Proton Therapy for Hemithoracic Pleural Irradiation: A Step toward Safer Radiation Treatment.

Abstract

Malignant pleural mesothelioma (MPM), thymic malignancies with pleural metastases, and thoracic soft tissue sarcoma (STS) with pleural or chest wall involvement are typically aggressive malignancies requiring multimodal therapy. Hemithoracic pleural irradiation has historically been delivered using photon-based intensity-modulated pleural radiation therapy (IMPRINT). Proton-based IMPRINT may reduce dose to critical structures, and mitigate toxicity, however clinical data remains limited. This study evaluates dosimetric parameters and toxicities following intensity-modulated proton therapy (IMPT)-based IMPRINT. We retrospectively analyzed patients with MPM, thymic malignancies, and STS with pleural metastases treated with pencil beam scanning, IMPT-based IMPRINT at a single institution between December 2019 and September 2025, receiving ≥45 Gy. Dosimetric parameters and acute (≤6 months) and late toxicities were assessed using Common Terminology Criteria for Adverse Events v5.0. Thirty-one consecutive patients were included, with a median age of 50 years. 48% had MPM, 39% had thymic malignancies, and 13% had STS. 97% had ECOG of 0-1. The median pleural dose was 50.4 Gy in 28 fractions, with a boost to 59.4 Gy delivered via simultaneous integrated boost (n=10) or sequential boost (n=3). Median clinical target volume was 2,127 cm³ with V95% of 98%. Median mean total lung dose was 15.3 Gy, contralateral mean lung dose was 0.3 Gy, V5Gy of 1.2 % and V20Gy of 0.03%. Median dose to heart was 14.2 Gy, liver was 16.9 Gy, esophagus was 20.6 Gy, and spinal cord Dmax was 39.3 Gy. At a median follow-up duration of 13.8 months, eight patients (26%) developed grade ≥2 pneumonitis, two of which were grade 3 pneumonitis (6%). No other acute or late grade ≥3 events occurred. In the largest proton cohort of hemithoracic irradiation reported, IMPT-based IMPRINT demonstrated dosimetric advantages and favorable tolerability across a heterogeneous population. IMPT-based IMPRINT is feasible and well tolerated for pleural malignancies.