The impact of timing of temozolomide chemoradiotherapy for newly diagnosed glioblastoma on patient overall survival: A multicenter retrospective study.

Background: The optimal timing of initiating adjuvant temozolomide (TMZ) chemoradiotherapy after surgery in patients with glioblastoma is contentious. This study aimed to determine whether the timing of adjuvant treatment affects their overall survival (OS).

Methods: Consecutive adult patients with histologically-confirmed newly diagnosed glioblastoma treated with adjuvant TMZ chemoradiotherapy across all neurosurgical centers in Hong Kong between 2006 and 2020 were analyzed. The surgery-to-chemoradiotherapy (S-CRT) interval was defined as the date of the first surgery to the date of initiation of adjuvant TMZ chemoradiotherapy.

Results: Four hundred and forty-one patients were reviewed. The median S-CRT interval was 40 days (interquartile range [IQR]: 33-47) and the median overall survival (mOS) was 16.7 months (95% CI: 15.9-18.2). The median age was 58 years (IQR: 50-63). Multivariable Cox regression with restricted cubic splines identified a nonlinear relationship between the S-CRT interval and mOS. Post hoc analysis-derived S-CRT intervals revealed that early CRT (<5 weeks; adjusted hazard ratio [aHR]: 1.11; 95% CI 0.90-1.37) or late CRT (>9-12 weeks; aHR 1.07; 95% CI 0.67-1.71) were not significantly associated with OS. Subgroup analyses for the extent of resection (EOR) and pMGMT methylation status revealed no significant difference in treatment timing on OS.

Conclusion: The timing of adjuvant TMZ chemoradiotherapy, if commenced within 12 weeks after glioblastoma diagnosis, did not influence OS regardless of EOR or pMGMT methylation status. Clinical judgment should be exercised in optimizing the timing of initiating adjuvant therapy.