Trends in Selective Internal Radiation Therapy (SIRT) for Treating Hepatocellular Carcinoma, Cholangiocarcinoma, and Liver Metastasis: A Total Population Analysis from 2006 to 2021 in Germany.

The aim of this study was to investigate trends in selective internal radiation therapy (SIRT) for hepatocellular carcinoma (HCC), cholangiocarcinoma (CCC), and liver metastasis in Germany. We analyzed the nationwide German hospital billing database from 2006 to 2019 for the diagnosis of HCC, CCC or liver metastasis in combination with SIRT. For analyses of SIRT on the hospital level, we used the reimbursement.INFO tool based on German hospitals' quality reports from 2008 to 2021. Linear regression analysis was performed to detect changes over time. We included a total of 14,165 SIRT procedures. The annual numbers increased from 99 in 2006 to 1605 in 2015 (p < 0.001; increase by 1521%), decreasing to 1175 cases in 2019 (p < 0.001). In 2008, 6 of 21 hospitals (28.6%) performed more than 20 SIRTs per year, which increased to 19 of 53 (35.8%) in 2021. The share of SIRT for HCC increased from 29.8% in 2006 to 44.7% in 2019 (p < 0.001) and for CCC from 0% in 2006 to 9.5% in 2019 (p < 0.001), while the share of SIRT for liver metastasis decreased from 70.2% in 2006 to 45.7% in 2019 (p < 0.001). In-hospital mortality was 0.2% after the SIRT procedure. Gastritis (2.7%), liver failure (0.4%), and sepsis (0.3%) were the most common in-hospital complications reported. We observed an increase in SIRT procedures in Germany, with the number of hospitals offering the procedure going up from 21 in 2008 to 53 in 2021. While the treatment of liver metastasis remains the most common indication, SIRT for HCC and CCC increased significantly over the last few years. The mortality and complication rates show that SIRT is a relatively safe procedure.

Use of lenvatinib in the treatment of radioiodine-refractory differentiated thyroid cancer: a multidisciplinary perspective for daily practice.

Background: Most thyroid cancers of follicular origin have a favorable outcome. Only a small percentage of patients will develop metastatic disease, some of which will become radioiodine refractory (RAI-R). Important challenges to ensure the best therapeutic outcomes include proper, timely, and appropriate diagnosis; decisions on local, systemic treatments; management of side effects of therapies; and a good relationship between the specialist, patients, and caregivers. Methods: With the aim of providing suggestions that can be useful in everyday practice, a multidisciplinary group of experts organized the following document, based on their shared clinical experience with patients with RAI-R differentiated thyroid cancer (DTC) undergoing treatment with lenvatinib. The main areas covered are patient selection, initiation of therapy, follow-up, and management of adverse events. Conclusions: It is essential to provide guidance for the management of RAI-R DTC patients with systemic therapies, and especially lenvatinib, since compliance and adherence to treatment are fundamental to achieve the best outcomes. While the therapeutic landscape in RAI-R DTC is evolving, with new targeted therapies, immunotherapy, etc., lenvatinib is expected to remain a first-line treatment and mainstay of therapy for several years in the vast majority of patients and settings. The guidance herein covers baseline work-up and initiation of systemic therapy, relevance of symptoms, multidisciplinary assessment, and patient education. Practical information based on expert experience is also given for the starting dose of lenvatinib, follow-up and monitoring, as well as the management of adverse events and discontinuation and reinitiating of therapy. The importance of patient engagement is also stressed.

Normal organ dosimetry for thyroid cancer patients treated with radioiodine as part of the multi-centre multi-national Horizon 2020 MEDIRAD project.

PURPOSE: Dosimetry is rarely performed for the treatment of differentiated thyroid cancer patients with Na[131I]I (radioiodine), and information regarding absorbed doses delivered is limited. Collection of dosimetry data in a multi-centre setting requires standardised quantitative imaging and dosimetry. A multi-national, multi-centre clinical study was performed to assess absorbed doses delivered to normal organs for differentiated thyroid cancer patients treated with Na[131I]I. METHODS: Patients were enrolled in four centres and administered fixed activities of 1.1 or 3.7 GBq of Na[131I]I using rhTSH stimulation or under thyroid hormone withdrawal according to local protocols. Patients were imaged using SPECT(/CT) at variable imaging time-points following standardised acquisition and reconstruction protocols. Whole-body retention data were collected. Dosimetry for normal organs was performed at two dosimetry centres and results collated. RESULTS: One hundred and five patients were recruited. Median absorbed doses per unit administered activity of 0.44, 0.14, 0.05 and 0.16 mGy/MBq were determined for the salivary glands of patients treated at centre 1, 2, 3 and 4, respectively. Median whole-body absorbed doses for 1.1 and 3.7 GBq were 0.05 Gy and 0.16 Gy, respectively. Median whole-body absorbed doses per unit administered activity of 0.04, 0.05, 0.04 and 0.04 mGy/MBq were calculated for centre 1, 2, 3 and 4, respectively. CONCLUSIONS: A wide range of normal organ doses were observed for differentiated thyroid cancer patients treated with Na[131I]I, highlighting the necessity for individualised dosimetry. The results show that data may be collated from multiple centres if minimum standards for the acquisition and dosimetry protocols can be achieved.

Hypoparathyroidism - management, information needs, and impact on daily living from the patients' perspective: results from a population-based survey.

PURPOSE: Hypoparathyriodism (hypoPT) is a rare endocrine disorder. It is not known how hypoPT is managed in Germany or whether patients have unmet information needs or impairments in their daily living. METHODS: HypoPT patients at a minimum of 6 months' post-diagnosis were invited to participate in an online survey through their treating physician or through patient organizations. An extensive questionnaire, which was developed and pilot-tested with hypoPT patients, was administered. RESULTS: A total of 264 patients with a mean age of 54.5 years (SD: 13.3), 85.2% female and 92% with postsurgical hypoPT, participated in the study. In total, 74% of the patients reported regular monitoring of serum calcium at least every 6 months, with lower control frequencies for phosphate (47%), magnesium (36%), creatinine (54%), and parathyroid hormone (50%), and 24-h urine calcium excretion (36%) on a yearly basis. Information on symptoms of hypo- and hypercalcemia was available in 72 and 45% of the patients. Information needs were related to the disease and its treatment as well as to nutrition, physical activities/sports, and support opportunities. Statistically significant differences for all information needs in association with symptom burden were observed. Hospitalization for hypocalcemia was reported by 32%, nutritional impairments (38%) or impact on work ability (52%) was available among patients with hypoPT. CONCLUSION: HypoPT patients experience impairments in daily living and report unmet information needs. Patient and physician education regarding hypoPT is one of the key concepts for improving the management of patients with hypoPT.

Diagnostic Impact of Dual-Time PET/CT with 68Gallium-PSMA in Prostate Cancer and 68Gallium-DOTATOC in Neuroendocrine Tumors.

BACKGROUND: The timing of imaging for 68gallium (68Ga)-PSMA and 68Ga-DOTATOC are stated to be around 60 min post-injection (p.i.). In some lesions, late imaging (3-4 h p.i.) showed advantages. The aim of our evaluation was to demonstrate the relevance of an "early" late acquisition. METHODS: We retrospectively evaluated 112 patients who underwent 68Ga-DOTATOC-PET/CT and 82 patients who underwent 68Ga-PSMA-PET/CT. The first scan was acquired 60 min (±15 min) after application. In cases of diagnostic ambiguity, a second scan was performed 30-60 min later. Pathological lesions were analyzed. RESULTS: Almost half of all 68Ga-DOTATOC cases and about one-third of all 68Ga-PSMA examinations showed a change in findings due to the second acquisition. In total, 45.5% of neuroendocrine tumor (NET) patients and 66.7% of prostate cancer (PCa) patients showed relevant TNM classification changes. For 68Ga-PSMA, there were significant increases in sensitivity and specificity from 81.8% to 95.7% and from 66.7% to 100%, respectively. Statistically significant improvements in sensitivity (from 53.3% to 93.3%) and specificity (from 54.6% to 86.4%) were demonstrated for NET patients. CONCLUSION: Early second images can improve diagnostics with 68Ga-DOTATOC and 68Ga-PSMA PET/CT.

How to Xenograft Cancer Cells on the Chorioallantoic Membrane of a Fertilized Hen's Egg and Its Visualization by PET/CT and MRI.

The chorioallantoic membrane (CAM) of fertilized hen's eggs represents a unique and alternative model for cancer research. The CAM model provides an optimal platform for xenografting cancer cell lines and studying essential key factors. Tumor size and growth as well as angiogenesis can be investigated to evaluate the response of therapies and strategies against cancer. Preclinical imaging represented by magnetic resonance imaging and positron emission tomography/computed tomography can generate detailed anatomical and functional information and reveal excellent metabolic sensitivity. In the following, a guideline is introduced in order to find a simplified entrance to the CAM model in combination with modern preclinical imaging techniques. Finally, the presented procedures are additionally completed by histological studies in the form of hematoxylin and eosin as well as immunohistochemical staining.

[Therapy concepts for thyroid carcinoma]. / Therapiekonzepte beim Schilddrüsenkarzinom.

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.

Application of the American Thyroid Association Risk Assessment in Patients with Differentiated Thyroid Carcinoma in a German Population.

BACKGROUND: The American Thyroid Association (ATA) uses criteria to assess the risk for persistent disease in differentiated thyroid carcinoma (DTC) after radioiodine therapy (RAI). There are no data available showing that this classification can be adopted unadjusted by Germany. AIM: The aim of our study is to investigate whether the ATA classification can be applied to a German population for short-term prognosis. Furthermore, we investigated the influence of an age cutoff value. METHODS: We retrospectively analyzed 121 patients who were referred to our tertiary referral center. Patients were classified into risk categories, and the therapy response was determined according to ATA. RESULTS: A total of 73/83 (88%) ATA low-risk patients and 12/19 (63%) intermediate-risk patients showed an excellent response; 2/19 (11%) high-risk patients had a biochemical, and 6 (31%) had a structural incomplete response. Of all 39 patients ≥55 years, 84% had an excellent response. Using a cut off of 50 years, 50/62 (81%) of the older patients showed an excellent response. CONCLUSION: The ATA risk classification is able to estimate the response to RAI therapy in a German population. A shift from 55 to 50 years as an age cutoff value does not result in any relevant change in the treatment response.

Adoption of Lutetium-177 PSMA radioligand therapy for metastatic castration resistant prostate cancer: a total population analysis in Germany from 2016 to 2020.

PURPOSE: This study is to investigate the adoption and current trends of Lutetium-177 PSMA RLT for mCRPC in Germany. METHODS: We analyzed data from the reimbursement.INFO tool based on German hospitals' quality reports for Lutetium-177 PSMA RLT from 2016 to 2020 and from the nationwide German hospital billing database (Destatis) for general therapy with open radionuclides in combination with prostate cancer from 2006 to 2020. For validation of these billing data, we included the 177Lu-PSMA RLT cycles from two participating institutions from 2016 to 2020. For detection of trends over time we applied linear regression models. RESULTS: General therapy with open radionuclides increased from 2006 to 2020. We identified a total of 12,553 177Lu-PSMA RLT cycles. The number of 177Lu-PSMA RLTs steadily increased from a total of 1026 therapies in 2016 to 3328 therapies in 2020 (+ 576 RLT/year; p < 0.005). In 2016, 25 departments of nuclear medicine offered this treatment, which increased to 44 nuclear medicine departments in 2020. In 2016, 16% of nuclear medicine departments (4/25) performed more than 100 177Lu-PSMA RLTs, which increased to 36% (16/44) in 2020 (p < 0.005). In 2016, 88% (22/25) of 177Lu-PSMA RLTs were performed at a university hospital, which decreased to 70% (31/44) in 2020. The proportion of patients older than 65 years receiving 177Lu-PSMA RLT increased from 78% in 2016 to 81% in 2020. CONCLUSION: Treatment of mCRPC with 177Lu-PSMA RLT has been rapidly increasing in Germany in the recent years providing an additional therapy option. This development is remarkable, because of outstanding formal EMA approval.

Diagnostic value of FDG-PET/CT in the diagnostic work-up of inflammation of unknown origin.

Introduction The present study aims to evaluate the clinical diagnostic value of FDG-PET/CT in patients with inflammation of unknown origin. Material and methods We retrospectively analyzed data of 130 patients who presented general inflammatory symptoms and/or elevated level of CRP and underwent FDG-PET/CT for the purpose of identifying unknown foci of inflammation. The accuracy of PET/CT findings was assessed against the standard of eventual clinical diagnosis e.g. results of pathology, microbiology or other imaging methods. Results In 99/130 patients (76 %) a final diagnosis was established, FDG-PET/CT showed a sensitivity and specificity of each 93 %. A decreased pseudocholinesterase is associated with a higher SUVmax value and with a higher CRP value whereas no significant relationship was found between elevated CRP values and the SUVmax, although higher CRP values are associated significantly with a true positive PET/CT result. Conclusion FDG-PET/CT is a highly sensitive, specific and accurate method for the detection of foci of inflammation of unknown origin. The combination of decreased pseudocholinesterase and increased CRP levels may be a useful tool to select patients for FDG PET/CT.

[Is there an unmet need to establish a young talent section "Young DGN" within the German Society of Nuclear Medicine (DGN)? - Results of a 2021/2022 web-based survey among German Nuclear Medicine professionals]. / Besteht der Bedarf zur Gründung einer Nachwuchsorganisation "Young DGN" innerhalb der Deutschen Gesellschaft für Nuklearmedizin (DGN)? Ergebnisse einer webbasierten Umfrage in der deutschen Nuklearmedizin 2021/2022.

AIM: In various medical societies, dedicated young talent sections provide an important basis for promoting young members. However, the German Society of Nuclear Medicine (DGN) had not yet implemented such a section. Therefore, the aim of this work was to assess the opinion of nuclear medicine professionals in Germany on establishing a young talent section within the DGN ("Young DGN"). METHODS: An initiative group of young DGN members developed a survey questionnaire comprising 18 questions. The questionnaire was initially sent as a PDF to the members of the DGN University Committee (Hochschulausschuss) by e-mail on 10/12/2021. As an online survey, the questionnaire was then emailed at four additional time points between 12/23/2021 and 3/18/2022 via the DGN eBrief and on 2/23/2022 to the members of the mailing list of the Berufsverband Deutscher Nuklearmediziner (BDN). RESULTS: The survey closed on 3/31/2022 with 111 responses (n=104 online surveys, n=7 PDFs). The median age of participants was 32.5 years (range, 20-80). 86% of participants indicated that they were interested in a Young DGN section, of which 67% were willing to participate. 79% indicated that nuclear medicine was an exciting field for them. 96% expressed interest in additional education offers and 60% in the establishment of a mentoring program. 75% believed that Young DGN would improve the visibility of the specialty. CONCLUSION: The survey results indicate strong support for the establishment of a young talent section within the DGN among nuclear medicine professionals in Germany. A large proportion of those who participated in the survey would envision active involvement. There was a particular consensus on the desire to expand the range of education and training activities.

Position paper from the Endocrine Task Force of the European Organisation for Research and Treatment of Cancer (EORTC) on the management and shared decision making in patients with low-risk micro papillary thyroid carcinoma.

The incidence of differentiated thyroid cancer (DTC) has been increasing worldwide, mostly, as an increase in the incidental detection of micro papillary thyroid carcinomas (microPTCs), many of which are potentially overtreated, as suggested by the unchanged mortality. Several international guidelines have suggested a less aggressive approach. More recently, it has been shown that active surveillance or minimally invasive treatments (MIT) are good alternatives for the management of these patients. In this context, patient participation in the decision-making process is paramount. The Endocrine Task Force of the European Organisation for Research and Treatment of Cancer (EORTC) has undertaken the task to establish consensus and define its position based on the scientific evidence concerning, 1) the current state of diagnostic and management options in microPTCs, including the current opinion of physicians about shared decision making (SDM), 2) the available evidence concerning patients' needs and the available decision instruments, and 3) to provide practical suggestions for implementation of SDM in this context. To improve SDM and patients' participation, knowledge gaps and research directions were highlighted.

Long-term predictive value of highly sensitive thyroglobulin measurement.

OBJECTIVE: To examine the predictive value of unremarkable nonstimulated highly sensitive thyroglobulin (hsTg) measurement with regard to the results of stimulated thyroglobulin (Tg) measurement, diagnostic whole-body scintigraphy, recurrence and differentiated thyroid cancer (DTC)-related death. DESIGN, PATIENTS AND MEASUREMENTS: We retrospectively analysed the data of all 461 (410 without anti-Tg-antibodies [TgAbs], 51 with) DTC patients who were referred to our department for treatment and follow-up care of differentiated thyroid cancer from 2004 onwards, and in whom at least one posttreatment Tg value was measured in our hospital at least 3 months after I-131 ablation. RESULTS: In the group of TgAb-negative patients, 2.0% of patients with an unstimulated Tg < 0.1 ng/ml showed a stimulated Tg ≥ 1.0 ng/ml, whereas this happened in 77.6% with an unstimulated Tg ≥ 0.1 but <1.0 ng/ml. An unstimulated hsTg ≥ 0.1 ng/ml had a sensitivity specificity positive and negative predictive value of 90.0%, 94.1%, 77.6% and 97.6%, respectively, for a stimulated Tg ≥ 1.0 ng/ml. In TgAb-positive patients, this was 75%, 97%, 75% and 97%, respectively. An unstimulated Tg ≥ 0.1 ng/ml did not significantly discriminate with regard to the risk of DTC-related death (p = .06), but ≥1.0 ng/ml did (p = .012), as did a stimulated Tg ≥ 1.0 ng/ml (p = .029). Excluding patients with distant metastases at diagnosis nullifies this significance. CONCLUSION: Except for patients with distant metastases, both TgAb negative and TgAb positive patients with an undetectable nonstimulated hsTg measurement have a very good prognosis. The high net present value of unstimulated hsTg testing means that further diagnostic procedures can be omitted in such patients.

2022 European Thyroid Association Guidelines for the management of pediatric thyroid nodules and differentiated thyroid carcinoma.

At present, no European recommendations for the management of pediatric thyroid nodules and differentiated thyroid carcinoma (DTC) exist. Differences in clinical, molecular, and pathological characteristics between pediatric and adult DTC emphasize the need for specific recommendations for the pediatric population. An expert panel was instituted by the executive committee of the European Thyroid Association including an international community of experts from a variety of disciplines including pediatric and adult endocrinology, pathology, endocrine surgery, nuclear medicine, clinical genetics, and oncology. The 2015 American Thyroid Association Pediatric Guideline was used as framework for the present guideline. Areas of discordance were identified, and clinical questions were formulated. The expert panel members discussed the evidence and formulated recommendations based on the latest evidence and expert opinion. Children with a thyroid nodule or DTC require expert care in an experienced center. The present guideline provides guidance for healthcare professionals to make well-considered decisions together with patients and parents regarding diagnosis, treatment, and follow-up of pediatric thyroid nodules and DTC.

Real-Life Performance of F-18-FDG PET/CT in Patients with Cervical Lymph Node Metastasis of Unknown Primary Tumor.

BACKGROUND: Neoplasms in the head and neck region possess higher glycolytic activity than normal tissue, showing increased glucose metabolism. F-18-Flourodeoxyglucose (FDG) positron emission tomography/computed tomography (PET/CT) can identify an unknown primary tumor (CUP). AIM: The aim of this study was to assess the real-life performance of F-18-FDG-PET/CT in detecting primary sites in patients with cervical lymph node metastasis of CUP. METHODS: A retrospective data analysis of 31 patients who received FDG-PET/CT between June 2009 and March 2015 in a CUP context with histologically confirmed cervical lymph node metastasis was included. RESULTS: In 48% of the patients (15/31), PET/CT showed suspicious tracer accumulation. In 52% of the patients (16/31), there was no suspicious radiotracer uptake, which was confirmed by the lack of identification of any primary tumor in 10 cases until the end of follow-up. FDG-PET/CT had a sensitivity of 67%, specificity of 91%, PPV of 92%, and NPV of 63% in detecting the primary tumor. Additionally, PET/CT showed suspicious tracer accumulation according to further metastasis in 32% of the patients (10/31). CONCLUSION: FDG-PET/CT imaging is a useful technique for primary tumor detection in patients in a cervical CUP context. Furthermore, it provides information on the ulterior metastasis of the disease.

Progressive Olfactory Impairment and Cardiac Sympathetic Denervation in REM Sleep Behavior Disorder.

BACKGROUND: Isolated rapid eye movement sleep behavior disorder (iRBD) is prodromal for Parkinson's disease (PD) and dementia with Lewy bodies (DLB). OBJECTIVE: We investigated the use of cardiac [123I]meta-iodo-benzyl-guanidine scintigraphy ([123I]MIBG) and olfactory testing- in comparison to [123I]N-ω-fluoropropyl-2ß-carbomethoxy-3ß-(4-iodophenyl)nortropane single photon emission computed tomography ([123I]FP-CIT-SPECT)- for identifying iRBD patients as prodromal phenotype of PD/DLB. METHODS: 37 RBD subjects underwent cardiac [123I]MIBG and brain [123I]FP-CIT-SPECT at baseline. Olfactory (Sniffin' Sticks), cognitive and motor functions were tested annually for ∼4 years. RESULTS: 29/37 (78.4%) subjects had a pathological [123I]MIBG, of whom 86.2% (25/29) presented at least a moderate hyposmia at baseline (threshold/discrimination/identification-(TDI-)score ≤25). 20/37 (54.1%) subjects had a pathological [123I]FP-CIT-SPECT, always combined with a pathological [123I]MIBG. In subjects with pathological [123I]MIBG, olfactory function worsened (mainly due to threshold and discrimination subscores) from baseline to follow-up (p = 0.005). Olfaction was more impaired in subjects with pathological [123I]MIBG compared to those with normal [123I]MIBG at baseline (p = 0.001) and follow-up (p < 0.001). UPDRS-III scores increased in subjects with both pathological [123I]MIBG and [123I]FP-CIT-SPECT. In this group, seven subjects phenoconverted to PD, all- except for one- presented with at least moderate hyposmia at baseline. CONCLUSION: A combination of the biomarkers "pathological [123I]MIBG" and "hyposmia" likely identifies iRBD patients in an early prodromal stage of PD/DLB, i.e., before nigrostriatal degeneration is visualized. One-third of the subjects with pathological [123I]MIBG had a normal [123I]FP-CIT-SPECT. Noteworthy, in iRBD subjects with pathological [123I]MIBG, olfactory impairment is progressive independent of the [123I]FP-CIT-SPECT status.