174 - Long-Term Failure Patterns and Prognostic Factors in a Randomized Dose-Escalation Trial for Skull Base Chordomas: A Secondary Analysis from PROG 85-26
Presenter(s)
M. Ioakeim-Ioannidou1, B. Y. Yeap2, Z. Soetan3, D. W. Kim4, J. A. Adams5, H. M. Kooy5, P. Nielsen3, Y. P. Hung6, W. Curry7, G. Cote3, E. Choy8, M. E. Cunnane9, H. R. Kelly10, Y. S. Chang9, F. Giap1, Y. L. E. E. Chen1, T. F. DeLaney11, E. B. Hug12, H. A. Shih13, and S. M. MacDonald14; 1Department of Radiation Oncology, Mass General Brigham, Harvard Medical School, Boston, MA, 2Department of Biostatistics, Massachusetts General Hospital and Harvard Medical School, Boston, MA, 3Massachusetts General Hospital, Boston, MA, 4Inova Schar Cancer Institute, Fairfax, VA, 5Department of Radiation Oncology, Massachusetts General Hospital, Boston, MA, 6Department of Pathology, Mass General Brigham, Harvard Medical School, Boston, MA, 7Department of Neurosurgery, Massachusetts General Hospital, Boston, MA, 8Division of Hematology-Oncology, Massachusetts General Hospital, Boston, MA, 9Department of Diagnostic Radiology, Mass Eye and Ear, Harvard Medical School, Boston, MA, 10Massachusetts Eye and Ear Infirmary, Harvard Medical School, Boston, MA, 11Department of Radiation Oncology, Massachusetts General Hospital, Harvard Medical School, Boston, MA, 12MedAustron Ion Therapy Center, Wiener Neustadt, Austria, 13Department of Radiation Oncology, Massachusetts General Hospital and Harvard Medical School, Boston, MA, 14Southwest Florida Proton Center, Estero, FL
Purpose/Objective(s):
Chordomas are rare, locally aggressive tumors of the axial skeleton. The standard of care includes maximal safe resection followed by high-dose proton-based radiotherapy (PRT). Despite aggressive treatment, prognosis remains guarded, and recurrence patterns have not been extensively studied. This study aims to describe relapse patterns after surgery and PRT and evaluate prognostic factors affecting outcomes in patients with chordoma of the base of the skull (BOS).Materials/Methods:
We conducted a prospective trial involving 226 patients with BOS conventional chordomas, randomized into three dose arms: 70 Gy(RBE), 76 Gy(RBE), and 83 Gy(RBE) with conventionally fractionated PRT. The median patient age was 43 years (range: 18-87). Follow-up MRI/CT scans were analyzed to define failure patterns, and failure rates were compared across dose levels using Gray’s test, accounting for death without disease as a competing risk.Results:
At a median follow-up of 24.1 years (IQR: 21.0-27.6), 126 (56%) patients relapsed and 47 (21%) died without disease. The median time to relapse after PRT among patients who failed was 3.6 years (range: 0.2-21.1). With regards to the first relapse, the predominant pattern was local/locoregional failure (LF) (n=117, 93%), including 15 iatrogenic recurrences along the path of the surgical tract. Distant metastases occurred in 14 patients, with lung and spinal drop metastases being the most common sites. LF rates (excluding iatrogenic) at 5-, 10-, and 20 years were 32%, 43%, and 55% for the low-dose group, 28%, 41%, and 48% for the intermediate-dose group, 28%, 33%, and 41% for the high-dose group (p=0.50). Distant failure at 5-, 10-, and 20 years were 6%, 8%, and 8% for the low-dose group, 3%, 4%, and 5% for the intermediate-dose group, and 5%, 8%, and 8% for the high-dose group (p=0.60). Iatrogenic failure at 5-, 10-, and 20 years were 4%, 4%, and 4% for the low-dose group, 5%, 6%, and 7% for the intermediate-dose group, and 13%, 13%, and 16% for the high-dose group (p=0.06). There was no benefit in dose escalation for any failure outcomes. The median survival for the relapsed cases was 3.8, 3.8, and 2.5 years in the respective low-, intermediate, and high-dose groups. Older age, larger GTV, incomplete resection (STR), pre-RT progression, delay in PRT, and older treatment era were found to be significantly associated with worse overall survival (OS) outcomes.Conclusion: This is the first prospective trial examining recurrence patterns in patients with BOS chordomas after post-operative PRT. Unlike historical cohorts of spinal chordomas, BOS chordomas demonstrated lower metastatic potential with increased local failures. Larger disease volume at the time of RT, STR, and pre-RT progression/radiation avoidance adversely affected OS. Future studies should explore this finding in an era of improved imaging and surgical techniques, as well as smaller RT target volumes. Exploration of systemic therapies is critical to improve outcomes for patients with relapsed disease.