Survival Impact Of Delaying Postoperative Chemoradiotherapy In Newly Diagnosed High-Grade Glioma Patients

Maximal safe resection followed by adjuvant chemoradiotherapy (CRT) with temozolomide is the standard treatment for newly diagnosed high-grade glioma (HGG) patients. Time of initiation of postoperative adjuvant therapy has been demonstrated to impact on prognosis. For high-grade glioma 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 patient’s outcome. Fifty-six consecutive patients with newly-diagnosed HGG treated with surgery and adjuvant CRT from April 2014 to April 2018 attending our hospital were retrospectively reviewed. The impact of postoperative time from surgery to adjuvant treatment on patient’s overall survival (OS) was evaluated by univariate and multivariate Cox regression analyses. Factors including age, Karnofsky performance status (KPS), maximum diameter of primary tumor, single or multiple lesions, extent of resection, IDH mutation status, the volume of T1-enhancing on postoperative MRI (which reflects residual gross tumor) were also analyzed in Cox regression models. There were 16 Grade III (28.6%), and 40 Grade IV (71.4%) patients. Thirty-six cases (64.3%) had single lesion while 20 cases (35.7%) had multiple lesions. Gross total resection was achieved in 7 patients (12.5%), partial resection in 43 patients (76.8%), and biopsy only in 6 patients (10.7%). The median volume of T1-enhancing on postoperative MRI was 13.5 (0-76.1) cc and the median interval between surgery and postoperative CRT was 36 (6-166) days. The median follow-up time for the entire group was 15.5(3.9-53.9) months. A total of 25 patients (44.6%) died during follow-up. Thirty-three patients (58.9%) developed disease progression. The median OS was (22.0±2.7) months and the 1-year, 2-year and 3-year OS were 85.8, 43.9%, and 28.8% respectively. The median OS for patients who started CRT less than 6 weeks (n=35) and more than 6 weeks (n=21) were (26.6±4.7) months and (19.0±5.0) months (P=0.41). On multivariate Cox regression analysis, multiple lesions (P=0.03) and IDH wild type (P=0.02) were independent prognostic factors for worse OS. In the subgroup analysis of Grade IV patients, the median OS of the long interval (n=27) and short interval group (n=13) were (26.6±5.6) months and (14.1±3.5) months (P<0.01). On multivariate Cox regression analysis, initiation of CRT longer than 6 weeks after surgery (P<0.001) was an independent risk factor for unfavorable OS in Grade IV patients. In our data, multiple lesions and IDH wild type contributed to worse OS in HGG while the interval between surgery and CRT is not a significant prognostic factor. However, in Grade IV glioma patients, a survival benefit was found in those initiating adjuvant CRT within 6 weeks.