Quantitative assessment of residual tumor is a strong and independent predictor of survival in methylated glioblastoma following radiochemotherapy with lomustine/temozolomide

Abstract

Background: Maximum tumor resection improves overall survival (OS) in patients with glioblastoma. The extent of resection (EOR) is historically dichotomized. The response assessment in neuro-oncology (RANO) resects group recently proposed criteria for volumetry-based EOR assessment in patients that were treated according to Stupṕs protocol. The purpose of this study was (1) to investigate the prognostic value of EOR in patients receiving combined chemotherapy with lomustine (CCNU)/temozolomide (TMZ), and (2) to analyze the prognostic performance of binary EOR assessment compared to volumetric assessment. Methods: Seventy-eight patients with newly diagnosed MGMT-methylated GBM undergoing tumor resection followed by radiochemotherapy with CCNU/TMZ were included in this study. Residual contrast-enhancing (CE) tumor volume after the first resection was measured and its influence on OS and progression-free survival was analyzed using uni- and multivariable Cox regression analysis as well as two-sided log-rank test. Patients were divided into residual tumor volume (RTV) ≤1 cm³, >1-≤5 cm³, and >5 cm³ following the proposed criteria of the RANO resect group. Results: Prolonged OS was associated with age <60 years, low RTV, and gross total resection. RTV had a superior prognostic value compared to binary EOR assessment. Patients with total or near total resection of CE tumor (≤ 1 cm³ RTV) showed prolonged OS (median 54.4 months, 95% CI: 46.94-not reached), with a 5-year survival rate of 49%. Conclusions: Low RTV is associated with increased survival in glioblastoma patients undergoing radiochemotherapy with CCNU/TMZ. This study demonstrates the applicability of the recently proposed RANO resect criteria in this subgroup of patients.