Ablative Radiation Therapy to Restrain Everything Safely Treatable (ARREST): A Phase 1 Study of Stereotactic Ablative Radiation Therapy for Polymetastatic Disease

Purpose: This phase 1 study aimed to assess the safety and feasibility of SABR therapy delivery to all sites of polymetastatic disease (>10 metastases).<br /> Methods and Materials: A 3 + 3 study design was used with 5 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 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.<br /> 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 f SD quality of life (Functional Assessment of Cancer Therapy - General and European Quality of Life 5 Dimension 5 Level health state) was 80.4 f 21.9 and 77.4 f 20.9 at baseline versus 76.4 f 21.8 and 68.0 f 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 pound 5). DLT was not observed. (c) 2024 Elsevier Inc. All rights are reserved, including those for text and data mining, AI training, and similar technologies.