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Anaplastic Lymphoma Kinase Rearrangement and Tumor Spread Through Air Spaces Is Associated with Worse Clinical
Jinghan Shi1, Kuan Xu1, Xufeng Liu2
1Department of Thoracic Surgery, Shanghai Chest Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China.
Purpose:
Lung adenocarcinoma (LUAD) with anaplastic lymphoma kinase (ALK) rearrangements could be targeted with tyrosine kinase inhibitors (TKIs) to improve patient survival. However, the prognostic impacts of ALK rearrangements in resected early-stage LUAD still require clarification. This study evaluated potential clinical characteristics for ALK positivity in stage IA LUAD and identified post-resection prognostic implications.
Methods:
A total of 1212 non-mucinous stage IA LUAD patients who underwent curative resection were included in this retrospective analysis, and divided, based on the Ventana assay, into ALK-positive and negative groups. Uni- and multivariate logistic regression analyses investigated relationships between ALK rearrangements and clinical characteristics, while log-rank tests, Kaplan-Meier curves, and multivariate Cox regression analysis identified recurrence-free (RFS) and overall (OS) survival differences between different groups. Cumulative incidence of recurrence curves for different post-surgical groups was also calculated, and Gray's test assessed their differences. Potential confounder impacts were minimized by 1:2 greedy propensity score matching.
Results:
Out of 1212 cases of stage IA LUAD, 82 (6.8%) were ALK-positive. ALK-positivity was most strongly associated with tumor spread through air spaces (STAS) and International Association for the Study of Lung Cancer grade 3. STAS-positivity was also associated with worse RFS and OS. ALK- and STAS-positive patients, compared to ALK-negative, had significantly worse RFS and higher likelihood for distant metastases.
Conclusions:
ALK rearrangement-positivity in resected stage IA LUAD correlated with more aggressive histological features. STAS- and ALK-positive patients had worse survival and higher metastatic likelihood, compared to ALK-negative. Therefore, targeting STAS- and ALK-positive LUAD with TKIs may improve post-treatment survival rates and reduce metastatic spread.
Insights
Anaplastic lymphoma kinase (ALK) rearrangements in early-stage lung adenocarcinoma (LUAD) correlate with aggressive features and poorer survival. Targeting ALK and tumor spread through air spaces (STAS) may improve outcomes for these patients.
Area of Science:
- Oncology
- Thoracic Surgery
- Molecular Pathology
Background:
- Anaplastic lymphoma kinase (ALK) rearrangements are key targets in lung adenocarcinoma (LUAD) treatment with tyrosine kinase inhibitors (TKIs).
- Prognostic significance of ALK rearrangements in early-stage resected LUAD remains unclear.
- Understanding ALK positivity's clinical characteristics and survival impact is crucial for treatment stratification.
Purpose of the Study:
- Evaluate clinical characteristics associated with ALK positivity in stage IA LUAD.
- Determine the prognostic implications of ALK rearrangements in early-stage LUAD post-resection.
- Assess the impact of ALK status on recurrence-free survival (RFS) and overall survival (OS).
Main Methods:
- Retrospective analysis of 1212 non-mucinous stage IA LUAD patients undergoing curative resection.
- ALK status determined by Ventana assay; patients grouped into ALK-positive and ALK-negative.
- Logistic regression for clinical characteristics, Kaplan-Meier curves and Cox regression for survival analysis, propensity score matching for confounder control.
Main Results:
- 82 (6.8%) of 1212 stage IA LUAD cases were ALK-positive.
- ALK positivity strongly associated with tumor spread through air spaces (STAS) and high tumor grade.
- ALK-positive and STAS-positive patients showed significantly worse RFS, OS, and higher risk of distant metastases.
Conclusions:
- ALK rearrangement positivity in resected stage IA LUAD indicates more aggressive disease.
- Combined ALK and STAS positivity portends worse survival and increased metastatic potential.
- Targeting ALK and STAS in LUAD may enhance survival and reduce metastasis, warranting TKI consideration.
