Neuroblastoma is the most common extracranial solid tumor in early childhood. Its clinical behavior is highly variable, ranging from spontaneous regression to fatal outcome despite intensive treatment. The International Society of Pediatric Oncology Europe Neuroblastoma Group (SIOPEN) Radiology and Nuclear Medicine Specialty Committees developed consensus-based imaging recommendations for high-risk neuroblastoma at first presentation and throughout follow-up. These expert opinions aim to improve reproducibility and enhance diagnostic performance in order to advance the current standard of care and assist in the development of future trials.
PURPOSE:Detection of bone marrow disease has been a major component of rhabdomyosarcoma (RMS) staging with bilateral bone marrow aspirates/biopsies (BMAB) from the iliac crests considered the diagnostic gold standard. This study's goal was to determine if 2-18F-labeled fluorodeoxyglucose positron emission tomography/computed tomography ([18F]FDG PET/CT) or PET/magnetic resonance imaging (MRI) may replace BMAB in RMS staging. METHODS:Patients were recruited in Europe and North America. Medical records, FDG PET/CT or FDG PET/MRI (PET), and BMAB reports were collected retrospectively. Images were re-reviewed by nuclear medicine physicians at the patients' home institutions if PET reports indicated increased FDG uptake at bone/bone marrow sites or if tumor cells were detected in bone marrow samples. RESULTS:PET imaging and BMAB were performed before chemotherapy and tumor resection in 301 patients with FDG-avid RMS. Bone marrow metastases were detected by PET and BMAB in 54, by PET only in 24, and by BMAB only in one of 301 patients with FDG-avid primary tumors. Absence of bone marrow metastases was confirmed by PET and BMAB in 222 of 301 patients. These observations translated into 98% sensitivity and 90% specificity for PET in detecting bone marrow metastases when BMAB was considered as gold standard. FDG-avid marrow disease was patchy (1-5 foci) in one third of cases. Patients with marrow disease indicated by PET and BMAB had more FDG-avid bone marrow foci, more metastatic sites, and lower survival than those with marrow disease indicated by PET only, suggesting more advanced disease stages. CONCLUSION:Bone marrow sampling may be omitted in patients without evidence of FDG-avid bone marrow disease by PET. If there are FDG-avid bone marrow lesions, further investigation by MRI and/or biopsy should be considered.
Abstract: This study aimed to assess the prognostic value of medullary total metabolic tumor volume (mTMTV) derived from fluorodeoxyglucose–positron emission tomography/computed tomography ([18F]FDG-PET/CT) compared with conventional PET-derived features and biological/chromosomal abnormalities in patients with newly diagnosed multiple myeloma (NDMM) treated with daratumumab for induction/consolidation and/or maintenance and enrolled in CASSIOPET, a companion study of CASSIOPEIA, with long-term follow-up. Automated bone/liver CT–based segmentation were applied to the baseline [18F]FDG-PET images, with mTMTV being defined using the median liver background as the cut-off, including focal lesions and diffuse bone marrow (BM) involvement. Both univariate/multivariate Cox and machine learning (ML)–based survival models were performed. A total of 195 patients were included, 81% of them PET-positive. Multivariate analysis demonstrated independent prognostic value of mTMTV for progression-free survival (PFS) (P < .001) and overall survival (OS) (P < .001), complementary to Revised International Staging System (R-ISS) (P = .008 and P < .001, respectively). The ML model confirmed these findings, achieving concordance index of 0.609 and 0.659 and identifying mTMTV as the most informative feature for PFS and OS. Adding R-ISS, BM maximum standardized uptake value (SUVmax) and anemia to mTMTV accounted for >60% of the ML model explanation for PFS and adding R-ISS, the number of focal lesions and BM SUVmax for >60% of the model for OS. Combining R-ISS and mTMTV enabled the creation of 2 new-risk subgroups. In conclusion, this prospective study demonstrated the prognostic relevance of [18F]FDG-PET/CT–based parameters in the initial workup of patients with NDMM in the era of anti-CD38–based therapy. mTMTV was found to have strong independent prognostic value, complementary to R-ISS and refining risk stratification. This trial was registered at www.clinicaltrials.gov as #NCT02541383.
Purpose Altered bone marrow [18F]FDG uptake is frequently observed after granulocyte colony-stimulating factors (G-CSF) or anti-tumour treatment but has not been systematically analysed in paediatric neuroblastoma. This study evaluated the relationship between haematopoietic activity and bone marrow [18F]FDG uptake in neuroblastoma patients, and its variation with time since anti-tumour treatment. Methods A single-centre retrospective cohort study was conducted using [18F]FDG PET/CT scans from neuroblastoma patients. Clinical data were extracted from electronic patient records, including G-CSF and anti-tumour treatment and the interval between treatment and imaging. Mean lean body mass–corrected standardised uptake values (SUV) were extracted from the L4 vertebra, liver, and spleen. Laboratory blood values (haemoglobin, haematocrit, thrombocyte, leucocyte, neutrophil), measured within 7 days prior to each scan, were analysed for correlation with SUV. Patients after anti-tumour treatment were stratified by G-CSF status to account for potential effects on haematopoiesis and SUV. Results A total of 126 scans from 37 patients (median age 3.00 years, IQR 1.60 – 6.00) were included. In patients after anti-tumour treatment, bone marrow SUV showed significant negative correlation with haemoglobin (ρ = −0.45), haematocrit (ρ = −0.41) and thrombocytes (ρ = −0.25), and positive with leukocytes (ρ = 0.22), and neutrophils (ρ = 0.26). SUV was significantly higher in anaemic and thrombocytopenic patients, and lower in leukopenic patients. SUV peaked at 8–14 days after anti-tumour treatment (P < 0.001). Stratification based on treatment with G-CSF showed higher median SUV in G–CSF–treated patients (P < 0.001). Conclusion Bone marrow [18F]FDG uptake in neuroblastoma patients is enhanced after administration of G-CSF and anti-tumour treatment, reflecting haematopoietic recovery and potentially mimicking metastatic disease. Therefore, based on our findings, we recommend scheduling [18F]FDG PET imaging at least 21 days after the last administration of G-CSF or systemic anti-tumour treatment to avoid misinterpretation of reactive marrow uptake.
The widespread use of 18F-fluorodeoxyglucose positron emission tomography/computed tomography ([18F]FDG PET/CT) has led to increased detection of thyroid incidentalomas (TIs). Current guidelines cite malignancy rates of 31–33
Background In children with neuroblastoma, imaging plays a central role in staging, treatment planning and response assessment. Standardized imaging procedures, including cross-sectional imaging and MIBG scintigraphy are essential for consistency across international trials. However, the increasing use of PET tracers and variable access to imaging technologies may challenge harmonization. This study evaluated the availability, use, and challenges of neuroblastoma imaging modalities across participating centers. Methods A web-based survey was distributed to SIOPEN national delegates between August and December 2025. The survey covered respondent characteristics, sedation availability, MIBG scintigraphy with SPECT/CT and PET imaging practices, anatomical imaging modalities, and perceived challenges. Descriptive analyses were performed. Results In total, 151 responses representing 89 unique centers from 29 countries were analysed. Sedation for imaging was available in 98% of centers. In most centers MRI can be used for cross-sectional imaging of the primary tumor (73.1%). Most (74.2%) performed both planar and SPECT/CT MIBG scans, with 64.0% reporting use of the standardized SIOPEN scoring system. PET imaging was available in 84.3% of centers, most commonly using [¹⁸F]FDG (95.9%); [¹⁸F]MFBG was available in eight centers. Major challenges included limited tracer access (56.1%) and restricted cyclotron availability (25.8%). Conclusions This study reveals wide access to nuclear imaging modalities, including PET imaging, but with substantial heterogeneity in neuroblastoma imaging practices, tracer availability and image interpretation across responding centers. These findings highlight the need for broader implementation of standardized imaging criteria. While informative, these results should be interpreted with caution given the potential biases inherent to questionnaire-based studies.
OBJECTIVES:Treatment for neuroblastoma with chemotherapy and [131I]MIBG can induce endocrine adverse effects, including thyroid disorders, gonadal insufficiency or short stature. Neuroblastoma can also be targeted at the somatostatin receptor, using [ 177 Lu]Lu-DOTATATE peptide receptor radionuclide therapy. Thus far no endocrine effects have been reported after [ 177 Lu]Lu-DOTATATE treatment in children. CASE PRESENTATION:We report a first case of pituitary dysfunction, reflected as growth hormone deficiency and central hypothyroidism, following treatment with [ 177 Lu]Lu-DOTATATE for refractory neuroblastoma. CONCLUSIONS:We hypothesize that the GH and TSH deficiency in this case are caused by pituitary damage through binding of [ 177 Lu]Lu-DOTATATE to the somatostatin receptors in the pituitary gland. If [ 177 Lu]Lu-DOTATATE in the future becomes a more upfront treatment we strongly underline screening on pituitary dysfunction after exposure to [ 177 Lu]Lu-DOTATATE in childhood.
Background Ultrasound-guided fine-needle aspiration cytology (US-FNAC) is commonly used in the diagnostic work-up of head and neck cancer, but its ability to detect occult lymph node metastases in early-stage oral squamous cell carcinoma (OSCC) with a clinically negative neck remains unclear.Methods A retrospective analysis was performed in 578 patients with early-stage OSCC (cT1-3N0) who underwent US-FNAC prior to surgery. Histopathology, sentinel lymph node biopsy, and follow-up were used as reference standards.Results Occult nodal metastases were found in 179 patients (31.0%). US-FNAC showed low sensitivity (15.9%) and a negative predictive value of 72.9%, resulting in 149 false-negative cases (25.8%). Specificity (99.5%) and positive predictive value (90.3%) were high, with only 2 false-positive results.Conclusions In patients with early-stage oral cavity squamous cell carcinoma and a clinically negative neck, US-FNAC demonstrates high specificity but limited sensitivity and negative predictive value. These findings indicate that US-FNAC alone is insufficient to exclude occult nodal metastases and should be regarded as an adjunctive diagnostic tool rather than a stand-alone nodal staging strategy.
BACKGROUND:Pediatric differentiated thyroid carcinoma (DTC) is a rare disease, creating challenges for standardized care across Europe. The Netherlands published its first national pediatric DTC guideline in 2020. The 2022 European Thyroid Association (ETA) guideline introduced differences that required reconciliation with national practice. This article presents the 2026 update of the Dutch guideline, harmonized with European recommendations while retaining context-specific adaptations. METHODS:The 2020 Dutch guideline was systematically compared with the ETA 2022 guideline. Differences were discussed by the national pediatric DTC working group and addressed in a structured consensus meeting to agree on revisions and adaptations relevant to the Dutch context. RESULTS:Most European recommendations were adopted. Key national adaptations include performing total thyroidectomy without prior histology in Bethesda V-VI nodules with a proven BRAF mutation, expanded use of molecular diagnostics in selected nodules, and referral for genetic counseling in confirmed cases. In addition, less extensive surgery and selective omission of radioactive iodine therapy in low-risk patients were recommended, based on shared decision-making. Follow-up with neck ultrasound was limited to an initial 3-month assessment, with subsequent imaging only in case of rising thyroglobulin or anti-thyroglobulin concentrations. CONCLUSIONS:The 2026 Dutch guideline aligns with European recommendations while preserving context-specific adaptations. It provides a framework for consistent, patient-centered care and supports standardized clinical practice in the Netherlands, offering a model for harmonized pediatric DTC management across Europe.
Necrotizing otitis externa (NOE) is a rare but severe infection of the external ear canal that can progress to osteomyelitis of the temporal bone, often caused by Pseudomonas aeruginosa. Effective management requires prolonged systemic antibiotic therapy, as premature termination increases the risk of relapse. There is ongoing debate regarding the optimal duration of antibiotic treatment and the criteria for discontinuation. Functional imaging techniques, such as [67Ga]Gallium citrate SPECT/CT and [18F]FDG-PET/CT, have shown promise in assessing disease activity, but their roles in therapy evaluation remain underexplored. In this study, we describe the radiological disease activity during treatment and we relate activity at cessation of treatment to disease control in patients scanned with [67 Ga]Ga-citrate SPECT/CT and/or [18F]FDG-PET/CT. Secondly, inter-rater variability is assessed. Twenty patients with NOE, with a median duration of intravenous treatment of six months (range 1–24 months) were included. Relapse occurred in 3 patients. Qualitative assessment of 95 scans showed slight inter-rater agreement for [67Ga]Ga-citrate SPECT/CT (kappa = 0.167) and fair agreement for [18F]FDG-PET/CT (kappa = 0.400). Relapse was seen in patients both with and without complete resolution on imaging. In the semi-quantitative assessment, [67Ga]Ga-citrate SPECT/CT showed a decrease in countsmax ratio (1.93 to 1.35), but an increase in countsmean ratio (1.56 to 1.73) between baseline and end of treatment. [18F]FDG-PET/CT showed a 50
Extravasation of therapeutic radiopharmaceuticals during radioligand therapy is uncommon. We report the first published case of subcutaneous extravasation of 177 Lu-PSMA-I&T, presenting with acute upper-arm swelling, pain, and transient autonomic symptoms. Early planar scintigraphy and SPECT/CT demonstrated intense radiotracer accumulation in the left upper arm, with rapid redistribution and near-complete clearance by 20 hours. Dosimetric analysis estimated an absorbed dose of ~8 Gy at the injection site. Conservative management resulted in no radiation-induced tissue injury. The clinical course was comparable to previously reported cases of 177 Lu-PSMA-617 extravasation. This case highlights the value of early imaging in the case of extravasation for evaluating the extent of the extravasation and enabling absorbed dose estimation.
Purpose The somatostatin receptor subtype 2 (SSTR2) is highly expressed in neuroblastoma, a malignant paediatric solid tumour arising from the neural crest. This receptor plays an important role in both diagnostics (imaging with [68Ga]Ga-DOTATOC scans) and therapy ([177Lu]Lu-DOTATATE). Understanding the extent of SSTR2 expression is critical to evaluate the potential of these theranostics for neuroblastoma. Methods We retrospectively included patients with neuroblastoma who underwent [68Ga]Ga-DOTATOC PET/CT and had corresponding tumour tissue available for SSTR2 immunohistochemistry (IHC) between 2016 and 2025. IHC was assessed for SSTR2 expression and quantified by H-score, categorised as negative, weak, moderate or strong. [68Ga]Ga-DOTATOC PET/CT uptake was quantified using SUVmax and SUVpeak in tumour volume of interests (VOI). Statistical analysis included Spearman’s rankcorrelation, Kruskal-Wallis test, and linear regression. Changes in H-score over time were evaluated in patients with multiple tissue samples. Results Seventeen patients met the inclusion criteria. Higher H-scores correlated significantly with greater [68Ga]Ga-DOTATOC PET/CT uptake (SUVpeak) (Spearman’s ρ = 0.667, p = 0.0034). [68Ga]Ga-DOTATOC uptake differed significantly across the strong and negative (p<0.01) or weak/moderate (p<0.05) SSTR2 expression groups. Linear regression revealed a significant positive association between H-score and SUVpeak (β = 0.042; 95% CI: 0.016-0.068; p = 0.0034), accounting for approximately 45% of the variance in SUVpeak values (R2 = 0.45). SSTR2 expression over time showed intra- and inter-patient heterogeneity. Conclusion This study showed a statistically significant association between SSTR2 expression and [68Ga]Ga-DOTATOC PET/CT uptake in neuroblastoma. The heterogeneity in SSTR expression supports the need for personalised treatment and imaging strategies, in which H-score may serve as a useful biomarker to guide patient selection for [68Ga]Ga-DOTATOC PET/CT and SSTR2-targeted therapy. Prospective studies in larger cohorts are warranted to confirm these findings.
Meta-[1⁸F]fluorobenzylguanidine ([1⁸F]mFBG) PET-CT is a novel imaging modality for norepinephrine transporter-expressing tumours, such as neuroblastoma and phaeochromocytoma, enabling quantitative assessment and improved diagnostic accuracy compared to meta-[123I]iodobenzylguanidine ([123I]mIBG) scintigraphy. This study aims to: 1) Identify the optimal standardised uptake value (SUV) normalisation method: body weight (BW) or lean body mass (LBM); 2) Determine the most stable reference tissue with SUV uptake below pathological levels. We analysed 63 [1⁸F]mFBG PET-CTs from 35 patients (20 paediatric neuroblastoma, 15 adult phaeochromocytoma). SUVmean was measured in the liver, blood pool, bone marrow, and muscle, normalised using BW (SUVBW), LBM via James (SUVLBMJames), and LBM via Janmahasatian (SUVLBMJanma). Variability of SUVs and their correlation with weight were assessed. LBM-based normalisation reduced SUV variability compared to BW-based normalisation. Bone marrow demonstrated the lowest variability and least weight dependency (r2 0.45 for SUVBW versus 0.31 for SUVLBMJanma). The liver had the highest SUVs, increasing the risk of false negatives if used as reference tissue, while the blood pool had the lowest SUVs, raising the risk of false positives. Muscle showed relatively stable SUVs with increasing weight but higher variability than bone marrow. LBM-based SUV normalisation reduces weight dependency for [1⁸F]mFBG PET-CT. Bone marrow is the most reliable reference tissue due to its low variability and balanced SUVs, while muscle may serve as an alternative if diffuse bone marrow uptake is present. These findings support standardising LBM-adjusted SUV methods and using bone marrow as the primary reference tissue to enhance diagnostic accuracy. Clinical trial registration: EudraCT Number: 2019–003713-33; EU Clinical Trials Number: 2024–513622-35–00.
AIMS:This study aims to evaluate the diagnostic potential of [18F]TFB PET/CT for detecting pre-operative lymph node metastases and predicting [131I] therapy response in differentiated thyroid cancer (DTC). METHODS:This prospective, multicenter phase-2 clinical trial includes adult patients with DTC and pathologically confirmed cervical lymph node metastases scheduled for thyroidectomy and lymph node dissection (Group 1) and patients with recurrent or persistent DTC scheduled for radioiodine therapy (Group 2). [18F]TFB PET/CT will be compared to current imaging modalities and post-therapy scintigraphy. Primary outcomes include optimal imaging time points, sensitivity, specificity, SUVmax, and TBRmax for lymph node metastases and suspected lesions. Secondary outcomes involve [18F]TFB kinetics, NIS expression correlation, and safety profiles. In conclusion, [18F]TFB PET/CT holds the potential for enhancing pre-operative lymph node metastasis detection and predicting [131I] therapy response, potentially improving surgical and therapeutic outcomes for DTC patients.
OBJECTIVES:Optimize deep learning-based vertebrae segmentation in longitudinal CT scans of multiple myeloma patients using structural uncertainty analysis. MATERIALS & METHODS:Retrospective CT scans from 474 multiple myeloma patients were divided into train (179 patients, 349 scans, 2005-2011) and test cohort (295 patients, 671 scans, 2012-2020). An enhanced segmentation pipeline was developed on the train cohort. It integrated vertebrae segmentation using an open-source deep learning method (Payer's) with a post-hoc structural uncertainty analysis. This analysis identified inconsistencies, automatically correcting them or flagging uncertain regions for human review. Segmentation quality was assessed through vertebral shape analysis using topology. Metrics included 'identification rate', 'longitudinal vertebral match rate', 'success rate' and 'series success rate' and evaluated across age/sex subgroups. Statistical analysis included McNemar and Wilcoxon signed-rank tests, with p < 0.05 indicating significant improvement. RESULTS:Payer's method achieved an identification rate of 95.8% and success rate of 86.7%. The proposed pipeline automatically improved these metrics to 98.8% and 96.0%, respectively (p < 0.001). Additionally, 3.6% of scans were marked for human inspection, increasing the success rate from 96.0% to 98.8% (p < 0.001). The vertebral match rate increased from 97.0% to 99.7% (p < 0.001), and the series success rate from 80.0% to 95.4% (p < 0.001). Subgroup analysis showed more consistent performance across age and sex groups. CONCLUSION:The proposed pipeline significantly outperforms Payer's method, enhancing segmentation accuracy and reducing longitudinal matching errors while minimizing evaluation workload. Its uncertainty analysis ensures robust performance, making it a valuable tool for longitudinal studies in multiple myeloma.
Few studies have assessed body weight dependency of Standardised Uptake Value (SUV) formulations in paediatric patients. This study aims to compare different SUV formulations measured in reference tissues in paediatric patients and determine which correction method shows the least dependency on body weight. A single-centre, retrospective analysis of [18F]FDG PET/CT scans was performed. SUV measurements were taken from liver and blood pool using EARL1 reconstructions. SUV measurements were corrected for body weight (SUVBW), lean body mass (LBM) according to James (SUVLBMJames) and Janmahasatian (SUVLBMJanma), and body surface area (BSA) according to DuBois (SUVBSADuBois) and Haycock (SUVBSAHaycock). The coefficient of determination (r2) was used to assess the correlation between SUV and body weight. In total, 461 scans were analysed, including 185 (40