Neuroendocrine features in small cell lung cancer (SCLC) and associations with platinum-sensitivity, metastatic tropism, and overall survival.

e20113 Background: SCLC heterogeneity can be classified into neuroendocrine (NE) subtypes (ASCL1, NeuroD1, POU2F3, YAP1) with plasticity along its NE spectrum. SCLC harbors conventional NE features on immunohistochemistry (IHC) utilized for diagnosis. In the era of chemoimmunotherapy, insight into the role of conventional SCLC NE IHC with proclivity for metastatic site tropism and therapeutic outcomes, including chemotherapy-free interval (CTFI) and overall survival (OS), has not been studied. Methods: We retrospectively reviewed patients with SCLC who received antineoplastic therapy within the Indiana University (IU) Health System Affiliates from January 2018 to January 2024. Data was stored in an institutional review board approved RedCap. Demographics, treatment, metastases, TTF-1 and NE IHC markers, CTFI, and OS were recorded. IHC expression of Chromogranin A, synaptophysin, and INSM-1 were utilized to classify tumors into NE-low (1-3 negative markers), NE-moderate ( < 3 positive markers), and NE-high (3 positive markers). ANOVA, Kruskal-Wallis, Chi-square, Fisher’s Exact, and log-rank tests were applied. Results: One-hundred and fifty-three patients diagnosed with SCLC were included. Forty-six patients with limited-stage (LS-SCLC, 30.1%) and 107 patients with extensive-stage (ES-SCLC, 69.9%) were identified. Classification by conventional NE IHC included NE-low (n = 41), NE-moderate (n = 18), and NE-high (n = 94), with enrichment for the NE-high category ( P = < 0.0001). No differences were observed in age, sex, smoking history, or stage across NE categories. TTF-1 positivity by IHC independently predicted NE-high ( P = 0.04). The presence of metastases did not significantly differ ( P = 0.93), but trends in enrichment of bone ( P = 0.16) and pancreatic ( P = 0.15) metastases were observed in NE-low. No difference in CTFI was identified between NE cohorts ( P = 0.28) . Median 1-year OS across the NE-low, -moderate, and -high categories was 57.2% (95% CI, 40.4-70.8%), 36.1% (13.7-59.4%), and 53.3% (42.2-63.1%), respectively (log-rank, P = 0.09). Conclusions: Conventional NE IHC fails to predict CTFI in the era of chemoimmunotherapy. SCLC significantly enriches for NE-high. TTF-1 can independently predict NE-high SCLC. Trends in metastatic tropism and shorter 1-year OS in NE-moderate SCLC were identified but limited by sample size. Enrollment expansion is ongoing. Exploration into NE subtypes and multi-omics is in process.