The Clinical outcomes following pencil beam scanning proton therapy for skull base chordoma and chondrosarcoma: a single-institution experience

BACKGROUND: Chordomas and chondrosarcomas of the skull base are rare, locally aggressive tumors that pose significant therapeutic challenges due to their proximity to critical anatomical structures. While maximal safe surgical resection remains the cornerstone of management, the infiltrative nature of these tumors often precludes radical excision, necessitating adjuvant radiotherapy. Given their relative radioresistance, high-dose radiotherapy exceeding 70 Gray Relative Biological Effectiveness (GyRBE) is required to achieve durable local control. This study evaluated long-term outcomes and toxicity following pencil beam scanning (PBS) proton therapy in patients with skull base chordoma and chondrosarcoma. METHODS: We retrospectively analyzed 76 patients (50 chordoma, 26 chondrosarcoma) treated with curative-intent PBS between 2016 and 2020. Median prescribed doses were 74.0 GyRBE for chordomas and 70.0 GyRBE for chondrosarcomas. Clinical endpoints included overall survival (OS), local failure-free survival (LFFS), distant metastasis-free survival (DMFS), and toxicity graded according to CTCAE v5.0. RESULTS: At a median follow-up of 70.2 months, 5-year OS, LFFS, and DMFS for the entire cohort were 84.0, 86.9, and 92.7%, respectively. Local control was numerically higher in chondrosarcoma (96.1%) than in chordoma (81.9%; p = 0.116). Tumor contact with the optic apparatus or brainstem was associated with worse OS (p = 0.0034 and p = 0.0151, respectively) and proximity to the optic pathways correlated with poorer local control (p = 0.0182). Grade ≥ 3 late toxicity occurred in 9.2% of patients, predominantly hearing impairment and temporal lobe necrosis. CONCLUSIONS: PBS achieves excellent local control and survival with an acceptable safety profile in skull base chordoma and chondrosarcoma. Our findings align with ongoing efforts toward dose intensification, hypofractionation, and particle selection. Moreover, emerging integration of artificial intelligence for contouring, treatment adaptation, and toxicity prediction, along with augmented reality-assisted positioning and patient education, promises to further enhance treatment precision and outcomes. Through long-term follow-up and engagement with international research initiatives, our institution contributes to the global advancement of biologically guided, high-precision radiotherapy for rare skull base malignancies.