Construction of Brain Metastasis Prediction Model and Optimization of Prophylactic Cranial Irradiation Selection for Limited-Stage Small-Cell Lung Cancer

Simple Summary The brain is a common metastasis site of small-cell lung cancer (SCLC), and up to 50% of SCLC patients are at risk of brain metastasis (BM) within 2 years. Prophylactic cranial irradiation (PCI), as an essential treatment for reducing the risk of BM, inevitably leads to neurotoxicity. Differentiating the risk of BM in patients and individualized PCI treatment decisions may play an essential role in reducing the occurrence of BM, prolonging the overall survival, and improving the quality of life. Our study constructed and validated a clinical model to predict the incidence of BM and risk stratification for individualized PCI decisions. PCI could reduce the incidence of BM and improve overall survival (OS) in patients with a high risk of BM, but there was no significant difference between PCI and non-PCI groups in patients within a low-risk cohort. Prophylactic cranial irradiation (PCI), as an essential part of the treatment of limited-stage small-cell lung cancer (LS-SCLC), inevitably leads to neurotoxicity. This study aimed to construct a brain metastasis prediction model and identify low-risk patients to avoid PCI; 236 patients with LS-SCLC were retrospectively analyzed and divided into PCI (63 cases) and non-PCI groups (173 cases). The nomogram was developed based on variables determined by univariate and multivariate analyses in the non-PCI group. According to the cutoff nomogram score, all patients were divided into high- and low-risk cohorts. A log-rank test was used to compare the incidence of brain metastasis between patients with and without PCI in the low-risk and high-risk groups, respectively. The nomogram included five variables: chemotherapy cycles (ChT cycles), time to radiotherapy (RT), lactate dehydrogenase (LDH), pro-gastrin-releasing peptide precursor (ProGRP), and lymphocytes-monocytes ratio (LMR). The area under the receiver operating characteristics (AUC) of the nomogram was 0.763 and 0.782 at 1 year, and 0.759 and 0.732 at 2 years in the training and validation cohorts, respectively. Based on the nomogram, patients were divided into high- and low-risk groups with a cutoff value of 165. In the high-risk cohort, the incidence of brain metastasis in the non-PCI group was significantly higher than in the PCI group (p < 0.001), but there was no difference in the low-risk cohort (p = 0.160). Propensity score-matching (PSM) analysis showed similar results; the proposed nomogram showed reliable performance in assessing the individualized brain metastasis risk and has the potential to become a clinical tool to individualize PCI treatment for LS-SCLC.