Lena Cvetkovic1,2, Claudine Régis3,4, Corentin Richard2, Lisa Derosa5, Antoine Leblond3,6, Julie Malo1,2, Meriem Messaoudene1,2, Antoine Desilets1,2, Wiam Belkaid1,2, Arielle Elkrief1,2, Bertrand Routy7,8, Daniel Juneau9,10,11. 1. Department of Hematology and Oncology, Centre hospitalier de l'Université de Montréal (CHUM), Montréal, Québec, Canada. 2. Centre de recherche du Centre hospitalier de l'Université de Montréal (CRCHUM), Université de Montréal, Montréal, Québec, Canada. 3. Department of Radiology and Nuclear Medicine, Centre hospitalier de l'Université de Montréal (CHUM), Montréal, Québec, Canada. 4. Department of Radiology and Nuclear Medicine, Institut de Cardiologie de Montréal, Montréal, Québec, Canada. 5. Department of Tumor Immunology and Immunotherapy INSERM U1015, Gustave Roussy Cancer Center, Villejuif, France. 6. Department of Radiology and Nuclear Medicine, Centre Hospitalier Affilié Universitaire Régional (CHAUR), Trois-Rivières, Québec, Canada. 7. Department of Hematology and Oncology, Centre hospitalier de l'Université de Montréal (CHUM), Montréal, Québec, Canada. bertrand.routy@umontreal.ca. 8. Centre de recherche du Centre hospitalier de l'Université de Montréal (CRCHUM), Université de Montréal, Montréal, Québec, Canada. bertrand.routy@umontreal.ca. 9. Centre de recherche du Centre hospitalier de l'Université de Montréal (CRCHUM), Université de Montréal, Montréal, Québec, Canada. daniel.juneau@umontreal.ca. 10. Department of Radiology and Nuclear Medicine, Centre hospitalier de l'Université de Montréal (CHUM), Montréal, Québec, Canada. daniel.juneau@umontreal.ca. 11. University of Ottawa Heart Institute, Ottawa, Ontario, Canada. daniel.juneau@umontreal.ca.
Abstract
BACKGROUND: Immune checkpoint inhibitors (ICI) represent the backbone treatment for advanced non-small cell lung cancer (NSCLC). Emerging data suggest that increased gut microbiome diversity is associated with favorable response to ICI and that antibiotic-induced dysbiosis is associated with deleterious outcomes. 18F-FDG physiologic colonic uptake on PET/CT increases following treatment with antibiotics (ATB) and could act as a surrogate marker for microbiome composition and predict prognosis. The aim of this study was to determine if 18F-FDG physiologic colonic uptake prior to ICI initiation correlates with gut microbiome profiling and clinical outcomes in patients with advanced NSCLC. METHODS: Seventy-one patients with advanced NSCLC who underwent a PET/CT prior to ICI were identified. Blinded colonic contouring was performed for each colon segment and patients were stratified according to the median of the average colon SUVmax as well as for each segment in low vs. high SUVmax groups. Response rate, progression-free survival (PFS), and overall survival (OS) were compared in the low vs. high SUVmax groups. Gut microbiome composition was analyzed for 23 patients using metagenomics sequencing. RESULTS: The high colon SUVmax group had a higher proportion of non-responders (p = 0.033) and significantly shorter PFS (4.1 vs. 11.3 months, HR 1.94, 95% CI 1.11-3.41, p = 0.005). High caecum SUVmax correlated with numerically shorter OS (10.8 vs. 27.6 months, HR 1.85, 95% CI 0.97-3.53, p = 0.058). Metagenomics sequencing revealed distinctive microbiome populations in each group. Patients with low caecum SUVmax had higher microbiome diversity (p = 0.046) and were enriched with Bifidobacteriaceae, Lachnospiraceae, and Bacteroidaceae. CONCLUSIONS: Lower colon physiologic 18F-FDG uptake on PET/CT prior to ICI initiation was associated with better clinical outcomes and higher gut microbiome diversity in patients with advanced NSCLC. Here, we propose that 18F-FDG physiologic colonic uptake on PET/CT could serve as a potential novel marker of gut microbiome composition and may predict clinical outcomes in this population.
BACKGROUND: Immune checkpoint inhibitors (ICI) represent the backbone treatment for advanced non-small cell lung cancer (NSCLC). Emerging data suggest that increased gut microbiome diversity is associated with favorable response to ICI and that antibiotic-induced dysbiosis is associated with deleterious outcomes. 18F-FDG physiologic colonic uptake on PET/CT increases following treatment with antibiotics (ATB) and could act as a surrogate marker for microbiome composition and predict prognosis. The aim of this study was to determine if 18F-FDG physiologic colonic uptake prior to ICI initiation correlates with gut microbiome profiling and clinical outcomes in patients with advanced NSCLC. METHODS: Seventy-one patients with advanced NSCLC who underwent a PET/CT prior to ICI were identified. Blinded colonic contouring was performed for each colon segment and patients were stratified according to the median of the average colon SUVmax as well as for each segment in low vs. high SUVmax groups. Response rate, progression-free survival (PFS), and overall survival (OS) were compared in the low vs. high SUVmax groups. Gut microbiome composition was analyzed for 23 patients using metagenomics sequencing. RESULTS: The high colon SUVmax group had a higher proportion of non-responders (p = 0.033) and significantly shorter PFS (4.1 vs. 11.3 months, HR 1.94, 95% CI 1.11-3.41, p = 0.005). High caecum SUVmax correlated with numerically shorter OS (10.8 vs. 27.6 months, HR 1.85, 95% CI 0.97-3.53, p = 0.058). Metagenomics sequencing revealed distinctive microbiome populations in each group. Patients with low caecum SUVmax had higher microbiome diversity (p = 0.046) and were enriched with Bifidobacteriaceae, Lachnospiraceae, and Bacteroidaceae. CONCLUSIONS: Lower colon physiologic 18F-FDG uptake on PET/CT prior to ICI initiation was associated with better clinical outcomes and higher gut microbiome diversity in patients with advanced NSCLC. Here, we propose that 18F-FDG physiologic colonic uptake on PET/CT could serve as a potential novel marker of gut microbiome composition and may predict clinical outcomes in this population.
Entities:
Keywords:
18F-FDG colonic uptake; Gut microbiome; Immunotherapy; Metagenomics; Non-small cell lung cancer
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