Bone metastases from differentiated thyroid carcinoma: heterogenous tumor response to radioactive Iodine therapy and overall survival

Abstract

Purpose: Bone metastases (BM) from differentiated thyroid carcinoma (DTC) impact negatively the quality of life and the life expectancy of patients. The aim of the study was (a) to evaluate the overall survival (OS) and prognostic factors of OS and (b) to assess predictive factors of complete BM response (C-BM-R) using radioiodine treatment (RAI) either alone or in association with focal treatment modalities.

Methods: A total of 178 consecutive DTC patients harbouring BM, treated between 1989 and 2015, were enrolled in this retrospective study conducted in two tertiary referral centers. OS analysis was performed for the whole cohort, and only the 145 considered non-RAI refractory patients at BM diagnosis were evaluated for C-BM-R following RAI.

Results: The median OS from BM diagnosis was 57 months (IQR: 24-93). In multivariate analysis, OS was significantly reduced in the case of T4 stage, ¹⁸FDG uptake by the BM and RAI refractory status. Among the 145 DTC considered non-RAI refractory patients at BM diagnosis, 46 patients (31.7%) achieved a C-BM-R following RAI treatment, either alone in 32 (18%) patients or in association with focal BM treatment modalities in 14. The absence of extra-skeletal distant metastasis and of ¹⁸FDG uptake in BM were predictive for C-BM-R.

Conclusions: In nearly one-third of DTC patients with RAI avid BM, RAI alone or in combination with BM focal treatment can induce C-BM-R. The presence of ¹⁸FDG uptake in BM is associated with an absence of C-BM-R and with a poor OS. ¹⁸FDG PET-CT should be performed when BM is suspected.

Keywords: Bone metastases; Focal treatment; Radioiodine; Skeletal-related events; Thyroid carcinoma.

Fig. 1

Flowchart. DTC: Differentiated thyroid carcinomar, GR: Gustave-Roussy, BM: Bone metastases, RAI: radioactive iodine, RAI-R: Radioactive iodine Refractory, C-BM-R: Complete bone metastases response

Fig. 2

Overall survival univariate analysis of the overall BM cohort. Figure 2a: median OS of the overall BM cohort analysis with first or third interquartile range. 2b: OS analysis as a function ofage above or below 55 years. 2c: OS analysis depending on sex status ; 2d: OS analysis depending on histologicalmorphotype ; 2e: OS analysis depending on TNM T staging ; 2f: OS analysis depending on the presence of extra-skeletalmetastasis sites ; 2g: OS analysis as function of BM on cross-sectional imaging ; 2h: OS analysis depending on 18FDG-PET/CTuptake in BM ; 2i: OS analysis depending on new BM during RAI treatment ; 2j: OS analysis depending on the absence of RAIuptakein one or more BM ; 2k: OS analysis depending on the refractory status at diagnosis or during follow-up.The p values are presented for Log-rank tests.OS: Overall survival, DTC: Differentiated Thyroid Carcinoma, WDTC: Well-Differentiated Thyroid Carcinoma, PDTC: PoorlyDifferentiated Thyroid Carcinoma, BM: Bone metastasis, TNM: Tumor Node Metastasis. 18FDG PET-CT: 18-Fluorodesoxyglucose-positron emission tomography, RAI: radioactive iodine.

Fig. 3

Kaplan–Meier graph of overall survival in 178 patients with differentiated thyroid carcinomas and bone metastases depending on RAI and/or FDG-PET/CT uptake. RAI: radioactive iodine, FDG PET/CT: Fluoro-desoxyglucose-positron emission tomography

Fig. 4

Forest plot of multivariate-adjusted hazard ratios (HRs) for factors related to mortality outcome in DTC patients with BM. WDTC: Well Differentiated Thyroid Carcinoma BM: Bone metastases, RAI: radioactive iodine, SRE: Skeletal Related Events, FDG PET/CT: Fluoro-desoxyglucose-positron emission tomography. RAI refractory status at diagnosis and during follow-up

Fig. 5

Radioactive iodine and 18-FDG-uptake in bone metastases of patients with (n = 26) or without (n = 94) complete bone metastases responses. RAI: radioactive iodine, FDG: 18-Fluoro-desoxyglucose-positron emission tomography, C-BM-R: Complete-bone metastases-response.