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Increased thyroid uptake on 18F-FDG PET/CT is associated with the development of permanent hypothyroidism in stage IV melanoma patients treated with anti-PD-1 antibodies

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Abstract

Purpose

To determine performances of 2-deoxy-2-(18F)fluoro-d-glucose (18F-FDG) positron emission tomography (PET) to detect the development of permanent thyroid dysfunction (PTD), and to evaluate the prognostic value of early increased thyroid uptake in stage IV melanoma patients treated with anti-programmed death 1 (anti-PD-1) antibodies.

Methods

Twenty-nine patients were retrospectively enrolled. PTD was defined as symptomatic thyroid disorder requiring long-term specific treatment. On the first PET performed during follow-up, maximal standardized uptake value of the thyroid (SUVmax-Th) and SUVmax-Th/SUVmax-blood-pool ratio (Th/B) were measured. Areas under ROC curves (AUC) of these parameters for the diagnostic of PTD were compared. Cutoff values were defined to maximize the Youden’s index. Survival analyses were performed according to the Kaplan–Meier method and compared using the log-rank method between patients with and without enhanced thyroid uptake according to cutoff values defined with the Hothorn and Lausen method.

Results

Four patients presented PTD. Median SUVmax-Th and Th/B were, respectively, 2.11 and 1.00. The median follow-up period was 21.7 months. AUC were 1.0 (CI95% 0.88–1.0) for both parameters. Optimal cutoff values were, respectively, SUVmax-Th > 4.1 and Th/B > 2.0, both conferring sensitivities of 100% (CI95% 40–100%) and specificities of 100% (CI95% 86–100%). The median progression-free survival and overall survival were 11.3 months and 33.5 months, respectively. Using optimized cutoffs, there was no statistically significant difference of survival.

Conclusion

SUVmax-Th > 4.1 and Th/B > 2.0 provided perfect diagnostic performances to detect patients that developed PTD. No significant survival difference was found between patients with and without increased thyroid uptake.

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Abbreviations

18F-FDG:

2-Deoxy-2-(18F)fluoro-d-glucose

AJCC:

American joint committee of cancer

Anti-PD-1:

Anti-programmed death 1 antibodies

AUC:

Areas under ROC curves

CT:

Computed tomography

irAEs:

Immune-related adverse events

NA:

Not available

OS:

Overall survival

PET:

Positron emission tomography

PFS:

Progression-free survival

PTD:

Permanent thyroid dysfunction

ROC:

Receiver operating characteristics

SUVmax:

Maximal standardized uptake value

SUVmax-Th:

Maximal standardized uptake value of the thyroid

Th/B:

Ratio SUVmax-Th/SUVmax-blood-pool

TSH:

Thyroid stimulating hormone

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Authors and Affiliations

  1. Department of Oncology, Eugène Marquis Center, Rennes, France

    Alexandra Frelau, Julien Edeline & Thierry Lesimple

  2. Department of Nuclear Medicine, Eugène Marquis Center, Avenue de La Bataille Flandres-Dunkerque, 35000, Rennes, France

    Xavier Palard-Novello, Anne Devillers, Florence Le Jeune & Antoine Girard

  3. Department of Endocrinology, University Hospital, Brest, France

    Eva Jali

  4. Department of Dermatology, University Hospital, Rennes, France

    Lise Boussemart & Alain Dupuy

  5. Department of Gynecology, University Hospital, Brest, France

    Pandora James

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  1. Alexandra Frelau
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Contributions

AF, AG and TLS designed the study. AF, AG, EJ and LB participated in the collection of data. AG performed the statistical analysis. AF and AG drafted the manuscript. XPN, LB, AD, AD, FL, JE and PJ provided their critical revision of the manuscript. All authors read and approved the final manuscript.

Corresponding author

Correspondence to Antoine Girard.

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The authors have no potential conflicts of interest to disclose.

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This research study was conducted retrospectively from data obtained for clinical purposes.

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Because of the retrospective nature of this study, consent was not obtained. A simplified declaration to the French data protection authority (CNIL) under the number 208821 was performed for this study.

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262_2020_2712_MOESM1_ESM.tiff

Supplementary material. Histogram of maximum standardized uptake value in the thyroid (SUVmax-Th) and SUVmax-thyroid/SUVmax-blood-pool ratio (Th/B) in patients who developed permanent thyroid dysfunction (PTD) or not. file1 (TIFF 13125 kb)

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Frelau, A., Palard-Novello, X., Jali, E. et al. Increased thyroid uptake on 18F-FDG PET/CT is associated with the development of permanent hypothyroidism in stage IV melanoma patients treated with anti-PD-1 antibodies. Cancer Immunol Immunother 70, 679–687 (2021). https://doi.org/10.1007/s00262-020-02712-7

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