Abstract
Identification of a high-risk group of brain metastases (BM) in patients with non-small cell lung cancer (NSCLC) could lead to early interventions and probably better prognosis. The objective of the study was to identify this group by generating a multivariable model with recognized and accessible risk factors. A retrospective cohort from patients seen at a single center during 2010-2020, was divided into a training (TD) and validation (VD) datasets, associations with BM were measured in the TD with logit, variables significantly associated were used to generate a multivariate model. Model´s performance was measured with the AUC/C-statistic, Akaike information criterion, and Brier score. From 570 patients with NSCLC who met the strict eligibility criteria a TD and VD were randomly assembled, no significant differences were found amid both datasets. Variables associated with BM in the multivariate logit analyses were age [P 0.001, OR 0.96 (95% CI 0.93-0.98)]; mutational status positive [P 0.027, OR 1.96 (95% CI 1.07-3.56); and carcinoembryonic antigen levels [P 0.016, OR 1.001 (95% CI 1.000-1.003). BM were diagnosed in 24% of the whole cohort. Stratification into a high-risk group after simplification of the model, displayed a frequency of BM of 63% (P < 0.001). A multivariate model comprising age, carcinoembryonic antigen levels, and mutation status allowed the identification of a truly high-risk group of BM in NSCLC patients.
Highlights
Lung cancer (LC) is the most common malignancy and a leading cause of cancer-related death(1)
Some authors have reported individual risk factors associated with a higher risk of brain metastases (BM) such as age, gender, performance status, levels of tumor markers – including carcinoembryonic antigen (CEA), epidermal growth factor receptor (EGFR) mutation status, anaplastic lymphoma kinase (ALK) rearrangement(5); until now, there is no universal definition of an accurate high-risk group of BM
Mean age at lung cancer diagnosis was 61.1 years, female gender was more frequent, half of the patients had a smoking history, the most frequent histology was adenocarcinoma (88%), poorly differentiated NSLC was seen in 50%, mutational status [EGFR mutation (EGFRm) or ALK rearrangement (ALKr)] was positive in 47%, most patients had clinical stage IV at diagnosis (87%), mean CEA levels was 120 pg/mL (Min-Max 0.28–3416), mean initial tumor size was 5.2 cm (Min-Max 1.1–16 cm)
Summary
Lung cancer (LC) is the most common malignancy and a leading cause of cancer-related death(1). Up to 25–50% of non-small cell lung cancer (NSCLC) patients will develop brain metastases (BM) during their disease course(2), and LC is the most frequent primary tumor to metastasize to the brain(3). The identification of a high-risk group of BM in NSCLC could lead to earlier interventions including prophylactic cranial irradiation (PCI). PCI has been examined for several decades as a fraught gauge to prevent BM in NSCLC(4), probably because of the absence of a truly identified high-risk group. Some authors have reported individual risk factors associated with a higher risk of BM such as age, gender, performance status, levels of tumor markers – including carcinoembryonic antigen (CEA) –, epidermal growth factor receptor (EGFR) mutation status, anaplastic lymphoma kinase (ALK) rearrangement(5); until now, there is no universal definition of an accurate high-risk group of BM
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