Prophylactic Cranial Irradiation (PCI) and Brain MRI Surveillance versus Brain MRISurveillance Alone in Patients with Limited-Stage Small Cell Lung Cancer Achieving Complete Remission (CR) of tumor after Chemoradiotherapy: a Multicenter Prospective Randomized Study

Abstract Background Prophylactic cranial irradiation (PCI) is part of standard care in limited-stage small cell lung cancer (SCLC) at present. As evidence from retrospective studies increases, the benefits of PCI for limited-stage SCLC are being challenged. Methods A multicenter, prospective, randomized controlled study was designed. The key inclusion criteria were: histologically or cytologically confirmed small cell carcinoma, age ≥ 18 years, KPS ≥ 80, limited stage defined as tumor confined to one side of the chest including ipsilateral hilar, bilateral mediastinum, bilateral supraclavicular lymph nodes, patients have received definitive thoracic radiotherapy (regardless of the dose-fractionation of radiotherapy used) and chemotherapy, evaluated as complete remission (CR) of tumor 4–6 weeks after the completion of chemo-radiotherapy. Eligible patients will be randomly assigned to two arms: (1) PCI and brain MRI follow-up arm, receiving PCI (2.5Gy qd to a total dose of 25Gy in two weeks) followed by brain MRI follow-up once every three months for two years; (2) brain MRI surveillance alone arm, undergoing brain MRI surveillance once every three months for two years. The primary objective was to compare the 2-year brain metastasis-free survival (BMFS) rates between the two arms. Secondary objectives included 2-year overall survival (OS) rates, intra-cranial failure patterns, 2-year progression-free survival rates and neurotoxicity. In case of brain metastasis (BM) detected during follow-up, patients meeting the eligibility criteria will receive stereotactic radiosurgery (SRS). Discussion Based on our post hoc analysis of a prospective study, we hypothesize that in limited-stage SCLC patients with CR after definitive chemoradiotherapy, and ruling out of BM by MRI, it would be feasible to use brain MRI surveillance and omit PCI in these patients. If BM is detected during follow-up, treatment with SRS or whole brain radiotherapy (WBRT) does not appear to have a detrimental effect on OS. Additionally, this approach may reduce potential neurotoxicity associated with PCI.