Clinical Outcomes Following Dose-Escalated Proton Therapy for Skull-Base Chordoma

Adam L Holtzman; Ronny L Rotondo; Michael S Rutenberg; Daniel J Indelicato; Alexandra De Leo; Dinesh Rao; Jeet Patel; Christopher G Morris; William M Mendenhall

doi:10.14338/IJPT-20-00066.1

Clinical Outcomes Following Dose-Escalated Proton Therapy for Skull-Base Chordoma

Int J Part Ther. 2021 Jun 25;8(1):179-188. doi: 10.14338/IJPT-20-00066.1. eCollection 2021 Summer.

Authors

Adam L Holtzman¹, Ronny L Rotondo², Michael S Rutenberg¹, Daniel J Indelicato¹, Alexandra De Leo³, Dinesh Rao³, Jeet Patel³, Christopher G Morris¹, William M Mendenhall¹

Affiliations

¹ Department of Radiation Oncology University of Florida College of Medicine, Jacksonville, FL, USA.
² Department of Radiation Oncology, University of Kansas, Kansas City, KS, USA.
³ Department of Radiology, University of Florida College of Medicine, Jacksonville, FL, USA.

Abstract

Purpose: To evaluate the effectiveness of external-beam proton therapy (PT) on local control and survival in patients with skull-base chordoma.

Materials and methods: We reviewed the medical records of patients with skull-base chordoma treated with definitive or adjuvant high-dose PT and updated their follow-up when feasible. We assessed overall survival, disease-specific survival, local control, and freedom from distant metastasis. Radiotherapy toxicities were scored using the Common Terminology Criteria for Adverse Events, version 4.0.

Results: A total 112 patients were analyzed, of whom 105 (94%) received PT and 7 (6%) received combined proton-photon therapy between 2007 and 2019. Eighty-seven patients (78%) underwent a subtotal resection, 22 (20%) a gross total resection, and 3 (3%) a biopsy alone. The median radiotherapy dose was 73.8 Gy radiobiologic equivalent (GyRBE; range, 69.6-74.4). Ninety patients (80%) had gross disease at radiotherapy and 7 (6%) were treated for locally recurrent disease following surgery. Median follow-up was 4.4 years (range, 0.4-12.6); for living patients, it was 4.6 years (range, 0.4-12.6), and for deceased patients, 4.1 years (range, 1.2-11.2). At 5 years after radiotherapy, the actuarial overall survival, disease-specific survival, local control, and freedom from distant metastasis rates were 78% (n = 87), 83% (n = 93), 74% (n = 83), and 99% (n = 111), respectively. The median time to local progression was 2.4 years (range, 0.8-7). Local control and disease-specific survival by resection status was 95% versus 70% (P = 0.28) and 100% versus 80% (P = 0.06) for gross total, versus subtotal, resection or biopsy alone, respectively. There were no serious acute toxicities (grade ≥ 3) related to radiotherapy.

Conclusion: High-dose PT alone or after surgical resection for skull-base chordoma reaffirms the favorable 5-year actuarial local control rate compared with conventional techniques with acceptable late-complication-free survival. Outcomes following gross total resection and adjuvant PT were excellent. Further follow-up of this cohort is necessary to better characterize long-term disease control and late toxicities.

Keywords: chordoma; head and neck; particle therapy; proton therapy; radiation oncology; skull-based tumors.