Abstract
Abstract INTRODUCTION Radiotherapy is the primary local intervention for cerebral metastases (BMs). Despite decades of advancements in this field, inadvertent collateral irradiation of adjacent healthy tissue in proximity to neoplastic site remains a persistent challenge. Neural stem cells (NSCs), crucial for the establishment and preservation of the nervous system, exhibit heightened sensitivity to radiation. Consequently, radiation-induced damage to NSCs may influence Overall Survival (OS) in patients with BMs. NSCs are primarily located in the subventricular zone (SVZ) and the subgranular zone (SGZ) within the hippocampus (HPC). In this study, our objective is to assess the influence of unintended radiotherapy dose on NSCs and its subsequent effect on OS. METHODS In this retrospective study, we incorporated data from 138 Non-Small Cell Lung Cancer (NSCLC) patients with BMs, from a single academic institution. NSC regions were projected on non-enhanced T1 MR images with Computational Anatomy Toolbox 12 and Statistical Parametric Mapping. The association between regional mean doses to the SVZ and HPC and OS was examined using a Cox regression model. Additionally, survival differences between lesion contact and no direct contact with SVZ and HPC were investigated with Kaplan-Meier (KM) analysis. RESULTS Multivariable Cox regression analysis of the dose on the SVZ and HPC showed a significant negative correlation, with a hazard ratio (HR) of 1.366 (p = 0.041 [95% (CI) 1.013– 1.842]) and 1.194 (p = 0.037 [95% CI 1.010 – 1.411]), respectively. KM analysis did not identify a relationship between direct lesion contact with NSC-regions and OS. CONCLUSION Any unintended dose on the neurogenic niches is correlated with poorer OS in patients with BMs from NSCLC. Interestingly, there was no association between direct contact or invasion of these regions and the OS. We recommend conducting further investigation into the impact on neurocognitive function within this specific group in a prospective study design.
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