Prognostic impact of serum transthyretin in patients with non-small cell lung cancer.

The identification of novel biomarkers is of great importance for improving the outcome of patients with non-small cell lung cancer (NSCLC). Therefore, the aim of the present study was to determine whether the serum transthyretin (TTR) level could be used as a novel prognostic biomarker for patients with NSCLC. Serum TTR levels, and nutritional and inflammatory parameters were examined prior to treatment in 42 patients with NSCLC. Candidates for independent predictors of prognostic factors were subjected to univariate and multivariate analyses using a Cox proportional hazard model. IL-12-productivity, serum retinol binding protein, albumin and transferrin levels, and lymphocyte-to-monocyte ratio were significantly lower in the patients with TTR <22 mg/dl than those in the patients with TTR ≥22 mg/dl. Patients with serum TTR levels of <22 mg/dl exhibited a poorer overall (P=0.008) and recurrence-free survival (P=0.027) when compared with those with serum TTR levels of ≥22 mg/dl. The parameters, ≥T2 and age ≥75 years were independent prognostic factors for overall survival, and TTR <22 mg/dl and ≥T2 were independent prognostic factors for recurrence-free survival. In conclusion, anthropometric measurement of serum TTR, as well as T category, can be useful for predicting the 5-year recurrence-free survival of patients with NSCLC.

VV-ECMO during subsequent segmentectomy after right pneumonectomy.

Several reports have described subsequent pulmonary surgery after pneumonectomy. We herein report the case of an 82-year-old woman with metachronous multiple lung cancer who had undergone surgery for adenocarcinoma of the right upper lobe 17 years earlier. Completion pneumonectomy had been performed for residual lung adenocarcinoma 11 years before the presentation in question. The patient was elderly and had a poor pulmonary function, although her performance status and her cardiac function were good. Therefore, we decided to improve the safety of surgery with venovenous extracorporeal membrane oxygenation (VV-ECMO). Segmentectomy of S6 + S10a was performed under VV-ECMO support. The 30 months after surgery, the patient has had no complications but continues home oxygen therapy. Imaging has shown no evidence of recurrence.

[A Study of Biomarkers in Immuno-Oncology - Correlation between Gut Microbiome Composition and the Effects of Immune Checkpoint Inhibitors].

Currently, anti-PD-1 inhibitors(nivolumab and pembrolizumab)are used for patients with non-small cell lung cancer (NSCLC), although the role of this biomarker is not yet fully characterized. PD-L1 expression in the tumor has been established as a biomarker of the effects of pembrolizumab; however, a number of PD-L1-negative patients have benefited from nivolumab or other immune checkpoint inhibitors, suggesting that there might be additional relevant biomarkers. Notably, tumor mutation burden or tumor infiltrating lymphocytes might be useful biomarkers for these patients; the gut microbiome has received similar attention. It has been reported that mouse models of melanoma with certain types of microbiomes benefit from the use of immune checkpoint inhibitors. Even in human cases, those with certain types of microbiomes tended to benefit from immune checkpoint inhibitor treatment and exhibited elevated CD8-positive T cell counts. Additionally, when combined with antibiotics, the effect of the anti-PD-1 antibody was attenuated; conversely, mice that were treated with certain species of bacteria experienced beneficial outcomes from anti-PD-1 antibody treatment. This suggested that manipulation of the gut microbiome might alter treatment effects. Here, we analyzed the microbiome of 12 patients with advanced or recurrent NSCLC who were treated with anti-PD-1 antibody. There was no major difference between before and after administration in microbiome of each case. Cluster analysis indicated no significant differences in oral microbiomes among the patients before the administration of the anti-PD-1 antibody. Comparative analysis of the patients' gut microbiomes is ongoing. We plan to continue further examination to reveal whether the intestinal environment influences the effectiveness of immune checkpoint inhibitors in NSCLC patients.

Prognostic Impact of Tumor Mutation Burden in Patients With Completely Resected Non-Small Cell Lung Cancer: Brief Report.

INTRODUCTION: Tumor mutation burden (TMB) is thought to be associated with the amount of neoantigen in the tumor and to have an important role in predicting the effect of immune checkpoint inhibitors. However, the relevance of TMB to prognosis is not yet fully understood. In this study, we investigated the clinical significance of TMB in patients with NSCLC and examined the relationship between TMB and prognosis. METHODS: We calculated TMB within individual tumors by whole-exome sequencing analysis using next-generation sequencing. We included that there were 90 patients with NSCLC who underwent surgery in the Hospital of Fukushima Medical University from 2013 to 2016. No patients received chemotherapy or immunotherapy before surgery. We assessed the correlation between TMB and prognosis. RESULTS: TMB greater than 62 was associated with worse overall survival (OS) of patients with NSCLC (hazard ratio [HR] = 6.633, p = 0.0003). Multivariate analysis showed poor prognosis with high TMB (HR = 12.31, p = 0.019). In patients with stage I NSCLC, higher TMB was associated with worse prognosis for both OS (HR = 7.582, p = 0.0018) and disease-free survival (HR = 6.07, p = 0.0072). CONCLUSIONS: High TMB in NSCLC is a poor prognostic factor. If high TMB is a predictor of the efficacy of immune checkpoint inhibitors, postoperative adjuvant therapy with immune checkpoint inhibitors may contribute to improvement of recurrence and OS.