Risk Factors for Nonsynchronous Second Primary Malignancy and Related Death in Patients with Differentiated Thyroid Carcinoma

BACKGROUND: Differentiated thyroid cancer (DTC) survivors are at increased risk of developing nonsynchronous second primary malignancy (NSPM). This study aims to examine possible risk factors leading to occurrence of NSPM as well as risk factors leading to NSPM-related death in patients with DTC. METHODS: Of the 1,106 patients with DTC managed at our institution, 92 (8.3%) patients developed NSPM and 40 (3.6%) patients died of NSPM. All causes of death were confirmed by medical record, autopsy report or death certificate. Clinicopathological variables were compared between those without NSPM and with NSPM as well as between those who died of NSPM and did not die of NSPM. Significant variables on univariate analysis were entered into a Cox proportional hazards model. RESULTS: The median latency period from diagnosis of DTC to NSPM was 142.7 (range 16.8-511.0) months. For occurrence of NSPM, age at DTC diagnosis >/=50 years old [relative risk (RR) = 2.35], cumulative radioactive iodine (RAI) activity 3.0-8.9 GBq (RR = 2.38), and external local radiotherapy (ERT) (RR = 1.95) were significant risk factors. For NSPM-related death, age at DTC diagnosis >/=50 years old (RR = 3.32) and nonbreast cancer (RR = 5.76) were significant risk factors. CONCLUSIONS: NSPM accounted for 18.7% of all deaths in DTC, but mortality was high (43.5%). Age at DTC diagnosis >/=50 years old, cumulative RAI activity 3.0-8.9 GBq, and ERT were significant risk factors for occurrence of NSPM, whereas age at DTC diagnosis >/=50 years old and the diagnosis of nonbreast cancer were significant risk factors for NSPM-related death.published_or_final_versionSpringer Open Choice, 21 Feb 201

Nuclear Factor-Kappa B Inhibition Can Enhance Apoptosis of Differentiated Thyroid Cancer Cells Induced by 131I

Objective: To evaluate changes of nuclear factor-kappa B (NF-kB) during radioiodine 131 ( 131 I) therapy and whether NF-kB inhibition could enhance 131 I-induced apoptosis in differentiated thyroid cancer (DTC) cells in a synergistic manner. Methods: Three human DTC cell lines were used. NF-kB inhibition was achieved by using a NF-kB inhibitor (Bay 11-7082) or by p65 siRNA transfection. Methyl-thiazolyl-tetrazolium assay was performed for cell viability assessment. DNA-binding assay, luciferase reporter assay, and Western blot were adopted to determine function and expression changes of NF-kB. Then NF-kB regulated anti-apoptotic factors XIAP, cIAP1, and Bcl-xL were measured. Apoptosis was analyzed by Western blot for caspase 3 and PARP, and by flow cytometry as well. An iodide uptake assay was performed to determine whether NF-kB inhibition could influence radioactive iodide uptake. Results: The methyl-thiazolyl-tetrazolium assay showed significant decrease of viable cells by combination therapy than by mono-therapies. The DNA-binding assay and luciferase reporter assay showed enhanced NF-kB function and reporter gene activities due to 131 I, yet significant suppression was achieved by NF-kB inhibition. Western blot proved 131 I could increase nuclear NF-kB concentration, while NF-kB inhibition reduced NF-kB concentration. Western blot also demonstrated significant up-regulation of XIAP, cIAP1, and Bcl-xL after 131 I therapy. And inhibition of NF-kB could significantly downregulate these factors. Finally, synergism induced by combined therapy was displayed by significant enhancements o

A Sensitive Tg Assay or rhTSH Stimulated Tg: What's the Best in the Long-Term Follow-Up of Patients with Differentiated Thyroid Carcinoma?

Sensitivity of thyroglobulin (Tg) measurement in the follow-up of differentiated thyroid carcinoma (DTC) can be optimized by using a sensitive Tg assay and rhTSH stimulation. We evaluated the diagnostic yield of a sensitive Tg assay and rhTSH stimulated Tg in the detection of recurrences in the follow-up of DTC. Additionally the value of imaging techniques for the localization of recurrences was evaluated. We included 121 disease free patients in long-term follow-up for DTC (median 10 years, range 1–34). Tg during thyroid hormone suppression therapy (Tg-on) and rhTSH stimulated Tg were measured with a sensitive Tg assay. Patients with rhTSH stimulated Tg ≥1.0 ng/ml underwent imaging with neck ultrasound, FDG-PET and post therapy 131I WBS. Sensitive Tg measurement resulted in 3 patients with Tg-on ≥1.0 ng/ml, recurrence could be localized in 2 of them. RhTSH stimulation resulted in Tg ≥1.0 ng/ml in another 17 of 118 patients. Recurrence could be localized in only 1 additional patient (1 out of 118 patients). Recurrence was localized by neck ultrasound in 1 of 3, by FDG-PET in 2 of 3 and by post therapy 131I WBS in 2 of 3 patients. In the detection of recurrences in DTC, rhTSH stimulation had very limited additional value in comparison to Tg-on measurement with a sensitive Tg assay. We consider this too low to justify rhTSH stimulation in all patients during long-term follow up. Neck ultrasound, FDG-PET and post therapy 131I WBS showed complementary value in localization of disease, but were only positive in a small fracture of all procedures