Correlation of gut dysbiosis biomarkers and peripheral thyroid hormones conversion in patients with (pts) advanced lung cancer.

Abstract

e20517 Background: Changes in gut microbiota may affect benefit from immunotherapy (IO). Gut dysbiosis can be identified by a fecal metagenomic signature (TOPOSCORE SIG1+ vs SIG2+), and/or by low levels of sMAdCAM-1. Recent studies showed that peripheral thyroid hormones conversion (fT3/fT4 ratio) has a strong prognostic role in various cancers, with low fT3/fT4 ratio predicting worse outcomes. Correlation between gut dysbiosis and metabolic stress, such as altered fT3/fT4 conversion, has not been investigated yet. Methods: A total of 77 lung cancer pts treated at Gustave Roussy Cancer Center with IO-based treatment with available measurement of baseline fT3/fT4 ratio, metagenomic data defined by TOPOSCORE category SIG1+ vs SIG2+, and/or level of sMAdCAM1 (low vs high according to the median) from the ongoing ONCOBIOTICS multicentric prospective study (NCT04567446) were selected. fT3/fT4 low vs high groups were defined adopting the median value as cut-off. Correlation between the fT3/fT4 ratio categories with TOPOSCORE and sMAdCAM1 were tested by means of a 2-sided chi-square test. Results: Baseline fT3/fT4 ratio and TOPOSCORE and/or sMAdCAM-1 data were available for 62 and 57 patients, respectively. A significant correlation was observed between fT3/fT4 ratio and TOPOSCORE category, with a higher proportion of SIG1+ pts (64.5%) vs SIG2+ (35.5%) in fT3/fT4 low group, and higher rate of SIG2+ (61.3%) vs SIG1+ (38.7%) pts in fT3/fT4 high group (p = .042). Similarly, a significant association was observed between low levels of sMAdCAM-1 and the fT3/fT4 low group (p = .047). In a independent dataset of 42 NSCLC treated with 2nd line IO, pts with low fT3/fT4 ratio had a mPFS of 1.7 mos and a mOS of 2.4 mos compared to 6.8 and 18.7 mos respectively for fT3/fT4 high pts (PFS HR = 0.56, 95%CI 0.30-1.05, p = .040; OS HR = 0.50, 95%CI 0.26-0.99, p = .030). Conclusions: Our data confirm the prognostic value of fT3/fT4 in progressing metastatic NSCLC and its correlation with gut dysbiosis markers. These findings open the way to further research for exploring specific therapeutic applications, such as tailored nutritional support and microbiota-driven interventions. Clinical trial information: NCT04567446 .