Value of bone marrow biopsy in Hodgkin lymphoma patients staged by FDG PET: results from the German Hodgkin Study Group trials HD16, HD17, and HD18.

Background: Bone marrow (BM) involvement defines advanced-stage Hodgkin lymphoma and thus has impact on the assignment to treatment. Our aim was to evaluate whether the established BM biopsy may be omitted in patients if 18F-fluorodeoxyglucose positron emission tomography (PET) scanning is carried out during staging. Patients and methods: Our analysis set consisted of 832 Hodgkin lymphoma patients from the German Hodgkin Study Group trials HD16, HD17, and HD18 who underwent both PET scanning and BM biopsy before treatment. All PET studies were centrally reviewed and BM was categorized as showing focal involvement or not. Results: Taking BM biopsy as reference standard, baseline PET showed a negative predictive value of 99.9% [95% confidence interval (CI) 99.2% to 100%] with true-negative results in 702 of 703 cases. The sensitivity of PET for detecting BM involvement was 95.0% (95% CI 75.1% to 99.9%) as it could identify 19 out of 20 patients with positive BM biopsy. Moreover, PET found 110 additional subjects with focal BM lesions who would have been considered negative by biopsy. Conclusions: When compared with BM biopsy, PET was able to detect focal BM lesions in a large number of additional patients. This indicates that conventional BM biopsy may substantially underestimate the actual incidence of BM involvement. Given the high negative predictive value, baseline PET scanning can safely be used to exclude BM involvement in Hodgkin lymphoma. BM biopsy should be considered only in such patients in whom PET-detected lesions lead to a change of treatment protocol. Registered trials: The trials included in this analysis were registered at ClinicalTrials.gov: HD16-NCT00736320, HD17-NCT01356680, and HD18-NCT00515554.

[Guideline for Radioiodine Therapy for Benign Thyroid Diseases (6/2022 - AWMF No. 031-003)]. / DGN-Handlungsempfehlung (S1-Leitlinie): Radiojodtherapie bei benignen Schilddrüsenerkrankungen (Stand 6/2022 ­ AWMF-Registernummer: 031-003).

This version of the guideline for radioiodine therapy of benign thyroid disorders is an update of the version, which was published by the German Society of Nuclear Medicine (Deutsche Gesellschaft für Nuklearmedizin, DGN) in co-ordination with the German Society of Endocrinology (Deutsche Gesellschaft für Endokrinologie, DGE, Sektion Schilddrüse) and the German Society of General- and Visceral-Surgery (Deutsche Gesellschaft für Allgemein- und Viszeralchirurgie, DGAV) in 2015. This guideline was harmonized with the recommendations of the European Association of Nuclear Medicine (EANM). According to the German "Directive on Radiation Protection in Medicine" the physician specialised in nuclear medicine ("Fachkunde in der Therapie mit offenen radioaktiven Stoffen") is responsible for the justification to treat with radioiodine. Therefore, relevant medical indications for radioiodine therapy and alternative therapeutic options are discussed within the guideline. This procedure guideline is developed in the consensus of an expert group. This fulfils the level S1 (first step) within the German classification of Clinical Practice Guidelines.

Evaluation of interim PET response criteria in paediatric Hodgkin's lymphoma--results for dedicated assessment criteria in a blinded dual-centre read.

BACKGROUND: The aim of this study was to evaluate the use and reliability of the new positron emission tomography (PET)-based response criteria for interim positron emission tomography (iPET) in patients with paediatric Hodgkin's lymphoma (pHL). Particular emphasis was put on interobserver variability and on identification of a visual cut-off defining patients with very low risk for relapse. PATIENTS AND METHODS: The iPET scans of 39 pHL patients were evaluated in two independent centres by two PET-experienced specialists in nuclear medicine (blinded read, centre consensus) each. The iPET scans were interpreted using a 5-point scale and were compared with the outcome. Cohen's kappa-test (κ) was used to analyse the interobserver agreement. RESULTS: Concordant ratings were assessed in 19 patients with iPET-negative findings, in 11 patients with iPET-positive findings and in 2 patients with inconclusive ratings. A 'substantial agreement' between attended centres was achieved (κ = 0.748). All patients suffering relapse were concordantly identified, taking mediastinal blood pool structures (MBPS) as visual cut-off between PET-positive and PET-negative findings, respectively. All pHL patients with uptake lower than or equal to MBPS remained in complete remission. CONCLUSION(S): The iPET interpretation assured low interobserver variability. High sensitivity for identification of pHL patients suffering relapse is achieved if [18F]-fluorodeoxyglucose uptake above the MBPS value is rated as a PET-positive finding.

[18F]-fluorodeoxyglucose-positron emission tomography for the assessment of histopathologic response and prognosis after completion of neoadjuvant chemotherapy in gastric cancer.

BACKGROUND AND OBJECTIVES: Neoadjuvant chemotherapy is applied to improve the prognosis of patients with advanced gastric cancer. However, only a major histopathological response will provide a benefit. Recent studies suggest that [(18)F]-fluorodeoxyglucose-positron-emission-tomography (FDG-PET) correlates with response and survival in patients with gastroesophageal adenocarcinomas undergoing neoadjuvant chemotherapy. We evaluated the potential of FDG-PET for the assessment of response and prognosis in the multimodality treatment of gastric cancer. METHODS: Study patients were recruited from a prospective observation trial. Forty two patients with advanced gastric cancer received neoadjuvant chemotherapy and subsequently 40 patients underwent standardized gastrectomy (2 patients with tumor progression had therapy limited to palliative chemotherapy without surgery). Histomorphologic regression was defined as major response when resected specimens contained <10% vital tumor cells. FDG-PET was performed before and 2 weeks after the end of neoadjuvant chemotherapy with assessment of the intratumoral FDG-uptake [pre-treatment standardized uptake value (SUV1); post-treatment SUV (SUV2); percentage change (SUVDelta%)]. RESULTS: Histomorphological tumor regression was confirmed as a prognostic factor (P = 0.039). No significant correlations between SUV1, SUV2, or SUVDelta% and response or prognosis were found. CONCLUSION: FDG-PET seems not to be an imaging system that effectively characterizes major/minor response and survival in patients with gastric cancer following multimodality treatment.

[PET and diagnostic technology evaluation in a global clinical process. DGN's point of view]. / Vorbehalte der DGN zur Nutzenbewertung der PET durch das IQWiG.

The German Society of Nuclear Medicine (DGN) criticizes the methodological approach of the IQWiG for evaluation of PET and the conclusions, which represent the opposite point of view compared to the most other European countries and health companies in the USA: 1.) Real integration of experienced physicians into the interpretation of data and the evaluation of effectiveness should be used for best possible reporting instead of only formal hearing. 2.) Data of the National Oncologic PET Registry (NOPR) from the USA have shown, that PET has changed the therapeutic management in 38% of patients. 3.) The decision of the IQWiG to accept outcome data only for their benefit analyses, is controversial. Medical knowledge is generated by different methods, and an actual analysis of the scientific guidelines has shown that only 15 % out of all guidelines are based on the level of evidence demanded by the IQWiG. Health economics has created different assessment methods for the evaluation of a diagnostic procedure. The strategy chosen by the IQWiG overestimated the perspective of the population and undervalue the benefit for an individual patient. 4.) PET evaluates the effectiveness of a therapeutic procedure, but does not create an effective therapy. When the predictive value of PET is already implemented in a specific study design and the result of PET define a specific management, the trial evaluate the whole algorithm and PET is part of this algorithm only. When PET is implemented as test during chemotherapy or by the end of chemotherapy, the predictive value of PET will depend decisively on the effectiveness of the therapy: The better the therapy, the smaller the differences in survival detected by PET. 5.) The significance of an optimal staging by the integration of PET will increase. Rationale is the actual development of "titration" of chemotherapy intensity and radiation dose towards the lowest possible, just about effective dosage. 6.) The medical therapy of malignancies will be improved continuously. It is the claim of the health insurances to implement innovative therapeutic approaches in controlled clinical trials with tools of quality control. The monitoring committee is responsible for the safety of the patients. PET is part of the health care. Internationally accepted rules for clinical trials stipulate that any interim analyses of those trials are confidential as long as recruitment is active. The delay until evidence is documented by the published final analysis is methodologically accepted and not a characteristic of PET. 7.) Procedures in nuclear medicine without the use of PET-tracers with short half-life will increase the radiation exposure of the patients; the use of non-PET-tracers with longer half-life is in contravention of the German regulation of radiation protection.

[Nuclear medical inpatient treatment in Germany - analysis of structured quality reports 2004-2008]. / Stationäre nuklearmedizinische Therapie in Deutschland - Analyse der strukturierten Qualitätsberichte 2004 bis 2008.

UNLABELLED: All public licensed hospitals of Germany are obligated since 2004 to establish and to publish a structured biennial quality report. The aim of this study was to analyse the quality reports from 2008 of clinics with nuclear-medicine therapy ward and to investigate developments for the inpatient nuclear-medicine therapy by comparing the results with the quality reports of the years 2004 and 2006. METHODS: All available structured quality reports of clinics with a nuclear-medicine therapy ward of the years 2004, 2006 and 2008 were evaluated. RESULTS: The total number of inpatient treatment cases in 2008 amounted to 54190 (2006: 54884; 2004: 57366). This corresponds to a decrease of 5.5% in comparison to 2004. The number of the therapy wards decreased at the same time to currently 117 (2006: 120; 2004: 124). Remarkable changes were found in the spectrum of the main diagnosis. Thus, the most frequent diagnosis with the ICD-code E05 (hyperthyroidism) decreased continuously from 37747 treatments in 2004 and 34764 in 2006 to 31756 in the year 2008. In contrast, the ICD-diagnoses for thyroid cancer (C73, Z08) with 14761 cases in 2008 increased with time (2006: 13426; 2004: 12581). CONCLUSIONS: In analogy to the observations from Europe after introduction of an iodine prophylaxis the improved iodine supply in Germany has led to a decline of the radioiodine therapy due to hyperthyroidism.

Recombinant human TSH versus hypothyroidism. Cost-minimization-analysis in the follow-up care of differentiated thyroid carcinoma.

UNLABELLED: The primary aim of this study was to compare pharmacoeconomic effects of hypothyroidism secondary to hormone withdrawal (THW) and recombinant human TSH (rhTSH) for follow-up WBS in patients with differentiated thyroid cancer (DTC). The second aim was to determine patients' preference for one procedure or the other. PATIENTS, METHODS: This retrospective survey included 327 patients with DTC who underwent at least one in-hospital WBS with rhTSH between 1999 and 2006. They had also undergone THW for WBS. Patients received a two-page questionnaire via mail addressing five symptoms and ten items regarding managing their daily life which was answered by 61.6%. The responder group did not differ from the entire group. The medical and societal cost of both procedures for diagnostic WBS was calculated including direct and all ascertainable indirect cost for the reference year 2005. A sensitivity analysis included the German DRG system of 2007 and 2010. RESULTS: After THW, 94% of patients reported hypothyroid symptoms. Using rhTSH, symptoms occurred significantly less. As a result, 97% of patients favored rhTSH over THW. Mean absence from salaried work was 12.3 days after THW compared to 4 days with rhTSH. Family members of salaried employees missed 3 and 0.7 workdays after THW and rhTSH, respectively. Almost twice as often, medical attention was sought after THW (36%) compared to rhTSH (19 %). Undergoing THW, 48% of patients still used their car while hypothyroid. Our cost calculation revealed a slight benefit of about 89.00 Euro in favour of rhTSH stimulation. CONCLUSION: Hypothyroidism after THW causes significant morbidity and safety risks. The clinical and societal benefits associated with rhTSH are roughly gained at equivalent overall cost to that of THW.

Risk stratification of patients with locally aggressive differentiated thyroid cancer. Results of the MSDS trial.

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.

FDG-PET for assessment of early treatment response after four cycles of chemotherapy in patients with advanced-stage Hodgkin's lymphoma has a high negative predictive value.

BACKGROUND: As positron emission tomography (PET) seems to be a powerful prognostic marker in the treatment of Hodgkin's lymphoma (HL), we analysed the prognostic value of PET after four cycles of combination therapy with bleomycin, etoposide, doxorubicin, cyclophosphamide, vincristine, procarbazine and prednisone (BEACOPP) in patients with advanced-stage HL. PATIENTS AND METHODS: From January 2004 to March 2007, 50 patients with newly diagnosed HL in clinical stages IIB with large mediastinal mass or extranodal disease, III and IV were treated according to the HD15 protocol of the German Hodgkin Study Group. All patients received a PET scan after four cycles of BEACOPP (PET-4). RESULTS: Of the overall group, 14 of 50 patients had a positive PET-4 while 36 had a negative PET-4. At a median observation time of 25 months, 2 of the 14 patients with a positive PET-4 had progressed or relapsed, while there was no progression or relapse in PET-4-negative patients. CONCLUSION: Our results indicate a very good negative predictive value of PET-4 in advanced-stage HL patients treated with BEACOPP.

MIBI scintigraphy in hypofunctioning thyroid nodules--can it predict the dignity of the lesion?

AIM: Several authors have investigated the value of technetium-MIBI scanning to predict the dignity of hypofunctioning, cold thyroid nodules (HTN) in regions with differing levels of iodine supply. They concluded that an MIBI scan can exclude thyroid malignancy, although comparisons between the studies are of limited value owing to differences in methodology and wide variations in patient selection criteria. The present study investigates whether the above claim is also valid in Germany, a country with a long-standing and persistent, mild iodine deficiency and a high incidence of nodules in large goiters with a low prevalence of malignancy. PATIENTS, METHODS: The study compares the results of 99mTc-MIBI scintigraphy (incl. SPECT and planar images) in HTN (MIBI) with those of fine-needle aspiration biopsy (FNAB) and histology. Of 154 consecutive patients (121 women, 33 men; mean age 56 +/- 12 years), 73 underwent thyroid surgery from which the results of FNAB and MIBI were assessed. Selection criteria were risk estimation or conditions limiting the feasibility of FNAB. The mean thyroid volume was 42 +/- 25 ml, with 2.1 +/- 1.4 nodules per patient. RESULTS: Histology revealed thyroid malignancies in 8 out of 73 patients (11.0%). The negative predictive value for MIBI was 97%, which is comparable to FNAB (94%). However, in 19.5% of patients FNAB was indeterminate. Lower specificity (54%) and low positive predictive value (19%) showed that MIBI accumulation cannot differentiate between malignant and benign thyroid nodules. However, comparison with cytological and/or histological findings indicated that it could distinguish between lesions with differing rates of mitochondrial metabolism. CONCLUSION: Even in areas of former or mild iodine deficiency MIBI forms a basis for choosing between wait-and-see and surgical strategies if FNAB is unfeasible or not representative. However, even for pathological MIBI results, the prevalence of malignancy is not very high.

Combined Early and Late [68Ga]PSMA-HBED-CC PET Scans Improve Lesion Detectability in Biochemical Recurrence of Prostate Cancer with Low PSA Levels.

PURPOSE: Our aim was to evaluate the benefit of early (1 h post-injection (p.i.)) and late (3 h p.i.) [68Ga]PSMA-HBED-CC positron emission tomography (PET)/x-ray computed tomography (CT) imaging for detection of biochemical recurrence (BCR) of prostate cancer (PCa). PROCEDURES: Seventy patients with BCR of the PCa and prostate-specific antigen (PSA) levels of less than 2.0 µg/l were subjected to [68Ga]PSMA-HBED-CC PET (mean injected activity 180 MBq). While early imaging contained whole body scans, late imaging was confined to the pelvis and the lower abdomen. Uptake in suspicious lesions was analyzed by peak and maximum standardized uptake values (SUVpeak/max). Tumor-to-background ratios were calculated for all lesions in which the liver served as reference organ. The Wilcoxon matched-pair signed-rank test was used to compare the uptake in suspicious lesions between early and late imaging. Follow-up data were used to validate the existence of the additionally detected lesions. RESULTS: Forty-four of the 70 patients thus examined were interpreted as PSMA-positive in early and/or late scans while 26 remained without suspicion of PSMA tracer uptake. A total of 70 suspicious lesions were analyzed. Ten tumor-suspicious lesions from seven different patients were better or exclusively visible in the late measurements while three tumor-suspicious lesions from three different patients were better or exclusively visible in the early images. A validation by follow-up data was possible for 11 of these 13 additionally detected lesions. In direct comparison between early and late imaging, the mean SUVmax in PSMA-positive lesions was 74 % higher (p < 0.001) and the mean SUVpeak was 36 % higher (p = 0.001) in the late scans. The SUVmean in the reference regions was decreasing in the late measurements, whereas the mean TBR increased by a factor of 3 (p < 0.001). Taking confirmed lesions only into account, we estimated a 10 % gain in additionally detected PSMA-positive lesions (7/70) within the patient cohort. CONCLUSIONS: The time period between injection and data acquisition influences the detection rate of [68Ga]PSMA-HBED-CC PET/CT. In biochemical recurrence with low PSA levels, late [68Ga]PSMA-HBED-CC PET/CT imaging offers frequent advantages with regard to lesion contrast.

[Interactions between brain, psyche and thyroid]. / Interaktionen zwischen Gehirn, Psyche und Schilddrüse.

Interactions between brain, psyche and thyroid are known from historical descriptions of thyroidectomy (Kocher) and hyperthyroidism. However, their importance is often underscored in clinical routine. Thyroid hormone deficiency during pregnancy may result in irreversible mental retardation and requires levothyroxine substitution. TSH screening after delivery must identify newborns with congenital hypothyroidism: An early levothyroxine substitution and long term therapy control are required. Hypothyroidism and depression have many symptoms in common. Cognitive deficits and depressive states are often found in overt hypothyroidism, psychotic derangements are rare. Levothyroxine improves hypothyroid symptoms and mental performance, mood and motivation. Psychic symptoms of hyperthyroidism include agitation, irritability, mood disturbances, hyperactivity, anxiousness and even panic attacks. Manic and delusional states are rare. In geriatric patients hyperthyroidism may be oligosymptomatic. In psychiatric patients more frequent but unspecific disturbances of thyroid laboratory values being reversible without specific therapy have to be distinguished from rather rare but causative organic thyroid diseases with therapeutic consequences. Some psychiatric drugs influence thyroid laboratory results. Hypothyroidism in depressive patients is a negative prognostic parameter and requires therapy. Psychiatric symptoms associated with hypothyroidism are usually reversible under levothyroxine within 4-8 weeks. The standard for hypothyroidism is mono-levothyroxine therapy.

[Obesity, energy regulation and thyroid function: is borderline elevated TSH-level the cause or secondary phenomenon of obesity]. / Adipositas, Stoffwechsel und Schilddrüse. Ist der grenzwertig hohe TSH-Spiegel Ursache oder Sekundärphänomen der Adipositas?

Several population-based studies have shown a significant association between TSH-level and BMI (body mass index). About 30% of the rest energy expenditure are regulated by thyroid hormones, which generated the hypothesis that thyroid hormone substitution with TSH-titration into the lower reference levels may prevent body weight gain. The opposite effect of thyroid hormones is appetite stimulation, which may be responsible for body weight gain in case of substitutive medication. The association between TSH and BMI has become a complex topic in the light of the endocrine activity of adipocytes. Adipocytes are not a silent fat mass, but increase the hormone level of leptin, which influences neurones in the hypothalamus, the thyreotropic axis and TSH secretion. BMI is positively correlated with serum leptin. Elevated leptin levels, endogenous in individuals with high BMI or exogenous after leptin injection for treatment of hypothalamic amenorrhoea, shift TSH in the upper reference level. Borderline elevated TSH levels are reversible in case of body weight reduction in obese persons. It remains unclear whether high TSH levels or high leptin level are responsible for obesity or represent secondary phenomenon. Recommendation for daily practice: Borderline elevated TSH-levels in obese patients will decrease in case of body weight reduction without hormone medication. After definitive treatment of hyperthyroidism patient's history for use of carbohydrates (increased during hyperthyroidism) should be noticed and substitution with thyroid hormones aims at TSH in the lower reference level. As body weight gain is observed in all TSH groups, a special concept for prevention and therapy of obesity (diet, daily exercise, behaviour training) should be initiated early and additionally to medication.

[Routine measurement of serum calcitonin in patients with nodular thyroid disorders?]. / Calcitonin-Screening bei der Knotenstruma?

In spite of the fact that the German Society of Endocrinology has recommended calcitonin as screening-parameter the majority of physicians in Germany do not routinely use calcitonin in patients with thyroid nodules to exclude medullary thyroid cancer (MTC). The future revision of the recommendation should describe reference values for each commercially available assay, separately for men and women (basal and after pentagastrin-stimulation), and should define sonomorphological inclusion criteria. The epidemiological database of the prevalence of MTC is controversial and the specificity of basal elevated calcitonin levels is limited up to the 5-fold of the upper reference level. If renal insufficiency, bacterial infection, and an alcohol- or drug-induced stimulation of calcitonin is excluded, hypercalcitoninaemia should be confirmed by a second measurement (if necessary using another assay). Stimulation of calcitonin by use of pentagastrin is mandatory prior to the decision on thyroidectomy. A stimulated calcitonin level < 100 pg/ml justifies "wait and see". If stimulated calcitonin levels range between 100 and 200 pg/ml or higher, the differentiation between C-cell hyperplasia and MTC remains uncertain, especially in men. The implementation of calcitonin-screening requires the definition of sonographic inclusion criteria and validation of each assay. Additional pre-requisites are excellent logistic (short period between blood sampling and start of the laboratory test), knowledge of differential diagnoses, knowledge of the consumption of drugs and alcohol, availability of pentagastrin-testing and of moleculargenetic testing with full information to the patients and sufficient time before the decision on surgery is made. All this and the choice of a skilled surgeon, experienced in thyroidectomy and lymphadenectomy with a low rate of local complications are the rationale to recommend calcitonin-screening primarily in centers for thyroid disorders.

Survey of management of solitary thyroid nodules in Germany.

AIM: To compare the opinions of practitioners in primary care with those of thyroid specialists in Germany on the management of solitary thyroid nodules (Papillon 2005). METHODS: Questionnaires were filled in by 2,191 practitioners and 297 thyroid specialists between June 1 and September 30, 2005. The test cases and their modifications described a solitary thyroid nodule of 2-3 cm with different levels of thyroid function and a hypoechogenic nodule of 1 cm in diameter. RESULTS: TSH determination and sonography were found to be standard procedures, followed by scintigraphy (selected by 84.7% of practitioners and 95.1% of specialists, p < 0.001) and fine needle aspiration cytology (54.5% of practitioners, 57.4% of specialists). For a hypoechogenic nodule calcitonin determination was advocated by 54.0% of endocrinologists and by 32.2% of nuclear medicine physicians (p < 0.001). A euthyroid solitary thyroid nodule would be treated medically by 77.8% of practitioners and by 85.7% of specialists, the combination of levothyroxine and iodine being clearly preferred (60.9% of practitioners and 67.1% of specialists). For a hyperfunctioning nodule the preference of radioiodine therapy was significantly higher in the specialist group (88.8%) than among the practitioners (52.2%). CONCLUSIONS: The main differences of opinion between practitioners and specialists focused on calcitonin screening and referral to radioiodine therapy.

[FDG-PET in Hodgkin lymphoma]. / FDG-PET beim Hodgkin-Lymphom.

The high negative predictive value of FDG-PET in therapy control of Hodgkin lymphoma is proven by the data acquired up to now. Thus, the analysis of the HD15 trial has shown that consolidation radiotherapy might be omitted in PET negative patients after effective chemotherapy. Further response adapted therapy guided by PET seems to be a promising approach in reducing the toxicity for patients undergoing chemotherapy. The criteria used for the PET interpretation have been standardized by the German study groups for Hodgkin lymphoma patients and will be reevaluated in the current studies.

Graves' disease and radioiodine therapy. Is success of ablation dependent on the choice of thyreostatic medication?

AIM: This study was performed to analyse the impact of the choice of antithyroid drugs (ATD) on the outcome of ablative radioiodine therapy (RIT) in patients with Graves' disease. PATIENTS, MATERIAL, METHODS: A total of 571 consecutive patients were observed for 12 months after RIT between July 2001 and June 2004. Inclusion criteria were the confirmed diagnosis of Graves' disease, compensation of hyperthyroidism and withdrawal of ATD two days before preliminary radioiodine-testing and RIT. The intended dose of 250 Gy was calculated from the results of the radioiodine test and the therapeutically achieved dose was measured by serial uptake measurements. The end-point measure was thyroid function 12 months after RIT; success was defined as elimination of hyperthyroidism. The pretreatment ATD was retrospectively correlated with the results achieved. RESULTS: Relief from hyperthyroidism was achieved in 96% of patients. 472 patients were treated with carbimazole or methimazole (CMI) and 61 with propylthiouracil (PTU). 38 patients had no thyrostatic drugs (ND) prior to RIT. The success rate was equal in all groups (CMI 451/472; PTU 61/61; ND 37/38; p = 0.22). CONCLUSION: Thyrostatic treatment with PTU achieves excellent results in ablative RIT, using an accurate dosimetric approach with an achieved post-therapeutic dose of more than 200 Gy.

Graves' disease and radioiodine therapy. Is success of ablation dependent on the achieved dose above 200 Gy?

AIM: This study was performed to determine the results of ablative radioiodine therapy (RIT) when the achieved dose in the thyroid was above 200 Gy and to characterize predictive factors for treatment outcome. PATIENTS, METHODS: A total of 571 consecutive patients were observed for 12 months between July 2001 and June 2004. Inclusion criteria were a confirmed diagnosis Graves' disease, compensation of hyperthyroidism and withdrawal of antithyroid drugs two days before preliminary radioiodine-testing and RIT. The intended dose was 250 Gy and the therapeutically achieved dose was calculated from serial uptake measurements. The end-point measure was thyroid function 12 months after RIT; success was defined as elimination of hyperthyroidism. The relation between success rate and the achieved dose, thyroid volume, age and sex of patients, TSH- and TRAb-values and presence of ophthalmopathy was analysed. RESULTS: Relief from hyperthyroidism was achieved in 96% of patients who received more than 200 Gy, even for thyroid volumes >40 ml. The success of ablative RIT was not influenced by age or sex of patients, or by TSH- or TRAb values or concomitant ophthalmopathy. The mean achieved dose in the thyroid was 298 Gy with a standard deviation of 74.6 Gy. CONCLUSION: To achieve a dose of over 200 Gy with the above standard deviation, we recommend calculating an intended dose of 250 Gy and using a dosimetric approach with early and late uptake values in the radioiodine test, to allow early therapeutic intervention should the posttherapeutic thyroid dose fall unexpectedly below 200 Gy.

99mTc-MIBI SPECT in primary hyperparathyroidism. Influence of concomitant vitamin D deficiency for visualization of parathyroid adenomas.

UNLABELLED: AIM of the study was to analyse the influence of a concomitant vitamin D deficiency on the results of (99m)Tc-MIBI studies in patients (pts) with primary hyperparathyroidism (pHPT). PATIENTS, METHODS: Between January 1998 and May 2004, 71 pts with pHPT had undergone operation after a (99m)Tc-MIBI study of whom 54 pts (76%) had normal values of 25-OH-vitamin D3 and 17 pts (24%) had vitamin D deficiency. Results of a dual-phase (99m)Tc-MIBI protocol with SPECT were compared with histopathology. RESULTS: In 54 pts with normal vitamin D values late SPECT images identified more lesions (n=51, sensitivity 91%) than early planar (n=45, sensitivity 82%) or late planar images (n=50, sensitivity 88%). In 17 pts with vitamin D deficiency late SPECT images identified more lesions (n=13, sensitivity 72%) than early planar (n=10, sensitivity 56%) or late planar images (n=10, sensitivity 56%) too. In pts with vitamin D deficiency the sensitivity of a (99m)Tc-MIBI SPECT study was lower than in those with normal vitamin D status (72% vs. 91%) and dependent on the value for PTH. However, the results did not reach statistical significance: early planar: p=0.1625; late planar: p=0.0039; (99m)Tc-MIBI SPECT: p=0.1180. CONCLUSION: The likelihood of a pathological (99m)Tc-MIBI study being obtained in pts with pHPT is dependent on the parathyroid hormone level. However, a negative influence of a low vitamin D level on the scintigraphic detection rate of a parathyroid adenoma could not be proven which may be due to the low number of pts with vitamin D deficiency.

[Lutetium-177-PSMA radioligand therapy : Consensus within the framework of GKV-funded care between the university hospitals in Aachen, Bonn, Düsseldorf, Essen, and Cologne and the MDK Nordrhein]. / Lutetium-177-PSMA-Radioligandentherapie : Konsensus im Rahmen der GKV-finanzierten Versorgung zwischen den Hochschulkliniken in Aachen, Bonn, Düsseldorf, Essen und Köln und dem MDK Nordrhein.

In the last 3 years, Lutetium-177 prostate-specific membrane antigen radioligand therapy (Lu-177-PSMA-RLT) has received increasing attention in nuclear medicine as a new form of treatment for castration-resistant metastatic prostate cancer. This therapy combines the radionuclide Lutetium-177, which has been therapeutically used in nuclear medicine for many years, with a molecular target of the transmembrane prostate-specific membrane antigen expressed by prostate cancer cells. Since there are no prospective randomized studies on Lu-177-PSMA-RLT and the question of reimbursement has repeatedly been the subject of review by the MDK Nordrhein (Medischenische Dienst der Krankenversicherung), there was a desire because of the increasing number of patients being treated to clarify under which circumstances Lu-177-PSMA-RLT can be reimbursed by German statutory health insurance. The goals of this article are to help treating physicians understand how this new therapy option works, to integrate it in the overall therapy concept for castration-resistant metastatic prostate cancer, and, above all, to use Lu-177-PSMA-RLT-based on the current data-at the right place in the therapy sequence of castration-resistant metastatic prostate cancer.