Influence of levothyroxine concomitant treatment on treatment responses and outcomes in patients with metastatic colorectal adenocarcinoma.

Abstract

e15593 Background: Hypothyroidism is the most common thyroid disorder and levothyroxine is the mainstay treatment. Levothyroxine is mainly used to restore the euthyroid clinical and biochemical status in the gland. Recent literature has correlated chronic hormonal treatment with adverse effects on bone and heart function, as well as correlated with an increased risk of tumor onset. Data available in the literature are controversial, therefore the aim of our study was to evaluate the correlation between chronic levothyroxine intake and outcomes and response to first line treatments in patients affected by metastatic colorectal cancer. Methods: We retrospectively collected the data from 139 patients with metastatic colorectal adenocarcinoma, belonging to the Medical Oncology Department of the University Hospital of Cagliari from 2016 to 2019. All patients enrolled in the study had received metastatic first-line treatment with doublet or triplet chemotherapy associated with anti-VEGF or anti-EGR monoclonal antibody. Patients with ECOG PS ≤1 with no more than two relevant comorbidities were included in the study. The primary objective of the study was median overall survival (mOS) and secondary objectives were: median progression free progression (PFS), median overall survival (mOS) differences between RAS wild type and mutant tumour. BRAF mutant tumors were excluded from the evaluation. Results: Median age was 65 years (±10), 51% were male and 49% were female. 63% patients had an ECOG-PS 0, while 37% had an ECOG-PS 1. 67% developed from the left colon; 33% from the right colon and the transverse colon. All patients had synchronous metastases. 18% patients took levothyroxine and 82% patients did not take it. Among the patients receiving levothyroxine therapy, 64% had a RAS wild type and 36% a RAS mutated. Levothyroxine treated patients showed a significantly lower median OS than not treated patients (15 months versus not reached, p = 0,0001). Levothyroxine treated patients also showed a significantly lower median PFS than non treated patients (6 versus 8 months, p = 0,035). Within levothyroxine treated pts, no statistically significant differences were found in mOS and mPFS between RAS wt and RAS mut (mOS 15 versus 14 months, respectively, p = 0.9; mPFS 8 versus 7 months, respectively, p = 0,7). Conclusions: The results show a possible correlation between levothyroxine therapy and outcomes in mCRC. This would deserve further study to understand further biological-molecular aspects, to date partially explained by preclinical studies, in order to clarify some of the possible underlying mechanisms.