# Spine Metastasis Is Associated with the Development of Brain Metastasis in Non-Small-Cell Lung Cancer Patients

**Authors:** Hyung-Keun Cha, Woo-Kyung Ryu, Ha-Young Lee, Hyun-Jung Kim, Jeong-Seon Ryu, Jun-Hyeok Lim

PMC · DOI: 10.3390/medicina60010152 · Medicina · 2024-01-14

## TL;DR

This study finds that spine metastasis in non-small-cell lung cancer patients increases the risk of developing brain metastasis.

## Contribution

The study identifies spine metastasis as a novel risk factor for brain metastasis in NSCLC patients.

## Key findings

- Spine metastasis is associated with brain metastasis at diagnosis and subsequent development.
- Most BM lesions in patients with spine metastasis are located near the cerebrospinal fluid space.
- Spine involvement is a significant predictor of BM in NSCLC patients with bone metastasis.

## Abstract

Background and Objectives: The mechanisms involved in the development of brain metastasis (BM) remain elusive. Here, we investigated whether BM is associated with spine involvement in patients with non-small-cell lung cancer (NSCLC). Materials and Methods: A consecutive 902 patients with metastatic NSCLC were included from the Inha Lung Cancer Cohort. Patients with BM at diagnosis or subsequent BM development were evaluated for both spine involvement in NSCLC and anatomic proximity of BM to the cerebrospinal fluid (CSF) space. Results: At diagnosis, BM was found in 238 patients (26.4%) and bone metastasis was found in 393 patients (43.6%). In patients with bone metastasis, spine involvement was present in 280 patients. BM subsequently developed in 82 (28.9%) of 284 patients without BM at diagnosis. The presence of spine metastasis was associated with BM at diagnosis and subsequent BM development (adjusted odd ratios and 95% confidence intervals = 2.42 and 1.74–3.37, p < 0.001; 1.94 and 1.19–3.18, p = 0.008, respectively). Most patients with spine metastasis, either with BM at diagnosis or subsequent BM, showed BM lesions located adjacent (within 5mm) to the CSF space (93.8% of BM at the diagnosis, 100% of subsequent BM). Conclusions: These findings suggest that the presence of spine involvement is a risk factor for BM development in NSCLC patients with bone metastasis.

## Linked entities

- **Diseases:** non-small-cell lung cancer (MONDO:0005233)

## Full-text entities

- **Genes:** EGFR (epidermal growth factor receptor) [NCBI Gene 1956] {aka ERBB, ERBB1, ERRP, HER1, NISBD2, NNCIS}, MFGE8 (milk fat globule EGF and factor V/VIII domain containing) [NCBI Gene 4240] {aka BA46, EDIL1, HMFG, HsT19888, MFG-E8, MFGM}, TENM1 (teneurin transmembrane protein 1) [NCBI Gene 10178] {aka ODZ1, ODZ3, TEN-M1, TEN1, TNM, TNM1}, Alk (anaplastic lymphoma kinase) [NCBI Gene 11682] {aka CD246, Tcrz}, C3 (complement C3) [NCBI Gene 718] {aka AHUS5, ARMD9, ASP, C3a, C3b, CPAMD1}, Egfr (epidermal growth factor receptor) [NCBI Gene 13649] {aka 9030024J15Rik, Erbb, Errb1, Errp, Wa5, wa-2}, TXK (TXK tyrosine kinase) [NCBI Gene 7294] {aka BTKL, PSCTK5, PTK4, RLK, TKL}
- **Diseases:** small-cell lung cancer (MESH:D055752), adenocarcinoma (MESH:D000230), seizures (MESH:D012640), Brain or Bone Metastasis (MESH:D009362), injury to people or property (MESH:C000719191), BM Lesions (MESH:D001927), headaches (MESH:D006261), Spinal canal invasion (MESH:D009361), brain metastases (MESH:D001932), visual and speech problems (MESH:D014786), Spine Involvement (MESH:D016135), breast and lung tumors (MESH:D001943), squamous cell carcinoma (MESH:D002294), metastatic (MESH:D000092182), Lung Cancer (MESH:D008175), cancer (MESH:D009369), ataxia (MESH:D001259), NSCLC (MESH:D002289), cognitive deficits (MESH:D003072), spinal metastatic lesions (MESH:D013122)
- **Chemicals:** Lorlatinib (MESH:C000590786), AZD3759 (MESH:C000604577), osimertinib (MESH:C000596361), 18F-fluorodeoxyglucose (MESH:D019788), Alectinib (MESH:C582670)
- **Species:** Mus musculus (house mouse, species) [taxon 10090], Homo sapiens (human, species) [taxon 9606]
- **Cell lines:** S2 — Drosophila melanogaster (Fruit fly), Spontaneously immortalized cell line (CVCL_Z232)

## Full text

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## Figures

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## References

27 references — full list in the complete paper: https://tomesphere.com/paper/PMC10820916/full.md

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Source: https://tomesphere.com/paper/PMC10820916