Skull base chordomas and chondrosarcomas: clinical outcome and toxicity of high-dose proton beam therapy. Assessment of predictive factors for toxicity through radiobiology modeling

Purpose: The aim of our study is to report long term results on the use of pencil beam scanning PT for the treatment of skull base Chordoma and Chondrosarcoma. We subsequently evaluated the occurrence of brain radionecrosis (RN) and potential predictive factors through radiobiological models. Methods and materials: 83 consecutive patients with skull base CH and CHS were irradiated. The median prescription dose was 72 GyRBE/36 fractions for post-operative intent, 66 GyRBE/33 fractions for definitive and 60 GyRBE/30 fraction for reirradiation. We also analyzed the LET, RBE and DR distribution in each plan and their potential correlation with the onset of radionecrosis. Results: The 3-yr and 5-yr progression free survival (PFS) were 75.5% and 71.5%. Based on histology, the 3- and 5-year PFS were 71.6% and 69% for CH, while they were 93% and 79% for CHS. The 3- and 5-year PFS decreases from 83% and 74% with a radical resection to 74% and 62% with a subtotal resection (i.e., with a macroscopic residual tumor) in CH histology and from 100% to 87.5% in CHS. The 3-yr and 5-yr OS were 88% and 79%, respectively. Based on histology the 3-yr and 5-yr OS were 86% and 75% for CH and 100% for CHS. The 3- and 5-year OS for CH decreases from 100% and 83% with radical resection to 88% and 79% with macroscopic residual tumor. High grade (G ≥3) acute toxicity was observed only in 1.5%. RN were reported in 18% of the cases. LET distribution, RBE-variable and DR seems to not correlate with RN. Conclusions: Our case series confirms the efficacy and safety of proton therapy for patients with CH and CHS of the skull base. The extent of the surgery was shown to be a factor impacting the local control and overall survival of patients.