Quality of Life and Clinical Outcomes in Patients with Skull Base Chordoma and Chondrosarcoma Treated with Pencil-Beam Scanning Proton Therapy

<b>Background</b>: skull base chordoma (Ch) and chondrosarcoma (ChSa) are rare neoplasms prone to local relapse. Alongside surgery, proton therapy (PT) is a well-established treatment for them. Given the relatively long patient survival expectancy, post-treatment quality of life (QoL) is crucial. This study prospectively assessed long-term QoL in this collective. <b>Methods</b>: seventy-seven adult patients (median age, 50 years; male <i>n</i> = 31; 40.3%) with skull base Ch/ChSa completed at least two EORTC-QLQ-C30 and BN20 questionnaires during and after PT. Oncological outcomes and therapy-related toxicities were recorded during follow-up. QoL was analyzed, with post-treatment scores compared to each patient's baseline and correlated to oncological outcomes. <b>Results</b>: median follow-up was 51 months (range, 1-94), with 5-year overall survival (5yOS) and local control (5yLC) rates of 88.8% and 82.8%, respectively. The time to local or distant failure ranged from 8 to 58 (median, 22) months. QoL deteriorated directly at completion of PT and two to three years thereafter, especially in patients with local or distant failure. From the fifth year onward, QoL improved again. Complete resection before PT correlated to better QoL at all time points. Disease progression was associated with overall worse QoL, higher neurological symptoms already before PT, and higher symptom burden one year thereafter. Males reported better QoL before and one year after PT than females. <b>Conclusions</b>: PT achieves excellent OS and LC in patients with skull base Ch/ChSa. QoL declines directly after PT but remains close to reference population values. From the fifth year onward, QoL improves again. Gender, resection status, and disease progression significantly affect QoL in these patients.