e21097 Background: Immune checkpoint inhibitors (ICIs) has limited efficacy with unsatisfactory objective response for extensive stage small cell lung cancer (ES-SCLC). In this respective study, efficacy and toxicities of low dose radiotherapy (LDRT) plus ICIs for pretreated failure ES-SCLC has been evaluated, and marvelous objective response has been observed. Methods: From March 2018 to Dec 2019, ten pretreated failure ES-SCLC patients received LDRT (8-20Gy/2-10f, BED10 9.5-24Gy) for lesions located in lung or other sites plus ICIs (Nivolumab, Pembrolizumab, Ipilimumab, Durvalumab, and Sintilimab) were enrolled. Two patients received concurrent chemotherapy of etoposide plus cisplatin or albumin-bound paclitaxel monotherapy. ICIs were given within 7 days after LDRT. Efficacy, toxicities, and lung cancer symptom scale (LCSS) scores were evaluated. Results: Thirteen lesions (ten located in lungs, and the others located in adrenal gland, axillary lymph node, and abdomen) received LDRT. The gross tumor volume and planning target volume were 32.56 cc-430.19cc and 73.74 cc-771.41 cc, respectively. Eleven lesions did not receive radiotherapy. The objective response rate (ORR) of whole patients was 90% (9/10). The ORR and disease control rate (DCR) of radiated lesions were 92.3% (12/13) and 100% (13/13), compared to 9.1% (1/11) and 18.2% (2/11) for no radiated lesions. Volume shrinkage rates (VSRs) of radiated lesions were 35.16% to 95.91% (13.75cc-277.02cc), and 61.5% (8/13) of radiated lesions reduced more than 80%. VSRs for radiated lesions with volume > 100cc were 63.07% to 95.91% (122.38cc-277.02cc). LCSS improved significantly after treatment (465±13.02 vs. 380±17.8, p= 0.0013). Lymphocyte declined initially and then recovered in patients with disease not progressed, on the contrary, it declined continuously in patients with disease progressed. The most popular toxicities were lymphopenia (70%) and anemia (60%). Grade 3-4 toxicities included lymphopenia (40%), thrombocytopenia (20%), anemia (20%), and granulocytopenia (10%). Conclusions: LDRT might enhance the effectiveness of ICIs greatly for tumor lesions, and radiotherapy should be considered to be given initially for ES-SCLC received ICIs treatment.