Impact of timing to initiate adjuvant therapy on survival of elderly glioblastoma patients using the SEER-Medicare and national cancer databases

The optimal time to initiate adjuvant therapy (AT) in elderly patients with glioblastoma (GBM) remains unclear. We investigated the impact of timing to start AT on overall survival (OS) using two national-scale datasets covering elderly GBM populations in the United States. A total of 3159 and 8161 eligible elderly GBM patients were derived from the Surveillance, Epidemiology and End Results (SEER)-Medicare linked dataset (2004-2013) and the National Cancer Database (NCDB) (2004-2014), respectively. The intervals in days from the diagnosis to the initiation of AT were categorized based on two scenarios: Scenario I (quartiles), <= 15, 16-26, 27-37, and >= 38 days; Scenario II (median), < 27, and >= 27 days. The primary outcome was OS. We performed the Kaplan-Meier and Cox proportional hazards regression methods for survival analysis. A sensitivity analysis was performed using Propensity Score Matching (PSM) method to achieve well-balanced characteristics between early-timing and delayed-timing in Scenario II. Improved OS was observed among patients who underwent resection and initiated AT with either a modest delay (27-37 days) or a longer delay (>= 38 days) compared to those who received AT immediately (<= 15 days) from both the SEER-Medicare dataset [adjusted hazard ratio (aHR) 0.74, 95% CI 0.64-0.84, P < 0.001; and aHR 0.81, 95% CI 0.71-0.92, P = 0.002] and the NCDB (aHR 0.83, 95% CI 0.74-0.93, P = 0.001; and aHR 0.87, 95% CI 0.77-0.98, P = 0.017). The survival advantage is observed in delayed-timing group as well in Scenario II. For elderly patients who had biopsy only, improved OS was only detected in a longer delay (Scenario I: >= 38 days vs. <= 15 days) or the delayed-timing group (Scenario II: >= 27 days vs. < 27 days) in the NCDB while no survival difference was seen in SEER-Medicare population. For the best timing to start AT in elderly GBM patients, superior survivals were observed among those who had craniotomy and initiated AT with a modest (27-37 days) or longer delays (>= 38 days) following diagnosis using both the SEER-Medicare and NCDB datasets (Scenario I). Such survival advantage was confirmed when categorizing delayed-timing vs. early-timing with the cut-off at 27 day in both datasets (Scenario II). The increased likelihood of receiving delayed AT (>= 27 days) was significantly associated with tumor resection (STR/GTR), years of diagnosis after 2006, African American and Hispanics races, treatments at academic facilities, and being referred. There is no difference in timing of AT on survival among elderly GBM patients who had biopsy in the SEER-Medicare dataset. In conclusion, initiating AT with a modest delay (27-37 days) or a longer delay (>= 38 days) after craniotomy may be the preferred timing in the elderly GBM population.