Patterns of Failure Among Patients With Low-grade Glioma Treated With Proton Radiation Therapy

Proton treatment may be a useful radiation therapy modality for long-term surviving patients with glioma to reduce normal tissue toxicities. Photon studies demonstrate that most low-grade glioma (LGG) failures occur within the radiation field, supporting the use of more conformal treatment plans, yet it is unclear whether this can be translated to proton radiation therapy (PRT). Our objective is to examine our institutional experience to determine patterns of failure in patients with LGG with respect to the volume irradiated with PRT.

Patients with World Health Organization 2007 grade I to II or isocitrate dehydrogenase 1-positive mutation grade III LGG treated with PRT between 2005 and 2015 were retrospectively reviewed. Patients with documented local recurrences on magnetic resonance imaging after receipt of PRT underwent a comparison with the initial treatment plan dosimetry to evaluate patterns of failure. A total of 141 patients were included in the final cohort.

The median follow-up time was 46.7 months (range, 2.8-144 months), and 5-year overall survival was 84%. The median PRT dose delivered was 54 Gy (relative biological effectiveness) (range, 45-60 Gy). There were 42 failures after PRT (30%). The median time to progression after treatment was 32.7 months (range, 4.8-93.6 months). Thirty-one patients (74%) failed in-field (defined as within the 95% isodose volume), 5 patients (12%) failed out-of-field, and 5 patients (12%) had marginal failures (defined as within the 50%-95% isodose volume). The 5-year freedom from progression after PRT was 60.1% (95% confidence interval, 48.7-70.0). The 5-year cumulative incidence of overall survival was 33% among those with recurrence after PRT and 96% among those without recurrence after PRT (P < .001).

Of the patients with LGG who had documented failures after PRT, most recurred within the radiation field with few marginal failures, indicating that even with PRT, which often can have steeper dose gradients, coverage is adequate. Survival was poor for patients whose tumors recurred.