Abstract
SummaryBackgroundNon-small cell lung cancer (NSCLC), the most common type of lung cancer, often leads to brain metastases (BMs) with a poor prognosis. Radiotherapy is the main treatment for BMs, which despite decades of development, still results in radiation of healthy tissue. Neural stem cells (NSCs), crucial for the establishment and preservation of the nervous system, are sensitive to radiation, therefore radiation damage to NSCs may affect overall survival (OS). NSCs are primarily located in the subventricular zone (SVZ) and the subgranular zone (SGZ) within the hippocampus (HPC). Our study aims to evaluate the impact of radiotherapy dose on NSCs on OS in patients with BMs from NSCLC.MethodsWe have retrospectively included 138 NSCLC patients with BMs, irradiated at a single academic institute. NSC regions were delineated on the non-enhanced T1 MR images with CAT12 and SPM. The association between regional mean doses in 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.FindingsMultivariable Cox regression of 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 find a relationship between lesion contact with NSC-regions and OS.InterpretationRadiotherapy dose on the neurogenic niches is correlated with poorer OS and we found no association between direct lesion contact to NSC-regions and OS. We recommend further investigation into the impact of radiation on OS and neurocognitive function in a prospective study design in order to develop treatment approaches that minimize the potential harm to NSC’s while maximizing effectiveness.FundingReceived no funds, grants, or support.
Publisher
Cold Spring Harbor Laboratory