Genome-Wide DNA Methylation Profiling as Frontline Diagnostics for Central Nervous System Embryonal Tumors in Hong Kong.

This paper examines the link between CNS tumor biology and heterogeneity and the use of genome-wide DNA methylation profiling as a clinical diagnostic platform. CNS tumors are the most common solid tumors in children, and their prognosis remains poor. This study retrospectively analyzed pediatric patients with CNS embryonal tumors in Hong Kong between 1999 and 2017, using data from the territory-wide registry and available formalin-fixed paraffin-embedded tumor tissue. After processing archival tumor tissue via DNA extraction, quantification, and methylation profiling, the data were analyzed by using the web-based DKFZ classifier (Molecular Neuropathology (MNP) 2.0 v11b4) and t-SNE analysis. Methylation profiles were deemed informative in 85 samples. Epigenetic data allowed molecular subgrouping and confirmed diagnosis in 65 samples, verified histologic diagnosis in 8, and suggested an alternative diagnosis in 12. This study demonstrates the potential of DNA methylation profiling in characterizing pediatric CNS embryonal tumors in a large cohort from Hong Kong, which should enable regional and international collaboration in future pediatric neuro-oncology research.

Case Report: Primary Thoracic Low-Grade Fibromyxoid Sarcoma in a Young Girl Presenting With Mediastinal Mass Syndrome.

Low-grade fibromyxoid sarcomas (LGFMSs) are typically adult-onset tumors that arise from the extremities. Here, we report an exceptional case of primary thoracic LGFMS in an 8-year-old girl that resulted in mediastinal syndrome. In reporting this case, we discuss the clinical challenges, role of molecular profiling and review reported cases of pediatric thoracic LGFMSs.

Neurobehavioral Impairment in Pediatric Brain Tumor Survivors: A Meta-Analysis.

Purpose: The neurocognitive outcomes of pediatric brain tumor survivors have been extensively studied but the risk and predictors for neurobehavioral impairment are less clearly defined. We systematically analyzed the rates of emotional, psychosocial, and attention problems in pediatric brain tumor survivors. Methods: PubMed, Web of Science, Embase, Scopus, and Cochrane were searched for articles published between January 2012 to April 2022. Eligible studies reported neurobehavioral outcomes for PBTS aged 2 to <23 years with a brain tumor diagnosis before 18 years of age. A random-effect meta-analysis was performed in R. Results: The search yielded 1187 unique publications, of which 50 were included in the quantitative analysis. The estimated risk of having emotional, psychosocial, and attention problems were 15% (95%CI 10−20%), 12% (95%CI 9−16%), and 12% (95%CI 9−16%), respectively. PBTS were more likely to have emotional difficulties (Hedge's g = 0.43 [95%CI 0.34−0.52]), psychosocial problems (Hedge's g = 0.46 [95%CI 0.33−0.58]), and attention problems (Hedge's g = 0.48 [95%CI 0.34−0.63]) compared to normal/healthy control subjects. There was no significant difference in the rates of neurobehavioral impairment between children with and without history of cranial radiotherapy. Conclusions: PBTS are at elevated risk of neurobehavioral impairment. Neurobehavioral monitoring should be considered as the standard of care for PBTS.

Carboplatin-induced renal salt-wasting syndrome in pediatric patients with intracranial germ cell tumors and concomitant diabetes insipidus.

We report a case series of 14 children with intracranial germ cell tumor and concomitant central diabetes insipidus, who developed hyponatremia secondary to renal salt-wasting syndrome (RSWS) following the administration of carboplatin. Clinicians prescribing platinum-based chemotherapy for this group of patients should be alert to the risk of RSWS. Regular monitoring should be performed as hyponatremia can be asymptomatic until it is severe.

Brain Microstructural Changes Associated With Neurocognitive Outcome in Intracranial Germ Cell Tumor Survivors.

BACKGROUND: Childhood intracranial germ cell tumor (GCT) survivors are prone to radiotherapy-related neurotoxicity, which can lead to neurocognitive dysfunctions. Diffusion kurtosis imaging (DKI) is a diffusion MRI technique that is sensitive to brain microstructural changes. This study aimed to investigate the association between DKI metrics versus cognitive and functional outcomes of childhood intracranial GCT survivors. METHODS: DKI was performed on childhood intracranial GCT survivors (n = 20) who had received cranial radiotherapy, and age and gender-matched healthy control subjects (n = 14). Neurocognitive assessment was performed using the Hong Kong Wechsler Intelligence Scales, and functional assessment was performed using the Lansky/Karnofsky performance scales (KPS). Survivors and healthy controls were compared using mixed effects model. Multiple regression analyses were performed to determine the effects of microstructural brain changes of the whole brain as well as the association between IQ and Karnofsky scores and the thereof. RESULTS: The mean Intelligence Quotient (IQ) of GCT survivors was 91.7 (95% CI 84.5 - 98.8), which was below the age-specific normative expected mean IQ (P = 0.013). The mean KPS score of GCT survivors was 85.5, which was significantly lower than that of controls (P < 0.001). Cognitive impairments were significantly associated with the presence of microstructural changes in white and grey matter, whereas functional impairments were mostly associated with microstructural changes in white matter. There were significant correlations between IQ versus the mean diffusivity (MD) and mean kurtosis (MK) of specific white matter regions. The IQ scores were negatively correlated with the MD of extensive grey matter regions. CONCLUSION: Our study identified vulnerable brain regions whose microstructural changes in white and grey matter were significantly associated with impaired cognitive and physical functioning in survivors of pediatric intracranial GCT.

Incidence and Outcomes of CNS Tumors in Chinese Children: Comparative Analysis With the Surveillance, Epidemiology, and End Results Program.

PURPOSE: Despite being the most common pediatric solid tumors, incidence and outcome of CNS tumors in Chinese children have not been systematically reported. We addressed this knowledge gap by comparing the epidemiology of pediatric CNS tumors in Hong Kong and the United States. PATIENTS AND METHODS: Data between 1999 and 2016 from a population-based cancer registry in Hong Kong, China, on patients < 18 years old with CNS tumors (Hong Kong cohort) and from the US SEER Program (Asian/Pacific Islander and all ethnicities) were compared. Incidence and overall survival (OS) by histology were evaluated. RESULTS: During the study period, 526 children were newly diagnosed with CNS tumors in Hong Kong (crude incidence rate, 2.47 per 100,000; 95% CI, 2.26 to 2.69). Adjusted incidences were significantly lower in the Hong Kong (2.51; 95% CI, 2.30 to 2.74) than in the SEER (Asian/Pacific Islander: 3.26; 95% CI, 2.97 to 3.57; P < .001; all ethnicities: 4.10 per 100,000; 95% CI, 3.99 to 4.22; P < .001) cohorts. Incidences of germ cell tumors (0.57 v 0.24; P < .001) were significantly higher, but those of glial and neuronal tumors (0.94 v 2.61; P < .001), ependymomas (0.18 v 0.31; P = .005), and choroid plexus tumors (0.08 v 0.16; P = .045) were significantly lower in Hong Kong compared with SEER (all ethnicities) cohorts. Compared with the SEER (Asian/Pacific Islander) cohort, histology-specific incidences were similar except for a lower incidence of glial and neuronal tumors in Hong Kong (0.94 v 1.74; P < .001). Among cohorts, OS differed only for patients with glial and neuronal tumors (5-year OS: Hong Kong, 52.5%; SEER [Asian/Pacific Islander], 73.6%; SEER [all ethnicities], 79.9%; P < .001). CONCLUSION: We identified important ethnic differences in the epidemiology of CNS tumors in Chinese children. These results will inform the development of pediatric neuro-oncology services in China and aid further etiologic studies.

Outcome of Chinese children with craniopharyngioma: a 20-year population-based study by the Hong Kong Pediatric Hematology/Oncology Study Group.

PURPOSE: Craniopharyngioma is a rare low-grade neoplasm in children. Tumor progression occurs frequently, and survivors are at risk of long-term disease and treatment-related morbidities. We reviewed the population-based experience of managing pediatric craniopharyngioma in Hong Kong. METHODS: The Hong Kong Pediatric Hematology/Oncology Study Group database was interrogated for patients with craniopharyngioma younger than 18 years between 1999 and 2018. Patient demographics, clinical characteristics, outcomes, and long-term morbidities were summarized. RESULTS: Twenty-eight patients with craniopharyngioma were included (approximate incidence of 1.1 per 1,000,000 individuals). The treatment approaches were heterogeneous and included surgery only, surgery with adjuvant radiation, and surgery with intracystic interferon. With a median follow-up of 6.1 years, 12 (43%) patients experienced disease progression, and 3 patients died of progression, postoperative complication, and gastrointestinal bleeding. The 5-year progression-free survival (PFS) and overall survival (OS) rates were 56.8% (± 10.0%) and 92.0% (± 5.4%), respectively. The 10-year PFS and OS rates were 37.3% (± 11.4) and 92.0% (± 5.4%), respectively. Patients receiving treatment in a high-volume center had significantly better outcomes than did those treated at other centers (PFS, p = 0.007; OS, p = 0.029). Period of diagnosis, sex, age at diagnosis, greatest tumor dimension, extent of resection, and radiotherapy use did not significantly affect patient survival. Long-term visual impairment (60%) and endocrinopathies (92%) were common. CONCLUSION: Prognosis of pediatric craniopharyngioma in Hong Kong compares unfavorably with published reports. Centralization and standardization of treatment may prove valuable in mitigating patient outcomes.

Neurocognitive function, performance status, and quality of life in pediatric intracranial germ cell tumor survivors.

BACKGROUND: Intracranial germ cell tumors (GCT) are more common in Asia than in the West, accounting for about 15% of brain tumors in Asian children. The survival rate for intracranial GCT is excellent, but there are concerns about the effects of radiotherapy on neuropsychological function and quality of life of patients. METHODS: Intracranial germ cell tumors (GCT) are more common in Asia than in the West, accounting for about 15% of brain tumors in Asian children. The survival rate for intracranial GCT is excellent, but there are concerns about the effects of radiotherapy on neuropsychological function and quality of life of patients. Intracranial GCT survivors in Hong Kong aged ≥ 6 years who received cranial irradiation in the past 15 years were recruited. Neurocognitive function and performance status were assessed by the Hong Kong Wechsler Intelligence scale and Karnofsky/Lansky performance scales (KPS), respectively. Quality of life was assessed using the Pediatric Quality of Life Inventory (PedsQL) Generic Core Scales. A chart review was performed for tumor characteristics and complications related to the tumor and its treatment. RESULTS: Twenty-five intracranial GCT survivors were recruited. Longer length of time since treatment was associated with lower IQ scores. Larger tumor size was associated with lower KPS scores. Hemiparesis, poor manual dexterity, and complications with multi-organ involvement were associated with significantly lower KPS scores. Higher irradiation dosage was associated with lower PedsQL physical scores. CONCLUSIONS: The majority of GCT survivors had average intellectual functioning, satisfactory performance status and relatively good quality of life, except in the physical aspect. Comprehensive evaluation and long-term follow-up of GCT survivors are essential to provide timely support and improve long-term outcomes.

Excellent outcome of acute lymphoblastic leukaemia with TCF3-PBX1 rearrangement in Hong Kong.

OBJECTIVE: The aim of this study was to review clinical outcomes and prognosis of paediatric patients with acute lymphoblastic leukaemia (ALL) with TCF3-PBX1 rearrangement. PATIENTS: All children in Hong Kong diagnosed with ALL with TCF3-PBX1 rearrangement over the past two decades were included. METHODS: Six hundred and twenty-four newly diagnosed patients with ALL from four consecutive studies were enrolled from 1997 to 2016. Patients carrying TCF3-PBX1 rearrangement and patients at intermediate risk without the gene expression were compared for clinical characteristics, overall survival and event-free survival (EFS). RESULTS: The TCF3-PBX1 rearrangement was detected in 30 of 624 patients (4.8%). Results were consistent across the consecutive clinical trials employed in the past two decades. Compared with 239 intermediate risk patients without TCF3-PBX1 rearrangement, the 5-year overall survival and EFS for patients with TCF3-PBX1 rearrangement was superior, with both at 100% (P = 0.12 and P = 0.029). CONCLUSION: This population-based study over the past 20 years demonstrated that patients with TCF3-PBX1 rearrangement had favourable EFS compared with other intermediate risk patients treated with a similar chemotherapy backbone.