tbuckley/cabot-search huggingface dataset:
Domain-specific large language model for predicting prostate cancer treatment plan.
Authors: Umar Ghaffar, Amara Tariq, Mouneeb Choudry, Logan Briggs, Aneeta Channar, Imon Banerjee, Man Luo, Irbaz Bin Riaz, Haidar Abdul-Muhsin
Journal: Journal of Clinical Oncology (2025)

428 Background: Prostate cancer management presents a significant healthcare burden, with the need to efficiently triage patients for treatment. Our objective is to leverage large language models to predict physician-recommended treatment plans from unstructured clinical notes. By accurately predicting treatment plans, we aim to risk stratify and triage patients effectively, thereby optimizing the allocation of physician resources. Methods: 448 unstructured initial urology consultation patient notes following first positive prostate cancer biopsy were identified. The recommended and final treatments received were manually annotated to establish ground truth labels (Table 1). The dataset was split 80:20 for training and testing, preprocessed to remove plan sections and formatted into question-answer (QA) format. A domain-specific large language model (LLM) inspired by GPT and a specialized tokenizer (PCa- LLM) for prostate cancer terminology were developed. QA models were built using the PCa-LLM and compared with those using GPT-2 as the backbone to predict recommended and final treatments. Results: For the physician-recommended treatment plans, our LLM (PCa-LLM) showed superior performance with higher AUROC scores for curative vs. non-curative treatments (0.78 vs. 0.65), chemo-hormonal vs. other non-curative treatments (0.89 vs. 0.65), and surveillance vs. all other treatments (0.72 vs. 0.70), while both models achieved the same high AUROC of 0.99 for chemo-hormonal vs. all other treatments. For final treatments, PCa-LLM demonstrated better AUROC for curative vs. non-curative treatments (0.77 vs. 0.74) and chemo-hormonal vs. other non-curative treatments (0.71 vs. 0.66), while GPT2 outperformed PCa-LLM for surveillance vs. all other treatments (0.78 vs. 0.70). Both models achieved an AUROC of 0.99 for chemo-hormonal vs. all other treatments. Conclusions: PCa-LLM accurately predicted most treatment categories better than GPT2, with higher AUROC scores, and can be utilized to triage prostate cancer patients using initial consultation notes. Task Physician -Recommended Treatment Plan Final Treatment Received Curative Prostatectomy/Radiation 228 230 Non-Curative Focal Therapy 22 15 Active Surveillance 40 45 Chemo-hormonal 30 30 Model Predictions (AUROC) GPT2 PCa-LLM GPT2 PCa-LLM Curative vs. non-curative 0.65 0.78 0.74 0.77 Chemohormonal vs. other non-curative 0.65 0.89 0.66 0.71 Chemohormonal vs. all other 0.99 0.99 0.99 0.99 Surveillance vs. other non-curative 0.64 0.60 0.67 0.59 Surveillance vs. all other 0.70 0.72 0.78 0.70
Deciphering immune-genomic markers of hyperprogression in patients (Pts) with metastatic urothelial cancer (mUC) treated with immune checkpoint inhibitors (ICIs).
Authors: Nikhil Pramod, Paul G. Pavicic, Scott Dawsey, Ubenthira Patgunarajah, Kimberly Maroli, Riya Malhotra, Moshe C. Ornstein, Timothy D. Gilligan, Christopher Eing Wee, Omar Y. Mian, Amanda Nizam, Ying Ni, Jane Nguyen, C. Marcela Diaz-Montero, Shilpa Gupta
Journal: Journal of Clinical Oncology (2025)

840 Background: ICIs offer modest response rates (~20%) in mUC and there remains a critical need for validated biomarkers to predict patient benefit. Hyperprogressive disease (HPD), characterized by rapid tumor progression following ICI initiation, is a poorly understood phenomenon in mUC. No robust biomarkers currently exist to identify patients at risk for HPD, a condition that leads to unnecessary treatment and exacerbated toxicity. While patient factors associated with HPD have been studied, little is known about the tumor’s immune-genomic landscape in these cases. We investigate the immune-genomic features of mUC tumors associated with HPD to better understand and predict this response to ICI. Methods: We retrospectively analyzed 132 pts with mUC treated with atezolizumab or pembrolizumab between 2015-2023. All patients received at least 2 ICI cycles, and archival FFPE tumor samples were available for immune-genomic analysis. Pts were classified as responders (N=75, defined as complete/partial response or stable disease) or non-responders (N=57, progressive disease). HPD was defined as progression per RECIST within 14 weeks of ICI initiation. RNA was extracted from macrodissected FFPE samples, and transcriptomic profiling was performed using the Nanostring PanCancer IO 360 panel. Data were processed using nSolver 4.0 and nanostring data analysis service analyzed for differential gene expression. Receiver operator characteristic (ROC) analysis was conducted to assess the predictive power of immune signatures for HPD. Results: Of the 132 pts, 48 (36%) were classified as having HPD. Compared to non-responders without HPD, HPD tumors exhibited significant downregulation of immune signatures, including IFN Gamma, PD-L1, myeloid cells, and tumor inflammation signatures (TIS). Key chemokines and IFN downstream signaling were also downregulated (p-adj = 0.041). Single-gene analysis highlighted downregulation of CCL4 (logFC = -0.947, p = 0.00012), GBP1 (logFC = -0.8105, p = 0.00017), and NECTIN2 (logFC = -0.4792, p = 0.00032) in HPD tumors, though statistical significance was not reached after adjustment. ROC analysis demonstrated modest predictive power for HPD with AUCs of 0.66 for TIS and IFN Gamma, and 0.658 for the immunoproteasome. Conclusions: Our findings reveal a distinct immune-genomic profile in mUC tumors associated with HPD following ICI treatment, including reduced IFN Gamma, TIS, and myeloid cell signaling. These immune signatures may serve as potential biomarkers to identify pts at risk of HPD, warranting further validation in prospective trials. Ongoing analyses will continue to explore the genomic underpinnings of HPD and therapeutic resistance in mUC.
Natural history and risk-stratification of biochemical recurrence in prostate cancer treated with definitive radiotherapy.
Authors: Paul Riviere, Kylie Margaret Morgan, Tyler Nelson, Daniel Sabater Minarim, Leah N. Deshler, Matthew P. Banegas, Tyler F. Stewart, Rana R. McKay, Juan Javier-Desloges, Kellogg Parsons, Brent S Rose
Journal: Journal of Clinical Oncology (2025)

348 Background: Biochemical recurrence (BCR) of prostate cancer following radiation therapy often does not result in clinically significant events, but a subset of patients may be at higher risk of developing metastatic disease or death. Identifying these patients is critical for clinical decision making, but unlike in the post-prostatectomy setting, no method has been externally validated for BCR after radiation therapy. This study characterized outcomes after post-radiation BCR and validated a proposed risk stratification heuristic. Methods: This was a retrospective, multicenter, nationwide cohort study of patients having post-radiation BCR treated in the United States Veterans Administration Health System. High-risk post-radiation BCR was defined as either Gleason score ≥8 or BCR occurring within 18 months of radiation therapy. BCR was defined as post-treatment PSA greater or equal to PSA nadir + 2 ng/ml, initiation of androgen deprivation therapy distinct from the initial treatment course, or development of metastatic disease, whichever occurred first. Results: Median time to BCR was 42.5 months (interquartile range 22.9-73.0). Among 7,126 patients who experienced BCR, 35.5% of patients developed metastatic disease and 17.4% died of prostate cancer at 10 years. 38.5% of patients had at least one qualifying high-risk feature of whom 23.3% had high-risk recurrence based on time to recurrence alone, 57.6% based on Gleason/Grade Group alone, and 19.1% based on both criteria. High-risk BCR resulted in higher 5-year rates of metastatic disease (42.0% versus 24.5%, hazard ratio (HR) 1.83, 95% confidence interval (CI) 1.69-1.98, p &lt; 0.001), death from prostate-cancer (18.7% versus 8.78%, HR 1.82, 95% CI 1.63-2.03, p &lt; 0.001), and death from all causes (37.1% versus 30.8% rates, HR 1.18, 95% CI 1.11-1.26, p &lt; 0.001). Conclusions: A simple, two-element risk stratification tool using existing clinically data is the first validated tool for identifying patients at risk of metastases or PCSM following post-radiation BCR. Most patients experiencing BCR in this context do not develop metastases or lethal prostate cancer, making such stratification essential for treatment decision-making and refinement of patient populations for clinical trials. Further work remains on risk-adapted therapy intensification.
Outcomes of high-risk prostate-specific antigen level during active surveillance with targeted and systematic prostate biopsy.
Authors: Braden Millan, Jaskirat Saini, Mitchell J. Hwang, Charles Hesswani, Ruben Blachman-Braun, Christopher R Koller, Daniel Nethala, Brad Wood, Baris Turkbey, Sandeep Gurram, Peter A. Pinto
Journal: Journal of Clinical Oncology (2025)

343 Background: National Comprehensive Cancer Network (NCCN) recommendations for very low to intermediate-risk prostate cancer (PCa) include active surveillance (AS). Patients who develop a prostate-specific antigen (PSA) level over 20 ng/mL during AS, however, are re-classified as NCCN high-risk and are recommended to undergo definitive management. In the past decade, the diagnostic accuracy for PCa has significantly improved with a combined approach to prostate biopsies (magnetic resonance imaging and ultrasound fusion targeting + systematic). This study aims to describe the outcomes of patients who continued AS following a PSA of 20 ng/mL or higher. Methods: Patient information and clinical data were obtained from a prospectively maintained database at the National Cancer Institute (NCT02594202). Patients on AS with a minimum of one subsequent combined biopsy (fusion + systematic) following a PSA of 20 ng/mL or higher were identified. Descriptive statistics were obtained using GraphPad Prism 10.1 (Boston, Massachusetts USA). Results: A total of 20 patients were identified, of whom 15 (67.7%) subsequently underwent definitive management. Patients had a median age of 72.0 [IQR 71-74.8] years, with a median of 13 [IQR 10-12] years on AS. In the continued AS cohort, the most recent PSA was below 20 ng/mL in two patients with a median of 22.9 ng/mL [IQR 15.2 -23.6], while repeat biopsy showed benign tissue or grade group (GG) 1 disease. In those who underwent definitive management, the last PSA on AS was a median of 23.2 ng/mL [IQR 21.9-32.8], with all patients having GG 2 or higher disease. Twelve patients underwent surgery and three external beam radiotherapy with long-term androgen deprivation therapy, within a median time of 2 mos [IQR 2.0 - 2.5 mos] after their last biopsy. For those who underwent surgery, 4 (33.3%) had GG upstaging, 2 (16.7%) had GG downstaging, while 6 (50.0%) had no change in overall GG on final pathology. The first post-operative PSA was undetectable in all but one patient. Conclusions: A PSA greater than 20 ng/mL is a high-risk feature that continues to have clinical significance during AS in the contemporary era of combined prostate biopsies. In our small cohort, one quarter of the patients remain on AS, while three-quarters of the patients underwent definitive management. GG upgrading occurred in one third of patients and therefore continued AS in these patients should be approached with caution and limited to those with benign findings or GG 1 disease on follow-up combined biopsy.
Population-based assessment of treatment patterns for high-risk localized prostate cancer.
Authors: Christopher J.D. Wallis, Shawn Malone, Ilias Cagiannos, Robert James Hamilton, Naveen S. Basappa, Cristiano Ferrario, Geoffrey Gotto, Ricardo Fernandes, Tamim Niazi, Chris Morash, Ricardo A. Rendon, Fred Saad, Sebastien J Hotte, Brendan J.W. Osborne, Anousheh Zardan, Bobby Shayegan
Journal: Journal of Clinical Oncology (2025)

349 Background: Patients diagnosed with high- or very high risk (H/vHR) prostate cancer (PCa) are at substantial risk of disease recurrence, metastasis, and death after treatment. Historically, treatment paradigms for these patients have been similar to those with intermediate-risk (IR) disease [radiotherapy (RT) with androgen deprivation therapy (ADT) and radical prostatectomy (RP)] though there is a growing body of evidence supporting intensified systemic therapy in this group. To contextualize this emerging trial data, we characterized real world treatment patterns for these patients. Methods: We performed a retrospective population-based cohort study using province-wide linked administrative data in Ontario, Canada. We descriptively characterized initial treatment patterns (within 1 year of diagnosis) for men with H/vHR PCa and compared them to a concurrent cohort of patients with IR disease to assess differences in management. Results: We identified 13,206 patients diagnosed with H/vHR PCa from 2010-2021 who were compared to 18,365 with IR disease. Most patients received active treatment, though rates were statistically significantly higher in the H/vHR (n=12,606, 95.5%) than IR cohort (n=14,995, 81.6%; p&lt;0.001; standardized diff 0.44). 6207 (47%) of patients in the H/vHR cohort and 7286 (40%) of patients in the IR cohort underwent RP (p&lt;0.001; standardized difference 0.148). Median time to RP was 98 days in the HR cohort and 105 days in the IR cohort (Median time (Q1-Q3); p&lt;0.003; standardized difference 0.11). 6321 (47.9%) of those with H/vHR disease and 7427 (40.4%) of those with IR disease underwent radiotherapy (p&lt;0.001; standardized difference 0.150). Very few patients received intensified systemic therapy: 77 patients (0.2%) received chemotherapy and 49 (0.2%) received androgen receptor pathway inhibitors. While treatment patterns were similar, patients with H/vHR disease were more likely to progress to metastasis (46% vs 30%, p&lt;0.001) and more rapidly (2.6 vs 4.3 years, p&lt;0.001), with similar patterns observed for CRPC, mCRPC treatment, prostate cancer events, and death. Conclusions: Despite higher rates of treatment, patients with H/vHR localized disease experience significantly worse clinical outcomes than those with IR. These data highlight the need for therapies which can improve clinical outcomes in this patient population, such as the potential use of intensified systemic therapies including Androgen Receptor Pathway Inhibitors (ARPIs).
Association between sociodemographic marginalization and receipt of intensified treatment for metastatic castrate-sensitive prostate cancer.
Authors: Christopher J.D. Wallis, David-Dan Nguyen, Raj Satkunasivam, Khatereh Aminoltejari, Amanda Elizabeth Hird, Soumyajit Roy, Scott C. Morgan, Shawn Malone, Bobby Shayegan, Girish S. Kulkarni, Quoc-Dien Trinh, Laura Rosella, Rodney H Breau, Aly-Khan A. Lalani
Journal: Journal of Clinical Oncology (2025)

96 Background: Intensified treatment beyond androgen deprivation therapy (ADT) has been shown to improve survival in patients with metastatic castrate-sensitive prostate cancer (mCSPC). However, real-world utilization remains inadequate. To assess potential differential access to such life-prolonging treatments, we assessed the association between sociodemographic marginalization and receipt of intensified treatment in patients newly diagnosed with mCSPC within a universal healthcare system. Methods: We performed a population-based cohort study of men aged 66 years or older diagnosed with de novo mCSPC in Ontario, Canada from Jan 2014-Nov 2021. Hierarchical regression models adjusting for patient, tumor, and physician characteristics were used to estimate odds ratios (OR) and 95% confidence intervals (CI) for the association between patient marginalization, measured by the Ontario Marginalization Index (ON-MARG), and receipt of intensified treatment, within 6 months of diagnosis. ON-MARG, a validated measure created using Canadian census data, provides area-level measures of marginalization in four domains: (1) households and dwellings; (2) material resources; (3) age and labour force; and (4) racialized and newcomer populations. Results: Among 6,051 patients, 1,465 (24%) received intensified treatment. Higher levels of composite marginalization were associated with a lower likelihood of receiving intensified treatment (OR 0.91, 95% CI 0.83–0.99, p=0.03). When examining individual domains of marginalization (Table 1), the racialized and newcomer populations domain showed the strongest negative association with the receipt of intensified treatment (OR 0.89, 95% CI 0.81–0.97, p=0.01). Conclusions: Sociodemographic marginalization, particularly among racialized and newcomer populations, is associated with lower rates of intensified treatment in patients with de novo mCSPC, even within a universal healthcare system, further contributing to known disparities in prostate cancer outcomes. Association between ON-MARG domains and treatment intensification among patients with de novo mCSPC in adjusted models.* ON-MARG Domain Effect Estimate (95% CI) Households &amp; Dwellings OR 0.92 (0.85-0.98), p=0.02 Material Resources OR 0.93, (0.86-0.99), p=0.03 Age &amp; Labour Force OR 0.99, (0.94-1.04), p=0.65 Racialized &amp; Newcomer Populations OR 0.89, (0.81-0.97), p=0.01 *Each ON-MARG Domain was modelled in separate multivariable models adjusting for patient characteristics including age at diagnosis, Charlson comorbidity category, and area; tumor characteristics including Gleason score at diagnosis; as well as physician age, sex, years in practice, specialty, and group volume.
Phase II trial of image-guided oligometastatectomy and radiation therapy in recurrent prostate cancer (SOAR).
Authors: Alejandro Sanchez, Umang Swami, Bogdana Schmidt, Christopher B. Dechet, Kenneth M Boucher, Lisa Chapman, Hillary Davis, Jeff Linton, Erica Farr, Samuel Leonhart, Josiah Hawks, Skyler B Johnson, Jonathan David Tward, Bismarck Odei, Sumati Gupta, Neeraj Agarwal, Brock ONeil, Benjamin L. Maughan
Journal: Journal of Clinical Oncology (2025)

38 Background: In a subset of patients with molecular-imaging defined recurrent oligometastatic prostate cancer (PCa), salvage oligometastatectomy with surgery and/or radiation may provide improved androgen deprivation therapy (ADT)-free survival. Methods: This is a phase II trial with oligorecurrent PCa after primary prostatectomy or radiation therapy detected on Axumin (n=11) or Prostate-Specific Membrane Antigen (PSMA) (n=9) positron emission tomography. Oligometastatic disease was defined as ≤ 10 total sites, either of lymph node (LN) only (Group A), bone only (Group B), or LN and bone (Group C). Surgical intervention for patients with LN disease included extended pelvic and/or retroperitoneal LN dissection, depending on the location of the LNs. Groups A and C received adjuvant IMRT without ADT if PSA response was ≥ 1/3 decrease but remained ≥ 0.2 ng/dL. The primary outcome was a reduction in PSA by ≥ 50% at 6 months. Secondary objectives included PSA progression free-survival (PSA-PFS), ADT-free survival, and safety. Results: We accrued a total of 20 patients. The median age was 65 years (IQR 61-70), 95% (19/20) had an ECOG of 0, and 10% (2/20) were Hispanic. All patients had a prior prostatectomy, after which 45% (9/20) received adjuvant/salvage RT, with 33% (3/9) including the pelvis/ prostate bed. 30% (6/20) had exposure to ADT before trial treatment. The median time from definitive prostate cancer treatment to trial treatment was 2.8 years (IQR: 0.9-6.0). Oligorecurrent disease occurred as lymph nodes only (18/20; 90%) or bony (2/20; 10%). Within Group A, one patient completed adjuvant RT. The average number of imaging-identified positive LNs was 1.8 (range 1-6). The primary endpoint of reduction in PSA by ≥ 50% at 6 months was 40% (95%CI 19-64%) (Table 1). The secondary endpoint of PSA-PFS at 12 months was 84.4% (95%CI 66.6-100%). ADT-free survival at 12-months was 71.4% (95% CI 52.7% - 96.6%). There were no Clavien Grade III-IV complications. Conclusions: Salvage treatment of oligometastatic disease after prostatectomy or radiation identified on molecular imaging is feasible and safe. Nearly half the cohort had a good response to salvage treatment, demonstrated by a ≥ 50% reduction in PSA at 6 months. Ongoing analyses include comparing imaging and pathology correlations, and comparing complete/ partial responders and treatment failure. Further research is needed to identify ideal candidates for salvage treatment. Clinical trial information: NCT03796767 . PSA progression-free survival at 6- and 12-months (PFS). Time Estimate 95% Confidence Interval 6 months 100% --- 12 months 84.4% 66.6-100%
Utility of extended interval dosing of denosumab in patients with metastatic prostate cancer.
Authors: Stephanie Schneck, Rebecca Hassoun, Sandra K. Althouse, Jennifer King, Tareq Salous, Nabil Adra
Journal: Journal of Clinical Oncology (2025)

68 Background: Bone modifying agents, such as zoledronic acid and denosumab, are commonly used in patients (pts) with metastatic solid tumors to reduce the incidence of skeletal-related events (SREs). The FDA-approved administration schedule for both agents is every 4 weeks, however less frequent administration (i.e. every 12 weeks) is commonly observed in practice due to patient convenience. The efficacy and safety of these extended interval regimens is well-established for zoledronic acid, however there is little evidence available supporting this practice with denosumab. Methods: Pts with metastatic prostate cancer were evaluated for development of SREs during treatment with extended intervals of denosumab. 103 pts evaluated and treated at Indiana University Health between September 2019 and September 2024 were included in this analysis. A historical control group of pts receiving every 4-week dosing was used as comparison (1). SREs were defined as pathologic fracture, spinal cord compression, operation, or radiation to bone. Extended interval dosing is defined as an administration schedule &gt;4 weeks apart on a consistent basis. Results: Median age at starting bone preserving agent was 70.6 years (range, 49.5-90). 24 pts (23.3%) had metastatic castration-sensitive prostate cancer and 79 pts (76.7%) had metastatic castration-resistant prostate cancer (mCRPC) at time of last follow-up. Incidence of SREs in all patients receiving extended interval denosumab was 23.3%. The incidence of SREs in patients with mCRPC receiving extended interval dosing was 26.6%. This compares favorably to historical data with incidence of SRE in the every 4 weeks dosing group at 35.9% (p=0.10). Median time to development of SRE was not estimable when all patients in the denosumab extended interval group were included in analysis. Median time to SRE in the mCRPC extended interval dosing group was 42.8 months and 20.7 months in the historical every 4-week dosing group (p&lt;0.01). SREs identified for all patients receiving extended dosing interval denosumab were pathologic fracture (3, 2.9%), spinal cord compression (1, 1.0%), surgery (2, 1.9%), and radiation to bone (22, 21.4%). Conclusions: Our findings suggest that extended interval dosing of denosumab in patients with metastatic prostate cancer is not associated with an increased risk of development of SREs and may offer convenience for pts. Larger prospective studies are needed to validate these findings. 1. Fizazi K, Carducci M, Smith M, et al. Lancet 2011; 377: 813–822.