The Royal Aberdeen Children's Hospital or RACH is a children's hospital in Aberdeen, Scotland. It is situated on the Foresterhill site, with the Aberdeen Royal Infirmary and Aberdeen Maternity Hospital and provides services to children across the North of Scotland. It is managed by NHS Grampian.
ABSTRACT:We evaluated long-term outcomes of 288 children with refractory-Langerhans cell histiocytosis (R-LCH) from 26 countries, who were prescribed off-label MAPK inhibitors (MAPKis) according to clinical indications. MAPKi indications included 148 R-risk-organ-positive (R-RO+), 67 R-risk-organ-negative (R-RO-), 13 lung destruction (lung), 9 sclerosing cholangitis (SC), 49 neurodegeneration (ND), and 2 diabetes insipidus (DI) cases. Median ages at diagnosis and MAPKi onset were 1.3 and 2.3 years, respectively, with median follow-up of 3.7 years (1166 person-years). Agents mostly prescribed as monotherapies were 184 prescriptions of vemurafenib, 115 of dabrafenib, 3 of encorafenib, 42 of cobimetinib, 45 of trametinib, and/or 1 prescription of binimetinib; followed 51 times by various chemotherapies or hematopoietic stem-cell transplantation, or 28 times by combined anti-BRAF-anti-MEK. Short-term responses (<8 weeks) ranged from 98% (R-RO+ and R-RO-), to 30% (lung) to none (ND, DI, and SC); although long-term lung and ND responses could be observed. Skin rash was the most frequent adverse event (∼55%), and 7 others included 1 case of cardiomyopathy and 6 of retinitis. Five developed MAPKi-unrelated tumors and 9 patients died. Five-year survival was 98%. After 113 patients with R-LCH discontinued MAPKi, 69 experienced disease reactivation. None of the various empirical maintenance therapies were able to prevent secondary reactivation. Among the 143 assessable patients without ND-LCH at MAPKi onset, 60 developed ND (45%, 5-year risk). MAPKis appeared to be safe and effective in children with R-RO+/RO-LCH, whereas other indications' responses were less frequent or occurred later. Further studies are needed to find effective maintenance-therapy approaches, particularly to prevent frequently observed secondary ND.
OBJECTIVES:Scotland is known to have the highest incidence of paediatric-onset inflammatory bowel disease (PIBD) in the United Kingdom and one of the highest worldwide; however, data on prevalence is lacking. We aimed to calculate the PIBD incidence and prevalence rates in Scotland during 2015 to 2018. METHODS:Incident and prevalent cases of PIBD were prospectively recorded by the three Scottish regional paediatric gastroenterology networks covering all paediatric units nationwide. PIBD was defined as children <16 years of age with Crohn's disease, ulcerative colitis or inflammatory bowel disease type unclassified. The incidence rate for the period from 2015 to 2018, the point prevalence (30th June each year) and the period prevalence (calendar year) were each calculated using publicly accessible Scottish population data. RESULTS:In total, 438 patients were diagnosed with PIBD in Scotland over the 4-year study period, providing an overall incidence rate of 12.0/100,000 person-years. The number of prevalent patients per year ranged from 518 to 538, with the highest period prevalence 58.5/100,000 person-years (01 January 2016-31 December 2016) and the highest point prevalence 45.9/100,000 persons (30 June 17). One hundred and fifty-nine patients ≥16 years of age remained within paediatric services in 2017; differences in transition practices were observed across regions. CONCLUSIONS:The Scottish PIBD incidence and prevalence remain the highest reported in nationwide studies worldwide (aged < 16 years). The high prevalence is in keeping with the high incidence rate and minimal mortality rate, so continues to rise. The true caseload within paediatric services, including patients ≥16 years of age, may be up to 30% higher.
PURPOSE Intermediate-risk neuroblastoma patients older than 18 months, with non-MYCN amplified, International Neuroblastoma Risk Group Staging System localized, unresectable or International Neuroblastoma Staging System stage 3 tumors, and unfavorable histology have inferior outcomes compared with other intermediate-risk patients. This study aimed to identify genetic prognostic biomarkers within this rare subgroup. METHODS We conducted a large, international study including chromosomal copy number in all cases, next-generation DNA sequencing in most, and telomere maintenance mechanisms and gene expression in a subset, and correlated results with patient survival. RESULTS Among 98 tumors, 9/98 (9.2%) had oncogene amplifications (CDK4/MDM2/TERT coamplification (n = 1), CDK4/MDM2 coamplification (n = 4), CDK4 (n = 2), TERT (n = 1), and MYC (n = 1)), while 63/98 (64.3%) had typical segmental chromosomal aberrations (tSCAs). Patients with tumors with oncogene amplification had the worst 5-year event-free survival (EFS; 0%; P < .0001 log-rank test) and 5-year overall survival (OS; 44.4% [95% CI, 21.4 to 92.3]; P < .01 log-rank test). Patients with tumors harboring tSCAs had inferior EFS compared with those with numerical chromosomal aberrations only (51.7% [95% CI, 40.6 to 65.8] v 93.3% [95% CI, 81.5 to 100]; P < .01). Patients with p53 pathway tumor alterations (n = 10) had worse EFS than those without (0% v 61.1% [95% CI, 50.3 to 74.3]; P < .0001, log-rank test) and worse OS (26.7% [95% CI, 8.9 to 80.3] v 80.9% [95% CI, 71.8 to 91.3]; P < .001 log-rank test). Multivariable analysis identified tSCAs as an independent prognostic variable for EFS and oncogene amplification or p53 pathway abnormalities as independent prognostic variables for EFS and OS. CONCLUSION Oncogene amplification and/or p53 pathway abnormalities and/or typical SCAs identify patients with intermediate-risk neuroblastoma with inferior outcome for whom intensified or alternative treatments should be considered.
IntroductionAccess to cross-border clinical trials may represent the sole therapeutic option for children living with rare diseases for which no approved medicines exist. Many children are excluded from participation in trials due to language restrictions. There are insufficient comprehensive analyses of the experiences and preferences of parents across Europe concerning participation and exclusion of their child in international clinical trials, particularly regarding language support during enrollment in cross-border clinical research studies.MethodsAn anonymous online survey was designed and translated into 22 official European languages to collect data from parents of children living with a disease across Europe. The survey included five sections: (1) sociodemographic information; (2) experience participating in a clinical trial; (3) experience in cases where the patient was unable to take part in a study abroad; (4) experience participating in a clinical trial abroad; and (5) preferences regarding decentralized trial options.Results1,436 responses were analyzed from parents across 34 European countries. Key findings: 55.7% of the parents reported being able to communicate in English. 10.7% had prior clinical trial experience, of whom 30.1% traveled abroad to enable their child to participate. Among those reporting being excluded from cross-border trials, 34.7% cited language barriers or country of residence as the reason. Most families expressed a strong willingness to accept decentralized trial options, regardless of where the study may be conducted.ConclusionsAccommodating language translation to permit participation in a clinical trial abroad is feasible. While a significant percentage of caregivers of pediatric patients in Europe could communicate in English, approximately one-third of those excluded from clinical trials cited language barriers or country of residence as the reason. When translation was required, the most commonly offered solution was the use of professional interpreters, an accommodation that could enable broader patient participation in essential research.
