the possibility of confounding from other comorbidities, future efforts will focus on identifying the true attributable effect of CH on survival. However, CH clones have been shown to interact with tumor cells and may influence immune surveillance, potentially providing a molecular basis for these findings.