Completion of ≥6 cycles of adjuvant temozolomide is the strongest modifiable prognostic factor in glioblastoma: a 17-year real-world cohort of 319 glioma patients from a single Chinese center.

BACKGROUND

Level-1 evidence supports adjuvant temozolomide (TMZ) after chemoradiotherapy in newly diagnosed glioblastoma, but many patients discontinue before completing the six cycles the regimen calls for-particularly in China, where long-term outcome data anchored to treatment intensity remain scarce. We quantified the independent prognostic value of completing ≥6 cycles of adjuvant TMZ in a 17-year single-center Chinese glioma cohort.

METHODS

We retrospectively assembled 319 patients with pathologically confirmed glioma treated between 2009 and June 2026 at a tertiary Chinese center; 264 with complete grade, follow-up, resection, and radiotherapy data (tier A) formed the primary cohort. Overall survival (OS) was analyzed by Kaplan-Meier estimation and grade-stratified Cox regression. Robustness of the TMZ ≥6-cycle effect was probed by landmark analyses at 3, 6, 9, and 12 months; inverse-probability-of-treatment weighting (IPTW); restricted mean survival time (RMST); cause-specific Cox regression; prespecified subgroup/interaction analyses; and E-value sensitivity analysis.

RESULTS

Median follow-up was 79 months (IQR 42-115); 133 patients (50.4%) died. Five-year OS was 81.8% in WHO I-II, 42.2% in III, and 24.2% in IV (log-rank P < 0.0001). The stratified Cox model showed that ≥6 adjuvant TMZ cycles independently halved mortality (adjusted HR 0.46, 95% CI 0.31-0.67, P < 0.001), alongside age ≥60 (HR 1.97, 1.30-2.98) and radiotherapy boost/SIB (HR 1.59, 1.01-2.49). The effect held across all four landmarks (HR 0.44-0.60), after IPTW (HR 0.42, 0.29-0.62), and in the cause-specific model (HR 0.45, 0.31-0.67). RMST yielded 17.0 additional months at 5 years and 30.3 months at 10 years within WHO IV. In histologic glioblastoma, the pattern was threshold-shaped: 1-5 cycles fared no better than none (HR 0.86, P = 0.62), whereas ≥6 cycles conferred a 64% mortality reduction (HR 0.36, 0.17-0.75). E-values were 3.79 (point estimate) and 2.33 (CI limit nearer the null).

CONCLUSION

Completion of ≥6 cycles of adjuvant temozolomide was the strongest modifiable prognostic factor for OS in high-grade glioma, robust across multiple bias-mitigation frameworks, although residual confounding by unmeasured molecular subtype and baseline functional status cannot be fully excluded. Completion-not merely initiation-of adjuvant TMZ warrants explicit tracking as a quality-of-care metric.