Survival impact of delaying postoperative chemoradiotherapy in newly-diagnosed glioblastoma patients

Background: Maximal safe resection followed by adjuvant chemoradiotherapy (CRT) with temozolomide (TMZ) is the standard treatment for newly diagnosed glioblastoma multiforme (GBM) patients. Time of initiation of postoperative adjuvant therapy has been demonstrated to impact on prognosis. For GBM patients, the optimal interval between definitive surgery and CRT is still uncertain. Current study aims to find whether the delayed initiation of CRT after surgery has a negative impact on patients' outcome. Methods: Sixty-six consecutively patients with newly-diagnosed GBM treated with surgery and adjuvant CRT from April 2014 to September 2019 at Ruijin Hospital School of Medicine Shanghai Jiaotong University were retrospectively reviewed. The impact of postoperative time from surgery to adjuvant treatment on patient's overall survival (OS) and progression-free survival (PFS) were evaluated by univariate Log-rank test and multivariate Cox regression analysis. Factors including age, Karnofsky performance status (KPS), maximum diameter of primary tumor, extent of resection, isocitrate dehydrogenase (IDH) mutation status and O6-methylguanine-DNA-methyltransferase (MGMT) promoter methylation status were also analyzed in Cox regression model. Results: The median OS for patients who started CRT less than 6 weeks (n=48) and more than 6 weeks (n=18) were 26.6 months (95% CI: 18.3-34.9) and 15.7 months (95% CI: 9.2-22.3) (P=0.001). The median PFS for the short interval group was 16.3 months (95% CI: 14.7-18.0) and for the long interval group was 9.1 months (95% CI: 4.7-13.4) (P=0.006). On multivariate Cox regression analysis, high KPS and initiation of CRT less than 6 weeks were two independent prognostic factors for better OS and PFS (all P<0.05). Conclusions: Initiation of adjuvant CRT beyond 6 weeks contributed to worse survival in GBM patients, therefore CRT should be initiated within 6 weeks after surgery.