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Aim: To study the clinical yield of diagnostic whole body 131 I scintigraphy (DxWBS) in the follow-up of differentiated thyroid carcinoma (DTC) patients in relation to stimulated thyroglobulin (sTg) in the initial post-ablation setting, as well as in the setting of repeated monitoring in course of further DTC follow-up., Methods: Data of 1420 thyroidectomized and radioiodine remnant-ablated DTC patients following a well-defined therapy and standardized follow-up protocol were evaluated. DxWBS and sTg were evaluated separately and in combination for various follow-up time points. The factual administration of the recorded indication for further oncologic therapy (excluding radioiodine therapies given for minimal normal remnants) within the following 4 months after follow-up served as the standard of reference. Furthermore, DxWBS was compared to post therapy WBS and SPECT(/CT) if available. Subgroup analysis was carried out for DTC patients < 45 years old at diagnosis without distant metastasis. The diagnostic impact of cervical ultrasound was not assessed., Results: sTg can identify the patients at risk better than DxWBS. Furthermore, the most sensitive time point to assess response appears to be a time point beyond 3 months after RRA. When information received from both imaging and laboratory measurements are concordant, i.e. both construe absence of remaining disease, only a small fraction of patients (<2%) required treatment in the future. The strongest effect was observed 12 months after RRA. Only 0.9% of the negative DxWBS patients with concordant sTg below the functional sensitivity at this time point required treatment thereafter., Conclusion: A complete omission of DxWBS in the post-RRA surveillance of DTC is justified once DxWBS is negative and sTg is below the functional sensitivity (with no evidence of thyroglobulin antibodies), as patients showing this combination of test results (especially 12 months after RRA) show an at worst marginal risk of recurrence. In all other cases DxWBS may still be justified.

Background and Objectives: To investigate if patients with thyroid carcinoma having N1a disease are at the same risk with N1b using the collective of the well-defined European prospective Multicentre Study Differentiated Thyroid Cancer (MSDS)., Methods: Overall (OS) and event free survival (EFS) were calculated. Cox multivariable regression analysis was performed in order to calculate Hazard ratios (HR)., Results: EFS was significantly decreased only in patients with N1b metastasis as compared to N0 patients and became worse when N1a was concomitantly affected. A superior survival in favor of N1a patients as compared to N1b patients with regard to EFS was also observed. The patients having N1a disease showed no differences in the EFS as compared to N0. OS did not differ significantly in any of the groups. There was an increased HR for events with regards to histology, T-stage, tumor size, UICC stage and cervical lymph node metastasis. Tumor size showed a significantly increased risk for OS., Conclusions: Patients with pT3b and pT4a tumors with N1b are of higher risk for relapse, albeit not affecting overall survival. Patients with N1a are of no higher risk. The risk stratification of these patients may be adapted accordingly., (© 2015 Wiley Periodicals, Inc.)

Unlabelled: The aim of this study was to compare the overall survival of a large, single-center cohort of patients who had differentiated thyroid cancer (DTC) with that of a matched general population., Methods: We analyzed 2,428 consecutive patients who had DTC and underwent treatment from 1965 to 2013 at the Department of Nuclear Medicine, University Hospital of Münster, Münster, Germany, according to international standards. Patients were classified on the basis of the current, seventh edition of the American Joint Committee on Cancer/Union for International Cancer Control classification system. Additionally, a subgroup analysis with regard to age at diagnosis was performed. The overall survival of the patients was compared with the expected survival of the general population on the basis of age and sex, as provided by the Federal Statistical Office of Germany., Results: Compared with the expected survival, the overall survival of patients with stage I disease paradoxically was significantly better (P < 0.001). In the subgroup analysis, a significantly lower mortality rate was observed in elderly patients (≥60 y old) with stage I disease. On the other hand, patients between 20 and 45 y of age and with distant metastases at diagnosis had a significantly increased standardized mortality rate. In contrast, other patients with stage II disease and more than 45 y old had a normal mortality rate. The mortality rate was significantly increased in all patients with stage IVC disease., Conclusion: Older patients with more limited disease paradoxically had better survival than would be expected on the basis of age and sex, whereas young adults as well as patients more than 45 y old and with distant metastases had increased mortality rates. For all other DTC patients, regardless of age or TNM stage, no significant survival difference was seen., (© 2015 by the Society of Nuclear Medicine and Molecular Imaging, Inc.)

Objective: The seventh edition of the American Joint Committee on Cancer (AJCC) has more detailed staging categories for differentiated thyroid cancer (DTC) than the fifth edition. The aim was to compare potential alterations in the disease-specific (DSS), event-free (EFS) and overall survival (OS), after reclassification from the fifth to the seventh edition., Methods: Data of 2460 patients with DTC referred to our centre were reclassified from the fifth to the seventh edition of AJCC. DSS, EFS and OS were calculated using the Kaplan-Meier method and compared by the log-rank test. The relative abilities of each edition to predict survival were calculated by the proportion of variance explained (PVE)., Results: After reclassification to the seventh edition, there was an increase in stage I and IV patients from 58·1% to 65·0% and from 6·2% to 10·1%, respectively, and a corresponding decrease in stage II and III patients from 22·4% to 12·5% and 13·3% to 12·4%, respectively. As to DSS, the seventh edition had only a marginally higher PVE value than the fifth edition. With respect to EFS, the predictability of the seventh edition was even inferior to that of the fifth edition. Similarly, with regard to OS, the PVE value was slightly better for the older edition. Furthermore, a comparison only for those patients affected by the reclassification revealed no differences for DSS, EFS or OS between classifications., Conclusion: When comparing the stages of the seventh with the fifth edition of the AJCC for DTC, there was no significant difference in predicting DSS, EFS and OS., (© 2014 John Wiley & Sons Ltd.)

Background: Brain metastases arise in roughly 0.9% of all cases of differentiated thyroid cancer. The median survival of adult patients with thyroid carcinoma that has metastasized to the brain is less than one year. Radioactive iodine treatment is only rarely given because its efficacy is not documented. In children, the situation may be different., Method: In 2005, a 15-year-old girl underwent thyroidectomy, and an oxyphilic variant of papillary thyroid carcinoma was found in ectopic thyroid tissue. The patient underwent oral, high-dose radioactive iodine treatment. The post-therapeutic I-131 whole-body scan revealed multiple metastases in the skeleton, lungs, and the soft tissues, along with physiological uptake of the residual thyroid tissue. Magnetic resonance imaging of the head revealed two brain metastases., Results: When the initial treatment was completed, additional age-adapted high-dose radioactive iodine treatment was given, up to a total activity level of 35 GBq. There followed a complete remission of all metastases in the brain, bones, lungs, and soft tissues. Computed tomography of the chest revealed stable residuals. Over the ensuing 7.5 years of follow-up, the thyroglobulin values steadily declined to less than 2 ng/mL. The patient was asymptomatic at her last follow-up in May 2013. She did not develop any delayed reaction to high-dose radioactive iodine treatment (in particular, she did not develop leukemia or any other secondary malignancy). She remained fertile: after completion of the treatment, she had two healthy children., Conclusion: In this patient with multifocal thyroid carcinoma, a rare entity, radioactive iodine treatment was successful as the single treatment. This case illustrates the point that a given therapeutic modality might succeed in an individual case despite a total or near-total lack of efficacy for most patients in the same situation.

Introduction: Over the past years, the incidence of thyroid cancer has surged not only in Germany but also in other countries of the Western hemisphere. This surge was first and foremost due to an increase of prognostically favorable ("low risk") papillary thyroid microcarcinomas, for which limited surgical procedures are often sufficient without loss of oncological benefit. These developments called for an update of the previous practice guideline to detail the surgical treatment options that are available for the various disease entities and tumor stages., Methods: The present German Association of Endocrine Surgeons practice guideline was developed on the basis of clinical evidence considering current national and international treatment recommendations through a formal expert consensus process in collaboration with the German Societies of General and Visceral Surgery, Endocrinology, Nuclear Medicine, Pathology, Radiooncology, Oncological Hematology, and a German thyroid cancer patient support organization., Results: The practice guideline for the surgical management of malignant thyroid tumors includes recommendations regarding preoperative workup; classification of locoregional nodes and terminology of surgical procedures; frequency, clinical, and histopathological features of occult and clinically apparent papillary, follicular, poorly differentiated, undifferentiated, and sporadic and hereditary medullary thyroid cancers, thyroid lymphoma and thyroid metastases from primaries outside the thyroid gland; extent of thyroidectomy; extent of lymph node dissection; aerodigestive tract resection; postoperative follow-up and surgery for recurrence and distant metastases., Conclusion: These evidence-based recommendations for surgical therapy reflect various "treatment corridors" that are best discussed within multidisciplinary teams and the patient considering tumor type, stage, progression, and inherent surgical risk.

Unlabelled: The clinical significance of (18)F-FDG-PET/CT in the follow-up of patients with differentiated thyroid carcinoma was evaluated and the results were compared with those of (18)F-FDG-PET, (131)I-whole-body scintigraphy including SPECT/CT (WBS) and ultrasound. In addition, it was the aim to investigate the impact of (18)F-FDG-PET/CT on the therapeutic management., Patients, Methods: 327 patients (209 women, 118 men; mean age 53 ± 18 years) with differentiated thyroid cancer (242 papillary, 75 follicular, 6 mixed, 1 Hürthle cell and 3 poorly differentiated tumours) were analyzed retrospectively at four tertiary referral centres. 289 (18)F-FDG-PET/CT and 118 (18)F-FDG-PET studies were performed in these patients between 2007 and 2010. In addition, an overall clinical evaluation was performed, including cytology, histology, thyroglobulin level, ultrasound, WBS, and subsequent clinical course in order to compare the molecular imaging results. Finally, the change in therapeutic management due to findings of (18)F-FDG-PET/CT was investigated., Results: The sensitivity of (18)F-FDG-PET/CT was 92%, the specificity was 95%. Sensitivity and specificity of (18)F-FDG-PET alone were 67% and 93%, respectively. WBS showed a sensitivity of 65% and a specificity of 94%. The corresponding values of ultrasound were 37% and 94%, respectively. The sensitivity of (18)F-FDG-PET/CT in the group of patients with a negative WBS (n=194) amounted to 96%. When (18)F-FDG-PET/CT and WBS were considered in combination, tumour tissue was missed in only 2 out of 133 patients; when (18)F-FDG-PET and WBS were combined, tumour tissue was missed in 1 out of 24 patients. (18)F-FDG-PET/CT resulted in management change in 43% (n=57/133) with a decision on surgical approach in 20% (n=27/133)., Conclusions: (18)F-FDG-PET/CT is superior to (18)F-FDG-PET alone in patients with differentiated thyroid cancer and has a direct impact on the therapeutic management of patients with suspected local recurrence or metastases, particularly in those with negative WBS.

Unlabelled: Differentiated thyroid carcinomas (DTC) have an excellent prognosis, with 10-year overall survival rates over 90%. In addition, DTC patients benefit from their lifelong medical surveillance. The AIM of the study was to compare the patients' overall survival with that of a matched general population., Patients and Methods: We have analyzed 1497 consecutive patients with DTC, who underwent radioiodine therapy in Münster, Germany, according to international standards. We classified our patients according to the current 7th edition of the UICC (Union Internationale Contre le Cancer) classification and we compared the overall survival of the patients with the expected survival based on age and sex of the general population as provided by the Federal Statistical Office, Germany., Results: There were no significant differences in overall survival rates between DTC patients of the cohort in stages I to IVa compared to the expected survival based on age and sex of the general population. However, patients in stage IVc showed a significantly worse overall survival rate using the log-rank test (p < 0.0001)., Conclusion: Patients with DTC showed excellent overall survival rates in stages I, II, III and IVa. All patients, except for those in stage IVc (M1 ≥ 45 years), had overall survival rates similar to the general population.

Endothelin (ET) receptor dysregulation has been described in a number of pathophysiological processes, including cardiovascular disorders, renal failure, and cancer. The aim of this study was to evaluate the expression of the ET-A receptor (ET(A)R) in murine models of thyroid carcinoma using optical imaging methods. A recently developed near-infrared fluorescent tracer was first assessed in isolated artery preparations for its functional performance in comparison with known ET(A)R antagonists BQ123 and PD156707. Before evaluation of the tracer in vivo, different thyroid carcinoma cell lines were characterized with respect to their ET receptor expression by RT-PCR and autoradiography. In vivo, sc and orthotopic papillary thyroid tumor xenografts were clearly visualized by fluorescence reflectance imaging and fluorescence-mediated tomography up to 48 h after injection of the tracer. Binding specificity of the probe was demonstrated by predosing with PD156707 as a competing inhibitor. In conclusion, optical imaging with a fluorescent ET(A)R tracer allows the noninvasive imaging of tumor-associated ET(A)R expression in vivo. In the future, this technique may help surgeons to evaluate lesion dimensions in intraoperative settings (e.g. thyroidectomy).

Aim: Radioiodine remnant ablation (RRA) after (near-)total thyroidectomy (TE) is a key element in patients with differentiated thyroid cancer (DTC). The use of exogenous TSH stimulation (rhTSH) prior to RRA has shown promising results as compared to conventional thyroid hormone withdrawal (THW). As yet, the efficacy of RRA after brief THW and single rhTSH administration has not been assessed., Patients, Methods: The study sample comprised 147 patients with DTC referred to our center between May 2008 and September 2010. All patients received TE with subsequent RRA. None of these 147 patients had evidence of distant metastasis. 93 patients had endogenous TSH stimulation 4-5 weeks after surgery (group I) and twenty-six received two rhTSH injections (group II). 28 patients were treated with a single rhTSH injection after a brief THW (group III). RRA-Efficacy was assessed three months after therapy by diagnostic whole-body scan and measurement of the tumour marker thyroglobulin (Tg) under TSH stimulation., Results: Three categories of success were defined for remnant ablation. Based on the definition of successful remnant ablation no visible uptake and a Tg ≤ 2.0 ng/ml (category 1) was seen in 62/93 patients in group I, in 17/26 patients in group II (p = n.s.) and in 12/28 patients in group III (p < 0.05). Visible radioiodine uptake and a Tg ≤ 2.0 ng/ml (category 2) was seen in 16/28 patients of group III and thus significantly more frequent than in group I (28/93 patients) (p < 0.01). However, patients in group III (16/28 patients) and group II (8/26 patients) showed no significant difference in this category (p = n.s.). Visible radioiodine uptake and a Tg > 2.0 ng/ml (category 3) was found in 3/93 patients in group I and 1/26 patients in group II but in no patient in group III., Conclusion: The third strategy of remnant ablation using a single injection of rhTSH after a brief THW period resulted in a significant higher rate of patients with residual uptake in the thyroid bed and a Tg level below 2 ng/ml three months after remnant ablation in comparison to THW. However, the overall efficacy of the third protocol was not significantly different as compared to two rhTSH injections. Under the aspect of the supply shortage of rhTSH the combined endogenous and exogenous TSH stimulation may be an attractive alternative for remnant ablation in differentiated thyroid cancer.

Objective: The Multicentre Study Differentiated Thyroid Cancer (MSDS) collective represents a well-defined group of patients with thyroid carcinomas with extrathyroidal extension. The aim of the present study was to evaluate the relationship of the primary tumour size with clinicopathological features as well as the outcome of patients with minimum and extensive extrathyroidal growth (pT3b- and pT4a-tumours; UICC 2002/2003, 6th ed)., Methods: The tumour diameter was available in 324 out of 351 MSDS patients (244 females, 80 males). Mean age of patients was 47.7±12.0 years (range, 20.1-69.8 years), and the median follow-up was 6.2 years. The relationship between primary tumour size and the following clinicopathological data was investigated: age, gender, histological tumour type (papillary thyroid carcinomas (PTC) versus follicular thyroid carcinomas (FTC)) and UICC/AJCC TNM classification. In addition, the correlation between primary tumour size and event-free and overall survival was assessed., Results: The FTC of our series were significantly larger than PTC (3.46 vs 1.84 cm; P<0.001). Patients suffering from pT3b-tumours presented with significantly smaller tumour size than those with extensive extrathyroidal growth (pT4a-tumours) (1.9 vs 3.0 cm; P<0.01). All patients with distant metastases suffered from tumours >2 cm. Furthermore, event-free and overall survival were significantly correlated with increasing tumour size (P<0.05). Using multivariate analysis, a pT4a-category and a tumour diameter >2 cm remained independent predictors of survival., Conclusions: In patients suffering from differentiated thyroid carcinoma with extrathyroidal growth (pT3b and pT4a), the tumour size is an independent predictor of event-free and overall survival.

Unlabelled: The Multicentre Study Differentiated Thyroid Cancer (MSDS) collective represents a well defined group of patients with locally aggressive thyroid carcinomas (pT4; AJCC/UICC 1997). The aim of the present study was to compare the survival of patients with minimum and extensive extrathyroidal growth according to the new AJCC/UICC TNM staging system 2009., Patients, Methods: The follow-up data of 347 patients were analysed. Patients were reclassified according to the current AJCC/UICC 2009 classification. The event-free and overall survival was evaluated using Kaplan-Meier analysis. In addition, postoperative complications and status of disease were documented., Results: 327 patients were assigned to stage pT3 and 20 patients to stage pT4a, respectively. Median follow-up was 6.1 years (range 0.04-9.8 years). 92.5% of patients reached complete remission. There were 7.8 % recurrences in the thyroid bed, in locoregional lymph nodes and/or in distant sites. The overall survival was >98% both in pT3 and pT4a patients (p = n. s.). In contrast, the event-free survival was significantly less favourable in pT4a patients (p < 0.001). Using multivariate analysis the following parameters were significant predictors of event-free survival: histological tumour type, degree of extrathyroidal extension and nodal metastasis (p < 0.05)., Conclusions: The MSDS patients with locally aggressive differentiated thyroid cancer showed an excellent overall survival during a median follow-up of 6.1 years. According to the current AJCC/UICC 2009 classification, pT3 patients with minimal extrathyroidal extension revealed a significantly better event-free survival than pT4a patients with extensive extrathyroidal growth.

According to the literature, the prevalence of papillary thyroid microcarcinoma (PTMC) is increasing. To date, PMTC account for up to 30% of all differentiated thyroid cancers. Patients with PTMC have an excellent prognosis with a normal life expectancy. Because of the differential definitions of the PTMC, the therapeutic approaches of the national Scien-tific Societies have not been standardized. The therapeutic algorithms have to be adjusted with regard to thyroid surgery, radioiodine ablation and thyrotropin-suppressive therapy as well as follow-up. Recently, the Therapy Committee of the European Society of Nuclear Medicine (EANM) has recommended a risk-adapted therapy and follow-up. Risk factors which require a more aggressive therapeutic approach are multifocality, thyroid capsule infiltration, evidence of locoregional or distant metastasis and unfavourable histology. It was the aim of this review to evaluate the current therapeutic concepts in patients with PTMC from a nuclear medicine perspective.

Aim: Evaluate the clinical benefit of external beam radiotherapy (RTx) for locally invasive thyroid carcinoma with follicular cell differentiation (DTC)., Patients, Methods: The Multicentre Study on Differentiated Thyroid Cancer (MSDS) was planned as a prospective multicenter trial on the benefit of adjuvant RTx in locally invasive DTC (pT4; UICC 1997) with or without lymph node metastases and no known distant metastases. All patients were treated with thyroidectomy, 131I-therapy, and TSH-suppression and were randomized to receive additional RTx or not. In 4/2003 the trial became a prospective cohort study after only 45 of then 311 patients had consented to randomization. 351 of 422 patients met the trial's inclusion criteria. Age was 48 +/- 12 years (mean +/- SD). 25% were men. Tumours were papillary in 90% and follicular in 10%. Of 47 patients randomized or allocated to RTx, 26 actually received RTx., Results: Mean follow-up was 930 days. In an actual treatment analysis, 96% (25/26) of the RTx-patients reached complete remission (CR) vs. 86% in the non-RTx patients. Recurrences occurred in 0 vs. 3 % of patients: 6 reoperated for regional lymph node metastases, 1 tracheal invasion treated with tracheoplasty, 1 local invasion necessitating laryngectomy, 2 distant metastases (1 lung, 1 lung + bone). Serious chronic RTx toxicity occurred in 1/26 patients., Conclusion: The MSDS trial showed low mortality and recurrence rates and a weak benefit of RTx in terms of local control that did however not reach statistical significance. Routine RTx in locally invasive DTC can no longer be recommended.

Aim: According to the procedure guidelines of the German Society of Nuclear Medicine no radioiodine ablation is necessary in patients with papillary microcarcinomas in case of limited surgical resection. Few data are available with respect to the optimal management of patients with small follicular thyroid carcinomas. It was the aim to compare risk-profile and outcome of patients with small papillary (PTC) and follicular thyroid carcinomas (FTC)

Version 3 of the procedure guideline for (131)I whole-body scintigraphy (WBS) is the counterpart to the procedure guideline for radioiodine therapy (version 3) and specify the interdisciplinary guideline for thyroid cancer of the Deutsche Krebsgesellschaft concerning the nuclear medicine part. (131)I WBS 3-6 months after (131)I ablation remains a standard procedure in an endemic area for thyroid nodules and the high frequency of subtotal surgical procedures. Follow-up without (131)I WBS is only justified if the following preconditions are fulfilled: low-risk group pT1-2, pN0 M0 with histopathologically confirmed pN0, (131)I uptake <2%, (131)I WBS during ablation without any suspicious lesion, stimulated thyroglobulin (Tg)-level 3-6 months after ablation <2 ng/mL, and absence of anti-thyroglobulin-antibodies with normal recovery-testing. If patients from the low-risk group show normal (131)I WBS 3-6 months after ablation and stimulated Tg is of <2 ng/mL, there will be no need for additional routine (131)I WBS. If patients from the high-risk group show normal (131)I WBS and stimulated Tg-level of <2 ng/mL 3-6 months after ablation, the follow-up care should include repeated stimulated Tg-measurements. If the Tg-level remains below 2 ng/mL, an additional (131)I WBS will be not necessary. The recommended intervals for stimulated Tg-testing are adapted to the prior intervals for (131)I WBS-testing in the high-risk group. Increased anti-thyroglobulin-antibodies or incomplete recovery-testing make an individual strategy of follow-up care necessary, which include (131)I WBS.

The procedure guideline for radioiodine therapy (RIT) of differentiated thyroid cancer (version 3) is the counterpart to the procedure guideline for (131)I whole-body scintigraphy (version 3) and specify the interdisciplinary guideline for thyroid cancer of the Deutsche Krebsgesellschaft concerning the nuclear medicine part. Recommendation for ablative (131)I therapy is given for all differentiated thyroid carcinoma (DTC) >1 cm. Regarding DTC < or =1 cm (131)I ablation may be helpful in an individual constellation. Preparation for (131)I ablation requires low iodine diet for two weeks and TSH-stimulation by withdrawal of thyroid hormone medication or by use of recombinant human TSH (rhTSH). The advantages of rhTSH (no symptoms of hypothyroidism, lower blood activity) and the advantages of endogenous TSH-stimulation (necessary for (131)I-therapy in patients with metastases, higher sensitivity of (131)I whole-body scan) are discussed. In most centers standard activities are used for (131)I ablation. If pretherapeutic dosimetry is planned, the diagnostic administration of (131)I should not exceed 1-10 MBq, alternative tracers are (123)I or (124)I. The recommendations for contraception and family planning are harmonized with the recommendation of ATA and ETA. Regarding the best possible protection of salivary glands the evidence is insufficient to recommend a specific setting. To minimize the risk of dental caries due to xerostomia patients should use preventive strategies for dental hygiene.

The procedure guideline for radioiodine ((131)I) therapy and (131)I whole-body scintigraphy of differentiated thyroid cancer in paediatric patients is the counterpart to the procedure guidelines (version 3) for adult patients and specify the interdisciplinary guideline for thyroid cancer of the Deutsche Krebsgesellschaft concerning the nuclear medicine part. Characteristics of thyroid cancer in children are the higher aggressiveness of papillary thyroid cancer, the higher frequency of extrathyroidal extension and of disseminated pulmonary metastases as well as the high risk of local recurrences. Radioiodine therapy is generally recommended in children, the (131)I activity depends on the children's body weight. Radioiodine ablation in children with small papillary cancer (< or =1 cm) should be considered. TSH stimulation is reached two weeks (children) or three weeks (adolescents) after withdrawal of thyroid hormones. Anti-emetic drugs are highly recommended. CT of the chest and examination of pulmonary function are clearly indicated if there is any suspicion on metastases. 3-6 months after (131)I ablation, the (131)I whole-body scintigraphy is highly recommended as lymph node metastases are frequently detected in paediatric patients. Follow-up care should be arranged in shorter intervals than in adults to test the compliance and to adapt dosage of thyroid hormones to the children's body weight. Reference values of fT3 are higher in children than in adults. Evidence is insufficient to describe in which constellation the TSH may be kept within the low normal level. Therefore, TSH suppression is generally recommended.

Aim: For the examination of the impact on clinical practice of the guidelines for differentiated thyroid carcinoma (DTC), treatment data from the ongoing Multicenter Study Differentiated Thyroid Carcinoma (MSDS) were analyzed., Patients, Methods: Patients were randomized to adjuvant external beam radiotherapy (RTx) or no RTx in addition to standard therapy in TNM stages pT4 pN0/1/x M0/x (UICC, 5th ed. 1997). All patients were to receive the same treatment regimen consisting of thyroidectomy, ablative radioiodine therapy (RIT), and a diagnostic 131I whole-body scintigraphy (WBS) 3-4 months after RIT., Results: Of 339 eligible patients enrolled between January 2000 and March 2004, 273 could be analyzed. Guideline recommendations by the German Society for Nuclear Medicine from 1999 and 1992 were complied with within 28% and 82% with regard to the interval between surgery and RIT (4 vs. 4-6 weeks), in 33% and 84% with regard to 131I activity for RIT (1-3 vs. 1-4 GBq; +/- 10%), and in 16% and 60% with regard to 131I activity for WBS (100-300 vs. 100-400 MBq; +/- 10%)., Conclusions: The 1999 guideline revision appears to have had little impact on clinical practice. Further follow-up will reveal if guideline compliance had an effect on outcomes.

The procedure guidelines for radioiodine therapy (RIT) of differentiated thyroid cancer (version 2) are the counter-part to the procedure guidelines for (131)I whole-body scintigraphy (version 2) and specify the interdisciplinary guidelines for thyroid cancer of the Deutsche Krebsgesellschaft and the Deutsche Gesellschaft für Chirurgie concerning the nuclear medicine part. Compared with version 1 facultative options for RIT can be chosen in special cases: ablative RIT for papillary microcarcinoma

Papillary thyroid microcarcinomas

Background and Purpose: The indication for adjuvant postoperative radiotherapy in patients with differentiated thyroid carcinoma (DTC) extending beyond the thyroid capsule has been an issue of controversy during the past 2 decades. No randomized studies evaluating the benefit of radiotherapy have been published so far. In the Multicenter Study Differentiated Thyroid Carcinoma (MSDS), a randomization has been performed concerning external-beam radiotherapy in patients with DTC extending beyond the thyroid capsule (pT4 pN0/1/x cM0, TNM classification, 5th edition, 1997) following surgery and radioiodine therapy. Radiation-associated toxicity has been prospectively evaluated., Patients and Methods: Radiotherapy was performed with 50.4 Gy (pN0) or 54.0 Gy (pN1/x) to the cervical, supraclavicular and upper mediastinal lymph nodes. A total dose of 59.4 Gy (R0 resection) or 66.6 Gy (R1) was used to treat the tumor bed. Conventional fractionation was used with 1.8 Gy/d. At the time of the analysis, 36 patients were randomized or allocated to treatment arm A (with external-beam radiotherapy). Of these, 22 were treated with radiotherapy, and documentation of acute toxicity was available. Toxicity was evaluated prospectively according to the RTOG/EORTC criteria., Results: The maximal acute toxicity observed during radiotherapy was grade I in four patients, grade II in 16 patients, and grade III in two patients (9.1%; 95% confidence interval [95% CI] 1.1-29.2%). Toxicity was mainly observed at the pharynx, larynx, and skin. In 19 patients, residual toxicity within 100 days following radiotherapy was evaluated. No residual toxicity was observed in two patients. Maximal residual toxicity was grade I in 13 patients and grade II in four. No further grade III toxicity could be observed., Conclusion: The majority of patients experience mild to moderate side effects from adjuvant external-beam radiotherapy. At the first follow-up examination, most side effects have subsided. Acute toxicity is tolerable in these patients.

Aim: Elevated iodine intake is a serious problem in the diagnostic and therapeutic application of (131)iodine in patients with differentiated thyroid cancer. Therefore, iodine avoidance is necessary 3 months in advance. Additionally, endogenous stimulation requires withdrawal of thyroid hormone substitution for 4 weeks. Exogenous stimulation using recombinant human TSH (rhTSH) enables the continuous substitution of levothyroxine, which contains 65.4% of its molecular weight in iodine. Thus, a substantial source of iodine intake is maintained during exogenous stimulation. Although this amount of stable iodine is comparable to the iodine intake in regions of normal iodine supply, it may reduce the accumulation of radioiodine in thyroid carcinoma tissue. The aim of this study was to assess the iodine excretion depending on different ways of stimulation., Methods: Iodine excretion was measured in 146 patients in the long term follow up after differentiated thyroid carcinoma. Patients were separated into 2 groups, those on hormone withdrawal (G I) and rhTSH-stimulated patients on hormone substitution (G II)., Results: Iodine excretion was significantly lower in hypothyroid patients (G I, median 50 micro g/l, range: 25-600 micro g/l) than in those under levothyroxine medication (G II, median 75 micro g/l, 25-600 micro g/l, p <0.027). TSH in G I (median 57.0 micro U/ml, range: 14.4-183 micro U/ml) was significantly lower (p <0.001) than in G II (117 micro U/ml, 32.2-281 micro U/ml)., Conclusion: Iodine excretion was higher in patients under rhTSH-stimulation than after hormone withdrawal. This may indicate an increased iodine pool in rhTSH-stimulated patients (deiodination of levothyroxine), thus limiting the sensitivity of radioiodine scanning to the level of endogenous stimulation despite significantly higher TSH levels during rhTSH-stimulation.

Aim: The Multicenter Study Differentiated Thyroid Carcinoma (MSDS) is an ongoing study in Germany, Austria, and Switzerland on the clinical benefit of adjuvant external beam radiotherapy (RTx) for locally invasive differentiated thyroid carcinoma (DTC) in TNM stages pT4 pN0/1/x M0/x (5th ed. 1997)., Methods: MSDS was designed as a prospective randomized trial. Patients receive thyroidectomy, radioiodine therapy (RIT) to ablate the thyroid remnant, and TSH-suppressive L-thyroxine therapy with or without RTx after documented elimination of cervical iodine-131 uptake (http://msds-studie.uni-muenster.de)., Results: 311 patients were enrolled between January 2000 and March 2003. 279 patients met the trial's inclusion criteria. 45 consented to randomization, of whom 17 were randomized into treatment arm A (RTx) and 18 into arm B (no RTx). Advised by the trial's independent Data Monitoring and Safety Committee, the MSDS steering committee decided to terminate randomization in April 2003 and continue MSDS as a prospective cohort study. 23 of the 234 patients in the observation arm of the trial were prescribed RTx by their physicians. Thus, 14% of the trial cohort were randomized or assigned to receive RTx (in-tention-to-treat analysis). In contrast, at least 44% of all patients with pT4 papillary DTC in Germany in the nation-wide PCES study underwent RTx in 1996 (p <0.001, chi(2)-test)., Conclusions: Acceptance of external beam RTx as a treatment modality for DTC has receded to a degree that accrual of a sufficient number of patients for a randomized trial has been impossible. Observation of the trial cohort is continued in order to assess clinical event rates with and without RTx and chronic RTx toxicity.

The aim of this multicentre study was to evaluate the clinical significance of fluorine-18 fluorodeoxyglucose (FDG) positron emission tomography (PET) in differentiated thyroid carcinoma and to compare the results with both iodine-131 whole-body scintigraphy (WBS) and technetium-99m 2-methoxyisobutylisonitrile (MIBI) or thallium-201 chloride (Tl) scintigraphy. Whole-body PET imaging using FDG was performed in 222 patients: 134 with papillary tumours, 80 with follicular tumours and 8 with mixed-cell type tumours. Finally, for each case an overall clinical evaluation was done including histology, cytology, thyroglobulin level, ultrasonography, computed tomography and subsequent clinical course, to allow a comparison with functional imaging results. Sensitivity of FDG-PET was 75% and 85% for the whole patient group (n = 222) and the group with negative radioiodine scan (n = 166), respectively. Specificity was 90% in the whole patient group. Sensitivity and specificity of WBS were 50% and 99%, respectively. When the results of FDG-PET and WBS were considered in combination, tumour tissue was missed in only 7%. Sensitivity and specificity of MIBI/Tl were 53% and 92%, respectively (n = 117). We conclude that FDG-PET is a sensitive method in the follow-up of thyroid cancer which should be considered in all patients suffering from differentiated thyroid cancer with suspected recurrence and/or metastases, and particularly in those with elevated thyroglobulin values and negative WBS.

Adjuvant external radiation therapy in patients with locally advanced differentiated thyroid cancer was repeatedly controversially discussed. Results of various retrospective analyzes were contradictory and did not lead to a generally accepted consent. Nevertheless, they allow the assumption that at least subgroups of patients in a pT4 stage with no or microscopic residual disease may benefit from adjuvant external beam therapy. This publication is a review of the literature and illustrates the variety of "strategies" practiced in German clinical centers and the necessity of a prospective multicentric clinical trial.

Introduction: In patients with differentiated thyroid carcinoma, elevated serum levels of thyroglobulin (hTg) may occur in spite of otherwise negative diagnostic procedures and in particular in spite of a negative iodine-131 scan. Positron emission tomography with F-18-deoxyglucose (FDG-PET) is a potentially useful method for the detection of metastatic lesions or the recurrence of thyroid cancer. We aimed to investigate whether FDG-PET is capable of detecting metastatic lesions or recurrence in patients with differentiated thyroid carcinoma, elevated serum levels of thyroglobulin, and otherwise negative diagnostic procedures, including the iodine-131 scan., Methods: From a group of 500 patients with differentiated thyroid carcinoma, a subgroup of 32 patients had elevated serum hTg-levels, negative iodine- 131 scans, negative cervical and abdominal ultrasound, and negative X-ray of the chest. In 12 of these patients (hTg 77.8+/-94.3 ng/ml, range 1.5-277 ng/ml, median 20 ng/ml), FDG-PET was performed. All but one FDG-PET study was performed in a state of hypothyroidism (TSH 75.8+/-32.2 microIU/ml, range 31-116 microIU/ml, median 74.6 microIU/ml)., Results: In 6 of the 12 patients investigated, the FDG-PET was positive. In three of the patients, the diagnosis was confirmed by computed tomography or magnetic resonance imaging. In patients with a positive FDG-PET finding, the hTg level was 146.7+/-90.1 ng/ml (23-277 ng/ml, median 144.5 ng/ml). In contrast, in patients with a negative finding the hTg level was only 9.0+/-7.6 ng/ml (range 1.5-17 ng/ml, median 8.1 ng/ml), P=0.01., Conclusion: These preliminary results show that in patients with differentiated thyroid carcinoma, elevated hTg levels, and otherwise negative "conventional" diagnostic procedures, FDG-PET is helpful in detecting metastatic lesions.

Radioiodine scans are highly specific for detecting metastases of well-differentiated thyroid carcinomas. However, false-positive 131I whole-body scans may occur as illustrated in the following case report. In a 53-yr-old patient, abnormal 131I uptake was found in the right frontal skull 4 wk after total thyroidectomy and radioiodine therapy for papillary thyroid cancer. Bone scans and planar x-rays of the skull were unremarkable and the serum thyroglobulin level was within normal limits. X-ray CT revealed a small nodule in the right frontal sinus corresponding to the pathological focus of 131I uptake. Surgical removal and histopathological examination of this lesion yielded a mucocele, a slow-growing lesion of the paranasal sinuses accumulating mucous material. The postoperative 131I scan was unremarkable. The possibility of a false-positive finding on radioiodine scans should be considered, particularly when the serum thyroglobulin level is not elevated.

Purpose: To analyze the factors that influence survival of patients with differentiated thyroid carcinoma treated by surgical thyroidectomy, radioactive iodine, and early surgical reintervention with compartment-oriented lymphadenectomy in the case of locoregional recurrence., Methods: The survival of 500 patients with differentiated thyroid carcinoma was analyzed retrospectively with regard to mortality and survival rate (Kaplan-Meier). A total of 301 patients had papillary and 199 follicular thyroid carcinoma. The mean age of the 380 women and 120 men was 46.8 +/- 16.4 years at presentation. All patients were treated by surgical thyroidectomy, high-dose radioactive iodine, and early surgical reintervention with compartment-oriented lymphadenectomy in cases of locoregional recurrence, without routine adjuvant external radiotherapy of the neck. Patients were monitored up to 23 years, with a median follow-up time of 5.6 years., Results: Twenty-nine of 500 patients died, 19 of thyroid cancer. The corrected overall 5-year survival rate (Kaplan-Meier) was 0.92. Among patients with tumor stage pT1-3NO-1MO (low risk), none died of thyroid carcinoma (5-year survival rate, 0.97); in patients with tumor stage pT4 and/or M1 (high risk), the 5-year survival rate was 0.83. The cause of death was locoregional recurrence in eight and metastatic disease in 11. Using multivariate analysis, risk factors that significantly influence survival were local invasion (pT4), metastatic disease (M1), and age., Conclusion: In differentiated thyroid carcinoma, the use of total surgical thyroidectomy followed by high-dose radioiodine therapy and early surgical reintervention in case of locoregional recurrence yields high survival rates, even without adjuvant external radiotherapy of the neck.

Purpose: Results of survival rates in differentiated thyroid carcinoma and comparison with a review of literature are given., Patients and Methods: Four hundred and sixty-four patients with differentiated cancer of the thyroid (354 female, 110 male, range: 6 to 84 years, median: 46.8 years; 275 patients with papillary and 190 with follicular cancer) were analyzed retrospectively. All patients were treated with ablative doses of radioiodine after thyroidectomy including compartment oriented lymphadenectomy in 27 patients. All patients passed an individual systematic follow-up according to risk: "low risk" pT < or = 3NxM0 vs. "high risk" pT4 and/or M1. Early postoperative radiation was not included even in patients with local invasion (pT4)., Results: The corrected 5- and 10-year survival rates for papillary cancer are 0.91 and 0.91, for follicular cancer 0.94 and 0.78 respectively [correction of 0.94 bzw. 0.78] (p = 0.55), age ( < or = 40 years 0.96 and 0.96, > 40 years 0.90 and 0.80; p = 0.008), gender (female 0.93 and 0.92, male 0.90 and 0.70; p = 0.06) and invasion/distant metastases (pT4 and/or M1 0.83 and 0.71, other 0.97 and 0.97; p = 0.0001)., Conclusion: A systematic follow-up with an individually adapted standardized scheme is associated with high survival rates in patients with differentiated cancer of the thyroid. Early diagnosis of recurrences, locoregional lymph node and distant metastases with early surgical treatment including compartment oriented lymphadenectomy and radioiodine therapy yield high survival even without external radiation.

464 patients with differentiated thyroid carcinoma were scored and treated using a risk-oriented management scheme employing early surgical re-intervention including compartment-oriented lymph-node dissection in cases of lymph-node metastases or local recurrences without routine external radiotherapy. A multivariate analysis showed that there was no effect of lymph-node metastases on survival. The difference in survival between patients with (24%) and without (76%) lymph-node metastases (univariate analysis) were due to the coincidence of higher tumor stage (T4) and higher incidence of peripheral metastases (M1). Thus, provided surgery is efficient, N1 is not a risk factor influencing survival.

In the follow-up of differentiated thyroid carcinoma it is discussed whether the tumor-marker thyroglobulin can replace the 131I scan, especially when the thyroglobulin serum level is normal. A positive 131I scan of metastases in the follow-up of patients with differentiated thyroid carcinoma combined with a low serum thyroglobulin level is extremely rare. The literature shows a frequency of about 4%. Recently we found 3 cases with a positive 131I scan demonstrating pulmonary and bone metastases whereas the serum thyroglobulin level was low.

Twenty patients were submitted to thyroidectomy and treated with iodine-131. Ten out of them received 100 mCi, the other ten 200 mCi. The activity of the total body and of the blood was determined by experimental proceeding. The doses absorbed by blood and bone marrow were calculated on the basis of the experimentally determined values. For the exposure of the blood, a medium value of 0.44 rd/mCi was found after 100 mCi and a medium value of 0.47 rd/mCi after 200 mCi. The corresponding values for the bone marrow are 0.24 and 0.3 rd/mCi, respectively. The total exposure is thus not so high as has been indicated hitherto in literature.

During a ten-year period (1975-85) 56 patients with medullary carcinoma of the thyroid were under treatment. A family screening programme discovered such a tumour in the offspring of a 47-year-old female patient and her 56-year-old sister. In four of seven offspring from three lines of this family ultrasonography revealed changes in the thyroid. Positive preoperative pentagastrin test with stimulation of calcitonin as tumour marker resulted in the histological diagnosis of thyroid carcinoma.

59 post-therapeutic examinations of the bone marrow have been performed in 35 patients out of a group of 296 patients treated from 1969 through 1976 by postoperative iodine-131 irradiations for carcinoma of the thyroid gland. Seven patients had normal findings, twelve patients showed panmyelopathy as principal finding, and fourteen patients presented modifications of the three marrow systems in different degrees and combinations. Acute myeloid leukemia was demonstrated in two patients by examination of the bone marrow, in another case the same disease was diagnosed by an analysis of the peripheral blood count. Taking into account the dosimetric considerations of the authors and the three cases of leukemia observed within the total group of patients, a risk factor for leukemia of 7.0 X 10(-5) X rd-1 is calculated which is slightly higher than the leukemia induction rate communicated in literature (22/2646 patients; 1-2/100,000/rd/year).

Thyroid carcinoma is not a common disorder but the metastatic thyroid carcinoma manifesting thyrotoxicosis is exceedingly rare. Since Leiter et al. described the first patient with adenocarcinoma of the thyroid with functioning metastases and postoperative thyrotoxicosis in 1946, about 20 such cases have been reported. We have examined two cases of metastatic follicular thyroid carcinoma with T3-hyperthyroidism after surgical ablation of the gland. The thyrotoxicosis was induced by excessive iodine contamination during preoperative radiological examination.

Real-time ultrasound is a generally available, noninvasive and inexpensive tool allowing evaluation of the thyroid gland without any radiation exposure. The method is highly sensitive with regard to shape, size, localization and morphology of this gland. Owing to low specificity ultrasound does not yield sufficient information concerning the function and degree of malignancy of lesions in relation to the structure and echogenic pattern. In some cases it is possible to achieve the final diagnosis with ultrasound in combination with clinical and laboratory findings. The information is based on the morphology of lesions and is an ideal supplement to the functional information yielded by scintigraphic examination and makes it possible to perform fine-needle biopsy. For primary examination and during follow-up, ultrasound is indispensable as a basic imaging modality. It is extremely important that the physician should be experienced.

In a retrospective study, the hematologic parameters of 296 patients treated with iodine-131 (average: 536 mCi) for carcinoma of the thyroid gland were evaluated with respect to the different doses applied. The average observation period was 65 months. The most frequent hematologic modification was thrombocytopenia which was found in 35%, followed by erythrocytopenia in 24% of cases. The normal concentration of leucocytes was decreased in 11% and increased in 23% of cases, however, the medium value calculated for all patients showed a decrease of leucocytes by 7%. Pancytopenias were found in 4.4% of cases. The most severe decreases were presented after high doses of radio-iodine (greater than or equal to 1000 mCi). Pancytopenia may be considered as one of the causes of the death of three patients.