Challenges relating to solid tumour brain metastases in clinical trials, part 2: neurocognitive, neurological, and quality-of-life outcomes. A report from the RANO group.

Neurocognitive function, neurological symptoms, functional independence, and health-related quality of life are major concerns for patients with brain metastases. The inclusion of these endpoints in trials of brain metastases and the methods by which these measures are assessed vary substantially. If functional independence or health-related quality of life are planned as key study outcomes, then the reliability and validity of these endpoints can be crucial because methodological issues might affect the interpretation and acceptance of findings. The Response Assessment in Neuro-Oncology (RANO) working group is an independent, international, and collaborative effort to improve the design of clinical trials in patients with brain tumours. In this report, the second in a two-part series, we review clinical trials of brain metastases in relation to measures of clinical benefit and provide a framework for the design and conduct of future trials.