REVIEWProphylactic cranial irradiation in small cell lung cancer: an updateChu, Xiaoa,b,c,d; Zhu, Zhengfeia,b,c,d Author Information aDepartment of Radiation Oncology, Fudan University Shanghai Cancer Center bDepartment of Oncology, Shanghai Medical College, Fudan University cShanghai Clinical Research Center for Radiation Oncology dShanghai Key Laboratory of Radiation Oncology, Shanghai, China Correspondence to Zhengfei Zhu, Fudan University Shanghai Cancer Center, Shanghai 200032, China. Tel: +86 18017312901; fax: +86 21 64175242; e-mail: [email protected] Current Opinion in Oncology: November 25, 2022 - Volume - Issue - 10.1097/CCO.0000000000000910 doi: 10.1097/CCO.0000000000000910 Buy PAP Metrics Abstract Purpose of review The current review presents recent updates in the seminal literature of research on prophylactic cranial irradiation (PCI) in small cell lung cancer (SCLC). Recent findings Brain MRI restaging before the administration of PCI reveals a substantial proportion of brain metastasis in baseline brain metastasis free extensive-stage SCLC (ES-SCLC) and limited-stage SCLC (LS-SCLC). Posthoc analyses from the CASPIAN and IMpower133 trials revealed decreases in brain metastasis rates in ES-SCLC treated with chemoimmunotherapy relative to the brain metastasis rates in ES-SCLC treated with chemotherapy alone. A recent meta-analysis of literature published after the landmark 1999 Auperin meta-analysis confirmed the survival benefit of PCI in LS-SCLC patients. A recent study employing PET before and after PCI demonstrated that hippocampal avoidance -PCI (HA-PCI) preserved the metabolic activity of the hippocampi compared with regular PCI. Two phase III trials evaluating neurocognitive functions after HA-PCI versus PCI have yielded conflicting results. Ongoing clinical trials (MAVERICK, PRIMALung, NRG CC003, NCT04535739, NCT04829708 and NCT03514849) regarding PCI versus MRI surveillance and HA-PCI versus PCI were also discussed. Summary Currently, the indications for PCI in SCLC are under question in the modern MRI era. Result from prospective phase III, MRI staged and MRI monitored RCTs are expected to elucidate the role of PCI in LS-SCLC and ES-SCLC. Preliminary results indicated that adding immunotherapy to chemotherapy may reduce brain metastasis rate in SCLC. Further data to this aspect are warranted to determine the role of PCI in the immuno-chemotherapy era. The future direction for PCI should be the comprehensive integration of personalized patient selection, HA-PCI utilization and potential employment of other neurocognitive preservation strategies. Copyright © 2022 Wolters Kluwer Health, Inc. All rights reserved.