EJC paediatric oncology最新文献

Approved medicines for paediatric solid tumours in Europe: Lessons from the life cycle of a paediatric investigation plan 欧洲儿科实体瘤获批药物：儿科调查计划生命周期的经验教训

EJC paediatric oncology Pub Date : 2024-09-08 DOI: 10.1016/j.ejcped.2024.100190

{"title":"Approved medicines for paediatric solid tumours in Europe: Lessons from the life cycle of a paediatric investigation plan","authors":"","doi":"10.1016/j.ejcped.2024.100190","DOIUrl":"10.1016/j.ejcped.2024.100190","url":null,"abstract":"<div><h3>Background</h3><p>Despite the positive changes brought by the Paediatric Regulation in the European Union (EU) in 2007, drug development in children remains challenging.</p></div><div><h3>Methods</h3><p>To better understand the issues encountered to reach an authorisation for paediatric patients, we reviewed the pathway of the 11 Paediatric Investigational Plans (PIPs) with indications targeting paediatric solid tumours granted by the Committee for Medicinal Products for Human Use (CHMP) between 2007 and 2022.</p></div><div><h3>Results</h3><p>On average 5,5 years were necessary to reach approval after a PIP was agreed. All the PIPs underwent at least one modification (median 3 modifications per PIP). The use of single arm trials, in the context of refractory/relapsed disease in absence of standard of care treatment, was supportive for granting a paediatric indication in the majority of the cases. In 6 out of 11 approved products, extrapolation from adults was used. For 2/11 the approval focused on an older population first compared to the initial age group agreed in the PIP due to the development of a suitable formulation for younger children still ongoing at the time of first approval. Scientific advice sought on paediatric development use of extrapolation from adults, major objections raised by CHMP and post-marketing requirements were examined.</p></div><div><h3>Conclusion</h3><p>Analysing the process necessary to reach an authorisation for paediatric patients, we highlight the major challenges faced in the paediatric approval process and the positive examples of successful drug development that reached final approval. Our analysis is expected to provide useful insights to drug developers, investigators and regulators.</p></div>","PeriodicalId":94314,"journal":{"name":"EJC paediatric oncology","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2024-09-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S2772610X24000503/pdfft?md5=0a6abf9fea2a487ca1cd504fccb08040&pid=1-s2.0-S2772610X24000503-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142240032","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Common core variables for childhood cancer data integration 儿童癌症数据整合的共同核心变量

EJC paediatric oncology Pub Date : 2024-08-31 DOI: 10.1016/j.ejcped.2024.100186

{"title":"Common core variables for childhood cancer data integration","authors":"","doi":"10.1016/j.ejcped.2024.100186","DOIUrl":"10.1016/j.ejcped.2024.100186","url":null,"abstract":"<div><h3>Introduction</h3><p>Data-driven research has improved paediatric cancer outcomes for children. However, challenges in sharing data between institutions prevent the use of artificial intelligence (AI) to address substantial unmet needs in children diagnosed with cancer. Harmonising collected data can enable the application of AI for a greater understanding of paediatric cancers. The main goal of the paper was to analyse the currently used childhood cancer databases to identify a core of variables able to capture the most relevant data on the diagnosis and treatment of children and adolescents with cancer.</p></div><div><h3>Methods</h3><p>We arbitrarily identified different types of existing databases dedicated to collecting data of patients with solid tumours, Umbrella, FAR-RMS; PARTNER; ERN PAEDCAN Registry; INSTRUCT and INRG; the common data elements for Rare Disease by Joint Research Centre. The different elements of the CRFs were analysed and ranked “essential” and “good to have”. Domains that included a group of variables structurally connected were identified. Each variable was defined by name, data type, description, and permissible values.</p></div><div><h3>Results</h3><p>We identified six structural domains: Patient registration, Personal information, Disease History, Diagnosis, Treatment, and Follow-up and Events. For each of them, “essential” and “good to have” variables were defined.</p></div><div><h3>Discussion</h3><p>Data harmonisation is essential for enhancing integration and comparability in research. By standardizing data formats and variables, researchers can facilitate data sharing, collaboration, and analysis across multiple studies and datasets. Embracing data harmonization practices will advance application of AI, scientific knowledge, improve research reproducibility, and contribute to evidence-based decision-making in various fields.</p></div>","PeriodicalId":94314,"journal":{"name":"EJC paediatric oncology","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2024-08-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S2772610X24000461/pdfft?md5=fe6d34dd8fea9f6dd2eb50fc1c17e460&pid=1-s2.0-S2772610X24000461-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142094931","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Cross-border access to early phase clinical trials for children with cancer in the Nordic region 北欧地区儿童癌症早期临床试验的跨境准入问题

EJC paediatric oncology Pub Date : 2024-08-30 DOI: 10.1016/j.ejcped.2024.100188

{"title":"Cross-border access to early phase clinical trials for children with cancer in the Nordic region","authors":"","doi":"10.1016/j.ejcped.2024.100188","DOIUrl":"10.1016/j.ejcped.2024.100188","url":null,"abstract":"<div><h3>Introduction</h3><p>As 15 % of childhood cancers are still incurable, early phase clinical trials are essential in developing better therapies for children with cancer. Accessing relevant trials can be challenging, exacerbated by increasingly specialized therapies which are not available in every country. Copenhagen houses the main early phase trial center for children with cancer in the Nordic region, with about half of trial participants coming from abroad. We explored factors facilitating cross-border access to early phase pediatric cancer trials in Copenhagen.</p></div><div><h3>Methods and materials</h3><p>Interviews were conducted with 11 family members from five families and nineteen healthcare providers on socio-cultural aspects of traveling for the trial. A thematic analysis was conducted.</p></div><div><h3>Results</h3><p>Three major themes were identified: proximity to a trial center, facilitation of referral and logistics, and families’ and providers’ perceptions. Both geographic proximity and socio-cultural proximity facilitated access. Provider networks facilitated referrals and sponsors paid for travel, improving feasibility for families. Finally, families’ feelings of hope and providers’ positive perceptions of experimental therapy also promoted access to early phase trials.</p></div><div><h3>Conclusions</h3><p>Our findings highlight the importance of fully supporting families through logistics, expenses, and challenges associated with traveling to a clinical trial, the value of robust provider networks in facilitating referrals, and the need for awareness of potential socio-cultural bias in referring patients. While factors like geography and attitude also mitigate access, many barriers can be overcome by comprehensive support for families, improving access to early phase trials for children with cancer.</p></div>","PeriodicalId":94314,"journal":{"name":"EJC paediatric oncology","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2024-08-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S2772610X24000485/pdfft?md5=0db74d469eefaf7248a98a97b92e4013&pid=1-s2.0-S2772610X24000485-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142136387","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Multimodality imaging of bone marrow involvement in paediatric oncology 儿科肿瘤学中骨髓受累的多模式成像

EJC paediatric oncology Pub Date : 2024-08-13 DOI: 10.1016/j.ejcped.2024.100185

引用次数: 0

Cell state plasticity in neuroblastoma 神经母细胞瘤的细胞状态可塑性

EJC paediatric oncology Pub Date : 2024-08-02 DOI: 10.1016/j.ejcped.2024.100184

引用次数: 0

Re-irradiation for progressive Diffuse Intrinsic Pontine Glioma (DIPG): The Spanish experience 对进展期弥漫性桥脑胶质瘤（DIPG）进行再放射治疗：西班牙的经验

EJC paediatric oncology Pub Date : 2024-07-30 DOI: 10.1016/j.ejcped.2024.100183

{"title":"Re-irradiation for progressive Diffuse Intrinsic Pontine Glioma (DIPG): The Spanish experience","authors":"","doi":"10.1016/j.ejcped.2024.100183","DOIUrl":"10.1016/j.ejcped.2024.100183","url":null,"abstract":"<div><h3>Introduction</h3><p>Diffuse intrinsic pontine glioma (DIPG) is the most common malignant brainstem tumour in children. Despite advances in understanding its biology, current treatments have shown minimal impact on overall survival in this fatal disease. Focal radiotherapy (RT) is the only treatment proven to improve symptoms and extend progression-free survival. Albeit palliative, re-irradiation (rRT) has emerged as the best alternative for progressive disease. This study presents the Spanish experience with re-irradiation in DIPG.</p></div><div><h3>Results</h3><p>Between April 2015 and December 2023, 44 paediatric patients with progressive DIPG underwent rRT in 16 Spanish institutions. Median time from diagnosis to progression was 9.9 months (range, 4.2–24.3 months). Median dose of rRT was 20 Gy (range, 18–40 Gy) in 2 Gy fractions (range, 1.3–4 Gy). Twenty-two patients (50 %) received other treatments besides RT. Clinical improvement was seen in 77.3 %, and radiological improvement in 60 %. Treatment was well tolerated (1 case toxicity >grade 2 related to rRT). Median overall survival was 15.5 months (range, 8.2–63.2 months), with a median time from rRT to death of 4.2 months (range, 0.6–10.3 months). Longer time between diagnosis and rRT (>10 months) and dose of rRT >20 Gy were statistically significantly correlated with better overall survival. There was no survival benefit in patients receiving additional treatments.</p></div><div><h3>Conclusions</h3><p>Re-irradiation is safe and effective in progressive DIPG patients, not only improving symptoms but also prolonging survival. However, the ideal candidates for rRT remain undefined, as well as the best irradiation scheme. Prospective studies are needed.</p></div>","PeriodicalId":94314,"journal":{"name":"EJC paediatric oncology","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2024-07-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S2772610X24000436/pdfft?md5=fcd1dc01981db6b28e802799b38274bd&pid=1-s2.0-S2772610X24000436-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141952191","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

MYCN in neuroblastoma: The kings' new clothes and drugs 神经母细胞瘤中的 MYCN：国王的新衣和药物

EJC paediatric oncology Pub Date : 2024-07-27 DOI: 10.1016/j.ejcped.2024.100182

{"title":"MYCN in neuroblastoma: The kings' new clothes and drugs","authors":"","doi":"10.1016/j.ejcped.2024.100182","DOIUrl":"10.1016/j.ejcped.2024.100182","url":null,"abstract":"<div><p>Deregulated levels of the MYCN oncogene contribute to the tumorigenesis of several human tumors including neuroblastoma. <em>MYCN</em> amplification classifies neuroendocrine tumors as high-risk and as a consequence is an unfavorable prognostic factor. MYCN has long been primarily described as a transcription factor, which binds to active promoters after heterodimerizing with MAX and directly regulates gene expression programs. New findings show that MYC proteins have novel oncogenic functions that are tumor-promoting and go beyond the regulation of gene expression. This review describes how MYCN continuously drives tumor progression by forming various protein complexes, for example to resolve torsional stress, coordinate transcription and replication, repair DNA damage and regulate R-loops. Interfering with the described processes as well as interfering with MYCN chromatin binding emerge as novel treatment strategies to indirectly target the oncoprotein. Furthermore, we describe the role of MYCN in metabolism and we review how these newly described functions of MYCN could be used as vulnerabilities for MYCN-driven tumors. Recent studies show that MYC proteins are capable of multimerizing at sites of genomic instability to protect cancer cells from stress. Additionally, MYCN can bind aberrant RNA transcripts, another feature to enhance the stress resilience of cancer cells, once again highlighting the oncogenic potential of MYC. Taken together, we show that the diverse functions of MYCN depend on its temporal and spatial dynamic interactome, making those interaction partners and functions crucial factors in the treatment of MYCN-related cancer.</p></div>","PeriodicalId":94314,"journal":{"name":"EJC paediatric oncology","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2024-07-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S2772610X24000424/pdfft?md5=a6328b571860cad1d591dd9876f1d23a&pid=1-s2.0-S2772610X24000424-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141847252","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Robotics and 3D modeling for precision surgery in pediatric oncology 机器人技术和三维建模用于小儿肿瘤学的精准手术

EJC paediatric oncology Pub Date : 2024-07-20 DOI: 10.1016/j.ejcped.2024.100181

{"title":"Robotics and 3D modeling for precision surgery in pediatric oncology","authors":"","doi":"10.1016/j.ejcped.2024.100181","DOIUrl":"10.1016/j.ejcped.2024.100181","url":null,"abstract":"<div><p>In an attempt to minimize surgical trauma in already vulnerable patients, pediatric surgeons are increasingly using minimally invasive surgery in surgical oncology, with similar outcomes as open surgery. In addition to its technical benefits, robotic surgery allows integration of technological enhancements, such as artificial-intelligence-based software or tri-dimensional (3D) modeling, into the operating room. In this article, we report our experience in robotic-assisted surgery for the resection of pediatric tumors and present current developments in 3D modeling applied to pelvic tumors. Since 2016, 149 oncology cases have been undertaken using the robotic approach. Neuroblastic tumors account for the most part, with a median hospital stay of two days [1–7 days] and very few intraoperative events. The use of robotics was mainly extended to renal tumors (predominantly Wilms tumors) and endocrine tumors, but was found of particular interest for pelvic tumors. Our experience led us to publish a first set of guidelines on robotic surgical oncology, focusing on its apparent contraindications. 3D models derived from preoperative magnetic resonance imaging have been developed for more than 150 patients with solid tumors, but the pelvic area was made a key focus because of its anatomical complexity. In addition to their educational benefits, some of these 3D models were integrated into the robotic console as a surgical aid and proved invaluable for difficult dissections or nerve plexus preservation. As evidenced by the development of robotics and 3D modeling, pediatric oncology is leaning toward ultra-precise surgical resection tailored to the patient and the tumor.</p></div>","PeriodicalId":94314,"journal":{"name":"EJC paediatric oncology","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2024-07-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S2772610X24000412/pdfft?md5=2c14fac63f4ef10577bd0b7fa73a3acf&pid=1-s2.0-S2772610X24000412-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141840541","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Erratum regarding missing Ethical statements in previously published articles 关于以前发表的文章中缺少伦理声明的更正

EJC paediatric oncology Pub Date : 2024-07-18 DOI: 10.1016/j.ejcped.2024.100180

引用次数: 0

GD2 targeting CAR T cells for neuroblastoma 治疗神经母细胞瘤的 GD2 靶向 CAR T 细胞

EJC paediatric oncology Pub Date : 2024-07-10 DOI: 10.1016/j.ejcped.2024.100179

引用次数: 0