219 ISSN 2045-0907 CNS Oncol. (2014) 3(3), 219–230 part of CNS Oncology 10.2217/CNS.14.22 © 2014 Future Medicine Ltd REVIEW Prophylactic cranial irradiation: recent outcomes and innovations James W Snider III 1 , Vinai Gondi 2 , Paul D Brown 3 , Wolfgang Tome 4,5 & Minesh P Mehta*, 1 1 22 South Greene Street, Department of Radiation Oncology, Baltimore, MD 21201, USA 2 Cadence Health-CDH Cancer Center, Department of Radiation Oncology, 4405 Weaver Parkway, Warrenville, IL 60555, USA 3 The University of Texas MD Anderson Cancer Center, 1515 Holcombe Blvd, Unit 97, Houston, TX 77030, USA 4 Montefiore Medical Center, Department of Radiation Oncology, 111 East 210th Street, Bronx, NY 10463, USA 5 Albert Einstein College of Medicine, Institute for Onco-Physics, 1300 Morris Park Ave, Bronx, NY 10461, USA *Author for correspondence: Tel.: +1 410 328 6080; Fax: +1 410 3285279; mineshpmehta@gmail.com SUMMARY Brain metastases represent a frequent problem in several malignancies. They can shorten survival while causing signiicant morbidity and impairment in the patient’s quality of life. Prophylactic cranial irradiation (PCI) has become an integral part of the standard of care in small cell lung cancer (SCLC), yet its role in other malignancies remains the subject of signiicant discussion. Its role has been extensively investigated in non-small cell lung cancer and less so for breast cancer and other malignancies. Improvements in medical care as well as in whole brain radiotherapy (WBRT) techniques may improve the risk-beneit ratio of this therapy so as to expand its role in cancer care. The use of memantine in WBRT patients as well as the use of hippocampal avoidance techniques are of particular interest in this efort. Herein, we review the history of PCI, its current use, and areas of investigation in the application of PCI. KEYWORDS • brain metastasis • non-small-cell lung cancer • prophylactic cranial irradiation • small cell lung cancer • whole brain radiation therapy CNS involvement remains a common cause of significant morbidity and mortality among a number of malignancies. As such, a number of approaches have been employed in the treatment of this region immediately following diagnosis or early in the course of disease to eradicate micrometastatic depos- its, a strategy referred to as ‘prophylactic therapy’. Prophylactic cranial irradiation (PCI) arose as a modality for addressing such residual micrometastatic CNS disease in childhood leukemia [1] . The Practice Points ● Prophylactic cranial irradiation (PCI) draws historically from experience in the treatment of the CNS as a sanctuary site of childhood leukemia. ● Small cell lung cancer (SCLC) represented a logical leap to a disease well known to frequently and rapidly metastasize to the CNS. ● PCI has proven to improve both brain metastasis rates as well as overall survival in SCLC. ● PCI reduces brain metastasis in non-small-cell lung cancer, but as yet, has failed to demonstrate an overall survival beneit. Many of the more recent trials in the arena have failed to accrue or directly address this issue. ● As whole brain radiotherapy (WBRT) techniques and medical management improve, the role for PCI may expand. ● Hippocampal avoidance WBRT as well as memantine use in the WBRT setting represent promising techniques for reducing toxicity associated with PCI. ● PCI’s role in other malignancies, such as breast cancer, remains controversial. For reprint orders, please contact: reprints@futuremedicine.com