Specifically, our results suggest that patients with SCLC patients with NOTCH1-ICD–positive ASCL1 and NEUROD1 tumors by IHC may benefit from first-line ICB with chemotherapy, whereas SCLC patients with NOTCH1-ICD–negative ASCL1 and NEUROD1 tumors by IHC may benefit from first-line chemotherapy alone or additional combinatorial strategies. The gene discussed is NEUROD1; the disease is small cell lung carcinoma.