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. 2022 Apr 26:12:879554.
doi: 10.3389/fonc.2022.879554. eCollection 2022.

Prognostic Factors and Survival Benefits of Antitumor Treatments for Advanced Non-Small Cell Lung Cancer Patients With Central Nervous System Metastasis With or Without Driver Genes: A Chinese Single-Center Cohort Study

Xiaoxing Gao  1 , Minjiang Chen  1 , Xiaoyan Liu  1 , Yuequan Shi  1 , Hongge Liang  1 , Qing Zhou  1 , Jing Zhao  1 , Ruili Pan  1 , Wei Zhong  1 , Yan Xu  1 , Mengzhao Wang  1
Affiliations

Prognostic Factors and Survival Benefits of Antitumor Treatments for Advanced Non-Small Cell Lung Cancer Patients With Central Nervous System Metastasis With or Without Driver Genes: A Chinese Single-Center Cohort Study

Xiaoxing Gao et al. Front Oncol. .

Abstract

Background: The prognosis of non-small cell lung cancer (NSCLC) patients with central nervous system (CNS) metastasis is poor. The treatment for CNS metastasis could prolong the overall survival of NSCLC patients. We aimed to investigate the prognostic factors of Chinese NSCLC patients with CNS metastasis and the survival benefits of various treatments for CNS metastasis in NSCLC patients with or without driver genes.

Methods: Based on the CAPTRA-Lung database, NSCLC patients with CNS metastasis admitted at the Peking Union Medical College Hospital between January 2010 and October 2018 were enrolled in the study. The prognostic factors were analyzed using univariate and multivariate Cox regression analyses.

Results: Overall, 418 patients were enrolled in the study. A total of 206 patients (49.3%) had CNS metastasis with positive driver genes, while 97 patients (23.2%) had negative driver genes. The median survival time after CNS metastasis was 20.8 months. In the multivariable analysis, an Eastern Cooperative Oncology Group performance status of ≥2 (hazard ratio [HR]: 1.750, 95% confidence interval [CI]: 1.184-2.588, P=0.005), number of CNS metastases ≥5 (HR: 1.448, 95% CI: 1.084 -1.934, P=0.012), and CNS metastasis developed during treatment (HR: 1.619, 95% CI: 1.232-2.129, P=0.001) were independent risk factors for poor survival. Lung adenocarcinoma (HR: 0.490, 95% CI: 0.279-0.861, P=0.013) and driver gene positivity (HR: 0.464, 95% CI: 0.302-0.715, P=0.001) were independent predictors of prolonged survival. Radiotherapy for CNS metastasis showed a survival benefit in NSCLC patients in the entire groups (HR: 0.472, 95% CI: 0.360-0.619, P <0.001), and in patients with positive driver genes.

Conclusion: Performance status, number of CNS metastases, timing of CNS metastasis, histological subtype, and driver gene status are prognostic factors for NSCLC patients with CNS metastasis. Furthermore, radiotherapy improved the survival in NSCLC patients with CNS metastasis.

Keywords: central nervous system metastasis; cohort study; non-small-cell lung cancer; prognostic factors; treatment outcome.

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Conflict of interest statement

The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.

Figures

Figure 1
Figure 1
Kaplan–Meier curve showing OS since CNS metastasis developed based on different factors for NSCLC patients. (A) The median OS of NSCLC patients with CNS metastasis. The median OS since CNS metastasis developed (B) in NSCLC patients of age < 70 group vs. age≥70 group, (C) in female patients vs. male patients, (D) in NSCLC patients with different smoking status (non-smoker, smoker, and unknown), (E) in NSCLC patients without neurological symptoms vs. with neurological symptoms, (F) in NSCLC patients of ECOG 0-1 vs. ECOG ≥ 2, (G) in NSCLC patients of different histology subtype (LUSC, LUAD and unknown), (H) in NSCLC patients with different driver gene status (negative driver gene, positive driver gene, and unknown), (I) in NSCLC patients with non-LM vs. with LM, (J) in NSCLC patients with CNS metastasis number <5 vs. CNS metastasis number≥5 vs. unknown, and (K) in NSCLC patients with CNS metastasis developed during treatment vs. treatment naïve. CNS, central nervous system; ECOG, Eastern Cooperative Oncology Group; LM, leptomeningeal metastasis; LUAD, lung adenocarcinoma; LUSC, squamous cell lung carcinoma; NSCLC, non-small cell lung cancer; OS, overall survival.
Figure 2
Figure 2
Kaplan-Meier curve illustrating OS since CNS metastasis in NSCLC patients with various treatments: (A) with or without target therapy, (B) with or without chemotherapy, (C) with or without antiangiogensis therapy, (D) with or without neurosurgery, (E) with or without radiotherapy in all NSCLC patients with CNS metastasis, and (F) with or without radiotherapy in positive driver genes NSCLC patients with CNS metastasis. OS, overall survival; CNS, central nervous system; NSCLC, non-small cell lung cancer.
Figure 3
Figure 3
Multivariate analysis Cox proportional hazards for OS in NSCLC patients with CNS metastasis. CNS, central nervous system; ECOG, Eastern Cooperative Oncology Group; LM, leptomeningeal metastasis; LUAD, lung adenocarcinoma; LUSC, squamous cell lung carcinoma.
Figure 4
Figure 4
Multivariate analysis Cox proportional hazards for OS in NSCLC patients with CNS metastasis of positive driver genes group. ALK, anaplastic lymphoma kinase; CNS, central nervous system; ECOG, Eastern Cooperative Oncology Group; EGFR, epidermal growth factor receptor; LM, leptomeningeal metastasis; LUAD, lung adenocarcinoma; LUSC, squamous cell lung carcinoma.
Figure 5
Figure 5
Multivariate analysis Cox proportional hazards for OS in NSCLC patients with CNS metastasis of negative driver genes group. CNS, central nervous system; ECOG, Eastern Cooperative Oncology Group; LM, leptomeningeal metastasis; LUAD, lung adenocarcinoma; LUSC, squamous cell lung carcinoma.
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