Immune Checkpoint Inhibitor Therapy Achieved Complete Response for Drug-Sensitive EGFR/ALK Mutation-Negative Metastatic Pulmonary Large-Cell Neuroendocrine Carcinoma with High Tumor Mutation Burden: A Case Report.

Large-cell neuroendocrine lung carcinoma (LCNELC) is classified into lung neuroendocrine tumors according to WHO 2015 classification guidelines and represents approximately 3% of all lung cancer. Because of the rarity of LCNELC, there is a lack of prospective studies guiding treatment. Here, we report a case of a patient with pT2aN2M0 stage IIIA LCNELC (drug-sensitive EGFR/ALK mutation-negative, PD-L1-negative but tumor mutation burden (TMB) high), who progressed rapidly after surgery but achieved a complete response to subsequent immune checkpoint inhibitor (ICI) therapy. The concentration of circulating tumor DNA (ctDNA) following the treatment course strongly reflects the response to ICI therapy. This report highlights the efficacy of ICI treatment in metastatic LCNELC patients with a high TMB and suggests that ctDNA analysis in detecting molecular residual disease may facilitate the personalization of ICI therapy.