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ZusammenfassungIm Rahmen der Hybridbildgebung mit SPECT/CT und PET/CT wird die CT in der Regel als eine nicht diagnostische low-dose-Untersuchung (sog. auxiliäre CT) durchgeführt. Die CT-Daten dienen dabei der Schwächungskorrektur und bieten die Möglichkeit einer morphologischen Korrelation nuklearmedizinischer Befunde. Als Strahlungsanwendung unterliegt auch diese Form der CT dem allgemeinen Optimierungsgebot. Abhängig vom Anwendungsszenario sind dabei verschiedene Schwerpunkte zu berücksichtigen. Beispielhaft sind der potenzielle Einfluss der CT-Rekonstruktion auf die Schwächungskorrektur der Emissionsdaten, die Erkennbarkeit von anatomischen Strukturen oder auch die strahlenbiologische Optimierung für spezielle Patientengruppen (z. B. Kinder) zu nennen. Zu beachten ist, dass parallel zu den Optimierungsbestrebungen auch eine zunehmende Regulierung der auxiliären CT-Anwendungen stattfindet.

This paper presents the proof-of-concept study of an adaptor allowing the combination of a gamma probe with ultrasound (US) imaging, intending to improve the detectability of sentinel lymph nodes (SLNs). The performance of the adaptor in US imaging, in terms of depth of penetration and distance accuracy, and gamma scanning, in terms of sensitivity and spatial resolution, was investigated. We observed that the quality of the US imaging through the adaptor was promising and close to that of normal US imaging. However, the performance of the gamma probe through the adaptor was fairly poor, necessitating the improvement in the design of the adaptor for better gamma scanning. This study shall provide a basis for the development of a handheld gamma-US scanner for interventional procedures and small field-of-view (FOV) imaging in the future.

Ultrasound (US) imaging is used for the diagnosis and also evaluation of thyroid nodules. A Thyroid Imaging Reporting and Data System (TIRADS) is used for the risk stratification of thyroid nodules through US images. The composition of thyroid nodules plays an important role in the risk-stratification process. The percentages of cystic and solid components in a thyroid nodule are one of the features that are can be indicative of the risk of malignancy. In this work, we attempt to classify and estimate solid and cystic regions within nodules. 20x20 texture patches were extracted from solid and cystic regions and converted into signals. These signals are decomposed into low, mid, and high-frequency bands using Continuous Wavelet Transform (CWT). A total of 36 features were extracted from the decomposed signals using Auto- Regressive Modeling. The features were fed into three different Machine Learning (ML) algorithms (Artificial Neural Networks, K-Nearest Neighbors, and Random Forest Classifier) to provide us with a classification of solid versus cystic regions in thyroid nodule US images. The Random Forest Classifier obtained an Accuracy, Sensitivity, and Specificity of 90.41%, 99% and 91% respectively which was the highest among the three chosen ML algorithms. Additionally, the output from the classification phase was also be used to determine the percentage of cystic and solid regions with a given thyroid nodule US image.

Objectives: We aimed to assess the predictive value of the total metabolic tumor burden prior to treatment in patients with advanced non-small-cell lung cancer (NSCLC) receiving immune checkpoint inhibitors (ICIs). Methods: Pre-treatment 2-deoxy-2-[18F]fluoro-D-glucose positron emission tomography/computed tomography (PET/CT) scans performed in two consecutive years for staging in adult patients with confirmed NSCLC were considered. Volume, maximum/mean standardized uptake value (SUVmax/SUVmean), metabolic tumor volume (MTV) and total lesion glycolysis (TLG) were assessed per delineated malignant lesion (including primary tumor, regional lymph nodes and distant metastases) in addition to the morphology of the primary tumor and clinical data. Total metabolic tumor burden was captured by totalMTV and totalTLG. Overall survival (OS), progression-free survival (PFS) and clinical benefit (CB) were used as endpoints for response to treatment. Results: A total of 125 NSCLC patients were included. Osseous metastases were the most frequent distant metastases (n = 17), followed by thoracal distant metastases (pulmonal = 14 and pleural = 13). Total metabolic tumor burden prior to treatment was significantly higher in patients treated with ICIs (mean totalMTV ± standard deviation (SD) 72.2 ± 78.7; mean totalTLG ± SD 462.2 ± 538.9) compared to those without ICI treatment (mean totalMTV ± SD 58.1 ± 233.8; mean totalTLG ± SD 290.0 ± 784.2). Among the patients who received ICIs, a solid morphology of the primary tumor on imaging prior to treatment was the strongest outcome predictor for OS (Hazard ratio HR 28.04, p < 0.01), PFS (HR 30.89, p < 0.01) and CB (parameter estimation PE 3.46, p < 0.01), followed by the metabolic features of the primary tumor. Interestingly, total metabolic tumor burden prior to immunotherapy showed a negligible impact on OS (p = 0.04) and PFS (p = 0.01) after treatment given the hazard ratios of 1.00, but also on CB (p = 0.01) given the PE < 0.01. Overall, biomarkers on pre-treatment PET/CT scans showed greater predictive power in patients receiving ICIs, compared to patients without ICI treatment. Conclusions: Morphological and metabolic properties of the primary tumors prior to treatment in advanced NSCLC patients treated with ICI showed great outcome prediction performances, as opposed to the pre-treatment total metabolic tumor burdens, captured by totalMTV and totalTLG, both with negligible impact on OS, PFS and CB. However, the outcome prediction performance of the total metabolic tumor burden might be influenced by the value itself (e.g., poorer prediction performance at very high or very low values of total metabolic tumor burden). Further studies including subgroup analysis with regards to different values of total metabolic tumor burden and their respective outcome prediction performances might be needed.

ZusammenfassungDie Theranostik über den Natrium-Iodid-Symporter (NIS) bietet bei differenzierten Schilddrüsenkarzinomen eine einzigartige Option. Die diagnostischen und therapeutischen Nuklide weisen eine übereinstimmende Aufnahme und Kinetik auf, sodass der NIS das wichtigste theranostische Target bei dieser Erkrankung darstellt. Radioiodrefraktäre Schilddrüsenkarzinome (RRTC) zeichnen sich durch eine verminderte/fehlende NIS-Expression aus, sodass diese Struktur als theranostisches Ziel entfällt. Auch aufgrund eingeschränkter therapeutischer Optionen gibt es Ansätze, bei RRTC über die Expression von Somatostatinrezeptoren (SSTR) oder das Prostata-spezifische-Membranantigen (PSMA) neue theranostische Targets zu generieren, jedoch lässt die aktuelle Studienlage eine endgültige Bewertung der Erfolgsaussichten noch nicht zu.

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

We aimed to assess the frequency of additional primary malignancies detected incidentally on [18F]fluoro-D-glucose positron emission tomography/computed tomography (FDG-PET/CT) at staging in NSCLC patients. Moreover, their impact on patient management and survival was assessed. Consecutive NSCLC patients with available staging FDG-PET/CT between 2020 and 2021 were retrospectively enrolled. We reported whether further investigations of suspicious findings presumably not related to NSCLC were recommended and performed after FDG-PET/CT. Any additional imaging, surgery or multimodal management was considered as an impact on patient management. Patient survival was defined using overall survival OS and progression-free survival PFS. A total of 125 NSCLC patients were included, while 26 findings in 26 different patients were suspicious for an additional malignancy on FDG-PET/CT at staging. The most frequent anatomical site was the colon. A total of 54.2% of all additional suspicious lesions turned out to be malignant. Almost every malignant finding had an impact on patient management. No significant differences were found between NSCLC patients with suspicious findings versus no suspicious findings with regards to their survival. FDG-PET/CT performed for staging might be a valuable tool to identify additional primary tumors in NSCLC patients. Identification of additional primary tumors might have substantial implications for patient management. An early detection together with interdisciplinary patient management could prevent a worsening of survival compared to patients with NSCLC only.

This manuscript investigates cabozantinib, vandetanib, pralsetinib, and selpercatinib, four tyrosine kinase inhibitors (TKIs), which are used to treat advanced and/or metastatic medullary thyroid cancer (MTC). Data on efficacy and safety are presented with the main focus on treatment-related hypertension, a well-known adverse effect (AE) of these TKIs. Taken together, TKI-induced hypertension is rarely a dose-limiting side effect. However, with increasing survival times of patients under treatment, hypertension-associated complications can be expected to be on the rise without proper medication.

Background: Prostate-specific membrane antigen (PSMA)-directed radioligand therapy (RLT) is a novel treatment for patients with castration-resistant prostate cancer (CRPC). Given the mode of action, patients in an earlier disease stage, such as hormone-sensitive prostate cancer (HSPC), are also likely to benefit from [177Lu]Lu-PSMA- (177Lu-PSMA) or [225Ac]Ac-PSMA-radioligand treatment (225Ac-PSMA). In this retrospective study, we analyzed the safety and efficacy of PSMA-RLT in early-stage and hormone-sensitive metastatic prostate cancer patients. Methods: A retrospective study was performed in patients who received 177Lu-PSMA and/or 225Ac-PSMA with early-stage metastatic prostate cancer. The primary outcome parameter evaluated in this study was the progression-free survival (PFS) after PSMA-RLT and toxicity according to the Common Terminology Criteria for Adverse Events. Secondary outcome parameters were prostate-specific antigen (PSA) response and the date of onset of CRPC state. Results: In total, 20 patients were included of which 18 patients received 177Lu-PSMA radioligand and two patients received tandem treatment with both 177Lu-PSMA and 225Ac-PSMA radioligands. Patients received a median of 2 treatment cycles (range 1–6) and a median activity of 6.2 GBq 177Lu-PSMA per cycle (interquartile range (IQR) 5.2–7.4 GBq). PSMA-RLT was overall well-tolerated. The most common grade 1–2 side effects were xerostomia (n = 6) and fatigue (n = 8), which were only temporarily reported. One patient that received 225Ac-PSMA developed grade 3–4 bone marrow toxicity. The median PFS was 12 months (95% confidence interval (CI), 4.09–19.9 months). Seventeen (85%) patients had a ≥50% PSA response following PSMA-RLT. One patient developed CRPC 9 months following PSMA-RLT. Conclusions: In this small cohort study, PSMA-RLT appeared safe and showed encouraging efficacy for (metastasized) early-stage and hormone-sensitive prostate cancer patients. Prospective studies are awaited and should include long-term follow-up.

Objectives: We aimed to investigate the predictive value of baseline 2-deoxy-2-[18F]fluoro-D-glucose positron emission tomography/computed tomography (FDG-PET/CT) for durable responses to immune checkpoint inhibitors (ICIs) by linking the morphological and metabolic features of primary tumors (PTs) in nonsmall cell lung cancer (NSCLC) patients. Methods: For the purpose of this single-center study, the imaging data of the patients with a first diagnosis of NSCLC and an available baseline FDG-PET/CT between 2020 and 2021 were retrospectively assessed. The baseline characteristics were collected based on clinical reports and interdisciplinary tumor board documentation. The metabolic (such as standardized uptake value SUV maximum and mean (SUVmax, SUV mean), metabolic tumor volume (MTV), total lesion glycolysis (TLG)) and morphological (such as volume, morphology, margin, and presence of lymphangiosis through imaging) features of all the PTs were retrospectively assessed using FDG-PET/CT. Overall survival (OS), progression-free survival (PFS), clinical benefit (CB) and mortality rate were used as endpoints to define the long-term response to therapy. A backward, stepwise logistic regression analysis was performed in order to define the best model for predicting lasting responses to treatment. Statistical significance was assumed at p < 0.05. Results: A total of 125 patients (median age ± standard deviation (SD) 72.0 ± 9.5 years) were enrolled: 64 men (51.2%) and 61 women (48.8%). Adenocarcinoma was by far the most common histological subtype of NSCLC (47.2%). At the initial diagnosis, the vast majority of all the included patients showed either locally advanced disease (34.4%) or metastatic disease (36.8%). Fifty patients were treated with ICIs either as a first-line (20%) or second-line (20%) therapy, while 75 patients did not receive ICIs. The median values ± SD of PT SUVmax, mean, MTV, and TLG were respectively 10.1 ± 6.0, 6.1 ± 3.5, 13.5 ± 30.7, and 71.4 ± 247.7. The median volume of PT ± SD was 13.7 ± 30.7 cm3. The PTs were most frequently solid (86.4%) with irregular margins (76.8%). Furthermore, in one out of five cases, the morphological evidence of lymphangiosis was seen through imaging (n = 25). The median follow-up ± SD was 18.93 ± 6.98 months. The median values ± SD of OS and PFS were, respectively, 14.80 ± 8.68 months and 14.03 ± 9.02 months. Age, PT volume, SUVmax, TLG, the presence of lymphangiosis features through imaging, and clinical stage IV were very strong long-term outcome predictors of patients treated with ICIs, while no significant outcome predictors could be found for the cohort with no ICI treatment. The optimal cut-off values were determined for PT volume (26.94 cm3) and SUVmax (15.05). Finally, 58% of NSCLC patients treated with ICIs had a CB vs. 78.7% of patients in the cohort with no ICI treatment. However, almost all patients treated with ICIs and with disease progression over time died (mortality in the case of disease progression 95% vs. 62.5% in the cohort without ICIs). Conclusion: Baseline FDG-PET/CT could be used to predict a durable response to ICIs in NSCLC patients. Age, clinical stage IV, lymphangiosis features through imaging, PT volume (thus PT MTV due to a previously demonstrated linear correlation), PT SUVmax, and TLG were very strong long-term outcome predictors. Our results highlight the importance of linking clinical data, as much as morphological features, to the metabolic parameters of primary tumors in a multivariate outcome-predicting model using baseline FDG-PET/CT.

Background The introduction of hybrid SPECT/CT devices enables quantitative imaging in SPECT, providing a methodological setup for quantitation using SPECT tracers comparable to PET/CT. We evaluated a specific quantitative reconstruction algorithm for SPECT data using a 99mTc-filled NEMA phantom. Quantitative and qualitative image parameters were evaluated for different parametrizations of the acquisition and reconstruction protocol to identify an optimized quantitative protocol. Results The reconstructed activity concentration (ACrec) and the signal-to-noise ratio (SNR) of all examined protocols (n = 16) were significantly affected by the parametrization of the weighting factor k used in scatter correction, the total number of iterations and the sphere volume (all, p < 0.0001). The two examined SPECT acquisition protocols (with 60 or 120 projections) had a minor impact on the ACrec and no significant impact on the SNR. In comparison to the known AC, the use of default scatter correction (k = 0.47) or object-specific scatter correction (k = 0.18) resulted in an underestimation of ACrec in the largest sphere volume (26.5 ml) by − 13.9 kBq/ml (− 16.3%) and − 7.1 kBq/ml (− 8.4%), respectively. An increase in total iterations leads to an increase in estimated AC and a decrease in SNR. The mean difference between ACrec and known AC decreased with an increasing number of total iterations (e.g., for 20 iterations (2 iterations/10 subsets) = − 14.6 kBq/ml (− 17.1%), 240 iterations (24i/10s) = − 8.0 kBq/ml (− 9.4%), p < 0.0001). In parallel, the mean SNR decreased significantly from 2i/10s to 24i/10s by 76% (p < 0.0001). Conclusion Quantitative SPECT imaging is feasible with the used reconstruction algorithm and hybrid SPECT/CT, and its consistent implementation in diagnostics may provide perspectives for quantification in routine clinical practice (e.g., assessment of bone metabolism). When combining quantitative analysis and diagnostic imaging, we recommend using two different reconstruction protocols with task-specific optimized setups (quantitative vs. qualitative reconstruction). Furthermore, individual scatter correction significantly improves both quantitative and qualitative results.

ZusammenfassungBei der Anwendung ionisierender Strahlung ist prinzipiell mit der Induktion von Zweitmalignomen zu rechnen. Dies trifft auch auf die Radiojodtherapie beim differenzierten Schilddrüsenkarzinom bzw. bei benignen Erkrankungen der Schilddrüse zu. Bei der in der Regel höher dosierten Radiojodgabe zur Behandlung des differenzierten Schilddrüsenkarzinoms ist der Effekt in einigen groß angelegten retrospektiven Studien nachweisbar und muss dem therapeutischen und auch diagnostischen Nutzen gegenübergestellt werden. Das Strahlenrisiko bei der Behandlung von gutartigen Schilddrüsenerkrankungen ist als sehr gering einzuschätzen. Eine jüngst publizierte Studie mit sehr langem Follow-up beschreibt eine dosisabhängig steigende Sterblichkeit an Zweitmalignomen im Vergleich. Eine am gleichen Kollektiv durchgeführte weitere Analyse fand jedoch nur eine erhöhte Sterblichkeit im Vergleich zur Normalbevölkerung bei Langzeitthyreostase und nicht nach Radiojodgabe.Insgesamt gilt es, im Kontext von Radiojod auch bei der Interpretation von Studiendaten, die Strahlenrisiken mit den weiteren Risiken, den Vorteilen und Vorzügen bzw. Nachteilen der alternativen Therapieoptionen in Bezug zu setzen.

Notwithstanding regulatory approval of lenvatinib and sorafenib to treat radioiodine-refractory differentiated thyroid carcinoma (RAI-R DTC), important questions and controversies persist regarding this use of these tyrosine kinase inhibitors (TKIs). RAI-R DTC experts from German tertiary referral centers convened to identify and explore such issues; this paper summarizes their discussions. One challenge is determining when to start TKI therapy. Decision-making should be shared between patients and multidisciplinary caregivers, and should consider tumor size/burden, growth rate, and site(s), the key drivers of RAI-R DTC morbidity and mortality, along with current and projected tumor-related symptomatology, co-morbidities, and performance status. Another question involves choice of first-line TKIs. Currently, lenvatinib is generally preferred, due to greater increase in progression-free survival versus placebo treatment and higher response rate in its pivotal trial versus that of sorafenib; additionally, in those studies, lenvatinib but not sorafenib showed overall survival benefit in subgroup analysis. Whether recommended maximum or lower TKI starting doses better balance anti-tumor effects versus tolerability is also unresolved. Exploratory analyses of lenvatinib pivotal study data suggest dose-response effects, possibly favoring higher dosing; however, results are awaited of a prospective comparison of lenvatinib starting regimens. Some controversy surrounds determination of net therapeutic benefit, the key criterion for continuing TKI therapy: if tolerability is acceptable, overall disease control may justify further treatment despite limited but manageable progression. Future research should assess potential guideposts for starting TKIs; fine-tune dosing strategies and further characterize antitumor efficacy; and evaluate interventions to prevent and/or treat TKI toxicity, particularly palmar-plantar erythrodysesthesia and fatigue.

For the assessment of hyperparathyroidism besides cervical ultrasound, 99 mTc-Sestamibi (MIBI) imaging is being used on a routine basis in nuclear medicine practice. MIBI is a positively charged complex, which is bound in mitochondria rich parathyroidal tissue and shows a reduced washout as compared to normal thyroid tissue. This characteristic is used during dual-phase imaging by acquiring early and late images.In order to better localize adenomas, especially if they are ectopic, it is helpful to combine planar imaging with cross-sectional (-hybrid) imaging using SPECT or SPECT/CT. With this approach, in combination with ultrasound the sensitivity for adenomas is known to be over 80 % up to 100 %. For multiglandular involvement or hyperplasia, a significantly lower detection rate is known, which, however, can be improved by a combination of planar and tomografic imaging. To what extend medication can influence the results of MIBI imaging is not well known. Glucocorticoids and calcium channel antagonist might have a negative influence on the uptake of MIBI. Another potential influencing factor could be the presence of P-glykoprotein in some adenomas, leading to a faster efflux of MIBI out of the adenoma cells and consecutively a lower detection rate.

Introduction Thyroid Imaging Reporting And Data System (TIRADS) is helpful for risk stratification of thyroid nodules. However, there is a lack of data for TIRADS classification of different histological subtypes [classical papillary thyroid cancer (PTC), follicular variant of papillary thyroid cancer (FVPTC), and follicular thyroid cancer (FTC)], and benign thyroid nodules (follicular adenoma, oncocytic adenoma, and multinodular goiter (MNG)]. Methoxy-isobutyl-isonitrile (MIBI) imaging has a high negative predictive value for the exclusion of thyroid malignancy in hypofunctioning thyroid nodules. The aim of this analysis was to compare malignant and benign subtypes of thyroid nodule using three TIRADS and MIBI imaging. Methods Retrospective analysis of MIBI imaging studies. Hypofunctioning thyroid nodules were classified with Kwak-TIRADS, EU-TIRADS, and K-TIRADS. MIBI imaging was visually categorized. Results We included 242 thyroid nodules (32 malignant, 19 PTC, 7 FVPTC, and 6 FTC). When using Kwak-TIRADS 4C and 5 as a marker for high-risk nodules, we found 85.5% of the follicular adenoma, 80.8% of the MNG, 100% of the oncocytic adenoma, 100% of the FTC, 57.1% of the FVPTC, and 42.2% of the PTC to be below this cutoff. All PTC and FVPTC were MIBI-positive, 83% of the FTC, 78% of the follicular adenoma, 75% of the oncocytic adenoma, and 60% of the MNG were MIBI-positive. Conclusion TIRADS is useful to detect PTC, but FVPTC and FTC may be missed. MIBI imaging seems to be more suitable to detect FVPTC and FTC. However, neither TIRADS nor MIBI imaging are able to differentiate between follicular adenoma and FTC or FVPTC.

ZusammenfassungFür das fortgeschrittene Radiojod-refraktäre differenzierte Schilddrüsenkarzinom (DTC) als auch für das progrediente medulläre Schilddrüsenkarzinom sind seit mehreren Jahren Tyrosinkinase-Inhibitoren (TKI) als wirksame Therapieoptionen zugelassen. Nicht zuletzt aufgrund des Toxizitätsprofiles der TKIs erfolgt deren Einsatz individualisiert und risikoadaptiert nach Ausschöpfen lokaler palliativer Therapieverfahren und wenn bei großer Tumormasse und/oder signifikantem Fortschreiten ein weiteres Abwarten nicht mehr vertretbar erscheint. Für das DTC gibt es zwei zugelassene Tyrosinkinaseinhibitoren, Lenvatinib und Sorafenib; für das MTC sind es ebenfalls zwei, Vandetanib und Cabozantinib. Hinzu kommen, vor allem in letzter Zeit, (relativ) selektive Inhibitoren einzelner Tyrosinkinasen (z. B. BRAF, MEK, NTRK, RET und mTOR), die im Rahmen von Studien oder im individuellen Heilversuch zur Verfügung stehen. Kürzlich erlangten zwei NTRK-Inhibitoren die europäische Zulassung und können bei Vorliegen einer NTRK-Fusion eingesetzt werden; leider ist diese Fusion jedoch relativ selten beim Schilddrüsenkarzinom zu finden.In Summe sind die Nebenwirkungen der selektiven Inhibitoren meist geringer als die der bisher zugelassenen Medikamente, bei teils besserer, teils gleicher und teils etwas schlechterer Wirkung. Es steht zu erwarten, dass die selektiven Inhibitoren zukünftig das therapeutische Spektrum ergänzen werden. Grundvoraussetzung ist jedoch eine molekulare Analyse von Tumorgewebe mit Nachweis einer spezifischen Veränderung im Sinne eines „drugable target“. Um eine optimale individuelle Therapieplanung unter Berücksichtigung aller möglichen Therapieoptionen, inklusive Einschluss in klinische Studien, zu gewährleisten, sollten Patienten mit fortgeschrittenem MTC oder Radiojod-refraktären DTC interdisziplinär an spezialisierten Zentren (mit-)betreut werden.

The study examined the local dose distribution as well as the time course of skin exposure of hand and fingers from [ A compact calibrated electronic dosimeter (ED) with a miniaturized probe was used for real-time measurements of skin dose equivalent H The cumulative skin exposure from the production process measured by ED, was 74.7 ± 32.7 µSv/GBq and 40.1 ± 14.3 µSv/GBq for the right and left hand, respectively. The exposure recorded by the ED was in the average 19.4 % ± 40.0 % (median = 21.3 %) lower compared to the results from TLD. Highest exposure was recorded during synthesis (guided hand: 24.5 ± 12.2 µSv/GBq) and measuring of product yield including preparation of probes for quality control (guided hand: 36.1 ± 12.7 µSv/GBq). The highest local exposure was measured by a TLD close to the tip of the index finger of the guiding hand (range: 773-1257 µS/GBq). The chosen methodology using ED, proved to be a good concept for identifying procedure steps with an increased exposure level and to determine the time course of skin exposure and to identify procedure steps for further optimization of handling. Furthermore, miniaturized electronic dosimeters may be used for online surveillance of local exposure rates at hands and fingers.ZIEL: Diese Studie untersucht die lokale Dosisverteilung sowie den zeitlichen Verlauf der Hautexposition der Hände und Finger bei der [ Ein kompaktes kalibriertes elektronisches Dosimeter (ED) mit einer miniaturisierten Sonde wurde für die Echtzeitmessungen der Oberflächen-Personendosis H Die aus dem Herstellungsprozess akkumulierte Hautexposition betrug 74,7 ± 32,7 µSv/GBq bzw. 40,1 ± 14,3 µSv/GBq für die rechte sowie für die linke Hand. Die mit dem ED aufgezeichnete Exposition war im Durchschnitt 19,4 % ± 40,0 % (Median = 21,3 %) niedriger als die Ergebnisse der TLDs, die neben dem ED positioniert wurden. Die höchste Exposition resultierte aus der Synthese (führende Hand: 24,5 ± 12,2 µSv/GBq) und der Messung der Produktausbeute inklusive Vorbereitung der Proben für die Qualitätssicherung (führende Hand: 36,1 ± 12,7 µSv/GBq). Die höchste lokale Exposition wurde mittels TLD an der führenden Hand nahe der Zeigefingerspitze bestimmt (Spannweite: 773–1257 µS/GBq). Die mit dem ED gewählte Methodik erwies sich als geeignet zur Identifizierung von Prozessschritten mit einem erhöhten Expositionsniveau sowie zur Erfassung des zeitlichen Verlaufs der Hautexposition, um somit Prozessschritte für die weitere Optimierung des Umgangs zu identifizieren. Außerdem bietet die Nutzung von miniaturisierten elektronischen Dosimetern die Möglichkeit zur Online-Überwachung der lokalen Expositionsraten an Händen und Fingern.

in press A consensus statement about indications for post-surgical radioiodine therapy (RIT) in differentiated thyroid cancer patients (DTC) was recently published by the European Thyroid Association (ETA) 1. This publication discusses indications for RIT on the basis of an individual risk assessment. Many of the conclusions of this consensus statement are well founded and accepted across the disciplines involved. However, especially from the perspective of nuclear medicine, as the discipline responsible for indicating and executing RIT, some of the recommendations may require further clarification with regard to their compatibility with established best practice and national standards of care. Assessment of the indications for RIT is strongly dependent on the weighing up of benefits and risks. On the basis of longstanding clinical experience in nuclear medicine, RIT represents a highly specific precision medicine procedure of proven efficacy with a favorable side-effect profile. This distinguishes RIT significantly from other adjuvant oncological therapies and has resulted in the establishment of this procedure as a usually well-tolerated, standard safety measure. With regard to its favorable risk/benefit ratio, this procedure should not be unnecessarily restricted, in the interest of offering reassurance to the patients. Both patients' interests and regional/national differences need to be taken into account. We would therefore like to comment on the recent consensus from the perspective of authors and to provide recommendations based on the respective published data.

Purpose: (i) To examine the criterion taller-than-wide (TTW) for the sonographic assessment of thyroid nodules in areas of iodine deficiency in terms of frequency, anatomical distribution within the thyroid gland and risk of malignancy. (ii) To develop a model for nodule growth in the thyroid gland. Methods: German multicenter study consisting of two parts. In the prospective part, thyroid nodules were sonographically measured in all three dimensions, location within the thyroid gland and contact to a protrusion-like formation (horn) in the dorsal position of thyroid gland was noted. In addition, further sonographic features such as the composition, echogenity, margins and calcifications were investigated. All nodules from the prospective part were assessed for malignancy as part of clinical routine at the decision of the treating physician adhering to institutionally based algorithms. In the retrospective part, only nodules with fine needle aspiration and/or histology were included. The risk of malignancy in TTW nodules was determined by correlating them with cyotological and histological results. Results: Prospective part: out of 441 consecutively evaluated thyroid nodules, 6 were found to be malignant (1.4%, 95% CI 0.6–2.7%). Among the 74 TTW nodules (17%), 1 was malignant (1%, 95% CI 0–4%). TTW nodules were more often located in the dorsal half of the thyroid than non-TTW nodules (factor 2.3, p = 0.01, 95% CI 2.1–2.5) and more often located in close proximity to a horn than non-TTW nodules (factor 3.0, p = 0.01, 95% CI 2.4–3.8). Retrospective part: out of 1315 histologically and/or cytologically confirmed thyroid nodules, 163 TTW nodules were retrieved and retrospectively analyzed. A TTW nodule was 1.7 times more often benign when it was dorsal (95% CI 1.1–2.5) and 2.5 times more often benign when it was associated with a horn (95% CI 1.2–5.3). The overall probability of malignancy for TTW nodules was 38% (95% CI 30–46%) in this highly preselected patient group. Conclusion: TTW nodules are common in iodine deficient areas. They are often located in the dorsal half of the thyroid gland and are frequently associated with a dorsal protrusion-like formation (horn) of the thyroid. Obviously, the shape of benign nodules follows distinct anatomical preconditions within the thyroid gland. The frequency of TTW nodules and their predominant benignity can be explained by a pole concept of goiter growth. The difference between the low malignancy risk of TTW nodules found on a prospective basis and the high risk found retrospectively may be the result of a positive preselection in the latter.

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

During the last few years, especially since the American Thyroid Association guidelines was released in 2015, there has been an intense debate on the management of thyroid cancer with particular emphasis on the use of radioactive iodine for diagnostic and therapeutic purposes. The Society of Nuclear Medicine and Molecular Imaging (SNMMI) and The European Association of Nuclear Medicine (EANM) have just published joint practice guidelines on the nuclear medicine evaluation and therapy of differentiated thyroid cancer (DTC) [1]. Recently, the European Thyroid Association (ETA) also released the 2022 ETA Consensus Statement: “What are the indications for post-surgical radioiodine therapy in differentiated thyroid cancer?” [2]. In addition, not long ago, a German position paper from surgery and nuclear medicine was published in reaction to the ETA Consensus Statement with a very different perspective, similar to the newly published SNMMI/EANM guideline [3]. Overall, despite the use of the widely accepted risk-adapted therapy, its interpretation and relative approaches to DTC management, and in particular to the clinical use of radioactive iodine, still differ significantly in European countries [4].

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Differentiated thyroid cancer (DTC) usually has a good prognosis when treated conventionally with thyroidectomy, radioactive iodine (RAI) and thyroid-stimulating hormone suppression, but some tumors develop a resistance to RAI therapy, requiring alternative treatments. Sorafenib, lenvatinib and cabozantinib are multikinase inhibitors (MKIs) approved for the treatment of RAI-refractory DTC. The drugs have been shown to improve progression-free survival (PFS) and overall survival (OS) via the inhibition of different receptor tyrosine kinases (RTKs) that are involved in tumorigenesis and angiogenesis. Both sorafenib and lenvatinib have been approved irrespective of the line of therapy for the treatment of RAI-refractory DTC, whereas cabozantinib has only been approved as a second-line treatment. Adverse effects (AEs) such as hypertension are often seen with MKI treatment, but are generally well manageable. In this review, current clinical studies will be discussed, and the toxicity and safety of sorafenib, lenvatinib and cabozantinib treatment will be evaluated, with a focus on AE hypertension and its treatment options. In short, treatment-emergent hypertension (TE-HTN) occurs with all three drugs, but is usually well manageable and leads only to a few dose modifications or even discontinuations. This is emphasized by the fact that lenvatinib is widely considered the first-line drug of choice, despite its higher rate of TE-HTN.

Theranostics via the sodium iodide symporter (NIS) offer a unique option in differentiated thyroid carcinoma. The diagnostic and therapeutic nuclides have similar uptake and kinetics, making the NIS the most important theranostic target in this disease. Radioiodine refractory thyroid carcinomas (RRTC) are characterised by reduced/absent NIS expression, thus eliminating this structure as a theranostic target. Also due to limited therapeutic options, there are approaches to generate new theranostic targets in RRTC, via the expression of somatostatin receptors (SSTR) or the prostate-specific membrane antigen (PSMA), but the current evidence does not yet allow a final evaluation of the prospects of success.Die Theranostik über den Natrium-Iodid-Symporter (NIS) bietet bei differenzierten Schilddrüsenkarzinomen eine einzigartige Option. Die diagnostischen und therapeutischen Nuklide weisen eine übereinstimmende Aufnahme und Kinetik auf, sodass der NIS das wichtigste theranostische Target bei dieser Erkrankung darstellt. Radioiodrefraktäre Schilddrüsenkarzinome (RRTC) zeichnen sich durch eine verminderte/fehlende NIS-Expression aus, sodass diese Struktur als theranostisches Ziel entfällt. Auch aufgrund eingeschränkter therapeutischer Optionen gibt es Ansätze, bei RRTC über die Expression von Somatostatinrezeptoren (SSTR) oder das Prostata-spezifische-Membranantigen (PSMA) neue theranostische Targets zu generieren, jedoch lässt die aktuelle Studienlage eine endgültige Bewertung der Erfolgsaussichten noch nicht zu.

Context The clinical relevance of bone metastases (BM) in advanced medullary thyroid carcinoma (MTC) is poorly described. Objective The objectives of this work are to describe the prevalence of BM, frequency of skeletal related events (SREs), and impact of BM morphology and SREs on prognosis, and to assess the role of antiresorptive treatment (ART). Design A retrospective cohort study was conducted. Setting This study was conducted at 4 German referral centers. Patients A total of 1060 MTC patients were included. Main Outcome Measure Main outcome measures include descriptive statistics, overall survival (OS) by the Kaplan-Meier method, and risk factors by Cox proportional hazards modeling. Results A total of 120 of 416 patients (29%) with metastatic MTC had BM, of which 97% had concurrent nonosseous metastases. BM occurred 2.1 years (median, range –0.1 to 20.6 years) after initial diagnosis, were multifocal in 79%, and were located preferentially in the spine (86%) and pelvis (60%). BM morphology was osteolytic in 32%, osteoblastic in 25%, and mixed in 22% of cases (unknown: 21%). Within a median observation period of 26.6 months (range, 0-188 months) after BM diagnosis, 47% of patients experienced one or more SREs (bone radiation 50%, pathological fractures 32%), of which 42% occurred in osteolytic and 17% in osteoblastic BM (P = .047). Presence of osteolytic metastases (hazard ratio 3.85, 95% CI 1.52-9.77, P = .005) but not occurrence of SREs was associated with impaired OS. Among the 36 patients who received ART (no ART: n = 71), SREs were significantly less frequent than in untreated patients (P = .04). Conclusion BM are common in metastatic MTC and most often with an osteolytic morphology and an unfavorable prognosis. The majority of SREs occur in osteolytic metastases and may be prevented by ART.

To evaluate the diagnostic value of 18F-FDG PET/CT in distinguishing benign versus malignant cardiac tumors as well as to assess its prognostic value. We analyzed 38 patients with cardiac tumors who underwent 18F-FDG PET/CT and followed for median 8.5 ± 12.5 months. SUVmax and TBRmax (maximum tumor-to-background ratio) by receiver-operating characteristic (ROC) curve analysis were used to obtain threshold for the diagnosis of malignancy as defined by histology (n = 38). Survival was assessed and correlated with the dignity of the lesions and PET parameters. Optimal cut-off values indicating malignancy were as follows: SUVmax = 3.44, with 100% sensitivity and 92.9% specificity, and TBRmax = 1.55, with 95.8% sensitivity and 92.9% specificity. A significant difference of 18F-FDG uptake was observed between primary benign (n = 14, SUVmax = 2.35 ± 1.31, TBRmax = 1.05 ± 0.50) compared to primary malignant cardiac tumors (n = 11, SUVmax = 8.90 ± 4.23, TBRmax = 3.82 ± 1.44) as well as cardiac metastases and lymphoma (n = 13, SUVmax = 14.37 ± 8.05, TBRmax = 6.19 ± 3.38) (all P

To investigate the interobserver agreement (IA) and the impact of consensus reading using four risk stratification systems for thyroid nodules (TN). Four experienced specialists independently rated US images of 80 TN according to the Kwak-TIRADS, EU-TIRADS, ACR TI-RADS, and ATA Guidelines. The cases were randomly extracted from a prospectively acquired database (n > 1500 TN). The observers were blinded to clinical data. This study was divided into two sessions (S1 and S2) with 40 image sets each. After every session, a consensus reading was carried out (C1, C2). Subsequently, the effect of C1 was tested in S2 with 40 new cases followed by C2. Fleiss’ kappa (κ) was calculated for S1 and S2 to estimate the IA and learning curves. The results of C1 and C2 were used as reference for diagnostic accuracy calculations. IA significantly increased (p