By Marilynn Larkin
NEW YORK (Reuters Health) - 2/5/2019
"Radiation therapy has been an established standard for effectively palliating patients' pain with bone metastases at lower single fraction doses," lead author Dr. Quynh-Nhu Nguyen of the University of Texas MD Anderson Cancer Center in Houston told Reuters Health. "This phase 2 randomized trial was intended to address the longstanding criticism that single fraction radiation, historically delivered 8 Gy, was not a durable radiotherapy regimen." "Our aim was to test the hypothesis of equipoise between delivering a higher single fraction regimen with an advanced technology, SBRT, compared to standard MFRT 30 Gy in 10 fractions," he said by email. "We...demonstrate(d) more durable pain control with a higher SBRT dose in addition to better local control compared to the widely accepted multifraction standard regimen." "This trial supports previous randomized trials recommending that single fraction should be the standard radiotherapy regimen for bone metastases," he said. "It is practice-changing because it demonstrates that by delivering a higher single fraction dose, clinicians will be able to deliver a safe yet more effective durable treatment regimen, achieving better local control for patients than lower dose 8 Gy single fraction." For the phase 2 non-inferiority study, Dr. Nguyen and colleagues randomly assigned 160 patients with painful bone metastases (mean age, 62; 60% men) to single-fraction SBRT (12 Gy for lesions 4 cm and larger or 16 Gy for lesions smaller than 4 cm) or MFRT to 30 Gy in 10 fractions. Treatment groups were balanced in terms of sex, age, ethnicity, tumor histology, sites of bony metastases, baseline pain scores, number of sites irradiated, and Karnofsky performance status scores. The primary end point was pain response, defined by international consensus criteria as a combination of pain score and analgesic use. Lack of response was defined as worsening pain score (two or more points on a 0-to-10 scale), an increase in morphine-equivalent opioid dose of 50% or more, re-irradiation, or pathologic fracture. As reported online April 25 in JAMA Oncology, 16 patients in the MFRT group and 11 in the SBRT group were found to be ineligible and did not receive treatment. Among evaluable patients, the single-fraction group had more complete and partial pain responders than the MFRT group at two weeks (62% vs. 36%); three months (72% vs. 49%), and nine months (77% vs. 46%). A subset analysis of radiation dose in the SBRT group showed pain response rates were higher for those treated with 16 Gy (62%) than for those treated with 12 Gy (30%) or 30 Gy in 10 fractions (21%) at three months. At longer follow-up times, 16-Gy SBRT produced the most durable pain control: at nine months, pain response rates were 42.9% for the 16-Gy group versus 13.3% for the 12-Gy group and 15.2% in the 30-Gy MFRT group. Further analyses showed no differences between the groups in treatment-related toxic effects or quality-of-life scores, whereas local control rates at one and two years were higher in patients receiving single-fraction SBRT. The team will be starting a phase 3 randomized trial in the near future, Dr. Nguyen noted. Dr. Erik Sulman, Co-Director, Brain and Spine Tumor Center at NYU Langone's Perlmutter Cancer Center in New York City, commented in an email to Reuters Health, "This is an important study which, if validated in a multi-institutional phase 3 setting, may alter the patterns of care for patients and lead to greater acceptance of single day treatments." "Of note," he added, "the study excluded patients with fractures of the bone at the site treated or who had a history of prior radiation to the site. Few patients with metastases to the spine were included as treatment at this site requires a specialized approach given the proximity of the spinal cord."
JAMA Oncol 2019.