EJC paediatric oncology最新文献

{"title":"Preclinical assessment of combined BCL-2 and MCL-1 inhibition in high-risk neuroblastoma","authors":"Lindy Vernooij ,&nbsp;Alvin Kamili ,&nbsp;Kimberley Ober ,&nbsp;Jennemiek van Arkel ,&nbsp;Lina Lankhorst ,&nbsp;Enya Vermeulen ,&nbsp;Hanin Al-Khakany ,&nbsp;Gabor Tax ,&nbsp;Marlinde L. van den Boogaard ,&nbsp;Jamie I. Fletcher ,&nbsp;Selma Eising ,&nbsp;Jan J. Molenaar ,&nbsp;M. Emmy M. Dolman","doi":"10.1016/j.ejcped.2024.100168","DOIUrl":"10.1016/j.ejcped.2024.100168","url":null,"abstract":"<div><h3>Background</h3><p>Neuroblastoma is the most common extracranial pediatric solid malignancy with high-risk patients showing survival rates less than 50 %. These tumors frequently escape apoptosis through upregulation of the anti-apoptotic protein BCL-2. Unfortunately, monotherapy with the BCL-2 inhibitor venetoclax leads to therapy-induced resistance mediated by upregulation of MCL-1, thereby indicating that tumors could be responsive to dual inhibition of BCL-2 and MCL-1.</p></div><div><h3>Methods</h3><p>In vitro efficacy of venetoclax and multiple MCL-1 inhibitors (MIK665, S63845, AMG-176, AZD-5991) was studied in neuroblastoma cell lines with BCL-2 and/or MCL-1 dependency. Synergy assays were performed to identify the MCL-1 inhibitor with best performance in combination with venetoclax, followed by examining if dual BCL-2 and MCL-1 inhibition protects against resistance. Lastly, the combination was analyzed in two patient-derived xenograft (PDX) models.</p></div><div><h3>Results</h3><p>Venetoclax showed highest efficacy in neuroblastoma cell lines with high <em>BCL-2 mRNA</em> expression, BCL-2 protein levels or BIM:BCL-2 complex formation, while MCL-1 inhibitor efficacy was best correlated with BIM:MCL-1 complex levels. Most promising anti-tumor effects were observed following combination therapy with venetoclax and MIK665. Targeting BCL-2 and MCL-1 led to strong synergy and efficacy at low concentrations, induced apoptosis and prevented resistance. PDX validation studies combining venetoclax with MIK665 showed improved responses compared to monotherapies.</p></div><div><h3>Conclusion</h3><p>Dual inhibition of BCL-2 and MCL-1 in neuroblastoma cells showed highly efficacious and synergistic responses in vitro, but only led to mild additive effects in vivo. Hence, better understanding of in vivo efficacy and side effects of this combination treatment are warranted prior to clinical translation.</p></div>","PeriodicalId":94314,"journal":{"name":"EJC paediatric oncology","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2024-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S2772610X24000278/pdfft?md5=3225d22e4f1561488932aee2da1837c1&pid=1-s2.0-S2772610X24000278-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141229220","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}

{"title":"Impact of ciprofloxacin prophylaxis on blood stream infection during early treatment phase of pediatric acute lymphoblastic leukemia: An observational cohort study","authors":"Fenna Scharloo ,&nbsp;Tom F.W. Wolfs ,&nbsp;Tjomme van der Bruggen ,&nbsp;Inge M. van der Sluis ,&nbsp;Wim J.E. Tissing ,&nbsp;Angelica M.M. de Vrankrijker","doi":"10.1016/j.ejcped.2024.100167","DOIUrl":"https://doi.org/10.1016/j.ejcped.2024.100167","url":null,"abstract":"<div><h3>Purpose</h3><p>Data on the efficacy of antibiotic prophylaxis in children with acute lymphoblastic leukemia (ALL) is scarce and recent guidelines advise against its use. This study is conducted to evaluate if the use of ciprofloxacin prophylaxis is associated with a decrease in blood stream infection (BSI) incidence in children with newly diagnosed ALL.</p></div><div><h3>Methods</h3><p>This was a retrospective, observational cohort study. Patients were newly diagnosed with ALL between 2020 and 2021 (prophylaxis group) or 2021–2022 (no prophylaxis group). Primary outcome was occurrence of BSI caused by Gram-negative pathogens or <em>Staphylococcus aureus</em> during induction or consolidation I. Secondary outcomes were Pediatric Intensive Care Unit (PICU) admission, mortality, ciprofloxacin resistance and <em>Clostridioides difficile</em>-associated diarrhea (CDAD).</p></div><div><h3>Results</h3><p>Two hundred patients were included (prophylaxis group n=94, no prophylaxis group n=106). Ciprofloxacin prophylaxis was associated with significantly lower BSI-incidence (HR 0.37; 95 % CI 0.15–0.94) There was no significant difference for BSI-related PICU admission (OR 0.37; 95 % CI 0.04–3.61), BSI-related mortality (1.1 % vs 0 %), all-cause mortality (OR 0.55; 95 % CI 0.10–3.10), and short-term resistance rates (16.0 % vs 13.0, OR 1.2; 95 % CI, 0.57–2.74) or CDAD (0 % vs 0.9 %) between the prophylaxis group and no prophylaxis group.</p></div><div><h3>Conclusion</h3><p>The use of ciprofloxacin prophylaxis was associated with a significantly lower incidence of BSI. While this finding shows the beneficial effect of ciprofloxacin prophylaxis in the first treatment phase of ALL, RCTs with a large sample size are needed, particularly to assess the effect on ciprofloxacin resistance.</p></div>","PeriodicalId":94314,"journal":{"name":"EJC paediatric oncology","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2024-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S2772610X24000266/pdfft?md5=7e0baccda14f81ca8cf9a6aac284e0e1&pid=1-s2.0-S2772610X24000266-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141313133","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}

{"title":"DICER1 syndrome and its various paediatric presentations: Case series and review of the literature","authors":"Courtney L. Willis ,&nbsp;Angela K. Lucas-Herald ,&nbsp;Chamidri Naotunna ,&nbsp;Suet Ching Chen ,&nbsp;Rosemarie Davidson ,&nbsp;Jairam Sastry ,&nbsp;Dermot Murphy ,&nbsp;M.Guftar Shaikh ,&nbsp;Milind Ronghe","doi":"10.1016/j.ejcped.2024.100164","DOIUrl":"10.1016/j.ejcped.2024.100164","url":null,"abstract":"<div><p>DICER1 syndrome is a rare tumour predisposition syndrome, associated with a range of benign and malignant tumours, which may occur during childhood. A high index of suspicion is required to ensure appropriate diagnosis and testing, with early treatment and surveillance of at-risk individuals. In this report, we present 5 patients with variants in <em>DICER1</em> identified following diagnosis of a minimally invasive thyroid follicular cell carcinoma, a pineoblastoma, a pleuropulmonary blastoma, a urethral rhabdomyosarcoma and on sibling testing. Each of these children have presented at a young age, and 2 have presented with characteristic tumours prior to the ages currently recommended for initiation of routine screening. We discuss their presentation, management and follow up, as well as a review of the current literature on each associated tumour in relation to our patients. Overall, we demonstrate that DICER1 is a heterogenous condition and that there is a need for cascade testing of family members as well as regular screening for tumour development in affected children, although consideration should be made regarding initiating this screening at an earlier age depending on clinical findings.</p></div>","PeriodicalId":94314,"journal":{"name":"EJC paediatric oncology","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2024-05-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S2772610X24000230/pdfft?md5=e4bda84b926ca8558475d0c0e65ea326&pid=1-s2.0-S2772610X24000230-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141054260","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}

{"title":"From long-term follow-up Recommendations for clinical practice to plain language summaries for childhood, adolescent, and young adult cancer survivors","authors":"Selina R. van den Oever ,&nbsp;Tessa Fuchs ,&nbsp;Gill A. Levitt ,&nbsp;Riccardo Haupt ,&nbsp;Renée L. Mulder ,&nbsp;Ana Amariutei ,&nbsp;Edit Bardi ,&nbsp;Tom Becker ,&nbsp;Morven Brown ,&nbsp;Hannah Gsell ,&nbsp;Jaap den Hartogh ,&nbsp;Samira Essiaf ,&nbsp;Monica Muraca ,&nbsp;Emma Potter ,&nbsp;Carina Schneider ,&nbsp;Elaine Sugden ,&nbsp;Zuzana Tomášiková ,&nbsp;Herma Vermeulen ,&nbsp;Leontien C.M. Kremer ,&nbsp;Roderick Skinner ,&nbsp;Helena J.H. van der Pal","doi":"10.1016/j.ejcped.2024.100165","DOIUrl":"10.1016/j.ejcped.2024.100165","url":null,"abstract":"<div><h3>Background</h3><p>Having sufficient knowledge of cancer diagnosis, treatment and late effects in survivors of childhood, adolescent, and young adult (CAYA) cancer is important for effective self-management and optimising health outcomes. Therefore, in collaboration with different stakeholders, the PanCare PLAIN Information Group converted the PanCareFollowUp Recommendations for late effects surveillance into information summaries that are Person-centred, written in Lay language, Accessible, Internationally relevant, and Navigable (PLAIN).</p></div><div><h3>Methods</h3><p>The PanCare PLAIN Information Group, comprising 21 stakeholders from seven European countries, collaborated to provide concise information for survivors and their families. The aim was to deliver PLAIN summaries that are clear and accessible for the majority of survivors, while providing links to additional sources of information. The PLAIN summaries were drafted by the PanCare PLAIN Information Group and subjected to two internal and one external consultation round, the latter involving experts, CAYA cancer survivors and parents/caregivers.</p></div><div><h3>Results</h3><p>In total, 45 PLAIN summaries were developed, each corresponding to one of the PanCareFollowUp Recommendations for late effects surveillance. The summaries provide information about late effects, personal health risks, important symptoms and signs, recommended surveillance strategies, possible referral and treatment options, and self-care.</p></div><div><h3>Conclusions</h3><p>The PLAIN summaries are meant to increase knowledge in survivors and their families, while they may also inform healthcare professionals. Along with their translations, the PLAIN summaries will be made freely available on the PanCare website, with a link provided on the European Network of Youth Cancer Survivors information platform. In addition, they will become and integral part of the Survivorship Passport.</p></div>","PeriodicalId":94314,"journal":{"name":"EJC paediatric oncology","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2024-05-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S2772610X24000242/pdfft?md5=20610c0f9bbb6513f9bdaad32f0c5b26&pid=1-s2.0-S2772610X24000242-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141042270","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}

{"title":"SIOPE and ESOP recommendations for extemporaneous compounding of oral liquid medicine formulations in paediatric oncology","authors":"Marko Otsokolhich ,&nbsp;Maxime Annereau ,&nbsp;Tiene Bauters ,&nbsp;Laszlo Horvath ,&nbsp;Chahinez Nehal ,&nbsp;Sherif Kamal ,&nbsp;Gilles Vassal ,&nbsp;Svetlana Buraja","doi":"10.1016/j.ejcped.2024.100163","DOIUrl":"10.1016/j.ejcped.2024.100163","url":null,"abstract":"<div><h3>Introduction</h3><p>Scarcity of age appropriate formulations for orally administered medicines for paediatric malignancies is a critical and ongoing issue which necessitates urgent solutions. According to JARC Survey 27 % of oral medicines were never available in child-friendly formulations (Vassal et al., 2021 [2]). Pharmacists from the European Society of Oncology Pharmacy Global (ESOP) and the European Society for Pediatric Oncology (SIOPE) have collaborated to provide a document summarising literature data on this topic and a set of practical instructions on the preparation of extemporaneous oral liquid medicines.</p></div><div><h3>Material and methods</h3><p>Literature review was conducted for the preparation of oral medicines for paediatric cancer, through Pubmed 2.0. A table was drawn up with necessary information for medicine preparation. We adapted the classification model of the molecule stability ranking of the International database of stability for injectable drugs, Stabilis® (Class A–C).</p></div><div><h3>Results</h3><p>A total of 126 articles were selected and analysed. All commercially available marketed liquid oral medications used in paediatric cancer were overviewed using globally accessible drug databases and compiled in a table with appropriate indications. Based on the literature review, 28 formulations for 13 different active ingredients for chemotherapy and 35 formulations for 16 different active ingredients for supportive therapy were compiled.</p></div><div><h3>Conclusions</h3><p>Development of child-appropriate formulations of anticancer medicines by the pharmaceutical industry should be incentivised towards marketing authorisation to enhance accessibility. The results of this study could help facilitate creation of European standards for extemporaneous preparation and persuade researchers in the field of paediatric oncology on the way forward.</p></div>","PeriodicalId":94314,"journal":{"name":"EJC paediatric oncology","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2024-04-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S2772610X24000229/pdfft?md5=414a696357874c80cf0784960c63ee11&pid=1-s2.0-S2772610X24000229-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140783566","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}

{"title":"Psychological distress in grandparents of grandchildren who survived childhood cancer − Results from the GROkids project","authors":"Cristina Priboi ,&nbsp;Anica Ilic ,&nbsp;Pauline Holmer ,&nbsp;Peter Francis Raguindin ,&nbsp;Katharina Roser ,&nbsp;Eva Maria Tinner ,&nbsp;Rebecca Baechtold ,&nbsp;Marc Ansari ,&nbsp;Manuel Diezi ,&nbsp;Elena Lemmel ,&nbsp;Freimut H. Schilling ,&nbsp;Katrin Scheinemann ,&nbsp;Gisela Michel","doi":"10.1016/j.ejcped.2024.100162","DOIUrl":"https://doi.org/10.1016/j.ejcped.2024.100162","url":null,"abstract":"<div><h3>Introduction</h3><p>Having a grandchild who survived childhood cancer might affect grandparents’ mental health. We aimed to A) describe the psychological distress of grandparents of childhood cancer survivors (CCS) and compare their distress to the Swiss general population, and B) explore the associations between the psychological distress of grandparents with person-, child-, and cancer-related characteristics.</p></div><div><h3>Methods</h3><p>This is a cross-sectional study conducted in Switzerland. Grandparents were identified from families of eligible CCS (cancer diagnosis before 18 years old; 3–10 years after diagnosis). A subsample of a representative sample for the Swiss general population was used for comparison similar in age, gender and language region. The Brief Symptom Inventory-18 (BSI-18) was administered to assess psychological distress on three domains: somatization, depression, anxiety; and a Global Severity Index [GSI]. We ran Chi-squared and t-tests to compare grandparents and comparisons, and univariable, multivariable and multilevel regressions to analyze associations.</p></div><div><h3>Results</h3><p>In total, 122 grandparents (60.7% female, mean age=72.8; SD=6.8) and 354 comparisons participated (55.4% female; mean age=65.7; SD=5.5). Grandparents reported average distress levels and their scores did not differ significantly from the comparison sample (all p&gt;.05). Grandparents with worse health perception described more psychological distress (somatization: β=6.86, p&lt;.001; depression: β=4.17 p&lt;.001; anxiety: β=5.87, p&lt;.001; GSI: β=6.30, p&lt;.001), while single grandparents experienced more depression than those in a partnership (β=-6.21, p=.013).</p></div><div><h3>Discussion</h3><p>Our findings are encouraging, showing adequate psychological health among grandparents of CCS. However, grandparents who perceived their health as poorer encounter higher levels of distress and may benefit from access to support groups and tailored informational material.</p></div>","PeriodicalId":94314,"journal":{"name":"EJC paediatric oncology","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2024-04-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S2772610X24000217/pdfft?md5=32101f34211a210be7842c8316ee21fe&pid=1-s2.0-S2772610X24000217-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140639008","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}

{"title":"The neuroblastoma tumor microenvironment: From an in-depth characterization towards novel therapies","authors":"Kevin Louault ,&nbsp;Yves A. De Clerck ,&nbsp;Isabelle Janoueix-Lerosey","doi":"10.1016/j.ejcped.2024.100161","DOIUrl":"https://doi.org/10.1016/j.ejcped.2024.100161","url":null,"abstract":"<div><p>Neuroblastoma is a cancer of the sympathetic nervous system that develops in young children, either as low-risk or high-risk disease. The tumor microenvironment (TME) is now recognized as an important player of the tumor ecosystem that may promote drug resistance and immune escape. Targeting the TME in combination with therapies directly targeting tumor cells therefore represents an interesting strategy to prevent the emergence of resistance in cancer and improve patient’s outcome. The development of such strategies however requires an in-depth understanding of the TME landscape, due to its high complexity and intra and inter-tumoral heterogeneity. Various approaches have been used in the last years to characterize the immune and non-immune cell populations present in tumors of neuroblastoma patients, both quantitatively and qualitatively, in particular with the use of single-cell transcriptomics. It is anticipated that in the near future, both genomic and TME information in tumors will contribute to a precise approach to therapy in neuroblastoma. Deciphering the mechanisms of interaction between neuroblastoma cells and stromal or immune cells in the TME is key to identify novel therapeutic combinations. Over the last decade, numerous in vitro studies and in vivo pre-clinical experiments in immune-competent and immune-deficient models have identified therapeutic approaches to circumvent drug resistance and immune escape. Some of these studies have formed the basis for early phase I and II clinical trials in children with recurrent and refractory high-risk neuroblastoma. This review summarizes recently published data on the characterization of the TME landscape in neuroblastoma and novel strategies targeting various TME cellular components, molecules and pathways activated as a result of the tumor-host interactions.</p></div>","PeriodicalId":94314,"journal":{"name":"EJC paediatric oncology","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2024-04-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S2772610X24000205/pdfft?md5=980993c02d5131b2695ba02b7b673962&pid=1-s2.0-S2772610X24000205-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140549917","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}

{"title":"Osteosarcomas in retinoblastoma-survivors. A report of 28 affected patients from the Cooperative Osteosarcoma Study Group (COSS)","authors":"Stefan S. Bielack ,&nbsp;Daniel Baumhoer ,&nbsp;Stefanie Hecker-Nolting ,&nbsp;Simone Hettmer ,&nbsp;Leo Kager ,&nbsp;Petra Ketteler ,&nbsp;Matthias Kevric ,&nbsp;Christian P. Kratz ,&nbsp;Thomas Kühne ,&nbsp;Vanessa Mettmann ,&nbsp;Markus Metzler ,&nbsp;Dirk Reinhardt ,&nbsp;Benjamin Sorg ,&nbsp;Claudia Blattmann","doi":"10.1016/j.ejcped.2024.100158","DOIUrl":"https://doi.org/10.1016/j.ejcped.2024.100158","url":null,"abstract":"<div><h3>Purpose</h3><p>Many publications address the epidemiology of secondary osteosarcomas following retinoblastoma. Treatment- and outcome-related information is, however, scarce. We used a large cooperative group’s database to study this issue.</p></div><div><h3>Patients and methods</h3><p>The database Cooperative Osteosarcoma Study Group COSS was searched for patients with osteosarcoma following a previous retinoblastoma. Patients were then analyzed for demographic factors, local/systemic treatments received, and outcomes.</p></div><div><h3>Results</h3><p>28 eligible patients were identified. Median age at retinoblastoma was .5 years, 89% occurred bilaterally. Retinoblastoma-therapy was by surgery in 26/27, radiotherapy in 26/27, chemotherapy in 10/26 (rest unknown). Osteosarcoma was diagnosed after 13.7 (3.1 – 36.1) years, extremities and head/neck affected in 14/28, each. Four/28 patients had primary metastases. Osteosarcoma treatment included chemotherapy in all cases, local therapy surgery in 27/28. Histological response was good in 9/16 evaluable cases. Surgery of all sites was macroscopically complete in 23/27 operated tumors and microscopically complete in 17/26 (1 unknown). Radiotherapy was administered to 3 craniofacial tumors. Median follow-up was 3.5 (.4 – 30.1) years from osteosarcoma diagnosis, 8/28 patients remaining event-free. Altogether, five patients suffered further secondary malignancies. Actuarial overall and event-free survival at 2 and 5 years from osteosarcoma were 73% (standard error: 8%) / 50% (10%) and 47% (10%) / 22% (9%), respectively.</p></div><div><h3>Conclusion</h3><p>This comparatively large cohort of osteosarcomas after retinoblastoma proves that the latter may be treated curatively. While their prognosis is far worse than that of primary osteosarcomas, partly due to a predilection for craniofacial involvement, selected patients may still become long-term survivors with appropriate therapies.</p></div>","PeriodicalId":94314,"journal":{"name":"EJC paediatric oncology","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2024-03-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S2772610X24000175/pdfft?md5=f181efe2921dcefac8343255b80f04b8&pid=1-s2.0-S2772610X24000175-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140342197","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}

{"title":"CAR T cells redirected to B7-H3 for pediatric solid tumors: Current status and future perspectives","authors":"Rebecca Epperly,&nbsp;Stephen Gottschalk,&nbsp;Christopher DeRenzo","doi":"10.1016/j.ejcped.2024.100160","DOIUrl":"https://doi.org/10.1016/j.ejcped.2024.100160","url":null,"abstract":"<div><p>Despite intensive therapies, pediatric patients with relapsed or refractory solid tumors have poor outcomes and need novel treatments. Immune therapies offer an alternative to conventional treatment options but require the identification of differentially expressed antigens to direct antitumor activity to sites of disease. B7-H3 (CD276) is an immune regulatory protein that is expressed in a range of malignancies and has limited expression in normal tissues. B7-H3 is highly expressed in pediatric solid tumors including osteosarcoma, rhabdomyosarcoma, Ewing sarcoma, Wilms tumor, neuroblastoma, and many rare tumors. In this article we review B7-H3-targeted chimeric antigen receptor (B7-H3-CAR) T cell therapies for pediatric solid tumors, reporting preclinical development strategies and outlining the landscape of active pediatric clinical trials. We identify challenges to the success of CAR T cell therapy for solid tumors including localizing to and penetrating solid tumor sites, evading the hostile tumor microenvironment, supporting T cell expansion and persistence, and avoiding intrinsic tumor resistance. We highlight strategies to overcome these challenges and enhance the effect of B7-H3-CAR T cells, including advanced CAR T cell design and incorporation of combination therapies.</p></div>","PeriodicalId":94314,"journal":{"name":"EJC paediatric oncology","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2024-03-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S2772610X24000199/pdfft?md5=c747012f8719471c331ca17f416f2eef&pid=1-s2.0-S2772610X24000199-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140188205","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}

{"title":"A narrative review of 35 years of meta-[131I]iodobenzylguanidine therapy in neuroblastoma","authors":"Atia Samim ,&nbsp;Gitta Bleeker ,&nbsp;Kathelijne C.J.M. Kraal ,&nbsp;Max M. van Noesel ,&nbsp;Bart de Keizer ,&nbsp;Godelieve A.M. Tytgat","doi":"10.1016/j.ejcped.2024.100159","DOIUrl":"https://doi.org/10.1016/j.ejcped.2024.100159","url":null,"abstract":"<div><p>Neuroblastoma is the most common extracranial solid malignancy of childhood. Approximately half of the patients have high-risk neuroblastoma (HR-NBL), typically presenting as widespread metastatic disease at diagnosis. Despite aggressive multimodality treatment, patients with HR-NBL have a long-term survival rate of below 50%. This is primarily due to frequent progression and relapse, which often proves to be therapy resistant. To overcome therapy resistance in HR-NBL, researchers are exploring diverse treatment strategies, including radionuclide therapy. Radiolabelled meta-iodobenzylguanidine (mIBG) has served as a theranostic (<u>thera</u>peutic and diag<u>nostic</u>) radiopharmaceutical in the field of neuroblastoma for several decades. [¹²³I]mIBG scintigraphy is recognized as the international standard to evaluate disease dissemination at diagnosis and to monitor treatment response. In contrast, the role of [¹³¹I]mIBG therapy in the management of neuroblastoma is less clear. Over the past 35 years, [¹³¹I]mIBG therapy has been studied in more than 1500 patients with neuroblastoma. In initial studies, [¹³¹I]mIBG monotherapy was applied as a second-line treatment in patients who failed first-line treatment. In current applications, [¹³¹I]mIBG therapy is combined with chemotherapy, radiosensitizers, and/or immunotherapy, and is increasingly integrated in the first-line treatment of HR-NBL. This narrative review provides an overview of the literature on [¹³¹I]mIBG therapy in HR-NBL. Studies show that [¹³¹I]mIBG therapy can be an effective treatment in one-third of patients with acceptable toxicity. Further investigations, particularly randomized controlled trials, are needed to determine the efficacy and optimal use of [¹³¹I]mIBG therapy in HR-NBL.</p></div>","PeriodicalId":94314,"journal":{"name":"EJC paediatric oncology","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2024-03-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S2772610X24000187/pdfft?md5=3bf5965d3b5582c858f1f73cd517bf67&pid=1-s2.0-S2772610X24000187-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140190891","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}