Abstract BACKGROUND Current treatment guidelines for patients with IDH-mutant (IDHm) gliomas recommend radiation (XRT) and chemotherapy following surgery in most cases based on studies in which XRT was compared to XRT plus chemotherapy. Although XRT has been shown to improve time to tumor progression, there has never been a controlled study in this population in which adjuvant XRT demonstrated superior overall survival over initial observation. This study aimed to evaluate the effect of timing of XRT on survival in IDHm-glioma. MATERIAL AND METHODS We performed a retrospective observational cohort study of patients with Grade 2 or 3 IDHm-gliomas seen at two academic centers (University of Washington and Stanford) between 2007-2022. Patients were identified via research data registries. The primary comparison of interest were patients who received XRT within 3 months of diagnosis and prior to progression i.e., as adjuvant treatment (aXRT) compared to those who did not have aXRT (deferred, or dXRT). The primary outcome measures were median progression-free survival (PFS) and overall survival (OS). Survival analysis was performed via multivariable Cox proportional hazards modeling, propensity-matching, and subset analysis. RESULTS A total of 450 eligible patients were identified (mean age 39.7; 41% female). The median survival of the combined cohort was 19.1y (25-75th percentiles 9.75-27.8y). 47.1% of patients received aXRT. Patients receiving aXRT demonstrated similar Time to Next Intervention (HR=0.83, 95% confidence interval CI 0.65-1.07), but surprisingly, resulted in a markedly diminished overall survival (OS) compared to patients who had dXRT (HR of death 2.90, p0.001, CI 1.9-4.42). The shorter OS with aXRT was appreciated in all assessed subgroups, including patients considered high-risk by grade, age, and extent of resection. Shorter OS was also consistent in multivariable analysis and in propensity-matched cohorts. CONCLUSION While retrospective, the marked OS difference between aXRT and dXRT suggests that aXRT may be not be as beneficial as previously thought, especially regarding long term survival. These results offer justification for the use of a dXRT group in studies assessing adjuvant treatments. Given the recent introduction of IDHi, these results also support reconsideration of the current treatment paradigm for these patients.
Lanman et al. (Wed,) studied this question.