Stereotactic Reirradiation: Final Results From a Phase 1 Dose Escalation Trial (DESTROY-1)

Purpose: The final results of the Dose Escalation STereotactic RadiOtherapY-1 (DESTROY-1) trial arms focusing on stereotactic radiation therapy (SBRT) retreatment of recurrences occurring >4 months after prior in-field radiation therapy (RT) are reported. Methods and Materials: In the DESTROY-1 trial, a phase 1 multi-arm SBRT study, arms (d) and (e) focused on retreatment of recurrences after prior RT. Arm (d) included recurrences with doses >60 Gy or in locations with previous small intestinal irradiation, whereas arm (e) included recurrences with doses <60 Gy. The dose was escalated up to 45 Gy (arm d) or 50 Gy (arm e). All treatments were performed in 5 fractions. Each cohort of 6 patients was monitored for dose-limiting toxicity, defined as any >grade 3 toxicity within 6 months after SBRT. Results: From September 2004 to August 2023, 121 lesions (74 in the “d” arm, 47 in the “e” arm) in 97 patients were treated. Acute toxicity included 20 cases in arm “d” and 6 in “e” arm, all of which were low grade except for 1 G4 soft tissue toxicity in the “d” arm. Regarding late toxicity, with a median follow-up of 18 months in the “d” arm and 17 months in the “e” arm, we registered 5 G1 in the "d" arm and 7 events in the "e" arm, all G1-2, except 1 G4 skin toxicity. We registered 65 complete responses (53.7%), 35 partial responses (28.9%), and 19 stable diseases (15.7%), leading to a disease control rate of 98.3%. Progression was registered only in 2 cases (1.7%). The overall local control at 1-year was 87.6%, whereas it was 84.7% and 92.0% for the “d” and “e” arms, respectively. Overall, the 1-year distant metastasis free survival, disease free survival, and overall survival were 54.5%, 46.7%, and 78.1%, respectively. Conclusions: The reirradiation RT doses of 45 Gy for the “d” arm and 50 Gy for the “e” arm were delivered with acceptable toxicity and achieved local control rates consistent with existing literature.