Technical note: Quantifying radionuclide residues in hospital wastewater: A case study on [131I]I and [177mLu]Lu/[177Lu]Lu.

BACKGROUND: Historically, [131I]I has been a common isotope in radionuclide therapy, with [177Lu]Lu-labelled radiopharmaceuticals now seeing a surge in use. These can include no-carrier-added or carrier-added [177Lu]Lu with slight impurities of [177mLu]Lu with a significantly longer half-life than [131I]I. Wastewater from therapy wards can contain a mixture of these radioisotopes. In some countries, national regulations require wastewater to be stored in dedicated systems before it is discharged into the public sewage system. To fulfill legal requirements, the nuclide specific activity concentration must be verified. PURPOSE: We evaluate a method for determining the activity concentration of [177mLu]Lu /[177Lu]Lu at equilibrium and [131I]I in pure and mixed samples in order to prove that the determined values are reliably below the limits for release. METHODS: We analysed the emitted energy spectrum of 1 L samples with a wastewater counter using an energy window-based approach by evaluating measurements from two different time points. Based on the law of decay and the time and energy-dependent measured values, equation systems were set up to calculate the count rates for [131I]I and [177mLu]Lu, which were converted into activity concentration using calibration factors. RESULTS: There is strong linear correlation between the nominal and determined activity concentrations (correlation coefficients R = 0.99; coefficient of determinations R2 = 0.99). We underestimate the actual activity concentration by a median of -1.4% for [177mLu]Lu and overestimate the activity concentration for [131I]I by a median of 7.1%. CONCLUSION: We show that an undercut of the clearance levels for material release is measurable. We analyse and determine activity concentrations of mixed samples consisting of [131I]I and [177mLu]Lu/[177Lu]Lu in equilibrium. The method is simple to implement using a conventional wastewater counter, however with a slightly increased effort, as two samples and measurements are required. The methodology can be adapted for the analysis of other nuclide mixtures.

Thyroglobulin measurement is the most powerful outcome predictor in differentiated thyroid cancer: a decision tree analysis in a European multicenter series.

OBJECTIVES: An accurate prognostic assessment is pivotal to adequately inform and individualize follow-up and management of patients with differentiated thyroid cancer (DTC). We aimed to develop a predictive model for recurrent disease in DTC patients treated by surgery and 131I by adopting a decision tree model. METHODS: Age, sex, histology, T stage, N stage, risk classes, remnant estimation, thyroid-stimulating hormone (TSH), thyroglobulin (Tg), administered 131I activities and post-therapy whole body scintigraphy (PT-WBS) were identified as potential predictors and put into regression algorithm (conditional inference tree, c-tree) to develop a risk stratification model for predicting persistent/recurrent disease over time. RESULTS: The PT-WBS pattern identified a partition of the population into two subgroups (PT-WBS positive or negative for distant metastases). Patients with distant metastases exhibited lower disease-free survival (either structural, DFS-SD, and biochemical, DFS-BD, disease) compared to those without metastases. Meanwhile, the latter were further stratified into three risk subgroups based on their Tg values. Notably, Tg values >63.1 ng/mL predicted a shorter survival time, with increased DFS-SD for Tg values <63.1 and <8.9 ng/mL, respectively. A comparable model was generated for biochemical disease (BD), albeit different DFS were predicted by slightly different Tg cutoff values (41.2 and 8.8 ng/mL) compared to DFS-SD. CONCLUSIONS: We developed a simple, accurate and reproducible decision tree model able to provide reliable information on the probability of structurally and/or biochemically persistent/relapsed DTC after a TTA. In turn, the provided information is highly relevant to refine the initial risk stratification, identify patients at higher risk of reduced structural and biochemical DFS, and modulate additional therapies and the relative follow-up.

Lymphocyte Function at Baseline Could Be a New Predictor of Tumor Burden following Six Cycles of Radium-223 Therapy in Patients with Metastasized, Castration-Resistant Prostate Cancer.

Previous data indicate that one cycle of treatment with radium-223 (223Ra) did not significantly impair lymphocyte function in patients with metastasized, castration-resistant prostate cancer. The aim of the current study was to assess in 21 patients whether six cycles of this therapy had an effect on lymphocyte proliferation and interferon-γ and interleukin (IL)-10 ELISpot results. Lymphocyte proliferation after stimulation with microbial antigens and the production of interferon-γ continuously decreased after six cycles of radionuclide therapy, reaching statistical significance (p < 0.05) at months 1, 2, 4, and/or 6 after therapy. One month after the last cycle of therapy, 67% of patients showed a decrease in tumor burden. The tumor burden correlated negatively with IL-10 secretion at baseline, e.g., after stimulation with tetanus antigen (p < 0.0001, r = -0.82). As determined by receiver operating characteristic (ROC) curve analysis, tetanus-specific IL-10 spots at baseline had the highest predictive value (p = 0.005) for tumor burden at month 6, with an area under the curve (AUC) of 0.90 (sensitivity 100%, specificity 78%). In conclusion, we observed an additive effect of treatment with 223Ra on immune function and found that IL-10 secretion at baseline predicted tumor burden at month 6 after treatment.

Thyroid Imaging Reporting and Data Systems: Applicability of the "Taller than Wide" Criterium in Primary/Secondary Care Units and the Role of Thyroid Scintigraphy.

BACKGROUND: To examine the applicability of the "taller than wide" (ttw) criterium for risk assessment of thyroid nodules (TNs) in primary/secondary care units and the role of thyroid scintigraphy therein. METHODS: German bicenter study performed in a setting of primary/secondary care. Patient recruitment and analysis in center A was conducted in a prospective manner. In center B, patient data were retrieved from a database that was originally generated by prospective data collection. TNs were assessed by ultrasound and thyroid scans, mostly fine needle biopsy and occasionally surgery and others. In center A, only patients who presented for the first time were included. The inclusion criterion was any TN ≥ 10 mm that had at least the following two sonographic risk features: solidity and a ttw shape. In center B, consecutive patients who had at least ttw and hypofunctioning nodules ≥ 10 mm were retrieved from the above-mentioned database. The risk of malignancy was determined according to a mixed reference standard and compared with literature data. RESULTS: In center A, 223 patients with 259 TNs were included into the study. For further analysis, 200 nodules with a reference standard were available. The overall malignancy rate was 2.5% (upper limit of the 95% CI: 5.1%). After the exclusion of scintigraphically hyperfunctioning nodules, the malignancy rate increased slightly to 2.8% (upper limit of the 95% CI: 5.7%). Malignant nodules exhibited sonographic risk features additional to solidity and ttw shape more often than benign ones. In addition to the exclusion of hyperfunctioning nodules, when considering only nodules without additional US risk features, i.e., exclusively solid and ttw-nodules, the malignancy rate decreased to 0.9% (upper limit 95% CI: 3.7%). In center B, from 58 patients, 58 ttw and hypofunctioning TNs on thyroid scans with a reference standard were available. Malignant nodules from center B were always solid and hypoechoic. The overall malignancy rate of hypofunctioning and ttw nodules was 21%, with the lower limit of the 95% CI (one-sided) being 12%. CONCLUSIONS: In primary/secondary care units, the lowest TIRADS categories for indicating FNB, e.g., applying one out of five sonographic risk features, may not be appropriate owing to the much lower a priori malignancy risk in TNs compared to tertiary/quaternary care units. Even the combination of two sonographic risk features, "solidity" and "ttw", may only be appropriate in a limited fashion. In contrast, the preselection of TNs according to hypofunctioning findings on thyroid scans clearly warranted FNB, even when applying only one sonographic risk criterion ("ttw"). For this reason, thyroid scans in TNs may not only be indicated to rule out hyperfunctioning nodules from FNB but also to rule in hypofunctioning ones.

Correct and Incorrect Recommendations for or against Fine Needle Biopsies of Hypofunctioning Thyroid Nodules: Performance of Different Ultrasound-based Risk Stratification Systems.

PURPOSE: To evaluate the recommendations for or against fine needle biopsy (FNB) of hypofunctioning thyroid nodules (TNs) using of five different Ultrasound (US) -based risk stratification systems (RSSs). METHODS: German multicenter study with 563 TNs (≥ 10 mm) in 534 patients who underwent thyroid US and surgery. All TNs were evaluated with ACR TI-RADS, EU-TIRADS, ATA, K-TIRADS 2016 and modified K-TIRADS 2021. A correct recommendation was defined as: malignant TN with recommendation for FNB (appropriate) or benign TN without recommendation for FNB (avoided). An incorrect recommendation was defined as: malignant TN without recommendation for FNB (missed) or benign TN with recommendation for FNB (unnecessary). RESULTS: ACR TI-RADS demonstrated the highest rate of correct (42.3 %) and lowest rate of incorrect recommendations (57.7 %). The other RRSs showed similar results for correct (26.5 %-35.7 %) and incorrect (64.3 %-73.5 %) recommendations. ACR TI-RADS demonstrated the lowest rate of unnecessary (73.4 %) and the highest rate of appropriate (26.6 %) FNB recommendation. For other RSSs, the rates of unnecessary and appropriate FNB were between 75.2 %-77.1 % and 22.9 %-24.8 %. The lowest rate of missed FNB (14.7 %) and the highest rate of avoided FNB (85.3 %) was found for ACR TI-RADS. For the other RSSs, the rates of missed and avoided FNB were between 17.8 %-26.9 % and 73.1 %-82.2 %. When the size cutoff was disregarded, an increase of correct recommendations and a decrease of incorrect recommendations was observed for all RSSs. CONCLUSION: The RSSs vary in their ability to correctly recommend for or against FNB. An understanding of the impact of nodule size cutoffs seems necessary for the future of TIRADS.

Development and evaluation of a new high-TOF-resolution all-digital brain PET system.

Objective.Time-of-flight (TOF) capability and high sensitivity are essential for brain-dedicated positron emission tomography (PET) imaging, as they improve the contrast and the signal-to-noise ratio (SNR) enabling a precise localization of functional mechanisms in the different brain regions.Approach.We present a new brain PET system with transverse and axial field-of-view (FOV) of 320 mm and 255 mm, respectively. The system head is an array of 6 × 6 detection elements, each consisting of a 3.9 × 3.9 × 20 mm3lutetium-yttrium oxyorthosilicate crystal coupled with a 3.93 × 3.93 mm2SiPM. The SiPMs analog signals are individually digitized using the multi-voltage threshold (MVT) technology, employing a 1:1:1 coupling configuration.Main results.The brain PET system exhibits a TOF resolution of 249 ps at 5.3 kBq ml-1, an average sensitivity of 22.1 cps kBq-1, and a noise equivalent count rate (NECR) peak of 150.9 kcps at 8.36 kBq ml-1. Furthermore, the mini-Derenzo phantom study demonstrated the system's ability to distinguish rods with a diameter of 2.0 mm. Moreover, incorporating the TOF reconstruction algorithm in an image quality phantom study optimizes the background variability, resulting in reductions ranging from 44% (37 mm) to 75% (10 mm) with comparable contrast. In the human brain imaging study, the SNR improved by a factor of 1.7 with the inclusion of TOF, increasing from 27.07 to 46.05. Time-dynamic human brain imaging was performed, showing the distinctive traits of cortex and thalamus uptake, as well as of the arterial and venous flow with 2 s per time frame.Significance.The system exhibited a good TOF capability, which is coupled with the high sensitivity and count rate performance based on the MVT digital sampling technique. The developed TOF-enabled brain PET system opens the possibility of precise kinetic brain PET imaging, towards new quantitative predictive brain diagnostics.

Artificial Intelligence-powered automatic volume calculation in medical images - available tools, performance and challenges for nuclear medicine.

Volumetry is crucial in oncology and endocrinology, for diagnosis, treatment planning, and evaluating response to therapy for several diseases. The integration of Artificial Intelligence (AI) and Deep Learning (DL) has significantly accelerated the automatization of volumetric calculations, enhancing accuracy and reducing variability and labor. In this review, we show that a high correlation has been observed between Machine Learning (ML) methods and expert assessments in tumor volumetry; Yet, it is recognized as more challenging than organ volumetry. Liver volumetry has shown progression in accuracy with a decrease in error. If a relative error below 10 % is acceptable, ML-based liver volumetry can be considered reliable for standardized imaging protocols if used in patients without major anomalies. Similarly, ML-supported automatic kidney volumetry has also shown consistency and reliability in volumetric calculations. In contrast, AI-supported thyroid volumetry has not been extensively developed, despite initial works in 3D ultrasound showing promising results in terms of accuracy and reproducibility. Despite the advancements presented in the reviewed literature, the lack of standardization limits the generalizability of ML methods across diverse scenarios. The domain gap, i. e., the difference in probability distribution of training and inference data, is of paramount importance before clinical deployment of AI, to maintain accuracy and reliability in patient care. The increasing availability of improved segmentation tools is expected to further incorporate AI methods into routine workflows where volumetry will play a more prominent role in radionuclide therapy planning and quantitative follow-up of disease evolution.

An Innovative Non-Linear Prediction Model for Clinical Benefit in Women with Newly Diagnosed Breast Cancer Using Baseline FDG-PET/CT and Clinical Data.

Objectives: We aimed to develop a novel non-linear statistical model integrating primary tumor features on baseline [18F]-fluorodeoxyglucose positron emission tomography/computed tomography (FDG-PET/CT), molecular subtype, and clinical data for treatment benefit prediction in women with newly diagnosed breast cancer using innovative statistical techniques, as opposed to conventional methodological approaches. Methods: In this single-center retrospective study, we conducted a comprehensive assessment of women newly diagnosed with breast cancer who had undergone a FDG-PET/CT scan for staging prior to treatment. Primary tumor (PT) volume, maximum and mean standardized uptake value (SUVmax and SUVmean), metabolic tumor volume (MTV), and total lesion glycolysis (TLG) were measured on PET/CT. Clinical data including clinical staging (TNM) but also PT anatomical site, histology, receptor status, proliferation index, and molecular subtype were obtained from the medical records. Overall survival (OS), progression-free survival (PFS), and clinical benefit (CB) were assessed as endpoints. A logistic generalized additive model was chosen as the statistical approach to assess the impact of all listed variables on CB. Results: 70 women with newly diagnosed breast cancer (mean age 63.3 ± 15.4 years) were included. The most common location of breast cancer was the upper outer quadrant (40.0%) in the left breast (52.9%). An invasive ductal adenocarcinoma (88.6%) with a high tumor proliferation index (mean ki-67 expression 35.1 ± 24.5%) and molecular subtype B (51.4%) was by far the most detected breast tumor. Most PTs displayed on hybrid imaging a greater volume (12.8 ± 30.4 cm3) with hypermetabolism (mean ± SD of PT maximum SUVmax, SUVmean, MTV, and TLG, respectively: 8.1 ± 7.2, 4.9 ± 4.4, 12.7 ± 30.4, and 47.4 ± 80.2). Higher PT volume (p < 0.01), SUVmax (p = 0.04), SUVmean (p = 0.03), and MTV (<0.01) significantly compromised CB. A considerable majority of patients survived throughout this period (92.8%), while five women died (7.2%). In fact, the OS was 31.7 ± 14.2 months and PFS was 30.2 ± 14.1 months. A multivariate prediction model for CB with excellent accuracy could be developed using age, body mass index (BMI), T, M, PT TLG, and PT volume as predictive parameters. PT volume and PT TLG demonstrated a significant influence on CB in lower ranges; however, beyond a specific cutoff value (respectively, 29.52 cm3 for PT volume and 161.95 cm3 for PT TLG), their impact on CB only reached negligible levels. Ultimately, the absence of distant metastasis M displayed a strong positive impact on CB far ahead of the tumor size T (standardized average estimate 0.88 vs. 0.4). Conclusions: Our results emphasized the pivotal role played by FDG-PET/CT prior to treatment in forecasting treatment outcomes in women newly diagnosed with breast cancer. Nevertheless, careful consideration is required when selecting the methodological approach, as our innovative statistical techniques unveiled non-linear influences of predictive biomarkers on treatment benefit, highlighting also the importance of early breast cancer diagnosis.

Combination of tumor asphericity and an extracellular matrix-related prognostic gene signature in non-small cell lung cancer patients.

One important aim of precision oncology is a personalized treatment of patients. This can be achieved by various biomarkers, especially imaging parameters and gene expression signatures are commonly used. So far, combination approaches are sparse. The aim of the study was to independently validate the prognostic value of the novel positron emission tomography (PET) parameter tumor asphericity (ASP) in non small cell lung cancer (NSCLC) patients and to investigate associations between published gene expression profiles and ASP. This was a retrospective evaluation of PET imaging and gene expression data from three public databases and two institutional datasets. The whole cohort comprised 253 NSCLC patients, all treated with curative intent surgery. Clinical parameters, standard PET parameters and ASP were evaluated in all patients. Additional gene expression data were available for 120 patients. Univariate Cox regression and Kaplan-Meier analysis was performed for the primary endpoint progression-free survival (PFS) and additional endpoints. Furthermore, multivariate cox regression testing was performed including clinically significant parameters, ASP, and the extracellular matrix-related prognostic gene signature (EPPI). In the whole cohort, a significant association with PFS was observed for ASP (p < 0.001) and EPPI (p = 0.012). Upon multivariate testing, EPPI remained significantly associated with PFS (p = 0.018) in the subgroup of patients with additional gene expression data, while ASP was significantly associated with PFS in the whole cohort (p = 0.012). In stage II patients, ASP was significantly associated with PFS (p = 0.009), and a previously published cutoff value for ASP (19.5%) was successfully validated (p = 0.008). In patients with additional gene expression data, EPPI showed a significant association with PFS, too (p = 0.033). The exploratory combination of ASP and EPPI showed that the combinatory approach has potential to further improve patient stratification compared to the use of only one parameter. We report the first successful validation of EPPI and ASP in stage II NSCLC patients. The combination of both parameters seems to be a very promising approach for improvement of risk stratification in a group of patients with urgent need for a more personalized treatment approach.

Molecular Theranostics in Radioiodine-Refractory Differentiated Thyroid Cancer.

Differentiated thyroid cancer (DTC) is the most common subtype of thyroid cancer and has an excellent overall prognosis. However, metastatic DTC in certain cases may have a poor prognosis as it becomes radioiodine-refractory. Molecular imaging is essential for disease evaluation and further management. The most commonly used tracers are [18F]FDG and isotopes of radioiodine. Several other radiopharmaceuticals may be used as well, with different diagnostic performances. This review article aims to summarize radiopharmaceuticals used in patients with radioiodine-refractory DTC (RAI-R DTC), focusing on their different molecular pathways. Additionally, it will demonstrate possible applications of the theranostics approach to this subgroup of metastatic DTC.

Thyroid Nodule Detection and Region Estimation in Ultrasound Images: A Comparison between Physicians and an Automated Decision Support System Approach.

BACKGROUND: Thyroid nodules are very common. In most cases, they are benign, but they can be malignant in a low percentage of cases. The accurate assessment of these nodules is critical to choosing the next diagnostic steps and potential treatment. Ultrasound (US) imaging, the primary modality for assessing these nodules, can lack objectivity due to varying expertise among physicians. This leads to observer variability, potentially affecting patient outcomes. PURPOSE: This study aims to assess the potential of a Decision Support System (DSS) in reducing these variabilities for thyroid nodule detection and region estimation using US images, particularly in lesser experienced physicians. METHODS: Three physicians with varying levels of experience evaluated thyroid nodules on US images, focusing on nodule detection and estimating cystic and solid regions. The outcomes were compared to those obtained from a DSS for comparison. Metrics such as classification match percentage and variance percentage were used to quantify differences. RESULTS: Notable disparities exist between physician evaluations and the DSS assessments: the overall classification match percentage was just 19.2%. Individually, Physicians 1, 2, and 3 had match percentages of 57.6%, 42.3%, and 46.1% with the DSS, respectively. Variances in assessments highlight the subjectivity and observer variability based on physician experience levels. CONCLUSIONS: The evident variability among physician evaluations underscores the need for supplementary decision-making tools. Given its consistency, the CAD offers potential as a reliable "second opinion" tool, minimizing human-induced variabilities in the critical diagnostic process of thyroid nodules using US images. Future integration of such systems could bolster diagnostic precision and improve patient outcomes.

Long-Term Survival Analysis and Prognostic Factors of Arabic Patients with Differentiated Thyroid Carcinoma: A 20-Year Observational Study at the King Hussein Cancer Center (KHCC) Involving 528 Patients.

DTC accounts for the majority of endocrine tumors. While the incidence of thyroid cancer has been increasing globally over the past few decades, papillary thyroid carcinoma (PTC) generally shows an excellent prognosis, except in cases with aggressive clinicopathological features. This study aimed to assess the 5- and 10-year overall survival (OS) and progression-free survival (PFS) of 528 Arabic patients diagnosed with primary DTC from 1998 to 2021. Additionally, the study aimed to analyze the impact of various factors on both OS and PFS. An univariable survival analysis was conducted using Kaplan-Meier curves. The 5- and 10-year OS for patients with DTC have exceeded 95%. Additionally, PFS showed very good rates (ranging between 96.5 and 85% at 5 and 10 years, respectively). Age, male gender, risk of recurrence, and distant metastasis were identified as the main negative prognostic factors for both OS and PFS, while RAI treatment was found to be a significant factor in improving OS. Moreover, adherence to the King Hussein Cancer Center's (KHCC) CPG demonstrated significant improvement in PFS. These findings highlight common prognostic factors and favorable outcomes in Arabic patients with DTC treated at a tertiary cancer center using standard of care approaches.

Predictive Value of Total Metabolic Tumor Burden Prior to Treatment in NSCLC Patients Treated with Immune Checkpoint Inhibition.

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.

It is the locus coeruleus! Or is it?: a proposition for analyses and reporting standards for structural and functional magnetic resonance imaging of the noradrenergic locus coeruleus.

The noradrenergic locus coeruleus (LC) is one of the protein pathology epicenters in neurodegenerative diseases. In contrast to PET (positron emission tomography), MRI (magnetic resonance imaging) offers the spatial resolution necessary to investigate the 3-4 mm wide and 1.5 cm long LC. However, standard data postprocessing is often too spatially imprecise to allow investigating the structure and function of the LC at the group level. Our analysis pipeline uses a combination of existing toolboxes (SPM12, ANTs, FSL, FreeSurfer), and is tailored towards achieving suitable spatial precision in the brainstem area. Its effectiveness is demonstrated using 2 datasets comprising both younger and older adults. We also suggest quality assessment procedures which allow to quantify the spatial precision obtained. Spatial deviations below 2.5 mm in the LC area are achieved, which is superior to current standard approaches. Relevant for ageing and clinical researchers interested in brainstem imaging, we provide a tool for more reliable analyses of structural and functional LC imaging data which can be also adapted for investigating other nuclei of the brainstem.

Current perspectives on the management of patients with advanced RET-driven thyroid cancer in Europe.

The incidence of thyroid cancer is increasing worldwide with the disease burden in Europe second only to that in Asia. In the last several decades, molecular pathways central to the pathogenesis of thyroid cancer have revealed a spectrum of targetable kinases/kinase receptors and oncogenic drivers characteristic of each histologic subtype, such as differentiated thyroid cancer, including papillary, follicular, and medullary thyroid cancer. Oncogenic alterations identified include B-Raf proto-oncogene (BRAF) fusions and mutations, neurotrophic tyrosine receptor kinase (NTRK) gene fusions, and rearranged during transfection (RET) receptor tyrosine kinase fusion and mutations. Multikinase inhibitors (MKIs) targeting RET in addition to multiple other kinases, such as sorafenib, lenvatinib and cabozantinib, have shown favourable activity in advanced radioiodine-refractory differentiated thyroid cancer or RET-altered medullary thyroid cancer; however, the clinical utility of MKI RET inhibition is limited by off-target toxicity resulting in high rates of dose reduction and drug discontinuation. Newer and selective RET inhibitors, selpercatinib and pralsetinib, have demonstrated potent efficacy and favourable toxicity profiles in clinical trials in the treatment of RET-driven advanced thyroid cancer and are now a therapeutic option in some clinical settings. Importantly, the optimal benefits of available specific targeted treatments for advanced RET-driven thyroid cancer require genetic testing. Prior to the initiation of systemic therapy, and in treatment-naïve patients, RET inhibitors may be offered as first-line therapy if a RET alteration is found, supported by a multidisciplinary team approach.

Prospective Evaluation of Quantitative F-18-FDG-PET/CT for Pre-Operative Thoracic Lymph Node Staging in Patients with Lung Cancer as a Target for Computer-Aided Diagnosis.

PURPOSE: Pre-operative assessment of thoracic lymphonodal (LN) involvement in patients with lung cancer (LC) is crucial when choosing the treatment modality. Visual assessment of F-18-FDG-PET/CT (PET/CT) is well established, however, there is still a need for prospective quantitative data to differentiate benign from malignant lesions which would simplify staging and guide the further implementation of computer-aided diagnosis (CAD). METHODS: In this prospective study, 37 patients with confirmed lung cancer (m/f = 24/13; age: 70 [52-83] years) were analyzed. All patients underwent PET/CT and quantitative data (standardized uptake values) were obtained. Histological results were available for 101 thoracic lymph nodes. Quantitative data were matched to determine cut-off values for delineation between benign vs. malignant lymph nodes. Furthermore, a scoring system derived from these cut-off values was established. Statistical analyses were performed through ROC analysis. RESULTS: Quantitative analysis revealed the optimal cut-off values (p < 0.01) for the differentiation between benign and malignant thoracic lymph nodes in patients suffering from lung cancer. The respective areas under the curve (AUC) ranged from 0.86 to 0.94. The highest AUC for a ratio of lymph node to healthy lung tissue was 0.94. The resulting accuracy ranged from 78.2% to 89.1%. A dedicated scoring system led to an AUC of 0.93 with a negative predictive value of 95.4%. CONCLUSION: Quantitative analysis of F-18-FDG-PET/CT data provides reliable results for delineation between benign and malignant thoracic lymph nodes. Thus, quantitative parameters can improve diagnostic accuracy and reliability and can also facilitate the handling of the steadily increasing number of clinical examinations.

[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.

Gestational and Non-gestational Trophoblastic Neoplasia. Guideline of the DGGG, OEGGG and SGGG (S2k-Level, AWMF Registry No. 032/049, April 2022).

Purpose The aim was to develop and update a guideline which would improve the quality of care offered to women with gestational and non-gestational trophoblastic disease, a group of diseases characterized by their rarity and biological heterogeneity. Methods In accordance with the method used to compile S2k-guidelines, the guideline authors carried out a search of the literature (MEDLINE) for the period 1/2020 to 12/2021 and evaluated the recent literature. No key questions were formulated. No structured literature search with methodical evaluation and assessment of the level of evidence was carried out. The text of the precursor version of the guideline from 2019 was updated based on the most recent literature, and new statements and recommendations were drafted. Recommendations The updated guideline contains recommendations for the diagnosis and therapy of women with hydatidiform mole (partial and complete moles), gestational trophoblastic neoplasia after pregnancy or without prior pregnancy, persistent trophoblastic disease after molar pregnancy, invasive moles, choriocarcinoma, placental site nodules, placental site trophoblastic tumor, hyperplasia at the implantation site und epithelioid trophoblastic tumor. Separate chapters cover the determination and assessment of human chorionic gonadotropin (hCG), histopathological evaluation of specimens, and the appropriate molecular pathological and immunohistochemical diagnostic procedures. Separate chapters on immunotherapy, surgical therapy, multiple pregnancies with simultaneous trophoblastic disease, and pregnancy after trophoblastic disease were formulated, and the corresponding recommendations agreed upon.

Postoperative thyroglobulin as a yard-stick for radioiodine therapy: decision tree analysis in a European multicenter series of 1317 patients with differentiated thyroid cancer.

PURPOSE: An accurate postoperative assessment is pivotal to inform postoperative 131I treatment in patients with differentiated thyroid cancer (DTC). We developed a predictive model for post-treatment whole-body scintigraphy (PT-WBS) results (as a proxy for persistent disease) by adopting a decision tree model. METHODS: Age, sex, histology, T stage, N stage, risk classes, remnant estimation, TSH, and Tg were identified as potential predictors and were put into regression algorithm (conditional inference tree, ctree) to develop a risk stratification model for predicting the presence of metastases in PT-WBS. RESULTS: The lymph node (N) stage identified a partition of the population into two subgroups (N-positive vs N-negative). Among N-positive patients, a Tg value > 23.3 ng/mL conferred a 83% probability to have metastatic disease compared to those with lower Tg values. Additionally, N-negative patients were further substratified in three subgroups with different risk rates according to their Tg values. The model remained stable and reproducible in the iterative process of cross validation. CONCLUSIONS: We developed a simple and robust decision tree model able to provide reliable informations on the probability of persistent/metastatic DTC after surgery. These information may guide post-surgery 131I administration and select patients requiring curative rather than adjuvant 131I therapy schedules.