In high-income countries, the overall survival of children with Wilms tumors (WT) is ~90%. However, overall, 15% of patients experience tumor recurrence. The adverse prognostic factors currently used for risk stratification (advanced stage, high risk histology, and combined loss of heterozygosity at 1p and 16q in chemotherapy-naïve WTs) are present in only one third of these cases, and the significance of these factors is prone to change with advancing knowledge and improved treatment regimens. Therefore, we present a comprehensive, updated overview of the published prognostic variables for WT recurrence, ranging from patient-, tumor- and treatment-related characteristics to geographic and socioeconomic factors. Improved first-line treatment regimens based on clinicopathological characteristics and advancing knowledge on copy number variations unveil the importance of further investigating the significance of biological markers for WT recurrence in international collaborations.

Delay in adopting effective treatment has serious consequences.1 Hundreds of thousands more infants could have lived had antenatal corticosteroids been introduced sooner after evidence to support their use was published in 1972.2,3 A systematic review, published in this issue of Pediatrics , by Deshpande et al4 of 11 randomized, controlled trials (RCTs) in 2176 infants of <34 weeks' gestation revealed that oral probiotics reduced all-cause mortality and necrotizing enterocolitis (NEC) by more than half ( P < .00001). These results suggest that current probiotics could prevent tens of thousands of deaths annually. The unusually large effect implies that most deaths or cases of NEC in eligible infants who are not given probiotics may, on balance of probability, be ascribed to that omission. Few infants receive probiotics outside RCTs. Should this practice change? After birth at term, the gut is colonized with probiotic organisms such as lactobacilli and bifidobacteria. Probiotics upregulate local and systemic immunity, increase anti-inflammatory cytokines and gut impermeability to bacteria and toxins, and suppress pathogens associated with NEC.5 Probiotics are susceptible to antibiotics, which could explain why prolonged antibiotic use is associated with NEC6,7 and death.7 The authors of a Cochrane review article recommended probiotics for infants of >1000 g birth weight but also recommended more research in smaller infants.8 However, in a subsequent … Address correspondence to William Odita Tarnow-Mordi, BA(Cantab), MBChB, MRCP(UK), DCH, FRCPCH, Westmead Hospital WINNER Centre and Centre for Newborn Care, University of Sydney, Hawkesbury Road, Wentworthville, Sydney, New South Wales 2122, Australia. E-mail: williamtm{at}med.usyd.edu.au

Meta-[¹²³I]iodobenzylguanidine ([¹²³I]MIBG) scintigraphy with SPECT/CT is the standard of care for diagnosing and monitoring neuroblastoma. Replacing [¹²³I]MIBG with the new PET tracer meta-[¹⁸F]fluorobenzylguanidine ([¹⁸F]MFBG) and further improving sensitivity and reducing noise in a new long-axial-field-of-view (LAFOV) PET/CT scanner enable increased image quality and a faster acquisition time, allowing examinations to be performed without sedation or general anesthesia (GA). Focusing on feasibility, we present our first experience with [¹⁸F]MFBG LAFOV PET/CT and compare it with [¹²³I]MIBG scintigraphy plus SPECT/CT for imaging in neuroblastoma in children. Methods: A pilot of our prospective, single-center study recruited children with neuroblastoma who were referred for [¹²³I]MIBG scintigraphy with SPECT/CT. Within 1 wk of [¹²³I]MIBG scintigraphy and SPECT/low-dose CT, [¹⁸F]MFBG LAFOV PET/ultra–low-dose CT was performed 1 h after injection (1.5–3 MBq/kg) without sedation or GA, in contrast to the 24-h postinjection interval needed for scanning with [¹²³I]MIBG, the 2- to 2.5-h acquisition time, and the GA often needed in children less than 6 y old. Based on the spirocyclic iodonium-ylide precursor, [¹⁸F]MFBG was produced in a fully automated good manufacturing practice–compliant procedure. We present the feasibility of the study. Results: In the first paired scans of the first 10 children included (5 at diagnosis, 2 during treatment, 2 during surveillance, and 1 at relapse), [¹⁸F]MFBG PET/CT scan showed a higher number of radiotracer-avid lesions in 80% of the cases and an equal number of lesions in 20% of the cases. The SIOPEN score was higher in 50% of the cases, and the Curie score was higher in 70% of the cases. In particular, intraspinal, retroperitoneal lymph node, and bone marrow involvement was diagnosed with much higher precision. None of the children (median age, 1.6 y; range, 0.1–7.9 y) had sedation or GA during the PET procedure, whereas 80% had GA during [¹²³I]MIBG scintigraphy with SPECT/CT. A PET acquisition time of only 2 min without motion artifacts was the data requirement of the 10-min acquisition time for reconstruction to provide a clinically useful image. Conclusion: This pilot study demonstrates the feasibility of performing [¹⁸F]MFBG LAFOV PET/CT for imaging of neuroblastoma. Further, an increased number of radiotracer-avid lesions, an increased SIOPEN score, and an increased Curie score were seen on [¹⁸F]MFBG LAFOV PET/CT compared with [¹²³I]MIBG scintigraphy with SPECT/CT, and GA and sedation was avoided in all patients. Thus, with a 1-d protocol, a significantly shorter scan time, a higher sensitivity, and the avoidance of GA and sedation, [¹⁸F]MFBG LAFOV PET/CT shows promise for future staging and response assessment and may also have a clinical impact on therapeutic decision-making for children with neuroblastoma. Visual Abstract

Background: Nausea and vomiting are common and distressing side effects for children receiving chemotherapy. Limited evidence is available to guide antiemetic recommendations; therefore, prospective and reliable evaluation of antiemetic efficacy is needed. Smartphone apps can be used to effortlessly and precisely collect patient-reported outcomes in real time. Objective: Our objective was to develop a smartphone app to monitor nausea and vomiting episodes in pediatric cancer patients aged 0 to 18 years and to test its usability and adherence to its use. Methods: We used a user-centered design process and the evolutionary prototype model to develop and evaluate the app. Multidisciplinary group discussions and several rounds of patient feedback and modification were conducted. We translated the validated Pediatric Nausea Assessment Tool to assess nausea severity in children aged 4 to 18 years. The child’s own term for nausea was interactively incorporated in the nausea severity question, with response options expressed as 4 illustrative faces. Parent-reported outcomes were used for children aged 0 to 3 years. Reminders were sent using push notifications in order to ensure high response rates. Children aged 0 to 18 years who were undergoing chemotherapy were recruited from the Department of Pediatric Oncology at Copenhagen University Hospital Rigshospitalet to evaluate the app. Results: The app’s most important function was to record nausea severity in children. After assistance from a researcher, children aged 4 to 18 years were able to report their symptoms in the app, and parents were able to report symptoms for their children aged 0 to 3 years. Children (n=20, aged 2.0-17.5 years) and their parents evaluated the app prospectively during a collective total of 60 chemotherapy cycles. They expressed that the app was user-friendly, intuitive, and that the time spent on data entry was fair. The response rates were on average 92%, 93%, and 80% for the day before, the first day of, and the next 3 days after chemotherapy, respectively. Researchers and clinicians were able to obtain an overview of the patient’s chemotherapy dates and responses through a secure and encrypted web-based administrative portal. Data could be downloaded for further analysis. Conclusions: The user-friendly app could be used to facilitate future pediatric antiemetic trials and to refine antiemetic treatment during chemotherapy.