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

Introduction Locoregional failures after (chemo)radiotherapy 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. Methods The goal of this study was to treat recurrent lung cancer with high-dose (chemo)radiotherapy to reach a median overall survival (OS) of 12 months. Patients with recurrent lung cancer in the thorax (tumor <5cm from 50Gy 10 EQD 2 isodose line of previous radiotherapy) were reirradiated with ≥45Gy 10 EQD 2. The secondary endpoints were local control (LC), disease-free survival (DFS) and toxicity. Results From 2018 to 2022, 64 patients were included, of which 60 were analyzed. The median dose of the first radiotherapy course was 68Gy 10 EQD 2 . All patients were reirradiated using image-guided IMRT or VMAT: 38 patients (63%) using conventional fractionated radiotherapy (median dose 53Gy 10 ) and 22 (37%) using stereotactic body radiation treatment (median dose 77Gy 10 ). Median reirradiation PTV was 106cc. 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%), most common was pneumonitis (12%). Conclusions This trial showed that high-dose thoracic reirradiation for recurrent lung cancer is effective and achieved good OS higher than our null hypothesis. It resulted in good LC and DFS with low toxicity.