ArticleJournal of translational medicine2025
Clinicopathologic features and therapeutic outcomes in EGFR/ALK-aberrations NSCLC with histologic transformation.
Article in Journal of translational medicine, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 2 papers.
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Who cites it
2 citing papers in PubMed.
- Squamous transformation of EGFR-mutant lung adenocarcinoma after EGFR-TKI therapy: clonal continuity, tissue-based diagnosis, and therapeutic evidence gaps.Frontiers in oncology · 2026Review
- Advanced and underlying therapeutic strategies in transformed small cell lung cancer.Frontiers in medicine · 2026Review
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6 authors.
Funding
Abstract
backgroundThe aim of this study is to delineate clinicopathologic features, therapeutic outcomes, and tumor microenvironment (TME) remodeling in non-small cell lung cancer (NSCLC) patients with epidermal growth factor receptor/anaplastic lymphoma kinase (EGFR/ALK) aberrations who experience histologic transformation (HT), with emphasis on post-transformation treatment efficacy.
methodsThis single-center retrospective cohort study included 6,230 patients with advanced NSCLC treated between December 2017 and January 2024. Patients who experienced histologic transformation after progression were identified through high-quality tumor biopsies or cytological samples. Treatment regimens for post-HT, including chemotherapy combined with tyrosine kinase inhibitors (CTK), chemotherapy combined with anti-angiogenic/immunotherapy (CAI), and palliative care (PC), were analyzed. Multiplex immunofluorescence was used to profile the tumor microenvironment in a subset of patients.
resultsOf the 6,230 patients, 84 (1.35%) experienced HT, with 73.81% transforming to small cell lung cancer (SCLC). The median time to HT was 22.27 months. Patients receiving CTK exhibited significantly longer median overall survival (OS1) after HT (OS1: 15.40 months) compared to CAI (11.23 months) and PC (4.37 months; P = 0.003). While CTK improved OS1, progression-free survival (PFS1) did not differ significantly across groups. In second-line treatment, incorporating tyrosine kinase inhibitors (TKIs) significantly prolonged PFS2 (PFS2; median: 6.70 months, compared with 2.87 months for regimens not incorporating TKIs; P = 0.016). Uncommon EGFR mutants exhibited paradoxical tumor microenvironment (TME) features, with elevated CD8+ infiltration (128.5 vs. 64.2 cells/mm²; p = 0.028) accompanied by Treg dominance (Foxp3+CD25+/CD8+ ratio: 0.41 vs. 0.19; p = 0.039). Immunotherapy-containing regimens improved PFS1 in uncommon mutants (3.10 vs. 1.83 months; P = 0.007); however, overall survival remained comparable. Conclusions: Histologic transformation poses a significant challenge in advanced NSCLC management. Chemotherapy combined with TKIs appears to offer the best survival benefit for post-HT, while second-line inclusion of TKIs improves PFS. Personalized strategies accounting for histologic subtype, molecular alterations, and immune contexture are essential for optimizing outcomes in this clinically distinct population. Further large-scale studies are warranted to refine therapeutic approaches.
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