The utility of quantitative 18F-FDG PET/CT-derived parameters as prognostic factors for predicting overall survival in radioiodine-refractory differentiated thyroid cancer

Document Type : Original Article

Authors

Department of Nuclear Medicine, Hospital 108, Hanoi, Vietnam

10.22038/aojnmb.2025.84029.1596

Abstract

Objective(s): This study investigates the relationship between quantitative 18F-FDG PET/CT metabolic parameters and overall survival (OS) in patients with radioiodine-refractory differentiated thyroid cancer (RAI-R DTC).
Methods: We conducted a prospective analysis of 127 patients with RAI-R DTC. Quantitative metabolic parameters including SUVmax, SUVmean, SUVpeak, total metabolic tumor volume (MTV), and total lesion glycolysis (TLG) were assessed in 18F-FDG -avid recurrent or metastatic lesions via 18F-FDG PET/CT imaging. Patients were monitored for disease progression and mortality for at least one-year post PET/CT imaging. Receiver operating characteristic (ROC) curves were used to establish cut-off values for predicting 5-year mortality, while the Kaplan-Meier method estimated the 5-year survival rate. Univariate and multivariate Cox regression analyses identified prognostic factors associated with OS.
Results: The metabolic parameters derived from 18F-FDG PET/CT demonstrated high sensitivity and specificity for predicting 5-year OS. ROC curve analysis established optimal cut-off values for SUVmax (20.27 g/mL), SUVmean (7.46 g/mL), SUVpeak (7.8 g/mL), TLG (45.74 g/mL×cm³), and MTV (5.78 cm3) (AUC: 0.82, 0.78, 0.82, 0.82, and 0.86, respectively; p<0.001). Kaplan-Meier analysis revealed significantly lower OS in patients with higher values of these parameters compared to those with lower ones (survival rates: 42.1% vs. 95.6%, 65.5% vs. 96%, 52.3% vs. 96.3%, 46.5% vs. 97.3%, and 57.3 % vs. 98.3%, respectively; p<0.001). Univariate Cox regression identified SUVmax, SUVmean, SUVpeak, TLG, and MTV as significant predictors of 5-year OS (p<0.05). In multivariate analysis, SUVpeak and MTV emerged as independent predictors of OS.
Conclusion: Quantitative 18F-FDG PET/CT-derived parameters are significant predictors of 5-year OS, exhibiting high sensitivity and specificity. Elevated values of these parameters correlate with increased mortality rates. Our findings suggest that SUVpeak and MTV are independent prognostic factors for 5-year OS in patients with radioiodine-refractory DTC.

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  1. Worden F. Treatment strategies for radioactive iodine-refractory differentiated thyroid cancer. Therapeutic advances in medical oncology. 2014; 6(6): 267-79.
  2. Xing M, Haugen BR, Schlumberger M. Progress in molecular-based management of differentiated thyroid cancer. Lancet (London, England). 2013; 381(9871): 1058-69.
  3. Durante C, Haddy N, Baudin E, Leboulleux S, Hartl D, Travagli J, et al. Long-term outcome of 444 patients with distant metastases from papillary and follicular thyroid carcinoma: benefits and limits of radioiodine therapy. The Journal of Clinical Endocrinology Metabolism. 2006; 91(8): 2892-9.
  4. Nixon IJ, Whitcher MM, Palmer FL, Tuttle RM, Shaha AR, Shah JP, et al. The impact of distant metastases at presentation on prognosis in patients with differentiated carcinoma of the thyroid gland. Thyroid: official journal of the American Thyroid Association. 2012; 22(9): 884-9.
  5. Fleeman N, Houten R, Chaplin M, Beale S, Boland A, Dundar Y, et al. A systematic review of lenvatinib and sorafenib for treating progressive, locally advanced or metastatic, differentiated thyroid cancer after treatment with radioactive iodine. BMC cancer. 2019; 19: 1-16.
  6. Schlumberger M, Brose M, Elisei R, Leboulleux S, Luster M, Pitoia F, et al. Definition and management of radioactive iodine-refractory differentiated thyroid cancer. The lancet Diabetes & endocrinology. 2014; 2(5): 356-8.
  7. Wartofsky L, & Van Nostrand, D., editor. Thyroid cancer: A comprehensive guide to clinical management. 3rd New York, NY: Springer; 2016.
  8. Schlumberger M, Lacroix L, Russo D, Filetti S, Bidart J-M. Defects in iodide metabolism in thyroid cancer and implications for the follow-up and treatment of patients. Nature clinical practice Endocrinology & metabolism. 2007; 3(3): 260-9.
  9. Volpe F, Nappi C, Zampella E, Di Donna E, Maurea S, Cuocolo A, et al. Current advances in radioactive iodine-refractory differentiated thyroid cancer. Current Oncology. 2024; 31(7): 3870-84.
  10. Haugen BR, Alexander EK, Bible KC, Doherty GM, Mandel SJ, Nikiforov YE, et al. 2015 American thyroid association management guidelines for adult patients with thyroid nodules and differentiated thyroid cancer: The American thyroid association guidelines task force on thyroid nodules and differentiated thyroid cancer. Thyroid: Official Journal of the American Thyroid Association. 2016; 26(1): 1-133.
  11. Wang H, Dai H, Li Q, Shen G, Shi L, Tian R. Investigating (18)F-FDG PET/CT parameters as prognostic markers for differentiated thyroid cancer: A systematic review. Frontiers in oncology. 2021; 11: 648658.
  12. Robbins RJ, Wan Q, Grewal RK, Reibke R, Gonen M, Strauss HW, et al. Real-time prognosis for metastatic thyroid carcinoma based on 2-[18F]fluoro-2-deoxy-D-glucose-positron emission tomography scanning. The Journal of clinical endocrinology and metabolism. 2006; 91(2): 498-505.
  13. Manohar PM, Beesley LJ, Bellile EL, Worden FP, Avram AM. Prognostic value of FDG-PET/CT metabolic parameters in metastatic radioiodine-refractory differentiated thyroid Clinical nuclear medicine. 2018; 43(9): 641-7.
  14. Lamartina L, Grani G, Arvat E, Nervo A, Zatelli MC, Rossi R, et al. 8th edition of the AJCC/TNM staging system of thyroid cancer: what to expect (ITCO#2). Endocrine-Related Cancer. 2018; 25(3): L7-L11.
  15. Golger A, Fridman TR, Eski S, Witterick IJ, Freeman JL, Walfish PG. Three-week thyroxine withdrawal thyroglobulin stimulation screening test to detect low-risk residual/ recurrent well-differentiated thyroid Journal of Endocrinological Investigation. 2003; 26(10): 1023-31.
  16. Boellaard R, Delgado-Bolton R, Oyen WJG, Giammarile F, Tatsch K, Eschner W, et al. FDG PET/CT: EANM procedure guidelines for tumour imaging: version 2.0. European Journal of Nuclear Medicine and Molecular Imaging. 2015; 42(2): 328-54.
  17. Larson SM, Erdi Y, Akhurst T, Mazumdar M, Macapinlac HA, Finn RD, et al. Tumor treatment response based on visual and quantitative changes in global tumor glycolysis using PET-FDG imaging. The visual response score and the change in total lesion glycolysis. Clinical positron imaging: Official Journal of the Institute for Clinical PET. 1999; 2(3): 159-71.
  18. Luo Y, Jiang H, Xu W, Wang X, Ma B, Liao T, et Clinical, pathological, and molecular characteristics correlating to the occurrence of radioiodine refractory differentiated thyroid carcinoma: a systematic review and meta-analysis. Frontiers in oncology. 2020; 10: 549882.
  19. Treglia G, Annunziata S, Muoio B, Salvatori M, Ceriani L, Giovanella L. The role of fluorine‐18‐fluorodeoxyglucose positron emission tomography in aggressive histological subtypes of thyroid cancer: an overview. International Journal of Endocrinology. 2013; 2013(1): 856189.
  20. Deandreis D, Al Ghuzlan A, Leboulleux S, Lacroix L, Garsi JP, Talbot M, et al. Do histological, immunohistochemical, and metabolic (radioiodine and fluorodeoxy-glucose uptakes) patterns of metastatic thyroid cancer correlate with patient outcome? Endocrine-related cancer. 2011; 18(1): 159-69.
  21. Masson-Deshayes S, Schvartz C, Dalban C, Guendouzen S, Pochart J-M, Dalac A, et al. Prognostic value of 18F-FDG PET/CT metabolic parameters in metastatic differentiated thyroid cancers. Clinical nuclear medicine. 2015; 40(6): 469-75.
  22. Creff G, Devillers A, Depeursinge A, Palard-Novello X, Acosta O, Jegoux F, et al. Evaluation of the prognostic value of FDG PET/CT parameters for patients with surgically treated head and neck cancer: a systematic review. JAMA Otolaryngology–Head & Neck Surgery. 2020; 146(5): 471-9.
  23. Hou G, Zhao N, Li F, Jing H, Zheng R. Prognostic value of pretreatment 18F-FDG PET/CT metabolic parameters in esophageal high-grade neuroendocrine carcinoma: A bicenter retrospective study. Frontiers in oncology. 2023; 13: 1145557.
  24. Albano D, Dondi F, Mazzoletti A, Bellini P, Rodella C, Bertagna F. Prognostic role of 2-[18F] FDG PET/CT metabolic volume parameters in patients affected by differentiated thyroid carcinoma with high thyroglobulin level, negative 131I WBS and positive 2-[18F]-FDG PET/CT. Diagnostics. 2021; 11(12): 2189.
  25. Jentzen W, Freudenberg L, Eising EG, Heinze M, Brandau W, Bockisch A. Segmentation of PET volumes by iterative image thresholding. Journal of Nuclear Medicine. 2007; 48(1): 108.
  26. Schinagl DAX, Hoffmann AL, Vogel WV, van Dalen JA, Verstappen SMM, Oyen WJG, et al. Can FDG-PET assist in radiotherapy target volume definition of metastatic lymph nodes in head-and-neck cancer? Radiotherapy and Oncology. 2009; 91(1): 95-100.
  27. Daisne JF, Sibomana M, Bol A, Doumont T, Lonneux M, Grégoire V. Tri-dimensional automatic segmentation of PET volumes based on measured source-to-background ratios: influence of reconstruction algorithms. Radiotherapy and oncology: journal of the European Society for Therapeutic Radiology and Oncology. 2003; 69(3): 247-50.
  28. Hatt M, Laurent B, Ouahabi A, Fayad H, Tan S, Li L, et al. The first MICCAI challenge on PET tumor segmentation. Medical image analysis. 2018; 44: 177-95.
  29. Im HJ, Bradshaw T, Solaiyappan M, Cho SY. Current methods to define metabolic tumor volume in positron eEmission tomography: Which one is better? Nuclear Medicine and Molecular Imaging. 2018; 52(1): 5-15.
  30. Kaalep A, Sera T, Oyen W, Krause BJ, Chiti A, Liu Y, et al. EANM/EARL FDG-PET/CT accreditation - summary results from the first 200 accredited imaging systems. Eur J Nucl Med Mol Imaging. 2018; 45(3): 412-22.