<p>Carbon Ion Beam Reirradiation in Recurrent High-Grade Glioma</p>

Abstract

Background: Patients with recurrent glioma after prior radiotherapy have a poor prognosis. Carbon ion beam radiotherapy offers highly conformal dose distributions and more complex biological radiation effects eventually resulting in optimized normal tissue sparing and improved outcome. The aim of this study was to analyze toxicity, local control and overall survival after reirradiation of recurrent high-grade glioma with carbon ion radiotherapy. Methods: Between 10/2015 and 12/2018, 30 patients (median age: 59 years) with recurrent high-grade glioma were reirradiated with carbon ion beams and retrospectively analyzed. Diagnosis of recurrent glioma was based on magnetic resonance imaging. Thirteen patients had repeated resection prior to reirradiation and 24 patients underwent additional chemotherapy. The median initial radiation dose was 60 Gy and the median time interval between the initial and repeated radiotherapy was 10 months. The reirradiation dose was 45 Gy (relative biological effectiveness) applied in 15 fractions. All patients received regular follow-up imaging after reirradiation. Kaplan-Meier estimation, log rank test and Cox regression analysis were used for statistical assessment. Results: Applying common toxicity criteria, there were no grade 5 or 4 adverse events, while 8 patients showed grade 3 adverse events. The median follow-up after reirradiation was 11 months and the median overall survival after diagnosis of recurrent high-grade glioma was 13 months. The 6-, 12-and 24-month overall survival rates after diagnosis of recurrent high-grade glioma were 76%, 50% and 19%, respectively. Upon multivariate Cox regression analysis, a Ki67 score of the initial tumor histology of less than 20% was prognostic. Repeated resection or chemotherapy for the recurrent disease did not result in significantly prolonged survival. Conclusion: Carbon ion reirradiation in recurrent high-grade glioma is safe and feasible. No radiation-associated grade 4 toxicities were documented and treatment was tolerated well.

NRG Oncology/RTOG1205: A Randomized Phase II Trial of Concurrent Bevacizumab and Reirradiation Versus Bevacizumab Alone as Treatment for Recurrent Glioblastoma

“…3,[34][35][36][37] Advances in RT techniques including fractionated stereotactic radiotherapy, heavy particles, and intensity-modulated RT have enabled increasingly conformal treatment, reducing the likelihood of acute and late CNS toxicity. [4][5][6][38][39][40] A recent meta-analysis of re-RT revealed a 12-month OS rate of 36% (95% CI, 32 to 40) and a 6-month PFS rate of 43% (95% CI, 35 to 50). 41 Previous studies have reported improved 6-month functional status and reduction or discontinuation of corticosteroid usage.…”

Comparison of carbon ion and photon reirradiation for recurrent glioblastoma

“…A median overall survival of 12 months after MRI diagnosis of recurrence was achieved. Toxicity levels were low, no grade 4 or 5 toxicities occurred [24].…”

“…Only patients with a complete dataset regarding IDH1/2 mutation status, MGMT promotor methylation, Karnofsky performance index, PTV volume, age, gender, and performance of second surgery were included in the analysis. Data from a part of the previously reported reirradiation high-grade glioma cohort (glioblastoma with complete dataset, n = 19) was updated and included in this analysis, too [24].…”

“…Preliminary results for proton or carbon ion re-RT for WHO grade III and IV glioma from other centers are encouraging [22][23][24][25][26][27]. Favorable overall survival and low toxicity rates have been reported.…”

MDM2/X Inhibitors as Radiosensitizers for Glioblastoma Targeted Therapy

“…CIRT is also being investigated in recurrent GB, with results of the randomized phase I/II CINDERELLA trial pending ( 64 ). For recurrent high-grade glioma, the recent study of Eberle et al deemed carbon ion reirradiation as safe and feasible ( 65 ).…”