Ablative Radiation Therapy to Restrain Everything Safely Treatable (ARREST): A Phase I study of Stereotactic Ablative Radiotherapy (SABR) for poly-metastatic disease

Abstract

This phase 1 study aimed to assess the safety and feasibility of SABR delivery to all sites of polymetastatic disease (>10 metastases). A 3+3 study design was used with five dose levels from 6 Gy (6 Gy x 1) to 30 Gy (6 Gy weekly x 5). Dose-limiting toxicity (DLT) was defined as any grade 4 or 5 toxicity, or more than three grade 3 toxicities within six 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 (QOL; FACT-G and EQ-5D-5L) at 6-weeks post-treatment, progression-free survival (PFS) and overall survival (OS). Thirteen patients were accrued: 12 Gy (n=3), 18 Gy (n=3), 24 Gy (n=4), 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 QOL (FACT-G and EQ-5D-5L 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 (p=0.009 and p=0.055, respectively). With a median follow-up of 8.7 months post-treatment (IQR: 2.4-24 months), 8 of 13 patients had disease progression (62%). The median and 12-month PFS were 3.6 months and 11.3% respectively. The median and 12-month OS were 13.8 months and 62% respectively. In this phase I trial, SABR for polymetastatic disease was technically feasible with acceptable acute toxicity at dose levels up to 30 Gy (6 Gy weekly x 5). DLT was not observed.