Proton Beam Therapy for the Post-Operative Treatment of Skull Base Sarcoma: The Results of Two Phase II Single Arm Protocols

Abstract

We sought to determine the efficacy of proton beam therapy (PBT) for the post-operative treatment of skull base chordoma and chondrosarcoma (SBS). Two prospective single arm phase II trials were conducted examining the role of post-operative PBT for patients with SBS (one enrolling patients with chondrosarcoma, one enrolling patients with chordoma). Included patients had undergone maximal safe surgical resection. The primary endpoints were local failure free survival. Secondary endpoints were overall survival and treatment related toxicity including neurocognition (this will be reported separately) and endocrine function scored according to the common terminology criteria for adverse events version 3.0. Thirty-three patients were enrolled and treated with post-operative PBT (15 chondrosarcoma, 18 chordoma). Median radiotherapy dose was 70Gy (RBE) at 2Gy (RBE) per fraction (range 66 – 70 Gy (RBE)). With a median follow up of 6.3 years, local failure free survival at five years was 100% for patients with chondrosarcoma and 89% (95% CI 61 – 97%) for patients with chordoma. Overall, four patients had died at the time of analysis (one with chondrosarcoma, three with chordoma). All patients with the exception of one had evidence of local or distant failure before death. The remaining patient died from a non-cancer related cause with no evidence of disease recurrence. At five years, overall survival was 100% and 89% (95% CI 62 – 97%) for patients with chondrosarcoma and chordoma respectively. Three patients (9.1%) experienced a Grade 3 or higher late adverse event. One patient developed grade 4 brainstem necrosis two years following PBT and two additional patients developed a grade 3 cranial neuropathy. Twenty seven patients (81.8%) had no evidence of endocrine dysfunction at the time of last follow up. Post-operative PBT is effective for patients with skull base chordoma and chondrosarcoma resulting in high rates of local control combined with 82% preservation of endocrine function.