tbuckley/cabot-search huggingface dataset:
Inclusion of patients with reduced performance status (ECOG 2 or higher) in FDA registrational trials for renal cell carcinoma (RCC).
Authors: Ronit Juthani, Panah Parab, Kala Seetharaman
Journal: Journal of Clinical Oncology (2025)

453 Background: Clinical trials often use performance status indicators to include only those participants with good baseline functional status. The Eastern Cooperative Oncology Group (ECOG) Performance Status (PS) and the Karnofsky Performance Scale (KPS) are two such scales that determine a cancer patient’s ability to perform common tasks. As a result, the study population does not accurately represent the real-world population. We evaluated the inclusion of patients with ECOG 2 or greater/ KPS less than 70 in RCC clinical trials leading to FDA approvals between 2014 and 2024. Methods: The US Food and Drug Administration (FDA) approvals for drugs approved in RCC and associated clinical evidence were collected from the FDA website from 2014-2024. Data from each registrational trial was searched in public databases using drug name, trial name, and registration number. The total number and percentage of participants in each ECOG/KPS category were recorded and analyzed. Results: The FDA approved 13 drugs and combinations for the treatment of RCC from 2014 - 2024. A cumulative total of 8731 participants were included in these trials, with only 24 (0.3%) participants with ECOG PS 2 or greater (KPS &lt;70). Only 3 of the 13 trials included participants with ECOG 2 (KPS &lt;70) with 2 trials having &lt;1% ECOG 2 participants. Only CABOSUN trial had &gt;10% enrolment of ECOG 2 participants. There was no participation of ECOG 3 in any of the trials. Of the total participants, over 70% belonged to ECOG score 0 or KPS 90-100 (excluding CheckMate 214 for which PS distribution data was unavailable). Conclusions: There is poor enrollment of participants with ECOG 2 and greater in registrational clinical trials for RCC. This limits the therapeutic options available for patients with poor PS and is not representative of the real-world population. Greater inclusion of poor PS patients is needed in future trials. Percentage enrollment of patients with reduced PS in registrational trials for RCC. Clinical trial Year Reduced PS% (ECOG 2 or higher/KPS &lt;70) CABOSUN 2017 12.7% S-TRAC 2017 0.2% CheckMate 025 2015 0.4% LITESPARK-005, KEYNOTE-564, TIVO-3, CLEAR, CHECKMATE-9ER, JAVELIN Renal 101, KEYNOTE-426, CheckMate 214, METEOR, Lenvatinib+Everolimus 2016-2023 0.0%
Chemosensory and cardiometabolic improvements after a fasting-mimicking diet: A randomized cross-over clinical trial
Authors: Alessandro Micarelli, Simona Mrakic-Sposta, Alessandra Vezzoli, Sandro Malacrida, Sara Caputo, Beatrice Micarelli, Ilaria Misici, Valentina Carbini, Ilaria Iennaco, Ivan Granito, Valter D Longo, Marco Alessandrini
Journal: Cell Reports Medicine (2025)
Patterns of split-dose gemcitabine and cisplatin (GC) use in patients with locally advanced or metastatic urothelial carcinoma (la/mUC): Results of a 10-country physician survey.
Authors: Richard Thomas O'Dwyer, Sophia Junker, Robert Szulkin, Scarlette Kienzle, Mairead Kearney, Srikala S. Sridhar
Journal: Journal of Clinical Oncology (2025)

699 Background: Gemcitabine + cisplatin (GC) is a highly effective treatment for la/mUC. For patients who are ineligible for standard GC, split-dose GC is a promising alternative. This study aimed to provide insights into the use of split-dose GC and factors influencing treatment choice across 10 countries. Methods: Between January and March 2024, an international cross-sectional study was conducted via an online survey of physicians treating patients with la/mUC in Australia, Brazil, Canada, France, Germany, India, Italy, Spain, the UK, and the US. Demographics, practice patterns, and clinical parameters influencing treatment choice were collected. Multivariate logistic regression was used to determine factors influencing the use of split-dose GC. Results: The study included 791 physicians, mostly male (73%), who had a mean age of 43 years and an average of 13.2 years in practice, with 59% in academic practice. Most (85%) reported using split-dose GC across different treatment settings, including in 41% in neoadjuvant treatment, 40% in adjuvant treatment, and 43% in the metastatic setting. Physicians with the following characteristics were more likely to use split-dose GC: longer time in practice (per 10 years: odds ratio [95% CI], 1.58 [1.18-2.16]), higher patient volume (per 10 patients: 1.06 [1.01-1.14]), and public vs private practice (1.94 [1.27-2.97]). The preferred schedule in la/mUC was GC 35 mg/m 2 on days 1+8 of a 21-day cycle (57%). Most physicians (80%) used avelumab maintenance treatment after split-dose GC in patients without progression. The table shows acceptable lower thresholds for creatinine clearance (CrCl) reported by physicians for patients receiving split-dose GC. Conclusions: This large international survey underscores the extensive use of split-dose GC as an alternative regimen for patients with la/mUC who are ineligible for standard GC. Physicians who are more experienced and manage more patients are more likely to use split-dose GC. The results highlight the need for evaluating split-dose GC prospectively and establishing consensus guidelines for optimal use of split-dose GC in clinical practice and clinical trials. Physiciansn=635 CrCl in patients with ECOG performance status 0-1, n (%) 50 mL/min 573 (90.2) 40 mL/min 407 (64.1) 30 mL/min 195 (30.7) CrCl in patients with ECOG performance status 2, n (%) 50 mL/min 443 (69.8) 40 mL/min 290 (45.7) 30 mL/min 119 (18.7)
CV1-secreting sCAR-T cells potentiate the abscopal effect of microwave ablation in heterogeneous tumors
Authors: Bihui Cao, Manting Liu, Zecong Xiao, Dongliang Leng, Yubo Zhou, Zhenfeng Zhang, Lu Wang, Xinkun Huang, Qianqian Ni, Wei Cheng, Yehuda G Assaraf, Qi Zhao, Jia Shen, Kangshun Zhu
Journal: Cell Reports Medicine (2025)
Assessing molecular heterogeneity of prostate cancer biopsy sampling: Insights from the MAST trial.
Authors: David J Lee, Brandon A. Mahal, Sanoj Punnen
Journal: Journal of Clinical Oncology (2025)

240 Background: Prostate cancer is heterogeneous and multi-focal, and biopsy sampling often undersamples the tumor or samples different tumor foci. Such heterogeneity can lead to inaccurate molecular classifications of tumor biology on tissue-based prognostic tests. Consequently, this impacts treatment decision making and management in localized prostate cancer. Herein, we evaluate the degree of variability in transcriptomic profiles when assessing genomic profiles from MRI-guided versus template biopsy using the Decipher GRID platform. Methods: A total of 205 men enrolled in the Miami MRI selection for Active Surveillance versus Treatment (MAST) trial (NCT02242773), from which 408 biopsy samples from 159 patients with successful genomic profiling were used in this study. Across the whole time-course, all biopsy cores with successful gene expression profiling were categorized by mpMRI-targeted (149 samples) or template (259 samples) sampling. Three main prognostic signatures (Decipher genomic classifier DGC, derived cell cycle progression CCP, and derived Genomic Prostate score GPS) were used to assess the variation in genomic risk between MRI targeted and template cores and among different PI-RADS lesions. Similar analysis was performed in a selected cohort with Gleason grade 1 disease only to exclude the impact of grade on genomic risk assessment. Results: Using the main genomic signatures in unpaired analysis (comparing all targeted and template biopsies), targeted lesions had higher scores as compared to the random biopsies, except for Decipher score (p=0.105). However, in the paired analysis (only including targets and templates from the same patient), we saw no difference between the groups in all three of the signatures. In the subset of patients with GG1, there was no difference between random and targeted biopsies in paired analysis. Among MRI targeted biopsy cores, PI-RADS level was correlated to Decipher and CCP scores with higher PI-RADS levels resulting in higher genomic scores (p=0.007 and 0.002, respectively). However, when restricting to a subgroup of patients with only GG1 cancer, there was no longer an association between PIRADS and genomic score. Higher concordance of DGC scores between visible and non-visible lesions were observed in the low-risk group. Conclusions: mpMRI sampling showed higher genomic scores compared to template sampling. While we see an association between higher PI-RADS scores and higher genomic scores, this relationship appeared to be driven by grade. Among the subgroup of men with GG1 cores, we found no association between PI-RADS and genomic scores. These findings need further validation in a larger cohort to truly understand the impact of MRI targeting on genomic risk assessment among AS patients. Clinical trial information: NCT02242773 .
Impact of belzutifan on anemia and hypoxia in sporadic and <i>VHL</i> -syndrome-associated renal cell carcinoma.
Authors: Paulo Siqueira do Amaral, Aaron Winer, Katy Beckermann, Heidi Chen, Morgan Lambrecht, Elizabeth Kaiser, Brian I. Rini
Journal: Journal of Clinical Oncology (2025)

522 Background: Inactivation of the tumor suppressor von Hippel-Lindau ( VHL ) gene is associated with VHL -syndrome-associated renal cell carcinoma ( VHL- RCC) and sporadic renal cell carcinoma (spRCC). The inactivation of the VHL results in the accumulation of HIF-2a, promoting the expression of genes involved in angiogenesis and cycle-cell progression. Belzutifan, a HIF2α inhibitor, is approved for the treatment of VHL -RCC and spRCC patients (pts). Understanding the safety differences of belzutifan in these two populations can inform clinical management. Methods: This is a single-center, retrospective analysis of pts with spRCC and advanced VHL- RCC treated with belzutifan monotherapy between November 2018 and August 2024. The study population was separated into groups based on RCC type: spRCC and VHL- RCC. Demographic and clinical data were collected from medical records. The primary endpoints were the incidence of anemia and hypoxia. Continuous variables were reported as median with interquartile ranges (IQR) and compared using Wilcoxon rank-sum test. Categorical variables were presented as frequencies and percentage, with group comparisons performed using the Pearson Chi-Square test. Results: Pts with spRCC were older than those with VHL -RCC pts, with a median age of 67 y vs 41 y (p&lt; 0.001), and were predominantly male, (68% vs 36%, p = 0.035). Reduced glomerular filtration rate (defined as &lt; 50ml/min), was more prevalent in spRCC pts (36.5% vs 4.5%, p = 0.009). Baseline hemoglobin levels were similar between groups 13 g/dL (IQR: 10 – 14) vs.13 g/dL (IQR: 12.8 – 14.8). VHL- RCC pts received belzutifan for longer duration than spRCC pts (30.9 m vs 3.4 m, p &lt; 0.001). In terms of safety, any-grade and Grade 3 anemia were similar between groups, 82% vs 91% (ns) and 54% vs 36% (ns), respectively. However, anemia developed more rapidly in spRCC pts, 29 d vs. 82 d (p &lt;0.01) for any-grade, and 46 d vs. 104 d (p = 0.018) for grade 3 anemia. The need for blood transfusion was more frequent in spRCC patients (18% vs 0%, p &lt; 0.05) as was the use of erythropoietin-stimulating agents 2% vs 4.5%, p = 0.08). Any-grade hypoxia was more frequent in spRCC pts (59% vs 18%, p 0.005), and there was a trend towards more grade 3 hypoxia (54.5% vs 9%, p = 0.052). Grade 3 hypoxia developed faster in spRCC pts (29 d vs 225 d, p = 0.039), the need for oxygen was more frequent in this population (52.5% vs 9.5%, p =0.003). Treatment discontinuations were more frequent in spRCC pts than in the VHL -RCC pts, 36.4% vs 4.5% (p = 0.009), 75% of discontinuations in spRCC were due to toxicity. Conclusions: Our cohort demonstrates differences in the safety profile of belzutifan between spRCC and VHL -RCC patients. These findings underscore the importance for personalized monitoring and management for each patient population.
Efficacy and safety of SABR with TKI and IO therapy in patients with mRCC.
Authors: Kaiwei Yang, Mingwei Ma, Wei Yu, Zhisong He, Xianshu Gao
Journal: Journal of Clinical Oncology (2025)

529 Background: Metastatic RCC is a deadly disease and TKI in combination with IO has become a standard therapy for most patients. But some of the pts may present with oligo-metastasis and some with meta site related symptoms. SABR (Stereotactic Ablative Body Radiotherapy) has been proved to be highly effective for RCC in some studies and with potential immune-enhancing ability. The purpose is to investigate the efficacy and safety of SABR with TKI and IO therapy in pts with mRCC. Methods: This is an ambispective cohort study including pts receiving SABR with TKI and IO at the same time. The primary endpoint was PFS. Secondary endpoints included OS, ORR, DCR and TTTC (Time to treatment change). We also analyzed some of the pts’ gene characteristics to investigate the relationship between gene alterations and prognosis. Adverse events were evaluated according to CTCAE 5.0. Results: Until Aug 2024, we retrospectively analyzed pts from Mar 2020 to Mar 2024, and prospectively from Mar 2024 to May 2024. A total of 79 pts were included, of whom 72.2% were with ccRCC, 68.4% were with oligo-metastases (≤5 meta sites), and 83.5% were combined with SABR before 1st-line systemic therapy failure. All pts were categorized to IMDC intermediate or poor prognosis group and TKI and IO combination was used in all pts. All pts with oligo-metastases received SABR for all tumor sites and others were for cytoreductive purpose.The median follow-up was 20.3 mo. The mPFS was 28.6 mo and TTTC was 31.8 mo. The ORR was 68.4% and the DCR was 89.9%. The DCR of radiation lesions was 96.2%. The mOS was 44.8 mo. For pts received SABR before or after 1 st -line systemic therapy failure, the mPFS were 30.6 mo vs. 9.6 mo, respectively (p=0.004). In addition, The NGS analysis was performed in 25 pts tumor samples. The most frequent genes mutated were VHL (60%), SETD2 (24%), ARID1A (24%), TP53 (20%), PTEN (20%), TEF3 (16%), BAP1 (12%), RET (12%), and PBRM1 (12%). We discovered a favorable trend in the prognosis for PFS in pts with tumors purely driven by VHL loss. Mutations in the mTOR pathway genes, PTEN and HRR-related genes appeared to lead to poorer PFS. However, due to limited sample size, statistical significance was not reached. Grade 3 or above AE was 50.2%, and there was no treatment-related death. Conclusions: Targeted therapy combined with immunotherapy and stereotactic radiotherapy has achieved satisfactory survival results for mRCC, and early intervention by SABR may lead to a better PFS. Clinical trial information: ChiCTR2200059204 .
Abortion Changes Among Residents of an Abortion Rights Protective State
Authors: Kelly A. DeBie, Margaret J. Gutilla, Kayleigh P. Keller, Jennifer L. Peel, Andreas M. Neophytou
Journal: JAMA Network Open (2025)

This cross-sectional study examines whether passage of a 6-week abortion ban in Texas in 2021 was associated with changes in abortion rates among Colorado residents.
Pathogenic Germline Variants in Patients With Metaplastic Breast Cancer
Authors: Kaitlin Demarest, Arravinth Anantharajah, Kara N. Maxwell, Mersedeh Rohanizadegan, Angela Bradbury, Katherine L. Nathanson, Anne Marie McCarthy, Susan M. Domchek, Anupma Nayak, Payal D. Shah
Journal: JAMA Network Open (2025)

Importance Metaplastic breast cancer (MpBC) is a rare, heterogeneous disease often associated with inferior outcomes. A growing body of literature describes the clinical and molecular features of MpBC, yet limited data describe the pathogenic germline variants (PGVs) in breast cancer susceptibility genes among affected individuals. Objective To examine the frequency and types of PGVs in breast cancer genes among patients with MpBC. Design, Setting, and Participants This is a descriptive retrospective cohort study of patients who received a diagnosis of MpBC at the University of Pennsylvania between January 2010 and May 2023. Electronic medical records were reviewed for demographic, clinicopathologic, and germline genetic testing information. Germline variant status was independently confirmed by a licensed genetic counselor and a physician with expertise in genetics. MpBC diagnosis and subtype were confirmed by a breast pathologist. Participants were identified via query of an institutional pathology database for reports signed between January 2010 and May 2023 including the term metaplastic . Among 320 initially obtained reports, 272 individuals had confirmed MpBC and were included in the study. Exposure Germline genetic testing to investigate the presence of PGVs in breast cancer susceptibility genes. Main Outcomes and Measures The primary outcome measurement was the prevalence of PGVs in breast cancer susceptibility genes among participants. The hypothesis that individuals with MpBC have an enrichment of PGVs in genes associated with inherited breast cancer risk was formulated before data collection. Results The total sample size was 272 women, and the median age at diagnosis was 58 years (range, 20-102 years); all were biological female patients; 143 of 272 (52.6%) had documentation of germline genetic testing; and participants with testing were significantly younger than those without (median age, 53 years [range, 20-79 years] vs 63 years [range, 29-102 years]; P &amp;amp;lt; .001). Of the 143 patients, 24 (16.8%) had a PGV in a breast cancer susceptibility gene ( BRCA1 , n = 17; BRCA2 , n = 5; PALB2 , n = 1; CHEK2 , n = 1). Patients with PGV-associated MpBC received a diagnosis at a younger age than those with sporadic disease, but there were no significant differences in hormone receptor positivity, ERBB2 status, or metaplastic subtype. Conclusions and Relevance In this cohort study of patients with MpBC, a substantial proportion of clinically tested patients had a PGV in a breast cancer susceptibility gene, most commonly BRCA1 . Germline testing was high yield in patients with MpBC, many of whom would be included in current germline testing eligibility criteria.
Discrepancies in neglected tropical diseases burden estimates in China: comparative study of real-world data and Global Burden of Disease 2021 data (2004-2020)
Authors: Guo-Jing Yang, Han-Qi Ouyang, Zi-Yu Zhao, Wei-Hao Li, Ibrahima Socé Fall, Amadou Garba Djirmay, Xiao-Nong Zhou
Journal: BMJ (2025)

Abstract Objectives To assess the discrepancies between real-world data and the Global Burden of Disease (GBD) 2021 estimates for six neglected tropical diseases in China. Additionally, to evaluate the applicability of the GBD model within the Chinese context and to assess the effectiveness of China's historical prevention and control policies for neglected tropical diseases. Design Comparative study of real-world data and GBD 2021 (2004-2020). Main outcome measures Disability adjusted life years (DALYs). Methods DALYs based on reported data for leprosy, echinococcosis, schistosomiasis, visceral leishmaniasis, dengue, and rabies from 2004 to 2020 were compared with the estimated DALYs from the GBD 2021 database. Additionally, we combined and analysed China's historical policies on prevention and control of neglected tropical diseases with real-world DALYs. Data sources Reported data were sourced from the Chinese Center for Disease Control and Prevention’s China Public Health Science data centre and related reports. Data for GBD 2021 and GBD 2019 were obtained from GBD databases. These data included all of China’s 31 provinces (including autonomous regions and municipalities) and the Xinjiang Production and Construction Corps. Results The total real-world DALYs based on reported data of six neglected tropical diseases decreased from 260 000 person years in 2004 to 19 000 person years in 2020, with a 93% (241 000/260 000 person years) reduction. The 17 year average real-world DALYs from 2004 to 2020 versus the GBD 2021 estimates for the same period were 42 v 500 for leprosy, 960 v 11 000 for echinococcosis, 64 000 v 98 000 for schistosomiasis, 56 v 16 000 for visceral leishmaniasis, 190 v 780 for dengue, and 47 000 v 67 000 for rabies. The ratios of the GBD estimates to the real-world DALYs for the six neglected tropical diseases were 17 for leprosy, 11 for echinococcosis, 1.5 for schistosomiasis, 280 for visceral leishmaniasis, 4.2 for dengue, and 1.4 for rabies. Conclusions The findings indicate that reliance solely on global estimates, such as those of the GBD, may not sufficiently capture the dynamics of neglected tropical diseases in China. Integrating local epidemiological data into global health assessments is crucial to develop accurate and effective public health policies. This study highlights the importance of continuously updating and improving data collection and surveillance methods to adapt public health strategies to evolving disease patterns.
Neuropathy, skin rash, and hyperglycemia as predictors of response to enfortumab vedotin in locally advanced and metastatic bladder and upper tract urothelial carcinoma.
Authors: Tareq Salous, Rebecca Hassoun, Sandra K. Althouse, Stephanie Schneck, Jennifer King, Nabil Adra
Journal: Journal of Clinical Oncology (2025)

771 Background: Enfortumab vedotin (EV) in combination with pembrolizumab is FDA approved for treatment of locally advanced and metastatic urothelial cancer. Neuropathy, skin rash, and hyperglycemia are common side effects of EV. We evaluated the impact of presence of neuropathy, skin rash, and hyperglycemia on progression free survival (PFS) in patients (pts) with bladder or upper tract urothelial carcinoma treated with EV. Methods: The Indiana University bladder cancer database was queried for pts with locally advanced and metastatic bladder and upper tract urothelial carcinoma who were treated with EV with or without pembrolizumab. Pts with variant histology were included. Toxicities were documented throughout the course of treatment. Association of neuropathy, skin rash and hyperglycemia and PFS were compared to patients without any of the side effects using the log-rank test. Results: Between 2018-2024, a total of 83 pts were treated with EV with at least 2 doses. The median age was 69 years (range, 39-89). 47 pts had EV + pembrolizumab, while 36 pts had EV as single agent. 43 pts received EV as 1st, 28 pts as 2nd, 10 pts as 3rd, and 2 pts as 4th line of treatment. Metastatic sites were lymph nodes in 42 pts, lungs in 34 pts, bones in 29 pts, liver in 16 pts, and brain in 7 pts. Median follow-up from the start of EV treatment was 14 months (range, 1-33). Neuropathy was reported in 30 (36%) pts, skin rash in 32 (39%) pts, and hyperglycemia in 6 (7%) pts. The median PFS in patients who did not experience neuropathy/skin rash/hyperglycemia was 4.5 months (95% CI, 2.4-11.0), 10.6 months (95% CI, 7.2-15.7) in pts who experienced neuropathy (P = 0,01), 8.6 months (95% CI, 7.3-20.2) in pts who experienced skin rash (P = 0.01), and 15.9 months (95% CI, 5.1-15.9) in pts who experienced hyperglycemia (P = 0.03). Conclusions: The presence of neuropathy, skin rash, or hyperglycemia in patients with metastatic bladder or upper tract urothelial carcinoma treated with EV was associated with improved PFS.