Modeling therapeutic response to radioiodine in metastatic thyroid cancer: a proof-of-concept study for individualized medicine.

Dominique Barbolosi,David Taïeb,Claire Schvartz,Isabelle Keller,Raphaël Serre,Michel Toubeau,Antony Kelly,Claire Bournaud,Christophe Meille,Ilyssa Summer,Slimane Zerdoud,Marie-Elisabeth Toubert

doi:10.18632/oncotarget.16637

Abstract

PurposeRadioiodine therapy (RAI) has traditionally been used as treatment for metastatic thyroid cancer, based on its ability to concentrate iodine. Propositions to maximize tumor response with minimizing toxicity, must recognize the infinite possibilities of empirical tests. Therefore, an approach of this study was to build a mathematical model describing tumor growth with the kinetics of thyroglobulin (Tg) concentrations over time, following RAI for metastatic thyroid cancer.Experimental DesignData from 50 patients with metastatic papillary thyroid carcinoma treated within eight French institutions, followed over 3 years after initial RAI treatments, were included in the model. A semi-mechanistic mathematical model that describes the tumor growth under RAI treatment was designed.ResultsOur model was able to separate patients who responded to RAI from those who did not, concordant with the physicians' determination of therapeutic response. The estimated tumor doubling-time ( was found to be the most informative parameter for the distinction between responders and non-responders. The model was also able to reclassify particular patients in early treatment stages.ConclusionsThe results of the model present classification criteria that could indicate whether patients will respond or not to RAI treatment, and provide the opportunity to perform personalized management plans.

Highlights

Radioiodine therapy (RAI) has been used in the treatment of metastatic thyroid cancer since the 1940’s [1].This therapeutic radiation is based on the ability of welldifferentiated papillary or follicular thyroid cancer cells to absorb and concentrate iodine
Experimental Design: Data from 50 patients with metastatic papillary thyroid carcinoma treated within eight French institutions, followed over 3 years after initial RAI treatments, were included in the model
The results of the model present classification criteria that could indicate whether patients will respond or not to RAI treatment, and provide the opportunity to perform personalized management plans

Summary

Introduction

Radioiodine therapy (RAI) has been used in the treatment of metastatic thyroid cancer since the 1940’s [1]. This therapeutic radiation is based on the ability of welldifferentiated papillary or follicular thyroid cancer cells to absorb and concentrate iodine. These cells show reduced expression of the sodium/iodide symporter www.impactjournals.com/oncotarget (NIS) and thyroid peroxidase (TPO) compared to thyroid epithelial cells, which may account for the lower values of radioiodine uptake and effective period in thyroid cancer tissue. The use of supra-physiologic thyroid hormone replacement to achieve TSH suppression between therapeutic cycles

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