Background
COVID-19, the novel coronavirus has caused a global pandemic affecting millions of people around the world. Although children, including children with cancer, have been found to be ...affected less commonly and less severely than adults, indirect effects of the pandemic on the diagnosis and treatment of children with cancer have been less described.
Methods
A survey was performed in the four largest tertiary pediatric hematology-oncology medical centers in Israel. Clinical and laboratory data were collected from the medical files of patients diagnosed or treated with cancer during April–October 2020.
Results
Seventeen patients are described, who had a significant delay in diagnosis or treatment of cancer. These represent approximately 10% of all pediatric cancer diagnosed during the study period in these centers. A main cause of delay was fear of exposure to COVID-19 (fears felt by the patient, parent, physician, or decision-makers at the institution; or the implementation of national guidelines). Delays also resulted from co-infection with COVID-19 and the attribution of the oncologic symptoms to the infection. In addition, treatment was delayed of patients already diagnosed with cancer, due to COVID-19 infection detected in the patient, a family member, or a bone marrow donor.
Conclusion
Fear from the COVID-19 pandemic may result in delayed diagnosis and treatment of children with cancer, which may carry a risk to dismal prognosis. It is crucial that pediatricians and patients alike remember that other diseases still prevail and must be thought of and treated in a timely fashion.
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EMUNI, FIS, FZAB, GEOZS, GIS, IJS, IMTLJ, KILJ, KISLJ, MFDPS, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, SBMB, SBNM, UKNU, UL, UM, UPUK, VKSCE, ZAGLJ
Seventeen children at six institutions with neurofibromatosis type 2 (NF2)‐related vestibular schwannomas received bevacizumab. Eight of the 13 patients with initial hearing loss (61%) showed ...objective hearing improvement within six months of treatment. No patients showed hearing deterioration during therapy; however, only two patients showed objective radiological response. Seven of eight patients had tumor progression or worsening hearing loss upon cessation of treatment. Bevacizumab was well tolerated with no patients discontinuing therapy. Bevacizumab appears to postpone hearing loss in childhood NF2‐associated vestibular schwannomas, but responses are not durable, suggesting that either longer maintenance therapy or new strategies are required.
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BFBNIB, FZAB, GIS, IJS, KILJ, NLZOH, NUK, OILJ, SAZU, SBCE, SBMB, UL, UM, UPUK
In pediatric brain tumours, dissemination of malignant cells within the central nervous system confers poor prognosis and determines treatment intensity, but is often undetectable by imaging or ...cytology. This study describes the use of fluorescence lifetime (FLT) imaging microscopy (FLIM), a novel diagnostic tool, for detection of metastatic spread. The study group included 15 children with medulloblastoma and 2 with atypical teratoid/rhabdoid tumour. Cells extracted from the tumour and the cerebrospinal fluid (CSF) 2 weeks postoperatively and repeatedly during chemo/radiotherapy were subjected to nuclear staining followed by FLT measurement and cytological study. Control CSF samples were collected from patients with infectious/inflammatory disease attending the same hospital. Median FLT was prolonged in tumour cells (4.27 ± 0.28 ns; P < 2.2*10
) and CSF metastatic cells obtained before chemo/radiotherapy (6.28 ± 0.22 ns; P < 2.2*10
); normal in inflammatory control cells (2.6 ± 0.04 ns) and cells from children without metastasis before chemo/radiotherapy (2.62 ± 0.23 ns; P = 0.858) and following treatment (2.62 ± 0.21 ns; P = 0.053); and short in CSF metastatic cells obtained after chemo/radiotherapy (2.40 ± 0.2 ns; P < 2.2*10
). FLIM is a simple test that can potentially identify CSF spread of brain tumours. FLT changes in accordance with treatment, with significant prolonged median values in tumours and metastases. More accurate detection of metastatic cells may guide personalised treatment and improve the therapeutic outcome.
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IZUM, KILJ, NUK, PILJ, PNG, SAZU, UL, UM, UPUK
As treatment protocols for medulloblastoma (MB) are becoming subgroup-specific, means for reliably distinguishing between its subgroups are a timely need. Currently available methods include ...immunohistochemical stains, which are subjective and often inconclusive, and molecular techniques—e.g., NanoString, microarrays, or DNA methylation assays—which are time-consuming, expensive and not widely available. Quantitative PCR (qPCR) provides a good alternative for these methods, but the current NanoString panel which includes 22 genes is impractical for qPCR. Here, we applied machine-learning–based classifiers to extract reliable, concise gene sets for distinguishing between the four MB subgroups, and we compared the accuracy of these gene sets to that of the known NanoString 22-gene set. We validated our results using an independent microarray-based dataset of 92 samples of all four subgroups. In addition, we performed a qPCR validation on a cohort of 18 patients diagnosed with SHH, Group 3 and Group 4 MB. We found that the 22-gene set can be reduced to only six genes (
IMPG2
,
NPR3
,
KHDRBS2
,
RBM24
,
WIF1
, and
EMX2
) without compromising accuracy. The identified gene set is sufficiently small to make a qPCR-based MB subgroup classification easily accessible to clinicians, even in developing, poorly equipped countries.
To investigate pediatric low-grade gliomas for alterations in
.
DNA and RNA were extracted from 62 pediatric gliomas. Molecular methods included PCR, RT-PCR, and RNA sequencing; Sanger sequencing was ...used for validation.
Analysis for hotspot genetic alterations in
R132 and
R172 (45 and 33 samples) was negative in all cases.
deletions were detected in exons 1 and 2 in 1 (pleomorphic xanthoastrocytoma) sample of 9 samples analyzed. Of 10 samples analyzed for
translocation, 4 each were positive for translocations with exon 2 and exon 3 of
. Six samples showed
rearrangement. The lack of
genetic alterations is in accordance with the literature in pediatric tumors. Alterations in
were recently reported to characterize diffuse grade II, but not grade I, gliomas.
We optimized methods for analyzing gene variations and correlated the findings to pathological grade. The high incidence of MYB and MYBL need further evaluation. We also compared DNA, RNA, and RNA sequencing results for fusion, translocation, and genetic alterations. More accurate identification of the underlying biology of pediatric gliomas has implications for the development of targeted treatment.
Background
COVID-19, the novel coronavirus, has caused a global pandemic affecting millions of people around the world. Risk factors for critical disease in adults are advanced age and underlying ...medical comorbidities, including cancer. Data are sparse on the effect of COVID-19 infection on pediatric patients with cancer during their active antineoplastic therapy. The optimal management of antineoplastic treatment during COVID-19 infection in this unique population is controversial.
Aim
To describe the severity and clinical course of COVID-19 infection in pediatric patients with cancer during active antineoplastic treatment and to study their course of treatment.
Methods
Clinical and laboratory data were collected from medical files of patients diagnosed with COVID-19, confirmed by polymerase chain reaction (PCR), who received active antineoplastic treatment between March 2020 and May 2021 in a large tertiary pediatric medical center.
Results
Eighteen patients with diverse pediatric cancers are described. They were infected with COVID-19 at different stages of their antineoplastic treatment regimen. Eight had an asymptomatic COVID-19 infection, nine had mild symptoms, and one had severe disease. All of them recovered from COVID-19 infection. Two patients experienced delays in their antineoplastic treatment; none of the other patients had delays or interruptions, including patients who were symptomatic for COVID-19.
Conclusion
In pediatric patients with cancer who test positive for COVID-19, yet are asymptomatic or have mild symptoms, the continuance of antineoplastic therapy may be considered.
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EMUNI, FIS, FZAB, GEOZS, GIS, IJS, IMTLJ, KILJ, KISLJ, MFDPS, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, SBMB, SBNM, UKNU, UL, UM, UPUK, VKSCE, ZAGLJ
Optic pathway glioma (OPG) presents in childhood and can cause significant morbidity and visual loss. Magnetic resonance imaging (MRI) is the current imaging modality of choice for evaluation of OPG ...progression, but it is a relatively limited resource often requiring sedation in the pediatric age group. Additionally, OPG progression on MRI does not always correlate with clinical progression. As a result, several other modalities for evaluating OPG are being investigated, including optical coherence tomography (OCT), a readily available imaging technique in ophthalmic practice. The purpose of the present study was to examine the association between retinal nerve fiber layer (RNFL) thickness measured using OCT and optic nerve function in children with OPG with and without neurofibromatosis-1 (NF-1). A retrospective chart review was conducted to identify children diagnosed with OPG from 2001 to 2015 at a tertiary pediatric medical center. The correlation between OCT measurements and clinical visual parameters was statistically analyzed. Included were 23 children with imaging-confirmed OPG and spectral domain OCT: 10 with NF-1 (mean age at diagnosis 5.8 years) and 13 without (mean age at diagnosis 5.9 years). The glioma involved the chiasma-hypothalamus in 19 patients, optic nerve in 11, and optic tract in 7; more than one anatomic site was affected in 15. Symptoms were reported in 2 patients with NF-1 and most patients without NF-1. Visual field defects included monocular, bitemporal, nasal, and homonymous hemianopia. Initial mean RNFL was 85.4 μm in the NF-1 group and 65 μm in the non-NF-1 group. Visual acuity deteriorated in 1/10 patients and 5/13 patients, respectively. Repeated OCT showed continued RNFL thinning in 3 patients (5 eyes) in the NF-1 group and in 8 patients (11 eyes) in the non-NF-1 group, often associated with a decrease in optic nerve function. In conclusion, visual function in children with OPG is correlated with repeated OCT measurements and weakly with neuroimaging. Children without NF-1 are usually symptomatic and have a worse clinical outcome. These findings may have important implications when considering initiating, continuing or stopping chemotherapy for OPG. The application of OCT in the assessment of OPG and the correlation of the findings to clinical progression can have a significant impact on OPG patient management.
Purpose:
To evaluate the role of the ophthalmologist in the management of children with arterial stroke, at presentation and during follow-up.
Methods:
This retrospective case series comprised ...children with arterial stroke who were followed for at least 12 months in a tertiary pediatric medical center in 2005–2016. Demographic data and findings on radiological neuroimaging and ophthalmological and neurological examination were retrieved from the medical files.
Results:
The cohort included 26 children with stroke. Underlying disorders included metabolic syndrome (
n
= 5, 19.2%), cardiac anomaly or Fontan repair (
n
= 3 each, 11.5%), vascular anomaly (
n
= 3, 11.5%), head trauma with traumatic dissection (
n
= 3, 11.5%), and hypercoagulability (
n
= 1, 3.8%); in eight patients (30.8%), no apparent cause was found. Eleven patients (42.3%) had a non-ophthalmological neurological deficit as a result of the stroke. Eye examination was performed in nine patients (34.6%) during follow-up. Ophthalmological manifestations included hemianopic visual field defect in seven patients (7.7%) and complete blindness and poor visual acuity in one patient each (3.8%). At the last visit, no change in visual function was detected.
Conclusion:
The variable etiology and presentation of pediatric stroke may mask specific visual signs. Children with arterial stroke should be referred for early ophthalmological evaluation and visual rehabilitation.
Abstract Background/Purpose The aim of the study was to investigate the incidence of nystagmus at diagnosis in children with optic pathway glioma involving the chiasm and hypothalamus. Methods ...Twenty-two patients with a measurable optic pathway/hypothalamic glioma (without neurofibromatosis-1) were followed in our center from 2001 to 2013. The medical files were retrospectively reviewed for demographic and clinical findings, and the imaging scans, for tumor characteristics. Results There were 9 boys and 13 girls of mean age 3.5 ± 4.4 years at diagnosis; 15 were aged <2 years. Tumor size ranged from 10 × 6 mm to 62 × 29 mm. Mean duration of follow-up was 8.3 ± 5.4 years. Nystagmus was detected at diagnosis in 10 children (45%), all <2 years old (66.6% of the younger group); no child older than 2 years presented with nystagmus. Nystagmus, once present, did not resolve and continued throughout follow-up. There were no cases of new onset of nystagmus during follow-up in the children in whom it was not detected at diagnosis. Treatment consisted of partial resection/biopsy with/without shunting (n = 13) and chemotherapy (n = 19) with (n = 2) or without adjuvant radiation. Of the 22 children, 6 had a radiographic response to treatment, 8 remained stable, and 8 (all of whom received chemotherapy) showed disease progression despite treatment. Conclusion In conclusion, monocular nystagmus is a more common presenting sign of optic pathway/hypothalamic glioma in children <2 years old than previously estimated. Although subtle, nystagmus has a very narrow differential diagnosis, and its presence should raise suspicions of a chiasmal tumor with prompt referral for imaging. The visual prognosis is moderate to poor.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UL, UM, UPCLJ, UPUK
Abstract Objective To investigate the use of peripapillary optical coherence tomography for monitoring optic neuropathy in pediatric craniopharyngioma. Design Retrospective, consecutive-cohort, ...single-centre chart analysis. Participants Twenty children with craniopharyngioma treated at a pediatric medical centre from 1999 to 2011. Methods The medical files were reviewed for demographics and optic nerve function. Findings for visual acuity and visual fields were analyzed against repeated optical coherence tomography (OCT) measurements of peripapillary nerve fibre layer thickness (using either time-domain Stratus OCT or spectral-domain Cirrus OCT). Results Average age at diagnosis was 6.5 ± 3.88 years. The most common presenting symptom was headache; only 1 child complained of visual loss. Mean best corrected visual acuity (logMAR) was 0.036 ± 0.06 in the 17 healthy eyes and 1.05 ± 1.45 in the 23 eyes with optic neuropathy. Positive signs included relative afferent pupillary defect (8/20), visual acuity loss (7/20), temporal visual field loss (bilateral 4/15, unilateral 4/15), papilledema (3/20), and unilateral/bilateral optic disc pallor (14/20). RNFL thickness was significantly lower in eyes with optic neuropathy than in healthy eyes (65 ± 22 µm vs 86.2 ± 29 µm; p = 0.000) and correlated with visual acuity ( r = –0.43 to –0.17, p = 0.0001) and presence or absence of a visual field defect (mean difference, 26.1 ± 5.8 µm, p = 0.003). Ten children showed no change in RNFL thickness over time (mean 18 ± 14.2 months). Conclusions A thinner RNFL on ocular coherence tomography is correlated with poorer visual acuity and visual field loss. Ocular coherence tomography may serve as an objective method to quantify axonal loss caused by craniopharyngioma. Further investigation is needed to determine its use for evaluating progressive axonal loss over time.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UL, UM, UPCLJ, UPUK
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