2026-10-14T05:35:11Z https://api.figshare.com/v2/oai

oai:figshare.com:article/33942193 2026-09-19T11:02:56Z category_7 portal_147 item_type_3 month_year_09_2026

Supplemental Material for: Late Emergence of Small Cell Lung Cancer during Long-Term ALK Inhibitor Therapy in ALK-Rearranged NSCLC: A Case Report figshare admin karger (2628495) Tatsuo Kimura (2049088) Toshiyuki Nakai (25075795) Kazuhiro Yamada (209691) Yoshiya Matsumoto (13109887) Koichi Ogawa (138394) Hiroaki Nagamine (18231479) Kaho Hirai (25075801) Shigeki Kakuno (25075803) Kohei Niina (25075809) Koji Enomoto (25075810) Yuji Nadatani (482324) Yoko Tani (18207814) Takako Oka (25075816) Hiroyasu Kaneda (335979) Masanori Shiohara (14137824) Kenichi Kohashi (3501809) Tomoya Kawaguchi (1809079) Medicine Medicine <p dir="ltr">Introduction: Rearrangements of the anaplastic lymphoma kinase (ALK) gene, predominantly involving the echinoderm microtubule-associated protein-like 4 (EML4) -ALK fusion, occur in approximately 3-7% of non-small cell lung cancers (NSCLC) and are enriched in young, never-smoking patients with lung adenocarcinoma. Among patients who relapse after ALK tyrosine kinase inhibitor (TKI) therapy, transformation to small cell lung cancer (SCLC) is estimated to occur in under 5% of cases, with a median time to transformation of 20.5 months. In the recently reported 7-year update of the phase III CROWN study, the median progression-free survival with first-line lorlatinib had not been reached after a median follow-up of 83 months, leading to the view that ALK-rearranged lung cancer may now be regarded as a chronic disease. However, the patterns of recurrence following long-term treatment remain poorly understood.</p><p dir="ltr">Case Presentation: A 58-year-old man with stage IV ALK-rearranged lung adenocarcinoma was diagnosed with SCLC after more than 10 years of cumulative ALK-TKI therapy, comprising 7 years and 3 months of alectinib, 3 years of brigatinib, and 4 months of lorlatinib. SCLC histology was confirmed by re-biopsy on the basis of morphology and neuroendocrine marker expression. No ALK fusion was detected in the re-biopsy specimen on a targeted panel assay; however, clonal continuity with the original ALK-rearranged adenocarcinoma could not be definitively established, as orthogonal testing including ALK immunohistochemistry and FISH was not performed on the transformed tissue. The patient achieved a partial response to carboplatin plus etoposide after two cycles.</p><p dir="ltr">Conclusion: This case adds to the limited but growing body of evidence suggesting that SCLC may emerge as a mechanism of resistance across all generations of ALK-TKIs, and demonstrates that such histologic change can occur even after more than 10 years of cumulative ALK inhibitor exposure. </p> 2026-09-19T11:02:56Z Dataset Dataset 10.6084/m9.figshare.33942193.v1 https://figshare.com/articles/dataset/Supplemental_Material_for_Late_Emergence_of_Small_Cell_Lung_Cancer_during_Long-Term_ALK_Inhibitor_Therapy_in_ALK-Rearranged_NSCLC_A_Case_Report/33942193 CC BY 4.0