Improved survival duration in patients with unresected solitary brain metastasis using accelerated hyperfractionated radiation therapy at total doses of 54.4 gray and greater results of radiation therapy oncology group 85–28

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Abstract
Background. Although there have been occasional reports of improved response with greater doses of irradiation for unresected brain metastases, dose escalation has not been systematically studied in a cohort of patients with solitary brain metastasis. The current study examines this group of patients to evaluate dose escalation using accelerated hyperfractionated radiation therapy (XRT) with regard to survival, patterns of failure, and toxicity. Method. Radiation Therapy Oncology Group (RTOG) 85–28, a Phase I/II randomized trial of accelerated hyperfractionated XRT for patients with unresected supratentorial brain metastases, enrolled 153 patients with solitary brain metastasis. Whole brain dose was 32 Gray (Gy) administered in 1.6 Gy fractions twice a day with an interfraction interval of 4–8 hours. Boost dose was escalated to total doses of 48.0, 54.4, 64.0, and 70.4 Gy. Results. Acute and late toxicities were acceptable. The median survival time and 1‐year survival rates were 4.9 months and 20% at 48 Gy; 5.4 months and 33% at 54.4 Gy; 7.2 months and 28% at 64 Gy; and 8.2 months and 37% at 70.4 Gy, respectively. Comparison of the upper three dose treatment arms to the 48 Gy treatment arm revealed a superior survival time with doses of 54.4 Gy and greater (P = 0.05). Improvement in neurologic function appeared to increase with dose escalation, with 25% of patients experiencing improvement at doses of 48 Gy, 38% at 54.4 Gy, 50% at 64 Gy, and 63% at 70.4 Gy (P = not significant). Conclusion. A radiation dose response for survival time appears to exist with the use of accelerated hyperfractionated XRT for patients with unresected solitary brain metastasis.