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A Prospective Phase I/II Clinical Trial of High-Dose Proton Therapy for Chordomas and Chondrosarcomas

ADVANCES IN RADIATION ONCOLOGY(2024)

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摘要
The purpose of this study was to evaluate the feasibility and safety of dose-escalated proton beam therapy for treating chordomas and chondrosarcomas of the skull base and spine. A prospective cohort of 54 patients (42 with chordomas and 12 with chondrosarcomas) was enrolled between 2010 and 2018. The primary endpoints were feasibility and <20% rate of acute grade ≥3 toxicity, while secondary endpoints included cancer-specific outcomes and toxicities. Patients were followed with MRI or CT at three-month intervals. Proton beam therapy was delivered with doses up to 79.2 Gy using protons only, combination protons/IMRT, or IMRT only. Feasibility endpoints were met, with only 2 out of 54 patient RT plans failing to meet dosimetric constraints with protons and 4 out of 54 experiencing a delay or treatment break >5 days, none for toxicities related to treatment. There were no grade 4 acute toxicities, and one grade 3 acute toxicity (sensory neuropathy). The only two grade 3 late toxicities recorded, osteoradionecrosis and intranasal carotid blowout (mild and not emergently treated), occurred in a single patient. We report overall survival as 83% at 5 years, with local failure-free survival and progression-free survival rates of 72% and 68%, respectively. Five patients developed distant disease, and among the 9/54 patients who died, 4 deaths were not attributed to treatment or recurrence. Our findings suggest that high-dose proton therapy alone or in combination with IMRT is a safe and effective treatment option for chordomas and chondrosarcomas of the skull base and spine.
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关键词
Chordoma,chondrosarcoma,proton therapy,radiation therapy,high-dose radiation
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