Brain Imaging in Patients with Non-Small Cell Lung Cancer-A Systematic Review

Abstract

Background: Lung cancer frequently metastasizes to the brain, liver, and adrenal glands with a significant negative prognostic impact on overall survival and quality of life (QoL). To optimize treatment and prognosis, adequate staging with the detection of distant metastases is crucial. The incidence of brain metastases in potentially resectable early-stage non-small cell lung cancer (NSCLC) is as low as 3%; hence, the need for preoperative brain imaging has been a constant matter of debate, especially in stage II. In stages III and IV NSCLC, neuroimaging is an essential part of staging. Methods: A systematic literature search was performed. Publications from 1999 to 2024, focusing on preoperative brain imaging (BI) in the staging of stages I-IV NSCLC, were included. Data extraction included study population characteristics, the modality of BI, the incidence of brain metastases (BMs), and the main outcomes of the studies. The final included studies were selected according to the PRISMA criteria. In the second step, guidelines on BI in NSCLC staging of major importance were identified and compared. Results: A total of 530 articles were identified, of which 25 articles were selected. Four prospective studies and 21 retrospective investigations were included. Most of the investigations focused on BI in the early stages. The main imaging modality for BI was magnetic resonance imaging (MRI), followed by computed tomography (CT). Besides the identified 25 studies, the most important internationally applied guidelines on brain imaging in the staging of NSCLC were reviewed. While some guidelines agree on preoperative BI in NSCLC stage III (Union for International Cancer Control-UICC eighth edition) patients, other guidelines recommend earlier BI starting from clinical stage II. All mentioned guidelines homogenously recommend BI in patients with symptoms suggestive of brain pathologies. Conclusions: BI in NSCLC staging is recommended in neurologically symptomatic patients suggestive of brain metastases as well as NSCLC patients with stage III disease. Neuroimaging in stage IA patients, as well as in pure GGO (Ground-Glass Opacity) lesions, was considered unnecessary. The predominantly applied imaging modality was ce-MRI (contrast-enhanced magnetic resonance imaging). Inconsistency exists concerning BI in stage II. The identification of prognostic factors for developing BM in patients with early-stage NSCLC could help to clarify which subgroup might benefit from preoperative BI.

Keywords: MRI; brain imaging; brain metastases; non-small cell lung cancer (NSCLC); preoperative staging.

Figure 1

Identification and selection of studies according to The Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) statement criteria for the systematic review process. Abbreviations: No. = number of.

Figure 2

Risk of bias assessment performed using the robvis generic tool. Risk of bias was defined as high, some concerns, low, or not applicable. Domains D1 = bias arising from the randomization process, D2 = bias due to deviation from the intended intervention, D3 = bias due to missing outcome data, D4 = bias in the measurement of the outcome, and D5 = bias in the selection of the reported results were assessed [11,12,15,27,28,31,32,33,34,35,36,37,38,39,40,41,42,43,44,45,46,47,48,49,50].

Figure 3

MRI in the detection of BMs. Red arrows indicate the identified BM in different MRI modalities and locations with an (A) infratentorial metastasis in flair, (B) a supratentorial metastasis in the T2-sequence, and (C) a paramedian metastasis in the T1-sequence. Abbreviations: BM = brain metastases, MRI = magnetic resonance imaging.

Figure 4

ce-CT vs. PET-CT in the detection of brain metastases (BMs). A large right frontotemporal BM with surrounding edema was clearly diagnosed in the ce-CT head (A), while PET-CT was suggestive of an FDG-avid lesion in this area (B). Abbreviations: ce-CT = contrast-enhanced computed tomography, PET-CT = positron emission computed tomography.