Site-Specific Inflammatory Signatures in Metastatic NSCLC: Insights from Routine Blood Count Parameters

<i>Background and Objectives</i>: Systemic inflammatory markers from an ordinary complete blood count (CBC) may foreshadow where non-small-cell lung cancer (NSCLC) will first spread, but organ-specific signatures remain poorly defined. <i>Materials and Methods</i>: We retrospectively reviewed 302 adults (mean age 60.7 ± 13.4 years; 80.8% men) with stage IV NSCLC managed at OncoHelp Medical Center, Timișoara, between January 2022 and December 2024. Eligibility demanded a single radiologically confirmed distant site at diagnosis and pre-treatment CBC. Neutrophil-to-lymphocyte (NLR), platelet-to-lymphocyte (PLR), and lymphocyte-to-monocyte (LMR) ratios were compared across pleural (<i>n</i> = 52), bone (<i>n</i> = 86), liver (<i>n</i> = 66), and brain (<i>n</i> = 98) metastases using Kruskal-Wallis tests with Bonferroni adjustment; z-standardized logistic models identified independent predictors. <i>Results</i>: Metastases clustered most often in brain (32.5%), followed by bone (28.5%), liver (21.9%), and pleura (17.2%). Median PLR rose selectively in pleural disease (274 vs. 217-253 in other sites; <i>p</i> = 0.006). LMR fell to 2.0 in bone but climbed to 2.8 in brain lesions (<i>p</i> = 0.032 and 0.008, respectively). NLR was globally elevated (6.7-7.6), yet differed significantly only for bone and liver deposits. Logistic modeling showed that each standard-deviation rise in absolute neutrophil count quadrupled the odds of hepatic involvement (Odd Ratio (OR) 4.26; 99% Confidence inerval (CI) 2.20-6.25), monocytosis nearly doubled bone risk (OR 1.83; 1.01-3.33), while higher erythrocytes, eosinophils, and lymphocytes independently protected against pleural seeding (all <i>p</i> < 0.01). Age-stratified analysis revealed that osseous and cerebral metastases predominated in patients ≤ 50 years, whereas inflammatory indices were age-invariant. <i>Conclusions</i>: Routine CBC ratios encode distinct "inflammatory fingerprints" that mirror the first metastatic destination in NSCLC: platelets herald pleural spread, neutrophils favor liver and bone, and divergent lymphocyte-monocyte balances separate bone from brain. Although no substitute for cross-sectional imaging, these low-cost markers could refine clinical suspicion, guide targeted work-up, and illuminate the biology of organ-selective dissemination, particularly in resource-limited settings.