Brain irradiation is associated with several adverse events. One that is becoming more recognized in recent years is neurocognitive dysfunction (NCD), which has primarily been studied in the context of whole-brain radiotherapy (WBRT) for brain metastases. Thought to be caused by radiation-induced destruction of hippocampal neural stem cell components, NCD can involve a constellation of symptoms related to memory, speech, executive function, and processing speed.
Historically, NCD following WBRT was not well studied because it was thought to be a later-occurring adverse event in a population that generally experienced limited survival. However, contemporary research illustrates that NCD can start manifesting as early as 8 weeks from WBRT completion.1 Moreover, patients with metastatic cancers now remain alive for considerably longer than those from historical studies, in part owing to better systemic therapies (eg, immunotherapy and other targeted agents), so late adverse events from radiotherapy have become a greater concern. As a result, sparing the hippocampus from radiation is a major area of active investigation in the treatment of patients with brain metastases. After encouraging phase 2 data, the NRG Oncology CC001 phase 3 trial2 was launched, which compared conventional WBRT with hippocampal-sparing WBRT for brain metastases. The study revealed significantly attenuated NCD at 4 and 6 months in the hippocampal-sparing WBRT arm, along with superior results on patient-reported domains such as memory, speech, cognition, and symptom interference.