Efficacy of re-irradiation with carbon ions (RiCi) in patients with recurrent high-grade glioma (rHGG) compared to the standard re-irradiation with photons (RiP): The reference multicenter cohort of the German Cancer Consortium Radiation Oncology Group (DKTK-ROG).

Abstract

2057 Background: Local recurrence after surgery and radio(chemo)therapy remains a major obstacle in curative treatment of patients with HGG. Eradication of radioresistant glioma subpopulations (hypoxic- and stem cell like cells) together with formation of an antiangiogenic and immuno-permissive glioma niche are among beneficial radiobiological effects recently attributed to carbon ion irradiation in preclinical models. The impact of this novel therapy in management of rHGG patients remains elusive. Methods: 197 patients with rHGG (grade III: 71, IV: 126) received RiCi between Nov 2009 and Feb 2018 at HIT with a median dose of 42GyRBE in 14 fractions. In DKTK-ROG multicenter cohort n:565 rHGG patients (grade III: 63, IV: 479) underwent RiP between 1997-2016 with a median dose of 36 Gy in 14 fractions. Median follow up was 34.2 months (M) for RiCi and 7.1 M for RiP (DKTK) cohort. All three prognostic scores validated in DKTK-ROG cohort were evaluated and re-irradiation risk score (RRRS) considering initial grade, Karnofsky Performance Score and age at re-irradiation was utilized for stratification and matched comparisons. Results: Median PFS was 5.08 [4.26-5.87] M (grade III: 6.79, grade IV: 3.64) after RiCi, data was not available for RiP. Median OS was 10.52 [9.28-12.66] M (grade III: 28.2, grade IV: 8.53) after RiCi compared to 7.93 [7.15-8.79] M (grade III: 10.89, grade IV: 7.93) after RiP. Among the three prognostic scores evaluated, RRRS most robustly correlated with OS. RiCi was associated with HR of 0.52 ([0.49-0.72], p = 0.0000002), and HR 0.66 ([0.51-0.85], p = 0.001) for RRRS matched analysis. Conclusions: Carbon ions demonstrated activity in rHGG. This effect is most prominent in grade III while grade IV patients may further benefit from innovative multimodal strategies. Based on these encouraging results prospective randomized trials utilizing RRRS for stratification are recommended.