Spread Through Air Spaces is Significantly Associated With Brain Metastases in Less Than 2 cm Lung Adenocarcinomas

This study analysed the correlation between spread through air spaces (STAS) and brain metastasis, as a distant recurrence site in patients with early-stage (less than 2 cm tumour size) lung adenocarcinomas.

Data of 207 patients with ≤2 cm adenocarcinomas were retrospectively analysed. Fifty-two patients (25.1%) had STAS (STAS-P group) and 155 patients (74.9%) had no STAS (STAS-N group). Study period was from January 1, 2010 till December 31, 2021. The end of follow-up was December 31, 2024. The incidence of the brain metastasis was collected from the national health system database.

The mean age of the 2 groups was 69 years in the STAS-P and 65.9 years in the STAS-N group. Brain metastasis occurred in 19.2% (10/52) and 7.7% (12/155) (P = .019) in the STAS-P and STAS-N groups, respectively. The disease-free interval till brain metastases was 24 (10-77) and 26 (6-71) months (P = .832) in the STAS-P and STAS-N groups, respectively. In brain metastasis cases, the most frequent adenocarcinoma subtype was acinar (36.3%) and solid (27.3%). In a subgroup analysis of 117 patients, operated between 2015 and 2021, the median progression-free survival (PFS) was 59 (0-113) months in the STAS-P and 71 (1-119) months in the STAS-N group (P = .046).

The presence of STAS in ≤2 cm adenocarcinomas is significantly associated with brain metastasis. In case of STAS, brain metastasis developed earlier, and PFS was significantly shorter. Brain metastases developed most typically after solid and acinar adenocarcinomas.