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Purpose: Fifteen percent to 20% of human neuroblastomas show amplification of the MYCN oncogene physiologically located at chromosome 2p24-25, indicating an aggressive subtype of human neuroblastoma with a poor clinical outcome. Recent findings revealed that the structure of the amplicon differs interindividually and that coamplification of genes in telomeric proximity to MYCN might play a relevant role in neuroblastoma development and response to treatment, respectively. We now asked if the amplicon structure is an invariable attribute of an individual tumor or if the coamplification pattern could change during progress or in case of recurrent disease.Experimental Design: We used a previously described multiplex PCR approach to analyze the coamplification status of MYCN-amplified human neuroblastomas (n = 33) in tumor tissue at the time of initial diagnosis and in consecutive tissue specimens at later time points after initial treatment or from relapsing disease. The MYCN copy number per haploid genome (Mcn/hg) in these specimens was determined in a separate duplex PCR.Results: In 32 of the 33 investigated tumors, the amplicon structure showed no changes after initial chemotherapy and in recurrent disease. Mcn/hg showed a decrease after initial treatment (n = 23), whereas we found a significant increase in recurrent disease (n = 10).Conclusion: Our data indicate that the initial determined structure of the 2p24-25 amplicon is a consistent attribute in the great majority of the individual MYCN-amplified neuroblastomas and shows no plasticity during or after chemotherapy. Observed changes in the Mcn/hg over the course of disease are in line with preexisting cell culture findings.

Supplementary Figure 1 from The Coamplification Pattern of the MYCN Amplicon Is an Invariable Attribute of Most MYCN-Amplified Human Neuroblastomas

Supplementary Figure Legend from The Coamplification Pattern of the MYCN Amplicon Is an Invariable Attribute of Most MYCN-Amplified Human Neuroblastomas

Supplementary Table 1 from Loss of Caspase-8 Expression Does Not Correlate with MYCN Amplification, Aggressive Disease, or Prognosis in Neuroblastoma

Inactivation of caspase-8 because of aberrant gene methylation has been associated with amplification of the MYCN oncogene and aggressive disease in neuroblastoma, suggesting that caspase-8 may function as tumor suppressor. However, the prognostic effect of caspase-8 in neuroblastoma has remained obscure. Therefore, we investigated caspase-8 expression and its correlation with established prognostic markers and survival outcome in a large cohort of neuroblastoma patients. Here, we report that loss of caspase-8 protein expression occurs in the majority (75%) of neuroblastoma and is not restricted to advanced disease stages. Surprisingly, no correlation was observed between caspase-8 expression and MYCN amplification. Similarly, ectopic expression of MYCN or antisense-mediated down-regulation of MYCN had no effect on caspase-8 expression in neuroblastoma cell lines. In addition, caspase-8 expression did not correlate with other variables of high-risk disease (e.g., 1p36 aberrations, disease stage, age at diagnosis, or tumor histology). Most importantly, loss of caspase-8 protein had no effect on event-free or overall survival in the overall study population or in distinct subgroups of patients. By revealing no correlation between caspase-8 expression and MYCN amplification or other established variables of aggressive disease, our findings in a large cohort of neuroblastoma patients show that inactivation of caspase-8 is not a characteristic feature of aggressive neuroblastoma. Thus, our study provides novel insight into the biology of this tumor, which may have important clinical implications. (Cancer Res 2006; 66(20): 10016-23)

Supplementary Figure 1 from Loss of Caspase-8 Expression Does Not Correlate with MYCN Amplification, Aggressive Disease, or Prognosis in Neuroblastoma

Recent evidence suggests that illness perceptions in paediatric patients and their parents may differ, with parents holding more negative views compared to their children. Little is known about illness perceptions of very young patients and their parents. This study investigates illness perceptions in paediatric cancer patients aged 4-18 years and their parents in acute treatment or follow-up care, distinguishing patients by age (4-11, 12-18) and stage of medical treatment.N = 45 patient-parent dyads in acute treatment and n = 95 dyads in follow-up care were examined. Parents and older children aged 12-18 years completed the Illness Perception Questionnaire-Revised (IPQ-R) and younger children aged 4-11 years were examined using an age-adapted hand puppet interview containing the IPQ-R questions. Difference scores of illness perceptions (symptoms, timeline-acute/chronic, timeline-cyclical, personal control, illness coherence, consequences, emotional representations) between children and parents were tested for significance using Wilcoxon signed-rank tests.Overall, parents perceived more symptoms associated with their child's illness/treatment than the children themselves. In acute treatment, younger children indicated more negative and older children more positive views regarding chronicity than parents. Younger children held less negative views on consequences, and all children reported less negative emotional representations than parents. In follow-up care, all children held less negative views on consequences and emotional representations. Older children reported less negative views on chronicity, cyclicity and illness coherence.Differences in illness perceptions of paediatric patients and their parents should be considered during and after treatment/medication and psychosocial care to support illness coping in person- and family-centred interventions.

(1) Background: Gastric carcinoma is an exceptionally rare tumor in childhood. Little is known about the etiology, epidemiology, and clinical features of pediatric gastric carcinomas. This analysis aimed to fill this gap by increasing knowledge about the occurrence of gastric carcinoma in childhood. (2) Material and methods: Data from gastric carcinoma cases diagnosed between 2000 and 2017/2018 were retrieved from the Surveillance, Epidemiology, and End Results Program (SEER) and the German Center for Cancer Registry Data. Data from patients

Background: Recent data suggest that anesthesiologic interventions—e.g., the choice of the anesthetic regimen or the administration of blood products—might play a major role in determining outcome after tumor surgery. In contrast to adult patients, only limited data are available regarding the potential association of anesthesia and outcome in pediatric cancer patients. Methods: A retrospective multicenter study assessing data from pediatric patients (0–18 years of age) undergoing surgery for nephroblastoma between 2004 and 2018 was conducted at three academic centers in Europe. Overall and recurrence-free survival were the primary outcomes of the study and were evaluated for a potential impact of intraoperative administration of erythrocyte concentrates, the use of regional anesthesia and the choice of the anesthetic regimen. The length of stay on the intensive care unit, the time to hospital discharge after surgery and blood neutrophil-to-lymphocyte ratio were defined as secondary outcomes. Results: In total, data from 65 patients were analyzed. Intraoperative administration of erythrocyte concentrates was associated with a reduction in recurrence-free survival (hazard ratio (HR) 7.59, 95% confidence interval (CI) 1.36–42.2, p = 0.004), whereas overall survival (HR 5.37, 95% CI 0.42–68.4, p = 0.124) was not affected. The use of regional anesthesia and the choice of anesthetic used for maintenance of anesthesia did not demonstrate an effect on the primary outcomes. It was, however, associated with fewer ICU transfers, a shortened time to discharge and a decreased postoperative neutrophil-to-lymphocyte ratio. Conclusions: The current study provides the first evidence for a possible association between blood transfusion as well as anesthesiologic interventions and outcome after pediatric cancer surgery.

We recently identified Galectin-1 (Gal-1), a β-galactoside-binding lectin, as a novel immune regulator in neuroblastoma (NB). Here, we characterized the tolerogenic function of Gal-1 within the CD8+ T cell compartment and further evaluated its relevance as an antigen for effective DNA vaccination against NB in a mouse model. NB cells with Gal-1 knockdown (NXS-2L) exhibited significantly reduced tumor growth compared to NXS-2 NB cells. Administration of anti-CD8 antibodies prevented this antitumor effect, with primary tumor growth comparable to that from Gal-1 (G1)-sufficient NB cells. Peptide epitope screening with online databases and in silico docking experiments predicted the sequences "FDQADLTI" (#1), "GDFKIKCV" (#2), and "AHGDANTI" (#3) to have superior H2-KK binding affinities and "KFPNRLNM" (#4), "DGDFKIKCV" (#5), and "LGKDSNNL" (#6) to have superior H2-DD binding affinities. Minigenes encoding G1-KK (#1-#2-#3), G1-DD (#4-#5-#6) and the triplet with the highest affinity, G1-H (#1-#2-#4), were generated and cloned into a ubiquitin-containing plasmid (pU). Mice receiving pU-G1-KK or pU-G-1H presented a reduction in the s.c. tumor volume and weight of up to 80% compared to control mice; this reduction was associated with increased cytotoxicity of isolated splenocytes from vaccinated animals. Vaccination with pUG1-DD showed a lower capability to suppress primary tumor progression. In conclusion, Gal-1 expression by NB negatively regulates CD8+ T cells. Vaccination with DNA plasmids encoding Gal-1 epitopes overcomes immune escape, enhances CD8+ T cell-dependent immunity and displays effective antitumor activity against NB.

Cancers 14(5), 1261 (2022). doi:10.3390/cancers14051261, Published by MDPI, Basel

This study investigated the association of individual and dyadic coping strategies with fear of progression (FoP) in mothers and fathers of children with hematologic cancer. Parental couples (N = 44) whose children had been diagnosed with hematologic cancer were recruited at a university hospital and a rehabilitation clinic in Germany between 03/2017 and 08/2017. Data included parents' self-report on FoP (Fear of Progression Questionnaire-parent version, FoP-Q-SF/PR), individual coping (Coping Health Inventory for Parents, CHIP-D), and dyadic coping (Dyadic Coping Inventory, DCI). Statistical analyses were carried out for mothers and fathers individually as well as for parental couples using dyadic data analyses (e.g., actor-partner interdependence model, APIM). Individual and dyadic coping strategies were significantly correlated with FoP in mothers, but not in fathers. Fathers' evaluation of the couple's dyadic coping significantly predicted mothers' FoP. The more frequent use of familial integration (CHIP-D FAM) and maintaining social support (CHIP-D SUP) as well as a better evaluation of their partners' dyadic coping was significantly associated with lower FoP in mothers. Differences in individual and dyadic coping in parental couples were not associated with FoP. Individual and dyadic coping strategies should be addressed in the psychosocial care of mothers and fathers of children with hematologic cancer. Study results support the benefits of involving fathers in psychosocial interventions, for example, in couple-based interventions that acknowledge interpersonal effects of coping on FoP. Future research should further explore coping strategies applied by fathers of children with hematologic cancer for the regulation of FoP.Este estudio investigó la asociación de estrategias de afrontamiento individual y diádico con el miedo a la progresión (FoP por sus siglas en inglés) en madres y padres de niños con cáncer hematológico. Se reclutaron parejas de padres (N = 44) cuyos niños recibieron una diagnosis de cáncer hematológico en un hospital universitario y una clínica de rehabilitación en Alemania entre marzo de 2017 y agosto de 2017. Los datos incluyeron autoinformes de los padres sobre FoP (Cuestionario de miedo a la progresión, versión para padres, FoP-Q-SF/PR), afrontamiento individual (Inventario de salud de afrontamiento para padres, CHIP-D) y afrontamiento diádico (Inventario de afrontamiento diádico, DCI). Se realizaron análisis estadísticos para madres y padres de manera individual, así como para parejas de padres usando análisis de datos diádicos, (p.ej., Modelo de interdependencia actor-pareja, APIM). Las estrategias de afrontamiento individual y diádico tuvieron una correlación significativa con el FoP en las madres, pero no en los padres. La evaluación por los padres del afrontamiento diádico de la pareja predijo significativamente el FoP de las madres. El uso más frecuente de integración familiar (CHIP-D FAM) y mantenimiento de apoyo social (CHIP-D SUP), así como una mejor evaluación del afrontamiento diádico de sus parejas se asoció significativamente con un FoP más bajo en las madres. Las diferencias en el afrontamiento individual y diádico en parejas de padres no se asociaron al FoP. Las estrategias de afrontamiento individual y diádico deben ser enfrentadas durante el cuidado psicosocial de madres y padres de niños con cáncer hematológico. Los resultados del estudio respaldan los beneficios de involucrar a los padres en intervenciones psicosociales, es decir, en intervenciones basadas en parejas que reconocen los efectos interpersonales del afrontamiento en FoP. Investigaciones futuras deberán explorar más las estrategias de afrontamiento empleadas por los padres de niños con cáncer hematológico para regular el FoP.本研究调查了血液科癌症儿童患者的母亲和父亲面对病情继续变化的恐惧（FoP）时个人单独应对的策略和夫妻二人相互作用的二元应对策略。 研究对象为在德国的一家大学附属医院和一个康复诊所里就诊被诊断为血液科癌症的孩童的父母们, 一共招募到44对夫妻, 数据采集时间为2017年3月到8月期间。这些数据具体包括家长自己报告的FoP（FoP问卷-家长版本-FoP-Q-SF/PR), 个人应对(家长应对健康问题策略清单即 CHIP-D)和二元应对 (夫妻二人应对健康问题清单即DCI)。本研究对母亲和父亲各人单独作了统计学分析, 也对夫妻二人相互作用作了二元数据分析（比如: 主体-伴侣互相依赖模型, 即APIM）。 个人和夫妻二人应对策略和母亲的FoP有显著性相关性, 和父亲的没有。看父亲对夫妻二人的二元应对的评价就可以预测很多母亲方面的FoP。越多使用家庭凝聚整合功能和维护好社会关系支持（CHIO-D SUP）加上较好地评估伴侣的二元应对策略都和母亲方面较低的FoP有显著关联性。个人应对和夫妻二元应对之间的差异性和FoP并没有相关联。 在给予血液科癌症儿童患者的母亲和父亲心理社会方面关照时应该考虑到个人应对策略和二元应对策略。本研究的结果证明了父亲在心理社会干预中多起一些作用的好处, 例如在进行伴侣双方为基础的干预时, 意识到家长二人面对FoP的相互之间的影响。未来的研究可以进一步探究血液科癌症儿童患者的父亲在调节FoP时使用的应对策略。.

Belastende medizinische Maßnahmen wie bei einer Krebserkrankung führen bei Kindern und Jugendlichen zunehmend zu psychischen und psychosozialen Langzeitfolgen. Eine individuell angepasste psychologische Vorbereitung kann dabei helfen, den Patienten zu stabilisieren und Angst zu reduzieren.

Potenziell lebensbedrohliche oder -einschrankende padiatrische Erkrankungen sowie lebenseinschrankende Behinderungen und deren Behandlung bedeuten fur die gesamte Familie andauernde psychosoziale Anforderungen. Aus der Perspektive von gesunden Geschwistern im Jugend- und Erwachsenenalter werden die erlebten psychosozialen Auswirkungen der (andauernden) Krankheitserfahrung oder Verlusterfahrung auf die eigene (Personlichkeits-) Entwicklung und Biografie untersucht. Problemzentrierte Interviews werden mit n = 12 gesunden Geschwistern nach mindestens 5 Jahren der (andauernden) Krankheitserfahrung oder Verlusterfahrung gefuhrt und mittels qualitativer Inhaltsanalyse ausgewertet. Die gesunden Geschwister geben an, dass ihre Personlichkeit durch die Erfahrungen positiv beeinflusst ist und sie an der Situation gewachsen und gereift sind. Wahrend jedoch die einen Kontinuitat und Normalitat ihrer Entwicklung betonen, beschreiben andere eine Zasur im Leben: Aufgrund des Verlusts emotionaler Verfugbarkeit von Bezugspersonen oder alterstypischer Aktivitaten empfinden sie ihre Kindheit als zu zeitig beendet. Es werden Auswirkungen der Erfahrungen als gesundes Geschwister auf personliche Interessen und die schulische/berufliche Laufbahn sowie auf das Empfinden der eigenen Mutterschaft beschrieben. Zu empfehlen ist ein niedrigschwelliges psychosoziales Angebot fur gesunde Geschwister im Jugend- und Erwachsenenalter. Es sollte die Bildung eines Narrativs der Krankheits- oder Verlusterfahrung fokussiert werden, vor dessen Hintergrund Entscheidungen wie Berufswahl oder Familiengrundung reflektiert werden.

ZusammenfassungRegelmäßige körperliche Aktivität ist eine wichtige Voraussetzung für die Gesundheit und die Entwicklung von Kindern und Jugendlichen. Insbesondere während aber auch nach einer Krebserkrankung sind Kinder und Jugendliche jedoch in sehr geringem Umfang körperlich aktiv und weisen eine stark ausgeprägte körperliche Inaktivität auf. Diese chronische körperlich-motorische Unterforderung hat, zusätzlich zu den Nebenwirkungen der Behandlung, weitere negative Folgen für die Gesundheit, wie z. B. starke Einbußen der körperlichen Leistungsfähigkeit und der Lebensqualität. Um diese Folgen zu verringern, kann den PatientInnen im Rahmen von gezielten sporttherapeutischen Bewegungsangeboten Zugang zu regelmäßiger körperlicher Aktivität ermöglicht werden. Bewegungsförderung für Kinder und Jugendliche mit Krebserkrankungen stellt eine supportive Maßnahme zur Verbesserung und Erhaltung der funktionalen Mobilität, der körperlichen Leistungsfähigkeit und der gesundheitsbezogenen Lebensqualität dar. Für eine nachhaltige Bewegungsförderung müssen sowohl die Verhaltensebene (Person) als auch die Verhältnisebene (Lebenswelt) berücksichtigt werden. Anhand des Leipziger Bewegungskonzepts werden Einflussebenen auf die körperliche Aktivität von Kindern und Jugendlichen mit Krebserkrankungen erläutert sowie inhaltliche, systemische und strukturelle Voraussetzungen für die Implementierung einer behandlungsbegleitenden Bewegungsförderung in der Pädiatrischen Onkologie beschrieben. Zusätzlich werden Finanzierungsmöglichkeiten, basierend auf dem SGB V §43, aufgezeigt.

Simple Summary Currently, patients with high-risk neuroblastoma are uniformly treated with maximum therapy. This study investigated a high-risk subgroup characterized by the presence of the amplified MYCN oncogene in the tumor regardless of the stage. In contrast to the corresponding high-risk subgroup consisting of patients with metastases and age at diagnosis over 18 months, the investigated subgroup had generally a superior survival chance. However, the detection of mutations of specific genes in the tumor tissue (RAS and p53 pathway including ALK) had a strong, negative impact. These genes should be therefore also investigated in the future. Complete surgical removal of the primary tumor proved to be beneficial for high-risk neuroblastoma patients assigned to the high-risk category solely by MYCN amplification. Abstract Background: To identify variables predicting outcome in neuroblastoma patients assigned to the high-risk group solely by the presence of MYCN oncogene amplification (MNA). Methods: Clinical characteristics, genomic information, and outcome of 190 patients solely assigned to high-risk neuroblastoma by MNA were analyzed and compared to 205 patients with stage 4 neuroblastoma aged ≥18 months with MNA (control group). Results: Event-free survival (EFS) and overall survival (OS) at 10 years were 47% (95%-CI 39–54%) and 56% (95%-CI 49–63%), respectively, which was significantly better than EFS and OS of the control group (EFS 25%, 95%-CI 18–31%, p < 0.001; OS 32% 95%-CI 25–39%, p < 0.001). The presence of RAS-/p53-pathway gene alterations was associated with impaired 10-year EFS and OS (19% vs. 55%, and 19% vs. 67%, respectively; both p < 0.001). In time-dependent multivariable analyses, alterations of RAS-/p53-pathway genes and the extent of the best primary tumor resection were the only independent prognostic variables for OS (p < 0.001 and p = 0.011, respectively). Conclusions: Neuroblastoma patients attributed to high risk solely by MYCN amplification have generally a more favorable outcome. Mutations of genes of the RAS and/or p53 pathways and incomplete resection are the main risk factors predicting poor outcome.

Aim In 2015, the revised International Pediatric Non-Hodgkin Lymphoma Staging System was published. It mentions [18F]-FDG-PET/MRI as the latest method to perform whole-body imaging. However, supporting data are pending. Our aim was to investigate the performance of whole-body [18F]-FDG-PET/MRI in pediatric non-Hodgkin lymphoma patients by using a limited number of MRI sequences. Materials and methods Ten pediatric patients with histologically proven non-Hodgkin lymphoma underwent whole-body [18F]-FDG-PET/MRI at staging. The retrospective analysis included three steps: First, [18F]-FDG-PET and MR scans were evaluated separately by a nuclear medicine physician and a pediatric radiologist. Nineteen nodal and two extranodal regions as well as six organs were checked for involvement. Second, discrepant findings were reviewed together in order to reach consensus. Third, [18F]-FDG-PET/MRI findings were correlated with the results of other clinical investigations. Results Of the 190 lymph node regions evaluated, four were rated controversial. Consensus was reached by considering metabolic, functional and morphologic information combined. Concordantly, [18F]-FDG-PET and MRI detected Waldeyer’s ring involvement in two patients whose Waldeyer’s ring was negative on clinical assessment. In four patients MRI showed pleural effusion. However, in only two of them an increased glucose metabolism as a reliable sign of pleural involvement was detectable. In six patients [18F]-FDG-PET and MRI detected skeletal lesions although bone marrow biopsy was positive in only one of them. Conclusion Despite the small number of cases evaluated, whole-body [18F]-FDG-PET turned out to be a valuable tool for staging of pediatric non-Hodgkin lymphoma.

Introduction The survival of children with stage 4(M) neuroblastoma without MYCN amplification and below the age of 18 months is considered better than the still dismal outcome of older high-risk neuroblastoma patients. This study analyzes the impact of clinical and molecular characteristics on the long-term outcome. Patients and methods Clinical presentation, survival, and recurrence patterns of patients enrolled onto trials NB90, NB97, and NB2004 were retrospectively analyzed. Gene expression signatures based on RNA microarrays (TH10) were investigated if tumor material was available. Results Between 1990 and 2015, 177 patients with stage 4(M) MYCN nonamplified neuroblastoma aged less than 18 months at diagnosis were eligible. After a median follow-up of 9.7 years (IQR 5.0, 13.4), the proportions of 10-year event-free survival (EFS) and overall survival (OS) were 73% (95% confidence interval [CI] 67-79%) and 86% (95% CI 80-92%), respectively. Of the 27 neuroblastoma recurrences, 44% occurred in more than one site. Four additional patients presented histologically mature ganglioneuroma at recurrence. Six patients developed a secondary malignancy. The secondary 5-year EFS and OS of the 27 patients with neuroblastoma recurrence were 44% and 59%, respectively. TH10 gene expression signature was not prognostically predictive in the investigated subcohort. Conclusion The outcome of patients with stage 4(M) neuroblastoma aged less than 18 months is favorable when treated with high-risk or otherwise intensive therapy. The development of secondary malignancies and the potential of maturation to ganglioneuroma call for a controlled stepwise reduction of treatment intensity.

Recent research shows that parents of children suffer from fear of progression (FoP), the fear of further disease progression. It is most possible that children also develop FoP, which could impair treatment and psychological health. The aim of this study is to adapt the adult's version of the Fear of Progression Questionnaire - Short Form (FoP-Q-SF) for children and to examine the psychometric properties in pediatric cancer patients.32 pediatric cancer patients between 10 and 18 years with different diagnoses and in different treatment states participated in this study.In the cross-sectional study participants completed the adapted Fear of Progression Questionnaire - Short Form for Children (FoP-Q-SF/C) and self-report measures assessing quality of life, depression, fear and coping satisfaction.The questionnaire (FoP-Q-SF/C) showed adequate psychometric properties (Cronbachs α=0.86) and good results for construct validity. Significant medium to large correlations of children's FoP was observed with quality of life (r=- 0.37), depression (r=0.52), fear (r=0.33 - 0.76), and satisfaction with coping (r=- 0.44). One-fifth of the sample was classified as having high FoP with values over 37.The FoP-Q-SF/C is a short, economic questionnaire that is applicable in children with cancer. Clinicians can use the questionnaire to explore specific fear and the need for psychosocial support. Further research for specific treatment approaches for FoP in pediatric cancer patients are warranted.Aktuelle Forschungsergebnisse zeigen, dass Eltern krebskranker Kinder unter Progredienzangst (PA), der Angst vor dem Fortschreiten einer Erkrankung leiden. Es scheint naheliegend, dass auch Kinder diese Ängste entwickeln, was die Behandlung und die psychologische Gesundheit beeinflussen kann. Ziel der Studie ist die Adaption des Progredienzangst-Fragebogens (FoP-Q-SF) für Kinder und die Ermittlung der psychometrischen Eigenschaften für pädiatrische Onkologiepatienten.32 pädiatrische Krebspatienten zwischen 10 und 18 Jahren mit unterschiedlichen Krebsdiagnosen und in unterschiedlichen Behandlungsstadien nahmen an der Studie teil.In der Querschnittsstudie beantworteten die Teilnehmenden den adaptierten Progredienzangst-Fragebogen-Kurzversion für Kinder (FoP-Q-SF/C) und Selbstbeantwortungsfragebögen zu Lebensqualität, Depression, Angst und Copingzufriedenheit.Der Fragebogen (FoP-Q-SF/C) zeigte adäquate psychometrische Eigenschaften (Cronbachs α=0,86) und Konstrukvalidität. Signifikante Korrelationen wurden zwischen Progredienzangst und Lebensqualität (r=- 0,37), Depression (r=0,52), Angst (r=0,33-0,76), und Copingzufriedenheit (r=- 0,44) gefunden. Ein Fünftel der Stichprobe zeigte hohe Progredienzangstwerte mit Werten über 37.Der FoP-Q-SF/C ist ein kurzer, ökonomischer Fragebogen, der für krebskranke Kinder passend ist. Kliniker können den Fragebogen einsetzen, um PA und die Notwendigkeit von psychosozialer Unterstützung zu erfassen. Weitere Forschungsarbeiten für spezifische Behandlungsansätze von PA in der pädiatrischen Onkologie sind wünschenswert.Recent research shows that parents of children suffer from fear of progression (FoP), the fear of further disease progression. It is most possible that children also develop FoP, which could impair treatment and psychological health. The aim of this study is to adapt the adult’s version of the Fear of Progression Questionnaire – Short Form (FoP-Q-SF) for children and to examine the psychometric properties in pediatric cancer patients.32 pediatric cancer patients between 10 and 18 years with different diagnoses and in different treatment states participated in this study.In the cross-sectional study participants completed the adapted Fear of Progression Questionnaire – Short Form for Children (FoP-Q-SF/C) and self-report measures assessing quality of life, depression, fear and coping satisfaction.The questionnaire (FoP-Q-SF/C) showed adequate psychometric properties (Cronbachs α=0.86) and good results for construct validity. Significant medium to large correlations of children’s FoP was observed with quality of life (r=− 0.37), depression (r=0.52), fear (r=0.33 – 0.76), and satisfaction with coping (r=− 0.44). One-fifth of the sample was classified as having high FoP with values over 37.The FoP-Q-SF/C is a short, economic questionnaire that is applicable in children with cancer. Clinicians can use the questionnaire to explore specific fear and the need for psychosocial support. Further research for specific treatment approaches for FoP in pediatric cancer patients are warranted.Aktuelle Forschungsergebnisse zeigen, dass Eltern krebskranker Kinder unter Progredienzangst (PA), der Angst vor dem Fortschreiten einer Erkrankung leiden. Es scheint naheliegend, dass auch Kinder diese Ängste entwickeln, was die Behandlung und die psychologische Gesundheit beeinflussen kann. Ziel der Studie ist die Adaption des Progredienzangst-Fragebogens (FoP-Q-SF) für Kinder und die Ermittlung der psychometrischen Eigenschaften für pädiatrische Onkologiepatienten.32 pädiatrische Krebspatienten zwischen 10 und 18 Jahren mit unterschiedlichen Krebsdiagnosen und in unterschiedlichen Behandlungsstadien nahmen an der Studie teil.In der Querschnittsstudie beantworteten die Teilnehmenden den adaptierten Progredienzangst-Fragebogen-Kurzversion für Kinder (FoP-Q-SF/C) und Selbstbeantwortungsfragebögen zu Lebensqualität, Depression, Angst und Copingzufriedenheit.Der Fragebogen (FoP-Q-SF/C) zeigte adäquate psychometrische Eigenschaften (Cronbachs α=0,86) und Konstrukvalidität. Signifikante Korrelationen wurden zwischen Progredienzangst und Lebensqualität (r=− 0,37), Depression (r=0,52), Angst (r=0,33–0,76), und Copingzufriedenheit (r=− 0,44) gefunden. Ein Fünftel der Stichprobe zeigte hohe Progredienzangstwerte mit Werten über 37.Der FoP-Q-SF/C ist ein kurzer, ökonomischer Fragebogen, der für krebskranke Kinder passend ist. Kliniker können den Fragebogen einsetzen, um PA und die Notwendigkeit von psychosozialer Unterstützung zu erfassen. Weitere Forschungsarbeiten für spezifische Behandlungsansätze von PA in der pädiatrischen Onkologie sind wünschenswert.

Fear of Progression (FoP) is a commonly reported psychological strain in parents of children with cancer. This expert survey investigates how professionals in pediatric oncology estimate the burden and consequences of FoP in parents and how they assess and treat parental FoP.N=77 professionals in pediatric oncology (members and associates of the Psychosocial Association in Paediatric Oncology and Haematology, PSAPOH) were examined in an online survey with a self-developed questionnaire. Data were analyzed via descriptive statistics and qualitative content analysis.Three of four experts in clinical practice were (very) often confronted with parental FoP which was associated with more negative (e. g., psychosomatic reactions, reduced family functioning) than positive (e. g., active illness processing) consequences. N=40 experts indicated that they mainly assess parents' anxiety via clinical judgment (72.5%) and/or according to ICD-10/DSM-5 diagnostic criteria (37.5%), whereas standardized methods such as psycho-oncological questionnaires (12.5%) were applied less often. Only n=6 experts named a specific diagnostic approach to assess parental FoP. The most common treatment approaches for FoP were supportive counseling (74.0%), psychotherapy (59.7%) and/or relaxation techniques (55.8%).Parental FoP is frequently perceived by experts in clinical practice. A standardized diagnostic procedure would increase comparability of diagnostic judgments and harmonize treatment indications.Progredienzangst (PA) gehört zu den häufigsten psychischen Belastungen bei Eltern krebskranker Kinder. In dieser Studie wurden Experten hinsichtlich der Auftretenshäufigkeit und Konsequenzen von PA bei Eltern sowie zur diagnostischen Erfassung und Behandlung elterlicher PA befragt.N=77 Mitglieder und assoziierte Kollegen der Psychosozialen Arbeitsgemeinschaft in der Gesellschaft für Pädiatrische Onkologie und Hämatologie (PSAPOH) wurden mit einem selbstentwickelten Online-Fragebogen befragt. Es wurden Häufigkeitsanalysen sowie eine qualitative Inhaltsanalyse durchgeführt.Drei von vier Experten wurden in ihrer klinischen Tätigkeit (sehr) oft mit elterlicher PA konfrontiert und gaben mehr negative (z. B. psychosomatische Reaktionen, eingeschränkte Familienfunktion) als positive (z. B. aktive Krankheitsverarbeitung) Konsequenzen elterlicher PA an. N=40 Experten gaben an, elterliche Ängste vor allem durch klinisches Expertenurteil (72.5%) bzw. anhand diagnostischer Kriterien nach ICD-10/DSM-5 (37.5%) zu erfassen, während der Einsatz standardisierter Instrumente wie psychoonkologische Fragebögen (12.5%) seltener angegeben wurde. Nur n=6 Experten nannten einen spezifischen diagnostischen Ansatz zur Erfassung elterlicher PA. Supportive Beratung (74.0%), Psychotherapie (59.7%) und/oder Entspannungstechniken (55.8%) wurden als gängige Behandlungsansätze für PA genannt.PA wird bei Eltern krebskranker Kinder von Experten sehr oft beobachtet. Ein standardisiertes diagnostisches Vorgehen könnte klinische Urteile vergleichbar machen und Behandlungsempfehlungen vereinheitlichen.

Background: To identify variables predicting outcome in neuroblastoma patients assigned to the high-risk group solely by the presence of MYCN oncogene amplification (MNA). Methods: Clinical characteristics, genomic information, and outcome of 190 patients solely assigned to high-risk neuroblastoma by MNA were analyzed and compared to 205 patients with stage 4 neuroblastoma aged ≥18 months with MNA (control group). Results: Event-free survival (EFS) and overall survival (OS) at 10 years were 47% (95%-CI 39–54%) and 56% (95%-CI 49–63%), respectively, which was significantly better than EFS and OS of the control group (EFS 25%, 95%-CI 18–31%, p &lt, 0.001, OS 32% 95%-CI 25–39%, p &lt, 0.001). The presence of RAS-/p53-pathway gene alterations was associated with impaired 10-year EFS and OS (19% vs. 55%, and 19% vs. 67%, respectively, both p &lt, 0.001). In time-dependent multivariable analyses, alterations of RAS-/p53-pathway genes and the extent of the best primary tumor resection were the only independent prognostic variables for OS (p &lt, 0.001 and p = 0.011, respectively). Conclusions: Neuroblastoma patients attributed to high risk solely by MYCN amplification have generally a more favorable outcome. Mutations of genes of the RAS and/or p53 pathways and incomplete resection are the main risk factors predicting poor outcome.

We conducted a clinical trial and report the long-term outcome of 773 children with acute lymphoblastic leukemia upon risk-adapted therapy accrued in trial CoALL 07-03 (from the Cooperative Study Group for Childhood Acute Lymphoblastic Leukemia). In a 2-step stratification, patients were allocated to receive either low- or high-risk treatment, based on initial white blood cell count, age, and immunophenotype. A second stratification was performed according to the results of in vitro pharmacosensitivity toward prednisolone, vincristine, and asparaginase (PVA score) and in vivo response after induction therapy (minimal residual disease [MRD]). Therapy was reduced for both risk groups in patients with a low PVA score or negative MRD result, and intensified in patients with a high PVA score. Overall outcome improved significantly compared with the predecessor CoALL 06-97 trial, with identical therapy backbone despite treatment reduction in 15.8% of patients (10-year probability of event-free survival, 83.5% vs 73.9%; overall survival, 90.7% vs 83.8%). Outcome for patients in the reduced treatment arms was superior to that of patients in the standard arms, associated with a profound reduction in frequency and severity of infectious complications. Importantly, we observed a lack of correlation between in vitro and in vivo drug response, as well as a lower predictive value of in vitro drug testing, reflecting an intrinsic limitation of this methodology that prevents its use for treatment stratification in future trials. In conclusion, it might be possible to reduce chemotherapy in children with acute lymphoblastic leukemia selected by stringent in vivo measurement of MRD without jeopardizing overall outcome.

Regular physical activity is an important requirement for the development and the general health in childhood and adolescence. However, patients during and after treatment for childhood cancer show high levels of physical inactivity, and only a marginal extent of physical activity. In addition to the negative side effects of treatment, this lack of physical activity and exertion has further negative implications for their health, such as decrease in physical performance and health related quality of life. In order to reduce these negative effects and provide access to regular physical activity for children and adolescents with cancer, childhood cancer patients should participate in targeted physical exercise therapy sessions at the treating hospital. Physical activity promotion for children and adolescents with cancer is an effective measure to enhance or preserve functional mobility, physical performance and health related quality of life. Both the behavioral level (person) and the setting (environment) should be taken into account for a sustainable implementation of physical activity promotion in the treatment of childhood cancer. The Leipzig Movement Concept promotes physical activity both during and after treatment for childhood cancer. On the basis of the modular concept, factors influencing physical activity in childhood cancer, alongside requirements for the successful and long-term implementation of physical activity programs and clinical exercise therapy are described. Furthermore financing options, based on Book V § 43 of the German Social Welfare Code, are presented.Regelmäßige körperliche Aktivität ist eine wichtige Voraussetzung für die Gesundheit und die Entwicklung von Kindern und Jugendlichen. Insbesondere während aber auch nach einer Krebserkrankung sind Kinder und Jugendliche jedoch in sehr geringem Umfang körperlich aktiv und weisen eine stark ausgeprägte körperliche Inaktivität auf. Diese chronische körperlich-motorische Unterforderung hat, zusätzlich zu den Nebenwirkungen der Behandlung, weitere negative Folgen für die Gesundheit, wie z. B. starke Einbußen der körperlichen Leistungsfähigkeit und der Lebensqualität. Um diese Folgen zu verringern, kann den PatientInnen im Rahmen von gezielten sporttherapeutischen Bewegungsangeboten Zugang zu regelmäßiger körperlicher Aktivität ermöglicht werden. Bewegungsförderung für Kinder und Jugendliche mit Krebserkrankungen stellt eine supportive Maßnahme zur Verbesserung und Erhaltung der funktionalen Mobilität, der körperlichen Leistungsfähigkeit und der gesundheitsbezogenen Lebensqualität dar. Für eine nachhaltige Bewegungsförderung müssen sowohl die Verhaltensebene (Person) als auch die Verhältnisebene (Lebenswelt) berücksichtigt werden. Anhand des Leipziger Bewegungskonzepts werden Einflussebenen auf die körperliche Aktivität von Kindern und Jugendlichen mit Krebserkrankungen erläutert sowie inhaltliche, systemische und strukturelle Voraussetzungen für die Implementierung einer behandlungsbegleitenden Bewegungsförderung in der Pädiatrischen Onkologie beschrieben. Zusätzlich werden Finanzierungsmöglichkeiten, basierend auf dem SGB V §43, aufgezeigt.

Background HD is a B-lineage lymphoma characterized, depending on subtype, by a prominent inflammatory infiltrate and fibrosis. Clinically, inflammatory symptoms like fever, weight loss and night sweats (B-symptoms) and increased blood biomarkers of inflammation, including ESR and CRP, are characteristic of more advanced disease. The clinical trial EURONET-PHL-C2 (Second International Inter-Group Study for Classical Hodgkin's Lymphoma in Children and Adolescents) is a randomized, prospective trial that compares chemo- and radiotherapy treatment concepts of different intensities in patients with intermediate and advanced HD. Patients are stratified by risk into 3 therapy groups (TL-1 to TL-3). An ESR> 30mm/h had been a risk factor for relapse in previous studies and leads to upstaging from the lowest (TL-1, Ann Arbor stage I and IIa without additional risk factors) to the intermediate risk group TL-2 in the current study. This addon pilot study tested urine proteomic patterns from pediatric patients with HD at diagnosis and compared them to the patterns of normal children. The questions were: Is there a HD-specific pattern, a pattern that identifies high risk or a pattern that correlates with inflammatory markers? Patients and methods Capillary electrophoresis coupled to mass spectrometry (CE-MS) was used to compare the peptide profiles in the mass range of 0.8 to 20 kDa of urine samples (N=34) from 16 children with pediatric Hodgkin lymphoma (PHL) as case and 32 age-matched children with no evidence of a disease (N=28) or with urinary tract infection (N=4) as control groups. Marker selection was based on a two-step strategy. First, a group-wise comparison of rank sum differences was performed on a set of 2418 annotated peptides with distribution frequencies above 30% in at least one of the groups with subsequent adjustment for multiple testing by the method of Bonferroni. In the second step marker candidates were further restricted to those demonstrating a significant positive or negative Spearman rho correlation coefficient (≥0.34 or ≤-0.34) to the Ann-Arbor classification criteria. From the resulting peptides a multivariate peptide marker classifier was established by support vector machine modeling and applied to an independent confirmation set of PHL (N=16, 31 urine samples) and control (N=18, 18 urine samples) patients to determine classification accuracy in receiver operating characteristics (ROC) analysis. Peptides included in the PHL classifier were resolved in their amino acid sequence by tandem mass spectrometry to identify the proteins from which the peptide markers are derived. Results The established multivariate peptide marker model consisting of 40 naturally occurring urinary peptides enabled absolute differentiation between PHL patients and children without signs of disease or urinary tract infection in independent validation as revealed by an area under the ROC curve value of 1.0 (95% confidence interval: 0.93 to 1.00, p Conclusions and perspective We were able to identify a proteomic pattern characteristic for HD, markers for relapse risk group or HD-associated inflammation were not yet identified. Disclosures Metzger: Mosaiques Diagnostics: Employment.

Anthracyclines are integral components of antileukemic treatment. Apart from cardiotoxicity, myelosuppression and infectious complications have been described for doxorubicin (DOX) and daunorubicin (DNR) as predominant side effects, but little is known about their differential toxicities. To address the question whether DNR is associated with a lower rate of infectious complications compared with DOX, 307 children with newly diagnosed acute lymphoblastic leukemia, enrolled in trial CoALL 08-09, were randomized to receive either DOX 30 mg/m

We determined the indication, outcome, and risk factors of single and multiple hematopoietic stem cell transplantation(s) (HSCT) in children and adolescents mostly with advanced disease. Forty-one out of 483 patients (8.5 %; median age 9 years) diagnosed at the University of Leipzig with hematological and oncological diseases required HSCT from 1999 to 2011. Patients had overall survival (OS) of 63 ± 10 and 63 ± 16 %, event-free survival (EFS) of 57 ± 10 and 42 ± 16 %, relapse incidence (RI) of 39 ± 10 and 44 ± 18 % and nonrelapse mortality (NRM) of 4 ± 4 and 13 ± 9 % at 10 years after one or more allogeneic and autologous HSCT, respectively. One patient in CR1 and five with advanced disease received two HSCT. Four of the six patients maintained/achieved CR for a median of 13 months. Three died of progression and one of NRM. Two patients had a third HSCT and one survived in CR +231 days after HSCT. Risk factors for OS and EFS were disease stage at HSCT and EBMT risk score. Center (pediatric or JACIE accredited pediatric/adult) was not a determinant for survival. Pediatric single and multiple HSCT are important curative approaches for high-risk malignant diseases with low NRM. Efforts to reduce high RI remain the major aim.

Heme oxygenase (HO)-1 catalyzes the degradation of cytotoxic heme into biliverdin and blocks antitumor immune responses, thus protecting cancer against host defense. Whether this scenario also applies to neuroblastoma (NB), the most common extracranial solid childhood tumor, is not known. Here, we demonstrate for the first time a prognostic relevance of HO-1 expression in samples from NB patients and show that targeting of HO-1 prevents both cancer resistance against cellular stress and immune escape in the syngeneic NXS2 A/J mouse model of NB. High HO-1 RNA expression in NB tissues emerged as unfavorable prognostic marker, in particular for patients older than 18 months as indicated by univariate as well as multivariate survival probability analyses including disease stage and MYCN status. On the basis of this observation we aimed to target HO-1 by systemic as well as tumor-specific zinc protoporphyrin-mediated HO-1 suppression in a syngeneic immunocompetent NB mouse model. This resulted in 50% reduction of primary tumor growth and a suppression of spontaneous liver metastases. Importantly, HO-1 inhibition abrogated immune cell paralysis affecting CD4 and CD8 T-effector cells. This in turn reverted HO-1-dependent immune escape mechanisms in NB by increasing NB apoptosis and improved DC maturation. In summary, HO-1 emerges as a novel immune regulator in NB and emerges as a promising target for the development of therapeutic approaches.

OBJECTIVES: To assess knowledge deficits of patients/parents and prevention strategies. METHODS: After receiving ethics approval, we performed a controlled, quasi-randomised, prospective intervention study. We enrolled patients/parents involved in managing oral medicines in three groups: control (routine care only), handbook intervention and pharmaceutical counselling intervention group. At baseline and after the interventions, we assessed patients’/parents’ knowledge deficits (incorrect or missing answers) by questionnaire. RESULTS: We enrolled 64 patients/parents. At baseline, knowledge deficits among the groups were similar: 17% in controls, 22% in the handbook group and 24% in the pharmaceutical counselling group. After the intervention, knowledge deficits decreased to 13% in the handbook group and to 8% in the pharmaceutical counselling group (NS; p=0.003 compared with controls, respectively). For controls, knowledge deficits remained almost unchanged (19%). Results for the pharmaceutical counselling group showed a strong correlation between baseline knowledge deficits and the extent of the deficit decrease after the intervention (τ=−0.74; p

In pediatric patients, brain tumors have been estimated to be the cause for seizures in only 0.2-0.3% of cases, whereas seizures occurred in about 13% of pediatric brain tumor patients at presentation. This survey was conducted to analyze EEG findings in pediatric tumor patients over the past 14 years to evaluate the diagnostic value of preoperative EEG for diagnosis of brain tumors. Surface EEG was obtained in awake patients using the international 10- to 20-electrode placement in all pediatric patients with intracranial neoplasms between 2000 and 2013 at the University Hospital of Leipzig except for those who needed emergency operative treatment. One hundred forty-two pediatric patients with 80 infratentorial and 62 supratentorial tumors (WHO grades I-II: 91 patients; WHO grades III-IV: 46 patients). Symptomatic hydrocephalus was found in 37. Sensitivity and specificity of ophthalmologic examination for predicting hydrocephalus was 0.39 and 0.72. Preoperative EEG has been conducted in 116 patients, showing normal activity in 54 patients (47%). Out of 62 pathologic EEGs, 40 indicated correctly to the site of the lesion, 15 were pathologic despite of infratentorial location of the tumor. Nineteen patients had a history of seizures of which six had normal EEGs. Sensitivity for and specificity of EEG examination for symptomatic epilepsy was 0.68 and 0.7. Conclusion Preoperative routine EEG provides no additional value in the diagnostic algorithm of pediatric train tumors. The low specificity and sensitivity of EEG (even in patients with clinical seizures as primary symptom of a brain tumor) underline that EEG does not contribute to diagnosis and a normal EEG might even delay correct diagnosis.

Hintergrund: Progredienzangst (PA), die Angst vor dem Fortschreiten einer Erkrankung, zahlt zu den haufigsten psychischen Belastungen chronisch kranker Patienten und konnte auch bei gesunden Partnern von erwachsenen Krebspatienten beobachtet werden. Eltern krebskranker Kinder konnen ebenso Angste entwickeln, die auch nach der Behandlung des Kindes fortbestehen. Ziel dieser Studie war es, einen Fragebogen zur Erfassung der PA bei Eltern krebskranker Kinder zu entwickeln und Zusammenhange mit krankheits- bzw. behandlungsrelevanten Informationen, aktuellen Beschwerden des Kindes und der Lebensqualitat der Eltern zu untersuchen. Patienten: An der Studie nahmen 76 Eltern (51 Mutter, 25 Vater) teil, deren Kinder sich in stationarer Behandlung oder in der Nachsorge befanden. Methoden: Zur Erfassung der PA wurden die Items der Kurzform des Progredienzangst-Fragebogens an die Elternperspektive angepasst (PA-F-KF/E). Ergebnisse: Der PA-F-KF/E zeigt adaquate psychometrische Eigenschaften (Cronbachs α=0,90) und Konstruktvaliditat. Signifikante Korrelationen mit der Auspragung der PA konnten fur aktuelle korperliche Beschwerden des Kindes (r=0,35), Zeitraum seit der Diagnosestellung (r=− 0,30), Angstbewaltigung (r=− 0,45) und Lebensqualitat der Eltern (r=− 0,55) gezeigt werden. Ein Cut-off-Wert von 46 wird vorgeschlagen. Schlussfolgerung: Mit dem PA-F-KF/E liegt ein Kurzfragebogen vor, der okonomisch einsetzbar und sensitiv hinsichtlich ausgepragter krankheitsbezogener Angste ist. Fur den Kliniker ergibt sich aus der fallbezogenen Auswertung ein erster Einblick in die spezifischen Problembereiche der betroffenen Eltern. Der Fragebogen ist somit fur den Einsatz in der psychosozialen Versorgung von Familien in der padiatrischen Onkologie sehr gut geeignet.

Pediatric tumors of the central nervous system composed of oligoid tumor cells showing diffuse leptomeningeal spread without a primary mass lesion seem to represent a novel tumor entity. The terms “diffuse leptomeningeal glioneural tumor” or—preferably—“disseminated oligodendroglial-like leptomeningeal tumor of childhood” (DOGLT) were proposed. Four patients were identified with clinico-neuropathologic findings compatible with DOGLT and a mean follow-up time of 54 months was determined. Seven different biopsies obtained from the four patients were histologically evaluated. Clinical course, diagnostic measures, histopathologic and radiologic features and treatment suggestions were recorded, on the basis of which diagnostic and therapeutic algorithm was proposed. Patients with DOGLT presented with hydrocephalus as first symptom, requiring neurosurgical therapy. Open arachnoid biopsy was necessary to confirm diagnosis. The oligoid cells in a desmoplastic or focally myxoid matrix showed OLIG2-, MAP2-, S-100 and rare HuC/HuD protein-immunopositivity. IDH1 (R132H)- and CD99-immunohistochemistry was negative in all patients. None of the evaluable biopsies of three patients showed chromosome 1p/19q deletion, neither as isolated nor combined allelic loss. Chemotherapy according to the SIOP-LGG 2004 standard induction and consolidation protocol resulted in complete response and partial response, respectively, in 50 % of the patients. However, after discontinuation of chemotherapy, two patients experienced tumor progression and one of them succumbed to the disease after 19 months. Radiological criteria as well as preliminary treatment results are presented after observation of four clinical cases. Prognosis and long-term clinical courses remain to be observed.

Objective Psychometric properties of the Fear of Progression Questionnaire - Short Form (FoP-Q-SF) were shown to be good in samples of adult cancer patients and their partners but have so far not been investigated in parents of children with cancer. This study therefore aimed to examine psychometric properties of the previously adapted parent version of the Fear of Progression Questionnaire (FoP-Q-SF/PR) in pediatric oncology. Methods N = 181 parents (119 mothers, 62 fathers) of n = 128 children with diverse cancer entities, up to ten years after diagnosis were recruited at six hospitals and six registered parent associations in Germany and Austria between 06/2015 and 05/2016 (cross-sectional design). Parents provided medical information about their child and completed standardized questionnaires (Hospital Anxiety and Depression Scale, HADS; State-Trait Anxiety Inventory, STAI; Impact of Event Scale-Revised, IES-R; Ulm Quality of Life Inventory for Parents, ULQIE; Giessen Physical Complaints Inventory for children and adolescents, GBB-KJ). Results Exploratory factor analysis yielded two factors (50.2% explained variance) and internal consistency was good (Cronbach's α = 0.89). Significant medium to large correlations of the FoP-Q-SF/PR were observed with anxiety (HADS: r = 0.68; STAI: r = 0.60–0.61), depression (HADS: r = 0.58), posttraumatic stress (IES-R: r = 0.42–0.64) and quality of life (ULQIE: r = − 0.59). The FoP-Q-SF/PR discriminated between sub-groups, e.g. parents with and without clinical anxiety levels (Cohen's d = 1.26). Conclusion The FoP-Q-SF/PR demonstrated good reliability and validity for parents of children with cancer. The FoP-Q-SF/PR is a feasible screening instrument, which is suitable for the assessment of parental FoP in pediatric oncology.

Die PET/MRT ist die neueste und innovativste Entwicklung auf dem Gebiet der bildgebenden Diagnostik. Die wesentlich geringere Strahlenexposition im Vergleich zur PET/CT stellt gerade fur kinderonkologische Fragestellungen einen ganz entscheidenden Vorteil dar. Die gleichzeitige Abbildung von Metabolismus, verschiedenen funktionellen Parametern und hochaufgeloster Anatomie ermoglicht zudem eine noch genauere Diagnostik und verspricht neue Erkenntnisse zur Pathophysiologie padiatrischer Tumoren. So ist zu erwarten, dass mit der PET/MRT neue Wege hinsichtlich weiterer Individualisierung von kinderonkologischen Therapien beschritten werden konnen. Der vorliegende Artikel beschreibt zunachst allgemeine Vorteile dieser Kombinationsbildgebung, geht auf praktische Aspekte der Untersuchungsdurchfuhrung ein und erlautert die Anwendbarkeit von PET/MRT-Protokollen einmal zur Beurteilung eines Lokalgeschehens am Beispiel von kindlichen Hirntumoren und zum anderen zur Ausbreitungsdiagnostik am Beispiel des Neuroblastoms.

An integrated PET/MRI scanner has been used in selected cases of pediatric brain tumor patients to obtain additional metabolic information about lesions for preoperative biopsy planning and navigation.Four patients, age 9-16 years, received PET/MRI scans employing [(11)C]methionine positron emission tomography (PET) and contrast-enhanced 3D-MR sequences for neuronavigation. PET and MR sequences have been matched for neurosurgical guidance. An infrared camera-based neuronavigation system was employed with co-registered MR and PET images fused to hybrid images for preoperative planning, stereotactic biopsy planning, and/or intraoperative guidance.All patients showed hot spots of increased amino acid transport in PET and contrast-enhancing lesions in MRI. In three of the four patients, PET hot spots were congruent with contrast-enhancing areas in MRI. In two patients, frame-based stereotactic biopsies were taken from thalamo-mesencephalic lesions. One patient underwent second-look surgery for the suspicion of recurrent malignant glioma of the posterior fossa. One incidental frontal mass lesion was subtotally resected. No complications occurred. Hybrid imaging was helpful during the procedures to obtain representative histopathologic specimens and for surgical guidance during resection. Co-registered images did match with intraoperative landmarks, tumor borders, and histopathologic specimens.The integrated PET/MRI scanner offers co-registered multimodal, high-resolution data for neuronavigation with reduced radiation exposure compared to PET/CT scans. One examination session provides all necessary data for neuronavigation and preoperative planning, avoiding additional anesthesia in the small patients. Hybrid multimodality imaging may improve safety and yield additional information when obtaining representative histopathologic specimens of brain tumors.

The original publication contains the following errors: In the title, the words ‘oligodendroglial cell-like’ should read ‘oligodendroglial-like’. (The correct title is shown in this erratum.) The images in Figs. 3 and 4 were incorrect. The correct figures are shown below. All the figure citations except the citation of Fig. 1 were incorrect. All citations of Fig. 2 actually concern Fig. 5, all citations of Fig. 3 actually concern Fig. 6, all citations of Fig. 4 actually concern Fig. 2, all citations of Fig. 5 actually concern Fig. 3 and all citations of Fig. 6 actually concern Fig. 4.

Background. Cancer in childhood is rare, but nevertheless one of the most frequent causes of disease related death. Initial symptoms are often unspecific, frequently leading to a delay of cancer diagnosis. As a timely diagnosis can be crucial for the clinical outcome, our aim is to point out when unspecific symptoms should be considered suspect of being associated with specific cancer entities. Data sources. A systematic literature research in PubMed and current biliographies, as well as an evaluation of published epidemiologic data was performed. Results. This article reviews the typical presenting features and epidemiologic characteristics of the more common childhood malignancies, elucidates when specific and virtually unspecific symptoms require further evaluation, and gives advice how to start a rational diagnostic workup. Furthermore, genetic syndromes requiring increased watchfulness for cancer in childhood are demonstrated. Conclusion. Patients showing suspect symptoms should early be referred to specialized centres to assure optimal diagnostic and therapeutic capabilities.

Whereas in the adult population 5-Aminolevulinic acid (5-ALA) fluorescence guidance has been widely accepted for improving the extent of tumor resection, the application in children remains an off-label use. Even though most pediatric study protocols require a complete resection for improving outcome parameters, only few pediatric patients have been operated with fluorescence guidance, and it remains questionable, whether and which pediatric tumors show useful fluorescence. We present casuistic reports of application of 5-ALA in children collected from three different neurosurgical departments. In children with suspected malignant intracerebral tumor or recurrence, individual informed consent was obtained in each case from the parents. 5-ALA was administered according to the adult protocol, with 20 mg/kg, 2 h before induction of anesthesia. We retrospectively analyzed 18 patients (13 male, 5 female; age 3–18 years), using the intraoperative neurosurgical protocol, the postoperative MRI results, and the follow-up clinical examinations. The use of 5-ALA fluorescence guidance proved to be safe in our group of pediatric patients. Fluorescence guidance was most useful for recurrent glioblastoma resection. Medulloblastoma tissue displayed fluorescence only inconsistently, and most pilocytic astrocytoma remained without staining. Ganglioglioma showed partial staining in the central tumor areas, without allowing the use for circumferent resection. The off-label use of 5-ALA fluorescence guidance in pediatric patients appears to be most useful in recurrent high-grade gliomas. Fluorescence accumulation in other pediatric brain tumor entities is not predictable and should be evaluated in future clinical studies before being integrated into the current treatment protocols.

Attenuated Salmonella is an approved oral life vaccine that is currently entering pre-clinical cancer vaccination studies as a promising DNA carrier. In a syngeneic mouse model for neuroblastoma, oral gavage of Salmonella typhimurium (SL7207) carrying recent generated survivin DNA vaccines induced a stronger cellular anti-NB immune response than gene gun application or injection of lentivirally transduced bone marrow-derived DCs. The level of Salmonella-associated side effects was not significant as indicated by unaffected survivin-mediated hematopoiesis and wound healing. We believe that our findings provide an important baseline to translate Salmonella-based DNA vaccination into a clinical application for neuroblastoma.

Aufgrund besserer Heilungschancen bei Krebserkrankungen im Kindes- und Jugendalter treten zunehmend psychische und psychosoziale Langzeitfolgen in den Vordergrund. Vor allem die posttraumatische Belastungsstorung steht derzeit im Fokus. Sie stellt eine mogliche Langzeitfolge von Krebserkrankungen im Kindesalter dar. Jungere Kinder berichten haufig uber Angst vor medizinischen Untersuchungen und konnen diese traumatisch erleben. Eine psychologische Begleitung vor, wahrend und nach belastenden medizinischen Masnahmen kann sowohl die Compliance bezuglich der Prozedur sichern, als auch entstandene psychische Storungen therapieren bzw. praventiv verhindern. Sie gehort deswegen zum Standard innerhalb der Versorgung krebskranker Kinder und Jugendlicher und deren Familien. Das aktuelle Fallbeispiel des 10-jahrigen Patienten Tom stellt praxisnah psychologische Interventionen vor, die individuell an den Bedurfnissen des Kindes angepasst, die Stabilisierung des Patienten, die Reduktion von Angst und das Erleben von Selbstwirksamkeit im Kontext belastender medizinischer Masnahmen sicherstellen.

ZusammenfassungIm Kindesalter stellen Hirntumoren nach den Leukämien die zweitgrößte Gruppe maligner Erkrankungen dar. Die ersten Symptome sind meist unspezifisch und sehr heterogen, abhängig von der Tumorlokalisation und vom Alter des Patienten. Psychische Veränderungen finden sich nicht nur am häufigsten überhaupt bei Patienten mit einem Hirntumor, sondern sind in zahlreichen Fällen auch erste Symptome der Grundkrankheit (14). Um Verhaltens- und Wesensänderungen richtig einordnen zu können, ist eine subtile Berücksichtigung zusätzlicher Symptome auf neurologischem, neuropsychologischem und neuroradiologischem Gebiet erforderlich (14). Der vorliegende Fall zeigt, wie wichtig es sein kann, bei anhaltender Beschwerdesymptomatik die primäre Diagnose zu hinterfragen.

Purpose To evaluate the impact of a predefined gene expression–based classifier for clinical risk estimation and cytotoxic treatment decision making in neuroblastoma patients. Patients and Methods Gene expression profiles of 440 internationally collected neuroblastoma specimens were investigated by microarray analysis, 125 of which were examined prospectively. Patients were classified as either favorable or unfavorable by a 144-gene prediction analysis for microarrays (PAM) classifier established previously on a separate set of 77 patients. PAM classification results were compared with those of current prognostic markers and risk estimation strategies. Results The PAM classifier reliably distinguished patients with contrasting clinical courses (favorable [n = 249] and unfavorable [n = 191]; 5-year event free survival [EFS] 0.84 ± 0.03 v 0.38 ± 0.04; 5-year overall survival [OS] 0.98 ± 0.01 v 0.56 ± 0.05, respectively; both P < .001). Moreover, patients with divergent outcome were robustly discriminated in both German and international cohorts and in prospectively analyzed samples (P ≤ .001 for both EFS and OS for each). In subgroups with clinical low-, intermediate-, and high-risk of death from disease, the PAM predictor significantly separated patients with divergent outcome (low-risk 5-year OS: 1.0 v 0.75 ± 0.10, P < .001; intermediate-risk: 1.0 v 0.82 ± 0.08, P = .042; and high-risk: 0.81 ± 0.08 v 0.43 ± 0.05, P = .001). In multivariate Cox regression models based on both EFS and OS, PAM was a significant independent prognostic marker (EFS: hazard ratio [HR], 3.375; 95% CI, 2.075 to 5.492; P < .001; OS: HR, 11.119, 95% CI, 2.487 to 49.701; P < .001). The highest potential clinical impact of the classifier was observed in patients currently considered as non–high-risk (n = 289; 5-year EFS: 0.87 ± 0.02 v 0.44 ± 0.07; 5-year OS: 1.0 v 0.80 ± 0.06; both P < .001). Conclusion Gene expression–based classification using the 144-gene PAM predictor can contribute to improved treatment stratification of neuroblastoma patients.

SummaryIn human neuroblastoma, amplification of the MYCN gene predicts poor prognosis and resistance to therapy. In a shRNA screen of genes that are highly expressed in MYCN-amplified tumors, we have identified AURKA as a gene that is required for the growth of MYCN-amplified neuroblastoma cells but largely dispensable for cells lacking amplified MYCN. Aurora A has a critical function in regulating turnover of the N-Myc protein. Degradation of N-Myc requires sequential phosphorylation by cyclin B/Cdk1 and Gsk3. N-Myc is therefore degraded during mitosis in response to low levels of PI3-kinase activity. Aurora A interacts with both N-Myc and the SCFFbxw7 ubiquitin ligase that ubiquitinates N-Myc and counteracts degradation of N-Myc, thereby uncoupling N-Myc stability from growth factor-dependent signals.

In response to stimuli that activate p53, cells can undergo either apoptosis or cell cycle arrest, depending on the precise pattern of p53 target genes that is activated. We show here that Zbtb4, a transcriptional repressor protein, associates with the Sin3/histone deacetylase co-repressor and represses expression of P21CIP1 as part of a heterodimeric complex with Miz1. In vivo, expression of ZBTB4 is downregulated in advanced stages of multiple human tumours. In cell culture, depletion of ZBTB4 promotes cell cycle arrest in response to activation of p53 and suppresses apoptosis through regulation of P21CIP1, thereby promoting long-term cell survival. Our data suggest that Zbtb4 is a critical determinant of the cellular response to p53 activation and reinforce the notion that p21Cip1 can provide an essential survival signal in cells with activated p53.

BACKGROUND: Radiation therapy is an integral component in the management of childhood malignancies and undergoes a continuous process of optimization within the prospective trials of the GPOH. At present there are approximately 20 active protocols, some specifying radio-oncological study questions, in which about 500 to 600 children annually are given radiotherapy. MATERIALS/METHODS: The Pediatric Radiation Oncology Working Group (APRO) of the German Society for Radiation Oncology (DEGRO) represents the organizational link between GPOH and DEGRO. Their activities range from phrasing guidelines of radio-oncological therapy, through writing a protocol for a prospective study on radiation-induced late effects (RISK - in co-operation with GPOH, 695 patients registered so far) and organizing meetings for information transfer, to implementing radio-oncology within the prospective studies of the GPOH by establishing study chairs for radio-oncology when radio-oncological questions are a primary focus and/or to function as a reference institution for quality assurance. These activities also include individual case consultations outside the study proper. Twice annually the members of the APRO meet for an update on current knowledge and future directions where a representative of the GPOH is invited to contribute special aspects of pediatric oncology. CONCLUSIONS: In the future, modern technology (intensity modulated radiotherapy, proton therapy, inclusion of imaging in treatment planning) will be part of disease management in pediatric oncology. A working group for modern radiotherapy technology was established to enhance this development. Prospective studies of the GPOH with primary or secondary radio-oncological questions require the implementation of corresponding tasks (documentation, monitoring, etc.) in order to meet future demands on clinical trials and to achieve the aims of the protocol. Consequently adequate financial support is indispensable.