Carbon ion radiotherapy for skull base chordomas and chondrosarcomas: a systematic review and meta-analysis of local control, survival, and toxicity outcomes

Background: Carbon ion radiotherapy (CIRT) is an emerging radiation therapy to treat skull base chordomas and chondrosarcomas. To date, its use is limited to a few centers around the world, and there has been no attempt to systematically evaluate survival and toxicity outcomes reported in the literature. Correspondingly, the aim of this study was to qualitatively and quantitatively assess these outcomes. Methods: A systematic search of seven electronic databases from inception to November 2019 was conducted following PRISMA guidelines. Articles were screened against pre-specified criteria. Outcomes were then pooled by random-effects meta-analyses of proportions. Results: A total of nine studies provided unique metadata for assessment, with six originating from Heidelberg, Germany. The surveyed cohort size was 632 patients, with 389 (62%) chordomas and 243 (38%) chondrosarcomas of the skull base. Across all studies, median cohort age at therapy and female proportion were 46 years and 51% respectively. Estimates of local control incidence at 1-, 5-, and 10-years in chordoma-only studies were 99%, 80%, and 56%, and in chondrosarcoma-only studies were 99%, 89%, and 88%. Estimates of overall survival probability at 1-, 5-, and 10-years in chordoma-only studies were 100%, 94%, and 78%, and in chondrosarcoma-only studies were 99%, 95%, and 79%. The incidence of early and late toxicity (Grade ≥ 3) ranged from 0 to 4% across all study groups. Conclusions: The emerging use of CIRT to treat skull base chordomas and chondrosarcomas appear promising with regard to tumor control, overall survival, and risk profile of early and late toxicity. The current literature suffers from the fact only a few centers in the world currently employ this technology.