Among adults with newly diagnosed advanced glioblastoma, a delay of 4 to 8 weeks for adjuvant radiotherapy (RT) resulted in improved survival compared with patients who received RT earlier or later, according to a large retrospective cohort study.1
The current standard of care for adults with glioblastoma is maximal safe surgical resection followed by adjuvant RT and chemotherapy. However, the optimal timing of initiation of RT is unknown, as data from other retrospective studies have been mixed. The purpose of this study was to use a large cohort to determine the affect of timing of RT initiation and survival outcomes among patients with glioblastoma.
This retrospective analysis included 45,942 adult patients with newly diagnosed, grade IV glioblastoma from the National Cancer Database who were treated between 2004 and 2015. Univariate and multivariate modeling with Cox regression analysis were used to identify predictors for overall survival (OS), and Kaplan-Meier and log-rank tests were used to estimate OS.
The cohort included patients with a mean age of 61 years at diagnosis, 59% who were male, 91% who were of white ethnicity, and 55% had an unknown Karnofsky performance status.
Of the entire cohort, 11,470 patients (25%) underwent a gross total resection (GTR) and 13,594 (30%) underwent a subtotal resection or biopsy (STR). The median time to RT after surgical resection was 29 days (range, 1-179 days), with the majority of patients receiving RT within 4 weeks after resection (47%) or between 4.1 and 6 weeks (38%).
Both higher RT dose and delay of at least 4 weeks were associated with prolonged OS among all cohorts. The univariate analysis demonstrated that higher RT dose (hazard ratio [HR], 0.99; P <.001), and delay of RT of 5.1 to 6 weeks (HR, 0.91; P <.001), 6.1 to 8 weeks (HR, 0.93; P <.001), or >8 weeks (HR, 0.9; P <.001) was significantly associated with prolonged OS. These data were similar among patients who underwent GTR or STR.
Median OS was longest among patients with had an RT delay of 4.1 to 6 weeks at 15.2 months compared with patients who had an RT delay of >8 weeks at 14.6 months and <4 weeks at 13.9 months (P <.0001).
The multivariate analysis of the entire cohort demonstrated that higher RT dose (HR; 0.99; P <.001) and RT delay of 4.1 to 6 weeks (HR, 0.95; P =.001) or 6.1 to 8 weeks (HR, 0.92; P =.004) were significantly associated with improved OS. Among patients who underwent GTR or STR, only higher RT dose was associated with improved OS. For patients who underwent GTR, RT delay of >8 weeks was associated with significantly worse survival than those who received RT ≤8 weeks (HR, 1.23; P =.007).
Multivariate analysis also found that female gender, black ethnicity, and higher Karnofsky performance status were significantly associated with prolonged OS (all P ≤.002).
The authors concluded that “for patients with newly diagnosed glioblastoma, an RT delay of 4 to 8 weeks following resection is associated with better OS.” They also noted that for patients who underwent GTR, delays of longer than 8 weeks were associated with worse survival, “making them comparable to patients who receive STR.”
Buszek SM, Al Feghali KA, Elhalawani H, Chevli N, Allen PK, Chung C. Optimal timing of radiotherapy following gross total or subtotal resection of glioblastoma: a real-world assessment using the National Cancer Database. Sci Rep. 2020;10(1):4926.