ABSTRACT
BACKGROUND: Cancer immunotherapy is under development as a promising alternative strategy for treating advanced non-small cell lung cancer (NSCLC). However, the development of novel biomarkers to optimize the use of immune checkpoint inhibitors (ICIs) is still ongoing. Gut microbiota are known to regulate a host's immunity and are associated with the response to ICIs in melanoma. Therefore, we analyzed the association between ICI treatment efficacy and bowel movement condition in patients with NSCLC. METHODS: This retrospective study analyzed patients with advanced NSCLC who were treated with ICIs between December 2015 and March 2018 at University Hospital Kyoto Prefectural University of Medicine in Kyoto, Japan. The association between stool abnormalities and ICI efficacy was investigated. We defined patients with constipation or those who used a laxative as the stool abnormality group. RESULTS: We retrospectively enrolled 40 patients with advanced NSCLC who were treated with ICIs. The median age was 69.5 years; 20 patients had a stool abnormality and 20 patients did not. The disease control rates were lower in NSCLC patients with stool abnormalities than in those without stool abnormalities (20% vs. 77.8%, respectively; P = 0.0016). The time to treatment failure with ICI treatment was shorter in NSCLC patients with stool abnormalities compared with those without stool abnormalities (P = 0.003; odds ratio, 3.09; 95% confidence interval 1.41-6.78). CONCLUSION: Stool abnormality might be a predictive biomarker for the clinical benefit of ICI treatment in patients with NSCLC. Further investigations are warranted to validate our findings.
Subject(s)
Carcinoma, Non-Small-Cell Lung/drug therapy , Constipation/epidemiology , Genes, cdc/drug effects , Immunotherapy/adverse effects , Aged , Aged, 80 and over , B7-H1 Antigen/antagonists & inhibitors , B7-H1 Antigen/genetics , C-Reactive Protein/genetics , Carcinoma, Non-Small-Cell Lung/epidemiology , Carcinoma, Non-Small-Cell Lung/microbiology , Carcinoma, Non-Small-Cell Lung/pathology , Constipation/chemically induced , Constipation/microbiology , Constipation/pathology , Fecal Incontinence/chemically induced , Fecal Incontinence/microbiology , Fecal Incontinence/pathology , Female , Gastrointestinal Microbiome/drug effects , Gastrointestinal Microbiome/immunology , Humans , Immunity/drug effects , Immunity/immunology , Kaplan-Meier Estimate , Male , Middle Aged , Programmed Cell Death 1 Receptor/antagonists & inhibitors , Programmed Cell Death 1 Receptor/genetics , Retrospective StudiesABSTRACT
AIMS: This paper aims to report the rationale, design, and the specific methodology of an ongoing nested observational study that will determine the association of the metabolite and microbial composition of stool with fecal incontinence (FI). METHODS: Eligible cases are participants with FI enrolled in the Controlling Anal Incontinence in women by Performing Anal Exercises with Biofeedback or Loperamide (CAPABLe) trial, a Pelvic Floor Disorders Network trial across eight clinical centers in the United States. Women of similar age without FI in the last year served as controls. All subject collected stool samples at the baseline and 24-week visit at home using a standardized collection method. Samples were shipped to and stored at centralized laboratories. RESULTS: Specimen collection commenced December 2014 and was completed in May 2016. Fecal water and DNA has been extracted and is currently being analyzed by targeted metabolic profiling for stool metabolites and 16S rRNA gene sequencing for stool microbiota. CONCLUSIONS: This article describes the rationale and design of a study that could provide a paradigm shift for the treatment of FI in women.
Subject(s)
Fecal Incontinence/metabolism , Fecal Incontinence/microbiology , Adult , Female , Humans , Microbiota , Middle Aged , RNA, Ribosomal, 16S , Research DesignABSTRACT
AIM: An increase in intestinal gas production due to small intestinal bowel overgrowth (SIBO) is a contributing factor for flatus incontinence. The aims of our study were to assess the efficacy of metronidazole in a select population of patients with flatus incontinence associated with SIBO and to compare its efficacy with that of a combination of simethicone and activated charcoal (SC; Carbosylane) in randomized experimental arms. METHODS: Adult patients suffering from flatus incontinence associated with SIBO diagnosed by a glucose breath test were enrolled in the study. They were given metronidazole or Carbosylane (SC) for 10 days. The reduction in the mean daily number of gas leakages reported in a 3-day diary before and at the end of the treatment was used as the primary endpoint. RESULTS: Of 52 consecutive subjects with flatus incontinence, 23 (44%) had SIBO, 16 (33%) of whom were included in and completed the study. The relative reduction in flatus incontinence episodes was significantly higher in the metronidazole than in the SC group (66.8±34.8% vs. 25±50%, P = 0.03), decreasing by more than 50% in 7 (87.5%) of the subjects in the metronidazole group compared with only 1 (12.5%) in the SC group (odds ratio 1.9, 95% confidence interval 0.9-56.9, P = 0.06). CONCLUSION: Our results show a promising trend indicating that metronidazole might significantly improve flatus incontinence associated with SIBO and might be more successful in treating flatus incontinence than gas absorbents.
