A Prospective Outcomes Study of Proton Therapy for Skull-Base Chondrosarcomas

Abstract

To evaluate the effectiveness of definitive or adjuvant external beam proton therapy on local control and survival in patients with base of skull chondrosarcoma. Between January 2007 and February 2016, 43 patients with a median age of 49 years (range, 23 - 80 years) with base of skull chondrosarcoma were treated with double-scattered proton therapy on an IRB-approved prospective outcomes protocol at our institution. The median total dose delivered was 73.8 Gy(RBE) [range, 64.5 - 74.4 Gy(RBE] with 33 patients treated with 1.8 Gy(RBE) daily fractionation and 10 patients treated with 1.2 Gy(RBE) twice daily fractionation. Primary site included skull base tumors involving the clivus, cavernous sinus, petrous bone, sella, and tumors involving the ethmoid or sphenoid sinuses. Surgical resection and biopsy alone were performed in 36 (83.7%) and 7 (16.3%) patients respectively. Tumor grade was as follows: 19 (44.2%) grade 1, 22 (51.1%) grade 2, and 2 (4.7%) grade 3. Forty patients had gross disease at the time of radiotherapy and 7 patients were treated for locally recurrent disease following initial surgery. Distant metastases, overall survival, cause-specific survival, local control, and disease-free survival were calculated. Proton therapy-related toxicities were scored using CTCAE v4.0. The median follow-up time was 3.7 years (range, 0.7 -10.1 years). The 3-year actuarial rate of overall survival was 95%; cause-specific survival was 100%, disease-free survival was 93%, local control was 93%, and freedom from distant metastases was 100%. Across all time points, 3 patients experienced local recurrence with no regional or distant recurrence observed. At the time of last follow-up, 38 patients were alive with no evidence of recurrent disease, 2 patients were alive with recurrent disease, 2 patients were dead from intercurrent disease, and 1 patient was dead of recurrent disease. The time to local progression was 2 years, 2.5 years, and 3 years (n = 3) following proton therapy. We did not observe any ≥ grade 3 acute toxicities. 9.3% (n=4) of patients experienced ≥ 3 grade late toxicity following proton therapy: grade 3 hearing loss (n = 3) and a grade 3 radiation-induced tumor consisting of a meningioma 9 years 9 months after treatment. We observed a grade 2 temporal lobe and brainstem radiation necrosis, both occurring in the same patient. High-dose, conformal proton therapy alone or following surgical resection for skull base chondrosarcoma is an effective treatment with a high rate of local control and with a relatively low toxicity profile. Further follow-up of this cohort is necessary to better characterize long-term disease control and late toxicities.