tbuckley/cabot-search huggingface dataset:
Punch: Preliminary results from a phase II study of intra-arterial chemotherapy (IAC) combined with tislelizumab and bacillus Calmette-Guerin (BCG) in high-risk non-muscle-invasive bladder cancer (HR NMIBC).
Authors: Zongren Wang, Wenhao Zhan, Bin Huang, Cheng Luo, Lingwu Chen, Junxing Chen
Journal: Journal of Clinical Oncology (2024)

618 Background: Previous studies have proved IAC could reduce the recurrence and progression of HR NMIBC. The KEYNOTE-057 study has supported the benefits of PD-1 inhibitor in HR NMIBC patients (pts). Our study was established to evaluate the efficacy and safety of IAC combined with tislelizumab and BCG as a bladder-preserving treatment for HR NMIBC pts. Methods: This open-label, single arm phase II study enrolled BCG-naïve HR NMIBC pts with papillary tumors (high-grade Ta or T1 tumors). Firstly, the papillary tumors should be removed all visible lesions by transurethral resection of bladder tumor (TURBT). Secondly, angiographic catheter was placed into the internal iliac arteries with Seldinger’s percutaneous technique, cisplatin (60 mg/m 2 ) and epirubicin (50 mg/m 2 ) were administered arterially in day 1 (D1), every 3 weeks for 2-4 cycles. And pts received tislelizumab 200 mg IVGTT in D1, every 3 weeks for 2-4 cycles. Finally, pts received 18 instillations of BCG plus at least 8 cycles of tislelizumab (200 mg IVGTT, every 3 weeks). Specifically, pts were started on an induction course of BCG with 6 instillations every week, followed by maintenance with 3 instillations every 2 weeks and 9 instillations every 4 weeks. The primary end point was disease-free survival (DFS) rate at 12 months (defined as no reappearance of high grade or T1 tumors or clinical stage development after the therapy). Secondary end points were bladder-preservation rate, OS and safety. Our study estimated a DFS rate at 12 months was no less than 55% and the study would enroll 27 pts. Results: By Sep. 2023, 13 eligible pts were enrolled. Ten pts were analyzed (male 80.0%; median age 58 years (39-77); pure TCC 80.0%; median tumor size 2.5 cm (0.6-5.4); multiple papillary tumours=60.0%; high-grade Ta=40.0%, T1=60.0%). Median follow-up was 16.4 months (10.8-33.9), the mean number of IAC cycles was 2.4, mean number of tislelizumab cycles was 15.8, and the median BCG instillations was 16 (11-18). The DFS rate at 12 month was 90.0% (95%CI, 71.5%-98.6%). One pt showed reappearance of high-grade Ta and received TURBT. The bladder-preservation rate at 12 months was 100% (95%CI, 100%-100%). The OS rate at 12 months was 100% (95%CI, 100%-100%). 3 pts experienced treatment related adverse events, including nausea (n=1, G2), myalgia (n=1, G2), fatigue (n=1, G2), neutropenia (n=1, G2) and fever (n=1, G3). Conclusions: Our preliminary results supported the use of IAC combined with tislelizumab and BCG as a promising bladder-preserving strategy for HR NMIBC pts. Clinical trial information: ChiCTR2200067146 .
Outcomes with sacituzumab govitecan (SG) in patients (pts) with advanced urothelial carcinoma (aUC) and variant histologies (VH): Analysis of the UNITE study.
Authors: Amanda Nizam, Tanya Jindal, Cindy Y. Jiang, Omar Alhalabi, Matthew P. Davidsohn, Dimitra Rafailia Bakaloudi, Rafee Talukder, Charles B Nguyen, Eugene Oh, Amy K Taylor, Mehmet Asim Bilen, Arnab Basu, Deepak Kilari, Hamid Emamekhoo, Shilpa Gupta, Petros Grivas, Joaquim Bellmunt, Matthew T Campbell, Ajjai Shivaram Alva, Vadim S Koshkin
Journal: Journal of Clinical Oncology (2024)

667 Background: SG is approved in pts with aUC refractory to platinum-based chemotherapy (PBT) and checkpoint inhibitor therapy (CPI). Data on SG outcomes in pts with subtype/variant histologies (VH) are limited. We examined SG-treated pts in the UNITE study and hypothesized that outcomes would be similar between pts with pure urothelial histology (pUC) and any VH component. Methods: UNITE is a multi-site retrospective study of pts with aUC treated (Tx) with targeted agents, such as enfortumab vedotin (EV) and SG. Pts who received SG monotherapy were included in this analysis. Observed response rate (ORR) was assessed by investigators at each site for evaluable pts with scans after ≥ 1 SG cycle using χ 2 and logistic regression. Progression-free and overall survival (PFS, OS) from SG start were assessed using KM method and Cox proportional hazards model. Results: Among 633 total pts in UNITE, 116 received SG monotherapy at 11 US sites. Median age was 70; 79 (68%) male; 97 (84%) Caucasian; 86 (74%) ECOG PS 0/1; 84 (72%) lower tract tumor; 90 (78%) visceral or bone mets; 48 (41%) Bellmunt score ≥2; 72 pts (62%) had pUC and 44 (38%) VH, including 33 (28%) with UC predominant (&lt;50% VH) and 11 (9%) with variant predominant (≥50% VH). For prior therapy, 109 pts (94%) received &gt;2 prior lines; 75 (65%) PBT; 102 (88%) CPI; 109 (94%) EV. Median time from metastatic diagnosis to SG start was 18.6 months (mo) (0.9-84.5). Median follow up from SG start was 10.6 mo (8.5-15.4). Median time on SG was 1.6 mo (0.2-14.7). ORR to SG was 24% (20/84); median PFS and OS from SG start were 3.7 mo (95% CI 3.0-4.6) and 6.7 mo (95% CI 5.3-10.8). VH (n ≥1) included: squamous (SQH) (19, 16%), micropapillary (9, 8%), plasmacytoid (8, 7%), adenocarcinoma (3, 3%), neuroendocrine (NE) (2, 2%). In evaluable pts with VH, ORRs: squamous (3/14), micropapillary (1/4), plasmacytoid (0/6), adenocarcinoma (2/3), NE (1/2). No significant differences were observed in outcomes between pUC and any VH or pUC and SQH (Table). Conclusions: Pts with aUC treated with SG appear to have similar clinical outcomes between pUC and any VH. Responses to SG are observed across different VH. Limitations include low power, tumor heterogeneity, lack of central pathology/scan review, selection and confounding biases. These hypothesis-generating findings suggest activity of SG post-PBT, CPI, and EV in pts with VH, but should be validated in larger cohorts with adequate sample size of specific VH and longer follow up. [Table: see text]
An observational multicenter French study on unanswered questions in patients with advanced renal cell carcinoma (aRCC) treated with cabozantinib: OCTOPUS.
Authors: Constance Thibault, Loic Mourey, David Pasquier, Jean-Christophe Bernhard, Marion Boissier, Valérie Perrot, Laurence Albiges
Journal: Journal of Clinical Oncology (2024)

430 Background: Real-world studies with cabozantinib in aRCC have investigated its effectiveness and tolerability in routine practice, but questions remain unanswered including: Activity of systemic therapies after progression on Cabozantinib, patterns of long-responders and use in elderly patients. Methods: OCTOPUS study (NCT05444933) is a retrospective study of all consecutive patients (pts) treated with cabozantinib 2 nd line (2L) for aRCC from March 2018 to March 2021 in 26 French centers. Pre-defined analysis included: descriptive analysis of Cabozantinib 2L regimen, activity of subsequent line (defined by treatment duration), patterns of long-term responders (defined as duration of cabozantinib more than 12 months in patients with complete, partial response or stable disease); and in elderly pts (&gt;75 years). Results: In total, 252 patients were included. Median age was 63 years (20-86), 84.1% had clear-cell histology. At Cabozantinib 2L initiation, among 69 patients with available IMDC score, IMDC risk was favorable/intermediate/poor in 13.0 %, 49.3% and 37.7 % of the cases, respectively. Patients had an ECOG PS of 1 (45.8%) or 2 (25.8%). Bone, liver and brain metastasis (mets), were present in 130 (52.0%), 69 (27.6%) and 34 (13.6%) patients, respectively. 102 (40.5%) pts had 3 or more mets sites and 167 (66.3%) pts had a prior nephrectomy. 154 (61.1%) pts were pretreated with a tyrosine kinase inhibitor (TKi) based regimen and 94 (37.3%) were pretreated with an immunotherapy (IO) based regimen. Results are reported in the table. 157 patients received a 3 rd line (3L) treatment after cabozantinib: nivolumab (55.4%) or a VEGFR TKI (26.1%) including axitinib (85.4%). In this subgroup, the median duration of treatment (DOT) and median progression free survival (PFS) were respectively 8.2 months and 8.0 months, with a disease control rate (DCR) of 80.3 % for Cabozantinib 2L. Conclusions: We reported the pattern of use of Cabozantinib in RWE, highlighting feasibility in elderly and long-term exposure in long responders as well as subsequent therapy activity. [Table: see text]
Real-world treatment (tx) patterns and clinical outcomes in patients (pts) with locally advanced or metastatic urothelial carcinoma (la/mUC) in Germany: Results of a retrospective observational study (CONVINCE).
Authors: Stefan Machtens, Katrin Schlack, Thomas Kubin, Markus Ruhnke, Clemens Schulte, Anna Eisen, Ulrike Osowski, Silke Guenther, Mairead Kearney, Rainer Lipp, Stephan H. Schmitz
Journal: Journal of Clinical Oncology (2024)

551 Background: Platinum-based chemotherapy (PBC) is the standard-of-care first-line (1L) tx for pts with la/mUC (followed by avelumab 1L maintenance in pts without progressive disease since its approval in Germany in Jan 2021). This study describes demographics, tx patterns, and clinical outcomes for pts with la/mUC treated in routine clinical practice in Germany between 2019 and 2021. Methods: CONVINCE, a retrospective, multicenter medical chart review study, was initiated in Dec 2021 and included adult pts who received 1L tx for la/mUC between 2019 and 2021. All pts were required to have ≥6 months of follow-up data available after end/start of 1L, depending on the type of tx received. Fully anonymized data were obtained from 27 oncology or urology institutions (8 hospitals and 19 office-based practices) across Germany. Descriptive statistics were used to analyze the results, and Kaplan-Meier methods were used to compute time-to-event outcomes. Pts were classified into 3 groups: (A) PBC with end of tx between Jan 2019 and Sep 2021 and (B) immuno-oncology (IO) therapy and (C) other non-PBC tx, both with start of tx between Jan 2019 and Sep 2021. Results: Of 188 pts included, median age at start of 1L was 70 years, 72.3% were male, most had ECOG PS 0/1 (92.5%), and the majority (60.1%) were treated by medical oncologists. A total of 143 pts (group A) received PBC (PBC + gemcitabine, 88.1%; PBC + non-gemcitabine agents, 8.4%; and cisplatin monotherapy, 3.5%). Cisplatin + gemcitabine (82.5%) was used more often than carboplatin + gemcitabine (17.5%). Six pts were treated with avelumab 1L maintenance following PBC. In group B, 36 pts (19.1%) received IO monotherapy (atezolizumab, 44.4%; pembrolizumab, 41.7%). In group C, 9 pts (4.8%) received non-PBC tx. Clinical outcomes in groups A and B are shown in the Table. Results for group C are not shown due to small sample size. Conclusions: CONVINCE describes characteristics, tx patterns, and outcomes in pts with la/mUC in routine clinical practice in Germany. In adherence with tx guidelines, most pts received PBC in 1L. New IO approvals, including avelumab 1L maintenance and other novel agents, could improve outcomes in pts with la/mUC. Further real-world studies should be performed to evaluate the uptake of these options within routine care. [Table: see text]
Urinary minimal residual disease detection predicts recurrence in BCG-unresponsive NIMBC and quantifies molecular response to nadofaragene firadenovec.
Authors: Vikram M Narayan, Come Tholomier, Sharada Mokkapati, Alberto Martini, Vincent M. Caruso, Brian C. Mazzarella, Kevin G. Phillips, Vincent T. Bicocca, Trevor G. Levin, Seppo Yla-Herttuala, David Sawutz, Nigel Parker, David James McConkey, Colin P.N. Dinney
Journal: Journal of Clinical Oncology (2024)

635 Background: Urinary minimal residual disease (uMRD) profiling uses next-generation sequencing to identify mutations associated with urothelial carcinoma and can be used to predict recurrence and assess response to therapy. Nadofaragene firadenovec is a novel intravesical therapy recently approved for BCG-unresponsive non-muscle-invasive bladder cancer (NMIBC). We evaluate the utility of uMRD to identify molecular response to Nadofaragene in patients with high-grade (HG) BCG-refractory or relapsed NMIBC. Methods: This was an open-label, multicenter, parallel-arm, phase II study (NCT01687244) of 43 patients with BCG-unresponsive NMIBC who received intravesical nadofaragene. The primary endpoint was 12-month HG-recurrence-free survival (RFS). All patients who received at least one dose were included in the uMRD analysis. Urine samples were collected prior to induction and at 3 months. uMRD testing was done using the UroAmp MRD assay, which identifies single-nucleotide variants, copy-number variants (CNVs), insertion-deletions, copy-neutral loss of heterozygosity, microsatellite instability, and aneuploidy. Results: Among evaluable patients (n=35), initial pathological stages were Ta (n=3), T1 (n=9), and Tis (n=23), with concomitant CIS in six patients. In pre-treatment urine (n=32), TP53, TERT, PIK3CA, ARID1A, PLEKHS1, ELF3, and ERBB2 were among the most prevalently mutated genes. Most CNVs occurred in SOX4 and NIT1. uMRD identified patients with high (72%) and low (28%) recurrence risk in both pre- and post-induction collections. At 12 months, post-induction RFS rate was 100% for low-risk and 38% for high-risk patients (P = 0.038, log-rank test). Pre-induction RFS was 56% for low-risk and 22% for high-risk (P = 0.097, log-rank test). Using matched pre- and post-induction urine (n=15), quantitative drug response was measured and patients categorized as MRD Negative (7%), MRD Complete Responder (13%), MRD Partial Responder (27%), MRD Stable (20%), or MRD Refractory (33%). Recurrence correlated broadly with response groups: MRD Negative and Complete Responder groups did not recur on study, while 7 of 12 patients in the other groups recurred. Conclusions: uMRD enables quantitative assessment of molecular response to drug treatment. uMRD-determined pre-treatment disease burden assessment can support stratification of control and intervention arms in future treatment trials.
Infigratinib versus placebo in patients with resected urothelial cancer (UC) bearing FGFR3 mutation or fusion: Primary DFS analysis from the phase 3, randomized PROOF302 study.
Authors: Sumanta Kumar Pal, Petros Grivas, Shilpa Gupta, Begoña Pérez Valderrama, Alejo Rodriguez-Vida, Florian Roghmann, Elena Sevillano, Surena F. Matin, Yohann Loriot, Srikala S. Sridhar, Guru P. Sonpavde, Mark T. Fleming, Seth P. Lerner, Joaquim Bellmunt, Viraj A. Master, Abhishek Tripathi, Kim Davis, David Friedrich Van Veenhuyzen, Richard Weng, Siamak Daneshmand
Journal: Journal of Clinical Oncology (2024)

629 Background: In the subset of patients with UC bearing alterations in the fibroblast growth factor 3 ( FGFR3) gene, targeted therapies directed at this moiety have shown substantial antitumor effect in the metastatic setting. We examine infigratinib, a potent and selective inhibitor of FGFR3, as adjuvant therapy in patients with high-risk resected UC. Methods: In an international multicenter phase III clinical trial, we randomly assigned patients in a 1:1 ratio to receive either oral infigratinib (125 mg) or placebo daily for 21 days of a 28-day treatment cycle, for a maximum of 13 cycles or until disease recurrence. Eligible patients had confirmed invasive UC with susceptible FGFR3 alterations and had undergone radical surgery within 120 days of randomization. The primary endpoint of the study was centrally assessed disease-free survival (DFS), with secondary endpoints including investigator-assessed DFS, metastasis-free survival (MFS) and overall survival (OS). Results: Despite intensive efforts to enroll approximately 218 patients (with 822 patients consented to molecular pre-screening), only 39 patients were enrolled with 20 and 19 patients randomized to receive infigratinib and placebo, respectively. The frequency of FGFR3 alteration was significantly lower than anticipated, occurring in only 19% of patients overall; mutations were observed in 13% of patients with lower tract UC and 30% of patients with upper tract UC. No significant differences were observed in DFS, MFS or OS, and more frequent grade 3/4 adverse events were noted in the experimental arm (35% versus 16%). No fatal adverse events were observed. Conclusions: Our failure to accrue sufficient patients to the current trial precludes any definitive conclusions around the role of infigratinib as adjuvant therapy for FGFR3-altered UC. In the process of study conduct, however, we garnered substantial insights that may aid in the development of future precision oncology trials for adjuvant UC. Clinical trial information: NCT04197986 .
Clinical Presentation, Classification, and Outcomes of Cardiogenic Shock in Children
Authors: Kriti Puri, Jacob C. Jentzer, Joseph A. Spinner, Kyle D. Hope, Iki Adachi, Sebastian C. Tume, Hari P. Tunuguntla, Swati Choudhry, Antonio G. Cabrera, Jack F. Price
Journal: Journal of the American College of Cardiology (2024)
Sequencing of erdafitinib (erda) and enfortumab vedotin (EV) in patients (pts) with fibroblast growth factor receptor (FGFR2/3) altered (alt) advanced urothelial cancer (aUC): Analysis of UNITE database.
Authors: Cindy Y. Jiang, Hyunsoo Hwang, Tanya Jindal, Wei Qiao, Ilana Epstein, Charles B Nguyen, Shilpa Gupta, Sumit Shah, Mehmet Asim Bilen, Matthew I. Milowsky, Christopher J. Hoimes, Deepak Kilari, Yousef Zakharia, Hamid Emamekhoo, Petros Grivas, Joaquim Bellmunt, Ajjai Shivaram Alva, Vadim S Koshkin, Matthew T Campbell, Omar Alhalabi
Journal: Journal of Clinical Oncology (2024)

616 Background: The optimal therapy sequencing in aUC with FGFR2/3 alt is unclear. FGFR inhibition may increase Nectin-4 expression. We hypothesized that outcomes with EV would be more favorable when given after E compared to before E in pts with aUC harboring FGFR2/3 genomic alt. Methods: Pts with FGFR2/3 alts who received EV only (EVo), E then EV (E-&gt;EV), or EV then E (EV-&gt;E) were included. Overall survival (OS) measured from E or EV start (based on agent given first) and progression-free survival (PFS) measured from EV start were assessed with KM method and group comparison by log rank test with Cox proportional hazards regression model. Variables with p ≤0.2 were included in multivariate analysis (MVA). Wilcoxon rank sum and Fisher’s exact test were used to compare continuous and categorical variables, respectively. Observed response rate (ORR) was compared between groups using χ2 test. Results: Among 633 pts from 16 US sites, 487 had NGS data, and 94 (19%) had FGFR2/3 alterations with 24 receiving E-&gt;EV, 15 EV-&gt;E, and 55 EVo. Median age: 72 yrs; 87% Caucasian, 65% primary bladder tumor, 73% pure urothelial histology, 76% BMI &lt;30, 83% ECOG PS 0-1, 60% visceral metastases (mets) with 23% liver mets, 93% prior IO, and 63% prior Plt. Pts treated with E-&gt;EV vs EV-&gt;E had similar baseline characteristics, but at EV start ECOG PS 0-1 was 93% in EV-&gt;E vs 67% in E-&gt;EV (p=0.04). ORR to EV for E-&gt;EV pts was 32% (CI- 12%-51%) vs 67% (CI 54%-91%) for EV-&gt;E pts (p=0.04). ORR for EVo was 49%. Median OS was 21 months (mo) E-&gt;EV, 19 mo EV-&gt;E, and 12 mo EVo; median PFS was 5, 5, 6 mo, respectively. Univariate analysis (UVA) and MVA results are shown in Table. In MVA, longer OS was seen in pts who received both EV and E vs EVo. Conclusions: We showed longersurvival in pts with FGFR2/3 alt aUC who received both EV and E regardless of sequence, which may reflect guarantee-time bias. Additional limitations include retrospective nature, modest sample size, no central scan review, lack of data for pts who received E only, selection and confounding biases. Larger prospective studies are needed to determine optimal sequencing and putative biomarkers. [Table: see text]
Large-Scale Proteomics Identifies Novel Biomarkers and Circulating Risk Factors for Aortic Stenosis
Authors: Khaled Shelbaya, Victoria Arthur, Yimin Yang, Pranav Dorbala, Leo Buckley, Brian Claggett, Hicham Skali, Line Dufresne, Ta-Yu Yang, James C. Engert, George Thanassoulis, James Floyd, Thomas R. Austin, Anna Bortnick, Jorge Kizer, Renata C.C. Freitas, Sasha A. Singh, Elena Aikawa, Ron C. Hoogeveen, Christie Ballantyne, Bing Yu, Josef Coresh, Michael J. Blaha, Kunihiro Matsushita, Amil M. Shah
Journal: Journal of the American College of Cardiology (2024)
The association between social vulnerability and clinical trials awareness and participation: A HINTS-SEER analysis.
Authors: Rishi Sekar, Lindsey A. Herrel, Kristian Stensland
Journal: Journal of Clinical Oncology (2024)

546 Background: Clinical trials are integral to science and can ensure access to standard of care treatments, providing benefits to individual participants and society. Unfortunately, fewer than 5% of eligible cancer patients participate in clinical trials, and large facets of the population remain starkly underrepresented, excluding them from these benefits and potentially compromising the generalizability of biomedical knowledge. Adverse social determinants of health (SDOH), or social vulnerability, may affect awareness and the decision to participate in a clinical trial, especially in underrepresented or historically excluded populations. In this study, we evaluate the association between population-level SDOH and clinical trials awareness and participation. Methods: We performed a cross-sectional analysis of the 2021 Health Information National Trends – Surveillance, Epidemiology, and End Results (HINTS-SEER), a nationally representative survey of 1,234 cancer survivors. The primary outcomes of interest included awareness of clinical trials “as a possible treatment option for your cancer” and “participation in a clinical trial for treatment of your cancer”. The primary exposure was the Centers for Disease Control and Prevention Social Vulnerability Index (CDC SVI), which was linked to each survey respondent by ZIP code of residence. Survey weighted multivariable logistic regression analyses were performed to evaluate the association between SVI quintile and clinical trial awareness and participation, adjusting for age, sex, race/ethnicity, and education level. Results: This survey weighted analysis represents a population of over 400,000 patients. Only 15.1% of patients were aware of clinical trials, with the most socially vulnerable patients having lower rates of awareness compared to the least socially vulnerable patients (8.5% vs. 17.9%). Similarly, only 7.7% of patients participated in a clinical trial, with the most socially vulnerable patients having lower rates of participation compared to the least socially vulnerable patients (3.0% vs. 10.1%). On multivariable analysis, the most socially vulnerable patients had significantly lower odds of clinical trials awareness (OR 0.43, CI 0.20 – 0.94) and clinical trials participation (OR 0.15, CI 0.03 – 0.73) compared to the least socially vulnerable patients, adjusting for age, sex, race/ethnicity, and education level. Conclusions: In this analysis of HINTS-SEER, a contemporary and novel survey of cancer survivors, rates of clinical trial awareness and participation remain concerningly low. Notably, adverse SDOH has a strong influence, with the most vulnerable patients being far less likely to be aware of or participate in a clinical trial. With the goal of achieving equitable cancer care, identifying and alleviating barriers to clinical trial participation, especially those rooted in SDOH, is critical.
Cutting-edge novel device in the treatment of obesity
Authors: Jan Kral, Jana Selucka, Katerina Waloszkova, Marek Buzga, Julius Spicak, Evzen Machytka
Journal: Endoscopy (2024)

A 57-year-old patient with arterial hypertension, dyslipidemia, and obesity grade I (BMI 34.9 kg/m2, 95 kg, 165 cm) underwent a new and unique sleeve gastroplasty procedure for weight reduction ([Video 1]).
Reply to Bowen et al.
Authors: Hugo I. Uchima, Raquel Muñoz-González, Anna Calm, Maria Pellisé
Journal: Endoscopy (2024)

Letter to: Therapeutic endoscopy and appendiceal lesions – train and evaluate before interveningEndoscopy 2024; 56(02): 159-160DOI: 10.1055/a-2185-3802