Five-Fraction Proton Therapy for Chordomas and Chondrosarcomas of the Skull Base: Preliminary Results of a Prospective Series

Abstract

To describe the first series of patients with clival chordomas and chondrosarcomas treated with extremely hypofractionated proton therapy in a single institution with focus on acute tolerance and dosimetric parameters. A total of 11 consecutive patients with biopsy proven chordomas and chondrosarcomas were prospectively included in a five-fraction proton therapy protocol between June 2022 and January 2023. The inclusion criteria for this protocol were: Age > 18 yo., Karnofsky Performance Status (KPS) ≥ 70%, absence of metastases, no previous radiation courses, clinical target volume (CTV) up to 50 cc and CTV location relative to organs at risk that allowed compliance with the necessary dose restrictions for hypofractionated treatments in 5 fractions, according to the international guidelines. Treatment was delivered with a Proteus®ONE cyclotron using Pencil Beam Scanning (PBS) Intensity-Modulated Proton Therapy (IMPT). Patient setup was performed with CBCT imaging at isocenter and X-Ray obliques, allowing a robust planning with 1 mm setup uncertainty and 3.5% range uncertainty. IMPT plans were obtained with RayStation employing 4 to 6 non-coplanar beams. In 7 patients' apertures were used in 2 of the beams, to reduce lateral penumbra and to optimize dose gradient. A total of 11 patients (7 males and 5 females) with an age range between 29 and 79 yo, were included. 6 patients with classic chordomas and 5 patients with grade I-II chondrosarcomas were treated with a total dose of 37.5 GyRBE and 35 GyRBE, respectively, in 5 daily fractions. All the patients had received previous surgery with complete resection in 2 patients, subtotal resection in 7 patients and partial resection in 2 patients. Most common symptoms at diagnosis were diplopia and headache and baseline median KPS after surgery was 90% (70 - 100%). Median CTV was 30.62 cc (10.56 - 47.47 cc). Median CTV coverage was V95% = D95.5%. Median maximal dose for the brainstem was 26.5 GyRBE (30 - 24.7 GyRBE) and for the optic pathway was 20.7 GyRBE (8.9 - 23.6 GyRBE). Median follow-up was 3 months (8 - 1 months). Acute toxicity during follow-up was mild, with grade I - II headache (64%), grade I asthenia (45%), grade I nausea (27%), grade I dysphagia (18%) and reversible alopecia (45%). Only one patient showed nystagmus and mild loss of strength in left lower limb related with an ischemic brainstem lesion, in a low dose region, not clearly radiation related. 8 patients had a 3-month follow-up MRI with no signs of progression. Five-fraction proton therapy for the treatment of clival chordomas and chondrosarcomas is dosimetrically feasible and well tolerated for selected patients. Proton therapy remains a limited resource, consequently, reducing treatment time can have significant financial and psychosocial implications. Longer follow up is needed to validate these results.