Lorlatinib with or without chemotherapy in ALK-driven refractory/relapsed neuroblastoma: phase 1 trial results.

Neuroblastomas harbor ALK aberrations clinically resistant to crizotinib yet sensitive pre-clinically to the third-generation ALK inhibitor lorlatinib. We conducted a first-in-child study evaluating lorlatinib with and without chemotherapy in children and adults with relapsed or refractory ALK-driven neuroblastoma. The trial is ongoing, and we report here on three cohorts that have met pre-specified primary endpoints: lorlatinib as a single agent in children (12 months to <18 years); lorlatinib as a single agent in adults (≥18 years); and lorlatinib in combination with topotecan/cyclophosphamide in children (<18 years). Primary endpoints were safety, pharmacokinetics and recommended phase 2 dose (RP2D). Secondary endpoints were response rate and 123I-metaiodobenzylguanidine (MIBG) response. Lorlatinib was evaluated at 45-115 mg/m2/dose in children and 100-150 mg in adults. Common adverse events (AEs) were hypertriglyceridemia (90%), hypercholesterolemia (79%) and weight gain (87%). Neurobehavioral AEs occurred mainly in adults and resolved with dose hold/reduction. The RP2D of lorlatinib with and without chemotherapy in children was 115 mg/m2. The single-agent adult RP2D was 150 mg. The single-agent response rate (complete/partial/minor) for <18 years was 30%; for ≥18 years, 67%; and for chemotherapy combination in <18 years, 63%; and 13 of 27 (48%) responders achieved MIBG complete responses, supporting lorlatinib's rapid translation into active phase 3 trials for patients with newly diagnosed high-risk, ALK-driven neuroblastoma. ClinicalTrials.gov registration: NCT03107988 .

Assessment of germinal matrix hemorrhage on head ultrasound with deep learning algorithms.

BACKGROUND: Germinal matrix hemorrhage-intraventricular hemorrhage is among the most common intracranial complications in premature infants. Early detection is important to guide clinical management for improved patient prognosis. OBJECTIVE: The purpose of this study was to assess whether a convolutional neural network (CNN) can be trained via transfer learning to accurately diagnose germinal matrix hemorrhage on head ultrasound. MATERIALS AND METHODS: Over a 10-year period, 400 head ultrasounds performed in patients ages 6 months or younger were reviewed. Key sagittal images at the level of the caudothalamic groove were obtained from 200 patients with germinal matrix hemorrhage and 200 patients without hemorrhage; all images were reviewed by a board-certified pediatric radiologist. One hundred cases were randomly allocated from the total for validation and an additional 100 for testing of a CNN binary classifier. Transfer learning and data augmentation were used to train the model. RESULTS: The median age of patients was 0 weeks old with a median gestational age of 30 weeks. The final trained CNN model had a receiver operating characteristic area under the curve of 0.92 on the validation set and accuracy of 0.875 on the test set, with 95% confidence intervals of [0.86, 0.98] and [0.81, 0.94], respectively. CONCLUSION: A CNN trained on a small set of images with data augmentation can detect germinal matrix hemorrhage on head ultrasounds with strong accuracy.

Imaging of congenital genitourinary anomalies.

Congenital genitourinary anomalies are among the most frequent types of birth defects in neonates. Some anomalies can be a significant cause of morbidity in infancy, while others remain asymptomatic even until adulthood and can be at times the only manifestation of a complex systemic disease. The spectrum of these anomalies results from the developmental insults that can occur at various embryologic stages, and an understanding of the formation of the genitourinary system is helpful in the evaluation and treatment of a child with a congenital genitourinary anomaly. Imaging plays an essential role in the diagnosis of congenital genitourinary anomalies and treatment planning. In this article, we highlight the embryologic and characteristic imaging features of various congenital genitourinary anomalies, demonstrate the utility of different imaging modalities in management, and review specific imaging modalities and protocols for image optimization.

Contrast-enhanced voiding urosonography part 2: urethral imaging.

Ultrasound (US) has been increasingly used as an important imaging tool to assess the urethra in children. The earliest reports of pediatric urethral sonography involved imaging the urethra in a non-voiding state, during physiological voiding of urine, and after instillation of saline. The introduction of US contrast agents has continued to improve visualization of urethral anatomy. Contrast-enhanced US of the urethra can be performed during the voiding phase of a standard contrast-enhanced voiding urosonography (ceVUS) exam or with retrograde instillation of a contrast agent, depending on the exam indication. Both techniques are well tolerated by children and provide accurate information about urethral pathology and periurethral soft tissues. This article reviews the technical aspects and imaging findings of urethral pathologies in children using contrast-enhanced US, both by the voiding and retrograde instillation techniques.

Contrast-enhanced ultrasound of the kidneys and adrenals in children.

Pediatric applications of contrast-enhanced ultrasound (CEUS) are growing. Evaluation of the kidneys and adrenal glands in children using intravenous administration of US contrast agents, however, is still an off-label indication. Pediatric CEUS applications for kidneys are similar to those in adults, including ischemic disorders, pseudo- versus real tumors, indeterminate lesions, complex cystic lesions, complicated pyelonephritis, and abscesses. CEUS applications for evaluation of adrenal glands in children are limited, mainly focusing on the assessment and follow-up of adrenal trauma and the differentiation between an adrenal hemorrhage and a mass. This review addresses the current experience in pediatric CEUS of the kidneys and adrenal glands. By extrapolating the established knowledge for US contrast evaluations in the adult kidney to the pediatric context we can note opportunities for CEUS clinical use in children.

Radiation in Pediatric Imaging: A Primer for Pediatricians.

Medical imaging in children makes up a considerable percentage of all imaging procedures performed in the United States. Although in recent years there has been a 15% to 20% reduction in the exposure to ionizing radiation from medical imaging in the US population, the total number of computed tomography (CT) scans has increased from 2006 to 2016, and about 85% of all medical ionizing radiation in children is due to CT. [Pediatr Ann. 2020;49(9):e370-e373.].

Virtual Read-Out: Radiology Education for the 21st Century During the COVID-19 Pandemic.

Technologic advances have resulted in the expansion of web-based conferencing and education. While historically video-conferencing has been used for didactic educational sessions, we present its novel use in virtual radiology read-outs in the face of the COVID-19 pandemic. Knowledge of key aspects of set-up, implementation, and possible pitfalls of video-conferencing technology in the application of virtual read-outs can help to improve the educational experience of radiology trainees and promote potential future distance learning and collaboration.

Pediatric Mediastinal Masses:: Role of MR Imaging as a Problem-Solving Tool.

Computed tomography (CT) is the imaging modality of choice for evaluating mediastinal masses detected by radiography or clinical presentation. However, CT results can often be indeterminate. Thoracic magnetic resonance (MR) imaging is a noninvasive way to characterize mediastinal lesions, site of origin, and involvement of adjacent structures by providing higher soft tissue contrast than CT, with superior tissue characterization and higher diagnostic specificity. Thoracic MR imaging of mediastinal masses can increase diagnostic certainty, reduce the number of surgical interventions, and improve clinical decision making. In this review article, current imaging techniques and clinical applications of MR imaging as a problem-solving tool for assessing mediastinal masses in pediatric patients are discussed.

Pediatric Renal Neoplasms:: MR Imaging-Based Practical Diagnostic Approach.

Pediatric renal tumors may be malignant or benign. Wilms tumor, the most common malignant pediatric renal tumor, arises sporadically or with various syndromes. Renal cell carcinoma typically presents in older children. Renal clear cell sarcoma and rhabdoid tumor are typically less common, more aggressive, and present in younger children. Benign renal tumors include mesoblastic nephroma, multilocular cystic renal tumor, angiomyolipoma, and metanephric adenoma. Lymphoma and leukemia may secondarily involve the kidney. Although there is overlap in the imaging appearance of several pediatric renal tumors, magnetic resonance characteristics and clinical data narrow the differential diagnosis and suggest a specific diagnosis. This article reviews current MR techniques, as well as the common MR imaging characteristics of malignant and benign pediatric renal neoplasms.

Pediatric contrast-enhanced ultrasound in the United States: a survey by the Contrast-Enhanced Ultrasound Task Force of the Society for Pediatric Radiology.

BACKGROUND: The United States Food and Drug Administration (FDA) recently approved an ultrasound (US) contrast agent for intravenous and intravesical administration in children. OBJECTIVE: Survey the usage, interest in and barriers for contrast-enhanced US among pediatric radiologists. MATERIALS AND METHODS: The Contrast-Enhanced Ultrasound Task Force of the Society for Pediatric Radiology (SPR) surveyed the membership of the SPR in January 2017 regarding their current use and opinions about contrast-enhanced US in pediatrics. RESULTS: The majority (51.1%, 166) of the 325 respondents (26.7% of 1,218) practice in either a university- or academic affiliated group. The most widely used US contrast agent was Lumason® 52.3% (23/44). While lack of expertise and training were reported barriers, all respondents who are not currently using US contrast agents are considering future use. CONCLUSION: Interest in pediatric contrast US is very high. Education and training are needed to support members who plan to adopt contrast US into practice.

Response Evaluation Criteria in Solid Tumors (RECIST) following neoadjuvant chemotherapy in osteosarcoma.

BACKGROUND: In osteosarcoma, patient survival has not changed in over 30 years. Multiple phase II trials have been conducted in osteosarcoma using the Response Evaluation Criteria in Solid Tumors (RECIST) as a primary endpoint; however, none of these have revealed new treatment strategies. We investigated RECIST in newly diagnosed patients who received neoadjuvant chemotherapy proven to be beneficial. METHODS: Patients treated from 1986 to 2011 for newly diagnosed osteosarcoma with paired tumor imaging before and after adequate neoadjuvant chemotherapy were included in this retrospective study. Two radiologists performed independent, blinded (to image timing) RECIST measurements of primary tumor and lung metastases at diagnosis and post-neoadjuvant chemotherapy. Association between RECIST and histological necrosis and outcome were assessed. RESULTS: Seventy-four patients met inclusion criteria. Five-year overall survival and progression-free survival (PFS) were 77 ± 7% and 61 ± 8%, respectively. No patients had RECIST partial or complete response in the primary tumor. Sixty-four patients (86%) had stable disease, and 10 (14%) had progressive disease (PD). PD in the primary tumor was associated with significantly worse PFS in localized disease patients (P = 0.02). There was no association between RECIST in the primary tumor and necrosis. There were an insufficient number of patients with lung nodules ≥1 cm at diagnosis to evaluate RECIST in pulmonary metastases. CONCLUSIONS: PD by RECIST predicts poor outcome in localized disease patients. In bone lesions, chemotherapy proven to improve overall survival does not result in radiographic responses as measured by RECIST. Further investigation of RECIST in pulmonary metastatic disease in osteosarcoma is needed.