Impact of high-dose proton radiotherapy on underlying bone quality in patients undergoing treatment for clival chordoma

Introduction: Chordoma, a rare primary vertebral column malignancy originating from notochord remnants, commonly affects the skull base and is estimated to occur in 0.08-0.05 per 100,000 individuals globally. Standard treatment comprises of gross total resection with adjuvant therapies like proton beam radiotherapy (PBRT), shown to enhance survival but also correlated with bony injury detectable by reduced Hounsfield units (HU) on computed tomography (CT) scans. This study aims to assess radiographic bony injuries as measured with HU post-PBRT in skull base chordoma patients and explore potential correlations between these changes and the necessity for occipitocervical fusion, a procedure often required either due to radiation-induced or tumor-associated craniocervical instability.

Methods: We reviewed institutional records to identify adults (>18 years) with skull base chordoma treated with surgical resection and PBRT. Inclusion criteria required pre – and post-PBRT non-contrast CT scans and documented radiotherapy details. Pediatric cases and those lacking necessary imaging were excluded. Data collection focused on demographics, surgical approach, radiotherapy details (including modality, total dose, and dose fractionation), and HU measures within cancellous bone across 14 regions of interest. Linear regressions were performed to determine correlations of post-radiotherapy charge in HU with patient age, radiation dose, and radiation fractionation. Significance was set at p-value > 0.05.

Results: Eighteen patients diagnosed with skull base chordoma were included (median age: 50.7 years; 7 female). Correlations between radiotherapy dose, patient age, and radiotherapy dose per fraction were by-in-large nonsignificant, except for the odontoid, where there was a significant negative correlation of patient age with post-radiotherapy change in HU (r=0.58; p=0.03). Post-radiotherapy HU in the right (ΔHU -72; p=0.04) and left C1 lateral masses (ΔHU -100; p=0.003) were significantly lower than pre-radiotherapy, suggesting diminution of bone quality. Three of the four patients undergoing occipitocervical fusion underwent fusion at the index operation.

Conclusion : Proton radiotherapy was associated with significant decreases in occipital condyle bone quality among patients undergoing treatment for skull base chordoma. Patients with skull base chordoma undergoing high-dose PBRT may be at risk for post-PBRT fracture.