tbuckley/cabot-search huggingface dataset:
Hospitalizations in veterans treated with monotherapy vs combination therapy for metastatic hormone sensitive prostate cancer.
Authors: Kara Ingram, Robert Wilson, Jason M Doherty, Daniel B. Eaton, Martin W. Schoen
Journal: Journal of Clinical Oncology (2025)

72 Background: Current treatment of metastatic hormone sensitive prostate cancer (mHSPC) includes androgen deprivation therapy (ADT) monotherapy or combination therapy (ADT + docetaxel or an androgen receptor pathway inhibitor). However, no comparative studies have been conducted to assess the hospitalization rates and causes of admission between the two treatment groups. We assessed the hospitalization rates of the different therapies to determine adverse events and improve treatment selection in mHSPC. Methods: A nationwide retrospective study of 6,651 US Veterans with de novo mHSPC in the Veterans Health Administration between 2013-2021. Baseline characteristics for each treatment group were obtained including age, prostate serum antigen (PSA), total number of cardiac drugs, and total number of Anatomic Therapeutic Chemical (ATC) drugs. The five most frequent ICD codes associated with hospitalizations were obtained for each group, excluding the ICD codes for prostate cancer and bone metastases. Quasi-Poisson regression was used to determine differences in hospitalization rates between the two groups. Results: Evaluation of the median baseline characteristics between the two groups showed increased age and decreased PSA (Table). There was no difference between the number of cardiac drugs and total number of ATC drugs between the groups. The 5 most frequent ICD codes for monotherapy were AKI (17%), UTI (11%), essential hypertension (7%), sepsis (5%), and acute post-hemorrhagic anemia (4%). The 5 most frequent ICD codes for combination therapy were AKI (17%), UTI (13%), acute hypoxic respiratory failure (8%), sepsis (7%), and malnutrition (6%). The monotherapy group had a greater increase in hospitalization rates after therapy initiation when compared to combination therapy ( see table ). Quasi-Poisson regression for the hospitalization rates between the two groups had a p-value of 0.018. Conclusions: The rate of hospitalizations increased in the monotherapy treatment group compared to combination therapy. This is likely due to the monotherapy treatment group having a more advanced age and more severe comorbidities. Future directions could include comparing hospitalization rates of combination therapy with ARPI vs docetaxel. This analysis will guide physicians in selecting the more appropriate therapy according to a patient’s individual risk profile and co-morbidities. Age (p &lt; 0.001) PSA(p = 0.008) Pre-treatment hospitalization rate Post-treatment hospitalization rate ADT monotherapy(n = 5146) 75.0 76.2 120 per 1000 person-years 340 per 1000 person-years ADT combination therapy (n = 1505) 72.0 86.3 100 per 1000 person-years 260 per 1000 person-years
Paclitaxel, ifosfamide, cisplatin (TIP) in patients with advanced urethral adenocarcinoma: A single center, retrospective analysis.
Authors: Gwanhyun Park, Inkeun Park, Shinkyo Yoon, Jae Lyun Lee
Journal: Journal of Clinical Oncology (2025)

656 Background: Urethral adenocarcinoma (UA) is a very rare subtype of cancers arising in urethra, which is known for female predominance and poor prognosis. Rarity of UA impedes the conduction of prospective clinical trial, thus the treatment option for advanced UA is very limited. Usually platinum-based chemotherapy is given based on case reports. We conducted retrospective single center cohort review of TIP regimen in patients (pts) with locally advanced, recurrent or metastatic UA to evaluate its efficacy and safety. Methods: Clinical data of 18 pts with locally advanced, metastatic, or recurrent UA who received TIP regimen at the Department on Oncology, Asan Medical Center from Jul 2016 to Jan 2024 were collected. To be eligible, pts should have histologic confirmation of adenocarcinoma, adequate clinical information, and baseline and follow-up imaging test results. TIP regimen consists of paclitaxel 200 mg/m 2 over 3 hours intravenously (iv) on day 1 (D1), ifosfamide 1,500 mg/m 2 over 1 hour iv on D1-3 with mesna 300 mg/m 2 3 times a day iv on D1-3, and cisplatin 70 mg/m2 over 1 hour iv on D1. We recommended pegylated G-CSF for prevention of severe neutropenia and febrile neutropenia. The primary endpoint was objective response rate (ORR) according to RECIST v1.1, and secondary end points were progression-free survival (PFS), overall survival (OS), and toxicity. Results: A total of 18 pts were enrolled. All pts were female, and median age was 62 (range 43-74). Disease status was locally advanced (32%), recurrent (47%), and initially metastatic (16%), and ECOG PS were 0 (22%), 1 (72%), and 2 (6%). Most common site of metastasis were lymph nodes (50%), surgical bed (22%), lung (22%), and peritoneum (17%). Patients received TIP as 1 st line (67%) and 2 nd line (33%). Thirteen pts received prophylactic pegylated G-CSF. Median 4 cycles (range 1-6) of TIP were administered, and ORR was 44% (partial response 44%, stable disease 50%, and progressive disease 6%). With a median follow-up duration of 38.7 months, median PFS and OS were 7.0 months [95% confidence interval (CI) 3.8-10.2] and 40.0 months (15.6-63.7), respectively. Most common adverse events included anemia, peripheral neuropathy, anorexia, nausea, fatigue, neutropenia, thrombocytopenia. Most adverse events were manageable, and no unexpected toxicities were found. Conclusions: TIP showed promising efficacy in pts with advanced UA. TIP might be considered as one of treatment options for pts with advanced UA, although efficacy and safety should be validated in larger cohort.
A phase 1/2 study of detalimogene voraplasmid (EG-70) intravesical monotherapy for patients with high-risk non-muscle invasive bladder cancer (NMIBC).
Authors: Shreyas Joshi, Sam S. Chang, Rian J. Dickstein, Gautam Jayram, Neal D. Shore, Jen-Jane Liu, Yair Lotan, Raj Satkunasivam, Anne K. Schuckman, Gary D. Steinberg, John R. Taylor, Tammy Linback, Raj Pruthi, James C. Sullivan, Christine Tosone, Ashish M. Kamat
Journal: Journal of Clinical Oncology (2025)

TPS886 Background: High-risk NMIBC is generally treated with adjuvant intravesical bacille Calmette-Guérin (BCG); however, ~50% of patients experience recurrence and/or progression after BCG and are considered unresponsive. Detalimogene voraplasmid (EG-70) is an investigational, intravesically administered therapy designed to elicit local stimulation of anti-tumor immune responses in the bladder and drive durable efficacy in BCG-unresponsive NMIBC, while mitigating the risk of systemic toxicities from immune stimulation. The Phase 1 (dose-escalation) portion of the first-in-human Phase 1/2, open-label, multicenter study (LEGEND; NCT04752722) of detalimogene voraplasmid is complete. The Phase 2 dose was identified, treatment was generally well tolerated, and the overall complete response (CR) rate was 73% [Kalota S, et al. AUA 2024]. Here we describe the ongoing Phase 2 portion of the study, which opened to enrollment in May 2023; a new cohort of papillary only (no carcinoma in situ [CIS]) disease is being included. Methods: Eligibility criteria: age ≥18 years; ECOG PS 0−2; NMIBC, with/without resected coexisting papillary tumors, ineligible for, or elected not to undergo, cystectomy; satisfactory bladder function. Patients receive detalimogene voraplasmid 0.8 mg/mL in 50 mL (intravesical administration, Weeks 1, 2, 5 &amp; 6, 12-week cycle) for 4 cycles: BCG-unresponsive with CIS (Cohort 1); BCG-exposed or BCG-naïve with CIS (Cohort 2); BCG-unresponsive with high-grade papillary bladder cancer without CIS (Cohort 3). Phase 2 primary endpoints: efficacy (CR rate at Week 48); safety. Secondary endpoints: progression-free survival; CR rate at Weeks 12, 24, 36, and 48; duration of response. The study is being conducted in accordance with the ethical principles of the Declaration of Helsinki and is consistent with ICH/GCP. All patients provide written informed consent. The Phase 2 portion of the study is enrolling and will recruit up to 300 patients from sites in the USA, Canada, Europe, and the Asia-Pacific region. Clinical trial information: NCT04752722 .
Mature phase 1 follow up of alpha emitter 225Ac-J591 with 177Lu-PSMA-I&amp;T in advanced prostate cancer.
Authors: Gabriel Raab, Tobechukwu Joseph Okobi, Aaron N. Holmes, Sandra Huicochea Castellanos, Vasilios Avlonitis, Amie Patel, Charlene Thomas, Jones T. Nauseef, Ana M. Molina, Zachary Davidson, Cora N. Sternberg, David M. Nanus, Joe Reginald Osborne, Neil Harrison Bander, Scott T. Tagawa
Journal: Journal of Clinical Oncology (2025)

185 Background: Targeted radionucleotide therapy (TRT) has become a standard of care. α-emitters have a higher energy transfer over a shorter range than β-emitters. PSMA-targeting antibodies have different biodistribution than small molecules and may improve intracellular retention based on pre-clinical models. Here, we present mature follow up of a phase 1 dose-escalation trial of 225Ac-J591 plus 177Lu-PSMA-I&amp;T (aka PNT2002). Methods: Inclusion criteria:progressive mCRPC with ≥1 prior AR pathway inhibitor (ARPI), prior chemo (or unfit/refused), and with ≥1 lesion on PSMA PET where SUVmax &gt;liver. 177Lu-PSMA-I&amp;T (6.8 GBq) and 225Ac-J591 (30, 35, or 40 KBq/kg) given up to 2 doses 8 weeks apart. Primary outcome was dose-limiting limiting toxicity and recommended phase 2 dose (RP2D). Preliminary efficacy outcomes examined were overall survival (OS), progression-free survival (PFS), PSA response, and circulating tumor cell (CTC) changes. Results: 18 patients (6 at each dose level) with median age 70, median PSA of 54.4 (2.43-9614). Previous therapies: 11 (61%) with &gt;1 ARPI, 12 (67%) chemo, 5 (28%) sip-T, 3 (17%) radium-223. Baseline CTCs: 15 detectable, 9 unfavorable. The median SUVmax of the most avid lesion on PSMA-PET was 31.4 (95% CI 11-82.7). Metastatic sites: 13 bone, 9 lymph node, 4 visceral. 8 (44%) were Halabi high risk. Treatment emergent adverse events (AEs) included neutropenia in 3 patients (17%), all Grade &lt;2; thrombocytopenia occurred in 12 (67%) (3 GR 3); anemia in 10 (56%, 3 GR 3); 12 (67%) xerostomia (one Gr2); one (6%) with acute renal failure. Other AEs: 10 (56%) pain flare (1 Gr3 in pt with cord compression), 11 (61%) nausea (all Gr 1), 9 (50%) fatigue (all Gr 1). The RP2D of 225Ac-J591 was 35 KGBq/kg. 17 (94%) patients experienced a decline in PSA levels, with 11 out of 17 (64%) achieving PSA50 response. 4/5 patients (80%) converted from unfavorable to favorable CTC count, 4/8 (50%) from detectable to undetectable, 1 of 2 (50%) remained undetectable. Median biochemical PFS was 7.3 months (95% CI 2.7-15.8), and median OS was 29.8 mo (95% CI 7.4-NR), with 10 patients still alive at time of submission. 5 were progression free at one year, including 3 of 6 treated at RP2D. With longer follow up, no new safety signals were identified. Conclusions: The combination of PSMA-targeted alpha (via antibody) plus beta (via small molecule) was feasible. High grade AEs were rare and no new safety signals emerged with longer term follow up. Nearly all patients had PSA decline, and 5 had durable disease control off therapy. Clinical trial information: NCT04886986 .
Surveillance with plasma ctDNA in non-muscle invasive bladder cancer.
Authors: Santosh Kagathur, Shaniza Haniff, Joshua Jonathan Christy, Dan Isaac
Journal: Journal of Clinical Oncology (2025)

864 Background: Non-muscle invasive bladder cancer (NMIBC), constitutes 70% of all bladder cancer. Routine surveillance methods for detecting patients at risk of progression to muscle-invasive or metastatic disease are invasive and may delay intervention. Circulating tumor DNA (ctDNA) analysis presents a non-invasive alternative for monitoring minimal residual disease, potentially allowing for earlier detection of disease progression or recurrence. This study evaluates the role of plasma ctDNA in the early detection and monitoring of high-risk NMIBC. Methods: Eleven high-risk NMIBC patients were enrolled in this study. All patients underwent standard transurethral resection of bladder tumors (TURBT) before enrollment. Blood samples were collected prior to initiation of intravesical therapy and then every three months for two years (from January 12, 2022, to February 1, 2024). Plasma ctDNA was analyzed using Natera's Signatera, employing multiplex PCR and next-generation sequencing to detect tumor-specific mutations. Individual mutation profiles were established via whole-exome sequencing of tumor and matched normal tissue. Detection of ctDNA was compared with results from routine cystoscopy, urine cytology, and upper-tract imaging. Disease outcomes of interest included relapse, progression to muscle-invasive disease, and metastasis. Results: Of the eleven high-risk patients, one patient developed diffuse bilateral upper tract high-grade recurrence followed by metastatic disease that was preceded by positive ctDNA. Another patient was noted to have muscle-invasive disease again following the detection of ctDNA and subsequently underwent radical cystectomy. This patient eventually developed metastasis six months later. One patient elected to withdraw from the study. In our study, 20% of patients with high-grade papillary NMIBC had detectable ctDNA nine months post-diagnosis. Notably, both patients with positive ctDNA had normal findings on routine surveillance. However, they eventually progressed to stage IV urothelial carcinoma. In contrast, ctDNA was undetectable in the remaining eight patients, all of whom remained recurrent free to-date. These findings suggest ctDNA may serve as an early predictor of relapse and progression, with a number needed to test of 5 to prevent one delayed identification of disease progression. Conclusions: Plasma ctDNA analysis shows promise as a non-invasive tool for identifying NMIBC patients at risk of disease progression. Early ctDNA detection may enable more personalized treatment approaches, improving patient outcomes. Larger studies are warranted to confirm these findings and support the integration of ctDNA into standard NMIBC surveillance protocols.
GLP1R expression in prostate cancer patients and effects of GLP1R agonism on prostate cancer cells.
Authors: Jordan Vellky, Natalie Marie Reizine, Donald Vander Griend
Journal: Journal of Clinical Oncology (2025)

182 Background: As a disease of aging, metabolic co-morbidities are managed concurrently with prostate cancer. Recent FDA approvals have launched widespread use of GLP1 receptor agonist semaglutide for Type II Diabetes Mellitus and obesity. Mechanistically, semaglutide primarily activates GLP1 receptors in the pancreas. However, GLP1R is also expressed in advanced prostate cancer tissues where GLP1 agonism could affect signaling and disease progression. Understanding the effects of semaglutide treatment in prostate cancer is critical to gain a complete picture of the systemic effects this drug and potentially expose additional contexts where semaglutide can be therapeutically valuable in this disease space. Methods: RNA-sequencing data was accessed from dbGaP (consolidated, n=664) and Gene Expression Omnibus (GSE204057, n=55) to assess GLP1R expression in prostate cancer patients. Bioinformatics analyses were utilized to identify signaling pathways associated with GLP1R expression. Proliferation, metabolism, and signaling after GLP1R agonism with semaglutide were assessed in vitro in prostate cancer cell line models using incucyte, Seahorse, and a kinase proteome profiler array. Results: We identified GLP1R expression in advanced prostate cancer samples including 145/310 (46.8%) of metastases, 59/115 (51.3%) of castration-resistant prostate cancer (CRPC), and 9/15 (60%) of neuroendocrine prostate cancer (NEPC), where it was associated with Notch and Hedgehog Signaling. Semaglutide treatment in pre-clinical prostate cancer models resulted in decreased cell proliferation, decreased glycolytic function, and decreased activation of kinase-mediated signaling. This overall suppression of signaling downstream of GLP1R is consistent with Gai-coupled GPCR signaling, which was confirmed using a cAMP assay. Interestingly, in a trans-differentiation model there was a significant negative correlation between GLP1R and AR expression. Further, proliferation of prostate cancer cells was significantly decreased with combination treatment of enzalutamide with semaglutide compared to either treatment alone. Conclusions: GLP1R was expressed in advanced prostate cancer patients and treatment with semaglutide suppressed growth, metabolism, and signaling. This is clinically significant due to concurrent treatment for metabolic co-morbidities in men with prostate cancer. Our preliminary data shows that co-targeting AR and GLP1R decreased cell growth, suggesting GLP1R agonism may be therapeutically useful in combination with androgen receptor antagonists in advanced prostate cancer.
Biofabrication Directions in Recapitulating the Immune System‐on‐a‐Chip (Adv. Healthcare Mater. 5/2025)
Authors: Robine Janssen, Laura Benito‐Zarza, Pim Cleijpool, Marta G. Valverde, Silvia M Mihăilă, Shanna Bastiaan‐Net, Johan Garssen, Linette E. M. Willemsen, Rosalinde Masereeuw
Journal: Advanced Healthcare Materials (2025)
Neurodevelopmental outcomes at five years in children born very preterm (24–31 weeks) exposed to opioids with or without midazolam: results from the French nationwide EPIPAGE-2 cohort study
Authors: Elizabeth Walter-Nicolet, Laetitia Marchand-Martin, Andrei S Morgan, Monique Kaminski, Valérie Benhammou, Pierre-Yves Ancel, Pierre Tourneux, Véronique Pierrat, Xavier Durrmeyer
Journal: The Lancet Regional Health - Europe (2025)
Enhancement of Bone Tissue Regeneration with Multi‐Functional Nanoparticles by Coordination of Immune, Osteogenic, and Angiogenic Responses (Adv. Healthcare Mater. 5/2025)
Authors: Hyewoo Jeong, Hayeon Byun, Jinkyu Lee, Yujin Han, Seung Jae Huh, Heungsoo Shin
Journal: Advanced Healthcare Materials (2025)
Polymerized Salicylic Acid Microparticles Reduce the Progression and Formation of Human Neutrophil Extracellular Traps (NET)s (Adv. Healthcare Mater. 5/2025)
Authors: Emma R. Brannon, Logan D. Piegols, Gillian Cady, Daniel Kupor, Xueqi Chu, M. Valentina Guevara, Mariana R.N. Lima, Yogendra Kanthi, David J. Pinsky, Kathryn E. Uhrich, Omolola Eniola‐Adefeso
Journal: Advanced Healthcare Materials (2025)
Gut microbiome changes with micronutrient supplementation in children with attention–deficit/hyperactivity disorder: the MADDY study
Authors: Hayleigh K. Ast, Matthew Hammer, Shiqi Zhang, Alisha Bruton, Irene E. Hatsu, Brenda Leung, Ryan McClure, Priya Srikanth, Yuliya Farris, Lydia Norby-Adams, Lisa M. Robinette, L. Eugene Arnold, Jonathan R. Swann, Jiangjiang Zhu, Lisa Karstens, Jeanette M. Johnstone
Journal: Gut Microbes (2025)

Micronutrients have demonstrated promise in managing inattention and emotional dysregulation in children with attention-deficit/hyperactivity disorder (ADHD). One plausible pathway by which micronutrients improve symptoms is the gut microbiome. This study examines changes in fecal microbial composition and diversity after micronutrient supplementation in children with ADHD (N = 44) and highlights potential mechanisms responsible for the behavioral improvement, as determined by blinded clinician-rated global improvement response to micronutrients. Participants represent a sub-group of the Micronutrients for ADHD in Youth (MADDY) study, a double blind randomized controlled trial in which participants received micronutrients or placebo for 8 weeks, followed by an 8-week open extension. Stool samples collected at baseline, week 8, and week 16 were analyzed using 16S rRNA amplicon sequencing targeting the V4 hypervariable region. Pairwise compositional analyses investigated changes in fecal microbial composition between micronutrients versus placebo and responders versus non-responders. A significant change in microbial evenness, as measured by alpha diversity, and beta-diversity, as measured by Bray-Curtis, was observed following micronutrients supplementation. The phylum Actinobacteriota decreased in the micronutrients group compared to placebo. Two butyrate-producing bacterial families: Rikenellaceae and Oscillospiraceae, exhibited a significant increase in change following micronutrients between responders versus non-responders. These findings suggest that micronutrients modulated the composition of the fecal microbiota and identified specific bacterial changes associated with micronutrient responders.
Deconer: An Evaluation Toolkit for Reference-based Deconvolution Methods Using Gene Expression Data
Authors: Wei Zhang, Xianglin Zhang, Qiao Liu, Lei Wei, Xu Qiao, Rui Gao, Zhiping Liu, Xiaowo Wang
Journal: Genomics Proteomics & Bioinformatics (2025)

Abstract In recent years, computational methods for quantifying cell type proportions from transcription data have gained significant attention, particularly those reference-based methods which have demonstrated high accuracy. However, there is currently a lack of comprehensive evaluation and guidance for available reference-based deconvolution methods in cell proportion deconvolution analysis. In this study, we introduce Deconvolution Evaluator (Deconer), a comprehensive toolkit for the evaluation of reference-based deconvolution methods. Deconer provides various simulated and real gene expression datasets, including both bulk and single-cell sequencing data, and offers multiple visualization interfaces. By utilizing Deconer, we conducted systematic comparisons of 16 reference-based deconvolution methods from different perspectives, including method robustness, accuracy in deconvolving rare components, signature gene selection, and building external reference. We also performed an in-depth analysis of the application scenarios and challenges in cell proportion deconvolution methods. Finally, we provided constructive suggestions for users in selecting and developing cell proportion deconvolution algorithms. This work presents novel insights to researchers, assisting them in choosing appropriate toolkits, applying solutions in clinical contexts, and advancing the development of deconvolution tools tailored to gene expression data. The tutorials, manual, source code, and demo data of Deconer are publicly available at https://honchkrow.github.io/Deconer/.