Definitive High-Dose, Proton-Based Radiation for Unresected Mobile Spine and Sacral Chordomas

Abstract

Spine chordoma is treated primarily by surgical resection. However, the local recurrence rate is high. Adjuvant radiotherapy to adequate dose improves local control. In certain locations, such as high sacrum, resection may result in significant neurological dysfunction, so definitive radiation has been used as an alternative to surgery. The purpose of this study is to report the results of high-dose, proton-based definitive radiotherapy for unresected spinal and sacral chordomas. We retrospectively reviewed 67 patients with newly diagnosed, previously untreated spinal chordomas (biopsy only; no prior resection) treated with high-dose definitive, proton-based radiotherapy at our center from 1975 to 2019. Reasons for radiotherapy alone included medical inoperability and/or concern for neurological dysfunction based on spine level or patient choice. Median age at diagnosis was 66.6 years. Male 53.7 %; female 46.3%. Tumor locations included cervical (n = 10), thoracic (n = 1), lumbar (n = 4) spine, and sacrum (n = 52). Median maximal tumor diameter was 7.4 cm (range 1.8- 25 cm). Most patients were irradiated in daily fraction sizes of 1.8-2 GyRBE, although some patients were irradiated with daily doses as high as 2.5 GyRBE per fraction, so doses were normalized to daily dose of 1.8 GyRBE daily (using an alpha/beta ratio of 3). Median total dose was 77.4 GyRBE. Analysis with median follow-up of 48.7 months (maximum 22 years) showed overall survival of 88.1 % (95%CI:73.2-95.0%) and 69.3% (95%CI: 47.0-83.7%), chordoma-free survival of 58.3% (95%CI: 40.7 – 72.3 and 40.3%(95%CI: 22.4 – 57.7%), local control of 78% (95%CI: 59.2-88.8%) and 62.9%(95%CI: 40.7 – 78.7%), and distant control of 78.6% (95%CI: 63.2-88.1%) and 72.5%( 95%CI: 52.8 – 85.1%) at 5 and 8 years respectively. In Cox model for local control (Likelihood Ratio Statistic), total dose: HR 0.73 (95%CI: 0.48-1.03) p = 0.079. LC at 5 years with dose 73.8-77.42 GyRBE was 76.0% (95%CI: 52.2-89.1) compared to 84.0% (95%CI: 46.8-96.0) with 78.0-85.9 GyRBE. LC at 8 years with dose = 73.8-77.42 GyRBE was 53.7% (95%CI: 27.1-74.4) compared to 84.0%% (95%CI: 46.8-96.0) with 78.0-85.9 GyRBE, p = 0.3492. In Cox model for distant control, size: HR 1.10 (95%CI: 1.01-1.20), p = 0.0318 and site, HR:3.65 (95% CI:0.71-66.7) p = 0.1389. Distant control for tumors ≤ 7.4 cm at 8 years was 81.2% (95%CI: 56.3-92.7%) compared to only 56.4% (95%CI: 18.9-82.1%) for tumors > 7.4 cm, p = 0.2041. Distant control at 8 years for sacral tumors was 56.5% (95%CI: 28.1-77.4%) vs. 87.5% (95%CI: 38.7-98.1%) for other sites, p = 0.1833. The most common late side effect was insufficiency fracture. These results support the use of high-dose definitive radiotherapy for patients with medically inoperable or otherwise unresected mobile spine or sacrococcygeal chordomas. There is a trend towards better local control with doses >78.GyRBE. There is a trend towards higher rates of metastatic disease with large and sacral tumors.