# Association of regional specificity of blood-brain barrier permeability with pathological subtypes in cerebral white matter of patients with non-brain metastatic lung cancer

## TL;DR

This study shows that lung cancer patients without brain metastases still have blood-brain barrier issues, and these issues vary by cancer subtype, especially in white matter regions of the brain.

## Contribution

The study reveals regional BBB permeability differences in non-brain metastatic lung cancer patients, linked to specific histopathological subtypes.

## Key findings

- Adenocarcinoma (ADC) lung cancer shows higher BBB permeability in deep white matter and posterior periventricular regions compared to other subtypes.
- Small Cell Lung Cancer (SCLC) exhibits distinct patterns of interstitial disruption, primarily in deep white matter regions.
- BBB permeability in lung cancer patients is comparable to those with brain metastases but distinct from healthy controls.

## Abstract

To investigate blood-brain barrier (BBB) permeability abnormalities in cerebral white matter regions of non-brain metastatic lung cancer (LC) patients and their association with histopathological subtypes.

221 subjects (74 Healthy Controls [HC], 78 LC, 69 LC with Brain Metastasis [LCBM]) were enrolled. LC was subdivided into Adenocarcinoma (ADC), Squamous Cell Carcinoma (SCC), Small Cell Lung Cancer (SCLC). Dynamic Contrast-Enhanced MRI (DCE-MRI) assessed Ktrans, Kep, Ve, Vp in deep (frontal/parietal/temporal/occipital lobes) and periventricular (anterior/posterior horns) white matter. Non-parametric tests were used (p<0.05 significant).

LC group had Ktrans comparable to LCBM but higher than HC (p<0.05), mainly in deep white matter and posterior periventricular regions (anterior periventricular: p>0.05). ADC showed higher Ktrans, Kep, Vp than SCC (all p<0.001) and SCLC (Ktrans/Kep p<0.001; Vp p=0.71); Ve was lower than SCLC (p=0.003) but higher than SCC (p=0.001). SCLC had higher Ve than SCC (p<0.0001), with higher Ktrans/Vp than SCC (p<0.01). Vp correlated positively with Ktrans in ADC/SCC (r=0.433/0.359, p<0.001), not in SCLC.

LC impairs BBB integrity via paraneoplastic effects, with subtype heterogeneity: ADC (high perfusion/leakage) involves global white matter; SCLC (prominent interstitial disruption) affects mainly deep regions. Findings aid LC brain metastasis risk stratification and neuroprotective strategies.