tbuckley/cabot-search huggingface dataset:
Safety and efficacy of immune checkpoint inhibitor rechallenge in metastatic fumarate hydratase-deficient renal cell carcinoma: A retrospective study.
Authors: Yanfeng Tang, Minghao Wang, Jiayu Liang, Hao Zeng
Journal: Journal of Clinical Oncology (2025)

500 Background: Fumarate hydratase–deficient renal cell carcinoma (FH-deficient RCC) is a rare subtype of kidney cancer characterized by FH-inactivating alterations. Studies have revealed highly immunogenic features in this lethal disease, providing molecular evidence for implement of immune checkpoint inhibitor (ICI). Due to the lethal nature of FH-deficient RCC, a significant proportion of patients continue to have disease progression after receiving ICI combination therapy (ICI plus tyrosine kinase inhibitors, TKI). Herein, we aim to evaluate the safety and efficacy of immune checkpoint inhibitor rechallenge in metastatic fumarate hydratase-deficient renal cell carcinoma in real-world settings. Methods: A multicenter database of patients diagnosed with FH-deficient RCC, identified through IHC evidence of negative FH and/or positive 2SC, was explored. The study enrolled patients with metastatic FH-deficient RCC who received ICI combination therapy within three months of discontinuing prior ICI treatments between January 2018 and July 2023. Results: A total of 18 patients, each receiving at least two lines of ICI combination therapy, were included in the study. The majority of patients (n=15) experienced disease progression following prior-line immunotherapy. Among these, with 66.7% (10/15) showed progression in the original lesions, while 33.3% (5/15) developed new metastatic lesions. Three patients transitioned to later-line immunotherapy due to immune-related adverse events (irAEs) of grade 3 or higher. The incidence of grade 1-2 irAEs was comparable between prior and later-line therapies (28.15% vs. 27.30%, p=0.8932), as was the incidence of grade 3 or higher irAEs (0.86% vs. 0.29%, p=0.594). For the entire cohort, the median progression-free survival (mPFS) for prior-line ICI combination therapy was 16.2 months (95% CI: 5.565-26.835 months), and the mPFS for later-line ICI combination therapy was 15.2 months (95% CI: 3.915-26.485 months). The objective response rate (ORR) and disease control rate (DCR) for later-line therapy were 17% and 78%, respectively, compared to an ORR of 28% and a DCR of 67% for prior-line therapy. Conclusions: This cohort study demonstrated that ICI rechallenge achieved mPFS of 15.2 months and DCR of 78%, with a favorable safety profile in patients with FH-deficient RCC. Therefore, the resumption of ICI combination therapy may be a viable option for managing this lethal subtype of RCC.
Comprehensive investigation of CPSF3's role in the progression of bladder cancer.
Authors: Zhiyang Ma, Danfeng Xu, Chenghe Wang
Journal: Journal of Clinical Oncology (2025)

829 Background: Bladder cancer (BC) is a global health issue, with a significant number of new cases diagnosed annually. Despite advances in treatment, many patients experience recurrence or progression, emphasizing the need for novel prognostic biomarkers and therapeutic targets. This study aimed to investigate the prognostic significance and biological function of Cleavage and Polyadenylation Specificity Factor 3 (CPSF3) in BC. Methods: We analyzed CPSF3 expression using The Cancer Genome Atlas (TCGA) data and immunohistochemistry (IHC) on a cohort of 203 BC patients. A nomogram incorporating CPSF3 expression was constructed to predict overall survival (OS) and disease-free survival (DFS). In vitro experiments were conducted to assess the effect of CPSF3 knockdown on BC cell proliferation, colony formation and cell cycle distribution. Bioinformatics analyses, including Gene Set Enrichment Analysis (GSEA) and immune infiltration analysis, were performed to explore potential mechanisms. Results: High CPSF3 expression was significantly associated with poor OS and DFS in TCGA and our cohort. The nomogram incorporating CPSF3 showed superior predictive performance compared to traditional models. Downregulation of CPSF3 inhibited BC cell proliferation, colony formation and transition from G1 phase to S phase. GSEA revealed enrichment of oncogentic pathways in CPSF3 high-expression phenotype. CPSF3 expression was correlated with immune cell infiltration and expression of immune checkpoints in the tumor microenvironment. Conclusions: Our study demonstrates that CPSF3 is a promising prognostic biomarker for BC and may play a crucial role in BC progression. The nomogram incorporating CPSF3 expression provides an improved tool for predicting BC patient outcomes. These findings suggest that CPSF3 could be a potential therapeutic target for BC treatment.
Clinical experience with EMACO chemotherapy in male choriocarcinoma: A single-center study.
Authors: Gwanhyun Park, Inkeun Park, Shinkyo Yoon, Jae Lyun Lee
Journal: Journal of Clinical Oncology (2025)

640 Background: Choriocarcinoma is an aggressive subtype of germ cell tumor that frequently metastasizes and progresses rapidly. In gestational trophoblastic tumors in females, the etoposide, methotrexate, actinomycin D, cyclophosphamide, and vincristine (EMACO) regimen is commonly used, but there are limited reports of its use in male choriocarcinoma. The purpose of this study was to retrospectively describe the clinical outcomes of the EMACO regimen in male patients with pathologically confirmed or clinically highly suspected choriocarcinoma at a single institution. Methods: We conducted a retrospective review of the medical records of male patients who received at least one cycle of EMACO chemotherapy between February 2013 and September 2023 at a tertiary hospital in Korea. We analyzed their baseline characteristics, tumor response, survival outcomes, and adverse events. Resection of residual tumors following EMACO chemotherapy was also considered part of the treatment process. The evaluation of tumor response was based on radiological examinations and changes in tumor markers. Results: In total, 15 patients were included in the study with a median age of 26 years. During diagnosis, 7 patients were found to have pure choriocarcinoma cell components on pathological examination, but all patients had elevated beta-hCG levels (median 177,000 mIU/mL, range 312–11,478,883 mIU/mL). At the time of EMACO administration, lung metastasis was the most frequent, observed in 12 patients, followed by brain metastasis in 7 patients. Seven patients received EMACO chemotherapy as 1 st or 2 nd -line treatment. The median number of chemotherapy cycles was 6. Tumor marker reduction or a decrease in tumor size was observed in 11 patients. Residual tumor resection was performed immediately after EMACO treatment in 7 patients, and no recurrence was observed in 6 patients during the follow-up period. Regarding Grade 3-4 toxicity, anemia was observed in 10 patients, thrombocytopenia in 6 patients, neutropenia in all patients, and elevated alanine aminotransferase levels in 6 patients. The median OS was not reached, with a median follow-up time of 24 months and a median PFS of 10.2 months. Conclusions: EMACO chemotherapy is an effective regimen for male germ cell tumors with pathologically confirmed choriocarcinoma components or markedly elevated hCG levels, and it may offer a curative treatment option when combined with resection of residual tumors.
The prognostic utility of preoperative β2 microglobulin in patients with renal cell carcinoma.
Authors: Gregory Palmateer, Edouard Nicaise, Taylor Goodstein, Dattatraya H. Patil, Shreyas Joshi, Vikram M. Narayan, Kenneth Ogan, Viraj A. Master
Journal: Journal of Clinical Oncology (2025)

565 Background: β2 microglobulin is a nonglycosylated protein synthesized by all nucleated cells. It has been utilized as a tumor marker in several different malignancies, however, studies examining its role in renal cell carcinoma (RCC) are limited. Methods: Using the Emory kidney cancer database, patients with any stage or histology RCC who underwent partial or radical nephrectomy from 2000 to 2022 and had an available β2 microglobulin within 90 days before surgery were included. β2 microglobulin ≥ 2.34 mg/L was considered elevated. Patient and surgical characteristics were recorded. Kaplan-Meier curves and multivariable Cox hazards models were used to assess the association between an elevated β2 microglobulin and overall (OS) and cancer-specific survival (CSS). Subgroup analysis was performed based on renal function (estimated glomerular filtration rate (eGFR) ≤ or &gt; 60 mL/min/1.73m 2 ) and metastatic disease status. Results: Of 429 patients who met inclusion criteria, 178 (41.5%) had an elevated preoperative β2 microglobulin. After adjusting for confounders, an elevated β2 microglobulin was independently associated with worse CSS (HR 2.08 [95% CI 1.20–3.60]; p = 0.009) and OS (HR 1.58 [95% CI 1.03–2.41]; p = 0.035) compared to a normal β2 microglobulin. On subgroup analysis, however, elevated β2 microglobulin remained significantly associated with worse OS/CSS only in patients with normal renal function and non-metastatic disease (Table). Conclusions: A preoperatively elevated β2 microglobulin level is independently associated with worse OS and CSS in patients with RCC undergoing nephrectomy. The utility of β2 microglobulin as a prognostic indicator is most relevant for patients with normal renal function and non-metastatic disease. Multivariable Cox hazards model for the effect of preoperative β2 microglobulin on cancer-specific and overall survival in patients with renal cell carcinoma according to renal function and metastatic disease status. Covariants n(%) Cancer-specific SurvivalHazard Ratio (95% CI) p-value Overall SurvivalHazard Ratio (95% CI) p-value β2 microglobulin ≥ 2.34 mg/L metastatic disease 102 (63) 0.95 (0.51-1.76) 0.872 0.93 (0.56-1.55) 0.779 non-metastatic disease 76 (28.5) 4.55 (1.24-16.77) 0.023 2.99 (1.37-6.54) 0.006 eGFR ≤ 60* 99 (23.1) 1.31 (0.69-2.49) 0.410 1.51 (0.95-2.41) 0.083 eGFR &gt; 60* 79 (18.4) 2.90 (1.54-5.44) &lt; 0.001 2.00 (1.19-3.36) 0.009 β2 microglobulin &lt; 2.34 mg/L eGFR ≤ 60* 50 (11.7) 1.24 (0.55-2.78) 0.600 1.39 (0.74-2.60) 0.309 eGFR &gt; 60* 201 (46.9) Ref Ref *Calculated using Chronic Kidney Disease Epidemiology Collaboration 2021 equation. Variables in model include age, sex, race, Body Mass Index (BMI), Charlson Comorbidity Index (CCI) pT stage, Fuhrman grade, presence of IVC thrombus, receipt of systemic therapy, and IMDC risk score (metastatic patients only).
Assessing the clinical impact of tumor volume on response to <sup>177</sup> Lu-PSMA radioligand therapy in metastatic castration-resistant prostate cancer.
Authors: Yalda Nikanpour, Mohamed E. Ahmed, Carter A Day, Mindie L Mahon, Rimki Haloi, Zeina Wael, Eugene D. Kwon, Jack Andrews
Journal: Journal of Clinical Oncology (2025)

175 Background: 177 Lu-PSMA-617, a PSMA-directed radionuclide therapy, is an emerging treatment for metastatic castration-resistant prostate cancer (mCRPC). This retrospective study evaluates clinical outcomes of 177 Lu-PSMA-617 in low volume (LV) and high volume (HV) mCRPC, classified using the CHAARTED criteria. Methods: We conducted a retrospective review of the Mayo Clinic Prostate Cancer Registry, including mCRPC patients treated with 177 Lu-PSMA-617 at Mayo Clinic Rochester, MN, from August 2017 to August 2024. Patients were categorized based on CHAARTED criteria, which define high-volume disease by the presence of visceral metastases and/or four or more bone metastases, with at least one outside the vertebral column and pelvis. PSA-response rate (PSA-RR), overall survival (OS), PSA-progression-free survival (PSA-PFS), and radiographic progression-free survival (rPFS) were analyzed using Kaplan-Meier curves with log-rank tests, as well as uni- and multivariate Cox regression. Results: Of the 264 patients treated with 177 Lu-PSMA-617, 83 were classified as LV (median follow-up: 17.1 months) and 177 as HV (median follow-up: 13.7 months). LV patients had lower serum PSA levels (P &lt; 0.0001), higher hemoglobin levels (P &lt; 0.0001), and a longer time from diagnosis to treatment initiation (10.3 years vs. 7.2 years, P = 0.04). In the HV group, 92% had bone metastases, 60% had lymph node involvement, 54% had both, and 35% had visceral metastases. In the LV group, 64% had bone metastases, 84% had lymph node involvement, 25% had both, and none had visceral metastases. Median OS was 14.4 months for HV patients and 17.6 months for LV patients (P &lt; 0.0001). Median PSA-PFS was 11.4 months for HV patients and 13 months for LV patients. Median rPFS was 9.1 months for HV patients and 10.6 months for LV patients. PSA-RR significantly differed between groups (P &lt; 0.0001). In the HV group, 20% achieved CR (PSA &lt; 0.2 ng/mL), 29% had PR (PSA decreased by ≥50%), 16% experienced SD, and 35% had PD (PSA increased ≥25% from nadir). In contrast, the LV group had 51% achieving CR, 10% achieving PR, 18% with SD, and 11% with PD. Conclusions: Lower disease volume in mCRPC is strongly associated with improved outcomes following 177 Lu-PSMA-617 therapy. These findings suggest that tumor burden is a key predictor of response to PSMA radioligand therapy.
Exploring social vulnerability in prostate cancer management: Insights into utilization of watchful waiting and active surveillance from 1998 to 2017.
Authors: Nana Shakhnazaryan, Jenna Winebaum, Lufan Wang, Angad Jhandi, Nathan Nguyen, Janet E Cowan, Peter Carroll, June M. Chan, Salma Shariff-Marco, Samuel L Washington
Journal: Journal of Clinical Oncology (2025)

322 Background: Active surveillance (AS) and watchful waiting (WW) represent different conservative management strategies for prostate cancer (PCa), with AS being the preferred strategy. The Social Vulnerability Index (SVI) is enhancing our understanding of healthcare treatment disparities and social risk factors in the cancer care, but its impact in prostate cancer care remains unclear. We examine how social vulnerability influences the choice of WW vs AS in managing men with low and intermediate risk prostate cancer. Methods: The Cancer of the Prostate Strategic Urologic Research Endeavor (CaPSURE) database was used to identify men diagnosed with localized, low, and intermediate-risk prostate cancer (i.e., those potentially eligible for active surveillance) from 1998 to 2017. Participants' data were geocoded and de-identified, then combined with Social Vulnerability Index (SVI) data, which is based on four themes: socioeconomic status, household composition, minority status, and housing &amp; transportation. We used multinomial logistic regression to examine the association between SVI and conservative management strategies of WW and AS. Results: Among 681 low-risk and intermediate-risk prostate cancer patients diagnosed from 1998 to 2017, 135 were assigned to watchful waiting (WW) and 546 to active surveillance (AS), reflecting a trend toward AS. The mean Social Vulnerability Index (SVI) was higher in the WW group (0.30) than in the AS group (0.21). Significant differences were noted by Socioeconomic Status (0.33 vs 0.15, p = 0.02). Conclusions: For patients with low and intermediate risk localized prostate cancer higher SVI, particularly in communities with greater socioeconomic challenges and higher proportion of racial while the overall proportion of AS increased over time. Our findings underscore how patients with higher SVI may experience considerable undertreatment, even with the concomitant increase in AS utilization over time. Identifying these communities remains a crucial step in addressing local drivers of treatment disparities in PCa care.
Application of radiomics as a risk stratification tool in node positive penile cancer.
Authors: Adnan Nazir Fazili, Brian Morse, Abraham Ahmed, Jongphil Kim, Daniel Jeong, Philippe E. Spiess, Jad Chahoud
Journal: Journal of Clinical Oncology (2025)

3 Background: The risk level of lymph node metastasis in penile cancer is determined using the Graafland criteria which determines how patients are treated. These imaging-based criteria have critical implications on patient care yet have not been extensively validated. The purpose of this study was to validate the Graafland criteria and to assess the use of radiomics analysis of CT scans to standardize risk stratification. Methods: Thirty-eight patients with squamous cell penile cancer with CT scans prior to regional lymphadenectomy were included in this retrospective cohort. Patients with prior chemotherapy for PSCC or any inguinal and pelvic radiotherapy were excluded. All CT scans were performed using IV contrast with axial slice thickness of 3mm. CT scans were analyzed by two experienced oncologic radiologists using Graafland criteria. The largest inguinal lymph node in each patient was segmented and radiomics features were extracted and compared to pathologic evidence of high-risk disease. 308 radiomic features were identified. Features with poor predictive value (i.e. AUC &lt;0.5) were excluded. Pearson’s correlation coefficient was used to find the clusters of features (absolute value of correlation of ≥0.95), and the most predictive feature of each cluster was selected.199 features with best predictive value were selected for analysis. Two logistic regressions were performed using stepwise selection and LASSO approach. Results: In 38 subjects, 16 of 38 patients were identified as harboring lymph node metastasis on surgical pathology. Applying Graafland criteria had an inter-reader concordance of 89.5% (34/38), an accuracy of 86.8% (95%CI: 71.9% - 95.6%); AUC: 0.869 (95% CI: 0.758– 0.981); Sensitivity 87.5%; and Specificity 86.4% in predicting high-risk disease. CT radiomics analysis yielded a model including two features F54 (compactness) and F279 (3D wavelet_P1_L2_C1) which is a multi-order texture-based feature. The logistic regression with stepwise selection included two features (F54 and F279) and had an (AUC = 0.921 ± 0.096) after five-fold cross validation. Conclusions: Graafland criteria accurately predicted the presence of high-risk nodal disease on pre-operative CT scans when assessed by expert radiologists. Radiomic analysis shows promise in further refining and standardizing the detection of high-risk nodal disease with the advantage in ease of training and/or clinical application.
An online clustering algorithm predicting model for prostate cancer based on PHI-related variables and PI-RADS in different PSA populations.
Authors: Gejun Zhang, Jiyuan Hu
Journal: Journal of Clinical Oncology (2025)

328 Background: Prostate cancer is the most common male malignancy. Current diagnostic methods using single TPSA and PHI lack specificity. Some researches have created nomograms for predicting risk, but these are not easily visualized. Our study aims to find the best negative predictive value (NPV) for PHI, then build a clustering model to display prostate cancer risk categories, particularly useful for patients with PSA&gt;20 and be actually applied in clinical work. Methods: We collected 708 patients in the training cohort and 143 in the validation cohort, divided into three groups based on their PSA levels. Next, we determined optimal and customized PHI cut-off values, calculated NPV and PPV, and selected logistic regression as the best method among several machine-learning algorithms. Subsequently, the significant variables were identified, and then a clustering algorithm was constructed. Finally, the model was validated and made available online for further clinical application. Results: The Optimal PHI cut-off lower limits for PSA&gt;4, PSA4-20, PSA&gt;20 subgroups were 23.85, 24.35, and 40.75, with upper limits of 142.9, 143, and 135.6, respectively. The clustering model of the optimal cohort for PSA&gt;4 and PSA 4-20 sub-groups showed a superior Silhouette coefficients of 0.433 and 0.526 than that of the customized PHI cohort (0.432, 0.452). The PSA&gt;20 subgroup owned the highest Silhouette coefficient of 0.572. The validation cohort showed AUC values of 0.761, 0.823, 0.833 for these 3 sub-groups, with accuracy rates of 88.81%, 90.38%, and 82.05%. Conclusions: In conclusion, our clustering model effectively categorizes patients into distinct risk groups with clear visualization and has demonstrated stability and reliability in the validation cohort, potentially aiding in early diagnosis of prostate cancer in clinical practice.
A non-coding RNA based classifier for favorable outcomes in clinically organ confined bladder cancer.
Authors: Yair Lotan, Joep de Jong, James A. Proudfoot, Siamak Daneshmand, Robert S. Svatek, Vikram M. Narayan, Ewan Gibb, Elai Davicioni, Shreyas Joshi, Roger Li, Brant A. Inman, Paras H Shah, Jonathan L. Wright
Journal: Journal of Clinical Oncology (2025)

831 Background: Long non-coding RNA (lncRNA)-based genomic profiling has suggested utility to identify a distinct tumor subgroup corresponding to a favorable prognosis in patients with bladder cancer. Here, we further evaluate a genomic classifier in a cohort of patients undergoing radical cystectomy (RC). Methods: Transcriptome-wide expression profiling using Decipher Bladder was performed on TURBT samples from a cohort of patients with high grade, clinically organ confined (cTa-T2N0M0) UC who subsequently underwent RC without any neoadjuvant therapy (n=226). LncRNA-based luminal favorable status was determined using a previously developed genomic classifier. The primary endpoint was overall survival (OS) following surgery. Secondary endpoints included cancer-specific mortality and upstaging at RC. Results: In the study, 134 patients were clinical NMIBC (cTa/Tis/T1) and 92 patients were cT2. We identified 60 patients with luminal favorable subtype, all of which showed robust gene expression patterns associated with less aggressive bladder cancer biology. On MVA, patients with the luminal favorable subtype (vs. without) were significantly associated with lower odds of upstaging to pT3+ disease (OR [95% CI] 0.32 [0.12-0.82], p = 0.02), any upstaging (OR [95% CI] 0.41 [0.20-0.83], p = 0.01), and any upstaging and/or pN+ (OR [95% CI] 0.50 [0.25-1.00], p = 0.05). Luminal favorable bladder cancer was significantly associated with better OS (HR 0.33 [95% CI 0.15-0.74], p=0.007). Conclusions: This study validates the performance of the genomic classifier for identifying urothelial carcinomas with a luminal favorable subtype, harboring less aggressive tumor biology.