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Does Molecular Genotype Provide Useful Information in the Management of Radioiodine Refractory Thyroid Cancers? Results of a Retrospective Study

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Abstract

Introduction

Whether mutation status should be used to guide therapy is an important issue in many cancers. We correlated mutation profile in radioiodine-refractory (RAIR) metastatic thyroid cancers (TCs) with patient outcome and response to tyrosine kinase inhibitors (TKIs), and discussed the results with other published data.

Materials and Methods

Outcome in 82 consecutive patients with metastatic RAIR thyroid carcinoma prospectively tested for BRAF, RAS and PI3KCA mutations was retrospectively analyzed, including 55 patients treated with multikinase inhibitors.

Results

Papillary thyroid carcinomas (PTCs) were the most frequent histological subtype (54.9 %), followed by poorly differentiated thyroid carcinoma [PDTC] (30.5 %) and follicular thyroid carcinoma [FTC] (14.6 %). A genetic mutation was identified in 23 patients (28 %) and BRAF was the most frequently mutated gene (23 %). Median progression-free survival (PFS) on first-line TKI treatment was 14.6 months (95% CI 9.9–18.4). BRAF mutation positively influenced median PFS, both in the entire TKI-treated cohort (median PFS 34.7 months versus 11.6 months; hazard ratio [HR] 0.29; 95% CI 0.09–0.98; p = 0.03) and in the TKI-treated PTC cohort (n = 22) [log-rank p = 0.086; HR 2.95; 95 % CI 0.81–10.70). However, in TKI-treated patients, PDTC histologic subtype was the only independent prognostic factor for PFS identified in the multivariate analysis (HR 2.36; 95% CI 1.01–5.54; p = 0.048).

Conclusion

Patients with BRAF-mutant PTC had a significantly longer PFS than BRAF wild-type when treated with TKIs. However, due to the small number of BRAF-mutant patients, further investigations are required, especially to understand the potential positive effect of BRAF mutations in RAIR TC patients while having a negative prognostic impact in RAI-sensitive PTC patients.

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Acknowledgments

Rob Stepney (Medical Writer, Charlbury, UK) contributed to the editing of this paper.

Compliance with Ethical Standards

ᅟ

Conflicts of Interest

Grants, fees and honoraria: Christelle de la Fouchardiere (Roche, Bayer); Anne-Laure Giraudet (Genzyme, travel for meetings); Pierre-Paul Bringuier (Roche)

Board membership: Christelle de la Fouchardiere (Bayer, Sobi, Celgene, Astra-Zeneca).

Olfa Derbel, Myriam Decaussin-Petrucci, Marie-Eve Fondrevelle, Qing Wang, Claire Bournaud-Salinas, Jean-Louis Peix, Jean-Christophe Lifante, Jonathan Lopez, Nadia Oussaid, and Françoise Borson-Chazot have no conflicts of interest to declare.

Funding

This research did not receive any specific grants from any funding agency in the public, commercial, or not-for-profit sector.

Author Contributions

Christelle de la Fouchardiere conceived the study, participated in its design and coordination, and helped draft the manuscript. Françoise Borson-Chazot and Christelle de la Fouchardiere participated in the design of the study. Myriam Decaussin-Petrucci and Marie-Eve Fondrevelle were in charge of pathological analysis. Qing Wang and Pierre-Paul Bringuier carried out the molecular genetic studies and drafted the manuscript, and Nadia Oussaid performed the statistical analysis. All authors read and approved the final manuscript.

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Authors and Affiliations

  1. Medical Oncology Department, Centre Leon Berard, University Lyon I, 28 rue Laennec, 69003, Lyon, France

    Christelle de la Fouchardiere & Olfa Derbel

  2. Pathology Department, Hospital Lyon-Sud, University Lyon I, Pierre-Benite, France

    Myriam Decaussin-Petrucci

  3. Pathology Department, Centre Leon Berard, University Lyon I, Lyon, France

    Marie-Eve Fondrevelle

  4. Molecular Biology Platform, Clinical Science Center, Centre Leon Berard, University Lyon I, Lyon, France

    Qing Wang

  5. Department of Pathology, Edouard Herriot Hospital, University Lyon I, Lyon, France

    Pierre-Paul Bringuier

  6. Department of Nuclear Medicine, Hospital Louis Pradel, University Lyon I, Bron, France

    Claire Bournaud-Salinas

  7. Department of General and Endocrine Surgery, Hospital Lyon-Sud, University Lyon I, Lyon, France

    Jean-Louis Peix & Jean-Christophe Lifante

  8. Department of Nuclear Medicine, Centre Leon Berard, University Lyon I, Lyon, France

    Anne-Laure Giraudet

  9. Department of Biostatistics, Centre Leon Berard, University Lyon I, Lyon, France

    Nadia Oussaid

  10. Department of Biochemistry, Hospital Lyon-Sud, University Lyon I, Lyon, Pierre-Bénite, France

    Jonathan Lopez

  11. Inserm UMR-S1052, CNRS UMR5286, Centre Leon Berard, University Lyon I, Lyon, France

    Jonathan Lopez

  12. Endocrinology Department-INSERM, UMR 1052, Hospital Louis Pradel, University Lyon I, Lyon, France

    Françoise Borson-Chazot

Authors
  1. Christelle de la Fouchardiere
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  8. Claire Bournaud-Salinas
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  12. Jonathan Lopez
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  13. Françoise Borson-Chazot
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Corresponding author

Correspondence to Christelle de la Fouchardiere.

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de la Fouchardiere, C., Oussaid, N., Derbel, O. et al. Does Molecular Genotype Provide Useful Information in the Management of Radioiodine Refractory Thyroid Cancers? Results of a Retrospective Study. Targ Oncol 11, 71–82 (2016). https://doi.org/10.1007/s11523-015-0380-y

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  • DOI: https://doi.org/10.1007/s11523-015-0380-y

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