The value of FDG-PET in the follow-up of differentiated thyroid cancer: a review of the literature.

Well differentiated (follicular and papillary) thyroid cancer (DTC) is characterized by rare occurrence and a good prognosis. However, up to 20% of patients with DTC develop locoregional recurrences, whereas even 8% of patients with such recurrences will eventually die from disease. In some of these patients it is related to incomplete initial treatment, whereas in others it indicates the presence of an aggressive tumor. In this latter case, dedifferentiation may occur with negative I-131 whole body scintigraphy (WBS) results and unreliable Tg measurements. In patients with thyroid cancer metastases that lost the capability of I-131 uptake, other imaging techniques are required to depict the non-functioning metastases, irrespective of the Tg-levels and irrespective of the site of recurrent disease. In this respect, some reports have discussed the value of ultrasonography of the head and neck region with good results for the detection of locoregional disease. We have assessed the role of FDG-PET in patients with I-131 negative WBS and its relation with Tg values and TSH-stimulation based on data that have appeared in the literature. In this review article, a discussion is given on the results published so far.

Familial Paget's disease in The Netherlands: occurrence, identification of new mutations in the sequestosome 1 gene, and their clinical associations.

OBJECTIVE: To estimate the occurrence of familial Paget's disease of bone in The Netherlands, to examine the prevalence of mutations of the sequestosome 1 gene (SQSTM1) in identified families, and to assess potential genotype-phenotype associations. METHODS: We performed a case-control study of patients with Paget's disease and a mutation analysis of the SQSTM1 gene of index patients with familial disease and of the relatives of those with a mutation. Serum alkaline phosphatase (AP) activity was assessed, and bone scintigraphy was performed. RESULTS: Five percent of patients had at least 1 first-degree relative with the disease, compared with 0.5% of the controls (relative risk 10; 95% confidence interval 1.3-75.6). In 38.9% of patients with familial disease, heterozygous mutations in the SQSTM1 gene were identified. These were the previously described P392L mutation, which was present in 22.2% of patients, and 3 new mutations, S399P, G425R, M404T, 9 of which were present in 3 different families. All mutations were located in the ubiquitin-associated domain of the gene. There was a relationship between serum AP activity, as a marker of the disease, and the presence or absence of the G425R and P392L mutations, the subject's age, and the presence of Paget's disease. CONCLUSION: Our data provide further evidence of a causal role of SQSTM1 gene mutations in the pathogenesis of Paget's disease and allow the design of a strategy based on measurements of serum AP activity and age for investigating asymptomatic relatives of patients with familial Paget's disease of bone.

Feasibility of a randomized trial on adjuvant radio-iodine therapy in differentiated thyroid cancer.

BACKGROUND: Justification for adjuvant radio-iodine (I-131) therapy in differentiated thyroid cancer (DTC) is purely based on retrospective data. This is true for ablative therapy and even more so for high-dosage adjuvant schedules. Randomized trials on the latter application are considered impossible due to anticipated formidable sample sizes required in a disease with an overall excellent prognosis like DTC. OBJECTIVE: To develop and validate a model that could stratify for risk of recurrence, rather than survival, as is usually done in prognostic indices, and secondly, to use this model to estimate the sample size required for a randomized trial. DESIGN, PATIENTS AND RESULTS: From databases of three large Dutch centres, we identified 342 consecutive patients without known residual DTC after (near-) total thyroidectomy. Using Cox proportional hazards analysis, a model was validated that clearly distinguished risk categories of recurrence using commonly available baseline variables. The model included age, N stage at presentation and T stage in papillary carcinoma. According to this stratification, a subset of patients at substantial risk for relapse (30-40%) was identified. They could be eligible for a trial assessing the impact of high-dose adjuvant I-131 on recurrence rates. Assuming a clinically relevant effect of 30% reduction of relapses, 290 patients would have to be entered in either arm (alpha 0.05, power 80%). CONCLUSION: We conclude that even though a randomized trial on this issue will be difficult to design and conduct, sample size is not the main problem.