Impact of proton versus photon adjuvant radiotherapy on overall survival in the management of skull base and spinal chordomas: a National Cancer Database analysis.

Objective: Chordomas are rare tumors that originate from undifferentiated remnants of the notochord. Currently, there are no established guidelines regarding the choice of adjuvant radiation modality for patients surgically treated for chordomas. Using a nationwide, multicenter database, the authors aimed to compare long-term survival outcomes associated with the use of proton or photon adjuvant therapy for the management of chordomas of skull base and spine.

Methods: The National Cancer Database (NCDB) was queried for chordoma cases from 2004 to 2017. Patient, tumor, and treatment characteristics were extracted from the database. The primary outcome was overall survival (OS). Kaplan-Meier survival analyses were conducted to investigate differences in outcome on propensity score-matched cohorts of patients treated with proton or photon adjuvant radiotherapy.

Results: Of the 3490 patients available, 424 met the inclusion criteria for this study. In the prematching analysis, patients receiving adjuvant photon therapy were significantly older (median age 57.0 vs 45.0 years, p < 0.001) and were more commonly male (61% vs 43%, p < 0.001) compared with those receiving proton therapy. Races were equally distributed among radiotherapy modalities (p = 0.64). Patients with chordomas of the mobile spine or sacrum were less likely to receive proton compared with photon therapy (37% vs 58%). Patients receiving proton therapy were more often represented among private insurance holders (69% vs 52%, p < 0.001) as well as in the highest income quartile (52% vs 40%, p = 0.008). Patients traveled farther to receive proton, as opposed to photon, therapy (median 59.0 vs 34.9 miles, p < 0.001). On postmatching Kaplan-Meier analysis encompassing all chordoma cases, no difference in OS between photon and proton therapy was revealed (HR 0.75, 95% CI 0.39-1.44; p = 0.39). A Kaplan-Meier analysis only including patients with skull base chordomas reached similar results (HR 0.83, 95% CI 0.31-2.22; p = 0.71). In patients with spine chordomas, however, a significant difference was found, as proton therapy exhibited a superior OS over photon therapy (HR 0.28, 95% CI 0.09-0.81; p = 0.012).

Conclusions: Based on this nationwide analysis, patients with private insurance and higher income were more likely to receive proton adjuvant radiotherapy, while those with spinal or sacral chordomas were less likely to receive this modality. Despite this disparity, an OS benefit was observed in patients with chordomas of the spine and sacrum who received adjuvant proton therapy, in comparison with a matched cohort of patients treated with photon therapy. Conversely, this advantageous outcome was not evident in cases of chordomas located at the skull base.