We report a novel intergenic anaplastic lymphoma kinase (ALK) fusion identified in a patient with resected stage IIIA lung adenocarcinoma. A 75-year-old woman underwent lobectomy for a left lower lobe tumor, with final pathology revealing pT3N2aM0 disease with high-risk features (pleural invasion, vascular tumor thrombus, and spread through air spaces). Comprehensive next-generation sequencing (NGS) of the surgical specimen identified a previously unreported in-frame fusion between an intergenic region of chromosome 6 (between STPLC1P2 and LOC100128365) and exon 20 of ALK on chromosome 2, retaining the entire kinase domain. Immunohistochemistry confirmed strong ALK protein expression (D5F3, Ventana). Based on the high-risk pathological stage and the presence of a targetable ALK driver, adjuvant therapy with the ALK tyrosine kinase inhibitor ensartinib was initiated instead of conventional chemotherapy. The patient tolerated treatment well, and a follow-up chest CT at approximately 6 months showed no evidence of local recurrence or distant metastasis. Long-term outcomes remain to be determined. This case expands the spectrum of ALK rearrangements and highlights the critical role of molecular profiling in guiding adjuvant treatment decisions for early-stage, high-risk non-small cell lung cancer (NSCLC).
Li et al. (2026) studied this question.