Four-dimensional computed tomography as first-line imaging in primary hyperparathyroidism, a retrospective comparison to conventional imaging in a predominantly single adenoma population.

BACKGROUND: To determine the use of four-dimensional CT as first-line imaging compared to the traditional combination of ultrasound and [99mTc]Tc-Sestamibi SPECT. MATERIALS AND METHODS: Retrospective review of preoperative imaging in patients with primary hyperparathyroidism, who underwent parathyroidectomy between 2012 and 2021. In one group, the combination ultrasound and [99mTc]Tc-Sestamibi SPECT was used as first-line imaging (n = 54), in the other group four-dimensional CT was the first-line imaging modality (n = 51). Sensitivity and positive predictive value were calculated on patient, lateralisation and localisation level. The need for additional imaging was also assessed for both groups. RESULTS: Four-dimensional CT had a significantly higher sensitivity compared to the combination of ultrasound/[99mTc]Tc-Sestamibi SPECT on patient and localisation level (70.6% vs. 51.9%, p = 0.049 and 60.8% vs. 35.2%, p = 0.009 respectively). Sensitivity for lateralisation also appeared higher, but did not reach significance (62.7% vs. 44.4%, p = 0.060). Positive predictive value was not significantly higher for four-dimensional CT compared to ultrasound and [99mTc]Tc-Sestamibi SPECT (88.9% vs. 85.7% for lateralisation and 86.1% vs. 67.9% for localisation respectively). Additional imaging was required in 14 patients with four-dimensional CT as first-line imaging (27.4%) consisting of 2 ultrasound/[99mTc]Tc-Sestamibi SPECT and 13 [18F]fluorocholine PET/CT, compared to 24 patients with ultrasound/[99mTc]Tc-Sestamibi SPECT as first-line imaging (44.4%), requiring 22 four-dimensional CT and 9 [18F]fluorocholine PET/CT. CONCLUSIONS: Four-dimensional CT as the sole first-line parathyroid imaging modality had higher sensitivity than the combination of ultrasound and [99mTc]Tc-Sestamibi SPECT, therefore requiring fewer additional procedures. Although the most costly, [18F]fluorocholine PET/CT was the most effective technique to localise parathyroid adenoma in case all other imaging was negative.

The Impact of Baseline PSMA PET/CT Versus CT on Outcomes of 223Ra Therapy in Metastatic Castration-Resistant Prostate Cancer Patients.

Imaging before 223Ra-dichloride (223Ra) therapy is crucial for selecting metastatic castration-resistant prostate cancer (mCRPC) patients with bone-only disease. The purpose of this study was to evaluate if baseline prostate-specific membrane antigen (PSMA) PET/CT (bPSMA) versus CT is associated with outcomes of 223Ra therapy. Methods: A secondary analysis of the data of a prospective observational study (NCT04995614) was performed. Patients received a maximum of 6 223Ra cycles and were retrospectively divided into the bPSMA or baseline CT (bCT) groups. All patients received baseline bone scintigraphy. Primary endpoints were alkaline phosphatase and prostate-specific antigen response. Secondary endpoints were overall survival (OS) and radiologic response. Results: Between 2017 and 2020, 122 mCRPC patients were included: 18 (14.8%) in the bPSMA group and 104 (85.2%) in the bCT group. All baseline characteristics were comparable. No significant differences in alkaline phosphatase or prostate-specific antigen response were found. The bCT group showed an OS significantly shorter than that of the bPSMA group (12.4 vs. 19.9 mo, P = 0.038). In 31 of 76 patients (40.1%) in the bCT group who also received posttherapy CT, lymph node or visceral metastases (soft-tissue involvement [STI]) were detected after 223Ra therapy, compared with 0 of 15 patients in the bPSMA group who received posttherapy PSMA PET/CT or CT. No significant difference in OS was found between patients in the bCT or posttherapy CT subgroup without STI (46/76) and the bPSMA group. Conclusion: bPSMA versus CT does not seem to impact biochemical response during 223Ra therapy in mCRPC patients. Nevertheless, patients in the bCT group had a significantly shorter OS, most likely due to underdetection of STI in this group. Therefore, replacing bCT with PSMA PET/CT appears to be a valuable screening method for identifying patients who will benefit most from 223Ra therapy.

Molecular imaging predicts lack of T-DM1 response in advanced HER2-positive breast cancer (final results of ZEPHIR trial).

Efficacy of the human epidermal growth factor receptor (HER)2-targeting trastuzumab emtansine (T-DM1) in breast cancer (BC) relies on HER2 status determined by immunohistochemistry or fluorescence in-situ hybridization. Heterogeneity in HER2 expression, however, generates interest in "whole-body" assessment of HER2 status using molecular imaging. We evaluated the role of HER2-targeted molecular imaging in detecting HER2-positive BC lesions and patients unlikely to respond to T-DM1. Patients underwent zirconium-89 (89Zr) trastuzumab (HER2) PET/CT and [18F]-2-fluoro-2-deoxy-D-glucose (FDG) PET/CT before T-DM1 initiation. Based on 89Zr-trastuzumab uptake, lesions were visually classified as HER2-positive (visible/high uptake) or HER2-negative (background/close to background activity). According to proportion of FDG-avid tumor load showing 89Zr-trastuzumab uptake (entire/dominant part or minor/no part), patients were classified as HER2-positive and HER2-negative, respectively. Out of 265 measurable lesions, 93 (35%) were HER2-negative, distributed among 42 of the 90 included patients. Of these, 18 (19%) lesions belonging to 11 patients responded anatomically (>30% decrease in axial diameter from baseline) after three T-DM1 cycles, resulting in an 81% negative predictive value (NPV) of the HER2 PET/CT. In combination with early metabolic response assessment on FDG PET/CT performed before the second T-DM1 cycle, NPVs of 91% and 100% were reached in predicting lesion-based and patient-based (RECIST1.1) response, respectively. Therefore, HER2 PET/CT, alone or in combination with early FDG PET/CT, can successfully identify BC lesions and patients with a low probability of clinical benefit from T-DM1.

Molecular Diagnostics and [18F]FDG-PET/CT in Indeterminate Thyroid Nodules: Complementing Techniques or Waste of Valuable Resources?

Background: An accurate preoperative workup of cytologically indeterminate thyroid nodules (ITN) may rule out malignancy and avoid diagnostic surgery for benign nodules. This study assessed the performance of molecular diagnostics (MD) and 2-[18F]fluoro-2-deoxy-d-glucose ([18F]FDG)-positron emission tomography/computed tomography (PET/CT) in ITN, including their combined use, and explored whether molecular alterations drive the differences in [18F]FDG uptake among benign nodules. Methods: Adult, euthyroid patients with a Bethesda III or IV thyroid nodule were prospectively included in this multicenter study. They all underwent MD and an [18F]FDG-PET/CT scan of the neck. MD was performed using custom next-generation sequencing panels for somatic mutations, gene fusions, and copy number alterations and loss of heterozygosity. Sensitivity, specificity, negative and positive predictive value (NPV, PPV), and benign call rate (BCR) were assessed for MD and [18F]FDG-PET/CT separately and for a combined approach using both techniques. Results: In 115 of the 132 (87%) included patients, MD yielded a diagnostic result on cytology. Sensitivity, specificity, NPV, PPV, and BCR were 80%, 69%, 91%, 48%, and 57% for MD, and 93%, 41%, 95%, 36%, and 32% for [18F]FDG-PET/CT, respectively. When combined, sensitivity and specificity were 95% and 44% for a double-negative test (i.e., negative MD plus negative [18F]FDG-PET/CT) and 68% and 86% for a double-positive test, respectively. Concordance was 63% (82/130) between MD and [18F]FDG-PET/CT. There were more MD-positive nodules among the [18F]FDG-positive benign nodules (25/59, 42%, including 11 (44%) isolated RAS mutations) than among the [18F]FDG-negative benign nodules (7/30, 19%, p = 0.02). In oncocytic ITN, the BCR of [18F]FDG-PET/CT was mere 3% and MD was the superior technique. Conclusions: MD and [18F]FDG-PET/CT are both accurate rule-out tests when unresected nodules that remain unchanged on ultrasound follow-up are considered benign. It may vary worldwide which test is considered most suitable, depending on local availability of diagnostics, expertise, and cost-effectiveness considerations. Although complementary, the benefits of their combined use may be confined when therapeutic consequences are considered, and should therefore not routinely be recommended. In nononcocytic ITN, sequential testing may be considered in case of a first-step MD negative test to confirm that withholding diagnostic surgery is oncologically safe. In oncocytic ITN, after further validation studies, MD might be considered. Clinical Trial Registration: This trial is registered with ClinicalTrials.gov: NCT02208544 (August 5, 2014), https://clinicaltrials.gov/ct2/show/NCT02208544.

A clinically applicable molecular classification of oncocytic cell thyroid nodules.

Whole chromosome instability with near-whole genome haploidization (GH) and subsequent endoreduplication is considered a main genomic driver in the tumorigenesis of oncocytic cell thyroid neoplasms (OCN). These copy number alterations (CNA) occur less frequently in oncocytic thyroid adenoma (OA) than in oncocytic carcinoma (OCA), suggesting a continuous process. The current study described the CNA patterns in a cohort of 30 benign and malignant OCN, observed using a next-generation sequencing (NGS) panel that assesses genome-wide loss of heterozygosity (LOH) and chromosomal imbalances using 1500 single-nucleotide polymorphisms (SNPs) across all autosomes and the X chromosome in DNA derived from cytological and histological samples. Observed CNA patterns were verified using multiparameter DNA flow cytometry with or without whole-genome SNP array analysis and lesser-allele intensity-ratio (LAIR) analysis. On CNA-LOH analysis using the NGS panel, GH-type CNA were observed in 4 of 11 (36%) OA and in 14 of 16 OCA (88%). Endoreduplication was suspected in 8 of 16 (50%) OCA, all with more extensive GH-type CNA (P < 0.001). Reciprocal chromosomal imbalance type CNA, characterized by (imbalanced) chromosomal copy number gains and associated with benign disease, were observed in 6 of 11 (55%) OA and one equivocal case of OCA. CNA patterns were different between the histopathological subgroups (P < 0.001). By applying the structured interpretation and considerations provided by the current study, CNA-LOH analysis using an NGS panel that is feasible for daily practice may be of great added value to the widespread application of molecular diagnostics in the diagnosis and risk stratification of OCN.

Preoperative imaging in primary hyperparathyroidism patients using 4DCT subtraction maps, a report of three cases.

Four-dimensional computed tomography (4DCT) is one of the preoperative imaging modalities that can be used to localize a parathyroid adenoma in primary hyperparathyroidism patients however, sensitivity differs in literature and could be improved especially for multiglandular hyperplasia or double adenomas. The most robust feature on the 4DCT for the differentiation between parathyroid adenoma and thyroid gland tissue is arterial enhancement. To make this better visible, we have developed a subtraction map that shows arterial enhancement as a color scale to increase sensitivity for 4DCT. In this report of 3 cases, we present the usefulness of this subtraction map in a 54-year-old male, a 57-year-old female and a 51-year-old male. Subtraction maps may increase sensitivity for 4DCT, especially for multiglandular hyperplasia or double adenomas.

Joint EANM/SNMMI procedure guideline for the use of 177Lu-labeled PSMA-targeted radioligand-therapy (177Lu-PSMA-RLT).

Prostate-specific membrane antigen (PSMA) is expressed by the majority of clinically significant prostate adenocarcinomas, and patients with target-positive disease can easily be identified by PSMA PET imaging. Promising results with PSMA-targeted radiopharmaceutical therapy have already been obtained in early-phase studies using various combinations of targeting molecules and radiolabels. Definitive evidence of the safety and efficacy of [177Lu]Lu-PSMA-617 in combination with standard-of-care has been demonstrated in patients with metastatic castration-resistant prostate cancer, whose disease had progressed after or during at least one taxane regimen and at least one novel androgen-axis drug. Preliminary data suggest that 177Lu-PSMA-radioligand therapy (RLT) also has high potential in additional clinical situations. Hence, the radiopharmaceuticals [177Lu]Lu-PSMA-617 and [177Lu]Lu-PSMA-I&T are currently being evaluated in ongoing phase 3 trials. The purpose of this guideline is to assist nuclear medicine personnel, to select patients with highest potential to benefit from 177Lu-PSMA-RLT, to perform the procedure in accordance with current best practice, and to prepare for possible side effects and their clinical management. We also provide expert advice, to identify those clinical situations which may justify the off-label use of [177Lu]Lu-PSMA-617 or other emerging ligands on an individual patient basis.

[89Zr]-immuno-PET prediction of response to rituximab treatment in patients with therapy refractory interstitial pneumonitis: a phase 2 trial.

INTRODUCTION: Immune-mediated interstitial pneumonitis may be treated with anti-CD20 therapy after failure of conventional therapies. However, clinical response is variable. It was hypothesized that autoreactive CD20-positive cells may play an important role in this variability. This prospective study aims to elucidate if imaging of CD20-positive cells in the lungs allows prediction of the response to anti-CD20 treatment. METHODS: Twenty-one patients with immune-mediated interstitial lung disease (ILD) with deteriorated pulmonary function received a dose of 1000 mg rituximab on day 1 and day 14 spiked with a tracer dose of radiolabeled [89Zr]-rituximab. PET/CT was performed on days 3 and 6. Standardized uptake values (SUV) were calculated as a measure for pulmonary CD20 expression. Based on pulmonary function tests (PFT), forced vital capacity (FVC), and diffusing capacity for carbon monoxide (DLCO), prior to and 6 months after treatment, patients were classified as responder (stable disease or improvement) or non-responder. RESULTS: Fifteen patients (71%) were classified as responder. Pulmonary [89Zr]-rituximab PET SUVmean was significantly correlated with the change in FVC and DLCO (K = 0.49 and 0.56, respectively) when using target-to-background ratios, but not when using SUVmean alone. [89Zr]-rituximab SUVmean was significantly higher in responders than in non-responders (0.35 SD 0.09 vs. 0.23 SD 0.06; P = 0.02). CONCLUSION: Rituximab treatment was effective in the majority of patients. As a higher pulmonary uptake of [89Zr]-rituximab correlated with improvement of PFT and treatment outcome, [89Zr]-rituximab PET imaging may serve as a potential predictive biomarker for anti-CD20 therapy. TRIAL REGISTRATION: Clinicaltrials.gov identifier NCT02251964.

[89Zr]Zr-DFO-girentuximab and [18F]FDG PET/CT to Predict Watchful Waiting Duration in Patients with Metastatic Clear-cell Renal Cell Carcinoma.

PURPOSE: Watchful waiting (WW) can be considered for patients with metastatic clear-cell renal cell carcinoma (mccRCC) with good or intermediate prognosis, especially those with <2 International Metastatic RCC Database Consortium criteria and ≤2 metastatic sites [referred to as watch and wait ("W&W") criteria]. The IMaging PAtients for Cancer drug SelecTion-Renal Cell Carcinoma study objective was to assess the predictive value of [18F]FDG PET/CT and [89Zr]Zr-DFO-girentuximab PET/CT for WW duration in patients with mccRCC. EXPERIMENTAL DESIGN: Between February 2015 and March 2018, 48 patients were enrolled, including 40 evaluable patients with good (n = 14) and intermediate (n = 26) prognosis. Baseline contrast-enhanced CT, [18F]FDG and [89Zr]Zr-DFO-girentuximab PET/CT were performed. Primary endpoint was the time to disease progression warranting systemic treatment. Maximum standardized uptake values (SUVmax) were measured using lesions on CT images coregistered to PET/CT. High and low uptake groups were defined on the basis of median geometric mean SUVmax of RECIST-measurable lesions across patients. RESULTS: The median WW time was 16.1 months [95% confidence interval (CI): 9.0-31.7]. The median WW period was shorter in patients with high [18F]FDG tumor uptake than those with low uptake (9.0 vs. 36.2 months; HR, 5.6; 95% CI: 2.4-14.7; P < 0.001). Patients with high [89Zr]Zr-DFO-girentuximab tumor uptake had a median WW period of 9.3 versus 21.3 months with low uptake (HR, 1.7; 95% CI: 0.9-3.3; P = 0.13). Patients with "W&W criteria" had a longer median WW period of 21.3 compared with patients without: 9.3 months (HR, 1.9; 95% CI: 0.9-3.9; Pone-sided = 0.034). Adding [18F]FDG uptake to the "W&W criteria" improved the prediction of WW duration (P < 0.001); whereas [89Zr]Zr-DFO-girentuximab did not (P = 0.53). CONCLUSIONS: In patients with good- or intermediate-risk mccRCC, low [18F]FDG uptake is associated with prolonged WW. This study shows the predictive value of the "W&W criteria" for WW duration and shows the potential of [18F]FDG-PET/CT to further improve this.

Health-related quality of life, psychological distress, and fatigue in metastatic castration-resistant prostate cancer patients treated with radium-223 therapy.

BACKGROUND: Radium-223 is a registered treatment option for symptomatic bone metastatic castration-resistant prostate cancer (mCRPC). Aim of this multicenter, prospective observational cohort study was to evaluate health-related quality of life (HR-QoL), psychological distress and fatigue in mCRPC patients treated with radium-223. METHODS: Primary endpoint was cancer-specific and bone metastases-related HR-QoL, as measured by the EORTC QLQ-C30 and BM-22 questionnaires. Secondary endpoints were psychological distress and fatigue, evaluated by the HADS and CIS-Fatigue questionnaires. Outcomes were analyzed for the total cohort and between subgroups (1-3 versus 4-5 versus 6 radium-223 injections). A trajectory analysis was performed to explore HR-QoL patterns over time. RESULTS: In total, 122 patients were included for analysis. Baseline HR-QoL, pain intensity, psychological distress and fatigue were worse in patients who did not complete radium-223 therapy. In patients who completed therapy, stabilization of HR-QoL was perceived and psychological distress and fatigue remained stable, whereas clinically meaningful and statistically significant deterioration of HR-QoL, psychological distress and fatigue over time was observed in patients who discontinued radium-223 therapy. Trajectory analysis revealed that HR-QoL deterioration over time was more likely in patients with baseline opioid use, low hemoglobin and high alkaline phosphatase levels. CONCLUSIONS: Patients who discontinued radium-223 therapy showed worse HR-QoL, psychological distress and fatigue at baseline and more frequent deterioration of HR-QoL, psychological distress and fatigue over time when compared to patients who completed therapy. Specific attention with regard to HR-QoL during follow-up is indicated in patients with opioid use, low hemoglobin and high alkaline phosphatase levels before radium-223 therapy initiation. CLINICAL TRIAL REGISTRATION NUMBER: NCT04995614.

[18F]FDG Uptake and Expression of Immunohistochemical Markers Related to Glycolysis, Hypoxia, and Proliferation in Indeterminate Thyroid Nodules.

PURPOSE: The current study explored the association between 2-[18F]fluoro-2-deoxy-D-glucose ([18F]FDG) uptake and the quantitative expression of immunohistochemical markers related to glucose metabolism, hypoxia, and cell proliferation in benign and malignant thyroid nodules of indeterminate cytology. PROCEDURES: Using a case-control design, 24 patients were selected from participants of a randomized controlled multicenter trial (NCT02208544) in which [18F]FDG-PET/CT and thyroid surgery were performed for Bethesda III and IV nodules. Three equally sized groups of [18F]FDG-positive malignant, [18F]FDG-positive benign, and [18F]FDG-negative benign nodules were included. Immunohistochemical staining was performed for glucose transporters (GLUT) 1, 3, and 4; hexokinases (HK) 1 and 2; hypoxia-inducible factor-1 alpha (HIF1α; monocarboxylate transporter 4 (MCT4); carbonic anhydrase IX (CA-IX); vascular endothelial growth factor (VEGF); sodium-iodide symporter (NIS); and Ki-67. Marker expression was scored using an immunoreactive score. Unsupervised cluster analysis was performed. The immunoreactive score was correlated to the maximum and peak standardized uptake values (SUVmax, SUVpeak) and SUVmax ratio (SUVmax of nodule/background SUVmax of contralateral, normal thyroid) of the [18F]FDG-PET/CT using the Spearman's rank correlation coefficient and compared between the three groups using Kruskal-Wallis tests. RESULTS: The expression of GLUT1, GLUT3, HK2, and MCT4 was strongly positively correlated with the SUVmax, SUVpeak, and SUVmax ratio. The expression of GLUT1 (p = 0.009), HK2 (p = 0.02), MCT4 (p = 0.01), and VEGF (p = 0.007) was statistically significantly different between [18F]FDG-positive benign nodules, [18F]FDG-positive thyroid carcinomas, and [18F]FDG-negative benign nodules. In both [18F]FDG-positive benign nodules and [18F]FDG-positive thyroid carcinomas, the expression of GLUT1, HK2, and MCT4 was increased as compared to [18F]FDG-negative benign nodules. VEGF expression was higher in [18F]FDG-positive thyroid carcinomas as compared to [18F]FDG-negative and [18F]FDG-positive benign nodules. CONCLUSIONS: Our results suggest that [18F]FDG-positive benign thyroid nodules undergo changes in protein expression similar to those in thyroid carcinomas. To expand the understanding of the metabolic changes in benign and malignant thyroid nodules, further research is required, including correlation with underlying genetic alterations.

[18F]FDG PET/CT in Large Vessel Vasculitis: The Impact of Expertise and Confounders on Image Analysis.

BACKGROUND: Diagnosis of vasculitis is challenging. To avoid invasive approaches, clinical guidelines recommend the use of diagnostic imaging. This study aimed at evaluating the diagnostic accuracy of [18F]-fluorodeoxyglucose ([18F]FDG) position emission tomography/computed tomography (PET/CT) in large vessel vasculitis (LVV) and how this is affected by inter-operator variability. METHODS: A total of 279 patients who performed [18F]-FDG PET/CT for suspicion of LVV were retrospectively analyzed. We tested the qualitative and semi-quantitative analysis and parameters influencing image quality and interpretation. Exams were evaluated by two readers with different experience and their performance was compared. RESULTS: LVV diagnosis was confirmed in 81 patients. [18F]-FDG PET/CT accuracy was 73% and 67% for the expert reader and less experienced reader, respectively. The expert reader overall performed better than the less experienced one, with higher accuracy in patients with normal BMI (77.3 vs. 63.8%), normal level of glycemia (73.3 vs. 65%), younger age (76.6 vs. 68.2%), and when no therapy was in course at time of imaging (76.7 vs. 66.7%). The diagnostic performance of both readers did not improve using semi-quantitative parameters. CONCLUSIONS: We confirmed the appropriateness of the recommended criteria for image acquisition and interpretation, underlining the importance of experience in image interpretation for the optimal diagnostic performance of [18F]FDG PET/CT in vasculitis.

Toward Improved Outcomes for Patients With Lung Cancer Globally: The Essential Role of Radiology and Nuclear Medicine.

PURPOSE: Key to achieving better population-based outcomes for patients with lung cancer is the improvement of medical imaging and nuclear medicine infrastructure globally. This paper aims to outline why and spark relevant health systems strengthening. METHODS: The paper synthesizes the global lung cancer landscape, imaging referral guidelines (including resource-stratified ones), the reliance of TNM staging upon imaging, relevant multinational health technology assessments, and precisely how treatment selection and in turn patient outcomes hinge upon imaging findings. The final discussion presents data on current global gaps in both diagnostics (including imaging) and therapies and how, informed by such data, improved population-based outcomes are tangible through strategic planning. RESULTS: Imaging findings are central to appropriate lung cancer patient management and can variably lead to life-prolonging interventions and/or to life-enhancing palliative measures. Early-stage lung cancer can be treated with curative intent but, unfortunately, most patients with lung cancer still present at advanced stages and many patients lack access to both diagnostics and therapies. Furthermore, half of lung cancer cases occur in low- and middle-income countries. The role of medical imaging and nuclear medicine in lung cancer management, as outlined herein, may help inform strategic planning. CONCLUSION: Lung cancer is the number one cancer killer worldwide. The essential role that medical imaging and nuclear medicine play in early diagnosis and disease staging cannot be overstated, pivotal in selecting the many patients for whom measurably improved outcomes are attainable. Prevention synergized with patient-centered, compassionate, high-quality lung cancer management provision mandate that strategic population-based planning, including universal health coverage strategies, should extend well beyond the scope of disease prevention to include both curative and noncurative treatment options for the millions afflicted with lung cancer.

EAU-EANM Consensus Statements on the Role of Prostate-specific Membrane Antigen Positron Emission Tomography/Computed Tomography in Patients with Prostate Cancer and with Respect to [177Lu]Lu-PSMA Radioligand Therapy.

BACKGROUND: Prostate-specific membrane antigen (PSMA) positron emission tomography (PET)/computed tomography (CT) is useful for selected clinical indications in patients with prostate cancer (PCa) but it may have broader clinical utility owing to the emergence of lutetium-177-PSMA-617 ([177Lu]Lu-PSMA) therapy. However, robust data regarding the impact of PSMA PET/CT on patient management and treatment are lacking, and in many areas, the role of next-generation imaging has not been defined. OBJECTIVE: To assess expert opinion on the use of PSMA-based imaging and therapy to develop interim guidance. DESIGN, SETTING, AND PARTICIPANTS: A panel of 21 PCa experts from various disciplines received thematic topics and relevant literature. A questionnaire to assess proposed guidance statements regarding PSMA PET/CT and [177Lu]Lu-PSMA therapy was developed for completion remotely in a first e-Delphi round. A subsequent panel discussion was conducted during a 1-d meeting, which included a second Delphi round. OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: Panellists voted anonymously on statements using a nine-point Likert scale from 1 = strongly disagree to 9 = strongly agree. Median scores were calculated and consensus was assessed using methods proposed by the Research and Development (RAND) corporation. RESULTS AND LIMITATIONS: Statements were developed to cover the following topics: PSMA PET/CT utility, clinical use, and choice of tracer; patient selection; and management of patients receiving [177Lu]Lu-PSMA for metastatic PCa. Consensus was reached for 33/36 statements. In-group bias is a potential limitation, as some statements were rephrased during discussions at the 1-d meeting. CONCLUSIONS: Adoption of PSMA PET/CT as an imaging tool to guide [177Lu]Lu-PSMA therapy should be supported by indications for appropriate use. PATIENT SUMMARY: A panel of experts in prostate cancer reached a consensus for the majority of statements proposed regarding the role of prostate-specific membrane antigen (PSMA)-based imaging and therapy, particularly the use of PSMA-based imaging in patients suitable for [177Lu]Lu-PSMA therapy and the need to perform PSMA-based imaging before considering patients as candidates for this therapy.

Health-related quality of life following FDG-PET/CT for cytological indeterminate thyroid nodules.

Objective: This study assessed the health-related quality of life (HRQoL) in patients undergoing 2-[18F]fluoro-2-deoxy-D-glucose (FDG)-PET/CT for an indeterminate (Bethesda III/IV) thyroid nodule. FDG-PET/CT accurately rules out malignancy and prevents 40% of futile diagnostic surgeries in these nodules. Design: Secondary analyses of HRQoL data from a randomised controlled multicentre trial (NCT02208544) in 126 patients from 15 hospitals in the Netherlands were done. Methods: Longitudinal HRQoL assessment was performed using the EuroQol 5-dimension 5-level (EQ-5D-5L), the RAND 36-item Health Survey v2.0 (RAND-36), and the Thyroid Patient-Reported Outcome (ThyPRO) questionnaire on baseline, 3, 6, and 12 months, relative to the date of the FDG-PET/CT scan. Results: Patients who were randomised to active surveillance following an FDG-negative nodule instead of diagnostic surgery reported stable HRQoL scores throughout the year. Univariate analysis indicated better HRQoL for patients undergoing surveillance than surgical patients with benign histopathology on multiple physical and psychosocial domains. Univariate within-group analysis suggested both temporary and continued HRQoL deteriorations in patients with benign histopathology over time. Multivariate within-group analysis demonstrated no significant longitudinal HRQoL changes in patients undergoing active surveillance. In contrast, in patients with benign histopathology, worse HRQoL was observed with regard to ThyPRO cognitive impairment (P = 0.01) and cosmetic complaints (P = 0.02), whereas goitre symptoms (P < 0.001) and anxiety (P = 0.04) improved over time. In patients with malignant histopathology, anxiety also decreased (P = 0.05). Conclusions: The reassurance of a negative FDG-PET/CT resulted in sustained HRQoL throughout the first year of active surveillance. Diagnostic surgery for a nodule with benign histopathology resulted in more cognitive impairment and physical problems including cosmetic complaints, but improved goitre symptoms and anxiety. Anxiety was also reduced in patients with malignant histopathology.

FDG-PET/CT in indeterminate thyroid nodules: cost-utility analysis alongside a randomised controlled trial.

PURPOSE: To evaluate cost-effectiveness of an [18F]FDG-PET/CT-driven diagnostic workup as compared to diagnostic surgery, for thyroid nodules with Bethesda III/IV cytology. [18F]FDG-PET/CT avoids 40% of futile diagnostic surgeries for benign Bethesda III/IV nodules. METHODS: Lifelong societal costs and quality-adjusted life years (QALYs) were assessed for 132 patients participating in a randomised controlled multicentre trial comparing [18F]FDG-PET/CT to diagnostic surgery. The observed 1-year trial results were extrapolated using a Markov model. The probability of cost-effectiveness was estimated using cost-effectiveness acceptability curves, taking uncertainty about sampling, imputation, and parameters into account. RESULTS: The observed 1-year cost difference of [18F]FDG-PET/CT as compared to diagnostic surgery was - €1000 (95% CI: - €2100 to €0) for thyroid nodule-related care (p = 0.06). From the broader societal perspective, the 1-year difference in total societal costs was - €4500 (- €9200 to €150) (p = 0.06). Over the modelled lifelong period, the cost difference was - €9900 (- €23,100 to €3200) (p = 0.14). The difference in QALYs was 0.019 (- 0.045 to 0.083) at 1 year (p = 0.57) and 0.402 (- 0.581 to 1.385) over the lifelong period (p = 0.42). For a willingness to pay of €50,000 per QALY, an [18F]FDG-PET/CT-driven work-up was the cost-effective strategy with 84% certainty. CONCLUSION: Following the observed reduction in diagnostic surgery, an [18F]FDG-PET/CT-driven diagnostic workup reduced the 1-year thyroid nodule-related and societal costs while sustaining quality of life. It is very likely cost-effective as compared to diagnostic surgery for Bethesda III/IV nodules. TRIAL REGISTRATION NUMBER: This trial is registered with ClinicalTrials.gov: NCT02208544 (5 August 2014), https://clinicaltrials.gov/ct2/show/NCT02208544 .