Shandong Cancer Hospital and Institute Jinan, Shandong
L. Li1, X. Song Jr1, N. Liu1, and S. Yuan1,2; 1Department of Radiation Oncology, Shandong Cancer Hospital and Institute, Shandong First Medical University and Shandong Academy of Medical Sciences, Jinan, Shandong, China, 2Department of Radiation Oncology, The First Affiliated Hospital of USTC, Division of Life Sciences and Medicine, University of Science and Technology of China, Hefei, Anhui, China, Hefei, China
Purpose/Objective(s): The standard of care for patients with limited-stage small-cell lung cancer (LS-SCLC) is definitive chemoradiotherapy (dCRT), typically accompanied by prophylactic cranial irradiation (PCI) for responsive patients. However, the treatment responses vary, and brain metastases (BM) are frequently encountered. Materials/
Methods: The cumulative incidence of BM was assessed in relation to baseline genomic features identified from 180 LS-SCLC patients who underwent frontline dCRT, considering death as a competing risk. Variables independently associated with BM occurrence risk were determined using the Fine-Gray model. Results: Four features were identified associated with the cumulative risk of BM, including two clinical factors and two genomic alterations. PCI consolidation treatment and the presence of FLT4 mutation in untreated LS-SCLC tumors were both independently linked to a decreased cumulative incidence of BM (P=0.001 and P=0.033, respectively). In great contrast, smoking and the presence of RB1 mutation were associated with an increased risk of BM occurrence (P=0.021 and P=0.008, respectively). The presence of RTK/RAS pathway variants exhibited better overall objective response (ORR) to dCRT, whereas genetic variants in ARID1A, GNAS, and TSC1 genes were likely correlated with an unfavorable ORR in LS-SCLC patients. Importantly, RB1 mutation, of which mostly were truncating mutations, continued to serve as a significant biomarker within the subset of patients who responded to dCRT and completed PCI treatment, suggesting an elevated risk of developing BM within this treatment regimen. Conclusion: By identifying risk factors associated with varying risks of BM development in baseline tumors, our study may assist clinicians in implementing close surveillance and exploring alternative treatment plans for LS-SCLC patients at high risk of BM.
