NCOG-06. N107C/CEC.3 (ALLIANCE FOR CLINICAL TRIALS IN ONCOLOGY/CANADIAN CANCER TRIALS GROUP): PHASE III TRIAL OF POST-OPERATIVE RADIOSURGERY COMPARED WITH WHOLE BRAIN RADIOTHERAPY FOR RESECTED METASTATIC BRAIN DISEASE: COGNITIVE FUNCTION OF LONG-TERM SURVIVORS

It has been our recent finding that, when substituted for whole brain radiotherapy (WBRT) as an adjuvant to resection of a brain metastasis, radiosurgery (SRS) results in improved cognitive outcomes and equivalent overall survival — this despite inferior long-term local control. A subgroup of patients will be long-term survivors following local treatment of their brain metastases. Here we report an unplanned analysis of the outcomes of patients surviving more than 12 months following surgery. Patients were randomized to either radiosurgery or WBRT after resection of a brain metastasis. The primary endpoints were neurocognitive progression and overall survival. In this report, cognitive deterioration is defined as a 1-SD drop in at least 1 cognitive test. This study is registered with ClinicalTrials.gov, number NCT01372774. Between July 2011 and December 2015, 194 patients were enrolled with a median follow-up of 11·1 months (maximum 49·0 months). Baseline characteristics were well-balanced between study arms. At 12 months, there were 47 patients alive in the SRS arm and 42 in the WBRT arm; at 24 months, there were 14 and 22 survivors in the SRS and WBRT arms, respectively. At 12 months the intracranial control was 72% in the WBRT arm and 34% in the SRS arm (p<0.0001). At 12 months, 60% of SRS patients tested had neurocognitive progression vs. 91% of WBRT-treated patients (p<0.02). At 24 months, 40% of SRS patients tested had neurocognitive progression vs. 75% of WBRT-treated patients (p=0.2). At 24 months, no radiosurgery patient had a significant decline in immediate recall (HVLT-R) vs. 50% of WBRT patients (p=0.015). Decline in cognitive function occurs early after treatment of brain metastases and remains relatively stable over time. Despite inferior intracranial control, the cognitive advantage of SRS is preserved in long-term survivors. SUPPORT: U10CA180821, U10CA180882, U10CA180868, UG1CA189823.