ABSTRACT
Background:In recent years, immune checkpoint inhibitors have been introduced into routine clinical practice for treating patients with a wide variety of malignant tumors, including advanced renal cell carcinoma (aRCC), resulting in the significant improvement of the prognosis of these patients. However, a reliable biomarker prediciting the clinical course in patients receiving nivolumab has not yet been developed; accordingly, the URivo study was planned to investigate the significance of various candidate biomarkers for aRCC patients treated with nivolumab.Methods:This was designed as a prospective multicenter intervention study, and will include a total of 200 aRCC patients who are scheduled to receive nivolumab followed by treatment with either 1 or 2 tyrosine kinase inhibitors (TKIs). Using resected tumor tissues and serum samples prior to the introduction of nivolumab, the following assessments will be conducted: programmed death ligand-1 (PD-L1) and PD-L2 gene copy number gains by fluorescence in situ hybridization, serum concentrations of PD-L1 and PD-L2 by enzyme-linked immunosorbent assay, and expression ofseveral proteins involved in apoptosis, epithelial-mesenchymal transition, signal transduction and immune reaction by immunohistochemical staining. The outcomes of these assays will be evaluated focusing on the association with the response to nivolumab, overall survival, progression-free survival and disease-specific survival.Conclusions: The significance of various types of candidate biomarker, particularly PD-L1 and PD-L2, will be intensively investigated in this study, and this may offer unique information to determine the optimal indication of nivolumab for aRCC patients following the failure of TKIs.Trial Registration:UMIN000030400; registered April 1, 2018
ABSTRACT
PURPOSE: To evaluate whether hydrodistention with fulguration of Hunner lesions (HD/FUL) plus maintenance dimethyl sulfoxide (DMSO) therapy prolongs the recurrence-free time in patients with Hunner type interstitial cystitis (IC).METHODS: The study enrolled patients with Hunner type IC who required repeat HD/FUL due to recurrence of IC symptoms after the first HD/FUL at our institution. All patients received a second HD/FUL plus maintenance DMSO therapy. The maintenance DMSO therapy was performed every 2 weeks for a total of 8 instillations, and then once every 4 weeks thereafter. The recurrencefree time from HD/FUL to therapeutic failure was estimated using the Kaplan-Meier method. The recurrence-free time between the first HD/FUL and second HD/FUL plus maintenance DMSO therapy was statistically compared using the log-rank test.RESULTS: A total of 21 patients (mean age, 66.3±10.8 years) with Hunner type IC were evaluated. The recurrence-free time for the second HD/FUL plus maintenance DMSO therapy was significantly longer than that for the first HD/FUL (P<0.0001). The median recurrence-free time for the first HD/FUL was 10.1 months, while that for the second HD/FUL plus maintenance DMSO therapy has yet to be reached. The recurrence-free rate for the first HD/FUL was 81.0% at 6 months, 38.1% at 1 year, 9.5% at 2 years, and 4.8% at 3 years. In contrast, the rate for the second HD/FUL plus maintenance DMSO therapy was 100% at 6 months, 94.7% at 1 year, 82.6% at 2 years, and 82.6% at 3 years. There were no significant differences in efficacy between the first and second HD/FUL.CONCLUSIONS: HD/FUL plus maintenance DMSO therapy clearly prolongs the recurrence-free time compared with HD/FUL alone in Hunner type IC.