Survival impact of the time gap between surgery and chemo-radiotherapy in Glioblastoma patients

Glioblastoma treatment protocol includes chemo-radiation (CRT) after maximal safe resection. However, the recommended time-gap between surgery and CRT is unclear, most trials protocol required an interval of less than 6 weeks. In the current study we evaluated the association of the time-gap between surgery and CRT to overall survival (OS) and progression free survival (PFS) in a tertiary center. After ethics committee approval, a retrospective study was conducted. Data was collected from the medical records of consecutive glioblastoma patients treated between 2005–2014. Parameters of interest included: background characteristics of patients, treatment dates and type of treatment, treatment interruptions and survival. Only patients who were diagnosed with WHO IV, underwent surgical resection (any type), and treated with postoperative CRT were included. For the analysis, patients were divided into 3 groups according to the time gap from surgery to CRT: <4 weeks, 4–6 weeks and >6 weeks. Overall survival and PFS were investigated using the Kaplan-Meier method and Cox proportional hazard model. Out of 465 patients, 204 were included. Median age was 60 years (range: 23–79 years) and 61.7% male vs. 38.3% female. There was a significant difference in OS (HR = 0.49, p-value = 0.002, 95% CI: 0.32–0.78) and PFS (HR = 0.51, p-value = 0.003, 95% CI: 0.33–0.79) in the group who was treated with CRT 6 weeks or more after surgery, compared with the other two groups tested. In our study, 6 weeks or more time-gap (median of 8 weeks) between surgery and CRT was associated with better OS and PFS among newly diagnosed glioblastoma patients. Our results are probably subjected to unaccounted biases of a retrospective study, and that CRT in this patient population is an effective therapy that overcomes the potential harm of initiating therapy later than 6 weeks. Our current approach is to initiate CRT within 6 weeks after surgery, similar to what is recommended in the literature, but the data from this study provide us with information that no major harms was done in patients who were delayed.