Neurocognitive outcome in brain metastases patients treated with accelerated-fractionation vs. accelerated-hyperfractionated radiotherapy: An analysis from Radiation Therapy Oncology Group study 91-04

Purpose: To evaluate neurocognitive outcome as measured by the Mini-Mental Status Examination (MMSE) among patients with unresectable brain metastases randomly assigned to accelerated fractionation (AF) vs. accelerated hyperf ractionated (AH) whole-brain radiation therapy (WBRT). Methods and Materials: The Radiation Therapy Oncology Group (RTOG) accrued 445 patients with unresectable brain metastases to a Phase III comparison o f AH (1.6 Gy b.i.d. to 54.4 Gy) vs. AF (3 Gy q.d. to 30 Gy). All had a KPS of greater than or equal to 70 and a neurologic function status of 0-2. Thr ee hundred fifty-nine patients had MMSEs performed and were eligible for th is analysis. Changes in the MMSE were analyzed according to criteria previo usly defined in the literature. Results: The median survival was 4.5 months for both arms. The average chan ge in MMSE at 2 and 3 months Was a-drop of 1.4 and 1.1, respectively, in th e AF arm as compared to a drop of 0.7 and 1.3, respectively, in the AH arm (p = NS). Overall, 91 patients at 2 months and 23 patients at 3 months had both follow-up MMSE and computed tomography/magnetic resonance imaging docu mentation of the status of their brain metastases. When an analysis was per formed taking into account control of brain metastases, a significant effec t on MMSE was observed with time and associated proportional increase in un controlled brain metastases. At 2 months, the average change in MMSE score was a drop of 0.6 for those whose brain metastases were radiologically cont rolled as compared to a drop of 1.9 for those with uncontrolled brain metas tases (p = 0.47). At 3 months, the average change in MMSE score was a drop of 0.5 for those whose brain metastases were radiologically controlled as c ompared to a drop of 6.3 for those with uncontrolled brain metastases (p = 0.02). Conclusion: Use of AH as compared to AF-WBRT was not associated with a sign ificant difference in neurocognitive function as measured by MMSE in this p atient population with unresectable brain metastases and limited survival. However, control of brain metastases had a significant impact on MMSE. (C) 2001 Elsevier Science Inc.