MRI Characteristics of Pediatric Renal Tumors: A SIOP-RTSG Radiology Panel Delphi Study.

BACKGROUND: The SIOP-Renal Tumor Study Group (RTSG) does not advocate invasive procedures to determine histology before the start of therapy. This may induce misdiagnosis-based treatment initiation, but only for a relatively small percentage of approximately 10% of non-Wilms tumors (non-WTs). MRI could be useful for reducing misdiagnosis, but there is no global consensus on differentiating characteristics. PURPOSE: To identify MRI characteristics that may be used for discrimination of newly diagnosed pediatric renal tumors. STUDY TYPE: Consensus process using a Delphi method. POPULATION: Not applicable. FIELD STRENGTH/SEQUENCE: Abdominal MRI including T1- and T2-weighted imaging, contrast-enhanced MRI, and diffusion-weighted imaging at 1.5 or 3 T. ASSESSMENT: Twenty-three radiologists from the SIOP-RTSG radiology panel with ≥5 years of experience in MRI of pediatric renal tumors and/or who had assessed ≥50 MRI scans of pediatric renal tumors in the past 5 years identified potentially discriminatory characteristics in the first questionnaire. These characteristics were scored in the subsequent second round, consisting of 5-point Likert scales, ranking- and multiple choice questions. STATISTICAL TESTS: The cut-off value for consensus and agreement among the majority was ≥75% and ≥60%, respectively, with a median of ≥4 on the Likert scale. RESULTS: Consensus on specific characteristics mainly concerned the discrimination between WTs and non-WTs, and WTs and nephrogenic rest(s) (NR)/nephroblastomatosis. The presence of bilateral lesions (75.0%) and NR/nephroblastomatosis (65.0%) were MRI characteristics indicated as specific for the diagnosis of a WT, and 91.3% of the participants agreed that MRI is useful to distinguish NR/nephroblastomatosis from WT. Furthermore, all participants agreed that age influenced their prediction in the discrimination of pediatric renal tumors. DATA CONCLUSION: Although the discrimination of pediatric renal tumors based on MRI remains challenging, this study identified some specific characteristics for tumor subtypes, based on the shared opinion of experts. These results may guide future validation studies and innovative efforts. LEVEL OF EVIDENCE: 3 Technical Efficacy Stage: 3.

Notifications and alerts in patient dose values for computed tomography and fluoroscopy-guided interventional procedures.

The terms "notifications" and "alerts" for medical exposures are used by several national and international organisations. Recommendations for CT scanners have been published by the American Association of Physicists in Medicine. Some interventional radiology societies as well as national authorities have also published dose notifications for fluoroscopy-guided interventional procedures. Notifications and alerts may also be useful for optimisation and to avoid unintended and accidental exposures. The main interest in using these values for high-dose procedures (CT and interventional) is to optimise imaging procedures, reducing the probability of stochastic effects and avoiding tissue reactions. Alerts in X-ray systems may be considered before procedures (as in CT), during procedures (in some interventional radiology systems), and after procedures, when the patient radiation dose results are known and processed. This review summarises the different uses of notifications and alerts to help in optimisation for CT and for fluoroscopy-guided interventional procedures as well as in the analysis of unintended and accidental medical exposures. The paper also includes cautions in setting the alert values and discusses the benefits of using patient dose management systems for the alerts, their registry and follow-up, and the differences between notifications, alerts, and trigger levels for individual procedures and the terms used for the collective approach, such as diagnostic reference levels. KEY POINTS: • Notifications and alerts on patient dose values for computed tomography (CT) and fluoroscopy-guided interventional procedures (FGIP) allow to improve radiation safety and contribute to the avoidance of radiation injuries and unintended and accidental exposures. • Alerts may be established before the imaging procedures (as in CT) or during and after the procedures as for FGIP. • Dose management systems should include notifications and alerts and their registry for the hospital quality programmes.

Whole-body MRI versus an FDG-PET/CT-based reference standard for staging of paediatric Hodgkin lymphoma: a prospective multicentre study.

OBJECTIVES: To assess the concordance of whole-body MRI (WB-MRI) and an FDG-PET/CT-based reference standard for the initial staging in children with Hodgkin lymphoma (HL) METHODS: Children with newly diagnosed HL were included in this prospective, multicentre, international study and underwent WB-MRI and FDG-PET/CT at staging. Two radiologists and a nuclear medicine physician independently evaluated all images. Discrepancies between WB-MRI and FDG-PET/CT were assessed by an expert panel. All FDG-PET/CT errors were corrected to derive the FDG-PET/CT-based reference standard. The expert panel corrected all reader errors in the WB-MRI DWI dataset to form the intrinsic MRI data. Inter-observer agreement for WB-MRI DWI was calculated using overall agreement, specific agreements and kappa statistics. Concordance for correct classification of all disease sites and disease stage between WB-MRI (without DWI, with DWI and intrinsic WB-MRI DWI) and the reference standard was calculated as primary outcome. Secondary outcomes included positive predictive value, negative predictive value and kappa statistics. Clustering within patients was accounted for using a mixed-effect logistic regression model with random intercepts and a multilevel kappa analysis. RESULTS: Sixty-eight children were included. Inter-observer agreement between WB-MRI DWI readers was good for disease stage (κ = 0.74). WB-MRI DWI agreed with the FDG-PET/CT-based reference standard for determining disease stage in 96% of the patients versus 88% for WB-MRI without DWI. Agreement between WB-MRI DWI and the reference standard was excellent for both nodal (98%) and extra-nodal (100%) staging. CONCLUSIONS: WB-MRI DWI showed excellent agreement with the FDG-PET/CT-based reference standard. The addition of DWI to the WB-MRI protocol improved the staging agreement. KEY POINTS: • This study showed excellent agreement between WB-MRI DWI and an FDG-PET/CT-based reference standard for staging paediatric HL. • Diffusion-weighted imaging is a useful addition to WB-MRI in staging paediatric HL. • Inter-observer agreement for WB-MRI DWI was good for both nodal and extra-nodal staging and determining disease stage.

Whole-body MRI versus an [18F]FDG-PET/CT-based reference standard for early response assessment and restaging of paediatric Hodgkin's lymphoma: a prospective multicentre study.

OBJECTIVES: To compare WB-MRI with an [18F]FDG-PET/CT-based reference for early response assessment and restaging in children with Hodgkin's lymphoma (HL). METHODS: Fifty-one children (ages 10-17) with HL were included in this prospective, multicentre study. All participants underwent WB-MRI and [18F]FDG-PET/CT at early response assessment. Thirteen of the 51 patients also underwent both WB-MRI and [18F]FDG-PET/CT at restaging. Two radiologists independently evaluated all WB-MR images in two separate readings: without and with DWI. The [18F]FDG-PET/CT examinations were evaluated by a nuclear medicine physician. An expert panel assessed all discrepancies between WB-MRI and [18F]FDG-PET/CT to derive the [18F]FDG-PET/CT-based reference standard. Inter-observer agreement for WB-MRI was calculated using kappa statistics. Concordance, PPV, NPV, sensitivity and specificity for a correct assessment of the response between WB-MRI and the reference standard were calculated for both nodal and extra-nodal disease presence and total response evaluation. RESULTS: Inter-observer agreement of WB-MRI including DWI between both readers was moderate (κ 0.46-0.60). For early response assessment, WB-MRI DWI agreed with the reference standard in 33/51 patients (65%, 95% CI 51-77%) versus 15/51 (29%, 95% CI 19-43%) for WB-MRI without DWI. For restaging, WB-MRI including DWI agreed with the reference standard in 9/13 patients (69%, 95% CI 42-87%) versus 5/13 patients (38%, 95% CI 18-64%) for WB-MRI without DWI. CONCLUSIONS: The addition of DWI to the WB-MRI protocol in early response assessment and restaging of paediatric HL improved agreement with the [18F]FDG-PET/CT-based reference standard. However, WB-MRI remained discordant in 30% of the patients compared to standard imaging for assessing residual disease presence. KEY POINTS: • Inter-observer agreement of WB-MRI including DWI between both readers was moderate for (early) response assessment of paediatric Hodgkin's lymphoma. • The addition of DWI to the WB-MRI protocol in early response assessment and restaging of paediatric Hodgkin's lymphoma improved agreement with the [18F]FDG-PET/CT-based reference standard. • WB-MRI including DWI agreed with the reference standard in respectively 65% and 69% of the patients for early response assessment and restaging.

Resection of primary tumor in stage 4S neuroblastoma: a second study by the Italian Neuroblastoma Group.

PURPOSE: To clarify the role of primary tumor resection in stage 4S neuroblastoma. METHODS: We investigated a cohort of 172 infants diagnosed with stage 4S neuroblastoma between 1994 and 2013. Of 160 evaluable patients, 62 underwent upfront resection of the primary tumor and 98 did not. RESULTS: Five-year progression-free and overall survival were significantly better in those who had undergone upfront surgery (83.6% vs 64.2% and 96.8% vs 85.7%, respectively). One post-operative death and four non-fatal complications occurred in the resection group. Three patients who had not undergone resection died of chemotherapy-related toxicity. Thirteen patients underwent late surgery to remove a residual tumor, without complications: all but one alive. Outcomes were better in patients diagnosed from 2000 onwards. CONCLUSION: Infants diagnosed with stage 4S neuroblastoma who underwent upfront tumor resection had a better outcome. However, this result cannot be definitely attributed to surgery, since these patients were selected on the basis of their favorable presenting features. Although the question of whether to operate or not at disease onset is still unsolved, this study confirms the importance of obtaining enough adequate tumor tissue to enable histological and biological studies to properly address treatment, to achieve the best possible outcome.

A Review of Infants With Localized Neuroblastoma That Evolve to Stage 4s Disease.

The authors describe a newborn diagnosed with localized neuroblastoma that evolved to stage 4s at the age of 5 months. Peculiar features of the case included a bilateral adrenal primary, the skin as the only metastatic site, and the development of a muscular lesion late in the clinical course. The patient underwent left adrenalectomy and all other lesions regressed without further therapy. The case prompted a search for similar cases both in the Italian Neuroblastoma Registry and in the literature. All patients identified, although variously treated, survived with the exception of the 2 with MYCN gene amplification. We conclude that infants with neuroblastoma who undergo a transition from a localized to stage 4s disease could be less rare than expected. In the absence of unfavorable biology, a wait-and-see policy with strict follow-up could be adopted for these patients, avoiding potentially damaging systemic therapy.

Whole-body magnetic resonance imaging in pediatric oncology - recommendations by the Oncology Task Force of the ESPR.

The purpose of this recommendation of the Oncology Task Force of the European Society of Paediatric Radiology (ESPR) is to indicate reasonable applications of whole-body MRI in children with cancer and to address useful protocols to optimize workflow and diagnostic performance. Whole-body MRI as a radiation-free modality has been increasingly performed over the last two decades, and newer applications, as in screening of children with germ-line mutation cancer-related gene defects, are now widely accepted. We aim to provide a comprehensive outline of the diagnostic value for use in daily practice. Based on the results of our task force session in 2018 and the revision in 2019 during the ESPR meeting, we summarized our group's experiences in whole-body MRI. The lack of large evidence by clinical studies is challenging when focusing on a balanced view regarding the impact of whole-body MRI in pediatric oncology. Therefore, the final version of this recommendation was supported by the members of Oncology Task Force.

Efficacy and Adverse Events During Janus Kinase Inhibitor Treatment of SAVI Syndrome.

OBJECTIVES: Mutations affecting the TMEM173 gene cause STING-associated vasculopathy with onset in infancy (SAVI). No standard immunosuppressive treatment approach is able to control disease progression in patients with SAVI. We studied the efficacy and safety of targeting type I IFN signaling with the Janus kinase inhibitor, ruxolitinib. METHODS: We used DNA sequencing to identify mutations in TMEM173 in patients with peripheral blood type I IFN signature. The JAK1/2 inhibitor ruxolitinib was administered on an off-label basis. RESULTS: We identified three patients with SAVI presenting with skin involvement and progressive severe interstitial lung disease. Indirect echocardiographic signs of pulmonary hypertension were present in one case. Following treatment with ruxolitinib, we observed improvements of respiratory function including increased forced vital capacity in two patients, with discontinuation of oxygen therapy and resolution of echocardiographic abnormalities in one case. Efficacy was persistent in one patient and only transitory in the other two patients. Clinical control of skin complications was obtained, and one patient discontinued steroid treatment. One patient, who presented with kidney involvement, showed resolution of hematuria. One patient experienced increased recurrence of severe viral respiratory infections. Monitoring of peripheral blood type I interferon signature during ruxolitinib treatment did not show a stable decrease. CONCLUSIONS: We conclude that targeting type I IFN receptor signaling may represent a promising therapeutic option for a subset of patients with SAVI syndrome and severe lung involvement. However, the occurrence of viral respiratory infection might represent an important cautionary note for the application of such form of treatment.

European Society of Paediatric Radiology Computed Tomography and Dose Task Force: European guidelines on diagnostic reference levels for paediatric imaging.

The recent European Council Directive 2013/59/EURATOM requires the establishment of diagnostic reference levels (DRLs) to optimise radiation dose in diagnostic and interventional radiology procedures. At the time this directive was enacted, just a few European countries had already set paediatric DRLs and many of these were outdated. For this reason, the European Commission launched a project addressing European Guidelines on Diagnostic Reference Levels for Paediatric Imaging that was awarded to a consortium led by the European Society of Radiology with the collaboration of the European Society of Paediatric Radiology and other European stakeholders involved in the radiation protection of children. The main aims of this project were to establish European DRLs to be used by countries without their own national paediatric DRLs and to provide a consistent method to establish new DRLs in the future. These European guidelines have been very recently endorsed by the European Commission and published in issue N° 185 of the Radiation Protection series. The purpose of this article is to introduce these guidelines to the wide community of paediatric radiologists.

Imaging of diseases of the vagina and external genitalia in children.

A wide range of congenital or acquired conditions, some pretty rare, may affect the vulva and vagina in children. Swelling, visible or palpable masses and abnormal discharges are common symptoms of conditions affecting the vulva and/or the lower genital tract. The majority of these diseases are benign. Ultrasonography is pivotal to elucidate the anatomical origin of these conditions and make the diagnosis. Magnetic resonance imaging can be relevant to improve diagnostic confidence and, if needed, to plan more accurate surgical treatment. The aim of this pictorial essay is to review the related imaging findings to help make radiologists familiar with these conditions.

European Society of Paediatric Radiology 2019 strategic research agenda: improving imaging for tomorrow's children.

The European Society of Paediatric Radiology (ESPR) research committee was established to initiate, drive forward and foster excellence in paediatric imaging, paediatric image-guided intervention and radiation protection research, by facilitating more evidence-based standards, protocols and multi-institutional collaborations. The ESPR Strategic Research Agenda outlines our current research approach, highlighting several areas of paediatric imaging where the society can help guide current and future research, and emphasizing those areas where early research ("seed") funding may need to be allocated by this and other societies as precursors to larger grant applications. The key aims are to evaluate normal variation in order to be able to confidently diagnose disease states, develop robust image-based classification systems to aid diagnosis and treatment monitoring, and help develop evidence-based clinical guidelines using current literature and experience to identify knowledge gaps. For this reason, the development of evidence-based imaging pipelines, broken down step-by-step to include diagnosis, classification and clinical effectiveness, should be the end goal for each disease entity for each affected child. Here, we outline the 2019 ESPR Strategic Research Agenda along three points in the clinical imaging pipeline: clinical referral, disease diagnosis and evolution, and clinical therapeutic evaluation and effectiveness. Through multicentre trials, using existing high-level experience and expertise, and nurturing the next generation of researchers, we will be able to achieve these aims.

Protecting sensitive patient groups from imaging using ionizing radiation: effects during pregnancy, in fetal life and childhood.

The frequency of imaging examinations requiring radiation exposure in children (especially CT) is rapidly increasing. This paper reviews the current evidence in radiation protection in pediatric imaging, focusing on the recent knowledge of the biological risk related to low doses exposure. Even if there are no strictly defined limits for patient radiation exposure, it is recommended to try to keep doses as low as reasonably achievable (the ALARA principle). To achieve ALARA, several techniques to reduce the radiation dose in radiation-sensitive patients groups are reviewed. The most recent recommendations that provide guidance regarding imaging of pregnant women are also summarized, and the risk depending on dose and phase of pregnancy is reported. Finally, the risk-benefit analysis of each examination, and careful communication of this risk to the patient, is emphasized.

Up-to-date imaging review of paediatric soft tissue vascular masses, focusing on sonography.

The purpose of this article is to provide an up-to-date overview on imaging of paediatric vascular soft tissue masses, including both neoplastic and non-neoplastic lesions. We describe the-often challenging-imaging diagnosis-mainly performed by ultrasound (and secondarily by MRI) and differential diagnosis of vascular soft tissue lesions in children. We underline how important it is to determine whether a vascular anomaly has a regional vascular origin, or if there are other entities, ranging from benign to malignant lesions, which have flow-signal or blood degradation products. Even though clinical examination and patient's history are the first and indispensable steps in the initial diagnosis, the role of imaging is crucial, not only to determine whether a mass represents a true tumour/pseudo-tumour, but also to achieve a more correct diagnosis and determine the extension of the tumour/pseudo-tumour and its relation with the nearby anatomic structures.

CT features of diffuse lung disease in infancy.

Diffuse lung disease in infancy includes a wide range of very rare and peculiar pulmonary conditions usually not seen in older children, in whom diffuse lung disease has much greater overlap with adult disorders. The acronym chILD (childhood Interstitial Lung Disease) commonly defines these disorders, although air spaces, airways, alveolar epithelium, vasculature, pleura, and pleural spaces can also be involved, besides the pulmonary interstitium. chILD can be caused by diffuse developmental disorders, alveolar growth abnormalities, surfactant dysfunction disorders, and other specific conditions of poorly understood etiology. Chest CT imaging studies play a pivotal role in the evaluation of chILD. In some conditions CT findings can be specific, and thus make it possible avoiding further testing. In other disorders, findings are nonspecific, although they may suggest a diagnostic pattern and guide further testing. Nevertheless, chILD disorders often remain unrecognized on imaging studies, as they are very rare. The aim of this article is to review the CT patterns of lung involvement in a series of infants with chILD.

Is MRI imaging in pediatric age totally safe? A critical reprisal.

Current radiological literature is strongly focussed on radiation imaging risks. Indeed, given there is a small but actual augment in cancer risk from exposure to ionizing radiation in children, it is important to understand what the risk of alternative techniques could be. We retrospectively review literature data concerning possible MR imaging risks, focussing on the biological effects of MR, sedation and gadolinium compound risks when dealing with infant patients. The main concerns can be summarized in: (1) Biological effects of non-ionizing electromagnetic fields (EMF) employed-whose mechanisms of interaction with human tissues are polarization, induced current, and thermal heating, respectively. (2) Risks associated with noises produced during MRI examinations. (3) Hazards from ferromagnetic external and/or implanted devices-whose risk of being unintentionally brought inside MR room is higher in children than in adults. (4) Risks associated with sedation or general anaesthesia, essential problem in performing MR in very young patients, due to the exam long-lasting. (5) Risks related to gadolinium-based contrast agents, especially considering the newly reported brain deposition.

Whole-body MRI reveals high incidence of osteonecrosis in children treated for Hodgkin lymphoma.

Osteonecrosis is a well-recognized complication in patients treated with corticosteroids. The incidence of osteonecrosis in children treated for Hodgkin lymphoma is unknown because prospective whole-body magnetic resonance imaging (MRI) studies are lacking in this patient population. Paediatric patients with newly diagnosed Hodgkin lymphoma who were treated according to a uniform paediatric Hodgkin protocol were eligible for inclusion in this prospective study. Whole-body MRI was performed in all 24 included patients (mean age 15·1 years, 12 girls) both before treatment and after 2 cycles of chemotherapy, and in 16 patients after completion of chemotherapy. Osteonecrosis was identified in 10 patients (41·7%, 95% confidence interval: 22·0-61·4%), with a total of 56 osteonecrotic sites. Osteonecrosis was detected in 8 patients after 2 cycles of OEPA (vincristine, etoposide, prednisone, doxorubicin), and in 2 additional patients after completion of chemotherapy. Epiphyseal involvement of long bones was seen in 4 of 10 children. None of the patients with osteonecrosis had any signs of bone collapse at the times of scanning. Whole-body MRI demonstrates osteonecrosis to be a common finding occurring during therapy response assessment of paediatric Hodgkin lymphoma. Detection of early epiphyseal osteonecrosis could allow for treatment before bone collapse and joint damage may occur.

Image-defined risk factors in unresectable neuroblastoma: SIOPEN study on incidence, chemotherapy-induced variation, and impact on surgical outcomes.

PURPOSE: To evaluate the impact of image-defined risk factor (IDRF) modification after chemotherapy on surgical outcomes, event-free survival (EFS), and overall survival (OS) among patients enrolled in the European Unresectable Neuroblastoma (EUNB) study. METHODS: IDRFs were assigned according to the corresponding surgical risk factors list reported in the database. Surgical outcomes, EFS, and OS were related to IDRF modification with chemotherapy. The predictive value of preoperative IDRF for surgical outcomes was analyzed. Cox proportional hazards models for EFS and OS, including preoperative IDRF, surgical outcomes, and other known clinical risk factors, were created. RESULTS: Of the 160 patients enrolled in the EUNB study, 143 patients met the inclusion criteria. A total of 228 IDRF were thus collected. Following chemotherapy, 76 (33%) IDRF disappeared in 32.2% of patients, 33 (14%) new IDRF appeared in 18.8% of patients, and 49% of patients did not show any IDRF change. Complete resection/minimal residual disease (71.2%) was more frequent among children who had disappearance/numerical reduction of IDRF (P = 0.005). Infiltration of the branches of the mesenteric artery was predictive of an unfavorable surgical outcome. Prolonged preoperative chemotherapy over five courses and encasement of the celiac axis and/or mesenteric artery origin impacted EFS and OS. CONCLUSIONS: The unchanged IDRF pattern in 50% of patients and the appearance of new IDRF during chemotherapy in approximately 20% of patients strengthens the idea that prolonged chemotherapy is useless for improving surgical resection in this population of patients. In addition, midline perivascular abdominal preoperative IDRF appeared to be predictive not only of surgical outcomes but also of EFS and OS.

Radiation exposure in diagnostic imaging: wisdom and prudence, but still a lot to understand.

Since 2000, a series of scientific articles on CT have been raising increasing concern about the risk of radiation induced cancer in children. The alarming conclusions of some of these articles had international echo through global media, provoking widespread public concern. Actually, many of these alarming scientific publications appeared to be flawed by poor study design, but their conclusions were not openly contradicted. In US and Europe pediatric radiologists had to face a huge challenge, which brought to the Image Gently campaign and the Eurosafe initiative with the aim to rebut misinformation and to support medical radiation protection. The Linear No Threshold model-which is the base of contemporary radioprotection-is increasingly questioned by new recent studies suggesting that low dose radiation would decrease cancer risk thanks to the enhancement of immune system response. Actually, pediatric radiologists have to cope with many important issues and contradictory messages. Good medical practice includes good communication about the benefits and risks of health procedures, thus the communication of radiation risk is a key component for radiologists. When considering benefits and risks, an important risk is too often ignored: the risk that skipping a diagnostic exam may cause a misdiagnosis, and therefore, a poor outcome. We should emphasize that a risk from a radiological investigation is very small, if a risk at all, and we are not sure that there is a risk at very low doses, like those doses in the majority of X-ray procedures including CT.

Juvenile eosinophilic fasciitis: three case reports with review of the literature.

OBJECTIVES: Eosinophilic fasciitis is an uncommon scleroderma-like disorder characterised by induration and thickening of skin and soft tissue, usually associated with peripheral eosinophilia, poorly characterised in childhood. METHODS: We report 3 paediatric cases of eosinophilic fasciitis showing unusual clinical and histopathological features with a review of the literature. RESULTS: All cases presented progressive motility impairment started from upper limbs with no skin abnormalities. All cases showed systemic inflammatory involvement and 2 patients had acute complications. Two patients developed disabling outcomes despite appropriate treatments. CONCLUSIONS: Eosinophilic fasciitis may present unusual clinical and histopathological features during childhood and requires early recognition in order to prevent acute complications and disabling outcomes.