Dilemmas in the Management of an Infant with Neuroblastoma Metastasized to the Muscles

The risk stratification of infants with metastatic neuroblastoma (NB) has evolved over time from stage 4/M or IVs/4S/MS/Ms according to various staging systems. Despite these developments for some genetic aberrations, the prognostic value and the impact of soft tissue metastases in infants are not fully understood, nor well described in the different classification systems, hampering the definitions to uniformly treat patients and predict prognosis. A literature review on staging of infants with M/MS disease was performed at the occasion of the diagnosis of NB in an 8-month-old boy who presented with atypical metastatic sites in soft tissue and an aberrant tumor biology. The definitions of stage 4/4S/4s/M/MS/Ms were evaluated and compared to enable tumor risk stratification and inform management. International NB groups use different criteria for defining stage of infants with metastasized NB, resulting in differences in management. Limited literature is available on soft tissue metastases, especially muscular metastases, and is poorly incorporated into management guidelines mainly due to the lack of data. The uncertain prognosis of rare genetic aberrancies may add to the difficulties in treatment decisions. In some rare cases of NB in infants, the international treatment classification is not sufficient for staging and treatment decisions. Based on tumor progression, biology of unknown significance and a lack of evidence to classify a child under 12 months with NB and multiple muscular metastases, the patient was treated as stage 4/M and intermediate-risk protocols with a favorable outcome

Future paradigms for precision oncology

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Accelerating drug development for neuroblastoma - New Drug Development Strategy: an Innovative Therapies for Children with Cancer, European Network for Cancer Research in Children and Adolescents and International Society of Paediatric Oncology Europe Neuroblastoma project

Introduction: Neuroblastoma, the commonest paediatric extra-cranial tumour, remains a leading cause of death from cancer in children. There is an urgent need to develop new drugs to improve cure rates and reduce long-term toxicity and to incorporate molecularly targeted therapies into treatment. Many potential drugs are becoming available, but have to be prioritised for clinical trials due to the relatively small numbers of patients. Areas covered: The current drug development model has been slow, associated with significant attrition, and few new drugs have been developed for neuroblastoma. The Neuroblastoma New Drug Development Strategy (NDDS) has: 1) established a group with expertise in drug development; 2) prioritised targets and drugs according to tumour biology (target expression, dependency, pre-clinical data; potential combinations; biomarkers), identifying as priority targets ALK, MEK, CDK4/6, MDM2, MYCN (druggable by BET bromodomain, aurora kinase, mTORC1/2) BIRC5 and checkpoint kinase 1; 3) promoted clinical trials with target-prioritised drugs. Drugs showing activity can be rapidly transitioned via parallel randomised trials into front-line studies. Expert opinion: The Neuroblastoma NDDS is based on the premise that optimal drug development is reliant on knowledge of tumour biology and prioritisation. This approach will accelerate neuroblastoma drug development and other poor prognosis childhood malignancies

Development of an integrated competency framework for postgraduate paediatric training : a Delphi study

Competency-based education (CBE) has transformed medical training during the last decades. In Flanders (Belgium), multiple competency frameworks are being used concurrently guiding paediatric postgraduate CBE. This study aimed to merge these frameworks into an integrated competency framework for postgraduate paediatric training. In a first phase, these frameworks were scrutinized and merged into one using the Canadian Medical Education Directives for Specialists (CanMEDS) framework as a comprehensive basis. Thereafter, the resulting unified competency framework was validated using a Delphi study with three consecutive rounds. All competencies (n = 95) were scored as relevant in the first round, and twelve competencies were adjusted in the second round. After the third round, all competencies were validated for inclusion. Nevertheless, differences in the setting in which a paediatrician may work make it difficult to apply a general framework, as not all competencies are equally relevant, applicable, or suitable for evaluation in every clinical setting. These challenges call for a clear description of the competencies to guide curriculum planning, and to provide a fitting workplace context and learning opportunities. Conclusion: A competency framework for paediatric post-graduate training was developed by combining three existing frameworks, and was validated through a Delphi study. This competency framework can be used in setting the goals for workplace learning during paediatric training. What is Known: Benefits of competency-based education and its underlying competency frameworks have been described in the literature. A single and comprehensive competency framework can facilitate training, assessment, and certification. What is New: Three existing frameworks were merged into one integrated framework for paediatric postgraduate education, which was then adjusted and approved by an expert panel. Differences in the working environment might explain how relevant a competency is perceived

Students in the picture : how to improve workplace ‘learning’ through the use of video recordings

Background Improving the learning process of medical students during undergraduate and postgraduate clinical training is challenging, as the working environment is focused on patientcare rather than student learning. To optimize learning at the workplace, there is a need for direct observation to provide specific feedback. Unfortunately, direct observation is often hindered by logistical and situational issues. This is why the implementation of video recordings of students’ performances might be helpful to guide and structure the learning process. Although there are many individual studies dedicated to video use in medical education, there is no thorough overview of the available recommendations to implement video use, or to design studies evaluating this tool during workplace learning so far. Objective This study aims (1) to provide an overview of existing literature of video usage in medical education, (2) to describe the advantages and pitfalls of implementation of video during workplace learning, and (3) to define recommendations for future study designs using video recordings of students as educational tools. Methods An extensive literature review was performed in two databases: MEDLINE and Web of Science. Search terms in different categories were combined to maximize output. Different concepts were defined: 1) the population (medicine, medical education, medical student, medical trainee, resident), 2) the intervention (video, video feedback, video learning, video training, video evaluation, video teaching, recording, filming, multimedia), 3) the setting (workplace learning, clinical setting, clinical work, clinical training, clinical learning), and 4) the outcome (feedback, evaluation, reflection, assessment). Results A total of 49 articles were found suitable for inclusion as they described video being used during authentic workplace learning, whereas 155 articles described video recordings in simulation settings. Only 1 article took the unpredictability of daily practice into account. Advantages included an improved learning process, more specific feedback, lower cognitive load, less scheduling issues, and many more. Pitfalls included costs, technical issues, feelings of stress and fear, and others. Among the recommendations, there was a need for a supportive learning climate, description of both student’s strengths and points of improvement, an emphasis on formative use, and implementing it among other forms of instruction and feedback practices. Conclusion Recording videos of students during workplace learning has already shown to improve the learning process in a structured clinical learning environment. Future studies might focus on implementing video during unpredictable daily practice, and their design could take into account the known advantages, pitfalls and recommendations that have been described in this literature review

Chemotherapy drug shortages in paediatric oncology: A 14-year single-centre experience in Belgium

Shortages of chemotherapy are a growing challenge for the healthcare system. We present the burden of drug shortages of chemotherapeutics in the paediatric hemato-oncology unit of a tertiary care hospital and solutions that were used to manage them. Between January 2001 and December 2014, 54 individual shortages were detected, affecting a total number of 21 different drugs. In total, 4127 shortage days were registered with a mean duration of 196.5 SD ± 144.0 days per individual drug shortage. Methotrexate, doxorubicin and carboplatin had the longest supply disruptions. Solutions to address the problems were purchase of a generic alternative, a change of individual treatment plans, cohorting of patients and import from abroad.status: publishe

Retrospective study of children with chronic myeloid leukemia treated in Belgium between 2000 and 2021

Introduction: Chronic myeloid leukemia (CML) in children and adolescents is a rare disease with an annual incidence of one case per million. The condition is characterized by the translocation t(9;22)(q34;q11.2) resulting in a BCR-ABL1 fusion oncoprotein localized on the newly formed Philadelphia (Ph) chromosome. With the current retrospective study, we aimed to identify the clinical and biological characteristics of Belgian CML patients up to 18 years treated in Belgium between 2000 and 2021, as well as to evaluate the response to treatment, potential long-term side effects, and prognosis. Methodology: Children and adolescents up to 18 years of age treated for CML in eight Belgian pediatric hemato-oncology centers between 2000 and 2021 were included in the present study as part of an international registry study (I-CML-Ped Study). The data of the pediatric CML patients were collected in a Belgian CML registry on case report forms (CRFs) after which they were inserted into a database. IBM SPSS Statistics was used for statistical analysis of the data. Survival curves were made using the Kaplan-Meier method. Results: A total of 30 pediatric CML patients treated between 2000 and 2021 in Belgium were included for data analysis. The population consisted of 10 boys and 20 girls with a mean age of 9 years (range 1-16 years). The mean follow-up time was 99 months with a range of 8 to 247 months. The first symptoms of CML were from most to least common: asthenia, weight loss, abdominal pain, fever, and bleeding. The spleen was palpable in 22 patients with a mean of 10 cm below the costal margin (range 1-20 cm). Twenty-nine patients were in the chronic phase (CML-CP) at diagnosis, while one patient was in the blast phase (CML-BC). In the pre-TKI era (before 2004), the majority of the patients were treated with an HSCT preceded by Hydrea. After 2004, the standard first treatment was imatinib. The overall survival (OS) of all included patients was 96.7%. Conclusion: In general, the clinical and biological characteristics of the Belgian pediatric CML population are in line with the literature. Although the outcome is excellent, it is essential to consider the long-term side effects of TKI treatment and a hematopoietic stem cell transplantation (HSCT) and weigh the advantages and disadvantages of both treatments