Xiansheng Qiu,1,2,* Zhenwei Lu,1,2,* Chongfei Li,1,2 Sifang Chen,2 Xiaoping Zhou,1,3 Zhizhu Peng,4 Li Chen,1 Wen peng Zhao,2 JingJing Shi,2 Jiawei He,2 Xuewei Xia,5,* Zhanxiang Wang1,* 

1The School of Clinical Medicine, Fujian Medical University, Fuzhou, Fujian, People’s Republic of China; 2The First Hospital Affiliated of Xiamen University, Xiamen, Fujian, People’s Republic of China; 3Ganzhou People’s Hospital, Ganzhou, Jiangxi, People’s Republic of China; 4Guangxi Second People’s Hospital, Guangxi Zhuang Autonomous Region, People’s Republic of China; 5The First Hospital Affiliated of Guilin Medical University, Guilin, Guangxi Zhuang Autonomous Region, People’s Republic of China

*These authors contributed equally to this work

Correspondence: Xuewei Xia, Department of Neurosurgery, Affiliated Hospital of Guilin Medical University, No. 15 Lequn Road, Guilin, Guangxi, 541001, People’s Republic of China, Tel +86-773-2800672, Fax +86-773-2812650, Email xxw7456@163.com Zhanxiang Wang, The School of Clinical Medicineh, Fujian Medical University, The First Hospital Affiliated of Xiamen University, Xiamen, Fujian, People’s Republic of China, Tel/Fax +86-0592-2139715, Email wangzx@xmu.edu.cn

Background: Lung cancer brain metastasis (LCBM) accounts for 40– 50% of intracranial malignancies, with emerging evidence of alternative metastatic pathways circumventing the blood-brain barrier. Existing prognostic models lack validation in Asian populations and molecular stratification. This multicenter study aimed to develop a clinical nomogram integrating clinicopathological and molecular determinants for personalized LCBM management.
Methods: Retrospective analysis of 522 surgically treated LCBM patients (2015– 2021) from four Chinese institutions was conducted. Patients were randomized 7:3 into training (n=365) and validation (n=157) cohorts. Multivariate Cox regression identified independent prognostic factors, which were incorporated into a nomogram predicting 6-/12-/18-month overall survival (OS). Model performance was assessed via time-dependent ROC curves (AUC), calibration plots, and decision curve analysis (DCA).
Results: The median OS after neurosurgery was 9 months (range: 4– 18 months), with 6-, 12-, and 18-month survival rates of 86.2%, 46.7%, and 17.2%, respectively. Independent predictive factors included brain metastasis size ≥ 5 cm, Leptomeningeal metastasis(LM), EGFR mutation with TKI treatment, and extracranial metastases. The nomogram demonstrated robust discriminative ability and calibration. EGFR-mutant patients receiving postoperative TKIs showed significantly prolonged survival attributable to enhanced blood-brain barrier permeability. Finally, the authors developed a web-based dynamic nomogram for LCBM patients to facilitate clinical implementation.
Conclusion: This study establishes a validated prognostic model integrating tumor burden, EGFR mutation status, and metastatic patterns. It demonstrates that EGFR-guided TKI therapy and bone metastasis surveillance critically influence LCBM outcomes. The nomogram provides a quantifiable framework for risk-adapted therapeutic decisions, advancing precision oncology in neuro-oncology practice.

Keywords: nomogram, overall survival, lung cancer brain metastases, cranial metastases, surgery