Differential Metastatic Patterns and Prognostic Value of Systemic Inflammation Scores in Anaplastic Lymphoma Kinase Rearranged Versus Anaplastic Lymphoma Kinase Negative Non-Small Cell Lung Cancer

<b>Background</b>: Non-small cell lung cancer (NSCLC) is the most prevalent form of malignancy and the leading cause of cancer-related fatalities. In clinical practice, metastatic sites are identified on a case-by-case basis. ALK rearrangements are detected in 3-5% of NSCLC cases and are known to have a tendency (tropism) to metastasize to the brain. <b>Methods</b>: Data from 81 ALK-positive and 91 ALK-negative metastatic NSCLC patients were retrospectively analyzed. Systemic markers, including HALP score, NLR, PLR, LMR, and LDH, were calculated from blood tests at the time of metastasis. Optimal cut-off values were determined using ROC analysis. Survival outcomes and prognostic factors were assessed using Kaplan-Meier and Cox regression analyses. <b>Results</b>: ALK-positive patients were significantly associated with female gender (<i>p</i> = 0.002), non-smoking status (<i>p</i> = 0.001), adenocarcinoma histology (<i>p</i> = 0.001), and a higher incidence of brain metastases (<i>p</i> = 0.001). In univariate analysis, age, time to metastasis, liver metastasis, and NLR were prognostic for survival. Crucially, multivariate analysis identified liver metastasis as an independent predictor of poor prognosis (HR = 1.618; 95% CI: 1.050-2.494; <i>p</i> = 0.029), indicating a 61.8% increased risk of death or progression. While inflammation markers (NLR, HALP, PLR, LMR) did not predict metastasis to specific sites, elevated LDH levels were significantly associated with liver metastasis (<i>p</i> = 0.007). <b>Conclusion</b>: ALK-positive NSCLC demonstrates a marked CNS tropism; however, liver metastasis remains a more critical adverse prognostic factor than brain metastasis in real-world settings. While routine inflammation markers showed limited utility in predicting site-specific metastasis, LDH levels correlated significantly with liver involvement. Aggressive management strategies are warranted for ALK-positive patients presenting with liver metastases.