A Retrospective Analysis of the Therapeutic Outcomes of 117 Neuroblastoma Patients Treated at a Single Pediatric Oncology Center in China.

OBJECTIVE: Recent therapeutic advances have greatly enhanced the survival rates of patients with neuroblastoma (NB). However, the outcomes of neuroblastoma patients in China, particularly those with high-risk (HR) NB, remain limited. METHOD: We retrospectively analyzed the clinical data and outcomes of NB patients who were treated at a tertiary pediatric cancer facility in China between January 2013 and October 2021. RESULTS: A total of 117 NB patients were recruited. Patients with very low-risk (VLR), low-risk (LR), intermediate-risk (IR), and HR-NB patients made up 4%, 27%, 15%, and 54% of total patient population, respectively. Patients diagnosed between 2013 and 2018 were treated according to the protocol of Sun Yat-Sen University Cancer Center and those diagnosed between 2019 and 2021 were treated according to the COG ANBL0531 or ANBL0532 protocol with or without autologous stem cell transplantation (ASCT). The 5-year EFS and OS of all risk groups of patients were 67.29% and 77.90%, respectively. EFS and OS were significantly decreased in patients with higher risk classifications (EFS: VLR/LR vs IR vs HR: 97.22% vs 67.28% vs 51.83%; ***P = .001; OS: VLR/LR vs IR vs HR: 97.06% vs 94.12% vs 64.38%; *P = .046). In HR-NB patients treated according to the COG protocol between 2019 and 2021, the 3-year OS of patients who received tandem ASCT was significantly greater than those who did not receive ASCT (93.33% % vs 47.41%; *P = .046; log-rank test). EFS was not significantly different between patients with and without ASCT (72.16% vs 60.32%). CONCLUSION: Our findings show that patients with lower risk classification have a positive prognosis for survival. The prognosis of patients with HR-NB remains in need of improvement. ASCT may enhance OS in HR-NB patients; however, protocol adjustment may be necessary to increase EFS in these patients.

Whole-Body MRI Is an Effective Imaging Modality for Hematological Malignancy Treatment Response Assessment: A Systematic Review and Meta-Analysis.

OBJECTIVES: To evaluate the diagnostic accuracy of whole-body MRI (WB-MRI) for assessment of hematological malignancies' therapeutic response. METHODS: PubMed, Embase, and Web of Science were searched up to August 2021 to identify studies reporting the diagnostic performance of WB-MRI for the assessment of hematological malignancies' treatment response. A bivariate random-effects model was applied for the generation of the pooled diagnostic performance. RESULTS: Fourteen studies with 457 patients with lymphoma, multiple myeloma, and sarcoma (very small proportion) were analyzed. Overall pooled sensitivity and specificity of WB-MRI were 0.88 (95% CI: 0.73-0.95) and 0.86 (95% CI: 0.73-0.93), respectively. Studies using whole-body diffusion-weighted imaging (WB-DWI) showed higher sensitivity than those that did not (0.94 vs. 0.55, p = 0.02). The pooled concordance rate of WB-MRI to assess hematological malignancies' treatment response with reference standard was 0.78 (95% CI: 0.59-0.96). WB-MRI and PET/CT showed similar diagnostic performance (sensitivity [0.83 vs. 0.92, p = 0.11] and specificity [0.87 vs. 0.76, p = 0.73]). CONCLUSION: WB-MRI has high diagnostic performance for hematological malignancies' treatment response assessment. The adding of WB-DWI is strongly associated with increased sensitivity.

The Safety and Effectiveness of Intravenous Contrast-Enhanced Sonography in Chinese Children-A Single Center and Prospective Study in China.

Background and Objective: Intravenous contrast-enhanced ultrasound (CEUS), using the second-generation ultrasound contrast agent SonoVue®, has been widely used in adults. In 2016, it was approved for pediatric applications by the American Food and Drug Administration (FDA). However, it has not been approved by the Chinese Food and Drug Administration (CFDA). The objective of the study was to evaluate the safety and effectiveness of CEUS in children prospectively at a single center in China. Methods: A total of 312 cases of Chinese children were enrolled in clinical trials. Contrast agent was given intravenously with two different doses, including 2.4 ml/time and 0.03 ml/kg. All CEUS was performed for evaluating adverse effect and the diagnostic accuracy compared with the pathology and enhanced CT. Results: All 312 subjects underwent CEUS successfully. The dose of contrast agent for CEUS was 2.4 ml between November 2015 and June 2016, which was modified to 0.03 ml/kg between July 2016 and April 2019, according to the recommendation of the FDA. With the two different doses of the contrast agent, the heart rate, respiration rate, oxygen saturation, and blood pressure of the participants had no statistically significant difference (P > 0.05) before and after administration. The blood pressure had been significantly decreased in participants who received combined anesthetic administration. Following 600 intravenous injections of the CEUS, there were three cases of transient rash and three cases of hypotension (n = 6, 1.92%). The six recovered quickly after receiving intravenous methylprednisolone and epinephrine. Most of the studies were performed for evaluating renal microcirculation and assisting renal biopsy (192/312 [61.5%]), which together had a 98.9% effectiveness in the identification of pathology in the specimens. Some studies were conducted to identify a mass in the liver, retroperitoneum, abdominal cavity, kidneys, testicles, thyroid, and so on (99/312 [31.4%]), which had a 97.6% accuracy. The other studies were conducted to identify trauma, vascular malformation, infection, hemorrhage, and so on (21/312 [6.73%]), which had a similar accuracy to enhanced CT. Conclusion: The adverse effects of CEUS in children are similar to that in adults. The results indicate that it is safe to use SonoVue® for CEUS in pediatric patients.

Accuracy of multi-echo Dixon sequence in quantification of hepatic steatosis in Chinese children and adolescents.

BACKGROUND: Nonalcoholic fatty liver disease (NAFLD) is currently the outstanding cause of chronic liver disease in children and adolescents, especially in overweight and obese groups. Liver biopsy is the reference standard to diagnose NAFLD but invasive, thus it is not the best choice in clinical diagnosis and follow-up. Magnetic resonance (MR) is widely used in clinical trials to noninvasively quantify liver fat content in adults and children in foreign countries. While currently, it is rarely used in Chinese children and adolescents. We postulated that quantifying hepatic steatosis by MR could be extended to children and adolescents in China. AIM: To investigate the accuracy of MR imaging (MRI) in quantifying liver fat with MR spectroscopy (MRS) as a reference. A secondary goal was to assess the prevalence of NAFLD in overweight and obese Chinese children and adolescents. METHODS: There were 86 children and adolescents enrolled in this study, including 65 overweight and obese children and 21 healthy children. The participants underwent MRI and MRS. MRI and MRS were performed using multi-echo Dixon and HISTO sequences, respectively, to calculate hepatic proton density fat fraction (PDFF). Hepatic steatosis was diagnosed using MRS-PDFF > 5% as the threshold. Spearman's analysis was used to evaluate the correlation between MRI and MRS. The agreement between these two methods was assessed by Bland-Altman analysis. RESULTS: The MRI-PDFF in the MRS region of interest and the entire liver was 9.9% ± 10.3% with a range of 0.3%-39.9%, and 10.6% ± 9.4% with a range of 1.9%-38.9%, respectively. The MRS-PDFF was 9.1% ± 10.0%, with a range of 0.5%-37.8%. The incidence of hepatic steatosis detected by MRS-PDFF was 46.5% (40/86) of all participants, all of whom belonged to the overweight and obese group. Spearman's analysis indicated an excellent correlation between multi-echo Dixon and MRS (r > 0.9, P < 0.01). Bland-Altman analysis also demonstrated a good agreement between these two methods. CONCLUSION: Multi-echo Dixon shows an excellent correlation and agreement with MRS in quantifying liver fat content and could be a potential tool to detect hepatic steatosis in Chinese children and adolescents.

Alterations in Spontaneous Brain Activity and Functional Network Reorganization following Surgery in Children with Medically Refractory Epilepsy: A Resting-State Functional Magnetic Resonance Imaging Study.

For some patients with medically refractory epilepsy (MRE), surgery is a safe and effective treatment for controlling epilepsy. However, the functional consequences of such surgery on brain activity and connectivity in children remain unknown. In the present study, we carried out a longitudinal study using resting-state functional magnetic resonance imaging in 10 children with MRE before and again at a mean of 79 days after surgery, as well as in a group of 28 healthy controls. Compared with the controls, children with epilepsy exhibited abnormalities in intrinsic activity in the thalamus, putamen, pallidum, insula, hippocampus, cerebellum, and cingulate gyrus both before and after surgery. Longitudinal analyses showed that the amplitude of low frequency fluctuations (ALFF) increased in the parietal-frontal cortex and decreased in the deep nuclei from pre- to post-surgery. The percentage changes in ALFF values in the deep nuclei were positively correlated with the age of epilepsy onset. Functional connectivity (FC) analyses demonstrated a reorganization of FC architecture after surgery. These changes in brain activity and FC after surgery might indicate that the previously disrupted functional interactions were reorganized after surgery. All these results provide preliminary evidence that the age of epilepsy onset may have some potential to predict the outcome of brain functional reorganization after surgery in children with MRE.

Diffusion tensor imaging detects early brain microstructure changes before and after ventriculoperitoneal shunt in children with high intracranial pressure hydrocephalus.

To explore the use of diffusion tensor imaging (DTI) parameters in the quantitative assessment of early brain microstructure changes before and after ventriculoperitoneal shunt in children with high intracranial pressure hydrocephalus.Ten patients with communicating hydrocephalus (age: 2-36 months) and 14 age-/gender-matched controls (age: 2-36 months) were enrolled in this study. All patients underwent the ventriculoperitoneal shunt procedure. The imaging data were collected before and 3 months after the operation. Regions of interests (ROIs) included the white matter near the frontal horn of the lateral ventricles (FHLV), the occipital horn of the lateral ventricles (OHLV), occipital subcortical (OS) area, frontal subcortical (FS) area, and thalamus. Fractional anisotropies (FA) and apparent diffusion coefficients (ADC) of the ROIs before and after ventriculoperitoneal shunt were compared between the patients and the controls.Three months after surgery, the patients recovered from the surgery with ameliorated intracranial pressure and slight improvement of clinical intelligence scale and motor scale. Before ventriculoperitoneal shunt, the FA values (except the right FHLV) were significantly decreased and the ADC values were significantly increased in the patients with hydrocephalus, compared with the controls. After the ventriculoperitoneal shunt, the FA values in the FHLV and OHLV of the patients were similar to the controls, but the FA values in other ROIs were still significantly lower than controls. The ADC values in the FS and OS white matter areas of the patients were similar to the controls; however, the ADC values in other ROIs were still significantly higher in patients.The increase of FA and the reduction in ADC in the ROIs preceded the clinical function improvement in patients with high intracranial pressure hydrocephalus and reflected the early changes in brain tissue microstructure, such as the compression of the white matter areas in the ROIs.