Ulrike Leiss

Antiangiogenic metronomic therapy for children with recurrent embryonal brain tumors

Median survival time of recurrent embryonal brain tumors is short regardless of salvage chemotherapy used. An evolving alternative approach to conventional chemotherapy is to target neovascularization by interfering with tumor angiogenesis at various levels.

Atypical teratoid rhabdoid tumor: improved long-term survival with an intensive multimodal therapy and delayed radiotherapy. The Medical University of Vienna Experience 1992-2012.

Atypical teratoid rhabdoid tumors (ATRTs) are recently defined highly aggressive embryonal central nervous system tumors with a poor prognosis and no definitive guidelines for treatment. We report on the importance of an initial correct diagnosis and disease‐specific therapy on outcome in 22 consecutive patients and propose a new treatment strategy. From 1992 to 2012, nine patients initially diagnosed correctly as ATRT (cohort A, median age 24 months) were treated according to an intensive multimodal regimen (MUV‐ATRT) consisting of three 9‐week courses of a dose‐dense regimen including doxorubicin, cyclophosphamide, vincristine, ifosfamide, cisplatin, etoposide, and methotrexate augmented with intrathecal therapy, followed by high‐dose chemotherapy (HDCT) and completed with local radiotherapy. Thirteen patients were treated differently (cohort B, median age 30 months) most of whom according to protocols in use for their respective diagnoses. As of July 2013, 5‐year overall survival (OS) and event‐free survival (EFS) for all 22 consecutive patients was 56.3 ± 11.3% and 52.9 ± 11.0%, respectively. For MUV‐ATRT regimen‐treated patients (cohort A) 5‐year OS was 100% and EFS was 88.9 ± 10.5%. For patients treated differently (cohort B) 5‐year OS and EFS were 28.8 ± 13.1%. All nine MUV‐ATRT regimen‐treated patients are alive for a median of 76 months (range: 16–197), eight in first complete remission. Our results compare favorably to previously published data. The drug combination and sequence used in the proposed MUV‐ATRT regimen appear to be efficacious in preventing early relapses also in young children with M1–M3 stage disease allowing postponement of radiotherapy until after HDCT.

Improving Care through Better Communication: Understanding the Benefits

Pediatricians spend many hours of their professional lives talking to families, but how much of their time is spent talking to children. Do they really understand their views on the issues being discussed? As mental health-related morbidity increasingly occupies more time of pediatricians, it appears self-evident that pediatricians should be able to effectively communicate with children and be both confident and competent to talk about the “difficult” or “taboo” areas, such as sex, domestic violence, abuse, self-harm, and even death of children with life-limiting conditions. In fact, pediatricians are taught to diagnose and to treat, and they often present a special and spontaneous motivation to offer child care with a high grade of emotional intelligence and social responsibility to their young patients, which had influenced them to become pediatricians. Pediatricians are also closely attached to their patients’ families, showing high empathy and acknowledging the important role of the child’s family during the healing process. Thus, the emotional scenarios concerning nonverbal and verbal communication in child ambulatory and hospital care and other settings are different from adult medicine. Competent pediatricians may no longer consider communication with children as a challenge by itself, believing that they have done it all the time and have learned by experience. In our opinion, this view seems to be wide-spread and may lead to the underestimation of additional skills for the pediatrician. Learning how to communicate with children of all ages and how to exchange adequate information of different cultural backgrounds should become an integral part of the curricula of postgraduate pediatric training. This also includes systematically learning to handle the child’s rights to health, participation of children during health care, and child-friendly health care in the multiperson setting including the child, the different members of the family, and the different caregivers. We will present a series of articles putting elements of the psychosocial and legal scenario into the center of a debate on inadequacy of child health care services. This report, opens the debate on the central role of communication between children and caregivers.

Improving Care through Better Communication: Continuing the Debate.

http://dx.doi.org/10.1016/j.jpeds.2015.05.040 E P A C hildren’s competence and autonomy develop through direct social personal experience, not only through general developmental age and physical growth. Some of the youngest children can be among the most informed and confident patients if adequately informed. The competence of children depends on the quality of communication with their parents and healthcare providers, and therefore, correlates with the competence of these caregivers to be supportive and generous when delegating knowledge and power to the child. “Children’s decisionmaking competence is dependent on others’, such as parents and healthcare professionals, attitudes and not only on their own capacity. Lack of competence, however, does not exclude children from the human right to have a say. It should be noted that it is a decision to leave the determination to a parent or healthcare professional.” Evaluating a child’s competence poses serious challenges and includes the need for pediatric decision aids (Table I; available at www.jpeds.com). Moreover, it is important to assess the competence of the pediatrician (Table II; available at www.jpeds.com). He or she must be able to understand all relevant information, to retain and explain all issues clearly and resolve misunderstandings, to assist children and parents in their informed decision making, and to respect their decisions, putting no undue pressure on them. Along with respect for children’s views and values, the whole healthcare team may have to test and stretch the children’s and their own boundaries to inform and involve the children. A realistic approach is needed that respects the limits of clinical knowledge, skills, and factual understanding of children and of the daunting risks and uncertainties in explaining treatment and science. Children have different concepts of health and disease than adults and institutional regulations (Table III; available at www.jpeds.com), depending mainly on their cognitive, emotional, social, psychological, and physical development (Figure; available at www.jpeds.com). They need time and space to tell their story, and caregivers need special skills to inspire them to do so. In a study by Horwitz et al, 80% of parents of 4to 8-yearolds reported having a psychosocial concernworthmentioning to their pediatrician, but only roughly 50%were actually able to have such a discussion. The doctors themselves may have consciously or unconsciously contributed to this hesitancy. Studies in pediatric primary care have shown that doctors tend to ignore ordismiss themajority of parents’ and children’s hints and disclosures regarding emotional distress. Many pediatricians are aware of health literacy–related problems and the need for good communication with families, but because of time constraints often struggle to implement communication skills learned previously.

Neuronal correlates of cognitive function in patients with childhood cerebellar tumor lesions

While it has been shown that cerebellar tumor lesions have an impact on cognitive functions, the extent to which they shape distant neuronal pathways is still largely undescribed. Thus, the present neuroimaging study was designed to investigate different aspects of cognitive function and their neuronal correlates in patients after childhood cerebellar tumor surgery. An alertness task, a working memory task and an incompatibility task were performed by 11 patients after childhood cerebellar tumor surgery and 17 healthy controls. Neuronal correlates as reflected by alterations in functional networks during tasks were assessed using group independent component analysis. We were able to identify eight networks involved during task performance: default mode network, precuneus, anterior salience network, executive control network, visual network, auditory and sensorimotor network and a cerebellar network. For the most ‘basic’ cognitive tasks, a weaker task-modulation of default mode network, left executive control network and the cerebellar network was observed in patients compared to controls. Results for higher-order tasks are in line with a partial restoration of networks responsible for higher-order task execution. Our results provide tentative evidence that the synchronicity of brain activity in patients was at least partially restored in the course of neuroplastic reorganization, particularly for networks related to higher-order cognitive processes. The complex activation patterns underline the importance of testing several cognitive functions to assess the specificity of cognitive deficits and neuronal reorganization processes after brain lesions.

Differences in attentional functioning between preterm and full-term children underline the importance of new neuropsychological detection techniques

The aim of this study was to investigate specific attentional components in preterm born children who had not yet started school.

Do we still need IQ-scores? Misleading interpretations of neurocognitive outcome in pediatric patients with medulloblastoma: a retrospective study

Over the past decades, many studies used global outcome measures like the IQ when reporting cognitive outcome of pediatric brain tumor patients, assuming that intelligence is a singular and homogeneous construct. In contrast, especially in clinical neuropsychology, the assessment and interpretation of distinct neurocognitive domains emerged as standard. By definition, the full scale IQ (FIQ) is a score attempting to measure intelligence. It is established by calculating the average performance of a number of subtests. Therefore, FIQ depends on the subtests that are used and the influence neurocognitive functions have on these performances. Consequently, the present study investigated the impact of neuropsychological domains on the singular “g-factor” concept and analysed the consequences for interpretation of clinical outcome. The sample consisted of 37 pediatric patients with medulloblastoma, assessed 0–3 years after diagnosis with the Wechsler Intelligence Scales. Information processing speed and visuomotor function were measured by the Trailmaking Test, Form A. Our findings indicate that FIQ was considerably impacted by processing speed and visuomotor coordination, which leaded to an underestimation of the general cognitive performance of many patients. One year after diagnosis, when patients showed the largest norm-deviation, this effect seemed to be at its peak. As already recommended in international guidelines, a comprehensive neuropsychological test battery is necessary to fully understand cognitive outcome. If IQ-tests are used, a detailed subtest analysis with respect to the impact of processing speed seems essential. Otherwise patients may be at risk for wrong decision making, especially in educational guidance.

Applying the International Classification of Functioning–Children and Youth Version to Pediatric Neuro-oncology:

Given the increased survival rates in patients with pediatric central nervous system tumors, late effects such as treatment- and/or illness-related neurologic sequelae as well as neuropsychological deficits and social difficulties have moved into focus in follow-up care. In order to provide personalized treatment recommendations for pediatric brain tumor survivors, it is crucial not only to assess cognitive impairments but also to measure a patient’s functional deficiencies, for example, restricted participation in everyday social activities. Thus, this article introduces the International Classification of Functioning–Children and Youth version (ICF-CY) as a conceptual framework for quantifying functional limitations and informing long-term care in pediatric neuro-oncology. A standardized self-report and proxy-report questionnaire for measuring participation is briefly discussed and specific recommendations based on so-called core sets for clinical practice in pediatric neuro-oncology are provided.

Cerebellar pilocytic astrocytoma in childhood: Investigating the long-term impact of surgery on cognitive performance and functional outcome

ABSTRACT Objective: Previous studies differ regarding the long-term effects of surgically removed pediatric cerebellar pilocytic astrocytomas (CPA). Thus, the aim of this study was to investigate the long-term impact on neurocognitive and functional outcome and to analyze age as an influencing factor. Methods: Fourteen CPA patients were compared to the age norm and to a group of 14 high-achieving peers regarding cognitive functioning, health-related quality of life (HRQoL), and stress regulation. Mean follow-up time after diagnosis was 13.29 years (range: 3–21 years). Results: Patients showed satisfactory academic achievement and did not differ from the norm except for the bodily dimension of HRQoL. However, there were marked differences in specific neurocognitive functions between patients and high achievers. Age at diagnosis did not influence neurocognitive outcome. Conclusion: CPA patients treated with surgery only seem to have a favorable long-term outcome, yet, in comparison with high achievers specific cognitive impairments become apparent.

PP10.2 – 2803: Is early detection of attention problems in preterm children possible? The value of neuropsychological assessment at preschool age

Background Advances in neonatal intensive care have improved the survival rate of preterm babies over the last decades. However, despite the increased survival rate of these babies, the risk for cognitive and behavioral problems at school age has increased too. These problems are often attributable to specific attentional deficits. The early detection of attentional problems is therefore a challenging but important endeavor for clinicians. Objective The investigation of attentional functioning and all its subcomponents in preterms at preschool age. Methods Preterm (N=56) and full-term children (N=56) between 5;5 and 6;11 years (average 5;7), matched for age and gender, were assessed for the following attentional components: alertness, sustained attention, processing speed, orienting, perception, focused attention, go/nogo, distractibility, divided attention and flexibility. Each construct was assessed through subtests of the following neuropsychological batteries: KITAP/TAP and HAWIK-IV. Further factors such as parental ratings and descriptive item-based evaluation of the childs behavior during the neuropsychological assessment were also considered. Results Preterms show poor attentional performance in sustained attention, focused attention and distractibility, as well as a reduction of processing speed in the visual search task, divided attention and flexibility. Decrease of volitional attention compared to automatic attention was also identified. No problems were detected in alertness and inhibition (go/nogo). In addition, a higher rate of test-aborts, decreased motivation, and poor parental ratings were detected among the preterm population. Conclusion The results highlight the difference of attentional functioning between preterm and full-term children, pointing out the importance of new neuropsychological techniques for the detection of specific attentive disorders.