Divergent outcomes of neoadjuvant therapy for locally advanced small-cell lung cancer: two cases report and literature review

This article reports two cases of stage IIIB small cell lung cancer (SCLC) patients who underwent neoadjuvant immunotherapy combined with chemotherapy, resulting in markedly different clinical outcomes, and explores the potential molecular mechanisms behind these differences. Both patients were diagnosed with stage IIIB small cell lung cancer through imageological examination and CT-guided percutaneous lung biopsy. They received three cycles of neoadjuvant treatment with “etoposide + carboplatin + serplulimab” followed by surgical resection of the lesions. Genetic testing for solid tumors was conducted before and after treatment. The results showed that Case 1 exhibited multiple gene mutations, including FBXW7 and KRAS, with a tumor mutational burden (TMB) of 17.65 muts/Mb before treatment. After neoadjuvant therapy, only the PTEN mutation remained, and TMB decreased to 0.00 muts/Mb, with no cancer cells observed in the postoperative pathology, leading to an assessment of pathological complete response (pCR). In contrast, Case 2 showed MET and PTEN mutations and MYC gene amplification both before and after treatment, with TMB increasing from 23.72 muts/Mb to 28.13 muts/Mb, resulting in an assessment of disease progression (PD) post-surgery. This study emphasizes the potential value of neoadjuvant therapy in locally advanced SCLC patients and highlights the importance of genetic testing in predicting treatment responses and guiding personalized treatment strategies. Further research is needed to explore more effective therapeutic strategies to improve the prognosis of SCLC patients.