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

PURPOSE: 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.

METHODS AND MATERIALS: 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 EQD2. The secondary endpoints were local control (LC), disease-free survival (DFS), and toxicity.

RESULTS

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%).

CONCLUSIONS

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.