Long-term Outcomes Following Proton-based Radiation Therapy for Pediatric Chordomas and Chondrosarcomas of the Mobile Spine and the Sacrum.

Abstract

To report the first cohort of children with spinal and sacrococcygeal chordomas (CH) and chondrosarcomas (CHS) treated with proton-based radiation therapy (PRT). Between 1989 and 2019, 52 pediatric patients ≤22 years old with spinal CH (n = 43) or CHS (n = 9) were treated with PRT at a single institution. The primary tumor originated in the C-spine (n = 37, 71%), T-spine (n = 6, 12%), L-spine (n = 7, 14%), or sacrum (n = 2, 3%). The CH group included 33 conventional and 10 atypical/poorly differentiated CH. The CHS group included 5 conventional and 4 mesenchymal CHS. Pre-RT chemotherapy was administered to 13 (25%) patients. Salvage radiation was delivered to 13 (25%) patients with progressive disease. The median total dose was 74.5 Gy (RBE) [IQR, 69.8-76 Gy (RBE)], delivered in 1.8 to 2.5 Gy (RBE) daily fractions. Primary endpoints were overall survival (OS), disease-specific survival (DSS), and progression-free survival (PFS). A univariate and multivariable Cox regression analysis was performed to identify prognostic and predictive factors. At a median follow-up of 11.4 years (IQR, 5.7-19.8) from the date of diagnosis, 17 (32.7%) patients recurred (8 local, 7 distant, and 2 iatrogenic). Fifteen of these patients died of disease. The 5-, 10-, and 20-year OS were 82.7%, 72.3% and 72.3%, respectively. The 5-, 10-, and 20-year DSS were 86.1%, 77.5%, and 77.5%, respectively. The 5-, 10-, and 20-year PFS were 72.3%, 70.1% and 70.1%, respectively. The 20-year OS, DSS, and PFS for conventional CH were 93.9%, 97%, and 87.9%, respectively. Factors significantly associated with worse outcomes were poorly differentiated CH subtype, pre-RT chemo, and low KPS (P < .05). Pre-RT tumor progression was found to be a significant prognostic factor for PFS (P = .02). Two patients developed late grade 3 toxicities. This is the largest study of pediatric spinal and sacrococcygeal CH/CHS to date. High-dose PRT following surgical resection offers high disease control rates for conventional CH/CHS.