Clinical determinants impacting overall survival of patients with operable brain metastases from non-small cell lung cancer

Abstract

Non-small cell lung cancer (NSCLC) is currently the leading cause of cancer-related death worldwide, and the incidence of brain metastases (BM) in NSCLC patients is continuously increasing. The recent improvements of systemic treatment in NSCLC necessitate continuous updates on prognostic subgroups and factors determining overall survival (OS). In order to improve clinical decision-making in tumor boards, we investigated the clinical determinants affecting survival in patients with resectable NSCLC BM. A retrospective analysis was conducted of NSCLC patients with surgically resectable BM treated in our institution between 01/2015 and 12/2020. The relevant clinical factors affecting survival identified by univariate analysis were included in a multivariate logistic regression model. Overall, 264 patients were identified, with a mean age of 62.39 ± 9.98 years at the initial diagnosis of NSCLC BM and OS of 23.22 ± 1.71 months. The factors that significantly affected OS from the time of primary tumor diagnosis included the systemic metastatic load (median: 28.40 ± 4.82 vs. 40.93 ± 11.18 months, p = 0.021) as well as a number of BM <2 (median: 17.20 ± 2.52 vs. 32.53 ± 3.35 months, p = 0.014). When adjusted for survival time after neurosurgical intervention, a significant survival benefit was found in patients <60 years (median 16.13 ± 3.85 vs. 9.20 ± 1.39 months, p = 0.011) and, among others, patients without any concurrent systemic metastases at time of NSCLC BM diagnosis. Our data shows that the number of BM (singular/solitary), the Karnofsky Performance Status, gender, and age but not localization (infra-/supratentorial), mass-edema index or time to BM occurrence impact OS, and postsurgical survival in NSCLC BM patients. Additionally, our study shows that patients in prognostically favorable clinical subgroups an OS, which differs significantly from current statements in literature. The described clinically relevant factors may improve the understanding of the risks and the course of this disease and Faid future clinical decision making in tumor boards.

Keywords: NSCLC; brain metastasis; metastasis; resectable; surgery; survival.

Figure 1

Overall survival (OS) in non-small cell lung cancer (NSCLC) brain metastases (BM) patients (A) Kaplan–Meier survival analysis of OS from the time point of initial diagnosis in patients <60 and >60 years of age, (B) in male vs. female patients, (C) in patients with a singular vs. solitary BM status, (D) depending on BM localization, (E) depending on the number of BM, (F) depending on the mass-edema index (MEI), (G) depending on the preoperative Karnofsky Performance Status (KPS) score, and (H) depending on the KPS score at discharge.

Figure 2

OS postneurosurgical intervention. (A) Kaplan–Meier survival analysis postneurosurgical intervention in patients <60 and >60 years of age, (B) in male vs. female patients, (C) depending on the time to BM diagnosis, (D) depending on the number of BM, (E) depending on the size of BM, (F) in patients with singular vs. solitary vs. multiple BM status, (G) depending on BM localization, (H) depending on the MEI, (I) depending on postdiagnosis treatment (at diagnosis—no treatment pre-non-small cell lung cancer (NSCLC) BM diagnosis, after CT—chemotherapy treatment pre-NSCLC BM diagnosis, and after immunotherapy (IT)— immune checkpoint blockade treatment pre-NSCLC BM diagnosis), (J) depending on the preoperative KPS score, (K) depending on the KPS score at discharge, and (L) depending on the KPS score change due to surgical intervention.

Figure 3

Identification of favorable clinical subgroups. (A) Cox regression of a singular vs. solitary BM status. (B) Cox regression of favorable vs. unfavorable patient groups.