RESUMEN
PURPOSE: This phase 1 study aimed to assess the safety and feasibility of SABR therapy delivery to all sites of polymetastatic disease (>10 metastases). METHODS AND MATERIALS: A 3 + 3 study design was used with 5 dose levels from 6 Gy (6 Gy × 1) to 30 Gy (6 Gy weekly × 5). Dose-limiting toxicity (DLT) was defined as any grade 4 or 5 toxicity or more than 3 grade 3 toxicities within 6 weeks of treatment. The primary endpoint was the maximal tolerated dose, defined as the dose level where ≥2/6 of patients experienced DLT. Secondary endpoints included quality of life (Functional Assessment of Cancer Therapy - General and European Quality of Life 5 Dimension 5 Level) at 6 weeks posttreatment, progression-free survival, and overall survival. RESULTS: Thirteen patients were accrued: 12 Gy (n = 3), 18 Gy (n = 3), 24 Gy (n = 4), and 30 Gy (n = 3), and 207 lesions were treated. Nine patients (69%) had acute toxicity: grade 1 (n = 6, 46%), grade 2 (n = 2, 15%; n = 1 pneumonitis and n = 1 fatigue), and grade 3 (n = 1, 7.7% neutropenia). There were no grade 4 or 5 toxicities. Mean ± SD quality of life (Functional Assessment of Cancer Therapy - General and European Quality of Life 5 Dimension 5 Level health state) was 80.4 ± 21.9 and 77.4 ± 20.9 at baseline versus 76.4 ± 21.8 and 68.0 ± 24.2 at 6-week follow-up, respectively (p = .009 and p = .055, respectively). With a median follow-up of 8.7 months posttreatment (IQR, 2.4-24 months), 8 of 13 patients had disease progression (62%). The median and 12-month progression-free survival were 3.6 months and 11.3%, respectively. The median and 12-month overall survival were 13.8 months and 62%, respectively. CONCLUSIONS: In this phase 1 trial, SABR therapy for polymetastatic disease was technically feasible with acceptable acute toxicity at dose levels up to 30 Gy (6 Gy weekly × 5). DLT was not observed.