For pediatric patients with cancer, a healthy lifestyle is important for treatment outcomes and beyond. General pediatricians play a major role in the care of these patients, particularly given the ...improved rates of survival. Pediatric obesity has many negative consequences, but it is an area where primary care providers can make an impact and provide support to childhood cancer survivors. To provide the best quality of care for this population, there must be collaboration between primary care and oncology providers. Additionally, general practioners should feel empowered to offer standard nutrition and physical activity recommendations to all childhood cancer survivors. For pediatric patients who carry a cancer diagnosis, cure is no longer the only goal. Pediatric providers across specialties need to work as a team to improve long-term quality of life for these patients, starting with modifiable healthy habits.
An estimated 8.6% of all pediatric patients with central nervous system tumors (CNSTs) have underlying hereditary cancer predisposition (HCP). Identifying HCP affects risk assessment and medical ...management options for the patients and their family members. However, there is a lack of consensus on the optimal germline genetic testing (GT) approach for pediatric patients with CNSTs. As a first step in addressing the need for consensus, we surveyed oncology and genetics providers from 47 institutions in professional organizations across the United States. We investigated their current practice (e.g., GT decisions and ordering practices) when assessing pediatric patients with CNSTs for HCP. We received 60 responses from 21 pediatric oncologists, 10 neuro‐oncologists, 28 genetics providers, and one neuro‐oncologist/geneticist. Results demonstrate genetic counselors, followed by oncologists, most often facilitated consent, ordered testing, and selected which test to order. The most ordered test was a multi‐gene panel (60%). Of 18 CNST diagnoses, choroid plexus carcinoma (CPC) was the diagnosis for which most providers (78%) reported they would offer GT. For medulloblastoma, 56% overall reported they would offer GT (64% of genetics providers, 62% of neuro‐oncologists, 20% of pediatric oncologists; p = .050). Findings suggest that even for the CNSTs most commonly known to be associated with HCP regardless of family history, there was variability in providers’ decisions to offer GT. The lack of consensus in GT decisions in our study indicates inconsistencies in the genetics care of pediatric patients with CNSTs, demonstrating a need for consensus guidelines to promote consistent genetics care.
Orthodenticle homeobox 2 (OTX2) is a known oncogenic driver of medulloblastoma. Germline duplication of 14q22.3 including OTX2 is a rare condition reported in patients with combined pituitary hormone ...deficiency, oculo‐auriculo‐vertebral spectrum, and hemifacial microsomia. There has been one previously published case of a patient carrying a 14q22.3 duplication that included OTX2 with hemifacial microsomia who also developed medulloblastoma. Here, we present a case of a 6‐year‐old girl with a history of delayed development who was diagnosed with medulloblastoma. Genetic evaluations revealed that she inherited a germline duplication of 14q22.3, which included OTX2. This genetic alteration was passed down from her mother, who also had a history of delayed development. Results from other genetic testing, including exome sequencing, fragile X syndrome, and mtDNA testing, were negative/normal. This is the second report of a 14q22.3 duplication that included OTX2 in a patient with medulloblastoma. Further studies are necessary to establish a clear association.
The late neurocognitive and psychosocial effects of treatment for pediatric brain tumor (PBT) represent important areas of clinical focus and ongoing research. Neurocognitive sequelae and associated ...problems with learning and socioemotional development negatively impact PBT survivors' overall health-related quality of life, educational attainment and employment rates. Multiple factors including tumor features and associated complications, treatment methods, individual protective and vulnerability factors and accessibility of environmental supports contribute to the neurocognitive and psychosocial outcomes in PBT survivors. Declines in overall measured intelligence are common and may persist years after treatment. Core deficits in attention, processing speed and working memory are postulated to underlie problems with overall intellectual development, academic achievement and career attainment. Additionally, psychological problems after PBT can include depression, anxiety and psychosocial adjustment issues. Several intervention paradigms are briefly described, though to date research on innovative, specific and effective interventions for neurocognitive late effects is still in its early stages. This article reviews the existing research for understanding PBT late effects and highlights the need for innovative research to enhance neurocognitive and psychosocial outcomes in PBT survivors.
This Special Issue of Bioengineering explores topics in Pediatric Neuro-Oncology ranging from preclinical modeling to translational research and neurocognitive outcomes. The topics are as below.
...Radiotherapy advances in pediatric brain tumors;
Neurofibromatosis 1 and brain tumors in children;
Molecular biology of pediatric gliomas and therapeutic insights;
Embryonal tumors of the central nervous system in children-era of targeted therapeutics;
Preclinical models in pediatric brain tumors—clinical relevance;
Molecular neuroimaging of brain tumors;
Palliative care for children with central nervous system malignancies;
Neurocognitive and psychosocial outcomes following pediatric brain tumors.
We present a unique case of radiation necrosis in a child with brain stem low‐grade glioma (LGG) presenting with trigeminal neuralgia. Despite extensive therapies, severe pain persisted. She received ...proton beam radiation with significant improvement. However, she developed radiation necrosis and hydrocephalus. Despite surgical correction of hydrocephalus, the patient remained critically ill. She was treated with dexamethasone and bevacizumab with rapid clinical improvement. Subsequent MRIs revealed almost complete resolution of the necrosis. This case illustrates the successful treatment of trigeminal neuralgia with radiation and a rare case of radiation necrosis in an LGG successfully treated with bevacizumab and dexamethasone.
Abstract
Background
Survivors of pediatric brain tumors are at risk for impaired development in multiple neuropsychological domains. The purpose of this study was to compare neuropsychological ...outcomes of pediatric brain tumor patients who underwent X-ray radiotherapy (XRT) versus proton radiotherapy (PRT).
Methods
Pediatric patients who underwent either XRT or PRT and received posttreatment age-appropriate neuropsychological evaluation—including measures of intelligence (IQ), attention, memory, visuographic skills, academic skills, and parent-reported adaptive functioning—were identified. Multivariate analyses were performed to assess differences in neuropsychological outcomes and included tests for interaction between treatment cohort and follow-up time.
Results
Between 1998 and 2017, 125 patients with tumors located in the supratentorial (17.6%), midline (28.8%), or posterior fossa (53.6%) compartments received radiation and had posttreatment neuropsychological evaluation. Median age at treatment was 7.4 years. The PRT patient cohort had higher estimated SES and shorter median time from radiotherapy completion to last neuropsychological evaluation (6.7 vs 2.6 y, P < 0.001). On multivariable analysis, PRT was associated with higher full-scale IQ (β = 10.6, P = 0.048) and processing speed (β = 14.4, P = 0.007) relative to XRT, with trend toward higher verbal IQ (β = 9.9, P = 0.06) and general adaptive functioning (β = 11.4, P = 0.07). Planned sensitivity analyses truncating follow-up interval in the XRT cohort re-demonstrated higher verbal IQ (P = 0.01) and IQ (P = 0.04) following PRT, with trend toward improved processing speed (P = 0.09).
Conclusions
PRT is associated with favorable outcomes for intelligence and processing speed. Combined with other strategies for treatment de-intensification, PRT may further reduce neuropsychological morbidity of brain tumor treatment.
Molecularly targeted therapy with MEK inhibitors has been increasingly incorporated into the treatment of pediatric low-grade gliomas, but this promising therapy is associated with distinctive and ...specific toxicities. Understanding life-threatening MEK inhibitor toxicities and their management is critical to MEK inhibitor safety, especially among young children. This report describes severe hyponatremia associated with trametinib in an infant with progressive low-grade glioma without underlying endocrine dysfunction, which recurred despite significant dose reduction. Therapy with an alternative MEK inhibitor, binimetinib, provided excellent tumor response without hyponatremia, suggesting that some toxicities may be avoided by changing MEK inhibitor agents within the same class.
Pediatric Neuro-Oncology is a highly specialized field encompassing molecular biology, clinical acumen, evidence based medicine, cancer genetics and neuropsychological care for the diagnosis and ...treatment of children with central nervous system (CNS) tumors. ....
Understanding the effect of selumetinib on FASI may help elucidate the biology, proliferative potential, and role in neurocognitive changes for these NF1-associated lesions.
Patients with ...NF1-associated LGG and FASI treated with selumetinib on PBTC-029B were age-matched to untreated patients with NF1-associated FASI at Cincinnati Children's Hospital Medical Center. Paired bidirectional measurements were compared over time using nonparametric tests.
Sixteen age-matched pairs were assessed (age range: 2.8-16.9 years, 60% male). Initial FASI burden was not different between groups (median range 138.7 cm
88.4-182.0 for the treated subjects vs. 121.6 cm
79.6-181.9 for the untreated subjects;
= 0.98). Over a mean follow-up of 18.9 (±5.9) months, the LGG size consistently decreased with treatment while no consistent change among the treated or untreated FASI size was seen. At the paired time points, the median treated LGG decreased significantly more than the treated FASI (-41.3% (LGG) versus -10.7% (FASI),
= 0.006). However, there was no difference in the median size change in the treated versus untreated FASI (-10.7% (treated FASI) versus -17.9% (untreated FASI),
= 0.08). Among the treated subjects, there was no correlation between the change in LGG and FASI (r = -0.04,
= 0.88).
Treatment with selumetinib did not affect the overall FASI size in children with NF1 treated for progressive low-grade glioma.
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