Proton Radiation Therapy for Pediatric Chordomas of the Base of Skull

Abstract

There are few data on clinical outcomes for base of skull (BOS) chordomas in the pediatric population due to its rarity. We report outcomes for pediatric patients with BOS chordomas treated with proton radiotherapy (PRT). Between 1981 and 2019, pediatric patients with BOS chordomas were treated with PRT or combined proton/photon approach (comboRT) at a single institution. The primary endpoints were overall survival (OS) and progression free survival (PFS). Univariable and multivariable analysis was used to identify prognostic factors for OS. Cox proportional hazards regression and Kaplan Meier estimates were used for survival analyses. 186 patients were identified [104 female (56%) and 82 male (44%]. Median age at diagnosis was 11 years (IQR 7-16, 1-21). 114 patients (61%) had chordomas located in the upper and/or middle clivus, 65 (35%) in the lower clivus and 7 (4%) in the cranio-cervical junction. The majority of the patients (n = 128, 68%) were diagnosed with conventional chordoma, 53 (28%) with a chondroid subtype and 7(4%) with poorly-differentiated chordoma. All patients underwent surgical resection (range, 1-8). 29 patients (16%) underwent gross total resection, 149 patients (80%) underwent STR while 8 patients (4%) had biopsy only. 2 patients (1%) were treated with pre- and post-op RT, while 184 patients (99%) received only post-op RT. 7 patients (4%) received radiation in a twice daily (BID) fashion. 13 patients (7%) received pre-RT chemotherapy. 54 patients (29%) developed progressive disease prior to RT. 37 patients (20%) were treated with PRT and 149 (80%) patients received comboRT. Median prescription dose was 77.4 Gy (RBE) (range, 59.3 – 83.3) delivered in 1.2 - 2.2 Gy (RBE) fractions (1.2 Gy for BID). The median maximum dose to the brainstem was 65.7 Gy (RBE) (range, 40.8 - 80). At a median follow-up of 7.3 years (range, 0.6 – 35.5) from the date of diagnosis 52 patients recurred (33 local, 13 distant and 6 iatrogenic). The median OS and PFS were 23.8 and 23.3 years, respectively. The 5- and 10-year OS rates were 83% and 78%, respectively. The 5- and 10-year PFS rates were 76% and 71%, respectively. On multivariate analysis, chondroid and cellular pathological subtype, the administration of chemotherapy prior to RT and the lower clivus location of the tumor were prognostic factors for OS and PFS. RT was well tolerated, with most acute side effects limited to moderate erythema and otitis media. Late toxicities included 4 cases of brainstem injury, and single case each of moyamoya disease, osteomyelitis, and esophageal stricture. 3 patients developed secondary radiation related malignancies. This is the largest cohort of pediatric skull base chordomas in the literature to date. High dose PRT following surgical resection is an effective treatment with a high rate of disease control and minimal late toxicity.