Hippocampal Metastasis Rate Based on Non-Small Lung Cancer TNM Stage and Molecular Markers

Sung Jun Ahn; Hyeokjin Kwon; Jun Won Kim; Goeun Park; Mina Park; Bio Joo; Sang Hyun Suh; Yoon Soo Chang; Jong-Min Lee

doi:10.3389/fonc.2022.781818

Hippocampal Metastasis Rate Based on Non-Small Lung Cancer TNM Stage and Molecular Markers

Front Oncol. 2022 May 10:12:781818. doi: 10.3389/fonc.2022.781818. eCollection 2022.

Authors

Sung Jun Ahn¹, Hyeokjin Kwon², Jun Won Kim³, Goeun Park⁴, Mina Park¹, Bio Joo¹, Sang Hyun Suh¹, Yoon Soo Chang⁵, Jong-Min Lee⁶

Affiliations

¹ Department of Radiology, Gangnam Severance Hospital, Yonsei University, College of Medicine, Seoul, South Korea.
² Department of Electronic Engineering, Hanyang University, Seoul, South Korea.
³ Department of Radiation Oncology, Gangnam Severance Hospital, Yonsei University, College of Medicine, Seoul, South Korea.
⁴ Biostatistics Collaboration Unit, Yonsei University College of Medicine, Seoul, South Korea.
⁵ Department of Internal Medicine, Gangnam Severance Hospital, Yonsei University, College of Medicine, Seoul, South Korea.
⁶ Department of Biomedical Engineering, Hanyang University, Seoul, South Korea.

Abstract

Hippocampal-avoidance whole-brain radiation therapy (HA-WBRT) is justified because of low hippocampal brain metastases (BM) rate and its prevention of cognitive decline. However, we hypothesize that the risk of developing BM in the hippocampal-avoidance region (HAR) may differ depending on the lung-cancer stage and molecular status. We retrospectively reviewed 123 patients with non-small cell lung cancer (NSCLC) at the initial diagnosis of BM. The number of BMs within the HAR (5 mm expansion) was counted. The cohort was divided into patients with and without BMs in the HAR, and their clinical variables, TNM stage, and epidermal growth factor receptor (EGFR) status were compared. The most influential variable predicting BMs in the HAR was determined using multi-variable logistic regression, classification and regression tree (CART) analyses, and gradient boosting method (GBM). The feasibility of HAR expansion was tested using generalized estimating equation marginal model. Patients with BMs in the HAR were more frequently non-smokers, and more likely to have extra-cranial metastases and EGFR mutations (p<0.05). Multi-variable analysis revealed that extra-cranial metastases were independently associated with the presence of BM in the HAR (odds ratio=8.75, p=0.04). CART analysis and GBM revealed that the existence of extra-cranial metastasis was the most influential variable predicting BM occurrence in the HAR (variable importance: 23% and relative influence: 37.38). The estmated BM incidence of patients without extra-cranial metastases in th extended HAR (7.5-mm and 10-mm expansion) did not differ significantly from that in the conventional HAR. In conclusion, NSCLC patients with extra-cranial metastases were more likely to have BMs in the HAR than those without extra-cranial metastases.

Keywords: Brain metastasis; Epidermal growth factor receptor; Hippocampal-avoidance whole-brain radiation therapy; Non-small cell lung cancer; lung-cancer stage.