Case Report: A Squamous Cell Lung Carcinoma Patient Who Responded to Neoadjuvant Immunochemotherapy but Died From Anastomosis Leakage or/and irAEs: Immune Microenvironment and Genomic Features Changes

Clinical trials indicated that PD-1/PD-L1 inhibitors significantly improve the survival rate of patients with advanced non-small cell lung cancer (NSCLC) and induce immune-related adverse events (irAEs). Thus, the molecular and immune characteristics during PD-1/PD-L1 inhibitor therapy are worth investigating further. We report the case of a 62-year-old male patient diagnosed with stage IIIA squamous cell lung carcinoma (SQCC) who responded to neoadjuvant and adjuvant nivolumab combined chemotherapy but died from anastomosis leakage or/and irAEs. In the pretreatment tumor biopsy, PD-L1 expression was negative and a few T cells, NK cells, and macrophages had infiltrated the tumor. Wild-type EGFR/STK11, mutant TP53, microsatellite stability, and low tumor mutational burden were also found at baseline. After neoadjuvant immunochemotherapy, the tumor was significantly reduced, PD-L1 expression levels were increased by 50%, and more CD8+ and CD8+ PD-1+ T cells had infiltrated the resected tumor tissue. Immune-related lung injury occurred during adjuvant immunochemotherapy, and serum levels of C-reactive protein, IL-13, IL-4, eotaxin, VEGF-A, IL-8, and IFN-gamma were increased. This case demonstrates a squamous cell lung carcinoma patient who responded to neoadjuvant immunochemotherapy that reshaped the tumor immune environment from “cold” to “hot.” Unfortunately, the patient eventually died from anastomosis leakage or/and irAEs during adjuvant immunochemotherapy.

Efficacy of adjuvant immunochemotherapy with polysaccharide k (PSK) for patients with curatively resected gastric cancer

14038 Background: An anti-tumor effect of non-specific immunomodulators, mainly PSK and OK-432, via an immunological response has been reported and combination immunochemotherapy has been examined. However, the survival benefit of immunochemotherapy for patients with curatively resected gastric cancer was unclear in the world. We performed a meta-analysis in order to evaluate the survival effect of immunochemotherapy employing a biological response modifier Polysaccharide K (PSK) in Japan. Methods: We reassessed by means of meta-analysis of data with central randomization from 5164 patients enrolled in Japanese eight clinical trials. In all eight trials patients were followed up for at least 5 years after surgery and enrollment of the last patient and outcomes for standard chemotherapy were compared with those for chemotherapy plus PSK. The endpoint was 5-year survival odds ratio. Data were analyzed by using a weighted average of the log odds ratios (using Peto’s method). Results: The 5-year odds ratio for all eligible patients was 0.88 (95% confidence interval: 0.78–0.98; p=0.021). There was a significant heterogeneity between the trials (p=0.016). Conclusions: The results of this meta-analysis suggest that adjuvant immunochemotherapy with PSK can improve survival of patients with curatively resected gastric cancer. No significant financial relationships to disclose.