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Supplementary Figure from Enhancing Radioiodine Incorporation into Radioiodine-Refractory Thyroid Cancer with MAPK Inhibition (ERRITI): A Single-Center Prospective Two-Arm Study

Purpose:Restoration of iodine incorporation (redifferentiation) by MAPK inhibition was achieved in previously radioiodine-refractory, unresectable thyroid carcinoma (RR-TC). However, results were unsatisfactory in BRAFV600E-mutant (BRAF-MUT) RR-TC. Here we assess safety and efficacy of redifferentiation therapy through genotype-guided MAPK-modulation in patients with BRAF-MUT or wildtype (BRAF-WT) RR-TC.Patients and Methods:In this prospective single-center, two-arm phase II study, patients received trametinib (BRAF-WT) or trametinib + dabrafenib (BRAF-MUT) for 21 ± 3 days. Redifferentiation was assessed by 123I-scintigraphy. In case of restored radioiodine uptake, 124I-guided 131I therapy was performed. Primary endpoint was the redifferentiation rate. Secondary endpoints were treatment response (thyroglobulin, RECIST 1.1) and safety. Parameters predicting successful redifferentiation were assessed using a receiver operating characteristic analysis and Youden J statistic.Results:Redifferentiation was achieved in 7 of 20 (35%) patients, 2 of 6 (33%) in the BRAF-MUT and 5 of 14 (36%) in the BRAF-WT arm. Patients received a mean (range) activity of 300.0 (273.0–421.6) mCi for 131I therapy. Any thyroglobulin decline was seen in 57% (4/7) of the patients, RECIST 1.1 stable/partial response/progressive disease in 71% (5/7)/14% (1/7)/14% (1/7). Peak standardized uptake value (SUVpeak) < 10 on 2[18F]fluoro-2-deoxy-D-glucose (FDG)-PET was associated with successful redifferentiation (P = 0.01). Transient pyrexia (grade 3) and rash (grade 4) were noted in one patient each.Conclusions:Genotype-guided MAPK inhibition was safe and resulted in successful redifferentiation in about one third of patients in each arm. Subsequent 131I therapy led to a thyroglobulin (Tg) decline in more than half of the treated patients. Low tumor glycolytic rate as assessed by FDG-PET is predictive of redifferentiation success.See related commentary by Cabanillas et al., p. 4164

Supplementary Data from Enhancing Radioiodine Incorporation into Radioiodine-Refractory Thyroid Cancer with MAPK Inhibition (ERRITI): A Single-Center Prospective Two-Arm Study

ZusammenfassungAus fachfremder Sicht wird der Stellenwert der „konventionellen“ Schilddrüsenszintigrafie zur Klärung diverser thyreologischer Fragestellungen international mittlerweile weit niedriger eingeschätzt, als dies dem hierzulande tätigen Nuklearmediziner bewusst ist. Dieser Aufsatz gibt einen Überblick über häufig geäußerte Kritikpunkte an der Schilddrüsenszintigrafie und möchte einiges hierzu klarstellen sowie in berechtigten Fällen fundierte Gegenargumente liefern. In diesem Rahmen wird ein Überblick über die weiterhin bestehenden Indikationen gegeben, es werden aber auch Aspekte angeschnitten, bei denen Verbesserungsbedarf besteht. Abschließend erfolgt eine Aussicht auf zukünftige Perspektiven und Weiterentwicklungen der funktionellen Charakterisierung von thyreoidalem Gewebe.

Purpose: Restoration of iodine incorporation (redifferentiation) by MAPK inhibition was achieved in previously radioiodine-refractory, unresectable thyroid carcinoma (RR-TC). However, results were unsatisfactory in BRAFV600E-mutant (BRAF-MUT) RR-TC. Here we assess safety and efficacy of redifferentiation therapy through genotype-guided MAPK-modulation in patients with BRAF-MUT or wildtype (BRAF-WT) RR-TC. Patients and Methods: In this prospective single-center, two-arm phase II study, patients received trametinib (BRAF-WT) or trametinib + dabrafenib (BRAF-MUT) for 21 ± 3 days. Redifferentiation was assessed by 123I-scintigraphy. In case of restored radioiodine uptake, 124I-guided 131I therapy was performed. Primary endpoint was the redifferentiation rate. Secondary endpoints were treatment response (thyroglobulin, RECIST 1.1) and safety. Parameters predicting successful redifferentiation were assessed using a receiver operating characteristic analysis and Youden J statistic. Results: Redifferentiation was achieved in 7 of 20 (35%) patients, 2 of 6 (33%) in the BRAF-MUT and 5 of 14 (36%) in the BRAF-WT arm. Patients received a mean (range) activity of 300.0 (273.0–421.6) mCi for 131I therapy. Any thyroglobulin decline was seen in 57% (4/7) of the patients, RECIST 1.1 stable/partial response/progressive disease in 71% (5/7)/14% (1/7)/14% (1/7). Peak standardized uptake value (SUVpeak) < 10 on 2[18F]fluoro-2-deoxy-D-glucose (FDG)-PET was associated with successful redifferentiation (P = 0.01). Transient pyrexia (grade 3) and rash (grade 4) were noted in one patient each. Conclusions: Genotype-guided MAPK inhibition was safe and resulted in successful redifferentiation in about one third of patients in each arm. Subsequent 131I therapy led to a thyroglobulin (Tg) decline in more than half of the treated patients. Low tumor glycolytic rate as assessed by FDG-PET is predictive of redifferentiation success. See related commentary by Cabanillas et al., p. 4164

to evaluate the time trend of epidemiology of follicular cell derived thyroid cancer (TC) based on data from a well documented cancer registry.Population based data on TC from Lower Franconia (LF), Germany, within 1981 and 2015 were analysed to estimate the regional epidemiology of TC. The incidence was assessed in 5-year-intervals for gender, histology, and tumor stage.Incidence of TC solely attributable to papillary TC (PTC) doubled mainly in T1- and T2-stages within the evaluation period from 4.5 to 8.7/100.000/y in females and 1.7 to 4.1/100.000/y in males. There was no significant change of follicular TC (FTC), whereas anaplastic TC (ATC) decreased in the same interval. The number of lymph-node metastases and T3-cases increased, while the frequency of T4-stage and distant metastases decreased. Increased incidences of T1- and T2-stages suggest an over-diagnosis. In contrast, increasing number of tumors at T3-stage and with lymph node involvement contradict the over-diagnosis as the only reason for rising incidence. Declining of T4-stages in spite of increasing of T3-stages and N1-cases indicates the value of timely detection and treatment of TC. In accordance, reduced incidence of advanced cancers with M1-stage and ATC cases promote our current management of TC.Timely diagnosis and adequate risk-adopted treatment of thyroid cancer reduce the frequency of high-risk cases with distant metastases and the possible protracted dedifferentiation of TC to anaplastic features. Our analyses support the management algorithm in thyroid cancer according to the recent guidelines of German Nuclear Medicine Society.ZIEL: Evaluierung des Trends der Epidemiologie von Schilddrüsenkrebs (TC) in Unterfranken (UF).Populationsbasierte Daten aus Unterfranken aus den Jahren 1981 bis 2015 wurden analysiert und die Änderung der Inzidenz des TC ermittelt. Die Inzidenz wurde in 5-Jahres-Intervallen in Bezug auf Geschlecht, Histologie, und Tumorstadium berechnet.Die TC-Inzidenz verdoppelte sich im Auswertungszeitraum, bei Frauen von 4,5 auf 8,7/100.000/J und von 1,7 auf 4,1/100.000/J bei Männern, was überwiegend den papillären Schilddrüsenkarzinomen (PTC) in T1- und T2-Stadien zuzuschreiben ist. Es gab keine signifikante Änderung beim follikulären TC (FTC), während die Häufigkeit des anaplastische TC (ATC) abnahm. Die Anzahl der Lymphknotenmetastasen und T3-Fälle stieg, während die Frequenz der T4-Fälle und der Fernmetastasen in diesem Intervall abnahm. Eine erhöhte Inzidenz von Karzinomen in T1- und T2-Stadien ließe sich durch Überdiagnostik erklären. Im Gegensatz dazu sprechen die Zunahme der Inzidenz von Tumoren in T3- und N1-Stadien gegen eine Überdiagnose als einzigen Grund für den Anstieg. Die abnehmende Zahl von Patienten mit T4-Stadium bei gleichzeitigem Anstieg der Fälle im T3- und N1-Stadium sprechen vielmehr für eine rechtzeitige Diagnose von Schilddrüsenkarzinomen. Die abnehmende Inzidenz der weit fortgeschnittenen Fälle mit Fernmetastasen und mit ATC im gleichen Zeitraum bestätigen das bei uns verfolgte Konzept.Die rechtzeitige Diagnose und adäquate risikoadaptierte Behandlung des Schilddrüsenkarzinoms im Frühstadium reduziert die Häufigkeit von Hochrisiko-Fällen mit Fernmetastasen und verhindert die mögliche Entdifferenzierung vom DTC zu anaplastischen Tumoren. Unsere Analysen bestätigen das therapeutische Management von Schilddrüsenkrebs gemäß Leitlinien der Deutschen Gesellschaft für Nuklearmedizin.

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.

ZusammenfassungDie vorliegende Handlungsempfehlung dient als Grundlage zur Qualitätssicherung der Somatostatinrezeptor (SSTR-) PET/CT bei onkologischen Patienten. Die Leitlinie wurde interdisziplinär erarbeitet und enthält neben der Definition und Zielsetzung einen Konsens hinsichtlich der erforderlichen klinischen Hintergrundinformationen, Indikationsstellung, Durchführung, Auswertung, Dokumentation und Befunderstellung. Dabei werden die beiden gebräuchlichsten Radiotracer der SSTRPET/ CT (68Ga-DOTATOC und 68Ga-DOTATATE) vertieft dargestellt. Die SSTR-PET/CT erfordert eine enge Interaktion zwischen den zuweisenden und ausführenden Fachdisziplinen unter Berücksichtigung bereits vorhandener Leitlinien und Handlungsempfehlungen europäischer und deutscher Fachgesellschaften, namentlich der European Association of Nuclear Medicine (EANM), der Deutschen Gesellschaft für Endokrinologie (DGE), Deutschen Gesellschaft für Nuklearmedizin (DGN) und Deutschen Röntgengesellschaft (DRG).

Background: The aim of this study was to evaluate the value of 18F-FDG PET/CT (PET/CT) and MRI for local and/or whole-body restaging of adenoid cystic carcinoma of the head and neck (ACC). Methods: Thirty-six patients with ACC underwent conventional MRI of the head and neck and a whole-body PET/CT and were analysed with regards to detection of a local tumor recurrence, lymph node or distant metastases. A consensus interpretation of all available imaging data was used as reference standard. Sensitivity, specificity, diagnostic accuracy, positive and negative predictive values were calculated for MRI and PET/CT. Results: The sensitivity of PET/CT and MRI was 96% (89%), specificity 89% (89%), PPV 96% (96%), NPV 89% (73%) and accuracy 94% (89%) for detection of local tumors. Additionally, PET/CT revealed lymph node metastases in one patient and distant metastases in 9/36 patients. In three patients secondary primaries were found. Conclusions: Whole-body PET/CT in addition to MRI of the head and neck improves detection of local tumour and metastastic spread in ACC. OA Förderung 2017

Although recent data are contradictory, it is still claimed that Pressurized Intra-Peritoneal Aerosol Chemotherapy (PIPAC) would deliver an aerosol which distributes homogeneously throughout the entire abdominal cavity. 99mTc-Pertechnetat was administered in four postmortem swine using either PIPAC or liquid intra-peritoneal chemotherapy (IPC). The animals were examined by planar scintigraphy and SPECT/CT. Planar distribution images were divided into four regions of interest (ROIs: right/left upper and lower abdominal quadrant). SPECT/CT slices were scanned for areas of intense nuclide accumulation (“hot spots”). The percentage of relative distribution for planar scintigraphy was calculated by dividing the summed individual counts of each ROI by total counts measured in the entire abdominal cavity. The relative distribution of the “hot spots” was analyzed by dividing the counts of the local volume of interest (VOI) by the summed volume counts measured in the entire abdominal cavity. In all four animals, planar scintigraphy showed inhomogeneous nuclide distribution. After PIPAC only 8–10% of the delivered nuclide was detected in one ROI with a mean deviation of 40% and 74% from a uniform nuclide distribution pattern. In all animals, SPECT/CT revealed “hot spots” beneath the PIPAC Micropump, catheter tip, and in the cul-de-sac region which comprise about 25% of the total amount of delivered nuclide in 2.5% of the volume of the entire abdominal cavity. Our present data indicate that the intra-abdominal aerosol distribution pattern of PIPAC therapy is non-homogeneous and that the currently applied technology has still not overcome the problem of inhomogeneous drug distribution of IPC.

To compare the diagnostic performance of 68Ga-DOTATOC PET/MRI and 68Ga-DOTATOC PET/CT in the whole-body staging of patients with neuroendocrine tumours (NET). Thirty patients with histopathologically confirmed NET underwent PET/CT and PET/MRI in a single-injection protocol. PET/CT and PET/MRI scans were prospectively evaluated with regard to lesion count, localization, nature (NET/non-NET), and conspicuity (four-point scale). Histopathology and follow-up imaging served as the reference standards. The proportions of NET and non-NET lesions rated correctly were compared using McNemar’s chi-squared test. The Wilcoxon test was used to assess differences in SUVmax and lesion conspicuity. The correlation between the SUVmax for the same lesions from each modality was analysed using Pearson’s correlation coefficient (r). According to the reference standard, there were 197 lesions (142 NET, 55 non-NET). Lesion-based analysis showed a higher proportion of correctly rated NET lesions on PET/MRI than on PET/CT (90.8% vs. 86.7%, p = 0.031), whereas on PET/CT there was a higher proportion of correctly rated non-NET lesions (94.5% vs. 83.6%, p = 0.031). SUVmax was strongly correlated (r = 0.86; p

Background: In the present study, we sought to describe a procedure for the creation of co-registered positron emission tomography (PET) and magnetic resonance imaging (MRI) polar plots of cardiac PET/MRI examinations, validate the resulting plots against available standard methods in patients with myocardial infarction and provide examples that demonstrate the advantage of the novel approach over existing standards. Methods: Co-registered LGE and PET short-axis images were transformed into polar maps based on a radial sampling pattern. LGE was automatically detected using an automated thresholding algorithm (ATA). In 20 PET/MRI examinations in patients with acute myocardial infarction, agreement between manual LGE assessment and the ATA classification was calculated. Also agreement between MRI-segmentation based PET polar plots and standard PET polar plots (created with the Corridor4DM software package) was assessed. Results: No statistically significant difference in infarct sizes between manual and ATA segmentation was found (p = 0.12). Both methods were highly correlated (Pearson’s r = 0.96, p < 0.01). Bland-Altman analysis revealed lower and upper limits of agreement of - 4.7 g and 3.6 g. Agreement between MRI-segmentation based PET polar plots and standard PET polar plots was very high (mean kappa of 0.91 ± 0.10; p < 0.01 in all cases). In three additional patients with myocardial inflammation, the software successfully created polar plots that demonstrate the location and extent of pathologic tracer uptake in the left ventricular myocardium. Conclusion: A straightforward software approach for the creation of co-registered PET and MRI polar plots was described and successfully demonstrated in PET/MRI studies of myocardial infarction and inflammation.

Summary Aim: To evaluate the diagnostic accuracy of FDG PET/CT in the detection of asymptomatic recurrence in patients with malignant melanoma who have had resection of their primary lesion. We also aimed to determine the pattern and factors predisposing to disease recurrence. Methods: Patients with malignant melanoma who have had surgical resection of their disease and without any clinical evidence of disease recurrence were followed- up with FDG PET/CT. The diagnostic accuracy of FDG PET/CT, pattern of recurrence and factors predictive of disease recurrence were determined. Results: A total of 144 patients were followed-up for a median period of 50.50 months. Asymptomatic recurrence was seen in 37 patients (25.7 %) with a median time to recurrence of 20 months. Lymph node was the commonest site of asymptomatic recurrence. Sex, tumour depth, histology type and presence of nodal metastasis were significant predictors of tumour recurrence. Age, race, site of primary lesion, type of lymph node resection were not significant predictors of disease recurrence. Race has a significant effect on the histological subtype of tumour (nodular maligna was more common in Caucasian while acral lentiginous was more prevalent in the Blacks) and the site of the primary lesion (lower limb in Blacks and trunk in Caucasians). Sensitivity, specificity and accuracy of FDG PET/CT for the detection of disease recurrence were 94.5 %, 87.6 % and 89.6 % respectively. Conclusion: FDG PET/CT is a suitable modality for early detection of asymptomatic recurrence of malignant melanoma. Asymptomatic recurrence most commonly occurs in lymph nodes. Sex, nodal metastasis and tumour pathologic features are predictors of recurrence.

Radioiodine therapy of thyroid cancer was the first successful radionuclide therapy in the treatments of cancer, although its clinical use is empirical and not based on precise dosimetry. 124I is a positron-emitting radionuclide and positron emission tomography/computed tomography (PET/CT) with 124I currently provides the most accurate estimation of the absorbed (radiation) dose to thyroid cancer lesions. In the application, serial 124I PET/CT scans are performed to determine the time uptake curves and to delineate the volumes of the lesions. The 124I data are then used to project the absorbed dose per unit administered 131I activity. The results are part of the decision-making process to individually guide treatment plans, in particular by tailoring the therapeutic 131I activity in radioiodine therapy. The aim of this review is to provide an overview of 124I PET/CT lesion dosimetry of differentiated thyroid cancer including: 1) an historical overview; 2) the general properties of 124I and its activity measurement; 3) the main factors impairing PET image quantification; 4) an optimized lesion dosimetry protocol used in our group to make this manuscript self-contained; as well as 5) a summary of important clinical studies.

The aim of this study is to evaluate and compare the diagnostic potential of integrated whole-body [18F]FDG-PET/MRI to [18F]FDG-PET/CT for detection of a potential primary cancer and metastases in patients suspected for cancer of unknown primary (CUP).A total of 20 patients (15 male, 5 female, age 53±13 years) suspect for CUP underwent a dedicated head and neckwhole-body [18F]FDG-PET/CT (Biograph mCT 128, Siemens Healthcare) and a subsequent simultaneous [18F]FDG-PET/MRI examination (Biograph mMR, Siemens Healthcare). Two readers rated the datasets (PET/CT; PET/MRI) regarding the detection of the primary cancer and metastases, lesion conspicuity (4-point ordinal scale) and diagnostic confidence (3-point ordinal scale). PET analysis comprised the assessment of maximum standardized uptake values (SUVmax) of all PET-positive lesions using volume of interest (VOI) analysis derived from the PET/CT and PET/MR datasets. All available data considering histology and imaging including prior and clinical follow-up examinations served as reference standard. Statistical analysis included comparison of mean values using Mann-Whitney U test and correlation of SUVmax using Pearson's correlation.In 14 out of 20 patients 49 malignant lesions were present. The primary cancer could be correctly identified in 11/20 patients with both PET/CT and PET/MRI. PET/CT enabled the detection of a total 38 metastases, PET/MR respectively of 37 metastases (one lung metastasis5mm was missed). PET/CT and PET/MRI showed comparably high lesion conspicuity (2.6±0.6 each), with superior assessment of cervical lesions in PET/MRI and an indicated superior assessment of pulmonary lesions in PET/CT. Diagnostic confidence was rated comparably high in PET/CT and PET/MRI (2.7±0.5 each). The mean values of SUVmax of all PET-positive lesions (PET/MRT 7.9±4.2 vs. PET/CT 7.2±3.5) showed a strong positive correlation between the SUVs derived from both hybrid imaging systems (Pearson's correlation r=0.927).Both hybrid imaging techniques provide a comparable diagnostic ability for detection of primary cancer and metastases in patients with CUP, with comparably high lesion conspicuity and diagnostic confidence, offering superior assessment of cervical lesions in PET/MRI and potentially of pulmonary lesions in PET/CT. Furthermore, due to the significantly lower dose of ionizing radiation, PET/MRI may serve as a powerful alternative to PET/CT, particularly for therapy monitoring and/or surveillance considering the long-term cumulative dose.

ZusammenfassungDiese Handlungsempfehlung soll eine Grundlage für die Qualitätssicherung der Radionuklidtherapie von Knochenmetastasen mit Radium-223 schaffen. Sie wurde interdisziplinär erarbeitet und beschreibt die allgemeine Zielsetzung, Definitionen und klinischen Hintergrundinformationen sowie Indikationen und Kontraindikationen dieser Radionuklidtherapie. Ausgeführt werden die Anforderungen, die an ein Behandlungszentrum gestellt werden, prätherapeutisch notwendige Untersuchungsbefunde sowie Empfehlungen, wie die Behandlung technisch und organisatorisch durchgeführt werden sollte. Ferner finden sich Angaben zur Kontrolle und Nachsorge der therapierten Patienten. Grundsätzlich sollen Behandlung und Nachsorge in Abstimmung und Zusammenarbeit der beteiligten Fachdisziplinen erfolgen.

The aim of this study was to compare integrated PET/CT and PET/MRI for their usefulness in detecting and categorizing cervical iodine-positive lesions in patients with differentiated thyroid cancer using (124)I as tracer.The study group comprised 65 patients at high risk of iodine-positive metastasis who underwent PET/CT (low-dose CT scan, PET acquisition time 2 min; PET/CT2) followed by PET/MRI of the neck 24 h after (124)I administration. PET images from both modalities were analysed for the numbers of tracer-positive lesions. Two different acquisition times were used for the comparisons, one matching the PET/CT2 acquisition time (2 min, PET/MRI2) and the other covering the whole MRI scan time (30 min, PET/MRI30). Iodine-positive lesions were categorized as metastasis, thyroid remnant or inconclusive according to their location on the PET/CT images. Morphological information provided by MRI was considered for evaluation of lesions on PET/MRI and for volume information.PET/MRI2 detected significantly more iodine-positive metastases and thyroid remnants than PET/CT2 (72 vs. 60, p = 0.002, and 100 vs. 80, p = 0.001, respectively), but the numbers of patients with at least one tumour lesion identified were not significantly different (21/65 vs. 17/65 patients). PET/MRI30 tended to detect more PET-positive metastases than PET/MRI2 (88 vs. 72), but the difference was not significant (p = 0.07). Of 21 lesions classified as inconclusive on PET/CT, 5 were assigned to metastasis or thyroid remnant when evaluated by PET/MRI. Volume information was available in 34 % of iodine-positive metastases and 2 % of thyroid remnants on PET/MRI.PET/MRI of the neck was found to be superior to PET/CT in detecting iodine-positive lesions. This was attributed to the higher sensitivity of the PET component, Although helpful in some cases, we found no substantial advantage of PET/MRI over PET/CT in categorizing iodine-positive lesions as either metastasis or thyroid remnant. Volume information provided by MRI for some iodine-positive lesions might be useful in dosimetry.

Korrespondenz zu 10.1055/s-0038-1636560

Die Leitlinie soll medizinisches Fachpersonal und onkologisch tätige Ärzte bei der Auswahl geeigneter Patienten, der Planung, Vorbereitung und Durchführung einer SIRT zur Behandlung primärer und sekundärer maligner Lebertumoren unterstützen. Schwerpunkte sind personelle, technische und organisatorische Anforderungen an das Therapiezentrum einschließlich Strahlenschutz, d. h. insbesondere die Notwendigkeit einer interdisziplinären Patientenselektion in Tumorboards und die Anforderungen an das Team, das die Therapie durchführt und einen Medizinphysikexperten einbeziehen muss. Die Zielsetzung der Therapie, die erforderlichen Daten und Voruntersuchungen für die Indikationsstellung und Therapieplanung und ihre Implikationen für die Vermeidung von Komplikationen werden dargestellt, ebenso Anforderungen an die Aufklärung des Patienten. Die Nachsorge wird beschrieben und auf die Notwendigkeit einer interdisziplinären Zusammenarbeit auch mit heimatnahen behandelnden Ärzten hingewiesen.

Purpose Interim positron emission tomography (PET) using the tracer, [18F]fluorodeoxyglucose, may predict outcomes in patients with aggressive non-Hodgkin lymphomas. We assessed whether PET can guide therapy in patients who are treated with cyclophosphamide, doxorubicin, vincristine, and prednisone (CHOP). Patients and Methods Newly diagnosed patients received two cycles of CHOP—plus rituximab (R-CHOP) in CD20-positive lymphomas—followed by a PET scan that was evaluated using the ΔSUVmax method. PET-positive patients were randomly assigned to receive six additional cycles of R-CHOP or six blocks of an intensive Burkitt’s lymphoma protocol. PET-negative patients with CD20-positive lymphomas were randomly assigned or allocated to receive four additional cycles of R-CHOP or the same treatment with two additional doses rituximab. The primary end point was event-free survival time as assessed by log-rank test. Results Interim PET was positive in 108 (12.5%) and negative in 754 (87.5%) of 862 patients treated, with statistically significant differences in event-free survival and overall survival. Among PET-positive patients, 52 were randomly assigned to R-CHOP and 56 to the Burkitt protocol, with 2-year event-free survival rates of 42.0% (95% CI, 28.2% to 55.2%) and 31.6% (95% CI, 19.3% to 44.6%), respectively (hazard ratio, 1.501 [95% CI, 0.896 to 2.514]; P = .1229). The Burkitt protocol produced significantly more toxicity. Of 754 PET-negative patients, 255 underwent random assignment (129 to R-CHOP and 126 to R-CHOP with additional rituximab). Event-free survival rates were 76.4% (95% CI, 68.0% to 82.8%) and 73.5% (95% CI, 64.8% to 80.4%), respectively (hazard ratio, 1.048 [95% CI, 0.684 to 1.606]; P = .8305). Outcome prediction by PET was independent of the International Prognostic Index. Results in diffuse large B-cell lymphoma were similar to those in the total group. Conclusion Interim PET predicted survival in patients with aggressive lymphomas treated with R-CHOP. PET-based treatment intensification did not improve outcome.

Thyroid resections represent one of the most common operations with 76,140 interventions in the year 2016 in Germany (source Destatis). These are predominantly benign thyroid gland diseases. Recommendations for the operative treatment of benign thyroid diseases were last published by the CAEK in 2010 as S2k guidelines (Arbeitsgemeinschaft der Wissenschaftlichen Medizinischen Fachgesellschaften e.V. [AWMF] 003/002) against the background of increasingly more radical resection procedures. Hemithyroidectomy and thyroidectomy are routinely performed for benign thyroid disease in practice. The operation-specific risks show a clear increase with the extent of the resection. Therefore, weighing-up of the risk-indications ratio between unilateral lobectomy or thyroidectomy necessitates an independent evaluation of the indications for both sides. This principle in particular has been used to update the guidelines. In addition, the previously published recommendations of the CAEK for correct execution and consequences of intraoperative neuromonitoring were included into the guidelines, which in particular serve the aim to avoid bilateral recurrent laryngeal nerve paralysis. Moreover, the recommendations for the treatment of postoperative complications, such as hypoparathyroidism and postoperative infections were revised. The updated guidelines therefore represent the current state of the science as well as the resulting surgical practice.

The radiolabeled somatostatin analogue, yttrium-90 DOTA-d-Phe(1)-Tyr(3)-octreotide (DOTATOC), is currently applied to treat advanced somatostatin receptor-positive tumors, e.g., neuroendocrine tumors of the pancreas, lung or gut. However, effects of this treatment on antimicrobial immune responses are not yet defined. In 20 patients treated with DOTATOC, cellular in vitro immune function was determined. Their antimicrobial lymphocyte responses were assessed by lymphocyte transformation test and enzyme-linked immunospot—measuring lymphocyte proliferation and on a single cell level production of pro- and anti-inflammatory cytokines (interferon-γ and interleukin-10)—prior to therapy, at day 1, day 7 and day 90 post-therapy. Proliferative lymphocyte responses and interferon-γ production after in vitro stimulation with microbial antigens were non-significantly suppressed at day 1 and significantly (p

To analyze risk factors for vitamin D insufficiency in Germany with respect to ethnicity, sex, and clothing style.We analyzed the routine diagnostic work-ups of 1,231 adult (45.9 ± 17.9 years old) German (n = 1,034) and Turk residents (n = 197) referred with nonspecific symptoms to the Thyroid Centers at St. Elisabeth-Hospital in Dorsten, Germany and Bottrop, Germany to assess for metabolic diseases. All subjects underwent a routine examination that consisted of a questionnaire, lab tests for 25-hydroxyvitamin-D (25OHD), and thyroid profile. Turk females with traditional clothing (headscarf and covered legs and arms) were considered to wear "covered clothing." Logistic-regression was performed to identify factors that could predict vitamin D deficiency (20 ng/mL) and insufficiency (20-30 ng/mL).Vitamin D insufficiency was seen in 33% of Germans and 74.1% of Turks, and vitamin D deficiency was present in 11.3% and 44.2% of Germans and Turks, respectively (P.001). The mean 25OHD value in Turk females with covered clothes was lower than that in Turk females with conventional clothing (16.3 ± 12.3 vs. 27.2 ± 15.8, P.001). Vitamin D insufficiency was present in 86.0% of Turk females with covered clothing versus 62.8% with conventional clothing (odds ratio [OR] = 3.6, P = .002). Ethnicity, body mass index (BMI), and clothing style were significant predictors of vitamin D deficiency and insufficiency by logistic regression (P.001).(1) Vitamin D insufficiency among Turk residents in Germany is higher compared to Germans. The highest prevalence was present in Turk females with covered clothing. (2) Monitoring vitamin D in Turk residents in Germany is warranted. (3) Vitamin D supplements and access to facilities with sunlight exposure for females with covered clothing and all individuals with poor diets or limited access to sun exposure may prevent future health burden due to vitamin D insufficiency.

This document describes the guideline for peptide receptor radionuclide therapy (PRRT) published by the German Society of Nuclear Medicine (DGN) and accepted by the Association of the Scientific Medical Societies in Germany (AWMF) to be included in the official AWMF Guideline Registry. These recommendations are a prerequisite for the quality management in the treatment of patients with somatostatin receptor expressing tumours using PRRT. They are aimed at guiding nuclear medicine specialists in selecting likely candidates to receive PRRT and to deliver the treatment in a safe and effective manner. The recommendations are based on an interdisciplinary consensus. The document contains background information and definitions and covers the rationale, indications and contraindications for PRRT. Essential topics are the requirements for institutions performing the therapy, e. g. presence of an expert for medical physics, intense cooperation with all colleagues involved in the treatment of a patient, and a certificate of instruction in radiochemical labelling and quality control are required. Furthermore, it is specified which patient data have to be available prior to performance of therapy and how treatment has to be carried out technically. Here, quality control and documentation of labelling are of great importance. After treatment, clinical quality control is mandatory (work-up of therapy data and follow-up of patients). Essential elements of follow-up are specified in detail. The complete treatment inclusive after-care has to be realised in close cooperation with the involved medical disciplines. Generally, the decision for PRRT should be undertaken within the framework of a multi-disciplinary tumour board.

The purpose of our study was to assess the immune function of patients with inoperable hepatic malignancies after treatment with selective internal radiotherapy (SIRT) and to identify possible correlations with clinical parameters. In 25 patients receiving SIRT lymphocyte proliferation and the production of pro- and anti-inflammatory cytokines (interferon-γ and interleukin-10) after stimulation with mitogens and microbial antigens were tested prior to therapy, directly after therapy (day 1) and at day 2, 7 and 28 post therapy using the lymphocyte transformation test and enzyme-linked immunospot assays. Absolute counts and percentages of leukocyte and lymphocyte subsets were determined by flow cytometry. The most prominent finding was an immediate and significant (p

Background The aim of this study was to evaluate the value of 18F–FDG PET/CT (PET/CT) and MRI for local and/or whole-body restaging of adenoid cystic carcinoma of the head and neck (ACC). Methods Thirty-six patients with ACC underwent conventional MRI of the head and neck and a whole-body PET/CT and were analysed with regards to detection of a local tumor recurrence, lymph node or distant metastases. A consensus interpretation of all available imaging data was used as reference standard. Sensitivity, specificity, diagnostic accuracy, positive and negative predictive values were calculated for MRI and PET/CT. Results The sensitivity of PET/CT and MRI was 96% (89%), specificity 89% (89%), PPV 96% (96%), NPV 89% (73%) and accuracy 94% (89%) for detection of local tumors. Additionally, PET/CT revealed lymph node metastases in one patient and distant metastases in 9/36 patients. In three patients secondary primaries were found. Conclusions Whole-body PET/CT in addition to MRI of the head and neck improves detection of local tumour and metastastic spread in ACC.

Background: Changes in glucose and energy metabolism contribute to the altered phenotype of cancer cells and are the basis for positron emission tomography with 18F-fluoro-2-deoxy-d-glucose (FDG) to visualize tumors in vivo. The molecular background of the enhanced glucose uptake and its regulation in lymphoma cells is not fully clarified and may provide new possibilities to reverse the altered metabolism. Thus in this study we investigated regulation of glucose uptake by different signaling pathways. Furthermore, the effect of the glucose analog 2-deoxy-d-glucose (2-DG) alone and in combination with other inhibitors on cell survival was studied. Methods: An FDG uptake assay was established and uptake of FDG by lymphoma cells was determined after incubation with inhibitors of the c-MYC and the PI3K signalling pathways that are known to be activated in lymphoma cells and able to regulate glucose metabolism. Inhibitors of MAPK signalling pathways whose role in altered metabolism is still unclear were also investigated. Expression of mRNAs of the glucose transporter 1 (GLUT1), hexokinase 2 (HK2), glucose-6-phosphatase (G6Pase) and lactate dehydrogenase A (LDHA) and of the glucose metabolism-regulating micro RNAs (miRNA) miR21, -23a, -133a, -133b, -138-1 and -143 was determined by RT-PCR. Cell viability was analysed by MTT assay. Results: Treatment with the c-MYC inhibitor 10058-F4 and inhibitors of the PI3K/mTOR pathway diminished uptake of FDG in all three cell lines, while inhibition of MAPK pathways had no effect on glucose uptake. Expression of glycolysis-related genes and miRNAs were diminished, although to a variable degree in the three cell lines. The c-MYC inhibitor, the PI3K inhibitor LY294002, the mTOR inhibitor Rapamycin and 2-DG all diminished the number of viable cells. Interestingly, in combination with 2-DG, the c-MYC inhibitor, LY294002 and the p38 MAPK inhibitor SB203580 had synergistic effects on cell viability in all three cell lines. Conclusions: c-MYC- and PI3K/mTOR-inhibitors decreased viability of the lymphoma cells and led to decreased glucose uptake, expression of glycolysis-associated genes, and glucose metabolism-regulating miRNAs. Inhibition of HK by 2-DG reduced cell numbers as a single agent and synergistically with inhibitors of other intracellular pathways. Thus, targeted inhibition of the pathways investigated here could be a strategy to suppress the glycolytic phenotype of lymphoma cells and reduce proliferation. OA gold

Introduction The aim of this study was to evaluate the ability of 18F-fluorodeoxyglucose positron emission tomography/magnetic resonance imaging (18F-FDG PET/MRI) to detect PET-positive cervical facet arthropathy and identify patients who benefit from facet block therapy. Methods Ten patients with cervical facet syndrome (mean age: 65 ± 12 years) underwent 18F-FDG PET/MRI of the neck. Focal 18F-FDG uptake in PET-positive facet joints served as target for computed tomography (CT)-guided facet blocks. In PET-negative patients, the target joint for facet block therapy was selected by current clinical standards considering the level of maximum facet arthrosis and pain. Neck pain was measured on visual analogue scale (VAS) before and after therapy. Bone marrow signal intensity (SI) ratio on turbo inversion recovery magnitude (TIRM) images and maximum standard uptake values (SUVmax) was calculated for each facet joint. Pearson's correlation coefficient (r) was calculated between bone marrow SI ratios on TIRM and SUVmax. Results 18F-FDG PET/MRI detected PET-positive facet arthropathy in six patients. Patients with PET-positive facet arthropathy had significantly less pain compared with the pretreatment pain 3 h (P = 0.002), 4 weeks (P = 0.002) and 3 months (P = 0.026) after facet block therapy. Pain did not change significantly in patients with PET-negative facet arthropathy. TIRM SI ratio was higher in PET-positive facet arthropathy than in PET-negative facet arthropathy (P < 0.001). Correlation was strong between bone marrow SI ratio on TIRM images and SUVmax (r = 0.7; P < 0.001). Conclusions 18F-FDG PET/MRI can detect PET-positive cervical facet arthropathy and help to identify patients benefitting from facet block therapy. Bone marrow TIRM SI ratio might be a surrogate for PET-positive facet arthropathy.

Item does not contain fulltext PURPOSE: The prostate-specific membrane antigen (PSMA) was shown to be overexpressed on the neovasculature of several malignancies. Here, the role of Ga-HBED-CC-PSMA PET/CT for the detection of PSMA expression in patients with metastasized differentiated thyroid cancer (DTC) was evaluated. METHODS: Six patients with iodine-negative and F-FDG-positive metastasized DTC (mean TG, 1616 ng/mL) received 71-93 MBq of the Ga-labeled PSMA ligand and underwent PET/CT at 62 +/- 7 minutes p.i.. Tumor accumulation capacity of the tracer and the detection rate of local recurrences and metastases were compared with F-FDG. Tracer uptake was quantified in terms of the SUVmax. RESULTS: In 5 of 6 patients, sites of putative metastatic disease could be identified using Ga-HBED-CC-PSMA PET/CT. All lesions detected with Ga-HBED-CC-PSMA PET/CT (n = 42) were confirmed by F-FDG PET/CT or conventional CT imaging. Using Ga-HBED-CC-PSMA PET/CT, all tumor lesions identified with F-FDG PET/CT imaging could be visualized in 3 of 5 patients. In 2 patients, only the most prominent lesions detected with F-FDG PET/CT imaging were visualized by Ga-HBED-CC-PSMA PET/CT. Ga-HBED-CC-PSMA uptake ranged from low in 1 patient (mean SUVmax 3.3) to intermediate (1 patient; mean SUVmax, 6.1) to intense (3 patients; mean SUVmax, 12.8, 16.2, and 18.3). The highest SUVmax values were observed for a bone lesion, reaching 39.7. CONCLUSIONS: These preliminary results indicate that Ga-HBED-CC-PSMA PET/CT might be suitable for staging of patients with metastasized DTC. Ga-HBED-CC-PSMA PET/CT could be useful for the identification of patients who might qualify for PSMA-targeted radionuclide therapy because of high PSMA uptake.

BACKGROUND A retrospective study using PET/CT imaging with 124I-labeled metaiodobenzylguanidine (124I-MIBG) was performed to estimate the (radiation) absorbed dose to the salivary glands in neuroendocrine cancer patients undergoing 131I-MIBG therapy and to compare these results with those in radioiodine (131I-iodide) therapy. METHODS Twenty-seven patients received individual 124I-MIBG-PET/CT dosimetries, among whom 18 had not previously undergone any MIBG therapies (patient group before treatment) and 9 had already received MIBG therapies prior to the tracer dosimetries (patient group after treatment). For each patient, three or four 124I-MIBG PET/CT scans were performed at approximately 4 and 24 hours, as well as at approximately 48 or/and ≥96 hours after tracer injection. The absorbed doses per administered 131I-MIBG activity to the submandibular and parotid glands were calculated based on the MIRD concept, with its assumption of a uniform glandular activity distribution. RESULTS The mean±standard deviation of the (self-)absorbed dose per activity averaged over both patient groups and salivary gland types was 0.53±0.24 Gy/GBq (median, 0.49 Gy/GBq; range, 0.17-1.38 Gy/GBq). The absorbed doses per activity of the patient group before treatment did not significantly deviate from those of the patient group after treatment (P=0.67). In the patient group after treatment, the mean±standard deviation of the cumulative 131I-MIBG activity was 20±12 GBq (median, 16 GBq; range, 10-50 GBq). Among the patient groups, no significant absorbed dose difference was found between the submandibular and parotid glands (P>0.24). In comparison to radioiodine therapy, the estimated absorbed dose per activity in MIBG was significantly higher (P

TO THE EDITOR: Deandreis et al. ([1][1]) compared the overall survival (OS) of 2 patient groups with metastatic differentiated thyroid cancer (mDTC). One group of patients underwent multiple 131I treatments using a standard administered activity (AA) of 3.7 GBq (100 mCi) at Gustave Roussy (GR)

Therapy with the alpha-emitter radium-223 chloride (In 11 patients receivingLymphocyte proliferation and the production of interferon-γ and interleukin-10 towards mitogens and antigens remained unchanged after therapy. Consistent with these in vitro data, we did not observe infectious complications after treatment.The results argue against an impairment of lymphocyte function after

124I PET/CT images from differentiated thyroid cancer patients were retrospectively analyzed to assess the relationship between absorbed radiation dose (AD) to lesions and their response after radioiodine therapy. Methods: Patients received serial 124I PET/CT scans before and after their first radioiodine treatment. The pretherapy PET data were used to segment the lesion volumes and to predict the therapy-delivered ADs after administration of the therapeutic 131I activity. The segmentation method’s lower volume limit of determinability was a sphere of 0.80 mL, which classified the lesions into a known-volume group (>0.80 mL) or a small-volume group (≤0.80 mL) with their respective average and minimum ADs. The posttherapy PET data were used to assess the lesion-based therapy success. In the known-volume group, the response rate was calculated on the basis of lesions that received average ADs above the generally accepted threshold of 85 Gy for metastases and 300 Gy for thyroid remnants (TRs) and was expressed as the percentage of completely responding lesions. In the small-volume group, the metastasis and TR responses were evaluated for 3 minimum-AD groups: 5 to 10 Gy (TR, 5 to 30 Gy), >10 to 85 Gy (TR, >30 to 300 Gy), and >85 Gy (TR, >300 Gy). Their response rates were calculated in terms of the percentage of completely responding lesions in each minimum-AD group. Results: In total, 59 lesions in 17 patients were amenable to reliable volume estimation. The response rates were 63%, 88%, and 90% for lymph node metastases (LMs), pulmonary metastases, and TRs, respectively. The response rates of 168 small lesions in 34 patients were more than 82% for LMs and more than 91% for TRs in each of the 3 minimum-AD groups; all small pulmonary metastases responded completely. Conclusion: In the known-volume group, the response rate for TRs matched well with historical data derived using 131I scintigraphy imaging, whereas the response rate for LMs was not as high as expected, which may be explained by too short a follow-up time for a few LMs and a higher sensitivity of PET imaging. Small lesions were treated effectively, suggesting that they are considerably smaller than 0.80 mL.

SummaryAim: Several studies described the ultrasound based real-time elastography (USE) having a high sensitivity, specificity and negative predictive value in the diagnosis of suspicious thyroid nodules. Recently published studies called these results into question. Until now the usefulness of USE in the diagnosis of scintigraphically hyperfunctional thyroid nodules is not examined. Patients, methods: This study included 135 hyperfunctional thyroid nodules of 102 consecutive patients. The following attributes of the nodules were analyzed: stiffness with the USE using scores of Rago or Asteria and ultrasound criteria using TIRADS. Results: 94 of the examined thyroid nodules (70%) were rated as hard (suspicious for malignancy) and 41 nodules (30%) as soft (not suspicious) with a specificity of 30%. The scoring systems of Rago and Asteria showed no sigificant difference. Applying the TIRADS criteria 44 nodules (33%) have a higher risk for malignancy (33 nodules TIRADS 4a, 11 nodules TIRADS 4b). Combining USE and TIRADS 32 nodules (24%) are categorized as suspicious (intersection of hard nodules that are categorized as TIRADS 4a or 4b). Conclusion: Ultrasound based real-time elastography cannot identify scintigraphically hyperfunctional thyroid nodules as benign nodules reliably. Its accuracy in the assessment of at least “hot” thyroid nodules is to be questioned.

Objectives To assess the value of PET/MRI with [ 18 F]-FDG using a whole body protocol for the depiction and characterization of liver lesions in comparison to PET/CT. Methods 70 patients (31 women, 39 men) with solid tumors underwent [ 18 F]-FDG PET/CT and followed by an additional PET/MRI using an integrated scanner. Two readers rated the datasets (PET/CT; PET/MRI) regarding conspicuity of hepatic lesions (4-point ordinal scale) and diagnostic confidence (5-point ordinal scale). Median scores for lesion conspicuity and diagnostic confidence were compared using Wilcoxon's rank sum test. Prior examinations, histopathology and clinical follow-up (116 ± 54 days) served as standard of reference. Results 36 of 70 (51%) patients showed liver lesions. Using PET/CT and PET/MRI all patients with liver metastases could correctly be identified. A total of 97 lesions were found (malignant n = 26; benign n = 71). For lesion conspicuity significantly higher scores were obtained for PET/MRI in comparison to PET/CT ( p p Conclusions PET/MRI, even in the setting of a whole body approach, provides higher lesion conspicuity and diagnostic confidence compared to PET/CT and may therefore evolve as an attractive alternative in oncologic imaging.