Outcome and Prognostic Factors in Recurrent Glioblastoma Multiforme Treated with Re-Irradiation: A Retrospective Study from a Tertiary Care Hospital

Background: Glioblastoma multiforme (GBM) continue to portend a dismal prognosis despite the use of multimodal approaches as nearly all patients will experience relapse. We aimed to determine the outcome and toxicity of re-irradiation (re-RT) for patients with recurrent GBM.
Methods: We retrospectively collected data for 57 patients with locally recurrent GBM who received re-RT from June, 2011 to January, 2018.
Results: The median time interval between primary RT and re-RT was 16 months. The type of recurrences was: “in-field” recurrence (n=41, 71.9%), marginal (n=12, 21.1%) and “out-of-field” (n=4, 7.0%). Of 33 chemo-naive patients, 27 patients (81.8%) received TMZ concomitantly and after re-RT, and 6 patients (18.2%) were medically unfit and received re-RT alone. All patients were treated using 3D conformal radiation therapy with three dose/fractionation schedules: 35 Gy/10 fractions (n=15, 26.3%), 36 Gy/18 fractions (n=34, 59.6%), and 25 Gy/5 fractions (n=8, 14.0%). The median tumor and planning volume at recurrence were 67 cm3 (range: 10 - 170 cm3) and 287 cm3 (range: 28 - 581 cm3) respectively. The median re-RT dose was 36 Gy (range: 31.3 – 39.4 Gy) and the median cumulative doses were 96 Gy (range: 91.3 – 99.4 Gy) for the two irradiation. The median cumulative biologic effective dose (α/β = 10 Gy) was 115.5 Gy (range, 109.5 – 119.3 Gy). The median follow-up duration was 10 months (range: 6 – 31 months). The median Overall and progression free survival was 11 and 8.0 months respectively. Multivariate analysis confirmed that younger age (P=0.022), longer time between primary RT and re-RT (P=0.002), and the combined chemoradiotherapy treatment (P=0.017) at recurrence were predictive for improved survival. All patients completed the planned reirradiation course with manageable toxicity. Only 7 of 57 patients (12.3%) had grade 3 or more toxicities. Late toxicity included radionecrosis in two patients who received 5 Gy per fraction.
Conclusion: Re-RT is tolerable and could be a salvage treatment for selected recurrent GBM patients with younger age, recurrence over a long time, and combined chemoradiation schedule. However, larger randomized studies are required to shed more light on this issue and to establish the optimal management strategy for recurrent GBM.