Proton beam and carbon ion radiotherapy in skull base chordoma: a systematic review, meta-analysis and meta-regression with trial sequential analysis

Chordomas are rare, locally aggressive tumors that have a high rate of recurrence, especially at the skull base. This systematic review and meta-analysis aimed to analyze the efficacy and safety of proton beam therapy (PBT) and carbon ion radiotherapy (CIRT) for skull base chordoma. We conducted a systematic search of MEDLINE, EMBASE, CENTRAL, Web of Science, and Ovid up to November 26, 2023, following the PRISMA statement. Studies involving more than 10 patients with skull base chordoma treated with PBT or CIRT were included. The outcomes analyzed were local control, overall survival, progression-free survival, and toxicities. Meta-analysis was performed using the Mantel–Haenszel method and the inverse variance method. Fourteen studies met the inclusion criteria, encompassing 1,145 patients (671 treated with PBT and 474 with CIRT). No significant difference was found between PBT and CIRT for 5-year local control (LC) and overall survival (OS). The only timepoint with a difference in local control was at 3 years, when PBT showed an advantage in local control (90% vs. 83% for CIRT; p = 0.05) and progression-free survival was similar (94% for PBT vs. 83% for CIRT; p = 0.09). Sensitivity analysis and meta-regression revealed no significant influence of predefined parameters on outcomes. Publication bias was suggested by asymmetrical funnel plots. Both PBT and CIRT are effective treatments for skull base chordoma, with comparable long-term efficacy. This meta-analysis underscores the need for individualized treatment approaches and further research to refine these therapies in clinical practice.