Cytogenetic Prognostication Within Medulloblastoma Subgroups

PURPOSE: Medulloblastoma comprises four distinct molecular subgroups: WNT, SHH, Group 3, and Group 4. Current medulloblastoma protocols stratify patients based on clinical features: patient age, metastatic stage, extent of resection, and histologic variant. Stark prognostic and genetic differences among the four subgroups suggest that subgroup-specific molecular biomarkers could improve patient prognostication. PATIENTS AND METHODS: Molecular biomarkers were identified from a discovery set of 673 medulloblastomas from 43 cities around the world. Combined risk stratification models were designed based on clinical and cytogenetic biomarkers identified by multivariable Cox proportional hazards analyses. Identified biomarkers were tested using fluorescent in situ hybridization (FISH) on a nonoverlapping medulloblastoma tissue microarray (n = 453), with subsequent validation of the risk stratification models. RESULTS: Subgroup information improves the predictive accuracy of a multivariable survival model compared with clinical biomarkers alone. Most previously published cytogenetic biomarkers are only prognostic within a single medulloblastoma subgroup. Profiling six FISH biomarkers (GLI2, MYC, chromosome 11 [chr11], chr14, 17p, and 17q) on formalin-fixed paraffin-embedded tissues, we can reliably and reproducibly identify very low-risk and very high-risk patients within SHH, Group 3, and Group 4 medulloblastomas. CONCLUSION: Combining subgroup and cytogenetic biomarkers with established clinical biomarkers substantially improves patient prognostication, even in the context of heterogeneous clinical therapies. The prognostic significance of most molecular biomarkers is restricted to a specific subgroup. We have identified a small panel of cytogenetic biomarkers that reliably identifies very high-risk and very low-risk groups of patients, making it an excellent tool for selecting patients for therapy intensification and therapy de-escalation in future clinical trials

Pain monitoring app leads to less pain in children with cancer at home:Results of a randomized controlled trial

Background: The authors developed a pain monitoring app offering educational information, and real-time health care professional feedback on clinically significant pain (&gt;4 numeric rating scale [NRS]-11) for children with cancer to reduce pain at home. Methods: This monocenter, nonblinded randomized controlled trial enrolled Dutch children (0–18 years old) receiving cancer treatment (≥3 months after diagnosis, ≥2 months treatment remaining). Children were randomly assigned to use the app or receive usual care (two parallel groups). We assessed whether use of the app yielded less clinically significant pain (aim 1) and whether it affected pain severity, duration, interference, pain management strategies, and parental emotional well-being (aim 2). The app was also evaluated by families (aim 3). Results: A total of 94 children were randomized to use the app (15 drop-outs), and 90 were to receive care as usual (11 drop-outs). The app group (n = 79, mean age: 7.5 [5.1] years, 48% girls, 63% hemato-oncology diagnosis) reported significantly less clinically significant pain compared to usual care (n = 79, mean age: 7.5 [5.4] years, 52% girls, 65% hemato-oncology diagnosis) (odds ratio [OR], 0.38; 95% confidence interval [CI], 0.198–0.734]) (aim 1), as well as significantly lower pain severity (β = –0.27; 95% CI, –0.407 to –0.142). No differences were found for duration, interference, or management strategies. Parents in the app group reported significantly less distress compared to usual care (β = –0.84; 95% CI, –1.61 to –0.03]) (aim 2). Families generally evaluated the app positively (aim 3). Conclusions: Use of the app resulted in less clinically significant pain at home. The exact working mechanisms of the app should be further elucidated.</p

Parents' experiences of pediatric palliative care and the impact on long-term parental grief

Context: approximately 25% of children diagnosed with cancer eventually die. Losing a child puts parents at increased risk for developing psychological problems.Objectives: to explore parents' perceptions of the interaction with health care professionals (communication, continuity of care, and parental involvement) and symptom management during the pediatric palliative phase, and to investigate the influence on long-term grief in parents who lost a child to cancer.Methods: a total of 89 parents of 57 children who died of cancer between 2000 and 2004 participated in this retrospective cross-sectional study by completing a set of questionnaires measuring grief (Inventory of Traumatic Grief), parents' perceptions of the interaction with health care professionals (communication, continuity of care, and parental involvement), and symptom management during the palliative phase. Care was assessed on a five point Likert scale (1 = disagree and 5 = agree).Results: parents highly rated communication (4.6 ± 0.6), continuity of care (4.3 ± 0.6), and parental involvement (4.6 ± 0.7) during the palliative phase. Parents' most often reported physical and psychological symptoms of their child during the palliative phase were fatigue (75%), pain (74%), anxiety to be alone (52%), and anger (48%). Higher ratings of parents on communication (? = ?9.08, P = 0.03) and continuity of care (? = ?11.74, P = 0.01) were associated with lower levels of long-term parental grief. The severity of the child's dyspnea (? = 2.96, P = 0.05), anxiety to be alone (? = 4.52, P &lt; 0.01), anxiety about the future (? = 5.02, P &lt; 0.01), anger (? = 4.90, P &lt; 0.01), and uncontrolled pain (? = 6.60, P &lt; 0.01) were associated with higher levels of long-term parental grief. Multivariate models combining the interaction with health care professionals and symptom management showed a significant influence of both aspects on long-term parental grief.Conclusion: both interaction with health care professionals, especially communication and continuity of care, and symptom management in children dying of cancer are associated with long-term parental grief level

Parents' faith and hope during the pediatric palliative phase and the association with long-term parental adjustment

BACKGROUND: The loss of a child is associated with an increased risk for developing psychological problems. However, studies investigating the impact of parents' faith and hope for a cure during the palliative phase on long-term parental psychological functioning are limited.OBJECTIVE: The study's objective was to explore the role of faith and hope as a source of coping and indicator of long-term parental adjustment.METHODS: Eighty-nine parents of 57 children who died of cancer completed questionnaires retrospectively, exploring faith, hope, and sources of coping, and measuring parents' current level of grief and depression.RESULTS: For 19 parents (21%) faith was very important during the palliative phase. The majority of parents remained hopeful for a meaningful time with their child (n=68, 76%); a pain-free death (n=58, 65%); and a cure (n=30, 34%). Their child (n=70, 79%) was parents' main source of coping. Twelve parents (14%) suffered from traumatic grief, and 22 parents (25%) showed symptoms of depression. Parents' faith was not associated with less long-term traumatic grief (OR=0.86, p=0.51) or symptoms of depression (OR=0.95, p=0.74), and parents' hope for a cure was not related to more long-term traumatic grief (OR=1.07, p=0.71) or symptoms of depression (OR=1.12, p=0.47).CONCLUSIONS: Faith was important for a minority of parents and was not associated with less long-term traumatic grief or symptoms of depression. The majority of parents remained hopeful. Hope for a cure was not associated with more long-term traumatic grief or symptoms of depression.<br/

Nagybánhegyesi Önkormányzat költségvetése összetételének változásai

Context: although a large percentage of children with advanced-stage cancer die at home, remarkably little information is available regarding the experience of general practitioners (GPs) with respect to providing home-based palliative care to children with incurable cancer.Objectives: to explore the perspectives of GPs who care for children with advanced-stage cancer in a home-based setting.Methods: in this cross-sectional study, 144 GPs who provided home-based palliative care to 150 children with incurable cancer from 2001 through 2010 were invited to complete a questionnaire addressing their perspectives regarding: 1) symptom management, 2) collaboration with other health care professionals, 3) the child’s death and care after death and 4) impact of having provided palliative care, scored on distress thermometer (range 0-10).Results: a total of 112 GPs (78%) responded, and 91 GPs completed the questionnaire for 93 patients. The median interval between the child’s death and completing the questionnaire was 7 years. The most prevalent symptoms reported in the patients were fatigue (67%) and pain (61%). Difficulties with communicating with (14%), coordinating with (11%), collaborating with (11%), and contacting (2%) fellow members of the multidisciplinary treatment team were rare. Hectic (7%) and shocking (5%) situations and panic (2%) around the child’s death were rare. GPs reported feelings of sadness (61%) and/or powerlessness (43%) around the time of the patient’s death, and they rated their own distress level as relatively high during the terminal phase (median score: 6, range: 0-9.5). The majority of GPs (94%) reported that they ultimately came to terms with the child’s death.Conclusion: in general, GPs appear to be satisfied with the quality of home-based palliative care that they provide pediatric patients with incurable cancer. Communication among healthcare professionals is generally positive and is considered important. Finally, although the death of a pediatric patient has a profound impact on the GP, the majority of GPs eventually come to terms with the child’s deat

Talking about death with children with incurable cancer: perspectives from parents

OBJECTIVE:To investigate the rationale and consequences associated with a parent's decision to discuss death with a child with incurable cancer.STUDY DESIGN:We present data from a larger retrospective study involving bereaved parents of a child who died of cancer. Parents were asked whether they had discussed the impending death with their child, whether they reflected on this discussion positively, their reasons for not discussing death with their child, and the manner in which the conversation regarding death occurred. The data were analyzed qualitatively using a framework approach.RESULTS:Of the 86 parents of 56 children who answered the questions regarding discussing death with their child, 55 parents of 35 children did not discuss the impending death with their child. The following themes were identified: the parents' inability to discuss the impending death; the parents' desire to protect their child; views regarding talking with children; parents' views of child characteristics; the child's unwillingness to discuss the subject; lack of opportunity to talk; and the child's disability. The parents who did discuss death with their child generally used symbolic and/or religious narratives, or they had brief, direct conversations regarding death. The majority of parents felt positive regarding their decision about whether to talk with their child about his/her impending death.CONCLUSION:Most parents in this study cited several reasons for not discussing death with their child. Our findings highlight the sensitive and complex issues surrounding these conversations, indicating that there may be a role for clinicians in supporting parents

A Dutch paediatric palliative care guideline:a systematic review and evidence-based recommendations for symptom treatment

Background: Children with life-threatening and life-limiting conditions can experience high levels of suffering due to multiple distressing symptoms that result in poor quality of life and increase risk of long-term distress in their family members. High quality symptom treatment is needed for all these children and their families, even more so at the end-of-life. In this paper, we provide evidence-based recommendations for symptom treatment in paediatric palliative patients to optimize care. Methods: A multidisciplinary panel of 56 experts in paediatric palliative care and nine (bereaved) parents was established to develop recommendations on symptom treatment in paediatric palliative care including anxiety and depression, delirium, dyspnoea, haematological symptoms, coughing, skin complaints, nausea and vomiting, neurological symptoms, pain, death rattle, fatigue, paediatric palliative sedation and forgoing hydration and nutrition. Recommendations were based on evidence from a systematic literature search, additional literature sources (such as guidelines), clinical expertise, and patient and family values. We used the GRADE methodology for appraisal of evidence. Parents were included in the guideline panel to ensure the representation of patient and family values. Results: We included a total of 18 studies that reported on the effects of specific (non) pharmacological interventions to treat symptoms in paediatric palliative care. A few of these interventions showed significant improvement in symptom relief. This evidence could only (partly) answer eight out of 27 clinical questions. We included 29 guidelines and two textbooks as additional literature to deal with lack of evidence. In total, we formulated 221 recommendations on symptom treatment in paediatric palliative care based on evidence, additional literature, clinical expertise, and patient and family values. Conclusion: Even though available evidence on symptom-related paediatric palliative care interventions has increased, there still is a paucity of evidence in paediatric palliative care. We urge for international multidisciplinary multi-institutional collaboration to perform high-quality research and contribute to the optimization of symptom relief in palliative care for all children worldwide.</p