Risk Stratification of Symptomatic Brain Metastases By Clinical and FDG PET Parameters for the Selective Use of Prophylactic Cranial Irradiation in Patients with Extensive Disease of Small Cell Lung Cancer

Abstract

The role of prophylactic cranial irradiation (PCI) remains controversial in extensive disease small cell lung cancer (ED-SCLC). This study is performed to identify the risk factors of symptomatic brain metastasis and to evaluate the impact of PCI on brain metastasis-free survival (BMFS) and overall survival (OS) according to the risk of symptomatic brain metastasis in ED-SCLC. From 2006 to 2017, a total of 190 patients diagnosed with ED-SCLC who underwent FDG-PET and brain MRI prior to treatment were enrolled in this retrospective study. Among these patients, 53 (27.9%) received PCI and 137 (72.1%) did not. Prognostic index predicting a high risk of symptomatic brain metastasis was calculated in the observation group (137/190) on Cox regression model and the prognostic index was generated by summating significant factors weighted by a hazard ratio of each. The role of PCI in each risk group was analyzed by using Kaplan-Meier survival analysis. Median follow-up time was 10.6 months. 1-year and 2-year symptomatic BMFS were 86.9% and 49.8%, and 1-year and 2-year OS were 52.5% and 12.7%, respectively. Multivariate Cox regression analysis showed that 4 risk factors were associated with high risk of symptomatic brain metastasis: presence of extrathoracic metastases (P = 0.005) and hypermetabolism of bone marrow (BM) or spleen (P < 0.001) on FDG PET, as well as progressive disease (PD) after chemotherapy (P = 0.010) and high hemoglobin (Hb) level (P = 0.006). The prognostic index significantly divided patients into two subgroups of high and low-risk of symptomatic brain metastasis (P < 0.001). PCI significantly improved BMFS in high-risk patients (P = 0.002, 1-year rate 95.5% vs. 61.8%), but not in low-risk patients (P = 0.522, 1-year rate 100.0% vs. 91.9%). However, PCI did not improve OS in patients at high risk for symptomatic brain metastasis (P = 0.801, 1-year rate 45.0% vs. 50.0%). Four prognostic factors are associated with a high risk of symptomatic brain metastasis in ED-SCLC: the presence of extrathoracic metastases, hypermetabolism of BM or spleen from FDG PET parameters, PD after chemotherapy and high Hb level. PCI was beneficial for patients at high risk of symptomatic brain metastasis in terms of BMFS, but not OS. Thus, selective use of PCI in ED-SCLC according to the risk stratification by the prognostic factors from FDG PET and clinical parameters may be recommended, after the completion of a further validation study with a prospective manner.