Proton-Based Radiation Therapy for Skull Base Chondrosarcomas in Children and Adolescents: 40-Year Experience From the Massachusetts General Hospital.

PURPOSE: The literature on skull base chondrosarcoma (CHS) is scarce. We report outcomes for pediatric and young patients ≤22 years with base of skull CHSs treated with proton-based radiation therapy (PBRT). METHODS AND MATERIALS: We retrospectively reviewed all patients treated with PBRT between 1981 and 2023. Primary endpoints were overall survival (OS), chondrosarcoma-specific survival (CSS), progression-free survival (PFS), local control, and distal control. RESULTS: Eighty-four patients were identified. Median age at diagnosis was 19 years (range, 6-22). Most patients (n = 79, 94%) had conventional CHS, whereas 5 (6%) had mesenchymal CHS. Nine patients (11%) underwent gross total resection, 64 (76%) subtotal resection, and 11 patients (13%) underwent biopsy. Twenty-four (29%) patients progressed before radiation therapy. The median prescription dose was 70 Gy (relative biological equivalent) (range, 50-79.7). At a median follow-up of 18.0 years (IQR, 9.2-26.2) from diagnosis, 11 patients recurred (7 local, 4 distant). Six patients died of disease. Five patients died of other causes. Ten-year OS, CSS, and PFS rates for all patients were 93.3%, 94.7%, and 88%, respectively. Twenty-year OS, CSS, and PFS rates for conventional CHS (n = 79) were 93.1%, 97.1%, and 89.2%, respectively. Mesenchymal histology was significantly associated with worse OS and PFS. Preradiation therapy tumor progression portended worse OS and CSS. Eight patients (9.9 %) experienced a late toxicity grade 3 or greater. CONCLUSIONS: This is the largest cohort of pediatric base of skull CHSs in literature to date. High-dose PBRT after surgical resection achieves excellent disease control with minimal toxicity.

Surgery and proton radiation therapy for pediatric base of skull chordomas: Long-term clinical outcomes for 204 patients.

BACKGROUND: Data on clinical outcomes for base of skull (BOS) chordomas in the pediatric population is limited. We report patient outcomes after surgery and proton radiotherapy (PRT). METHODS: Pediatric patients with BOS chordomas were treated with PRT or combined proton/photon approach (proton-based; for most, 80% proton/20% photon) at the Massachusetts General Hospital from 1981 to 2021. Endpoints of interest were overall survival (OS), disease-specific survival, progression-free survival (PFS), freedom from local recurrence (LC), and freedom from distant failure (DC). RESULTS: Of 204 patients, median age at diagnosis was 11.1 years (range, 1-21). Chordoma location included 59% upper and/or middle clivus, 36% lower clivus, 4% craniocervical junction, and 1% nasal cavity. Fifteen (7%) received pre-RT chemotherapy. Forty-seven (23%) received PRT, and 157 (77%) received comboRT. Median total dose was 76.7 Gy (RBE) (range, 59.3-83.3). At a median follow-up of 10 years (interquartile range, 5-16 years), 56 recurred. Median OS and PFS were 26 and 25 years, with 5-, 10-, and 20-year OS and PFS rates of 84% and 74%, 78% and 69%, and 64% and 64%, respectively. Multivariable actuarial analyses showed poorly differentiated subtype, radiographical progression prior to RT, larger treatment volume, and lower clivus location to be prognostic factors for worse OS, PFS, and LC. RT was well tolerated at a median follow-up of 9 years (interquartile range, 4-16 years). Side effects included 166 patients (80%) with mild/moderate acute toxicities, 24 (12%) patients with late toxicities, and 4 (2%) who developed secondary radiation-related malignancies. CONCLUSION: This is the largest cohort of BOS chordomas in the literature, pediatric and/or adult. High-dose PRT following surgical resection is effective with low rates of late toxicity.

Late Radiation-Induced Carotid Artery Stenosis and Stroke in Pediatric Patient Treated With Proton Radiation Therapy for Skull-Base Chordoma.

Radiation vasculopathy is a well-recognized late complication of radiation therapy. We present a case of a stroke 29 years after high-dose proton radiation therapy for skull-base chordoma due to occlusion of bilateral internal carotid arteries.