Despite therapeutic advances, survival following relapse for neuroblastoma patients remains poor. We investigated clinical and biological factors associated with length of progression-free and ...overall survival following relapse in UK neuroblastoma patients.
All cases of relapsed neuroblastoma, diagnosed during 1990-2010, were identified from four Paediatric Oncology principal treatment centres. Kaplan-Meier and Cox regression analyses were used to calculate post-relapse overall survival (PROS), post-relapse progression-free survival (PRPFS) between relapse and further progression, and to investigate influencing factors.
One hundred eighty-nine cases were identified from case notes, 159 (84.0%) high risk and 17 (9.0%), unresectable, MYCN non-amplified (non-MNA) intermediate risk (IR). For high-risk patients diagnosed >2000, median PROS was 8.4 months (interquartile range (IQR)=3.0-17.4) and median PRPFS was 4.7 months (IQR=2.1-7.1). For IR, unresectable non-MNA patients, median PROS was 11.8 months (IQR 9.0-51.6) and 5-year PROS was 24% (95% CI 7-45%). MYCN amplified (MNA) disease and bone marrow metastases at diagnosis were independently associated with worse PROS for high-risk cases. Eighty percent of high-risk relapses occurred within 2 years of diagnosis compared with 50% of unresectable non-MNA IR disease.
Patients with relapsed HR neuroblastomas should be treatment stratified according to MYCN status and PRPFS should be the primary endpoint in early phase clinical trials. The failure to salvage the majority of IR neuroblastoma is concerning, supporting investigation of intensification of upfront treatment regimens in this group to determine whether their use would diminish likelihood of relapse.
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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
Aim
Parents of children with cancer describe impaired physical and social functioning, sleep disturbance and poor mental health. Exercise‐related interventions impact positively on these quality of ...life domains, but have not been examined in this population. The aim of this longitudinal pilot study was to explore the feasibility of a 12‐week pedometer‐monitored walking intervention among parents of children with cancer, assessing adherence to a set activity target of 70,000 steps per week, and to explore the benefits of physical activity on mental and physical health.
Methods
Parents were provided with a pedometer and requested to achieve a daily step count of 10,000 steps per day for 12 weeks. Mood, well‐being and psychological distress were examined using validated questionnaires (Profile of Mood States 2nd edition POMS‐2, Distress Thermometer for Parents DT‐P and Depression Anxiety Stress Scales DASS‐42) at baseline, midpoint (6 weeks) and endpoint (12 weeks) to identify changes in these domains with increased activity.
Results
Fifteen parents were recruited. The majority increased their counts during the first 4 weeks of the study and maintained this to week 8 (n = 12). Time‐dependent improvements were identified in the following psychometric test outcomes at week 12: DT‐P score (likelihood ratio test LRT P = 0.02), POMS‐2 total mood disturbance (LRT P = 0.03), fatigue inertia (LRT P = 0.009), tension anxiety (LRT P = 0.007) and vigour activity (LRT P = 0.001).
Conclusions
Mental health benefits of a pedometer‐based exercise intervention for parents of children with cancer were identified. Such programs should be included in a holistic approach to improve the psychological outcomes of parents whose children are receiving treatment for cancer.
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BFBNIB, FZAB, GIS, IJS, KILJ, NLZOH, NUK, OILJ, SAZU, SBCE, SBMB, UL, UM, UPUK
•An adult brain tumor was misdiagnosed as a CNS embryonal tumor (NOS).•Integrated genomic analysis of the diagnostic tumor was used to inform treatment.•A revised diagnosis of IDH1-mutant astrocytoma ...resulted in improved outcome.
Central nervous system primitive neuro-ectodermal tumors (CNS-PNETs), have recently been re-classified in the most recent 2016 WHO Classification into a standby catch all category, “CNS Embryonal Tumor, not otherwise specified” (CNS embryonal tumor, NOS) based on epigenetic, biologic and histopathologic criteria. CNS embryonal tumors (NOS) are a rare, histologically and molecularly heterogeneous group of tumors that predominantly affect children, and occasionally adults. Diagnosis of this entity continues to be challenging and the ramifications of misdiagnosis of this aggressive class of brain tumors are significant. We report the case of a 45-year-old woman who was diagnosed with a central nervous system embryonal tumor (NOS) based on immunohistochemical analysis of the patient’s tumor at diagnosis. However, later genome-wide methylation profiling of the diagnostic tumor undertaken to guide treatment, revealed characteristics most consistent with IDH-mutant astrocytoma. DNA sequencing and immunohistochemistry confirmed the presence of IDH1 and ATRX mutations resulting in a revised diagnosis of high-grade small cell astrocytoma, and the implementation of a less aggressive treatment regime tailored more appropriately to the patient’s tumor type. This case highlights the inadequacy of histology alone for the diagnosis of brain tumours and the utility of methylation profiling and integrated genomic analysis for the diagnostic verification of adults with suspected CNS embryonal tumor (NOS), and is consistent with the increasing realization in the field that a combined diagnostic approach based on clinical, histopathological and molecular data is required to more accurately distinguish brain tumor subtypes and inform more effective therapy.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UL, UM, UPCLJ, UPUK, ZRSKP
Abstract
BACKGROUND
Whilst rates of survival following paediatric brain tumour have increased, quality of survival continues to present a significant challenge to children and their families. The ...neurocognitive impact of cranial radiotherapy (CRT) in childhood upon future intellectual development is well established. Both CRT and chemotherapy are associated with medium-term slowed speed of cognitive processing, attention, and memory impairment, and with longer-term failure to achieve pre-morbid intellectual potential and low Health-Related Quality of Life (HRQoL).Methylphenidate is a psychostimulant drug shown to be effective in alleviating some of the neurocognitive symptoms of cancer treatment, however the subjective experience of paediatric participants is not reported. AIM: The current study aimed to explore the subjective experience of HRQoL in paediatric neuro-oncology patients currently receiving methylphenidate.
METHODS
A retrospective audit was conducted on 12 paediatric neuro-oncology patients in receipt of methylphenidate. Both standardised and novel measures were used to assess aspects of HRQoL, specifically; social life, perceived independence, mood, confidence, school life, self-esteem, interpersonal relationships and fatigue levels. Data collected were analysed using Thematic Analysis.
RESULTS
Five key themes were identified; physical, emotional, social, academic and neuropsychological impact.
CONCLUSION
The current findings evidence the perception of patients that methylphenidate supported them to regain previously lost functionality. Methylphenidate has the potential to increase HRQoL in this population and to provide children with the opportunity to regain a sense of normality in their lives.
Abstract
OBJECTIVE
One of the most disabling side effects of treatment in survivors of brain tumours is the resultant reduction in level of processing speed and attention. This study aimed to ...evaluate intellectual and psychological benefit of short-acting methylphenidate to survivors of brain tumour.
METHODS
Paediatric BT patients attending a UK specialist treatment centre received assessment of cognitive performance. All patients identified with attentional difficulties were screened for contraindications to methylphenidate. Participants (N=23), mean age 11.09 years, completed a 6-month trial of methylphenidate. Measures of attention (Test of Everyday Attention for Children 2; SNAP-IV), side-effects (Stimulant Side-Effects Rating Scale), Health-Related Quality of Life (PEDS-QL), and experience of methylphenidate questionnaire (purpose-developed semi-structured questionnaire) were administered prior to medication and after six months.
RESULTS
Participants showed improvement in selective attention (t(18)=-5.4, p=<.001, d=.93) and processing speed (t(16)=-3.0, p=.01) at follow up. Family ratings of attention were significant (t(17)=14.46, p<.001, d=-1.19). Change in subjective measures of Health-Related Quality of Life (HRQoL) was also statistically significant as reported by children (t(16)=3.91, p=.001, d=-.99), and on a parental-report measure of child HRQoL (t(15)=-8.19, p<.001, d=-1.09). HRQoL measures show improvement to physical, academic, and emotional domains as reported by participants.
CONCLUSIONS
Paediatric BT survivors showed benefit from provision of methylphenidate in terms of reduced attentional and processing deficit, and in terms of emotional wellbeing. Treatment was well tolerated. Continued follow-up of the current participants in a longitudinal study aims to evidence longer-term benefit to participants.
Abstract
Low grade gliomas (LGG), including pilocytic astrocytoma (PCA), are the commonest paediatric brain tumours and their behaviour is well understood, typically following a benign course. BRAF ...fusion is common, particularly in PCA of the cerebellum and optic pathway. Here we present two patients whose LGG behaved in an unusual fashion. The first patient who was treated 6 years previously on LGG2 with vincristine and carboplatin for a tectal plate lesion was identified on routine imaging to have local tumour progression and underwent completion staging. This showed a new enhancing soft tissue abnormality within the spinal cord at the level of L2. Due to radiological dubiety both lesions were biopsied for histological and molecular analysis, confirming LGG of the tectal plate and finding the spinal lesion to be a myxopapillary ependymoma. The second patient presented with acute hydrocephalus following a 2 year history of neurocognitive impairments. He was found to have a large, complex tumour centred in and expanding the bodies of both lateral ventricles with significant mass effect. Radiologically this was most in keeping with a central neurocytoma but histological analysis confirmed it to be a PCA with KIAA1549-BRAF fusion. The first case demonstrates the utility of molecular analysis in confirming two distinct tumour types in one patient, in a situation where metastasis would not be expected and would significantly alter treatment and prognosis. The second is an example of how imaging can be misleading in a KIAA1549-BRAF fused PCA presenting as an intraventricular mass.
Central nervous system germ cell tumors (CNS-GCTs) comprise 4% of all pediatric CNS tumors, with one third being nongerminomatous GCT (CNS-NG-GCT) type. The majority of these tumors arise in the ...intracranial compartment with 20% having drop metastases in the spine. We present a rare case of a 2-year-old boy with a primary intradural-extramedullary NG-GCT arising from the lumbosacral spine with a trifecta of unfavorable features, that is, young age, alpha-feto protein >1000 ng/mL, and disseminated disease within the cranium. Owing to his young age, he was treated with chemotherapy alone, avoiding radiation. His tumor marker (alpha-feto protein) declined from 8468 to 10 k-U/L over 8 weeks, and he remained in remission at the last follow-up. This atypical presentation of an intradural-extramedullary tumor with cranial dissemination in a childhood NG-GCT has yet to be described in the literature. Here we use this opportunity to highlight the treatment strategies and challenges in this unique clinical case.
Abstract
Children with a Central Nervous System (CNS) tumour have frequent magnetic resonance imaging (MRI) scans during their disease trajectory. Younger children routinely have these performed ...under general anaesthetic (GA) with an associated risk and inconvenience. Our project over a two-year period was to introduce a structured programme to any child over the age of five years old to achieve an MRI scan without the need for a GA. Thirty-six patients took part. The motivation behind this project was to enhance the hospital experience for patients and their families, lessen time spent in hospital and minimise risk. In addition, there was an added incentive of cost saving and increased availability of GA scans for other specialities within the hospital setting. During the COVID pandemic, it has also resulted in a reduction of our patients requiring COVID swabs, and isolation and in turn a reduction in aerosol generating procedures. As part of the structured programme, each child had an initial assessment with the nurse specialist followed by a minimum of one play preparation session with the play specialist. Children were required to demonstrate they could follow simple instructions, engage in social stories and role-play with hospital equipment and specialised resources. During these sessions, the children visited the MRI department where they practiced lying flat on the MRI bed as it moved into the scanner. Over the two-year period, of the total number of MRI scans performed, the amount of MRI scans requiring a GA reduced from 41% to 31%. The quality of the MRI scans was scrutinised and shown not to be significantly affected. In summary, by introducing a structured programme, it is possible to significantly reduce the need for GA in children requiring CNS imaging as part of their tumour journey.
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