Abstract
Few studies investigated the association between the timing of initiating adjuvant therapies and survival in glioblastoma (GBM) patients. A total of 20511 and 4435 eligible GBM patients were derived from the National Cancer Database (NCDB) and the Surveillance, Epidemiology and End Results (SEER) - Medicare dataset, respectively (NCDB: 2005–2014; SEER-Medicare: 2004–2013). Times to starting adjuvant treatment were calculated as the days from the date of diagnosis to the initiation of adjuvant treatment [radiation therapy (RT), chemotherapy, or concurrent chemoradiation (CRT)] and categorized into quartiles (Q1: 0–21; Q2: 22–30; Q3: 31–39; Q4: ≥40, days). Kaplan-Meier method and Cox proportional hazards regression were applied for survival analysis. Multivariate logistic regression was performed to compare differences in treatment patterns, delayed treatment, and secondary outcomes. The patients underwent biopsy obtained significant survival benefit by having adjuvant treatment during Q2 and Q3 [NCDB: HR: Q1 (Ref.), Q2: 0.88, Q3: 0.86, Q4: 0.91; SEER-Medicare: Q1 (Ref.), Q2: 0.87, Q3: 0.86, Q4: 0.89]. For the patients with craniotomy, initiation of adjuvant treatment during Q2 and Q3 had significantly reduced risk of death [NCDB: HR: Q1 (Ref.), Q2: 0.95, Q3: 0.94, Q4: 1.03; SEER-Medicare: Q1 (Ref.), Q2: 0.98, Q3: 0.96, Q4: 1.00]. Furthermore, patients received more RT fractions [comparing to 10–29 fractions, 30–33 fractions: HR: 0.62 (biopsy), 0.62 (resection); ≥34 fractions: HR: 0.53 (biopsy), 0.62 (resection)] and higher-dose RT [comparing to 34–46 Gy, 50–60 Gy: HR: 0.91 (biopsy), 0.95 (resection); ≥ 60 Gy: HR: 0.77 (biopsy), 0.88 (resection)] experienced significantly survival benefit in both biopsy and resection groups. A similar analysis was performed in SEER-Medicare dataset as validation set and the findings remained consistent. The impact of time to adjuvant treatment on GBM survival varied by surgery procedures. Having adjuvant treatment immediately may not guarantee a significant survival benefit. More RT fractions and higher-dose RT are associated with better survival.