Abstract. Background: The use of prophylactic cranial irradiation (PCI) to treat brain metastases (BM) in non-small cell lung cancer (NSCLC) is restricted due to the potential associated toxicity and lack of survival benefit. BM can have a negative impact on neurocognitive function (NF) and quality of life (QOLProphylactic cranial irradiation (PCI) is a technique that delivers radiation therapy (RT) to the whole brain to prevent the occurrence of brain metastases (BM) in aggressive cancer types that commonly metastasise to the brain (1). The rationale behind PCI is to eliminate undetectable micrometastases before they become clinically apparent (1).According to the American Cancer Society, about 85-95% of all lung cancer cases are non-small cell lung cancer (NSCLC) (2). The brain is the first site of metastases for up to 30% of these patients (3), with 60% of BM occurring in the first 6 months (4). With modern advances in the management of NSCLC, the risk of developing BM increases as survival is prolonged (5). The reported incidence of BM from NSCLC ranges from 17% to 54%, with younger patients, those with locally advanced-stage disease, adenocarcinoma and large cell types at the higher end of this range of incidence (4, 6-9). BM are associated with high morbidity, poor prognosis (10) and neurocognitive and quality of life (QOL) deficits (10-12).Patients with small cell lung cancer derive an overall (OS) and BM-free survival benefit from PCI (13). PCI for patients with NSCLC is not widely used due to the lack of established evidence for OS benefit and the potential for neurological toxicity post RT. PCI for NSCLC may not have an impact on OS or disease-free survival (DFS) but it has been shown to reduce the incidence of BM (11,(14)(15)(16)(17)(18)(19), therefore it is a matter of debate if these patients benefit from PCI.Late cognitive toxicities are suggested to be associated with PCI and these may be a factor in the prescribing of this treatment. The Radiation Therapy Oncology Group trial (RTOG)-0214 reported a significant decline in memory at 1 year with PCI use (20). Neurocognitive function (NF) decline may occur as a direct result of vascular injury, demyelination or radionecrosis (20).This review aimed to investigate published literature on the use of PCI in patients with NSCLC to assess the impact of PCI on disease-specific outcomes and report the effects of PCI on NF and QOL outcomes. Materials and MethodsTo ensure all appropriate studies were included in this review, a systematic approach was used for searching and selecting relevant publications. As the technique for treating PCI has remained relatively unchanged over the years,