Oncotarget

Research Papers:

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

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

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Oncotarget. 2017; 8:39167-39176. https://doi.org/10.18632/oncotarget.16637

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Abstract

Dominique Barbolosi1, Ilyssa Summer1, Christophe Meille1, Raphaël Serre1, Antony Kelly2, Slimane Zerdoud3, Claire Bournaud4, Claire Schvartz5, Michel Toubeau6, Marie-Elisabeth Toubert7, Isabelle Keller8 and David Taïeb9

1SMARTc Pharmacokinetics Unit, Aix-Marseille Université, Inserm S911 CRO2, Marseille, France

2Service de Médecine Nucléaire, Centre Jean Perrin, 63011 Clermont-Ferrand Cedex 01, France

3Oncopole, 31059 Toulouse Cedex 9, France

4Hospices Civils de Lyon, Groupement Hospitalier Est, Service de Médecine Nucléaire, 69 677 Bron Cedex, France

5CLCC Institut Jean Godinot, 51056 REIMS CEDEX, France

6Service de Médecine Nucléaire, Centre Georges François Leclerc, 21079 Dijon Cedex, France

7Service de Médecine Nucléaire, Hôpital Saint-Louis APHP, 75475 Paris Cedex 10, France

8Service de Médecine Nucléaire, Hôpital Saint Antoine, APHP, 75012 Paris, France

9Service de Médecine Nucléaire, CHU La Timone, Aix-Marseille Université, 13385 Marseille 05, France

Correspondence to:

Dominique Barbolosi, email: dominique.barbolosi@univ-amu.fr

Keywords: metastatic thyroid cancer, radioactive iodine therapy, personalized medicine, mathematical model, therapeutic nuclear medicine

Received: December 21, 2016    Accepted: February 18, 2017    Published: March 29, 2017

ABSTRACT

Purpose: Radioiodine 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 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. A semi-mechanistic mathematical model that describes the tumor growth under RAI treatment was designed.

Results: Our 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 (Td 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.

Conclusions: 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.


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