tbuckley/cabot-search huggingface dataset:
Real world evidence from a retrospective multi-center analysis on first-line therapy for metastatic renal cell carcinoma with chromophobe histology.
Authors: Pia Paffenholz, Jozefina Casuscelli, Stefanie Zschaebitz, Emily Rinderknecht, Angelika Mattigk, Anna-Lisa Volk, Philipp Ivanyi, Thomas Hilser, Christopher Darr, Luka Flegar, Katrin Schlack, Daniel Seidl, Analena Handke, Melanie Klee, Tim Nestler, Marc Rehlinghaus, Sameh Hijazi, Axel Heidenreich, Viktor Grünwald
Journal: Journal of Clinical Oncology (2025)

488 Background: Chromophobe (chRCC) renal cell carcinoma are rare cancers and obtain a worse prognosis. We evaluated real-world treatment outcomes of 1 st line treatment in these cohort in Germany. Methods: We retrospectively analyzed patients with metastatic chRCC treated at 17 German tertiary cancer centres being treated from 2008-2023. Adverse events (AE) were reported according to CTCAE 5.0, objective response rate (ORR) according to local standard of radiological and clinical judgement. Progression free survival (PFS) and overall survival (OS) were calculated from start of treatment to progression or death, respectively and determined by KM plots. Results: We included 39 patients with a median age of 59 (IQR 55-71) years. ECOG PS was 0/1/≥2 in 70/17/12%. IMDC risk was favorable/intermediate/poor in 13/61/26%. 87% received prior nephrectomy. Lymphatic (58%), pulmonary (37%) bone (34%) and metastases were the most common metastatic sites. 52% patients received first-line IO-combinations (IO-IO: 43%, TKI-IO: 57%) and 48% patients TKI-monotherapy, predominantly sunitinib. Subsequent therapy was mostly Cabozantinib (after IO-IO), Lenvatinib/Everolimus (after IO-TKI) or Nivolumab (after TKI mono). AE of all grades occurred in 59% and 71% during IO-based therapy or TKI monotherapy, and CTCAE grade ≥3 in 29% or 25%, respectively. ORR and survival outcomes with median follow-up of 14 months (IQR 7-28) are described in the table. Conclusions: IO-combinations are frequently applied in chRCC. Our data suggests that first-line IO-/TKI-based combinations yields higher ORR compared to IO-/IO-based combinations and single agent TKI, but did not translate into an improved PFS or OS. The retrospective nature and small sample size are major limitations of our analysis. However, the rarity of metastatic chRCC contributes to inconsistent findings not only in our dataset but also across previously published studies, making it difficult to establish clear treatment guidelines. Further research is essential to refine treatment strategies for patients with metastatic chRCC. ORR and survival outcomes of study population. Parameter All therapies (n=31) IO/IO (n=8) IO/TKI (n=10) TKI (n=13) ORR (CR+PR) 19% 12,5% 30% 15% SD 16% 12,5% 40% 0% PD 65% 75% 30% 85% ORR vs. SD vs. PD - p=0.05 Parameter All therapies IO/IO IO/TKI TKI mPFS, months, 95% CI 3 (0,0-10,2) 3 (2,4-3,6) 8 (0,0-19,2) 4 (0,0-10,2) - P=0.077 mOS; months, 95% CI 24 (22,7-25,3) 12 (2,3-21,7) NR (NR-NR) 24 (22,5-25,5) - p=0.183
Radiographic progression without PSA progression in advanced prostate cancer patients.
Authors: Ruchi Chaudhary, Amitabha Bhaumik, Neeraj Agarwal, Kristin Michelle Shotts, Angela Lopez-Gitlitz, Sharon McCarthy, Suneel Dinkar Mundle, Kim N. Chi, Eric J. Small
Journal: Journal of Clinical Oncology (2025)

213 Background: Androgen Receptor Pathway Inhibitors (ARPIs) are frequently combined with Androgen Deprivation Therapy (ADT) to treat prostate cancer patients (pts) with castration sensitive (CSPC) or castration resistant (CRPC) disease. We sought to characterize pts who experienced radiographic progression without PSA progression (R-PD) while under treatment with ADT with or without an ARPI. Methods: We undertook a retrospective analysis of two phase 3 trials testing apalutamide (Apa) + ADT vs Placebo (Pbo) + ADT: TITAN (NCT02489318) in pts with metastatic CSPC (mCSPC) and SPARTAN (NCT01946204) in pts with non-metastatic CRPC (nmCRPC). We compared pts with R-PD with pts who experienced PSA progression before or concurrently with radiographic progression (PSA-PD). Kaplan-Meier and Cox proportional-hazard models were used to estimate time-to-event and hazard ratios. Results: The distribution of types of progression, and location of R-PD by study is shown in the table. Pts with R-PD had shorter overall survival (OS) compared with PSA-PD pts in both studies (median OS R-PD vs PSA-PD: 22.9 m vs 37.4 m in TITAN; 49.8 m vs 53.7 m in SPARTAN). Compared with Pbo, Apa delayed the time to R-PD in both studies (HR 0.51, 95% CI: 0.36 to 0.73 in TITAN; HR 0.17, 95% CI: 0.1 to 0.28 in SPARTAN). No pre-treatment variables predictive of R-PD vs PSA-PD were identified; transcriptional profile analysis is ongoing. Conclusions: Radiographic progression in the absence of PSA progression is not uncommon amongst patients with advanced prostate cancer, and carries a poor prognosis. The addition of Apa prolongs the median time to R-PD. Our findings underscore the importance of monitoring these pts with imaging, independent of PSA dynamics. The impaired survival of R-PD pts warrants evaluation of new therapeutic approaches for these pts. OVERALL TITAN (mCSPC; n=1052) SPARTAN (nmCRPC; n=1207) % pts with R-PD 12.4% 10.4% % pts with PSA-PD 41.2% 45.4% Sites of progression in R-PD pts (% of randomized pts) Bone only 6.3% 1% Non-bone 6% 8.8% Both 0.1% 0%
Trends in kidney cancer: Exploring the impact of sex and age on stage of disease, and prognosis during the past three decades in Denmark—A DaRenCa study.
Authors: Johanne Ahrenfeldt, Jesper Huitfeld Jespersen, Jens Ejrnæs Tønder, Laura Iisager, Anna Krarup Keller, Niels Fristrup, Tinne Laurberg, Iben Lyskjær
Journal: Journal of Clinical Oncology (2025)

485 Background: Over the past 30 years, renal cell carcinoma (RCC) management has undergone significant advancements, driven by increased diagnosis through imaging scans and the development of more effective systemic therapies for metastatic disease. Understanding the impact of early detection and evolving treatment strategies on patient outcomes is crucial for guiding future advancements in RCC care. This nationwide registry-based cohort study investigates how the number of RCC cases, stage at diagnosis, and prognosis have changed during the past 30 years in Denmark, and how these are associated with sex and age. Methods: A population-based cohort was established, including all Danish patients aged 18 and older diagnosed with RCC from 1992 to 2021, excluding individuals with a prior cancer history. Patients were identified and followed from the date of diagnosis until death or end of follow-up using nationwide register data. Comorbidities prior to RCC diagnosis were assessed using nationwide hospital admittance records. Results: A total of 17,423 RCC patients were diagnosed during the past 30 years in Denmark. The male-to-female ratio changed significantly from 0.59:0.41 in 1992-1996 to 0.72:0.28 in 2017-2021 (P &lt; 0.001). The age distribution of patients at diagnosis remained relatively constant (ranging from 65-67 years). The number of RCC cases increased from 2,244 in 1992-1996 to 3,947 in 2017-2021. We observed stage migration over time, with Stage I cases increasing from 30% in 2002-2006 to 55% in 2017-2021, and Stage IV cases decreasing from 45% in 2002-2006 to 20% in 2017-2021, while the absolute number of metastatic cases remained relatively unchanged. The median survival of patients with metastatic disease steadily increased by 314% from 4.1 months in 1992-1996 to 12.9 months in 2017-2021. Additionally, married patients showed better survival than divorced and unmarried patients. Conclusions: During the past 30 years, the number of RCC cases in Denmark has increased, primarily driven by early-stage tumors, while the number of metastatic cases has remained stable. Additionally, the proportion of female patients has decreased across all stages of RCC during the observation period. Overall survival has significantly improved over time, highlighting the impact of early detection and treatment advancements. Despite only studying Danish patients, this study serves as a reference for how patient dynamics have evolved with the advancements in the diagnosis and treatment of RCC.
Real-world discontinuation and efficacy data of abiraterone acetate/prednisone (AAP) plus androgen deprivation therapy and radiotherapy in localized prostate cancer.
Authors: Fabrizio Di Costanzo, Xue Yan Jiang, John A. Frew, Ian Pedley, Emma Shakespeare, Mariajulia Lagonera, Noor Md Haris, Saira Bashir, Ruth Plummer, Alastair Greystoke, Christoph Oing, Luigi Formisano, Pasquale Rescigno, Robert Chandler
Journal: Journal of Clinical Oncology (2025)

367 Background: Data from STAMPEDE trial confirmed Overall survival benefit for patients with high-risk localized or locally advanced prostate cancer treated with Radiotherapy (RT) plus 24-month Abiraterone/prednisone (AAP) and ADT. Nevertheless, a 17% discontinuation rate in the experimental arm of the trial was reported. Here we present a cohort of patients treated with this regimen at two Institutions. Methods: We conducted a retrospective analysis of patients with localized or locally advanced prostate cancer who underwent treatment with AAP+ADT+RT with at least 18 months of follow-up. Primary endpoint was the discontinuation rate of AAP in the ITT population. Secondary endpoints included PSA decline rate, PSA nadir &lt;0.02 ng/mL and safety. Clinical data were collected from patients’ electronic records. GraphPad Prism software was used for chart design, data comparison and statistical analysis. Results: Overall, 104 patients completed RT (60 Gy in 20#) and met inclusion criteria for this analysis. Of them, 61 (58.7%) patients had N0 disease, while 43 (41.3%) had N1 disease. AAP was discontinued prior the pre-planned two years in 29/104 (27.9%) patients. Among those who discontinued, median duration of AAP was 13.5 mo [3.2-23.5], while median duration of ADT was not reached [6.1-35.9]. Reasons for AAP discontinuation included hepatotoxicity (n=8), heart concerns and oedema (n=7 and 2, respectively), brain fog (n=2), hypokalaemia (n=2), quality of life deterioration (n=5), other (n=3). In total, 73/104 patients (70.2%) reached a PSA nadir &lt;0.02 ng/mL at the 18-month analysis. No significant difference in achieving a PSA &lt; 0.02 ng/mL was seen between those stopping AAP early (20/29 - 69%) and those who didn't (53/75 - 70.7%). Conclusions: Our analysis revealed a notably high rate of early discontinuation of AAP in the real-world setting in patients treated for their localized prostate cancer when compared to what observed in the STAMPEDE trial. Nonetheless, early discontinuation did not negatively impact on short-term treatment efficacy as a possible surrogate for long-term treatment benefit. Future studies on larger populations with longer follow-up are warranted to confirm these results.
Association between PD-1 expression on tumor-infiltrating regulatory T cells and resistance to first-line nivolumab in advanced clear cell renal cell carcinoma: Insights from the HCRN GU16-260 clinical trial.
Authors: Razan Mohanna, Berkay Simsek, Nourhan El Ahmar, Opeyemi Jegede, Sayed Matar, Morgan Paul, Yasmin Nabil Laimon, Gabriel Roberti De Oliveira, Andrew Delcea, Toni K. Choueiri, David A. Braun, Naomi Balzer Haas, Hans J. Hammers, Mehmet Asim Bilen, Mark N. Stein, Jeffrey A. Sosman, Catherine J. Wu, David F. McDermott, Michael B. Atkins, Sabina Signoretti
Journal: Journal of Clinical Oncology (2025)

590 Background: Inhibition of PD-1 signaling in regulatory T cells (Tregs) has been shown to enhance their immunosuppressive function. We previously demonstrated that high levels of PD-1 expression on tumor-infiltrating Tregs are associated with resistance to nivolumab (nivo) monotherapy in pretreated patients with advanced clear cell renal cell carcinoma (ccRCC) from the CheckMate-025 trial (Denize et al, 2024). Here, we aim to validate these findings in the first-line setting. Methods: Primary tumor tissues from patients with ccRCC (n=70) treated with first-line nivo in the HCRN GU16-260 clinical trial were analyzed using multiparametric immunofluorescence (IF). The percentage of tumor-infiltrating PD-1+ Tregs was quantified by image analysis. Associations with objective response rate (ORR) and progression-free survival (PFS) were evaluated using logistic and Cox regression models, along with Fisher’s exact test and log-rank test for statistical inference, as appropriate. The alpha level was set at 5% (one-sided). Results: In line with our previous findings, the percentage of PD-1+ Tregs, measured as a continuous variable, did not have a statistically significant association with PFS [HR = 2.62; p = 0.169] or ORR [OR = 0.72; p = 0.42]. Using an optimized cut-off based on the minimal p-value for ORR, patients with a high percentage (≥36%) of PD-1+ Tregs (8/70) experienced shorter median PFS (3.4 vs. 10.9 months; p = 0.001) and a trend toward lower ORR (12.5% vs. 43.6%; p = 0.093) compared to those with a low percentage (62/70). Conclusions: PD-1 expression on tumor-infiltrating Tregs is associated with worse outcomes to first-line nivo therapy in patients with advanced ccRCC, confirming our previous findings. These results highlight the therapeutic potential of targeting Tregs to overcome resistance and improve the efficacy of PD-1 blockade, which is currently being evaluated in a clinical trial (HCRN GU22-587).
Chronic obstructive pulmonary disease mortality risk in renal cell carcinoma: A population-based study from 1992-2021.
Authors: Oboseh John Ogedegbe, Olanipekun Lanny Ntukidem, Sakshi Bai, Ayobami Gbenga Olafimihan, Peter Egwom, Duresha Malik
Journal: Journal of Clinical Oncology (2025)

450 Background: Renal Cell Carcinoma (RCC) is one of the most common malignancies in the United States, with about 82000 new cases and 15000 deaths each year. Over the years, RCC mortality rates have been on a downward trend, and this is attributable to cutting-edge research and treatment modalities; however, non-cancer deaths continue to have an increasing trend. Chronic Obstructive Pulmonary Disease (COPD) plays a significant role in this trend. We holistically evaluated the COPD mortality risk in patients with RCC. Methods: We utilized the Surveillance, Epidemiology, and End Results (SEER) database to retrieve cases of RCC with mortality secondary to COPD from 1992 to 2021. The histologic code for RCC in the SEER database is 8312/3, which is part of the International Classification of Diseases for Oncology, Third Edition (ICD-O-3). We then obtained the standardized mortality rates (SMR) and absolute excess risk (AER). Results: We compared the COPD mortality risk of each group to the general US population and noted significantly increased COPD SMRs. Patients with non-COPD causes of death and patients with unknown age, race and cancer stage were excluded. Regarding race, Non-Hispanic American Indians had the highest risk of COPD mortality (SMR 15.30, CI 3.16-44.71, AER 1029.25), followed by Non-Hispanic Asian/Pacific Islanders (SMR 8.67, CI 5.22-13.55, AER 1781.62), then Hispanics (SMR 3.67, CI 2.63-4.97 994.43), Non-Hispanic Whites (SMR 2.69, CI 2.44-2.95, AER 788.19), Non-Hispanic Blacks (SMR 2.33, CI 1.67-3.16, AER 648.94). Based on cancer stage, distant had the highest risk of COPD mortality (SMR 16.65, CI 9.70-26.65, AER 3985.35) while regional had relatively the lowest risk (SMR 3.62, CI 2.18-5.65, AER 1174.61) with localized (SMR 4.00 CI 3.37-4.72, AER 1572.98). In terms of age, patients aged 40-59 years had an SMR of 5.33 (CI 4.28-6.56, AER 619.66), 60-79 years had an SMR of 2.73 (CI 2.45-3.03, AER 838.76), while 80 years and above had an SMR of 2.00 (CI 1.63-2.43, p&lt;0.05, AER 1261.89). Conclusions: We evaluated the extent of the risk of COPD-related deaths in RCC patients. Compared to the general United States population, patients with RCC have a higher risk of COPD mortality. Therefore, there is a need to improve primary and secondary preventive modalities and modify risk factors in this subset of patients to reduce morbidity and mortality.
Clinical and radiographic trends in patients with renal angiomyolipomas (AML).
Authors: Mouneeb Choudry
Journal: Journal of Clinical Oncology (2025)

458 Background: Renal angiomyolipoma (AML) is a common benign solid tumor of the kidney, typically found incidentally through imaging. These tumors can also present with symptoms like flank pain, hematuria, or retroperitoneal bleeding. AMLs are usually monitored and treated when they reach sizes between 4 and 6 cm based on clinical judgment, although the timing for intervention remains debated. This study aimed to investigate growth rates, assess radiographic features, and evaluate trends in clinical presentation. Methods: This multicenter, single-institution retrospective study reviewed patients diagnosed with renal AML at three Mayo Clinic locations (Rochester, Arizona, Jacksonville) from 1997 to 2021. Eligible patients had at least three abdominal scans over a minimum of two years and 36 months of follow-up. We reviewed radiologic reports, images, and charts to record demographics, tumor characteristics, imaging modalities, intervention rates, tumor sizes, and growth rates. The Mann-Whitney and Fisher exact tests were used for comparisons. Results: Among 839 patients, most were female (81.6%), with a median age of 58.55 years. Bleeding patients had significantly larger initial tumors (median 6.50 cm) compared to non-bleeding patients (median 1.20 cm), p &lt; 0.001. Treatment with everolimus was more common in bleeding patients (12.2% vs. 2.1%), and the prevalence of tuberous sclerosis was higher in the bleeding group (19.5% vs. 6.3%). All bleeding patients underwent intervention, while 22.3% of the overall cohort received treatment. Follow-up duration and total scans did not differ significantly between groups. Over 12 months, non-bleeding patients had a median growth change of 0.00 cm [IQR: 0.00, 0.30], whereas bleeding patients showed a median growth change of 0.40 cm [IQR: 0.15, 1.00], p = 0.002. Conclusions: This study reveals significant differences in characteristics and growth patterns of renal angiomyolipomas between bleeding and non-bleeding patients. Bleeding patients had larger initial tumors and greater growth changes over time. Further studies on radiographic features may help identify lesions needing earlier intervention. Demographic and clinical characteristics of patients with renal AML: Comparison bleeding vs non-bleeding groups. Overall Non-bleeding Bleeding P-Value N 839 798 41 Gender (%) Female 685 (81.6) 650 (81.5) 35 (85.4) 0.793 Male 152 (18.1) 146 (18.3) 6 (14.6) Unknown 2 (0.2) 2 (0.3) 0 (0.0) Age (median [IQR]) 58.55 [47.04, 66.95] 58.72 [47.32, 67.19] 53.84 [42.88, 60.82] 0.015 Follow up (months) (median [IQR]) 45.30 [37.12, 89.15] 46.45 [36.32, 89.52] 39.70 [36.30, 61.63] 0.233 Total scans (median [IQR]) 3.00 [3.00, 5.00] 4.00 [3.00, 5.00] 3.00 [3.00, 4.00] 0.282 Initial size (cm) (median [IQR]) 1.30 [0.80, 2.70] 1.20 [0.70, 2.50] 6.50 [3.00, 9.30] &lt;0.001 Everolimus (%) Yes 22 (2.6) 17 (2.1) 5 (12.2) 0.001 Tuberous sclerosis (%) Yes 58 (6.9) 50 (6.3) 8 (19.5) 0.003 Intervention (%) Yes 187 (22.3) 147 (18.4) 41 (100) &lt;0.001
Efficacy and safety of fexagratinib (Fexa) in combination with tislelizumab (T) in a phase II study of patients (pts) with locally advanced or metastatic urothelial carcinoma (mUC) harboring FGFR alterations (FGFRa).
Authors: Xiaojie Bian, Dingwei Ye, Lijun Chen, Changlu Hu, Shusuan Jiang, Nianzeng Xing, Qingyun Zhang, Shuang Zhang, Jimin Chen, Fan Cheng, Guiling Li, Bin Hu, Gongxian Wang, Haitao Niu, Hui Chen, Jinjian Yang, Peng Zhang, Quan Yuan, Xi Gu, Yichao Chen
Journal: Journal of Clinical Oncology (2025)

789 Background: A significant proportion of pts with mUC are intolerant to platinum-based chemotherapy, highlighting the urgent need for alternatives. Fexagratinib(former AZD4547)is a potent and selective inhibitor of FGFR and had showed promising anti-tumor activity in mUC pts with FGFRa. This Phase II study (NCT05775874) aimed to evaluate efficacy of Fexa plus T combination treatment (Tx) in mUC pts harboring FGFRa who were 1st-line platinum-ineligible or rejected chemotherapy. Methods: FGFR3 mRNA overexpression were detected by in situ hybridization (RNAscope). FGFR3 activating mutations or fusions were detected by NGS. Eligible pts received continuous oral Fexa 80mg BID plus T 200 mg infusion on day 1 of a 21-day cycle. Primary objectives were objective response rate (ORR) by Independent Review Committee (IRC) per RECIST 1.1. Results: As of data cut off (10 Aug 2024), 26 pts received combination Tx with the majority being treatment-naïve. Of those, 57.7% were male with median age of 68.5 years and 86% had an ECOG of 1. Nine pts had confirmed FGFR3 mutation or fusion and 24 pts were overexpression. In 22 pts with available PD-L1 expression status, 86.4% were negative (CPS&lt;10). Among 24 IRC evaluable pts, 9 (37.5%) partial responses (PRs) were confirmed. The median duration of response was 5.9 months. The median progression free survival mPFS was 5.3 months (95%CI 2.7-8.2) with 4 pts were still on Tx. Among the evaluable pts with FGFR3 overexpression but without mutation/fusion, ORR was37.5%,(6/16)pts.Most common treatment-related adverse events (TRAEs) were stomatitis (42%), anemia (38.5%), AST/ALT increased (27%). Grade ≥3 TRAEs occurred in 12 (46.2%) pts, incidence &gt;10% events included stomatitis (n=3, 12%), hand-foot syndrome(n=3, 12%). Immune-related AEs occurred in 23.0% of pts. The majority of TRAEs were reversible. Conclusions: 1st-line Tx with Fexa plus T were tolerable with a safety profile consistent with previously reported for both agents. The toxicity was overall manageable. Encouraging efficacy was observed in pts with FGFR3 overexpression, regardless of PD-L1 expression or FGFR3 mutations/fusions.Further exploration of these findings is warranted. Clinical trial information: NCT05775874 .