Abstract Background Controversy exists as to what may be defined as standard of care (including markers for stratification) for patients with atypical teratoid/rhabdoid tumors (ATRTs). The European Rhabdoid Registry (EU-RHAB) recruits uniformly treated patients and offers standardized genetic and DNA methylation analyses. Methods Clinical, genetic, and treatment data of 143 patients from 13 European countries were analyzed (2009–2017). Therapy consisted of surgery, anthracycline-based induction, and either radiotherapy or high dose chemotherapy following a consensus among European experts. Fluorescence in situ hybridization, multiplex ligation-dependent probe amplification, and sequencing were employed for assessment of somatic and germline mutations in SWItch/sucrose nonfermentable related, matrix associated, actin dependent regulator of chromatin, subfamily B (SMARCB1). Molecular subgroups (ATRT-SHH, ATRT-TYR, and ATRT-MYC) were determined using DNA methylation arrays, resulting in profiles of 84 tumors. Results Median age at diagnosis of 67 girls and 76 boys was 29.5 months. Five-year overall survival (OS) and event-free survival (EFS) were 34.7 ± 4.5% and 30.5 ± 4.2%, respectively. Tumors displayed allelic partial/whole gene deletions (66%; 122/186 alleles) or single nucleotide variants (34%; 64/186 alleles) of SMARCB1. Germline mutations were detected in 26% of ATRTs (30/117). The patient cohort consisted of 47% ATRT-SHH (39/84), 33% ATRT-TYR (28/84), and 20% ATRT-MYC (17/84). Age <1 year, non-TYR signature (ATRT-SHH or -MYC), metastatic or synchronous tumors, germline mutation, incomplete remission, and omission of radiotherapy were negative prognostic factors in univariate analyses (P < 0.05). An adjusted multivariate model identified age <1 year and a non-TYR signature as independent negative predictors of OS: high risk (<1 y + non-TYR; 5-y OS = 0%), intermediate risk (<1 y + ATRT-TYR or ≥1 y + non-TYR; 5-y OS = 32.5 ± 8.7%), and standard risk (≥1 y + ATRT-TYR, 5-y OS = 71.5 ± 12.2%). Conclusions Age and molecular subgroup status are independent risk factors for survival in children with ATRT. Our model warrants validation within future clinical trials.

The aim of this study was to examine whether irritable bowel syndrome (IBS) is associated with increased somatic pain sensitivity in a large population-based sample and to test whether this association was independent of sex, age, comorbid chronic pain, and psychological distress. Pain sensitivity tests included assessment of heat-pain threshold (N=4054) and pressure-pain threshold (N=4689) and of cold-pressor pain intensity and tolerance (N=10,487). Cox regression and analysis of variance (ANOVA) were used to assess the relationship between IBS and pain sensitivity in stepwise multivariate models. The prevalence of IBS symptoms meeting the ROME II criteria was 5.3%. Compared with control subjects, IBS cases had reduced cold-pressor tolerance (hazard ratio=1.4, P<.01), increased cold-pressor pain intensity ratings (z-score=+0.20, P<0.01), and lower heat-pain thresholds (z-score=-0.20, P<0.01), after adjusting for sex and age. These results were only slightly attenuated and remained significant when controlling for comorbid chronic pain and psychological distress. Results for pressure-pain threshold were not significant. Heat- and cold-pressor pain sensitivity was greatest for the IBS reporting severe chronic abdominal pain, indicating that hyperalgesia in IBS is related to degree of clinical pain rather than to the diagnosis per se. Because all pain tests were all carried out on the upper extremities, our findings indicate the presence of widespread hyperalgesia in IBS, which may be a contributing factor to the high rate of comorbid pain seen in this patient group.

Summary Obesity is associated with poor outcomes in childhood acute lymphoblastic leukaemia (ALL). We explored whether severe treatment‐related toxicity and treatment delays could explain this observation. This study included 1 443 children aged 2·0–17·9 years with ALL treated with the Nordic Society of Pediatric Haematology and Oncology (NOPHO) ALL2008 non‐high‐risk protocol. Prospective treatment‐related toxicities registered every three‐month interval were used. Patients were classified according to sex‐ and age‐adjusted international childhood cut‐off values, corresponding to adult body mass index: underweight, <17 kg/m2; healthy weight, 17 to <25 kg/m2; overweight, 25 to <30 kg/m2; and obese, ≥30 kg/m2. Obese children had a higher incidence rate ratio (IRR) for severe toxic events {IRR: 1·55 [95% confidence interval (CI) 1·07–2·50]}, liver and kidney failures, bleeding, abdominal complication, suspected unexpected severe adverse reactions and hyperlipidaemia compared with healthy‐weight children. Obese children aged ≥10 years had increased IRRs for asparaginase‐related toxicities compared with healthy‐weight older children: thromboses [IRR 2·87 (95% CI 1·00–8·21)] and anaphylactic reactions [IRR 7·95 (95% CI 2·15–29·37)] as well as higher risk for truncation of asparaginase [IRR 3·54 (95% CI 1·67–7·50)]. The high prevalence of toxicity and a higher risk of truncation of asparaginase may play a role in the poor prognosis of obese children aged ≥10 years with ALL.