# 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

## TL;DR

This study compares outcomes in lung cancer patients with and without a specific genetic change, finding that liver metastasis is a stronger predictor of poor survival than brain metastasis.

## Contribution

The study identifies liver metastasis as a more critical prognostic factor than brain metastasis in ALK-positive lung cancer patients.

## Key findings

- ALK-positive patients have a higher risk of brain metastasis but liver metastasis is a stronger predictor of poor survival.
- Elevated LDH levels are significantly associated with liver metastasis in ALK-positive patients.
- Liver metastasis increases the risk of death or progression by 61.8% in ALK-positive NSCLC patients.

## Abstract

Lung cancer is the foremost cause of cancer related fatalities on a global scale. A specific genetic subtype of lung cancer, designated as ALK positive, is characterised by its propensity to metastasise to the brain with high frequency. However, predicting patient outcomes in real-world settings remains a challenging endeavour. The objective of this study was to analyse the disparities between patients with and without this genetic alteration, with a particular focus on the dissemination of cancer and the potential of routine blood tests to predict these patterns. It was established that, while ALK positive patients do exhibit an elevated risk of brain metastasis, metastasis to the liver is a more significant predictor of poor survival. In addition, a standard blood test (LDH) was found to be significantly linked to liver involvement. These findings are of significance as they underscore the necessity for medical professionals to adopt a proactive approach in the management of liver metastases. The utilisation of simple blood tests holds immense potential in the enhanced monitoring of high risk patients, thereby facilitating the development of more personalised treatment strategies.

Background: 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. Methods: 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. Results: ALK-positive patients were significantly associated with female gender (p = 0.002), non-smoking status (p = 0.001), adenocarcinoma histology (p = 0.001), and a higher incidence of brain metastases (p = 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; p = 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 (p = 0.007). Conclusion: 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.