Pub Date : 2024-03-31DOI: 10.1016/j.ejcped.2024.100158
Stefan S. Bielack , Daniel Baumhoer , Stefanie Hecker-Nolting , Simone Hettmer , Leo Kager , Petra Ketteler , Matthias Kevric , Christian P. Kratz , Thomas Kühne , Vanessa Mettmann , Markus Metzler , Dirk Reinhardt , Benjamin Sorg , Claudia Blattmann
Purpose
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.
Patients and methods
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.
Results
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.
Conclusion
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.
{"title":"Osteosarcomas in retinoblastoma-survivors. A report of 28 affected patients from the Cooperative Osteosarcoma Study Group (COSS)","authors":"Stefan S. Bielack , Daniel Baumhoer , Stefanie Hecker-Nolting , Simone Hettmer , Leo Kager , Petra Ketteler , Matthias Kevric , Christian P. Kratz , Thomas Kühne , Vanessa Mettmann , Markus Metzler , Dirk Reinhardt , Benjamin Sorg , 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}
Pub Date : 2024-03-17DOI: 10.1016/j.ejcped.2024.100160
Rebecca Epperly, Stephen Gottschalk, Christopher DeRenzo
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.
尽管采用了强化疗法,但复发或难治性实体瘤儿科患者的治疗效果不佳,需要新的治疗方法。免疫疗法为传统治疗方案提供了另一种选择,但需要识别不同表达的抗原,将抗肿瘤活性引导到疾病部位。B7-H3(CD276)是一种免疫调节蛋白,在多种恶性肿瘤中表达,在正常组织中表达有限。B7-H3在小儿实体瘤中高度表达,包括骨肉瘤、横纹肌肉瘤、尤文肉瘤、Wilms瘤、神经母细胞瘤和许多罕见肿瘤。在这篇文章中,我们回顾了针对小儿实体瘤的B7-H3靶向嵌合抗原受体(B7-H3-CAR)T细胞疗法,报告了临床前开发策略,并概述了活跃的小儿临床试验情况。我们指出了CAR T细胞疗法成功治疗实体瘤所面临的挑战,包括定位和穿透实体瘤部位、避开恶劣的肿瘤微环境、支持T细胞扩增和持久性以及避免内在肿瘤耐药性。我们重点介绍了克服这些挑战并增强 B7-H3-CAR T 细胞疗效的策略,包括先进的 CAR T 细胞设计和联合疗法。
{"title":"CAR T cells redirected to B7-H3 for pediatric solid tumors: Current status and future perspectives","authors":"Rebecca Epperly, Stephen Gottschalk, 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}
Pub Date : 2024-03-16DOI: 10.1016/j.ejcped.2024.100159
Atia Samim , Gitta Bleeker , Kathelijne C.J.M. Kraal , Max M. van Noesel , Bart de Keizer , Godelieve A.M. Tytgat
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 (therapeutic and diagnostic) 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.
{"title":"A narrative review of 35 years of meta-[131I]iodobenzylguanidine therapy in neuroblastoma","authors":"Atia Samim , Gitta Bleeker , Kathelijne C.J.M. Kraal , Max M. van Noesel , Bart de Keizer , 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. [<sup>123</sup>I]mIBG scintigraphy is recognized as the international standard to evaluate disease dissemination at diagnosis and to monitor treatment response. In contrast, the role of [<sup>131</sup>I]mIBG therapy in the management of neuroblastoma is less clear. Over the past 35 years, [<sup>131</sup>I]mIBG therapy has been studied in more than 1500 patients with neuroblastoma. In initial studies, [<sup>131</sup>I]mIBG monotherapy was applied as a second-line treatment in patients who failed first-line treatment. In current applications, [<sup>131</sup>I]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 [<sup>131</sup>I]mIBG therapy in HR-NBL. Studies show that [<sup>131</sup>I]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 [<sup>131</sup>I]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}
Pub Date : 2024-03-13DOI: 10.1016/j.ejcped.2024.100157
Miho Nakajima, Ayumu Arakawa, Chitose Ogawa
Compared to Europe and the United States, where the development of pediatric oncology drugs is mandated by law, Japan hosts fewer clinical trials. This can lead to a significant drug lag, especially in the case of treatments for pediatric solid tumors. Notably, regulatory authorities and the government have initiated discussions on strategies to mitigate Japan’s drug lag problem in pediatric oncology. Over the past decade, we have actively sought opportunities to participate in international collaborative clinical trials through Japan’s involvement in ACCELERATE and its predecessor organizations. This approach has aimed to address the issue above, coinciding with the ongoing centralization of medical care and advancements in genomic medicine, among other systems that support pediatric cancer care in Japan. Inspired by the ACCELERATE initiatives and in response to patient advocacy groups’ requests for new pediatric oncology drugs, Japan established its inaugural pediatric oncology support platform in 2021, the National Childhood Cancer Consortium (N3C). N3C comprises patient advocacy groups, industries, and academia. This work outlines the current status of pediatric drug development in Japan and highlights the initial successful experience of NCCH’s participation in a global clinical trial through ACCELERATE resulting in rapid preparation and patient recruitment. Participation of Asian countries including Japan in global collaborative clinical trials may benefit both pharmaceutical companies and the participating countries partnering to advance the development of pediatric oncology drugs.
{"title":"Japan’s contribution to an ongoing global pediatric cancer clinical trial: The experience of the National Cancer Center Hospital (NCCH) in Tokyo","authors":"Miho Nakajima, Ayumu Arakawa, Chitose Ogawa","doi":"10.1016/j.ejcped.2024.100157","DOIUrl":"https://doi.org/10.1016/j.ejcped.2024.100157","url":null,"abstract":"<div><p>Compared to Europe and the United States, where the development of pediatric oncology drugs is mandated by law, Japan hosts fewer clinical trials. This can lead to a significant drug lag, especially in the case of treatments for pediatric solid tumors. Notably, regulatory authorities and the government have initiated discussions on strategies to mitigate Japan’s drug lag problem in pediatric oncology. Over the past decade, we have actively sought opportunities to participate in international collaborative clinical trials through Japan’s involvement in ACCELERATE and its predecessor organizations. This approach has aimed to address the issue above, coinciding with the ongoing centralization of medical care and advancements in genomic medicine, among other systems that support pediatric cancer care in Japan. Inspired by the ACCELERATE initiatives and in response to patient advocacy groups’ requests for new pediatric oncology drugs, Japan established its inaugural pediatric oncology support platform in 2021, the National Childhood Cancer Consortium (N3C). N3C comprises patient advocacy groups, industries, and academia. This work outlines the current status of pediatric drug development in Japan and highlights the initial successful experience of NCCH’s participation in a global clinical trial through ACCELERATE resulting in rapid preparation and patient recruitment. Participation of Asian countries including Japan in global collaborative clinical trials may benefit both pharmaceutical companies and the participating countries partnering to advance the development of pediatric oncology drugs.</p></div>","PeriodicalId":94314,"journal":{"name":"EJC paediatric oncology","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2024-03-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S2772610X24000163/pdfft?md5=2f7099c73d2c72937b2ee48f61f1ec60&pid=1-s2.0-S2772610X24000163-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140161006","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 : 2024-03-12DOI: 10.1016/j.ejcped.2024.100156
Lisa Werr , Carolina Rosswog , Christoph Bartenhagen , Sally L. George , Matthias Fischer
The clinical behaviour of neuroblastoma ranges from spontaneous tumour regression or maturation into benign ganglioneuroma to fatal progression despite intensive treatment [1,2]. The mechanisms underlying the distinct phenotypes have remained uncertain yet. A number of recent studies noticed that activation of telomere maintenance mechanisms (TMM) in the malignant neuroblasts is strongly associated with high-risk disease and poor outcome, whereas TMM are absent in spontaneously regressing low-risk tumours, suggesting that telomere maintenance is essential to drive neuroblasts into the fully malignant state. Stabilization of the telomeres above a critical threshold is essential for cancer cells to gain replicative immortality and has thus been considered a hallmark of cancer [3]. In most high-risk neuroblastomas, TMM is conferred by induction of telomerase, either through genomic rearrangements of the TERT locus, encoding for the catalytic subunit of telomerase, or amplification of the MYCN proto-oncogene, whereas the alternative lengthening of telomeres (ALT) pathway is activated in approximately one-quarter of high-risk tumours [4–8]. We here review recent advances on our understanding of the mechanistic role of telomere maintenance in neuroblastoma pathogenesis, and discuss potential implications on neuroblastoma risk assessment and on the development of novel therapies directed against TMM.
{"title":"Telomere maintenance mechanisms in neuroblastoma: New insights and translational implications","authors":"Lisa Werr , Carolina Rosswog , Christoph Bartenhagen , Sally L. George , Matthias Fischer","doi":"10.1016/j.ejcped.2024.100156","DOIUrl":"https://doi.org/10.1016/j.ejcped.2024.100156","url":null,"abstract":"<div><p>The clinical behaviour of neuroblastoma ranges from spontaneous tumour regression or maturation into benign ganglioneuroma to fatal progression despite intensive treatment [1,2]. The mechanisms underlying the distinct phenotypes have remained uncertain yet. A number of recent studies noticed that activation of telomere maintenance mechanisms (TMM) in the malignant neuroblasts is strongly associated with high-risk disease and poor outcome, whereas TMM are absent in spontaneously regressing low-risk tumours, suggesting that telomere maintenance is essential to drive neuroblasts into the fully malignant state. Stabilization of the telomeres above a critical threshold is essential for cancer cells to gain replicative immortality and has thus been considered a hallmark of cancer [3]. In most high-risk neuroblastomas, TMM is conferred by induction of telomerase, either through genomic rearrangements of the <em>TERT</em> locus, encoding for the catalytic subunit of telomerase, or amplification of the <em>MYCN</em> proto-oncogene, whereas the alternative lengthening of telomeres (ALT) pathway is activated in approximately one-quarter of high-risk tumours [4–8]. We here review recent advances on our understanding of the mechanistic role of telomere maintenance in neuroblastoma pathogenesis, and discuss potential implications on neuroblastoma risk assessment and on the development of novel therapies directed against TMM.</p></div>","PeriodicalId":94314,"journal":{"name":"EJC paediatric oncology","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2024-03-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S2772610X24000151/pdfft?md5=de1f29ad7bc35889849f4f9efb14f365&pid=1-s2.0-S2772610X24000151-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140138799","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 : 2024-03-08DOI: 10.1016/j.ejcped.2024.100155
Neimar de Paula Silva , Andrea Gini , Anastasia Dolya , Murielle Colombet , Isabelle Soerjomataram , Danny Youlden , Charles Stiller , Eva Steliarova-Foucher , the CRICCS consortium, Joanne Aitken , Freddie Bray , Murielle Colombet , Neimar de Paula Silva , Anastasia Dolya , Friederike Erdmann , Jeanette Falck Winther , Andrea Gini , Delphine Heenen , Lars Hjorth , Claudia E. Kuehni , Danny Youlden
Childhood cancer survivors (CCS) require specialized follow-up throughout their lifespan to prevent or manage late effects of cancer treatment. Knowing the size and structure of the population of CCS is crucial to plan interventions. In this scoping review we reviewed studies that reported prevalence of CCS in Europe. We searched Medline, Web of Science, and Embase using permutations of terms referring to childhood, cancer, survivors, prevalence, registries, and Europe. We followed PRISMA-ScR guidelines to select studies and The Joanna Briggs Institute Prevalence Critical Appraisal Tool to evaluate their quality. From 979 unique studies published between 1989 and 2022, 12 were included. Limited-duration prevalence (LDP) for all childhood cancers, assessed in three studies using counting method, varied between 450 and 1240 persons per million. Complete prevalence (CP) of survivors of any childhood cancer except skin carcinomas, reported in three studies using observed data complemented with modelled data for the unobserved period, varied between 730 and 1110 persons per million. CP of survivors of an embryonal tumour was estimated by completeness index method in six studies. In four of them CP ranged from 48 to 95 persons per million for all embryonal tumours, while CP for those occurring in central nervous system was 43 per million in one study and CP for rhabdomyosarcoma was 17 per million in another. Information on prevalence of CCS in Europe is fragmented and inconsistent. The large variations in LDP and CP estimates were linked to differences in data availability, the selection of populations, prevalence measure, statistical method, incidence period, index date, age at diagnosis and prevalence, cancer types, sex, and, for LDP, also the length of follow-up. Standardisation of methodology and reporting are needed to systematically monitor and compare CCS prevalence in Europe and provide data to help address survivors’ needs.
{"title":"Prevalence of childhood cancer survivors in Europe: a scoping review","authors":"Neimar de Paula Silva , Andrea Gini , Anastasia Dolya , Murielle Colombet , Isabelle Soerjomataram , Danny Youlden , Charles Stiller , Eva Steliarova-Foucher , the CRICCS consortium, Joanne Aitken , Freddie Bray , Murielle Colombet , Neimar de Paula Silva , Anastasia Dolya , Friederike Erdmann , Jeanette Falck Winther , Andrea Gini , Delphine Heenen , Lars Hjorth , Claudia E. Kuehni , Danny Youlden","doi":"10.1016/j.ejcped.2024.100155","DOIUrl":"https://doi.org/10.1016/j.ejcped.2024.100155","url":null,"abstract":"<div><p>Childhood cancer survivors (CCS) require specialized follow-up throughout their lifespan to prevent or manage late effects of cancer treatment. Knowing the size and structure of the population of CCS is crucial to plan interventions. In this scoping review we reviewed studies that reported prevalence of CCS in Europe. We searched Medline, Web of Science, and Embase using permutations of terms referring to childhood, cancer, survivors, prevalence, registries, and Europe. We followed PRISMA-ScR guidelines to select studies and The Joanna Briggs Institute Prevalence Critical Appraisal Tool to evaluate their quality. From 979 unique studies published between 1989 and 2022, 12 were included. Limited-duration prevalence (LDP) for all childhood cancers, assessed in three studies using counting method, varied between 450 and 1240 persons per million. Complete prevalence (CP) of survivors of any childhood cancer except skin carcinomas, reported in three studies using observed data complemented with modelled data for the unobserved period, varied between 730 and 1110 persons per million. CP of survivors of an embryonal tumour was estimated by completeness index method in six studies. In four of them CP ranged from 48 to 95 persons per million for all embryonal tumours, while CP for those occurring in central nervous system was 43 per million in one study and CP for rhabdomyosarcoma was 17 per million in another. Information on prevalence of CCS in Europe is fragmented and inconsistent. The large variations in LDP and CP estimates were linked to differences in data availability, the selection of populations, prevalence measure, statistical method, incidence period, index date, age at diagnosis and prevalence, cancer types, sex, and, for LDP, also the length of follow-up. Standardisation of methodology and reporting are needed to systematically monitor and compare CCS prevalence in Europe and provide data to help address survivors’ needs.</p></div>","PeriodicalId":94314,"journal":{"name":"EJC paediatric oncology","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2024-03-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S2772610X2400014X/pdfft?md5=4115c91bca18701bb5c80c478a2fce0c&pid=1-s2.0-S2772610X2400014X-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140138798","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 : 2024-02-28DOI: 10.1016/j.ejcped.2024.100153
Jelena Rascon , Renata Blackute , Alma Cerkauskiene , Sabine Taschner-Mandl , Nuno Andrade , Adriana Planinic , Stefan Rutkowski , Ulrich Schuller , Karsten Nysom , Ruta Tuckuviene , Jesper Brok , Kjeld Schmiegelow , Marry M. van den Heuvel-Eibrink , M.E. Madeleine van der Perk , Riccardo Haupt , Monica Muraca , Davide Saraceno , Birgit Geoerger , Giorgia Manuzi , Ruth Ladenstein
Inequalities in research and innovations affect childhood cancer survival across Europe. Vilnius University Hospital Santaros Klinikos (VULSK, the coordinator) and eight research-intensive institutions from seven European countries implemented the TREL project (Twinning in Research and Education to improve survival in childhood solid tumours in Lithuania) supported by the Horizon 2020 Widening programme. TREL aimed to enhance translational, clinical, and survivorship research in paediatric CNS, neuroblastoma, and renal tumours to improve future treatment outcomes in Lithuania. From January 2021 to December 2023, 49 VULSK professionals and 55 peers from partner institutions collaborated in this twinning program. Achievements after three years were: nine educational events, the initiation of basic and clinical research on fertility preservation, ten VULSK researchers joining international research groups, six signed agreements to participate in international academic clinical trials and the implementation of the European Survivorship Passport. Thirty patients received individual treatment recommendations following multidisciplinary discussions with experts from partner institutions. Twenty-five rare genetic variants were classified by the twinning bioinformatician teams with direct consequences on patient management. In conclusion, coordination of the Horizon 2020 project enhanced VULKS’s research capacities, networking channels and attractiveness for industry and academia-initiated innovative actions that will improve survival rates in the long run.
{"title":"Twinning to reduce research and innovation inequalities in paediatric solid tumours across Europe","authors":"Jelena Rascon , Renata Blackute , Alma Cerkauskiene , Sabine Taschner-Mandl , Nuno Andrade , Adriana Planinic , Stefan Rutkowski , Ulrich Schuller , Karsten Nysom , Ruta Tuckuviene , Jesper Brok , Kjeld Schmiegelow , Marry M. van den Heuvel-Eibrink , M.E. Madeleine van der Perk , Riccardo Haupt , Monica Muraca , Davide Saraceno , Birgit Geoerger , Giorgia Manuzi , Ruth Ladenstein","doi":"10.1016/j.ejcped.2024.100153","DOIUrl":"https://doi.org/10.1016/j.ejcped.2024.100153","url":null,"abstract":"<div><p>Inequalities in research and innovations affect childhood cancer survival across Europe. Vilnius University Hospital Santaros Klinikos (VULSK, the coordinator) and eight research-intensive institutions from seven European countries implemented the TREL project (Twinning in Research and Education to improve survival in childhood solid tumours in Lithuania) supported by the Horizon 2020 Widening programme. TREL aimed to enhance translational, clinical, and survivorship research in paediatric CNS, neuroblastoma, and renal tumours to improve future treatment outcomes in Lithuania. From January 2021 to December 2023, 49 VULSK professionals and 55 peers from partner institutions collaborated in this twinning program. Achievements after three years were: nine educational events, the initiation of basic and clinical research on fertility preservation, ten VULSK researchers joining international research groups, six signed agreements to participate in international academic clinical trials and the implementation of the European Survivorship Passport. Thirty patients received individual treatment recommendations following multidisciplinary discussions with experts from partner institutions. Twenty-five rare genetic variants were classified by the twinning bioinformatician teams with direct consequences on patient management. In conclusion, coordination of the Horizon 2020 project enhanced VULKS’s research capacities, networking channels and attractiveness for industry and academia-initiated innovative actions that will improve survival rates in the long run.</p></div>","PeriodicalId":94314,"journal":{"name":"EJC paediatric oncology","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2024-02-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S2772610X24000126/pdfft?md5=c32781086be65a384542762fae4be4dc&pid=1-s2.0-S2772610X24000126-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140031155","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 : 2024-02-28DOI: 10.1016/j.ejcped.2024.100152
Sarah Cohen-Gogo , Amer Shammas , Adam Shlien , Meredith Irwin , Daniel Morgenstern
{"title":"131-I-MIBG therapy in combination with PARP inhibitors for young adult patient with relapsed neuroblastoma and DNA repair pathway alterations","authors":"Sarah Cohen-Gogo , Amer Shammas , Adam Shlien , Meredith Irwin , Daniel Morgenstern","doi":"10.1016/j.ejcped.2024.100152","DOIUrl":"https://doi.org/10.1016/j.ejcped.2024.100152","url":null,"abstract":"","PeriodicalId":94314,"journal":{"name":"EJC paediatric oncology","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2024-02-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S2772610X24000114/pdfft?md5=d13c8be54bd68674569537c0f8ff2605&pid=1-s2.0-S2772610X24000114-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140016033","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 : 2024-02-28DOI: 10.1016/j.ejcped.2024.100148
Caroline C.C. Hulsker , Maya Schulpen , Annelies M.C. Mavinkurve-Groothuis , Otto Visser , József Zsiros , Marc H.W. Wijnen , Ronald R. de Krijger , Annette H. Bruggink , Leendert H.J. Looijenga , Henrike E. Karim-Kos , Alida F.W. van der Steeg
Background
Population-based studies assessing long-term patterns of incidence and disease characteristics of germ cell tumors (GCTs) in children are scarce. We investigated incidence and survival trends of malignant extracranial GCTs in children using population-based nationwide data from the Netherlands.
Methods
All malignant extracranial GCTs diagnosed in patients aged 0–18 years between 1990 and 2018 were selected from the Netherlands Cancer Registry. Incidence rates were calculated as the average annual number of cases per 1 million person-years. Five-year overall survival (OS) was calculated.
Results
A total of 815 cases were identified. Gonadal GCTs (n=665, testis n=485, ovarian n=180) were more common than extragonadal GCTs (n=149). Stage distribution for testicular and extragonadal GCTs shifted between 1990 and 2004 and 2005–2018 towards more localized disease. The overall incidence remained stable over time, but a significant increase was noted for extragonadal GCTs in the 0–9 years age group. Survival of extragonadal GCTs (5-year OS 84.1%, 95% CI 77.1–89.1), in particular mediastinal GCTs (5-year OS 66.7%, 95% CI 45.7–81.1), was lower than that of gonadal GCTs (5-year OS testis 95.0%, 95% CI 92.7–96.7;ovary 97.8%, 95% CI 94.2–99.2). The 5-year OS of our entire cohort was 93.6% (95% CI 91.7–95.1). Five-year OS significantly increased from 89.5% (95% CI 86.1–92.2) in 1990–2004–97.4% (95% CI 95.3–98.5) in 2005–2018.
Conclusions
Although the incidence of all malignant pediatric extracranial GCTs remained stable during 1990–2018, an increase was observed for extragonadal GCTs in younger children (0–9 years). There was a shift towards more localized disease for testicular and extragonadal GCTs. Five-year OS increased over time exceeding 90% (91.4%, 95% CI 82.7–95.8) in the most recent diagnostic period. Mediastinal GCTs had the lowest OS, supporting the need for future research.
背景评估儿童生殖细胞瘤(GCTs)长期发病模式和疾病特征的人群研究很少。我们利用荷兰全国人口数据调查了儿童恶性颅外GCT的发病率和生存趋势。方法从荷兰癌症登记处选取1990年至2018年间0-18岁患者中确诊的所有恶性颅外GCT。发病率按每100万人年的年平均病例数计算。计算了五年总生存率(OS)。性腺 GCT(665 例,睾丸 485 例,卵巢 180 例)比性腺外 GCT(149 例)更为常见。睾丸和睾丸外 GCT 的分期分布在 1990 年至 2004 年和 2005 年至 2018 年期间向更局部化的疾病转变。随着时间的推移,总体发病率保持稳定,但在0-9岁年龄组中,睾丸外GCT的发病率显著增加。性腺外GCT的生存率(5年OS 84.1%,95% CI 77.1-89.1),尤其是纵隔GCT(5年OS 66.7%,95% CI 45.7-81.1)低于性腺GCT(5年OS睾丸95.0%,95% CI 92.7-96.7;卵巢97.8%,95% CI 94.2-99.2)。整个队列的5年生存率为93.6%(95% CI 91.7-95.1)。5年OS从1990-2004年的89.5%(95% CI 86.1-92.2)明显上升至2005-2018年的97.4%(95% CI 95.3-98.5)。结论虽然1990-2018年期间所有恶性小儿颅外GCT的发病率保持稳定,但在年龄较小的儿童(0-9岁)中观察到颅外GCT的发病率有所上升。睾丸和睾丸外GCT的发病率向更局部化转变。五年生存率随着时间的推移而增加,在最近的诊断期超过了90%(91.4%,95% CI 82.7-95.8)。纵隔GCT的OS最低,这表明未来研究的必要性。
{"title":"Malignant extracranial germ cell tumors in the Netherlands between 1990 and 2018: Stable incidence and improved survival","authors":"Caroline C.C. Hulsker , Maya Schulpen , Annelies M.C. Mavinkurve-Groothuis , Otto Visser , József Zsiros , Marc H.W. Wijnen , Ronald R. de Krijger , Annette H. Bruggink , Leendert H.J. Looijenga , Henrike E. Karim-Kos , Alida F.W. van der Steeg","doi":"10.1016/j.ejcped.2024.100148","DOIUrl":"https://doi.org/10.1016/j.ejcped.2024.100148","url":null,"abstract":"<div><h3>Background</h3><p>Population-based studies assessing long-term patterns of incidence and disease characteristics of germ cell tumors (GCTs) in children are scarce. We investigated incidence and survival trends of malignant extracranial GCTs in children using population-based nationwide data from the Netherlands.</p></div><div><h3>Methods</h3><p>All malignant extracranial GCTs diagnosed in patients aged 0–18 years between 1990 and 2018 were selected from the Netherlands Cancer Registry. Incidence rates were calculated as the average annual number of cases per 1 million person-years. Five-year overall survival (OS) was calculated.</p></div><div><h3>Results</h3><p>A total of 815 cases were identified. Gonadal GCTs (n=665, testis n=485, ovarian n=180) were more common than extragonadal GCTs (n=149). Stage distribution for testicular and extragonadal GCTs shifted between 1990 and 2004 and 2005–2018 towards more localized disease. The overall incidence remained stable over time, but a significant increase was noted for extragonadal GCTs in the 0–9 years age group. Survival of extragonadal GCTs (5-year OS 84.1%, 95% CI 77.1–89.1), in particular mediastinal GCTs (5-year OS 66.7%, 95% CI 45.7–81.1), was lower than that of gonadal GCTs (5-year OS testis 95.0%, 95% CI 92.7–96.7;ovary 97.8%, 95% CI 94.2–99.2). The 5-year OS of our entire cohort was 93.6% (95% CI 91.7–95.1). Five-year OS significantly increased from 89.5% (95% CI 86.1–92.2) in 1990–2004–97.4% (95% CI 95.3–98.5) in 2005–2018.</p></div><div><h3>Conclusions</h3><p>Although the incidence of all malignant pediatric extracranial GCTs remained stable during 1990–2018, an increase was observed for extragonadal GCTs in younger children (0–9 years). There was a shift towards more localized disease for testicular and extragonadal GCTs. Five-year OS increased over time exceeding 90% (91.4%, 95% CI 82.7–95.8) in the most recent diagnostic period. Mediastinal GCTs had the lowest OS, supporting the need for future research.</p></div>","PeriodicalId":94314,"journal":{"name":"EJC paediatric oncology","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2024-02-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S2772610X24000072/pdfft?md5=503469431d7200fe24642a6af61277f3&pid=1-s2.0-S2772610X24000072-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139999308","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 : 2024-02-27DOI: 10.1016/j.ejcped.2024.100154
Gabriel Revon-Rivière, Pauline Tibout, Jennifer Cabral, Aiman Siddiqi, Ashley Doka, Denise Mills, Karen Fung, Sandra Judd, Daniel A. Morgenstern, Sarah Cohen-Gogo
In the context of hard-to-cure disease, pediatric oncologists may have to explore novel therapy options and explain their rationale, risks and constraints to patients and caregivers. The New Agents and Innovative Therapy (NAIT) program at Hospital for Sick Children in Toronto facilitates patient enrollment in clinical trials as well as access to innovative therapies outside of clinical trials. Here, we summarize our experience with helping patients, caregivers, and their primary oncology team navigate information and access to new therapeutic options through enrollment in clinical trials but also off-label and compassionate use. We expose our approach to exploring clinical trial and other therapy options. We share lessons learned from clinical practice regarding the specific role of NAIT consultant, as opposed to the primary oncologist or the disease expert. We expand on ways to communicate regarding the objectives of early phase clinical trials, their methods and the important commitment asked from participants. We describe our views on equipoise, uncertainty and hope in this very specific practice. We support a model of shared decision making and empowerment of patients and caregivers. We also detail the use, benefits and challenges of virtual care applied to NAIT consults. Overall, we hope to contribute and facilitate the NAIT practice not only for trained trialists but also less-specialized teams.
对于难以治愈的疾病,儿科肿瘤专家可能不得不探索新的治疗方案,并向患者和护理人员解释其原理、风险和限制因素。多伦多病童医院(Hospital for Sick Children)的 "新药与创新疗法"(NAIT)项目为患者参与临床试验以及获得临床试验以外的创新疗法提供了便利。在此,我们总结了我们在帮助患者、护理人员和他们的主要肿瘤团队了解信息和获取新的治疗方案方面的经验,这些信息和方案不仅包括临床试验登记,还包括标示外使用和同情性使用。我们揭示了探索临床试验和其他治疗方案的方法。我们分享从临床实践中汲取的有关 NAIT 顾问的特定角色的经验教训,而非肿瘤主治医生或疾病专家。我们阐述了如何就早期临床试验的目标、方法以及要求参与者做出的重要承诺进行沟通。我们阐述了在这一非常特殊的实践中,我们对平衡、不确定性和希望的看法。我们支持共同决策模式,并赋予患者和护理人员权力。我们还详细介绍了虚拟医疗在 NAIT 咨询中的应用、益处和挑战。总之,我们希望不仅为训练有素的试验人员,也为不太专业的团队提供NAIT实践的帮助和便利。
{"title":"How we approach early phase clinical trial and off-label therapy consults in pediatric oncology: The New Agents and Innovative Therapy (NAIT) team experience","authors":"Gabriel Revon-Rivière, Pauline Tibout, Jennifer Cabral, Aiman Siddiqi, Ashley Doka, Denise Mills, Karen Fung, Sandra Judd, Daniel A. Morgenstern, Sarah Cohen-Gogo","doi":"10.1016/j.ejcped.2024.100154","DOIUrl":"https://doi.org/10.1016/j.ejcped.2024.100154","url":null,"abstract":"<div><p>In the context of hard-to-cure disease, pediatric oncologists may have to explore novel therapy options and explain their rationale, risks and constraints to patients and caregivers. The New Agents and Innovative Therapy (NAIT) program at Hospital for Sick Children in Toronto facilitates patient enrollment in clinical trials as well as access to innovative therapies outside of clinical trials. Here, we summarize our experience with helping patients, caregivers, and their primary oncology team navigate information and access to new therapeutic options through enrollment in clinical trials but also off-label and compassionate use. We expose our approach to exploring clinical trial and other therapy options. We share lessons learned from clinical practice regarding the specific role of NAIT consultant, as opposed to the primary oncologist or the disease expert. We expand on ways to communicate regarding the objectives of early phase clinical trials, their methods and the important commitment asked from participants. We describe our views on equipoise, uncertainty and hope in this very specific practice. We support a model of shared decision making and empowerment of patients and caregivers. We also detail the use, benefits and challenges of virtual care applied to NAIT consults. Overall, we hope to contribute and facilitate the NAIT practice not only for trained trialists but also less-specialized teams.</p></div>","PeriodicalId":94314,"journal":{"name":"EJC paediatric oncology","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2024-02-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S2772610X24000138/pdfft?md5=a358b55bee4d9dda2b38d12d51888a4b&pid=1-s2.0-S2772610X24000138-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140016032","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}