No survival difference after successful (131)I ablation between patients with initially low-risk and high-risk differentiated thyroid cancer.

PURPOSE: To compare disease-specific survival and recurrence-free survival (RFS) after successful (131)I ablation in patients with differentiated thyroid carcinoma (DTC) between those defined before ablation as low-risk and those defined as high-risk according to the European Thyroid Association 2006 consensus statement. METHODS: Retrospective data from three university hospitals were pooled. Of 2009 consecutive patients receiving ablation, 509 were identified as successfully ablated based on both undetectable stimulated serum thyroglobulin in the absence of antithyroglobulin antibodies and a negative diagnostic whole-body scan in a follow-up examination conducted 8.1+/-4.6 months after ablation. Of these 509 patients, 169 were defined as high-risk. RESULTS: After a mean follow-up of 81+/-64 months (range 4-306 months), only three patients had died of DTC, rendering assessment of disease-specific survival differences impossible. Of the 509 patients, 12 (2.4%) developed a recurrence a mean 35 months (range 12-59 months) after ablation. RFS for the duration of follow-up was 96.6% according to the Kaplan-Meier method. RFS did not differ between high-risk and low-risk patients (p=0.68). RFS differed slightly but significantly between those with papillary and those with follicular thyroid carcinoma (p=0.03) and between those aged 45 years at diagnosis (p=0.018). CONCLUSION: After (near) total thyroidectomy and successful (131)I ablation, RFS does not differ between patients classified as high-risk and those classified as low-risk based on TNM stage at diagnosis. Consequently, the follow-up protocol should be determined on the basis of the result of initial treatment rather than on the initial tumour classification.

The success rate of I-131 ablation in differentiated thyroid cancer: comparison of uptake-related and fixed-dose strategies.

INTRODUCTION: The aim of the study was to compare the success rate of an uptake-related ablation protocol in which the dose depends on an I-131 24-h neck uptake measurement and a fixed-dose ablation protocol in which the dose depends on tumour stage. METHODS: All differentiated thyroid carcinoma patients with M0 disease who had undergone (near-) total thyroidectomy followed by I-131 ablation were included. In the uptake-related ablation protocol, 1100 (uptake >10%), 1850 (uptake 5-10%) and 2800 MBq (uptake <5%) were used. In the fixed-dosage ablation strategy, 3700 (T1-3, N0 stage) and 5550 MBq (N1 and/or T4 stage) were applied. We used I-131 uptake on whole-body scintigraphy and thyroglobulin-off values to evaluate the ablation 6-12 months after treatment. RESULTS: In the uptake-related ablation protocol, 60 out of 139 (43%) patients were successfully treated versus 111 out of 199 for the fixed-dose ablation protocol (56%) (P=0.022). The differences were not statistically significant for patients with T4 (P=0.581) and/or N1 (P=0.08) disease or for patients with T4N1 tumour stage (P=0.937). CONCLUSION: The fixed-dose I-131 ablation protocol is more effective in ablation of the thyroid remnant in differentiated thyroid carcinoma patients than an uptake-related ablation protocol. This difference is not observed in patients with a N1 and/or T4 tumour stage.

A new functional parameter measured at the time of ablation that can be used to predict differentiated thyroid cancer recurrence during follow-up.

BACKGROUND: This study addresses the questions whether patients with a high risk for recurrent thyroid cancer can be identified at initial stage, i.e. at the time of ablation. METHODS: We evaluated tumor recurrence in consecutive patients treated for differentiated thyroid cancer (DTC). Prognostic factors were statistically analyzed. We defined prognostic parameters based on thyroglobulin (Tg) levels, 24-h I-131 uptake rates and TSH values: (a) Tg/TSH, (b) Tg/24-h I-131 uptake value, and (c) Tg/(TSHx24-h I-131 uptake). RESULTS: We included 190 patients (50 male, 140 female; mean age 47 years) with DTC for analysis, 146 without distant metastases and 44 with M1 tumor stage at initial presentation. The mean period of follow-up was 10.4 years (s.d. +/- 3.7 years). In 18 out of the 146 DTC patients with M0 disease (12.4%), tumor recurrence was found during follow-up. Although tumor stage, age, and standard biochemical values significantly differ between patients with and without recurrent disease or between patients with M0 and M1 tumor stage, the newly defined parameter Tg/(TSHx24-h I-131 uptake) was the best independent significant prognostic parameter in the assessment whether patients will develop a tumor recurrence during follow-up or not. CONCLUSION: High Tg/(TSHx24-h I-131 uptake) ratios justify an adjustment of the I-131 activity for ablation therapy. To assess the optimal cut-off value for a dose adjustment, however, further studies are required in more patients, but the initial results are encouraging with respect to improving outcome in DTC patients.

The incidence of second primary tumors in thyroid cancer patients is increased, but not related to treatment of thyroid cancer.

OBJECTIVE: The aim of the present study is to assess the prevalence of second primary tumors in patients treated for thyroid cancer. Furthermore, we wanted to assess the standardized risk rates for all second primary tumors, but especially for breast cancer, as data in the literature indicate an excessive risk in differentiated thyroid cancer (DTC) patients for this tumor. MATERIALS AND METHODS: We included consecutive patients, who received ablation treatment with I-131 at the Leiden University Medical Center between January 1985 and December 1999 (n = 282). The mean period of follow-up was 10.6 +/- 4.1 years. RESULTS: Thirty-five of the 282 patients (12.4%) had a second primary tumor (SPT), either preceding or following the diagnosis of thyroid cancer. Five other patients had three primary tumors, including DTC. As a result, 40 additional tumors were found in this group, revealing an overall prevalence of 14.2%. Twenty tumors (7.1%) preceded the thyroid cancer with a mean interval of 5.7 years (range: 0.5-22.0 years), whereas 20 tumors (7.1%) occurred after this tumor with a mean interval of 6.7 years (range: 1.0-15.0 years). In 13 female patients, breast cancer was found as SPT. The standardized incidence rate (SIR) for all cancers after the diagnosis of DTC in this study population was not increased (1.13; confidence interval (CI): 0.68-1.69). However, we found an increased SIR of 2.26 (CI: 1.60-3.03) for all cancers either following or preceding DTC, which is mainly caused by a SIR of 3.95 (CI: 2.06-6.45) for breast cancer. CONCLUSION: Patients with DTC have an overall increased standardized incidence rate for second primary tumors, but not for second primary tumors following I-131 therapy. These findings suggest a common etiologic and/or genetic mechanism instead of a causal relation.

Six month follow-up after 111In-DTPA-octreotide therapy in patients with progressive radioiodine non-responsive thyroid cancer: a pilot study.

BACKGROUND AND AIM: 111In-DTPA-octreotide is internalized by thyroid and neuroendocrine cancer cells via somatostatin receptor subtypes and can cause DNA damage by the emission of conversion and Auger electrons. The aim of the study was to determine the effect of 111In-DTPA-octreotide therapy in patients with progressive radioiodine non-responsive thyroid cancer in relation to 111In-DTPA-octreotide uptake by tumour localizations assessed on pre-treatment diagnostic octreotide scans. METHODS: Eleven consecutive patients, selected on positive pretreatment diagnostic scans, were treated with fixed doses of approx. 7400 MBq of 111In-DTPA-octreotide with an interval of 2-3 weeks between the doses. In one patient, the dose was adjusted because of sickle-cell disease. To assess the effects during treatment with 111In-DTPA-octreotide thyroglobulin levels were gathered from 2 years before treatment, during treatment and up to 1 year after treatment. A computed tomography scan was performed 3 months after the last treatment. RESULTS: Two patients died during and shortly after the treatment course. Death was due to a sepsis and an insulin overdose, respectively. In 44% of the patients, stable disease was achieved up to 6 months after the first treatment according to both criteria. All four had relative low pretreatment thyroglobulin values (mean value 275 microg.l), representing limited metastasized disease. In two patients biochemical stable disease was observed, whereas computed tomography showed tumour progression. CONCLUSION: Treatment with high doses of 111In-DTPA-octreotide in differentiated thyroid cancer results in a stable disease in a subgroup of patients. Our results suggest that a low pre-treatment thyroglobulin value, representing a small tumour load, may be a selection criterion for treatment.

Radioiodine-131 in differentiated thyroid cancer: a retrospective analysis of an uptake-related ablation strategy.

In our hospital, a 24-h radioiodine-131 ((131)I) uptake-related ablation strategy is used in patients with differentiated thyroid cancer to destroy thyroid remnants after primary surgery. In this strategy, low doses of (131)I are used, but data in the literature on its efficacy are conflicting. Therefore, we performed the present study to evaluate the clinical outcome of this ablation strategy. In this study, patients ( n=235) were selected who underwent thyroidectomy for differentiated thyroid cancer, followed by an ablative dose of (131)I. Approximately 6 months after ablation, treatment efficacy was evaluated using radioiodine scintigraphy and thyroglobulin (Tg) measurements. Successful ablation was defined as the absence of radioiodine uptake in the neck region (criterion 1). Tg values were determined 3-12 months after ablation (criterion 2). Based on criterion 1, unsuccessful ablation was found in 43.0% of cases. Pre-treatment uptake values were statistically significantly lower ( P=0.003) in successfully ablated patients (mean 5.4%) than in unsuccessfully ablated patients (mean 8.2%). Based on criterion 2, unsuccessful ablation was found in 52.4% of patients. The uptake-related ablation strategy, using low doses of (131)I, shows a relatively high treatment failure rate. Based on these results it is suggested that a lower ablation failure rate could be achieved by applying higher (131)I doses in the ablation of thyroid remnants in differentiated thyroid carcinoma patients. In the case of lymph node metastases a further dose adjustment may be advisable.

Indium-111-Octreotide scintigraphy in differentiated thyroid carcinoma metastases that do not respond to treatment with high-dose I-131.

AIM: Differentiated thyroid cancer is characterized by a very good prognosis in the majority of the patients. The therapy of choice is surgery followed by ablation with Iodine-131 (I-131). However, some patients have metastases that have lost the capability of concentrating I-131, even when it is given in therapeutic doses. In the present study, we describe the value of Indium-111 Octreotide (Octreoscan) in differentiated thyroid cancer patients with increased Tg levels who failed to demonstrate a response to treatment with high-dose I-131. METHOD: Fifteen consecutive patients with progressive differentiated thyroid cancer (ten female, five male) (mean age: 59 years, range 13-81 years; eight papillary, six follicular, and one Hürthle cell carcinoma) were studied. Progression was based on increasing Tg levels and was confirmed by radiological evaluation. Whole body scintigraphy (WBS) was performed after the administration of 200 MBq of Indium-111-Octreotide. The images were assessed by two experienced observers and compared with post-treatment I-131 WBS. RESULTS: In seven out of 15 patients distant metastases were already present at initial stage, whereas in ten patients the primary tumor stage was T3 or T4 indicating that the majority of the patients had advanced disease. In two out of five patients with a positive I-131 WBS, Indium-111-Octreotide was false negative. In nine out of ten patients with a negative I-131 WBS, Indium-111-Octreotide demonstrated multiple metastases. In those patients with a positive SSR-scintigraphy, metastases were found in the lungs ( n=14), bone ( n=7), mediastinum ( n=3), liver ( n=2), brains ( n=1), and cutis ( n=1). Overall, three out of 15 patients had a negative Indium-111-Octreotide result revealing a sensitivity of 80%. CONCLUSION: Our findings demonstrate the diagnostic value of Indium-111-Octreotide in differentiated thyroid cancer that fails to respond to I-131 treatment. It opens the possibility for additional treatment with high doses of Indium-111-Octreotide or its analogs in a majority of the patients.