High-Dose REirradiation for In-Field Recurrent Lung Cancer in the THOrax (RETHO): Outcomes of a Phase 2 Prospective Clinical Trial.

Abstract

Locoregional failures after (chemo)radiation therapy for primary lung cancer account for 30% of relapses. Reirradiation in this setting is challenging. To evaluate the outcome after thoracic reirradiation with radical doses, a prospective phase 2 trial was conducted for marginal or in-field recurrences of lung cancer. The goal of this study was to treat recurrent lung cancer with high-dose (chemo)radiation therapy to reach a median overall survival (OS) of 12 months. Patients with recurrent lung cancer in the thorax (tumor <5 cm from 50 Gy₁₀ Equivalent Dose of 2 Gy per fraction [EQD₂] isodose line of previous radiation therapy) were reirradiated with ≥45 Gy₁₀ EQD_2. The secondary endpoints were local control (LC), disease-free survival (DFS), and toxicity. From 2018 to 2022, 64 patients were included, of whom 60 were analyzed. The median dose of the first radiation therapy course was 68 Gy₁₀ EQD₂. All patients were reirradiated using image guided intensity modulated radiation therapy or volumetric modulated arc therapy: 38 patients (63%) using conventional fractionated radiation therapy (median dose 53 Gy₁₀) and 22 (37%) using stereotactic body radiation treatment (median dose 77 Gy₁₀). Median reirradiation planning target volume (PTV) was 106 cc. In 50 patients, the current PTV overlapped with the previous PTV. After a median follow-up of 26.5 months, median OS was 30.1 months, LC was 28.2 months, and DFS was 13.6 months. No grade 4-5 toxicities were registered. Grade 3 toxicities occurred in 12 patients (20%); the most common was pneumonitis (12%). This trial showed that high-dose thoracic reirradiation for recurrent lung cancer is effective and achieved a good OS higher than our null hypothesis. It resulted in good LC and DFS with low toxicity.