Explore the vast range of titles available.

Increasing survival rates in childhood cancer have yielded a growing population of parents of childhood cancer survivors (CCSs). This systematic review compiles the literature on positive and negative long-term psychological late effects for parents of CCSs, reported at least five years after the child's diagnosis and/or two years after the end of the child's treatment. Systematic searches were made in the databases CINAHL, EMBASE, PsycINFO, and PubMed. Fifteen studies, published between 1988 and 2010, from 12 projects were included. Thirteen studies used quantitative methodology, one quantitative and qualitative methodology, and one qualitative methodology. A total of 1045 parents participated in the reviewed studies. Mean scores were within normal ranges for general psychological distress, coping, and family functioning. However, a substantial subgroup reported a clinical level of general psychological distress, and 21-44% reported a severe level of posttraumatic stress symptoms. Worry, disease-related thoughts and feelings, marital strains, as well as posttraumatic growth was reported. Several factors were associated with the long-term late effects, such as parents' maladaptive coping during earlier stages of the childs disease trajectory and children's current poor adjustment. Quality assessments of reviewed studies and clinical implications of findings are discussed and recommendations for future research are presented.

Neuroblastoma is the most common and deadly childhood tumor. Relapsed or refractory neuroblastoma has a very poor prognosis despite recent treatment advances. To investigate genomic alterations associated with relapse and therapy resistance, whole-genome sequencing was performed on diagnostic and relapsed lesions together with constitutional DNA from seven children. Sequencing of relapsed tumors indicates somatic alterations in diverse genes, including those involved in RAS-MAPK signaling, promoting cell cycle progression or function in telomere maintenance and immortalization. Among recurrent alterations, CCND1 -gain, TERT -rearrangements, and point mutations in POLR2A , CDK5RAP , and MUC16 were shown in ≥ 2 individuals. Our cohort contained examples of converging genomic alterations in primary-relapse tumor pairs, indicating dependencies related to specific genetic lesions. We also detected rare genetic germline variants in DNA repair genes (e.g., BARD1 , BRCA2 , CHEK2 , and WRN ) that might cooperate with somatically acquired variants in these patients with highly aggressive recurrent neuroblastoma. Our data indicate the importance of monitoring recurrent neuroblastoma through sequential genomic characterization and that new therapeutic approaches combining the targeting of MAPK signaling, cell cycle progression, and telomere activity are required for this challenging patient group.

Oral administration of medications to children requires age-appropriate dosage forms and strengths. In this study, we: (i) assessed the extent of oral dosage form manipulations, (ii) documented how it is carried out, and (iii) examined the attitudes and sources of information regarding the handling from healthcare professionals. Prospective reviews of electronic records, ward observations, and clinician surveys were performed at a paediatric neurology ward and a paediatric oncology ward in Sweden during April to May of 2018. Approximately 15% of oral medications were manipulated for the studied patient group (median age 12.9 years in oncology, 5.8 years in neurology) with approximately 30% of the patients having an enteral feeding tube. Manipulations were performed both to obtain an appropriate dose from, for example, a fraction of the original tablet or to obtain a powder that could be used to prepare a slurry for administration through enteral feeding tubes. Risks identified were related to patient safety such as cross contamination, suboptimal absorption/pharmacokinetics and inaccurate dose. When examining the working environment of nurses, we observed safe handling of hazardous substances but the nurses occasionally experienced stress and a fear of making mistakes due to absence of information. Paediatricians experienced a lack of time to search for proper information on manipulations. As a step towards improving safety in paediatric medication, we suggest the introduction of clinical pharmacists into the team and further evaluating the possibilities of using more ready-to-administer medications with necessary product information and pharmacovigilance support.

Purpose To evaluate the feasibility of oral cryotherapy (OC) in children and to investigate if OC reduces the incidence of severe oral mucositis (OM), oral pain, and opioid use in children undergoing hematopoietic stem cell transplantation (HSCT) . Methods Fifty-three children, 4–17 years old, scheduled for HSCT in Sweden were included and randomized to OC or control using a computer-generated list. OC instructions were to cool the mouth with ice for as long as possible during chemotherapy infusions with an intended time of ≥ 30 min. Feasibility criteria in the OC group were as follows: (1) compliance ≥ 70%; (2) considerable discomfort during OC < 20%; (3) no serious adverse events; and (4) ice administered to all children. Grade of OM and oral pain was recorded daily using the WHO-Oral Toxicity Scale (WHO-OTS), Children’s International Oral Mucositis Evaluation Scale, and Numerical Rating Scale. Use of opioids was collected from the medical records. Results Forty-nine children (mean age 10.5 years) were included in analysis (OC = 26, control = 23). The feasibility criteria were not met. Compliance was poor, especially for the younger children, and only 15 children (58%) used OC as instructed. Severe OM (WHO-OTS ≥ 3) was recorded in 26 children (OC = 15, control = 11). OC did not reduce the incidence of severe OM, oral pain, or opioid use. Conclusion The feasibility criteria were not met, and the RCT could not show that OC reduces the incidence of severe OM, oral pain, or opioid use in pediatric patients treated with a variety of conditioning regimens for HSCT. Trial registration ClinicalTrials.gov id: NCT01789658

Aim The objective was to determine the levels of and potential relationships between, procedure‐related fear and pain in children. Design Clinical based cross‐sectional. Methods Ninety children aged between 7–18 years were included consecutively and self‐reported levels of pain and fear on a 0–100 mm visual analogue scales (VAS) when undergoing routine needle insertion into a subcutaneously implanted intravenous port following topical anaesthesia. Results The needle‐related fear level was reported to be as high as the needle‐related pain level (mean VAS: 14 mm and 12 mm, respectively, N = 90). With fear as the dependent variable, age and pain were significantly associated and explained 16% of the variance. With pain as the dependent variable, fear was significantly associated and explained 11% of the variance. A post hoc analysis indicated that younger children reported their fear levels to be higher than their pain levels.

Background Children with brain tumors are at high risk of neurocognitive decline after radiotherapy (RT). However, there is a lack of studies on how RT doses to organs at risk (OARs) impacts neurocognition. The aim of this study was to examine dose-risk relationships for mean RT dose to different brain structures important for neurocognitive networks. We explored previously established OARs and potentially new OARs. Methods A sample of 44 pediatric brain tumor survivors who had received proton and/or photon RT were included. Correlations between mean RT doses to OARs and IQ were analyzed. Previously established OARs were cochleae, optic chiasm, optic nerve, pituitary gland, hypothalamus, hippocampus and pons. Potential new OARs for RT-induced neurocognitive decline were cerebellum, vermis and thalamus. Results Mean RT dose to different OARs correlated with several IQ subtests. Higher mean RT dose to cochleae, optic nerve, cerebellum, vermis and pons was correlated with lower performance on particularly full-scale IQ (FIQ), Perceptual Reasoning (PRI), Working Memory (WMI) and Processing Speed Index (PSI). Higher mean RT dose to hippocampus correlated with lower performance on processing speed and working memory. For those receiving whole brain RT (WBRT), higher mean RT dose to the pituitary gland correlated with lower performance on working memory. Conclusion A high dose-risk correlation was found between IQ subtests and mean RT dose in established and potential new OARs. Thus, in the lack of validated dose constraints for vulnerable brain structures, a parsimonious approach in RT planning should be considered to preserve neurocognitive networks.

In neuroblastoma, MYCN amplification and 11q-deletion are important, although incomplete, markers of high-risk disease. It is therefore relevant to characterize additional alterations that can function as prognostic and/or predictive markers. Using SNP-microarrays, a group of neuroblastoma patients showing amplification of one or multiple 12q loci was identified. Two loci containing CDK4 and MDM2 were commonly co-amplified, although amplification of either locus in the absence of the other was observed. Pharmacological inhibition of CDK4/6 with ribociclib or abemaciclib decreased proliferation in a broad set of neuroblastoma cell lines, including CDK4/MDM2 -amplified, whereas MDM2 inhibition by Nutlin-3a was only effective in p53 wild-type cells. Combined CDK4/MDM2 targeting had an additive effect in p53 wild-type cell lines, while no or negative additive effect was observed in p53 mutated cells. Most 12q-amplified primary tumors were of abdominal origin, including those of intrarenal origin initially suspected of being Wilms’ tumor. An atypical metastatic pattern was also observed with low degree of bone marrow involvement, favoring other sites such as the lungs. Here we present detailed biological data of an aggressive neuroblastoma subgroup hallmarked by 12q amplification and atypical clinical presentation for which our in vitro studies indicate that CDK4 and/or MDM2 inhibition also could be beneficial.

Background The aim was to investigate psychotropic medication use in parents of survivors of adolescent cancer from the acute post‐diagnostic phase and up to 2 years following the cancer diagnosis. Methods This study had a nationwide register‐based cohort design comparing psychotropic medication use in parents of adolescent survivors of cancer (n = 2323) to use in parents of cancer‐free controls (n = 20,868). Cox proportional hazards models, adjusted for cancer diagnostic group, parents' age, country of birth, education level, marital status and previous mental health problems estimated the risk of use from the time of the cancer diagnosis up to 2 years later. Results During the first 6 months after the cancer diagnosis, both mothers and fathers had an increased risk of use of anxiolytics (mothers: HRadj 1.71, 95% CI 1.30–2.25; fathers: HRadj 1.57, 95% CI 1.10–2.45) and hypnotics/sedatives (mothers: HRadj 1.53, 95% CI 1.23–1.90; fathers: HRadj 1.32, 95% CI 1.00–1.75). For fathers with a prescription of psychotropic medication during the first 6 months after the cancer diagnosis, the risk remained increased after 6 months (HRadj 1.66, 95% CI 1.04–2.65). From 6 months after the cancer diagnosis, only the risk of antidepressant use among mothers was increased (HRadj 1.38, 95% CI 1.08–1.76). Risk factors included being divorced/widowed, born in a non‐Nordic country, older age and having had previous mental health problems. Conclusion Our study results show that during the immediate post‐diagnostic phase, mothers and fathers of survivors of adolescent cancer are at increased risk of use of anxiolytics and sedatives, whereas only mothers are at increased risk of antidepressant use from 6 months until 2 years after the diagnosis. Further, previous mental health problems were shown to be the strongest risk factor for psychotropic medication use in both mothers and fathers, pointing to the particular vulnerability of these parents. Using high quality register data this study show that both mothers and fathers of adolescents diagnosed with cancer are at increased risk use anxiolytics and sedatives, pointing to clinical levels of anxiety and sleep disturbances, during the first six months after the cancer diagnosis. Also, from six months until two years after the cancer diagnosis mothers were at increased risk of antidepressant use.

Purpose To investigate the short‐ and long‐term risk of psychotropic medication use in parents who lose a child to cancer diagnosed in adolescence. Methods This is a Swedish nationwide register‐based study including 184 bereaved mothers and 184 bereaved fathers of 184 children diagnosed with cancer in adolescence. Logistic regression analyses, adjusted for sociodemographic characteristics and history of mental health problems, were performed to estimate risk of a prescription of psychotropic medication (anxiolytics, hypnotics/sedatives, antidepressants) in cancer‐bereaved parents from 1 year before to 5 years after the child's death, with a general population sample of non‐bereaved parents (n = 3291) as referents. Results At the year of the child's death, 28%–36% of mothers and 11%–20% of fathers had a prescription of anxiolytics, hypnotics/sedatives or antidepressants. The corresponding percentages for non‐bereaved mothers and fathers were 7%–12% and 4%–7%, respectively. Compared to non‐bereaved mothers, bereaved mothers showed higher odds of prescriptions from 1 year before up to four (anxiolytics) and 5 years (hypnotics/sedatives and antidepressants) after the child's death. Bereaved fathers showed higher odds than non‐bereaved fathers of prescriptions from 1 year before up to the year of (anxiolytics and hypnotics/sedatives) and 1 year after (antidepressants) the child's death. No differences in odds between bereaved and non‐bereaved fathers were found at 2 years after the child's death. Being unmarried, born outside Sweden, and having a history of mental health problems were associated with higher odds of prescribed medications. Conclusions Indicative of mental health problems of clinical importance, cancer‐bereaved parents had a higher prevalence of use of psychotropic medication. A decrease in medication use was evident with time, but still at 5 years after the child's death mothers displayed a higher use while fathers showed no difference to non‐bereaved fathers after 2 years.

Background The histologic classification of rhabdomyosarcoma (RMS) as alveolar (aRMS) or embryonal (eRMS) is of prognostic importance, with the aRMS being associated with a worse outcome. Specific gene fusions (PAX3/7::FOXO1) found in the majority of aRMS have been recognized as markers associated with poor prognosis and are included in current risk stratification instead of histologic subtypes in localized disease. In metastatic disease, the independent prognostic significance of fusion status has not been definitively established. The objective of this analysis was to evaluate survival outcomes of patients with localized and metastatic aRMS and its association with fusion status and subtype (PAX3/7::FOXO1, FOXO1 break), and clinical prognostic factors. Methods A total of 470 patients with aRMS ≤21 years of age enrolled in two CWS‐trials and two registries was eligible for the analysis. Results The 5‐year event‐free survival (EFS) and overall survival (OS) rates for all patients with localized vs. metastatic tumors were: 56% and 65% vs. 18% and 22%, respectively. Of the 368 (78%) tumors tested, specific fusion was found in 330 (90%), considered “fusion positive” FP (PAX3::FOXO1 in 280, PAX7::FOXO1 in 49, FOXO1 break in 59 tumors). In patients with localized tumors, univariate analysis revealed that clinical group, tumor invasiveness (T1 vs.T2), regional lymph node involvement (N0 vs. N1) and FOXO1 fusion were significantly associated with EFS and OS, tumor size and PAX variant with OS only. In patients with metastatic aRMS, age, bone/marrow (B/BM) metastases, FOXO1 fusion and PAX variant were associated with EFS and OS, T status with OS only. Multivariate analysis identified PAX3::FOXO1 fusion as an independent adverse prognostic factor for EFS in patients with localized disease and for EFS and OS in patients with metastatic disease, B/BM metastases for EFS. Conclusion PAX3::FOXO1 fusion should replace FOXO1 fusion as an adverse prognostic factor in risk stratification. The prognostic relevance of PAX7::FOXO1‐positive and FOXO1 fusion negative aRMS, along with the clinical factors described in this report, allows further refinement of risk assessment of patients with localized and metastatic aRMS. PAX3::FOXO1 fusion should replace FOXO1 fusion as an adverse prognostic factor in risk stratification of patients with rhabdomyosarcoma. The prognostic relevance of PAX7::FOXO1‐positive and FN alveolar rhabdomyosarcoma (aRMS), along with the clinical factors described in this report, allows further refinement of risk assessment of patients with localized and metastatic (aRMS).