Endocrine Abstracts

Background: Despite the use of aggressive, multimodal therapy (surgery + radiation therapy + systemic therapy), management of advanced thyroid cancers such as anaplastic thyroid cancer (ATC) remains a major challenge. Identifying predictive biomarkers of treatment response are primordial to improving overall survival for patients with ATC. Gut microbiota have been linked to both treatment response and levels of adverse effects to treatment in cancers such as melanoma or colorectal cancer, but there is yet to be an evaluation of the gut microbiome and its relation to thyroid cancer. Our goal is to interrogate the gut microbiome of patients diagnosed with ATC and evaluate potential predictive markers for treatment outcomes.

Methods: Between April 2019 and October 2023 and following informed written consent, stool samples were collected using a cold-chain temperature controlled at-home collection kit from patients diagnosed with histopathologically proven ATC. Patient demographic characteristics, molecular testing data, and treatment modalities were collected. Overall survival (OS) was measured from date of pathologic confirmation of disease to date of death, with patients censored at date of last follow-up. For the microbiome analyses,16Sv4 rRNA gene sequencing data was generated and processed with DADA2 and the SILVA database. Microbiome diversity and taxonomic analysis were carried out in R using the phyloseq, vegan, ape, and ancombc packages. The Kaplan-Meier method was used to estimate OS, while the log-rank test was used to assess between-group differences and the Cox proportional hazard was used to assess relative risk ratios.

Results: A total of 21 patients with ATC were included in this study (13 females and 8 males). Targeted therapy (71%), immunotherapy (IO) (86%), and external beam radiation therapy (62%) were the most frequent treatment modalities. Microbial alpha and beta-diversity indices were not associated with OS. However, the abundance of Turicibacter spp . was associated with increased OS in patients receiving different types of therapy including IO. In patients receiving IO, the presence of Proteobacteria was associated with poor OS.

Conclusions: To our knowledge, this is one of the first studies to evaluate the gut microbiome in a large cohort of anaplastic thyroid cancer patients. There was no association between alpha and beta-diversity and survival. The presence of Proteobacteria was associated with a poorer prognosis, while a higher abundance of Turicibacter spp. was associated with increased survival. These early signals warrant for further work in this field in an effort to improve patient outcomes with this deadly disease.