A Prospective Study Assessing the Efficacy and Toxicity of Stereotactic Body Radiation Therapy for Oligometastatic Bone Metastases

Abstract

Stereotactic body radiation therapy (SBRT) is a promising treatment for oligometastatic disease in bone due to its delivery of high dose to target tissue and minimal dose to surrounding tissue. The purpose of this study is to assess efficacy and toxicity of this treatment in patients with previously unirradiated oligometastatic bony disease. In this prospective phase II trial, patients with oligometastatic bone disease, defined as ≤3 active sites of disease, were treated with SBRT at one of two academic institutions between December 2016 and May 2019. Local progression-free survival (LPFS), progression-free survival (PFS), prostatic specific antigen (PSA) progression, and overall survival (OS) were reported. Treatment-related toxicity was also reported. A total of 98 patients and 131 lesions arising from various tumor histologies were included in this study. The median age of patients enrolled in the study was 72.8 years (80.6% male, 19.4% female). Median follow-up was 26.7 months. The most common histology was prostate cancer (68.4%, 67/98). The most common dose prescriptions were 27/30 Gy in 3 fractions (26.0%, 34/131), 30 Gy in 5 fractions (19.1%, 25/131), or 30/35 Gy in 5 fractions (16.0%, 21/131). Multiple doses per treatment regimen reflect dose painting employing the lower dose to the clinical target volume (CTV) and higher dose to the gross tumor volume (GTV). Four patients (4.1%, 4/98) experienced local progression at one site for each patient (3.1%, 4/131). Among patients who progressed locally, the median time to local recurrence was 25.8 months (31.0 months among prostate cancer patients, N = 2, and 14.5 months among non-prostate cancer patients, N = 2). Among the entire cohort, 2-year LPFS (including death without local progression) was 85.0%, 2-year PFS (including deaths as well as local, distant, and PSA-based progression) was 47.0%, and 2-year OS was 87.5%. Twenty-seven patients (27.6%, 27/98) developed treatment-related toxicities, and most were Grade 1 (19.4%, 19/98) and 2 (4.1%, 4/98). Four patients (4.1%, 4/98) developed Grade 3 toxicities; there were no Grade 4 toxicities. The most common toxicity was fatigue (10.2%, 10/98). Of 68 treated spine metastases, there were four (5.9%, 4/68) vertebral fractures. Among these four patients, median time to fracture was 23.5 months (range 14.2-39.2 months). Our study supports existing literature in showing that SBRT is effective and tolerable in patients with oligometastatic bone disease. Larger phase III trials are necessary and reasonable to determine long-term efficacy and toxicities.