Proton Radiation Therapy for Pediatric Skull Base Chondrosarcomas

Abstract

<h3>Purpose/Objective(s)</h3> Skull base chondrosarcomas are extremely rare tumors, accounting for 6% of skull base (BOS) neoplasms and 0.15% of all intracranial tumors. There are very few studies discussing chondrosarcomas in pediatric population. We report outcomes for children and young adults with BOS chondrosarcomas treated with proton radiotherapy (PRT). <h3>Materials/Methods</h3> Between 1984 and 2018, pediatric patients were treated with PRT or combined proton/photon RT (comboRT) at a single institution. The primary endpoints were overall survival (OS) and progression free survival (PFS). Univariable analysis was used to identify prognostic factors for PFS. Cox proportional hazards regression and Kaplan Meier estimates were used for survival analyses. <h3>Results</h3> 65 patients were identified [37 females (57%) and 28 males (43%)]. Median age at diagnosis was 18 years (range, 6 -21). 3 patients presented with Ollier's disease. 63 patients (97%) were diagnosed with low-grade (grade 1-2/3) chondrosarcoma and 2 patients (3%) with a grade 3 chondrosarcoma. The majority of the patients (n = 42, 65%) had a mixed hyaline and myxoid chondrosarcoma, 10 (15%) were diagnosed with a myxoid subtype, 4 (6%) with a hyaline one, and 4 (6%) patients had a mesenchymal chondrosarcoma. All patients underwent surgical resection (range, 1-6). 7 patients (6%) underwent gross total resection, 51 patients (78%) underwent STR while 7 patients (6%) had biopsy only. 3 patients (4%) received pre-RT chemotherapy. All patients received post-operative radiation therapy. 22 (34%) patients developed progressive disease prior to RT. The median time from the time of diagnosis to RT was 8.6m (range, 1.2 - 113.7). 22 patients (34%) were treated with PRT and 43 (66%) patients received comboRT. Median prescription dose was 70 Gy (RBE) (range, 55.8 – 76.3) delivered in 1.8 - 2 Gy (RBE) fractions. The median maximum dose to the brainstem was 66.3 Gy (RBE) (range, 26 – 74.6). The median maximum dose to the optic chiasm was 62.5 Gy (RBE) (range, 3.8 – 66.1). At a median follow-up of 10 years (range, 0.6 –33.7) from the date of diagnosis, 8 patients recurred (4 local, 2 distant, 2 both local and distant). 4 patients died of disease. 4 patients died of other causes The 10-year OS and PFS rates were 91.9% (95% CI: 79.4 – 97.0) and 84.9% (95% CI: 70.2-92.7), respectively. On univariate analysis, high grade, mesenchymal chondrosarcoma, pre-RT chemo and larger tumor size were worse prognostic factors for PFS. RT was well tolerated, with most acute side effects limited to moderate erythema and epilation, otitis media, and nausea. Late toxicities include 1 case of RT-induced GBM of the brainstem, 1 case of radiation necrosis, 2 cases of RT-related vascular malformations, 4 cases of temporal lobe injury, and 1 case of RT ocular neuromyotonia. <h3>Conclusion</h3> This is the largest cohort of pediatric BOS chondrosarcomas in the literature to date. High dose PRT following surgical resection achieves excellent disease control with minimal toxicity.