Abstract 4659: AI-powered assessment of morphologic likeness to small cell lung cancer (SCLC) predicts progression to SCLC and TKI response in EGFR-mutant NSCLC

作者：Soohyun Hwang, Hyukjung Kim, Yeong Hak Bang, Jun-Gi Jeong, Chang Ho Ahn, Seung‐Eun Lee, Sanghoon Song, Aaron Valero Puche, JaeWoong Shin, Sehhoon Park, Hyun Ae Jung, Jong‐Mu Sun, Yoon‐La Choi, Jin Seok Ahn, Myung-Ju Ahn, Siraj Ali, Chan‐Young Ock, Se‐Hoon Lee · 发表于：Cancer Research · 年份：2025 · DOI：10.1158/1538-7445.am2025-4659 · 研究领域：Radiomics and Machine Learning in Medical Imaging

Abstract Background: A subset of EGFR-mutant non-small cell lung cancers (NSCLC) progresses to small cell lung carcinoma (SCLC) during tyrosine kinase inhibitor (TKI) therapy, particularly in cases with inactivating RB1 mutations. As RB1 mutations are likely foundational events in SCLC transformation, we hypothesize that tumors susceptible to this transformation exhibit morphologic features resembling SCLC even at the time of the initial diagnostic biopsy. Methods: We developed a predictive model for identifying the SCLC phenotype using H&E-stained slides from cases with confirmed SCLC histological diagnosis. Morphological features of individual cells were extracted through a grid-based image retrieval method, enhanced by subcellular compartmental analysis with an emphasis on nuclear and cytoplasmic characteristics. These features were used to quantify the morphological SCLC-likeness for each case. The SCLC-like phenotype was defined as the top 25% of cases exhibiting the highest SCLC-likeness scores. The model was then applied to 106 real-world advanced-stage EGFR-mutant NSCLC cases to validate the extracted features and assess clinical correlations. The primary endpoints were progression-free survival (PFS) after TKI therapy according to SCLC-like phenotype versus others, along with the rate of SCLC transformation. Secondary endpoints were RB1 mutations confirmed by targeted panel sequencing or whole exome sequencing. Results: The SCLC-like phenotype case images correla...