tbuckley/cabot-search huggingface dataset:
Chlorhexidine vs Routine Foot Washing to Prevent Diabetic Foot Ulcers
Authors: Alison D. Lydecker, Justin J. Kim, Gwen L. Robinson, J. Kristie Johnson, Clayton H. Brown, Christopher C. Petruccelli, Michael L. Terrin, David J. Margolis, Mary-Claire Roghmann
Journal: JAMA Network Open (2025)

Importance Foot ulcers are a common and feared complication for people with diabetes because 20% of foot ulcers become infected and lead to a lower extremity amputation. Objective To evaluate the effect of daily foot care using chlorhexidine wipes vs soap-and-water wipes for 1 year on the risk of developing new foot complications in veterans with diabetes. Design, Setting, and Participants This double-blind, placebo-controlled, phase 2b randomized clinical trial was conducted at the Baltimore Veterans Affairs (VA) Medical Center between January 2019 to January 2023. Veterans were eligible if they had a diabetes diagnosis, were at high risk for diabetic foot complications, were ambulatory, had both feet, and did not have a current foot infection. Participants were randomly assigned 1:1 to receive either soap-and-water wipes (control group) or 2% chlorhexidine wipes (chlorhexidine group). Intention-to-treat data analysis was conducted from October 5, 2023, to April 24, 2024. Intervention Daily use of a 2% chlorhexidine wipe or a soap-and-water wipe on the feet for 1 year. Wipes were nearly identical in color, size, shape, thickness, feel, and scent. Both chlorhexidine and control groups received the same lotion for application on the feet after wipe use and education on foot self-care. Main Outcomes and Measures The primary outcome was time in days from randomization to new foot complication, including chronic foot ulcer, foot infection, or foot amputation. Results A total of 175 participants (170 males [97%]; mean [SD] age at enrollment, 68 [9] years; 1 Asian [1%], 117 Black or African American [67%], 53 White [30%] individuals) were randomly assigned to the chlorhexidine group (n = 88) or the control group (n = 87). Twelve participants (14%) in the chlorhexidine group and 14 participants (16%) in the control group developed a new foot complication within 1 year. Median (IQR) time from randomization to development of a new foot complication was 232 (115-315) days. The reduction in hazard of new foot complications in the chlorhexidine group compared with the control group was not significant (hazard ratio, 0.83; 95% CI, 0.39-1.80). The intervention was well tolerated, with 145 participants (83%) continuing it over the study period. Sixty adverse events occurred, but none was related to the study products or procedures. Conclusions and Relevance This randomized clinical trial found that daily use of chlorhexidine wipes for foot washing for 1 year did not lead to a significant reduction in the risk of new foot complications compared with daily use of soap-and-water wipes. The intervention was well tolerated, and the trial provides important lessons for future studies on diabetic foot ulcer prevention. Trial Registration ClinicalTrials.gov Identifier: NCT03503370
A randomized phase 3 trial of docetaxel added to ADT plus ARTA in patients with metastatic hormone-sensitive prostate cancer (Adding Docetaxel, KCSG- GU22-24).
Authors: Kwonoh Park, Inkeun Park, Jae Lyun Lee
Journal: Journal of Clinical Oncology (2025)

TPS276 Background: The doublet regimen, which adds docetaxel or androgen receptor-targeted agent (ARTA) such as abiraterone, enzalutamide, or apalutamide to androgen deprivation therapy (ADT) has been a standard of care in metastatic hormone-sensitive prostate cancer (mHSPC). A triplet regimen, adding abiraterone or darolutamide to ADT and docetaxel, has also demonstrated efficacy. However, while the benefit of docetaxel in mHSPC has been established in doublet regimen (ADT + docetaxel), the efficacy of adding docetaxel to ADT + ARTA has not been confirmed. Notably, the addition of docetaxel to ADT has shown benefit primarily in patients with high-volume disease. Pivotal trials of triplet regimens were based on administering ADT + docetaxel to all mHSPC patients. However, docetaxel is associated with significant toxicity and a reduction in quality of life, especially among elderly prostate cancer patients. Considering the limited evidence for adding docetaxel to ADT + ARTA and considerable toxicity of docetaxel, this phase 3 study aims to evaluate the effectiveness of adding docetaxel to ADT + ARTA. Methods: This study is a randomized, multicenter, open-label, investigator-initiated phase 3 study. Patients diagnosed with de novo mHSPC and initiated on ADT and ARTA are enrolled and randomized within 16 weeks of starting ADT. Patients are randomized 1:1 to either the Adding-Docetaxel arm or the Non-Docetaxel arm. Randomizations is stratified by ARTA type (abiraterone vs. apalutamide vs. enzalutamide), ECOG PS (0-1 vs. 2), disease volume (high vs. low). The Adding-Docetaxel arm adds 6 cycles of docetaxel 75 mg/m 2 in addition to ADT + ARTA, while the Non-Docetaxel arm receives only ADT + ARTA. The primary endpoint is clinical progression-free survival (cCFS), which defined the time from randomization to progression of soft tissue lesions (per RECIST v1.1), development of cancer pain requiring opioids for more than 7 days, worsening of ECOG PS, need for a change in prostate cancer-specific therapy, need for radiotherapy or surgical treatment, or death. The study is designed to detect a hazard ratio of 0.7 for cPFS, with a significance level of 5%, power of 80%, and an anticipated drop-out rate of 10%. A total of 430 patients (215 per arm) will be enrolled. Patient recruitment began in November 2023. This trial has been registered on the Clinical Research Information Service (http://cris.nih.go.kr) under ID No. KCT0008726 (Release date: August 22, 2023). Clinical trial information: KCT0008726 .
GLP-1 analogues and prostate cancer incidence: A systematic review and meta-analysis.
Authors: Selena Gong, Eric Yu, Tanvir Chakkal, Tahmina Shamsheri, Yousef Abumustafa, Declan CT Lavoie, Darryl Leong, Filipe Cirne, Rocio Consuelo Baro Vila, Germano Dallegrave Cavalli, Ahmed Aldarraji
Journal: Journal of Clinical Oncology (2025)

374 Background: Preliminary evidence from preclinical and observational data suggests that GLP-1 receptor agonists (GLP-1RAs) may reduce prostate cancer (PCa) incidence. We aimed to assess the effects of GLP-1RAs on PCa risk. Methods: Embase, Medline, Web of Science, and Cochrane databases were searched from inception to identify phase III randomized controlled trials (RCTs) comparing a GLP-1 RA with placebo/non-GLP-1 RA regimens. The primary outcome was incidence of PCa. A Mantel-Haenszel random-effect meta-analysis was carried out to estimate the pooled relative risk (RR) and 95% confidence interval (CI) for the occurrence of PCa among male participants. Results: Of the 27,103 abstracts identified, 56 trials including 59,334 male participants were included. Eligibility included type 2 diabetes mellitus in 48 studies, obesity in 7 studies, and heart failure in 1 study. The GLP-1 RA’s studied included liraglutide (18), semaglutide (13), dulaglutide (6), albiglutide (6), lixisenatide (5), exenatide (4), and others (5). One study included both liraglutide and semaglutide as interventions. Follow-up durations ranged from 12 weeks to 260 weeks (5 years), with a mean of 72.5 weeks (standard deviation = 50.85). The pooled incidence of PCa was 0.55% (150 of 27,126) for the control group and 0.46% (148 of 32,208) for the GLP-1 intervention group. The pooled RR of PCa incidence with all GLP-1 RAs compared to controls was 0.86 (95% CI: 0.69-1.06, p=0.16). Conclusions: There were proportionally fewer incident PCa cases among GLP-1 RA recipients as compared with control. However, this did not achieve statistical significance. Trials were limited in duration and by the lack of pre-specification of this outcome. Further research is needed to evaluate whether GLP-1 RAs have activity against established PCa.
Erratum: Protein tyrosine phosphatase receptor S acts as a metastatic suppressor in hepatocellular carcinoma by control of epithermal growth factor receptor–induced epithelial-mesenchymal transition
Authors: Zhi‐Chao Wang, Qiang Gao, Jie‐Yi Shi, Wei‐Jie Guo, Liu‐Xiao Yang, Xin‐Yang Liu, Long‐Zi Liu, Li‐Jie Ma, Meng Duan, Ying‐Jun Zhao, Yong‐Na Wu, Dong‐Mei Gao, Xiao‐Ying Wang, Guo‐Ming Shi, Zhen‐Bin Ding, Ai‐Wu Ke, Qi‐Qun Tang, Ya Cao, Jian Zhou, Jia Fan
Journal: Hepatology (2025)
The impact of pelvic radiotherapy on hematological outcomes in pediatric genitourinary rhabdomyosarcoma.
Authors: Kamil Malshy, Zijin Cheng, Trevor C Hunt, Timothy Campbell, Matthew Steidl, Jason Fairbourn, Ashley Li, Victor Kucherov, Jathin Bandari
Journal: Journal of Clinical Oncology (2025)

379 Background: Hematological toxicities are common with radiation therapy (RT), particularly pelvic RT, which affects nearly 50% of total body hematopoiesis. This study evaluates the impact of pelvic RT on hematological toxicities in pediatric patients with pelvic genitourinary rhabdomyosarcoma (GU-RMS). Methods: Following permission, a secondary analysis was conducted on 488 pediatric subjects with intermediate-risk RMS from the ARST0531 (NCT00354835) trial. This trial compared Vincristine, Dactinomycin, and Cyclophosphamide (VAC) to VAC alternating with Vincristine and Irinotecan (VI). Both arms received RT starting in week 4. Of these, 65 patients had pelvic GU-RMS (bladder/prostate = 60 [92.3%]; female-organ = 2 [3.1%]; paratesticular = 3 [4.6%]) and received pelvic RT, while 423 received non-pelvic RT. Multivariable logistic regression models assessed hematological toxicities (anemia, leukopenia, neutropenia, thrombocytopenia, lymphopenia) during weeks 1–43, adjusting for age, race, tumor size, and chemotherapy. Primary outcomes included any hematological toxicity, and secondary outcomes focused on febrile neutropenia (FN), infectious complications (IC), and the timing of toxicity at T1 (weeks 1–15), T2 (weeks 16–30), and T3 (weeks 31–43). Results: Subjects with GU-RMS receiving pelvic RT did not have a significantly higher risk of cytopenias compared to non-GU RMS patients. Neutropenia affected 79.4% of patients, with no significant difference between GU (73.8%) and non-GU (80.4%) (OR 0.64, p=0.16). Thrombocytopenia was significantly more common in GU-RMS patients during the first 15 weeks (OR 2.79, p=0.01). FN and IC were comparable across groups. Conclusions: Hematological toxicities were similar in pediatric GU and non-GU RMS patients. Pelvic RT was linked to an early rise in thrombocytopenia, though the difference diminished over time. Understanding these toxicities is key to improving management of pediatric RMS patients. Patient characteristics and hematological toxicities outcomes: pelvic GU vs. non-GU primary. Parameter Overall Cohort, N (%)N = 488 GU, N (%)N= 65 (14.51) Non-GU, N (%)N = 383 (85.49) p-value &lt; 10 y.o. 306 (68.30) 56 (86.15) 250 (65.27) 0.001 Male 241 (53.79) 48 (73.85) 193 (50.39) &lt;0.001 White Race 319 (71.21) 48 (73.85) 271 (70.76) 0.487 Cytopenia OR (95% CI, p ) Anemia 159 (35.5) 24 (36.9) 135 (35.2) 0.96(0.54-1.70, 0.89) Thrombocytopenia 131(29.2) 22 (33.8) 109 (28.4) 1.49 (0.81-2.73, 0.20) Leukopenia 196 (43.75) 26 (40) 170 (44.4) 0.73 (0.42-1.27, 0.27) Neutropenia 356 (79.4) 48 (73.8) 308 (80.4) 0.64 (0.34-1.19, 0.16) Lymphopenia 105 (23.4) 15 (23.1) 90 (23.5) 0.85 (0.45-1.61, 0.61) GU – Genitourinary; OR – Odds Ratios.
Efficacy of nivolumab plus ipilimumab in T1aN0M0 renal cell carcinoma (RCC) patients: Results from 3-year follow-up of the phase 2 pilot study.
Authors: Ilya Tsimafeyeu, Rustem Gafanov, Igor Myslevtsev, Andrey Andrianov, Axel Bex
Journal: Journal of Clinical Oncology (2025)

536 Background: Some patients with primary renal cell carcinoma (RCC) are not candidates for surgery or nephron-sparing interventions due to various factors, such as the presence of a functional single kidney with a central, high-complexity tumor. This study aimed to evaluate whether a combination of nivolumab and ipilimumab could eliminate the primary tumor in patients with T1aN0M0 RCC. Methods: This prospective, multicenter, phase 2 pilot study enrolled patients with biopsy-confirmed clear-cell RCC (cT1a) ≤4 cm, no metastases, and who were ineligible for surgery or nephron-sparing procedures. Patients were treated with ipilimumab (1 mg/kg) every 3 weeks for four doses, alongside nivolumab (240 mg) every 2 weeks for eight doses. The primary endpoint was the complete response rate. Simon's two-stage design was used, testing the null hypothesis of a true complete response rate of 11%. A type I error rate of 0.05 and a power of 0.9 were set, with the null hypothesis rejected if 3 or more responses were observed in 8 patients. Results: From February 2020 to June 2021, 8 patients were enrolled, with a median age of 77.9 years (range 73–89). The cohort was entirely Caucasian, predominantly male (75%), and 62.5% had centrally located tumors. Six patients had moderate to severe comorbidities. All patients completed the immunotherapy without experiencing grade ≥2 adverse events. After a median follow-up of 37.4 months (95% CI 31.7–44.5), no complete responses were observed. However, partial responses were seen in 4 patients (50%), with continued tumor reduction after therapy. The median tumor size decreased from 3.11 cm (range 2.2–3.9) to 1.89 cm (range 1.1–4.0). Tumor shrinkage was observed in 6 patients (75%), while 1 patient experienced a slight tumor enlargement (+0.5 cm, +13%) after 9 months. The 3-year progression-free survival rate was 100%. Data on 5-year overall survival will be reported later. Conclusions: Although complete tumor regression was not achieved, immunotherapy with nivolumab and ipilimumab led to significant and durable tumor shrinkage in two-thirds of T1aN0M0 RCC patients, with minimal toxicity, making it a viable option for patients with significant comorbidities. Further data on long-term survival are awaited. Clinical trial information: NCT04134182 .
A heterologous prime-boost strategy using RUTI vaccine to improve the BCG response in non–muscle-invasive bladder cancer patients (RUTIVAC-1 trial).
Authors: Oscar Buisan, Pol Servian, Sonia Pedreño-Lopez, Joan Pagès, Victor Urrea, Roberto Martinez, Elisabet Garcia, Mercè Amat, Joan Areal, Joaquim Bellmunt, Bonaventura Clotet, Cecilia Cabrera
Journal: Journal of Clinical Oncology (2025)

801 Background: Despite standard-of-care therapy with transurethral resection of bladder tumor and intravesical BCG instillation, a significant percentage of patients with non-muscle invasive bladder cancer (NMIBC) experience disease recurrence or progression. Therefore, novel combination therapies are needed to improve BCG efficacy. The RUTIVAC-1 trial, a randomized, double-blind, placebo-controlled, phase I study, was conducted to investigate the potential of a heterologous prime-boost strategy using RUTI, a nonlive vaccine composed of Mycobacterium tuberculosis cell wall fragments, as a primer to enhance the intravesical BCG-induced immune response in NMIBC patients. Methods: Forty high-grade, BCG-naïve NMIBC patients were randomized 1:1 to receive two subcutaneous doses of either placebo or RUTI (25 μg) before standard BCG treatment. The primary endpoint was the immunological changes after RUTI vaccination. Secondary endpoints included clinical efficacy (recurrence, progression and mortality rates) and safety at 5-year follow-up. Results: Baseline characteristics were similar in both groups (median age 70 years, 90% male, 65% T1, 32.5% Ta and 4% CIS). RUTI vaccination induced a vaccine-specific CD4 + and CD8 + T cell response prior to the initiation of intravesical BCG therapy. Following intravesical BCG treatment, the placebo group showed an increase in regulatory T cells (Tregs; CD4 + CD25 + CD27 + ), which was not observed in the RUTI group. Conversely, RUTI-vaccinated patients exhibited a more heterogeneous and polyfunctional specific immune response, with significant increases in PPD-specific CD25 + , CD137 + , OX40 + and CD69 + CD4 + T cells, as well as bi- and trifunctional CD4 + T cells expressing IFN-γ, TNF-α, and IL-2. Efficacy after 5 years of follow-up correlated with immunological changes, with RUTI vaccination associated with a significant increase in progression-free survival (100% vs. 72.2%; p=0.015), an 80% reduction in the risk of experiencing an event (EFS 89.5% vs. 50%; HR: 0.2, 95% CI 0.06–0.69; p=0.024) and a higher cancer-specific disease-free survival rate (100% vs. 83.3%; p=0.067). RUTI was safe, with only low-grade injection site reactions and no systemic effects. Conclusions: RUTI vaccination prior to intravesical BCG treatment in NMIBC patients is safe and effectively modulates the BCG-induced immune response, promoting a more balanced effective/suppressive response. This novel approach has the potential to significantly improve clinical outcomes in the management of NMIBC. Clinical trial information: NCT03191578 .
Cadonilimab (anti-PD-1 and CTLA-4 bispecific antibody) combined with axitinib for the first-line treatment of advanced or metastatic non-clear renal cell carcinoma: A prospective, single-arm, phase Ib/II study.
Authors: Xu Hu, Fengnian Zhao, Yuntian Chen, Junjie Zhao, Yifu Shi, Yanfeng Tang, Yongquan Wang, Xingming Zhang, Jiayu Liang, Jinge Zhao, Junru Chen, Qiang Wei, Xiang Li, Jiyan Liu, Ni Chen, Pengfei Shen, Jin Yao, Guangxi Sun, Zhenhua Liu, Hao Zeng
Journal: Journal of Clinical Oncology (2025)

544 Background: Non-clear cell renal cell carcinoma (nccRCC) accounts for approximately 25% of all renal cell carcinoma (RCC) and lacks standards of care. More recent data suggests the efficacy of anti-PD-(L)1 plus anti-CTLA-4 and immune checkpoint inhibitors combined with tyrosine-kinase inhibitors in the RCC. Cadonilimab (AK104) is a first-in-class tetravalent bispecific antibody that targets both PD-1 and CTLA-4, showing a manageable safety profile and favorable clinical benefits. Here we explore the efficacy and safety of cadonilimab in combination with axitinib in patients with advanced or metastatic nccRCC. Methods: Eligible patients had histologically confirmed advanced or metastatic nccRCC who had not previously received systemic therapy. Patients received cadonilimab (10 or 15 mg/kg q3w in phase Ib, and 10mg/kg q3w in phase II) in combination with axitinib (5mg bid) as first-line treatment until disease progression or intolerant to treatment. The primary endpoints were safety and objective response rate (ORR; RECIST v1.1). This study is registered with ClinicalTrials.gov, NCT05808608. Results: As of October 1, 2024, 26 patients were enrolled, median follow-up was 5.1 months (0.6-10.7 months). Twenty patients were available for efficacy assessment. Confirmed ORR was 55% (11/20), and disease control rate (DCR) was 95% (19/20). The median progression-free survival (PFS) was not reached. All patients experienced treatment-related adverse events (TRAEs), grade≥3 TRAEs occurred in 12 (46.2%) patients. Conclusions: Cadonilimab combined with axitinib demonstrated promising antitumoral efficacy and manageable toxicities in patients with advanced or metastatic nccRCC. The trial is an ongoing study, and complete results are awaited after completion of the enrollment and longer follow-up. Clinical trial information: NCT05808608 .
Clinicopathological features and prognosis of MED15-TFE3 rearrangement renal cell carcinoma: An updated report.
Authors: Sike He, Haoyang Liu, Xu Hu, Junru Chen, Zhenhua Liu, Pengfei Shen, Hao Zeng
Journal: Journal of Clinical Oncology (2025)

492 Background: TFE3-rearranged renal cell carcinoma (rRCC) is uncommon, and demonstrates unique heterogenous morphological features and distinct immune characteristics. MED15-TFE3 is a rare gene fusion that usually present as an extensive cystic mass with low malignant potential and is more susceptible to immune check point inhibitor. Identifying the clinical characteristics is crucial for the treatment. Methods: All samples were collected retrospectively from West China Hospital between 8/2011 and 5/2024. Diagnosis of MED15-TFE3 gene fusion was confirmed by RNA sequencing and fluorescence in situ hybridization. Both clinicopathological features and follow-up prognosis information were collected for further analysis. Results: The detailed information of 16 cases were described in the table. The median age was 47.5 years (range, 22 to 70 years). Majority of the cases were female (12/16). All patientes were surgically treated (radical nephrecomy: 8; partial nephrectomy: 7; cytoreductive surgery: 1). At initial diagnosis, most cases (14/16) were localized disease, while two patients had positive regional lymph nodes metastasis, and one patient had distant metastasis. For the patients without distant metastasis (n=15), two patients developed metastasis with disease-free survival of 11.4 and 29.0 months, respectively. As for the pathological features, 14 (87.5%) of the casess presented cystic morphologically, and other two (12.5%) were papillary. Except for one patient with diatant metastasis at initial diagnosis, all patients (15/16) were in G2 by ISUP score. For metastatic patients, 3 received first-line therapy (1 axitinib, 1 axitinib + sintilimab, 1 sunitinib), 2 received second-line therapy (1 axitinib + sintilimab, 1 axitinib + toripalimab), 1 received third-line therapy (axitinib + toripalimab and combined with everolimus). They are still under follow-up. Conclusions: MED15-TFE3rRCC mainly present low-grade cystic renal neoplasm with favorable prognosis. For metastatic MED15-TFE3 rRCC, there is no standard therapy currently. Clinicopathological characteristics and prognosis of 16 MED15-TFE3 rRCC cases. Characteristics Cases Age, median (range), years 47.5 (22, 70) Gender Male 4 Female 12 Morphology Cystic 2 Papillary 14 Tumor size, median (range), cm 5.6 (3.3, 14.0) Nephrectomy Radical 8 Partial 7 Cytoreductive 1 T stage T1 10 T2 3 T3 3 N stage N0 14 N1 2 M stage M0 15 M1 1 ISUP grade 2 15 3 1 Distant metastasis Synchronous 2 Metachronous 2 No 12 Survival status Alive 15 Dead 1