Final Results From a Phase I Dose Escalation Study (DESTROY-1) in Stereotactic Boost After Prior Radiotherapy

The aim of the study is to report the final results of the DESTROY-1 dose-escalation study evaluating an stereotactic body radiation therapy (SBRT) boost for persistent disease within 4 months after in-field radiotherapy.

Within the DESTROY-1 trial, arms (f) and (g) were designed to evaluate an SBRT boost for persistent disease after prior in-field radiotherapy. Arm (f) included patients previously irradiated with doses ≤50 Gy or with persistent disease in regions previously exposed to small bowel irradiation, whereas arm (g) enrolled patients with persistence in sites receiving prior doses >50 Gy. Dose escalation proceeded through three levels up to a total dose of 35 Gy in arm (f) and 30 Gy in arm (g), respectively. Each cohort was assessed for dose-limiting adverse events, defined as any radiation-related adverse events ≥ grade 3 occurring within 6 months after SBRT.

Sixty-nine lesions in 57 patients were treated between 2005 and 2018. Acute adverse events were mostly grade 1-2, with one grade 3 gastrointestinal event in arm (g). Late adverse events were limited, with a single grade 3 lower gastrointestinal event in arm (f). Clinical response was available for 65 lesions, with a disease control rate of 98.4%. One-year local control was 86.5%, while 1-year distant metastasis-free survival (DMFS), disease-free survival (DFS), and overall survival (OS) were 70.8%, 63.8%, and 91.9%, respectively.

Dose escalation up to 35 Gy and 30 Gy in the two study arms was feasible and associated with acceptable adverse events and favorable local control outcomes.