tbuckley/cabot-search huggingface dataset:
Observational study of tislelizumab (Tisle) combined with pazopanib in reducing venous tumor thrombus in clear cell renal cell carcinoma with venous invasion.
Authors: Baihetiya Azhati
Journal: Journal of Clinical Oncology (2025)

481 Background: Renal cell carcinoma with venous tumor thrombus (RCC-VTT) presents significant surgical challenges, often requiring complex interventions. Neoadjuvant therapies that can reduce primary tumor size and venous tumor thrombus may simplify surgical procedures and decrease associated risks. Methods: The data of pts with RCC-VTT who underwent Tisle combined with Pazopanib neoadjuvant therapy at the First Affiliated Hospital of Xinjiang Medical University from Nov. 2021 to Jan. 2024 were analyzed. Inclusion criteria were as follows: (1) age ≥ 18 years; (2) TNM stage T3-4N0-1M0-1; (3) Eastern Cooperative Oncology Group (ECOG) performance status ≤ 1; (4) a life expectancy of at least 3 months; and (5) adequate bone marrow, kidney, liver function, and normal blood test results. Exclusion criteria were as follows: (1) prior treatment with other antitumor drugs; (2) recent history of cardiac or vascular events or other conditions precluding surgical treatment; (3) participation in other clinical trials within the past 3 months; (4) lack of legal capacity or limited legal capacity; and (5) contraindications, allergies, or adverse reactions to pazopanib and tislelizumab. Eligible Pts received Tisle 200 mg IV. in day 1(D1), every 21 days for 4 cycles; Pazopanib was administered orally at a dose of 800 mg once daily for 12 weeks prior to the scheduled surgery. The primary endpoint of the study was the percentage change in the length of the VTT and the percentage reduction in the longest tumor diameter. Results: Nine patients with a median age of 58 years were treated. The median reduction in tumor diameter was 31.0% (range: 3.0%–48.7%), and the median reduction in VTT length was 29.2% (range: -153.1% to 100.0%). Treatment led to decreased surgical complexity in 88.9% of patients. The regimen was well-tolerated, with manageable adverse events primarily including vomiting, itching, and weight loss. No metastasis developed during the study period, though one patient required expedited surgery due to an increase in thrombus size. Conclusions: The combination of tislelizumab and pazopanib as neoadjuvant therapy effectively reduces the size of tumors and associated venous tumor thrombi in patients with RCC-VTT, facilitating less complex surgical interventions and potentially leading to better postoperative outcomes.
Genome-wide burden survival tests for patients with metastatic prostate cancer on androgen receptor-targeted therapies in the Million Veterans Program dataset.
Authors: Danielle Candelieri-Surette, Dan Berlowitz, Tyler Nelson, Hannah Carter, Brent S Rose, Rana R. McKay, Jason Vassy, Richard Hauger, Julie Ann Lynch, Craig Teerlink
Journal: Journal of Clinical Oncology (2025)

251 Background: Literature suggests various genes influence metabolism and treatment response in prostate cancer. While the androgen receptor gene is the primary target for hormonal treatment, studies increasingly highlight the roles of genes in lipid metabolism and pharmacogenetics, including APOE, BGN, AHSG, CYP2D6, SLC2A4 , and HSD3B1 . Genes allowing androgens to enter cells more efficiently may increase therapy resistance, worsening outcomes in recurrent or metastatic disease. An understanding of biomarkers and resistance mechanisms is essential to address this issue. We conducted a genome-wide search for genes that exhibit an effect on survival in patients on androgen receptor-targeted therapies. Methods: We developed two models: Model 1 identified 5,107 patients with metastatic prostate cancer receiving androgen deprivation therapy; model 2 focused on a subgroup 2,240 patients on abiraterone. We performed 18,544 distinct gene-level tests across the human genome using all coding variants within each gene, analyzing rare (minor allele frequency &lt;1%) loss-of-function variants, and rare loss-of-function and missense variants. All analyses used the Veterans Administration’s Million Veterans Program (MVP) whole genome Release2 genomic data (96K males). We conducted separate analyses for African and European ancestry subjects. Gene-level survival analysis was performed using the SeqMeta R package that performs burden, Skat, and Skat-O tests. A Bonferroni correction was applied for 82,567 tests, requiring p&lt;6.06E-7 to establish significance and p&lt;5.00E-6 for suggestive evidence. Individual survival analyses were conducted on all SNPs within each significant gene. Results: Gene-level tests identified OR1G1 (burden p=1.87E-7, OR=0.17), PCDHGB1 (burden p= 2.92E-07, OR=0.61) and CLPB (burden p=3.34E-07, OR=0.30) as significantly associated with prostate cancer survival, while SNX18 demonstrated a suggestive association (Skat-O p=3.40E-6) among European ancestry subjects in model 1. Among African ancestry subjects, the best performing gene was UBD (burden p= 2.61E-06, OR=0.76). Analyses of rare loss-of-function and loss-of-function or missense variants failed to achieve significant or suggestive evidence. Model 2 did not reveal any significant findings. Additional variant level survival analyses revealed 4 significant SNPs from UBD including chr6.29555893.C.A, chr6.29556082.G.C, chr6.29556095.A.G_A, chr6.29556226.A.G_A (1 copy HR 3.1, 2 copies HR 3.7, p &lt;.05) and SNP chr5.54519665.A.C_A from gene SNX18 (1 copy HR 1.5 p &lt;.05). Conclusions: Our results indicate variants within several genes may influence prostate cancer survival by causing resistance to androgen-receptor targeted therapies and warrant follow-up in external datasets for validation.
Treatment patterns and clinical outcomes in patients with metastatic urothelial carcinoma in England: A retrospective observational study.
Authors: Tinevimbo Shiri, Max Nievaart, Simran Gill, William Perkin
Journal: Journal of Clinical Oncology (2025)

740 Background: In England, platinum-based chemotherapy with or without an immune checkpoint inhibitor is the standard-of-care for mUC patients. However, treatment patterns following first-line therapy remain unclear. There is a need to collect real-world data to enable an improved understanding of the clinical management of mUC in the National Health Service (NHS) and associated outcomes. Methods: This retrospective study obtained routine data for all patients diagnosed with mUC in England between January 2016 and December 2021 from the National Cancer Registration and Analysis Service (NCRAS). A treatment-based algorithm was developed to approximate progression to metastatic disease for those patients who had non-metastatic UC (Stage I-III). Variables collected include patient demographics, tumour characteristics, diagnostic tests, comorbidities, healthcare resource use, systemic anti-cancer therapy (SACT) and distributions of patients by lines of treatment. Kaplan-Meier methods were used to calculate overall survival (OS). Results: Of 61,816 patients diagnosed with UC between 2016 and 2021, 10,787 patients had mUC (stage IV (79.7%) at diagnosis or stage I-III (20.3%). The median age at diagnosis was 73.9 years, with 66.0% being male. Patients treated with anti-PD-L1 had a median age of 68.8 years. Only 36.5% (n = 3,942) received first-line therapy, with 24.3% (n = 959) reaching second-line therapy, while third-line therapy was delivered to 4.0% (n = 158) and fourth-line therapy to just 0.5% (n = 19) of patients with derived lines of therapy. The most common first-line regimen was ‘carboplatin + gemcitabine’ (n = 1,497; 38.0%), followed by ‘cisplatin + gemcitabine’ (n = 1,153; 29.2%). Pembrolizumab was the most common regimen administered at second line (n = 284; 29.6%) and remained the most common regimen at third line (n = 52; 32.9%). For the entire cohort, including patients that did not receive an active treatment, 12-month survival probability was 29.0%. The survival probabilities for patients treated at first-line, and reaching second-line and third-line, were 45.0%, 34.0%, and 30.0%, respectively. For the entire cohort, including patients that did not receive an active treatment, 12-month survival probability was 29.0%. The survival probabilities for patients treated at first-line, and reaching second-line and third-line, were 45.0%, 34.0%, and 30.0%, respectively. Conclusions: A high attrition rate in SACT was observed in mUC patients, and a poor prognosis indicated by a median OS of only 5.4 months from diagnosis. New treatment options particularly in the second-line setting could improve outcomes for patients. Further real-world studies are needed to evaluate their impact within routine clinical practice.
A phase II study bolstering outcomes by optimizing immunotherapy strategies with evolocumab and nivolumab in patients with metastatic renal cell carcinoma (BOOST-RCC).
Authors: Tian Zhang, Qian Qin, Suzanne Cole, Andrew Zhuang Wang, Pavlos Msaouel, Andrew Warren Hahn, Amishi Yogesh Shah, Matthew T. Campbell, Song Zhang, Rebecca Slack Tidwell, Wadih Issa, Andrew DeVilbiss, Changchuan Jiang, Joseph Vento, Kevin Dale Courtney, Hans J. Hammers, James Brugarolas, Nizar M. Tannir, Eric Jonasch
Journal: Journal of Clinical Oncology (2025)

TPS612 Background: While metastatic renal cell carcinoma (mRCC) is known to be immunogenic, and there have been several recent advances with combinations of immunotherapy, the disease often progresses and immunotherapy resistance mechanisms remain unclear. For patients with mRCC refractory to immunotherapy checkpoint inhibitors (ICIs), further treatment options are not curative and improvements are needed. Proprotein convertase subtilisin/kexin type 9 (PCSK9) directs MHC-I molecules to the lysosome, and inhibition of PCSK9 improves MHC-I expression and tumor antigen presentation. Evolocumab is a PCSK9 inhibitor which was shown in preclinical studies to improve tumor antigen presentation, intratumoral CD8 T-cell infiltration (and activation), and overall tumor control. We designed a phase 2 trial with safety lead in adding evolocumab to the PD-1 inhibitor nivolumab in mRCC refractory to first-line ICI combinations. Methods: BOOST-RCC is an investigator-initiated, phase 2, multicenter, single cohort study investigating the efficacy of evolocumab and nivolumab for ICI refractory mRCC. A Simon 2-stage design will be used, with 10 patients treated in the first cohort. If at least 1 objective response is observed among the first 10 patients, enrollment will continue with 19 more patients, for a total of 29 patients. Primary endpoints are objective response rates based on RECIST v1.1 as well as trial limiting toxicities for the safety profiling of the combination of treatment. Patients will be treated until progression of disease, unacceptable toxicity, or up to 2 years if ongoing response. The study is funded by CPRIT and open within the DOD-supported Kidney Cancer Research Consortium. Enrollment is ongoing at UT Southwestern Simmons Comprehensive Cancer Center and MD Anderson Cancer Center (NCT06284564). Clinical trial information: NCT06284564 .
Association between site of metastases and survival stratification of the IMDC classification in metastatic renal cell carcinoma (mRCC).
Authors: Annalisa Zeppellini, Giorgio Patelli, Martino Pedrani, Caterina Vaghi, Rebecca Romanò, Laura Roazzi, Francesca Martinelli, Silvia Pierri, Gabriele Calvanese, Gabriele Ciarlo, Andrea Sartore-Bianchi, Francesco Spina, Salvatore Siena
Journal: Journal of Clinical Oncology (2025)

566 Background: The IMDC risk model is pivotal for prognostic stratification of mRCC, dividing patients into favorable (FAV), intermediate (INT) and poor-risk (POOR) groups with distinct overall survival (OS) estimates. While valuable for treatment decisions in first line, IMDC does not encompass sites of metastasis, potentially missing a significant prognostic factor. Methods: We retrospectively included mRCC patients receiving first-line therapy at Niguarda Cancer Center, Milan, Italy from 2008 to 2024. The primary aim was to evaluate if specific metastatic sites could redefine IMDC prognostic stratification. OS was analyzed using Kaplan-Meier estimates. Univariate and multivariate Cox regression analyses were performed including variables in the table. Results: 164 patients were eligible for analysis. Bone, liver and nodal metastases were independent negative prognostic factors both in univariate and multivariate analyses (HR 2.83, IC95% 1.78-4.49, p&lt;0.001; HR 1.79, IC95% 1.12-2.85, p=0.014; HR 1.92, IC95% 1.28-2.88, p=0.002, respectively). As expected, FAV IMDC and first-line immunotherapy-based combinations (IO-IO or IO-TKI) were positive prognostic factors (both p&lt;0.001). Having at least one bone and/or liver and/or nodal metastasis (B/L/N) was significantly associated with poorer prognosis and could re-stratify INT IMDC patients into two subpopulations with different OS (HR 1.88, p=0.046): B/L/N-positive INT OS rates were not different from POOR (p=0.193) and B/L/N-negative INT OS rates were comparable to FAV (p=0.193). Conclusions: B/L/N metastases are independent prognostic factors in mRCC, despite being unaddressed by IMDC. Present findings align with prior research supporting the inclusion of metastatic sites in prognostic scores. IMDC classification could be refined with inclusion of metastatic sites to improve prognostic accuracy. Patient characteristics. Age ≥50 147 (90) Sex Male 123 (75) IMDC FAV 42 (26) INT 85 (52) POOR 37 (22) Site of metastasis Bone 40 (24) Liver 31 (19) Nodal 85 (52) Oligometastases (&lt;4) 33 (20) First-line immunotherapy-based combinations 38 (23) Data are shown as number of patients (N) and, within brackets, percentage (%).
Efficacy of targeted therapies (TT) after HIF-2⍺ inhibitor-based treatment in advanced renal cell carcinoma (aRCC).
Authors: Patricia Rioja, Macarena Rey-Cárdenas, Jorge Esteban Villarrubia, David Plata, Ileana Sparagna, Fabio A. B. Schutz, Ray Manneh, Roberto Iacovelli, Ronan Flippot, Daniel Castellano, Guillermo de Velasco
Journal: Journal of Clinical Oncology (2025)

508 Background: Hypoxia-inducible factor 2⍺ (HIF) inhibitors are active in renal cell carcinoma refractory to prior treatment with tyrosine kinase inhibitors (TKI) and immunotherapy, including anti-PD-1 monotherapy or combinations with anti-CTLA-4, and represent a new therapeutic option. However, the efficacy of TT after HIF-2⍺ inhibitors has not been assessed. Methods: A retrospective review of medical records from aRCC patients (pts) treated with HIF-2a inhibitors at five academic institutions was conducted. Pts who received subsequent treatment with TT were identified to collect outcomes in terms of best radiological response by RECIST 1.1 criteria (BRR), time to treatment failure (TTF), defined as treatment failure can be defined as one or a combination of events, including disease progression, discontinuation of treatment due to toxicity, or death from any cause; and overall survival (OS). This work was approved by an ethics board and all patients provided approval. Results: Data of 35 pts were available: 30 (85%) were male and 18 (51%) were metastatic at diagnosis. IMDC risk group was favorable, intermediate and poor in 11 (31%), 20 (57%) and 4 (11%) pts, respectively. Belzutifan was administered as monotherapy in 27 (77%) and in combination in 8 (22%) pts. Regarding first subsequent TT, 30 (85%) received TKI and 5 (14%) received mammalian target of rapamycin (mTOR). TT post HIF-2a was administered as second-line, third-line, fourth-line and beyond fourth-line in 3 (8%), 4 (9%), 18 (51%) and 10 (28%) pts, respectively. Treatment was interrupted due to progression in 28 (80%), 1 (3%) discontinued due to toxicity and 7 (20%) remained on treatment after data cut-off. Median follow-up was was 19 months.Median TTF on subsequent TT was 5.74 months (95% CI: 2.82–8.00). Median OS was 10,49 months (95% CI: 6,13-NR) with 17% pts alive at 1 year from the initiation of subsequent TT. Investigator-assessed BRR to subsequent TT was available for 33 out of 35 pts. Partial response and stable disease were observed in 7 (20%) and 12 (34%), respectively. Progressive disease was observed in 14 (40%) pts. Conclusions: Both VEGF/VEGFR and mTOR inhibitors have activity following HIF-2α blockade. However, 40% of patients will be refractory to treatment. This highlights the need for new drugs with distinct mechanisms of action.
Expression of tissue factor (TF) in penile squamous cell carcinoma (PSCC) and enrichment in HPV-negative cases.
Authors: Andrew Johns, Jamaal Christopher Jackson, Leticia Campos Clemente, Luisa Maren Solis, Priya Rao, Christopher Matthew Manuel, Wei Qiao, Matthew T. Campbell, Jad Chahoud, Niki Marie Zacharias, Curtis Alvin Pettaway
Journal: Journal of Clinical Oncology (2025)

10 Background: Advanced/metastatic PSCC is an aggressive malignancy with limited treatment options. An antibody-drug conjugate (ADC) targeting TF is approved for treatment of advanced cervical cancer and may benefit patients with PSCC. We evaluated TF expression in PSCC which could support a future clinical trial of a TF-targeting agent for PSCC. Methods: We identified 33 pts with PSCC who underwent primary surgery at MD Anderson from 1999-2017 and had archived primary tumor tissue available for analysis. HPV-positive status was determined by either PCR testing or high-risk HPV in situ hybridization assay. A tissue microarray (TMA) was constructed with 3 cores per tumor. Anti-TF-1 antibody staining was performed by immunohistochemistry and mean H-scores for membrane and cytoplasm staining were assessed (range 0-300) for each tumor. Median H-scores were described and compared between HPV-positive and negative tumors. Percentage of pts with tumors staining positive for TF (≥10% of tumor cells with at least 1+ intensity in cytoplasm and/or membrane) was determined. Association of TF expression with tumor grade, presence of metastatic disease, lymphovascular invasion (LVI), perineural invasion (PNI), recurrence free survival (RFS), and overall survival (OS) was assessed. Results: 17 pts (51.5%) had HPV-positive disease; 19 pts (57.6%) had metastatic disease. 27 tumors (81.8%) stained positive for tissue factor. Median overall membrane TF H-score was 47 (range 1-232). HPV-negative tumors had significantly higher membrane expression of TF (median H-score 70, range 1-232) than HPV-positive tumors (median H-score 19, range 1-123; p=0.004). While analyses were limited by small sample size, we did not find a significant association of TF H-score with tumor grade, presence of metastatic disease, LVI, PNI, RFS, or OS. Conclusions: TF expression was highly prevalent in this PSCC pt cohort. HPV-negative tumors had significantly higher TF expression than HPV-positive tumors; this finding requires further study. These data support further investigation of TF-targeted therapy, such as an ADC, for treatment of PSCC. Variable Overall population HPV-positive(17 patients) HPV-negative(16 patients) Median (range) H-score Membrane 47 (1-232) 19 (1-123) 70 (1-232) Cytoplasm 29 (2-180) 18 (2-98) 59 (2-180) Positive TF expression (Percent of patients with ≥1 core having ≥10% of tumor cells with at least 1+ intensity in either cytoplasm or membrane) 27/33 (81.8%) 12/17 (70.6%) 15/16 (93.8%)
Impact of deferred cytoreductive nephrectomy in the era of the immunotherapy in metastatic renal cell carcinoma: A multicenter retrospective study.
Authors: Patricia Rioja, Carolina Passarella, Martin Angel, Wbeimar Valderrama, Freya Bosma, Georgia Anguera, Victoria Gomez, Álvaro Ruiz-Granados, David Plata, Martin Ignacio Zapata Laguado, Alberto Orta-Ruiz, Maria Natalia Gandur-Quiroga, Maria T. Bourlon, Enrique Grande, Ray Manneh, Javier Molina-Cerrillo, Pablo Maroto-Rey, Juan Pablo Sade, Daniel Castellano
Journal: Journal of Clinical Oncology (2025)

502 Background: Deferred cytoreductive nephrectomy (dCN) is an emerging, strategy in the management of metastatic renal cell carcinoma (mRCC), applied selectively to patients who demonstrate a favorable response to initial systemic therapy. This study aimed to assess the clinical impact of dCN within the context of sequential treatment management. Methods: A multi-institutional retrospective evaluation. The descriptive analysis was performed to examine the demographic and clinical characteristics. Progression-free survival (PFS) and overall survival (OS) were analyzed by the Kaplan-Meier method. A level of p &lt; 0.05 was considered significant. Results: With a median follow-up of 19 months (1-174 months), 50 patients were divided into three groups: 46% received IO+TKI, 24% received IO+IO, and 30% received TKI. Of the cohort, 66% were male, with median age of 60.6 years. All had clear cell histology, and 76% were intermediate IMDC risk. The most common metastatic sites were lungs (50%), lymph nodes (36%), and bone (32%). The median time from systemic therapy to cytoreductive nephrectomy (CN) was 6 months. Notably, 26% did not restart treatment post-CN, and 6% discontinued pre-CN (two due to toxicity, one due to progression). Median PFS was 36 months, with a 5-year PFS rate of 40%. Analysis by IMDC risk and type of treatment showed no significant differences. However, patients with a Karnofsky score (KS) ≤80% had a lower risk of progression than those with KS &gt;80% [HR: 0.31, 95% CI (0.13-0.75), p=0.01] and those achieving complete response had a significantly lower risk of progression [HR: 8.59, 95% CI (1.1-67), p=0.042]. Median OS was 91 months, with no significant differences between groups. Conclusions: This study demonstrates that dCN can offer a therapeutic advantage especially in selected patients who achieve favorable responses to upfront systemic therapy. Careful patient selection is crucial to maximize the potential benefits of delayed surgery, reduce perioperative risks and improve oncological outcomes. Larger patient cohorts and well-designed prospective clinical trials are essential to solidify these findings and establish evidence-based guidelines.