Limited value of genetic profiling in guiding radioiodine therapy for metastatic differentiated thyroid cancer

in Endocrine-Related Cancer
Authors:
Ziyan He Department of Nuclear Medicine, Shanghai Sixth People’s Hospital Affiliated to Shanghai Jiao Tong University School of Medicine, Shanghai, People’s Republic of China

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Congcong Wang Department of Nuclear Medicine, The Affiliated Hospital of Qingdao University, Qingdao, Shandong, People’s Republic of China

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Chang Liu Department of Nuclear Medicine, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, People’s Republic of China

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Ke Zhang Department of Nuclear Medicine, Shanghai Sixth People’s Hospital Affiliated to Shanghai Jiao Tong University School of Medicine, Shanghai, People’s Republic of China

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Junyao Wang Department of Nuclear Medicine, Shanghai Sixth People’s Hospital Affiliated to Shanghai Jiao Tong University School of Medicine, Shanghai, People’s Republic of China

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Xufu Wang Department of Nuclear Medicine, The Affiliated Hospital of Qingdao University, Qingdao, Shandong, People’s Republic of China

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Yifan Zhang Department of Nuclear Medicine, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, People’s Republic of China

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https://orcid.org/0000-0001-6488-6232
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Libo Chen Department of Nuclear Medicine, Shanghai Sixth People’s Hospital Affiliated to Shanghai Jiao Tong University School of Medicine, Shanghai, People’s Republic of China

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https://orcid.org/0000-0002-2822-9785

Correspondence should be addressed to X Wang: wangxufu@sina.com or Y Zhang: zyf11300@rjh.com.cn or L Chen: lbchen@sjtu.edu.cn

(Z He, C Wang and C Liu contributed equally as first authors)

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Assessing the 131I-avidity of metastatic differentiated thyroid cancer (mDTC) is pivotal to characterizing the nature of disease and optimizing the therapeutic strategy. In this prospective study, the predictive value of genetic profiling of 18 selected thyroid cancer-relevant genes for 131I-avidity and the response to radioiodine therapy (RT) was studied in comparison with those of diagnostic 131I scan. During univariate analysis, BRAF status (odds ratio, (OR) = 12.47, 95% confidence interval (CI): 5.03–30.89, P < 0.001) and TNM-M stage (P = 0.029) were found to be associated with 131I-avidity, but multivariate analysis identified BRAF V600E as the sole independent factor associated with the non-131I-avidity (OR = 12.98, 95% CI: 3.77–44.73, P < 0.001). The predictive values of BRAF wild-type for 131I-avidity and BRAF V600E for non-131I-avidity were 84.6 and 69.4%, respectively, both lower than those of diagnostic 131I scan (positive predictive value of 100%, P = 0.031; negative predictive value of 81.1%, P = 0.219). The predictive value of BRAF V600E for non-131I-avidity was not significantly improved when combined with TERT promoter mutation (76.9 vs 69.4%, P = 0.736). Moreover, the predictive value of BRAF V600E for biochemical non-response was 70.8% (17/24), while no correlation was found between BRAF status and structural response. In contrast, a negative diagnostic 131I scan was significantly associated with both biochemical and structural non-responses, with predictive values of 81 and 100%, respectively. The current study demonstrated that genetic profiling is of limited value in guiding RT for mDTC, while a diagnostic 131I scan proved superior in this respect.

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