Embryonal sarcoma of the liver in a girl with Cockayne syndrome.

The first reported malignancy associated with Cockayne syndrome.

Cognitive function in children with brain tumors in the first year after diagnosis compared to healthy matched controls.

BACKGROUND: Improved survival of children with brain tumors (BTs) has increased focus on ameliorating morbidity. To reduce the risk of progressive cognitive decline, remedial strategies need to be instituted early, based upon accurate appraisal of need, yet few studies have investigated cognition in BT children early post-diagnosis. The study aims were to investigate cognition in children with primary BTs 1, 6, and 12 months post-diagnosis compared with healthy children, exploring the impact of disease and treatment variables. METHODS: Forty-eight children aged 2-16 years with primary BTs, referred to a Regional Neurosurgical Unit over the 2-year study period were eligible for enrollment. The "best friends" model was used to recruit matched controls. Cognition was assessed using age-appropriate Wechsler Intelligence scales; Children's Memory Scale; Test of Everyday Attention for Children, and Wechsler Quicktest. RESULTS: Patients with BTs had significantly reduced performance compared to controls early post-diagnosis in tests of Performance IQ, processing speed, verbal and visual memory, and selective attention. Improved performance over 12 months was seen in patients with BTs although also, for some measures, in controls. Significant deficits in cognitive performance were seen one year post-diagnosis for Verbal IQ; processing speed, visual and verbal immediate memory, and selective attention. Infratentorial site, high tumor grade, hydrocephalus, radiotherapy, and chemotherapy were associated with poorer functioning. CONCLUSION: Early cognitive impairment is present in BT children, sometimes prior to radiotherapy/chemotherapy treatment, and is associated with hydrocephalus, high tumor grade and infratentorial site. Future studies should investigate the role of early rehabilitation in improving cognition.

Lineage switching of the cellular distribution of BRAFV600E in multisystem Langerhans cell histiocytosis.

Most children with high-risk Langerhans cell histiocytosis (LCH) have BRAFV600E mutation. BRAFV600E alleles are detectable in myeloid mononuclear cells at diagnosis but it is not known if the cellular distribution of mutation evolves over time. Here, the profiles of 16 patients with high-risk disease were analyzed. Two received conventional salvage chemotherapy, 4 patients on inhibitors were tracked at intervals of 3 to 6 years, and 10 patients, also given inhibitors, were analyzed more than 2 years after diagnosis. In contrast to the patients responding to salvage chemotherapy who completely cleared BRAFV600E within 6 months, children who received inhibitors maintained high BRAFV600E alleles in their blood. At diagnosis, mutation was detected predominantly in monocytes and myeloid dendritic cells. With time, mutation switched to the T-cell compartment, which accounted for most of the mutational burden in peripheral blood mononuclear cells, more than 2 years from diagnosis (median, 85.4%; range, 44.5%-100%). The highest level of mutation occurred in naïve CD4+ T cells (median, 51.2%; range, 3.8%-93.5%). This study reveals an unexpected lineage switch of BRAFV600E mutation in high-risk LCH, which may influence monitoring strategies for the potential withdrawal of inhibitor treatment and has new implications for the pathogenesis of neurodegeneration, which occurred in 4 patients.

A detailed prospective longitudinal assessment of health status in children with brain tumors in the first year after diagnosis.

PURPOSE: To compare health status (HS) in children with brain tumors at 1 (t1), 6 (t6), and 12 (t12) months after diagnosis with "normal" controls. To assess the relationship between parent-report and self-report HS for patients at t12. METHODS: HS was assessed using the Health Utilities Index Mark III parent-report at all time points and self-report at t12. Twenty-nine patients and 32 controls were included in analysis of parent-report, and 21 patients and 22 controls in self-report HS at t12. Nonparametric analyses were used. RESULTS: Patients scored significantly lower than controls for global overall HS at all time points for parent-report and at t12 for self-report (Pmax=0.009). For parent-report, patients scored significantly lower than controls in the attributes of emotion, cognition, and pain at t1 and t6, in ambulation at t1 and in dexterity at t6. At t12, the difference was statistically significant for parent-report cognition only (all P<0.01). No attributes reached significance for self-report at t12. For patients, correlations between parent-report and self-report were good (rs>0.73) for all Health Utilities Index Mark 3 scores with the exception of emotion and pain. CONCLUSION: HS is significantly compromised in children with brain tumors over the first year after diagnosis, but improves with time. Parent-report and self-report differ, and both should be considered in assessing outcomes or defining interventions.

Child-related determinants of health-related quality of life in children with brain tumours 1 year after diagnosis.

OBJECTIVES: Infratentorial tumour site and health-related quality of life (HRQL) 1 month after diagnosis have been shown to predict HRQL 1 year after diagnosis in children with brain tumours. This study aimed to identify additional early child-related determinants of parent- and child-report HRQL. METHODS: Longitudinal prospective study. Semi-structured interviews took place approximately 1 and 12 months after diagnosis. HRQL was measured using the self- and parent-report Pediatric Quality of Life Scales (PedsQL 4.0) Total Scale Score and Health Utilities Index Mark 3 (HUI3) multi-attribute utility function. Child variables included performance and verbal IQ, general memory, selective attention executive function, behaviour problems, adaptive behaviour, symptoms of depression and anxiety and event related anxiety. Univariate analyses were used to identify potential early predictors of HRQL. Regression analysis was then used to identify the most important determinants of HRQL at 1 year. RESULTS: Thirty-five patients completed the 12-month interviews. Multivariate analysis showed infratentorial tumour site remained an important determinant of HRQL 1 year after diagnosis. Infratentorial tumour site and selective attention at 1 month generally best predicted poor self- and parent-report HRQL at 12 months. Adaptive behaviour and performance IQ may be important. CONCLUSION: Selective attention and infratentorial tumour site are most important in predicting both parent- and self-report HRQL at 1 year after diagnosis. Larger prospective studies are needed to confirm these findings. Cognitive remediation or/and pharmacological intervention, particularly aimed at children with infratentorial tumours may improve attention and subsequently HRQL and both merit further investigation.

Symptom interval and treatment burden for patients with malignant central nervous system germ cell tumours.

OBJECTIVE: Patients with central nervous system germ cell tumours (CNS-GCTs) commonly initially present to primary care or general paediatricians. Prolonged symptom intervals (SI) are frequently seen in CNS-GCTs and have been associated with inferior outcomes in other brain tumours. This study reviewed the clinical presentation of CNS-GCTs and examined the effect of prolonged SI. DESIGN/SETTING/PATIENTS/OUTCOMES: International multicentre 10-year retrospective study (2002-2011 inclusive), across six international paediatric oncology treatment centres. All newly diagnosed patients with CNS-GCT were included. Main outcome measure was time interval from first symptom to diagnosis. RESULTS: The study cohort included 86 (58 males:28 female) patients (59 'germinoma' and 27 'non-germinomatous' GCTs), with tumours being pineal (n=33), suprasellar (n=25), bifocal (pineal+suprasellar; n=24) and 'other' site (n=4), of which 16 (19%) were metastatic. Median age at diagnosis was 14 years (0-23 years). The time to diagnosis from first symptom (SI) was 0-69 months (median 3 months, mean 9 months). A prolonged SI (>6 months) was observed in 28/86 patients (33%) and significantly associated with metastatic disease (11/28 (39%) vs 5/58 (9%); p=0.002)) at diagnosis, but not overall survival. With prolonged SI, endocrine symptoms, particularly diabetes insipidus, were more common (21/28 (75%) vs 14/58 (24%) patients; p<0.002), but raised intracranial pressure (RICP) was less frequent (4/28 (14%) vs 43/58 (74%) patients; p<0.001)) at first symptom. CONCLUSIONS: One-third of patients with CNS-GCT have >6 months of symptoms prior to diagnosis. Delayed diagnosis is associated with metastatic disease. Early symptom recognition, particularly related to visual and hormonal disturbances in the absence of RICP, may improve timely diagnosis, reduce metastatic disease frequency and consequently reduce treatment burden and late effects.

Psychosocial issues and quality of life.

The age group 20 to 39 years includes survivors of childhood cancer and those diagnosed with and treated for cancer during young adult life. Much of what is known about the psychosocial consequences of cancer in this age range is based on work involving survivors of cancer in childhood. We argue that the impact of cancer in young adults is different from experiences during childhood. Key developmental tasks include negotiation of independence from the nuclear family, achievement of intimacy, and generativity (concern to establish and guide the next generation). All of these tasks can be challenged by cancer, and have led to concern about health-related quality of life. Given the diverse ways in which cancer can compromise young adults, there is a need for timely interventions. Attempts to improve knowledge, re-integrate into normal life and work, and promote self-care (eg, awareness of risks associated with smoking) are described.

Family, demographic and illness-related determinants of HRQL in children with brain tumours in the first year after diagnosis.

AIMS: To evaluate the relationship between parent- and child-report Health-Related Quality of Life (HRQL) and demographic, tumour and family variables in children with a brain tumour in the first year after diagnosis and to identify determinants of HRQL at 12 months. PROCEDURE: Longitudinal prospective study: Semi-structured interviews took place approximately 1, 6 and 12 months after diagnosis. HRQL was measured using the self- and parent-report PedsQL 4.0 Total Scale Score. Tumour and treatment variables considered included tumour site and grade, hydrocephalus at diagnosis, chemotherapy and radiotherapy. Family variables included measures of family function, family support and family stress, the primary carer's coping strategies and symptoms of depression and anxiety. Univariate analyses were used at all three time points, and to identify potential early predictors of HRQL at 1 year. Regression analysis was then used to identify the most important determinants of HRQL at 1 year. RESULTS: Thirty-five patients completed the 12-month interviews. There were consistent significant negative correlations between concurrent family impact of illness and parent and self-report HRQL, and positive correlations between concurrent family support and parent-report HRQL. Treatment with radio- or chemotherapy correlated with child-report HRQL only at some time points. Multivariate analysis showed infratentorial tumour site, and poor HRQL at 1 month best predicted poor self- and parent-report HRQL at 12 months. CONCLUSION: Children with infratentorial tumours and poor HRQL early after diagnosis tend to have poor HRQL at 1 year. While family factors are important modulators of concurrent HRQL, they do not appear important in predicting HRQL.

Health related quality of life in the first year after diagnosis in children with brain tumours compared with matched healthy controls; a prospective longitudinal study.

This paper compares parent- and self-report health-related quality of life (HRQL) in children aged 2-16 years with brain tumours, one, six and twelve months after diagnosis with matched normal controls. HRQL was assessed using the PedsQL generic core scales. 37 tumour patients and 42 controls were included in analysis of parent-report, and 27 patients and 31 controls in self-report HRQL. Parent-report scores were significantly lower in patients than controls for all PedsQL scores at all time points (max p=0.002). Differences in self-report PedsQL between patients and controls were variable. The relationship between self- and parent-report in patients and controls was inconsistent; varied over time; and did not consistently correlate with parental depressive symptoms, suggesting parents and their children do not regard HRQL in a similar way. Prospective, longitudinal assessment of HRQL is important, but should be supplemented with other outcome measures such as health status and behaviour in this population.

Psychosocial Support in Adolescents and Young Adults With Cancer.

Various forms of psychosocial support have been suggested in working with adolescents and young adults (AYAs) as they attempt to cope with cancer, including peer-based interventions, individual psychoeducational counseling, and skill-based interventions. More recently, modern electronic applications created technology-based ways to deliver information and support and have grown in popularity to satisfy AYA needs for information and support. Such support should be offered routinely rather than in a response to a crisis. This article focuses on psychosocial interventions for AYAs aged 15 to 39 years with cancer at diagnosis, during treatment, and shortly after.

Long term survivors of childhood cancer: cure and care. The Erice statement.

The number of subjects that have successfully completed treatment for a cancer diagnosed during childhood and are entering adulthood is increasing over time. Members of the International Berlin-Frankfurt-Munster (I-BFM) Early and Late Toxicity Educational Committee (ELTEC) invited 45 paediatric cancer experts (representing oncologists, psychologists, nurses, epidemiologists, parents, and survivors) from 13 European countries (with five additional experts from North America) to Erice, Sicily (from October 27 to 29, 2006) to discuss the circumstances in which the word 'cure' should be used when speaking about children with cancer, and when and why continuing follow-up and care may be required. The objective of the gathering was to generate from the personal and professional experience of the participants an overview statement of the group's philosophy of cure and care of survivors of childhood cancer. The ten points reflect what the group considers essential in the survivors' cure and care.