Pub Date : 2025-03-28DOI: 10.1016/j.ejcped.2025.100228
Anne van Kuijk , Pamela Kearns , G.A. Amos Burke
Paediatric diffuse large B-cell lymphoma (DLBCL) is a rare but aggressive form of non-Hodgkin lymphoma. Although rituximab has significantly improved outcomes in both adult and paediatric patients, challenges remain for those who relapse or are resistant to the initial treatment. This review examines recent clinical trials investigating various immunotherapies for relapsed or refractory (R/R) paediatric DLBCL, including immunomodulatory agents, monoclonal antibodies, antibody-drug conjugates, bispecific antibodies, checkpoint inhibitors, and chimeric antigen receptor (CAR) T-cell therapy. A comprehensive search identified forty-eight relevant trials with significant focus on CAR-T cell therapy. This review highlights the potential benefits of these novel therapies for improving the survival rate and quality of life of paediatric patients. However, it also underscores the need for increased international collaboration and paediatric-specific research to address the unique challenges in treating this vulnerable population. Future directions include the integration of personalised medicine and development of chemotherapy-free regimens.
{"title":"Immunotherapy for paediatric diffuse large B-cell lymphoma: A review of current clinical trials and future directions","authors":"Anne van Kuijk , Pamela Kearns , G.A. Amos Burke","doi":"10.1016/j.ejcped.2025.100228","DOIUrl":"10.1016/j.ejcped.2025.100228","url":null,"abstract":"<div><div>Paediatric diffuse large B-cell lymphoma (DLBCL) is a rare but aggressive form of non-Hodgkin lymphoma. Although rituximab has significantly improved outcomes in both adult and paediatric patients, challenges remain for those who relapse or are resistant to the initial treatment. This review examines recent clinical trials investigating various immunotherapies for relapsed or refractory (R/R) paediatric DLBCL, including immunomodulatory agents, monoclonal antibodies, antibody-drug conjugates, bispecific antibodies, checkpoint inhibitors, and chimeric antigen receptor (CAR) T-cell therapy. A comprehensive search identified forty-eight relevant trials with significant focus on CAR-T cell therapy. This review highlights the potential benefits of these novel therapies for improving the survival rate and quality of life of paediatric patients. However, it also underscores the need for increased international collaboration and paediatric-specific research to address the unique challenges in treating this vulnerable population. Future directions include the integration of personalised medicine and development of chemotherapy-free regimens.</div></div>","PeriodicalId":94314,"journal":{"name":"EJC paediatric oncology","volume":"5 ","pages":"Article 100228"},"PeriodicalIF":0.0,"publicationDate":"2025-03-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143760069","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}
Pub Date : 2025-03-18DOI: 10.1016/j.ejcped.2025.100226
David King , Brigitte Bison , Ofelia Cruz , Claudia C. Faria , Iwona Filipek , Jonathan L. Finlay , Miklós Garami , Uwe R. Kordes , Ulrike Löbel , Jilly Maclean , Torben Stamm Mikkelsen , Denise Obrecht-Sturm , Guirish Solanki , Christian Thomas , Beate Timmerman , Michal Zapotocky , Jenny Adamski
Choroid plexus tumours (CPT) are rare epithelial brain tumours that primarily affect very young children. They can be classified as benign choroid plexus papilloma (CPP, WHO grade 1), intermediate grade atypical choroid plexus papilloma (aCPP, WHO grade 2) or highly malignant choroid plexus carcinoma (CPC, WHO grade 3). Treatment is dependent on tumour grade, surgical resection, the age of the child and somatic and germline TP53 mutational status. CPP and aCPP have a good prognosis and are frequently curable with surgery alone. In contrast, the prognosis in CPC is often poor, despite intensive multimodal treatment with surgery, chemotherapy and radiotherapy. Management is complicated by the increased incidence of germline TP53 mutations and cancer predisposition (Li-Fraumeni syndrome), especially in CPC, whilst the rarity of the diagnosis means there are a lack of robust clinical data on which to base treatment decisions. Studies generally comprise of retrospective, single arm and centre trials or case series, and patient numbers are small leading to conflicting results that are difficult to interpret. Standardised treatment protocols have historically been lacking.
The aim of this document is to provide a reference standard for the treatment of CPT on behalf of the European Society for Paediatric Oncology (SIOPE). We review the previously published literature and provide consensus key recommendations for the management of CPP, aCPP and CPC including surgical approaches and when appropriate, the role of chemotherapy and radiotherapy. Suggested follow-up and possible relapse strategies are also suggested.
{"title":"An overview of the European standard clinical practice recommendations for choroid plexus tumours","authors":"David King , Brigitte Bison , Ofelia Cruz , Claudia C. Faria , Iwona Filipek , Jonathan L. Finlay , Miklós Garami , Uwe R. Kordes , Ulrike Löbel , Jilly Maclean , Torben Stamm Mikkelsen , Denise Obrecht-Sturm , Guirish Solanki , Christian Thomas , Beate Timmerman , Michal Zapotocky , Jenny Adamski","doi":"10.1016/j.ejcped.2025.100226","DOIUrl":"10.1016/j.ejcped.2025.100226","url":null,"abstract":"<div><div>Choroid plexus tumours (CPT) are rare epithelial brain tumours that primarily affect very young children. They can be classified as benign choroid plexus papilloma (CPP, WHO grade 1), intermediate grade atypical choroid plexus papilloma (aCPP, WHO grade 2) or highly malignant choroid plexus carcinoma (CPC, WHO grade 3). Treatment is dependent on tumour grade, surgical resection, the age of the child and somatic and germline <em>TP53</em> mutational status. CPP and aCPP have a good prognosis and are frequently curable with surgery alone. In contrast, the prognosis in CPC is often poor, despite intensive multimodal treatment with surgery, chemotherapy and radiotherapy. Management is complicated by the increased incidence of germline <em>TP53</em> mutations and cancer predisposition (Li-Fraumeni syndrome), especially in CPC, whilst the rarity of the diagnosis means there are a lack of robust clinical data on which to base treatment decisions. Studies generally comprise of retrospective, single arm and centre trials or case series, and patient numbers are small leading to conflicting results that are difficult to interpret. Standardised treatment protocols have historically been lacking.</div><div>The aim of this document is to provide a reference standard for the treatment of CPT on behalf of the European Society for Paediatric Oncology (SIOPE). We review the previously published literature and provide consensus key recommendations for the management of CPP, aCPP and CPC including surgical approaches and when appropriate, the role of chemotherapy and radiotherapy. Suggested follow-up and possible relapse strategies are also suggested.</div></div>","PeriodicalId":94314,"journal":{"name":"EJC paediatric oncology","volume":"5 ","pages":"Article 100226"},"PeriodicalIF":0.0,"publicationDate":"2025-03-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143687632","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}
Pub Date : 2025-03-04DOI: 10.1016/j.ejcped.2025.100222
Bernice LZ Oh , Stephen P. Hunger , Allen EJ Yeoh , Shawn HR Lee
Childhood acute lymphoblastic leukemia (ALL) in the contemporary era of intensive chemotherapy is highly curable, but is associated with a plethora of toxicities, with persistent disparities in survival outcomes globally especially in low-middle income countries (LMIC). Because of limited supportive care in LMIC, treatment-related morbidity and mortality may be a more critical treatment factor than relapse. Therefore, the next frontier in childhood ALL is to cure low-risk ALL with as minimal therapy as possible. Here, we discuss how to identify the subset of low-risk patients for whom this is possible, along with the components of deintensification strategies across several regimens in recent clinical trials for low-risk ALL. In treating low-risk childhood ALL, the key is accurately identifying this curable subset. NCI standard-risk criteria at diagnosis (age 1–10 years, WBC < 50,000/uL) remains an effective cornerstone of stratification. Other favorable features such as identifying low risk genetics (ETV6::RUNX1, hyperdiploidy), early peripheral blood and bone marrow responses, and simplified flow MRD at the end of induction can be added depending on resources to enhance stratification. A reduced intensity induction particularly through anthracycline-free induction, allows early marrow recovery and reduces the need for intensive supportive care. Other key effective deintensification strategies in low-toxicity protocols include: replacing high-dose with low-dose escalating methotrexate; judicious or even omission of anthracyclines throughout therapy; non-augmentation of consolidation therapy; reducing or even omitting delayed intensification; decreasing thiopurine or methotrexate doses during maintenance; and lowering intensity of steroid pulses during maintenance. Future directions include potential implementation of immunotherapy upfront to low-risk ALL, which may allow for even further reducing toxic chemotherapy or treatment duration. Overall, the first effective step in achieving global ALL cure is to focus on curing low-risk ALL through as minimal therapy as possible.
{"title":"Curing using the minimal – Strategies for treatment reduction in childhood acute lymphoblastic leukemia","authors":"Bernice LZ Oh , Stephen P. Hunger , Allen EJ Yeoh , Shawn HR Lee","doi":"10.1016/j.ejcped.2025.100222","DOIUrl":"10.1016/j.ejcped.2025.100222","url":null,"abstract":"<div><div>Childhood acute lymphoblastic leukemia (ALL) in the contemporary era of intensive chemotherapy is highly curable, but is associated with a plethora of toxicities, with persistent disparities in survival outcomes globally especially in low-middle income countries (LMIC). Because of limited supportive care in LMIC, treatment-related morbidity and mortality may be a more critical treatment factor than relapse. Therefore, the next frontier in childhood ALL is to cure low-risk ALL with as minimal therapy as possible. Here, we discuss how to identify the subset of low-risk patients for whom this is possible, along with the components of deintensification strategies across several regimens in recent clinical trials for low-risk ALL. In treating low-risk childhood ALL, the key is accurately identifying this curable subset. NCI standard-risk criteria at diagnosis (age 1–10 years, WBC < 50,000/uL) remains an effective cornerstone of stratification. Other favorable features such as identifying low risk genetics (<em>ETV6</em>::<em>RUNX1</em>, hyperdiploidy), early peripheral blood and bone marrow responses, and simplified flow MRD at the end of induction can be added depending on resources to enhance stratification. A reduced intensity induction particularly through anthracycline-free induction, allows early marrow recovery and reduces the need for intensive supportive care. Other key effective deintensification strategies in low-toxicity protocols include: replacing high-dose with low-dose escalating methotrexate; judicious or even omission of anthracyclines throughout therapy; non-augmentation of consolidation therapy; reducing or even omitting delayed intensification; decreasing thiopurine or methotrexate doses during maintenance; and lowering intensity of steroid pulses during maintenance. Future directions include potential implementation of immunotherapy upfront to low-risk ALL, which may allow for even further reducing toxic chemotherapy or treatment duration. Overall, the first effective step in achieving global ALL cure is to focus on curing low-risk ALL through as minimal therapy as possible.</div></div>","PeriodicalId":94314,"journal":{"name":"EJC paediatric oncology","volume":"5 ","pages":"Article 100222"},"PeriodicalIF":0.0,"publicationDate":"2025-03-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143579539","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}
Pub Date : 2025-03-01DOI: 10.1016/j.ejcped.2025.100225
Miguel Vieira Martins , Anna Sofie Buhl Rasmussen , Jesper Heldrup , Linea Natalie Toksvang , Marianne Ifversen , Stine Nygaard Nielsen , Kjeld Schmiegelow , Inge Margriet van der Sluis
Treatment regimens for childhood acute lymphoblastic leukemia have developed steadily over the last decades, significantly improving patient outcomes. This has been achieved mainly by intensifying therapy, which also increased the risk of associated toxicity. To address this issue, therapeutic drug monitoring (TDM) has been introduced in clinical research and, for certain chemotherapeutic agents, as standard of care in protocols like the ALLTogether1. The goal of TDM is to optimize delivery of a given cytotoxic drug, while minimizing the risk of toxicity. Notwithstanding, only a subset of drugs included in the backbone of ALL treatment will be eligible for TDM, since specific pharmacokinetic and pharmacodynamic properties need to apply. Despite the recent rise of innovative therapies like immunotherapy, cytotoxic drugs remain a core component of ALL treatment, making the application of TDM crucial for improving patient outcomes. Among these chemotherapeutic agents, we focus on the monitoring of asparaginase, high-dose methotrexate, 6-mercaptopurine and low dose methotrexate in maintenance therapy, tyrosine kinase inhibitors and busulfan, in order to enhance clinical effectiveness. This narrative review further explains how TDM for these drugs should be conducted and offers practical recommendations for managing them in childhood ALL treatment. Moreover, ongoing research in TDM will allow for more personalized therapy delivery in frontline strategies, while optimizing care with lesser toxicity burden for patients.
{"title":"Therapeutic drug monitoring in the treatment of childhood acute lymphoblastic leukemia – A practical guideline","authors":"Miguel Vieira Martins , Anna Sofie Buhl Rasmussen , Jesper Heldrup , Linea Natalie Toksvang , Marianne Ifversen , Stine Nygaard Nielsen , Kjeld Schmiegelow , Inge Margriet van der Sluis","doi":"10.1016/j.ejcped.2025.100225","DOIUrl":"10.1016/j.ejcped.2025.100225","url":null,"abstract":"<div><div>Treatment regimens for childhood acute lymphoblastic leukemia have developed steadily over the last decades, significantly improving patient outcomes. This has been achieved mainly by intensifying therapy, which also increased the risk of associated toxicity. To address this issue, therapeutic drug monitoring (TDM) has been introduced in clinical research and, for certain chemotherapeutic agents, as standard of care in protocols like the <em>ALLTogether1</em>. The goal of TDM is to optimize delivery of a given cytotoxic drug, while minimizing the risk of toxicity. Notwithstanding, only a subset of drugs included in the backbone of ALL treatment will be eligible for TDM, since specific pharmacokinetic and pharmacodynamic properties need to apply. Despite the recent rise of innovative therapies like immunotherapy, cytotoxic drugs remain a core component of ALL treatment, making the application of TDM crucial for improving patient outcomes. Among these chemotherapeutic agents, we focus on the monitoring of asparaginase, high-dose methotrexate, 6-mercaptopurine and low dose methotrexate in maintenance therapy, tyrosine kinase inhibitors and busulfan, in order to enhance clinical effectiveness. This narrative review further explains how TDM for these drugs should be conducted and offers practical recommendations for managing them in childhood ALL treatment. Moreover, ongoing research in TDM will allow for more personalized therapy delivery in frontline strategies, while optimizing care with lesser toxicity burden for patients.</div></div>","PeriodicalId":94314,"journal":{"name":"EJC paediatric oncology","volume":"5 ","pages":"Article 100225"},"PeriodicalIF":0.0,"publicationDate":"2025-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143548379","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}
Pub Date : 2025-03-01DOI: 10.1016/j.ejcped.2025.100224
Logan G. Spector, Erin L. Marcotte
{"title":"Screening for childhood cancer: Several devils in the details","authors":"Logan G. Spector, Erin L. Marcotte","doi":"10.1016/j.ejcped.2025.100224","DOIUrl":"10.1016/j.ejcped.2025.100224","url":null,"abstract":"","PeriodicalId":94314,"journal":{"name":"EJC paediatric oncology","volume":"5 ","pages":"Article 100224"},"PeriodicalIF":0.0,"publicationDate":"2025-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143548378","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}
Pub Date : 2025-02-25DOI: 10.1016/j.ejcped.2025.100223
Naomi Michels , Jade Admiraal , Aurélie Boeree , Edwin Sonneveld , Anthony V. Moorman , Gabriele Escherich , Rosemary Sutton , H. Berna Beverloo , Rob Pieters , C. Michel Zwaan , Monique L. den Boer , Judith M. Boer
Background
The IGH locus is susceptible to translocations or insertions that contribute to B-cell precursor acute lymphoblastic leukemia (ALL) by ectopic or enhanced expression of a gene relocated to the IGH enhancer. The frequency of IGH rearrangements is relatively high in Down syndrome (DS) ALL. IGH rearrangements can be cryptic and might not be detected as a chimeric transcript, hence, their frequency, partner genes and prognostic value are largely unknown.
Methods
We performed RNA-sequencing and IGH break-apart fluorescent in-situ hybridization (FISH) to determine the genetic and clinical characteristics of IGH rearrangements in 50 DS ALL patients.
Results
We identified 10 patients with a chimeric IGH transcript and another 22 IGH-rearranged patients solely by FISH. The IGH rearrangement was clonal (≥ 50 % of leukemic cells) in 11 cases and subclonal (10–50 % of cells) in 21 cases. Almost one-third of the subclonal IGH rearrangements co-occurred with known oncogenic driver aberration. The partner gene was identified in 16 cases and the most frequent partners were CEBPD (n = 6) and CRLF2 (n = 4). A trend towards a worse event-free survival was seen for DS ALL patients with a clonal IGH rearrangement (clonal: HR 3.34, p = 0.053; subclonal: HR 1.80, p = 0.31) compared with DS ALL patients without an IGH rearrangement.
Conclusion
By combining RNA-sequencing and FISH, we identified IGH rearrangements in 64 % (n = 32) of DS ALL. A clonal IGH rearrangement (22 %) may point to an unfavorable outcome in DS ALL.
{"title":"IGH rearrangements in Down syndrome acute lymphoblastic leukemia","authors":"Naomi Michels , Jade Admiraal , Aurélie Boeree , Edwin Sonneveld , Anthony V. Moorman , Gabriele Escherich , Rosemary Sutton , H. Berna Beverloo , Rob Pieters , C. Michel Zwaan , Monique L. den Boer , Judith M. Boer","doi":"10.1016/j.ejcped.2025.100223","DOIUrl":"10.1016/j.ejcped.2025.100223","url":null,"abstract":"<div><h3>Background</h3><div>The <em>IGH</em> locus is susceptible to translocations or insertions that contribute to B-cell precursor acute lymphoblastic leukemia (ALL) by ectopic or enhanced expression of a gene relocated to the <em>IGH</em> enhancer. The frequency of <em>IGH</em> rearrangements is relatively high in Down syndrome (DS) ALL. <em>IGH</em> rearrangements can be cryptic and might not be detected as a chimeric transcript, hence, their frequency, partner genes and prognostic value are largely unknown.</div></div><div><h3>Methods</h3><div>We performed RNA-sequencing and <em>IGH</em> break-apart fluorescent in-situ hybridization (FISH) to determine the genetic and clinical characteristics of <em>IGH</em> rearrangements in 50 DS ALL patients.</div></div><div><h3>Results</h3><div>We identified 10 patients with a chimeric <em>IGH</em> transcript and another 22 <em>IGH-</em>rearranged patients solely by FISH. The <em>IGH</em> rearrangement was clonal (≥ 50 % of leukemic cells) in 11 cases and subclonal (10–50 % of cells) in 21 cases. Almost one-third of the subclonal <em>IGH</em> rearrangements co-occurred with known oncogenic driver aberration. The partner gene was identified in 16 cases and the most frequent partners were <em>CEBPD</em> (n = 6) and <em>CRLF2</em> (n = 4). A trend towards a worse event-free survival was seen for DS ALL patients with a clonal <em>IGH</em> rearrangement (clonal: HR 3.34, p = 0.053; subclonal: HR 1.80, p = 0.31) compared with DS ALL patients without an <em>IGH</em> rearrangement.</div></div><div><h3>Conclusion</h3><div>By combining RNA-sequencing and FISH, we identified <em>IGH</em> rearrangements in 64 % (n = 32) of DS ALL. A clonal <em>IGH</em> rearrangement (22 %) may point to an unfavorable outcome in DS ALL.</div></div>","PeriodicalId":94314,"journal":{"name":"EJC paediatric oncology","volume":"5 ","pages":"Article 100223"},"PeriodicalIF":0.0,"publicationDate":"2025-02-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143548380","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}
Pub Date : 2025-02-19DOI: 10.1016/j.ejcped.2025.100220
Christa Koenig , Roland A. Ammann , Eva Brack
Wearable devices (WDs) are capable of collecting large volumes of objective and clinically relevant patient data that is not yet routinely captured. This ability to collect continuous, real-time data offers a unique opportunity to gather health information in new and insightful ways. In paediatric oncology, advancement in treatment have led to significant improvements in survival rates. However, aggressive therapies often result in a range of distressing side effects, which can severely impact quality of life, and even can become life-threatening themselves. Supportive care plays a crucial role in mitigating these symptoms, aiming to prevent and manage side effects. Patient-reported outcomes should be used to guide initiation and choice of supportive care treatment whenever possible. In this context, continuous monitoring of vital signs, physical activity and other health parameters using WDs could add individual, patient specific information regarding a patient’s current condition. In this article we discuss the requirements of non-invasive WDs for their use in paediatric oncology, give an overview on possible areas of application in children with cancer and discusses challenges that must be addressed. Also we identify key research gaps and speculate on future perspectives.
{"title":"Non-invasive wearable devices in paediatric cancer care: Advancing personalized medicine, addressing challenges and shaping the future","authors":"Christa Koenig , Roland A. Ammann , Eva Brack","doi":"10.1016/j.ejcped.2025.100220","DOIUrl":"10.1016/j.ejcped.2025.100220","url":null,"abstract":"<div><div>Wearable devices (WDs) are capable of collecting large volumes of objective and clinically relevant patient data that is not yet routinely captured. This ability to collect continuous, real-time data offers a unique opportunity to gather health information in new and insightful ways. In paediatric oncology, advancement in treatment have led to significant improvements in survival rates. However, aggressive therapies often result in a range of distressing side effects, which can severely impact quality of life, and even can become life-threatening themselves. Supportive care plays a crucial role in mitigating these symptoms, aiming to prevent and manage side effects. Patient-reported outcomes should be used to guide initiation and choice of supportive care treatment whenever possible. In this context, continuous monitoring of vital signs, physical activity and other health parameters using WDs could add individual, patient specific information regarding a patient’s current condition. In this article we discuss the requirements of non-invasive WDs for their use in paediatric oncology, give an overview on possible areas of application in children with cancer and discusses challenges that must be addressed. Also we identify key research gaps and speculate on future perspectives.</div></div>","PeriodicalId":94314,"journal":{"name":"EJC paediatric oncology","volume":"5 ","pages":"Article 100220"},"PeriodicalIF":0.0,"publicationDate":"2025-02-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143471467","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}
Pub Date : 2025-02-16DOI: 10.1016/j.ejcped.2025.100221
Daniela Di Carlo , Lisa Lyngsie Hjalgrim , Beatrice Coppadoro , Michela Casanova , Andrea Ferrari , Véronique Minard-Colin , Hans Merks , Gianni Bisogno
Introduction
In the multicenter, open-label, randomized, controlled, phase 3 trial RMS2005, maintenance chemotherapy (MC), defined as vinorelbine (VNL) and low-dose cyclophosphamide (CPM), has been tested in high-risk patients affected by Rhabdomyosarcoma (RMS). The trial's results have shown that adding MC to 9 blocks of standard chemotherapy and surgery/radiotherapy improved overall survival. Following these results, MC has been incorporated into the standard of care for high-risk RMS patients. Drug doses were empirically titrated to avoid severe myelosuppression.
Aspects like treatment adherence and drug doses effectively administered may have an important impact on the survival results and deserve to be studied.
Methods
We analyzed 171 patients included in the RMS2005 protocol who received MC to quantify the deviation from the indications in terms of duration of maintenance and received doses and study its impact on survival.
Results
Considering both drugs, 101/169 (60 %) of patients received a delivered cumulative dose (DCD) of at least 80 % of the planned cumulative dose, with a median DCD of 83 % (IQR 71–96).
The median VNL and CPM relative dose intensity (RDI) was 0.88 (IQR 0.68–1).
When the DCD or RDI for VNL, CPM and VNL plus CPM are included in the univariate and multivariate Cox model, as continuous or categorical variables, the effect is not significant both on the risk of developing events or death.
Conclusion
The presented data about maintenance therapy suggested that dose modifications (as we registered them) did not affect event-free and overall survival.
{"title":"Maintenance therapy for pediatric patients with high-risk Rhabdomyosarcoma: A report of dose reductions and dose omissions on outcome","authors":"Daniela Di Carlo , Lisa Lyngsie Hjalgrim , Beatrice Coppadoro , Michela Casanova , Andrea Ferrari , Véronique Minard-Colin , Hans Merks , Gianni Bisogno","doi":"10.1016/j.ejcped.2025.100221","DOIUrl":"10.1016/j.ejcped.2025.100221","url":null,"abstract":"<div><h3>Introduction</h3><div>In the multicenter, open-label, randomized, controlled, phase 3 trial RMS2005, maintenance chemotherapy (MC), defined as vinorelbine (VNL) and low-dose cyclophosphamide (CPM), has been tested in high-risk patients affected by Rhabdomyosarcoma (RMS). The trial's results have shown that adding MC to 9 blocks of standard chemotherapy and surgery/radiotherapy improved overall survival. Following these results, MC has been incorporated into the standard of care for high-risk RMS patients. Drug doses were empirically titrated to avoid severe myelosuppression.</div><div>Aspects like treatment adherence and drug doses effectively administered may have an important impact on the survival results and deserve to be studied.</div></div><div><h3>Methods</h3><div>We analyzed 171 patients included in the RMS2005 protocol who received MC to quantify the deviation from the indications in terms of duration of maintenance and received doses and study its impact on survival.</div></div><div><h3>Results</h3><div>Considering both drugs, 101/169 (60 %) of patients received a delivered cumulative dose (DCD) of at least 80 % of the planned cumulative dose, with a median DCD of 83 % (IQR 71–96).</div><div>The median VNL and CPM relative dose intensity (RDI) was 0.88 (IQR 0.68–1).</div><div>When the DCD or RDI for VNL, CPM and VNL plus CPM are included in the univariate and multivariate Cox model, as continuous or categorical variables, the effect is not significant both on the risk of developing events or death.</div></div><div><h3>Conclusion</h3><div>The presented data about maintenance therapy suggested that dose modifications (as we registered them) did not affect event-free and overall survival.</div></div>","PeriodicalId":94314,"journal":{"name":"EJC paediatric oncology","volume":"5 ","pages":"Article 100221"},"PeriodicalIF":0.0,"publicationDate":"2025-02-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143508548","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}
Pub Date : 2025-02-15DOI: 10.1016/j.ejcped.2025.100217
Sarita Depani , Alexandre Vasiljevic , Martin Mynarek , Christelle Dufour , Elke Pfaff , Ata Ur Maaz , Léa Guerrini-Rousseau , Francois Doz , Martin Hasselblatt , Thankamma Ajithkumar , Kristian Aquilina , Martin U. Schuhmann , Eelco Hoving , Anna Tietze , Ulrike Löbel , Barry Pizer , Katja von Hoff , On behalf of the SIOP-Europe Rare Embryonal and Sarcomatous Tumours (REST) group
Paediatric tumours of the pineal region are rare CNS tumours accounting for 3% of brain tumours in children and adolescents; the majority of which are germ cell tumours. This review focuses on pineal parenchymal tumours (pineoblastoma, pineal parenchymal tumour of intermediate differentiation, pineocytoma) and those specifically arising in the pineal region (papillary tumours of the pineal region, desmoplastic myxoid tumour of the pineal region, SMARCB1-mutant and pineal cyst), which together account for up to a third of pineal tumours. In recent years, the diagnostic classification of these specific tumour-types has been refined by the integration of molecular pathology. Given the differences in grade, tumour biology and clinical behaviour, an accurate integrated neuropathological diagnosis is essential in deciding an appropriate treatment strategy which can range from surgery only to intensive multi-modal therapies. The most common of these tumours in children is WHO Grade 4 pineoblastoma, where specific molecular subgroups occurring in very young patients are difficult to treat successfully. Further challenges include the anatomical position and associated surgical risk together with a lack of molecularly annotated clinical data and consequent limited evidence to guide the therapeutic approach due to their rarity. These guidelines aim to provide a framework for diagnosis, prognostication and management based on current literature and expert opinion.
{"title":"European clinical practice recommendations for the diagnosis and treatment of paediatric pineal tumours","authors":"Sarita Depani , Alexandre Vasiljevic , Martin Mynarek , Christelle Dufour , Elke Pfaff , Ata Ur Maaz , Léa Guerrini-Rousseau , Francois Doz , Martin Hasselblatt , Thankamma Ajithkumar , Kristian Aquilina , Martin U. Schuhmann , Eelco Hoving , Anna Tietze , Ulrike Löbel , Barry Pizer , Katja von Hoff , On behalf of the SIOP-Europe Rare Embryonal and Sarcomatous Tumours (REST) group","doi":"10.1016/j.ejcped.2025.100217","DOIUrl":"10.1016/j.ejcped.2025.100217","url":null,"abstract":"<div><div>Paediatric tumours of the pineal region are rare CNS tumours accounting for 3% of brain tumours in children and adolescents; the majority of which are germ cell tumours. This review focuses on pineal parenchymal tumours (pineoblastoma, pineal parenchymal tumour of intermediate differentiation, pineocytoma) and those specifically arising in the pineal region (papillary tumours of the pineal region, desmoplastic myxoid tumour of the pineal region, SMARCB1-mutant and pineal cyst), which together account for up to a third of pineal tumours. In recent years, the diagnostic classification of these specific tumour-types has been refined by the integration of molecular pathology. Given the differences in grade, tumour biology and clinical behaviour, an accurate integrated neuropathological diagnosis is essential in deciding an appropriate treatment strategy which can range from surgery only to intensive multi-modal therapies. The most common of these tumours in children is WHO Grade 4 pineoblastoma, where specific molecular subgroups occurring in very young patients are difficult to treat successfully. Further challenges include the anatomical position and associated surgical risk together with a lack of molecularly annotated clinical data and consequent limited evidence to guide the therapeutic approach due to their rarity. These guidelines aim to provide a framework for diagnosis, prognostication and management based on current literature and expert opinion.</div></div>","PeriodicalId":94314,"journal":{"name":"EJC paediatric oncology","volume":"5 ","pages":"Article 100217"},"PeriodicalIF":0.0,"publicationDate":"2025-02-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143593277","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}
Pub Date : 2025-02-07DOI: 10.1016/j.ejcped.2025.100218
Daniel Betemariem , Leul Deribe , Aklil Hailu , Haileyesus Adam , Nataliya Berbyuk Lindström
Background
Parental preferences for involvement in treatment decision-making (TDM) in pediatric oncology can vary among passive, collaborative, and active roles, influenced by various factors. This study investigates the parental role in TDM for children with cancer in Ethiopia and identifies the key determinants of this role.
Methods
This research employs a mixed-methods approach, combining a cross-sectional survey and phenomenological interviews. A total of 167 parents of children with cancer participated in the survey, utilizing the Control Preference Scale for Pediatrics (CPS-P) and the Krantz Health Opinion Survey (KHOS) to assess parental roles in TDM. Additionally, 11 in-depth interviews were conducted with selected parents. Logistic regression and thematic analysis were used to analyze the quantitative and qualitative data, respectively.
Results
The findings reveal that Ethiopian parents predominantly prefer a passive role in TDM. Trust in healthcare providers and parental information preferences emerged as statistically significant predictors of this passive involvement. Other factors influencing parental decision-making included the quality of the parent-provider relationship, the child’s clinical condition, parental beliefs about TDM, and knowledge of cancer.
Conclusions
This study offers valuable insights into the parental role in TDM within Ethiopian pediatric oncology care, an area previously unexplored. Understanding parents’ preferences in TDM is crucial for Ethiopian healthcare providers to align communication and amplify patient voices. The findings highlight the need to promote more active parental involvement in TDM by facilitating educational sessions, developing parental education guidelines, and providing accessible cancer information across diverse regions of the country.
{"title":"Parental role in paediatric cancer treatment decision making at Tikur Anbessa Specialized Hospital, Ethiopia: A mixed method study","authors":"Daniel Betemariem , Leul Deribe , Aklil Hailu , Haileyesus Adam , Nataliya Berbyuk Lindström","doi":"10.1016/j.ejcped.2025.100218","DOIUrl":"10.1016/j.ejcped.2025.100218","url":null,"abstract":"<div><h3>Background</h3><div>Parental preferences for involvement in treatment decision-making (TDM) in pediatric oncology can vary among passive, collaborative, and active roles, influenced by various factors. This study investigates the parental role in TDM for children with cancer in Ethiopia and identifies the key determinants of this role.</div></div><div><h3>Methods</h3><div>This research employs a mixed-methods approach, combining a cross-sectional survey and phenomenological interviews. A total of 167 parents of children with cancer participated in the survey, utilizing the Control Preference Scale for Pediatrics (CPS-P) and the Krantz Health Opinion Survey (KHOS) to assess parental roles in TDM. Additionally, 11 in-depth interviews were conducted with selected parents. Logistic regression and thematic analysis were used to analyze the quantitative and qualitative data, respectively.</div></div><div><h3>Results</h3><div>The findings reveal that Ethiopian parents predominantly prefer a passive role in TDM. Trust in healthcare providers and parental information preferences emerged as statistically significant predictors of this passive involvement. Other factors influencing parental decision-making included the quality of the parent-provider relationship, the child’s clinical condition, parental beliefs about TDM, and knowledge of cancer.</div></div><div><h3>Conclusions</h3><div>This study offers valuable insights into the parental role in TDM within Ethiopian pediatric oncology care, an area previously unexplored. Understanding parents’ preferences in TDM is crucial for Ethiopian healthcare providers to align communication and amplify patient voices. The findings highlight the need to promote more active parental involvement in TDM by facilitating educational sessions, developing parental education guidelines, and providing accessible cancer information across diverse regions of the country.</div></div>","PeriodicalId":94314,"journal":{"name":"EJC paediatric oncology","volume":"5 ","pages":"Article 100218"},"PeriodicalIF":0.0,"publicationDate":"2025-02-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143387453","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}
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