RESUMEN
Background: The treatment of BRAF V600E gliomas with BRAF inhibitors (BRAFis) and MEK inhibitors (MEKis) has been increasingly integrated into clinical practice for pediatric low-grade gliomas (PLGGs) and pediatric high-grade gliomas (HGGs). However, some questions remain unanswered, such as the best time to start targeted therapy, duration of treatment, and discontinuation of therapy. Given that no clinical trial has been able to address these critical questions, we developed a Canadian Consensus statement for the treatment of BRAF V600E mutated pediatric as well as adolescent and young adult (AYA) gliomas. Methods: Canadian neuro-oncologists were invited to participate in the development of this consensus. The consensus was discussed during monthly web-based national meetings, and the algorithms were revised until a consensus was achieved. Results: A total of 26 participants were involved in the development of the algorithms. Two treatment algorithms are proposed, one for the initiation of treatment and one for the discontinuation of treatment. We suggest that most patients with BRAF V600E gliomas should be treated with BRAFis ± MEKis upfront. Discontinuation of treatment can be considered in certain circumstances, and we suggest a slow wean. Conclusions: Based on expert consensus in Canada, we developed algorithms for treatment initiation of children and AYA with BRAF V600E gliomas as well as a discontinuation algorithm.
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Consenso , Glioma , Mutación , Proteínas Proto-Oncogénicas B-raf , Adolescente , Niño , Femenino , Humanos , Masculino , Adulto Joven , Neoplasias Encefálicas/genética , Neoplasias Encefálicas/tratamiento farmacológico , Canadá , Glioma/genética , Glioma/tratamiento farmacológico , Inhibidores de Proteínas Quinasas/uso terapéutico , Proteínas Proto-Oncogénicas B-raf/genéticaRESUMEN
Cancer is the leading cause of disease-related death in children, adolescents, and young adults beyond the newborn period in North America. Improving survival rates for patients with hard-to-cure cancer remains a challenge. One approach that has gained particular traction is 'precision oncology', whereby next-generation sequencing is used to identify genomic or transcriptomic changes that can help clarify the diagnosis, refine prognosis, define an underlying genetic cause, or identify a unique treatment target for a patient's cancer. In this primer, we provide a brief overview of the evolution of precision paediatric oncology, its current application to clinical oncology practice, and its future potential as a foundational approach to paediatric oncology care in Canada and around the world. We also address the many challenges and limitations inherent to the implementation of precision oncology as the standard of care, including ethical and economic considerations.
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Neoplasias Cerebelosas , Mutismo , Humanos , Mutismo/epidemiología , Mutismo/etiología , Mutismo/terapia , SíndromeRESUMEN
OBJECTIVE: To evaluate the prognostic impact of gastrointestinal involvement on the survival of children with Langerhans cell histiocytosis (GI-LCH) registered with the international clinical trials of the Histiocyte Society. STUDY DESIGN: This was a retrospective analysis of 2414 pediatric patients registered onto the consecutive trials DAL-HX 83, DAL-HX 90, LCH-I, LCH-II, and LCH-III. RESULTS: Among the 1289 patients with single-system LCH, there was no single case confined to the GI tract; 114 of 1125 (10%) patients with multisystem LCH (MS-LCH) had GI-LCH at initial presentation. GI-LCH was significantly more common in children aged <2 years at diagnosis (13% vs 6% in those aged >2 years; P < .001) and in those with risk organ involvement (15% vs 6% in those without risk organ involvement; P < .001). The 5-year overall survival (OS) in patients without risk organ involvement was excellent irrespective of GI disease (98% vs 97% in patients with GI-LCH; P = .789). In patients with risk organ involvement, the 5-year OS was 51% in 70 patients with GI-LCH vs 72% in 394 patients without GI-LCH (P < .001). CONCLUSIONS: GI-LCH has an additive unfavorable prognostic impact in children with MS-LCH and risk organ involvement. The emerding need for more intensive or alternative treatments mandates prospective evaluation.
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Enfermedades Gastrointestinales/etiología , Histiocitosis de Células de Langerhans/diagnóstico , Histiocitosis de Células de Langerhans/mortalidad , Adolescente , Niño , Preescolar , Femenino , Enfermedades Gastrointestinales/diagnóstico , Histiocitosis de Células de Langerhans/complicaciones , Humanos , Lactante , Recién Nacido , Masculino , Pronóstico , Estudios Retrospectivos , Índice de Severidad de la Enfermedad , Análisis de SupervivenciaRESUMEN
Allogeneic hematopoietic stem cell transplantation (allo-HSCT) has become increasingly used as a therapeutic treatment for several pediatric conditions, however the long-term mental health sequelae remain understudied among these survivors. Our objective was to conduct a systematic literature review to determine the association between allo-HSCT and anxiety, depression, and psychological health-related quality of life (HRQOL) in pediatric allo-HSCT recipients compared to survivors of pediatric cancer or healthy children. A literature search of peer-reviewed databases was conducted. Data extraction was conducted using a standardized form. Due to the heterogeneity in studies, populations, and measurement instruments, only a qualitative synthesis was performed. A total of 24 studies met eligibility criteria. Rates of anxiety and depression were higher among survivors of pediatric allo-HSCT compared to population normal values or children treated for health conditions without allo-HSCT. Most allo-HSCT survivors self-reported psychological HRQOL within normal levels, although some studies in leukemia patients identified poorer psychological HRQOL. The presence of multiple chronic health conditions, chronic graft-versus-host-disease, and patient sex were important risk factors for worse mental health. Patients who receive allo-HSCT during childhood experience subsequent anxiety, depression, and poorer psychological HRQOL after transplant and several clinical characteristics contribute to these mental health sequelae.
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Enfermedad Injerto contra Huésped , Trasplante de Células Madre Hematopoyéticas , Ansiedad/etiología , Niño , Depresión/etiología , Enfermedad Injerto contra Huésped/etiología , Trasplante de Células Madre Hematopoyéticas/efectos adversos , Humanos , Calidad de Vida , SobrevivientesRESUMEN
Langerhans cell histiocytosis (LCH) is an inflammatory neoplasm of myeloid origin characterized by the presence of classic CD1a+/CD207+ cells. An ongoing debate over the grouping of LCH was finally settled in favor of neoplasm after the discovery of the BRAF V600E mutation in 2010. The pathologic cells were found to involve an almost universal activation of the MAPK/ERK pathway, with mutations identified in most kinases upstream of ERK (RAS/RAF/MEK). The clinical presentation of LCH is a mixed bag, ranging from self-resolving localized disease to fulminant, fatal disseminated disease. The current standard of care for patients with multisystem LCH, who have high relapse rates, continues to be combination treatment with vinblastine and prednisone. Patients treated with BRAF and MEK inhibitors have shown a significant and sustained response in early-phase trials. During the current decade, researchers have described an extensive genomic landscape for LCH that has significantly enlarged our understanding of the biology and pathogenesis of this disease, especially neurodegenerative LCH. These advances have opened the door to studies of precision medicine and targeted therapy in LCH. Disease reactivation, long-term sequelae, very high-risk disease, and neurodegenerative LCH represent ongoing challenges. A renewed understanding of the biology of this disease, coupled with targeted therapies, may help in overcoming most of these challenges.
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Histiocitosis de Células de Langerhans/diagnóstico , Histiocitosis de Células de Langerhans/terapia , Biomarcadores , Niño , Manejo de la Enfermedad , Susceptibilidad a Enfermedades , Histiocitosis de Células de Langerhans/etiología , Histiocitosis de Células de Langerhans/metabolismo , Humanos , Sistema de Señalización de MAP Quinasas , Terapia Molecular Dirigida , Mutación , Fenotipo , Índice de Severidad de la EnfermedadRESUMEN
Hitherto poor outcomes, paucity of data and heterogeneity in International approach to Pediatric NHL (Non-Hodgkin Lymphoma) prompted the need for guidelines for Indian population with vast variability in access, affordability and infrastructure across the country. These guidelines are based on consensus among the experts and best available evidence applicable to Indian setting. Evaluation of NHL should consist of easily doable and rapid tissue diagnosis (biopsy or flow cytometry of peripheral blood/malignant effusions), St Jude/IPNHLSS (International Pediatric Non-Hodgkin Lymphoma Staging System) and risk grouping with CSF (Cerebro-spinal fluid), bone marrow, whole body imaging [CECT (Contrast enhanced computerized tomography) ± MRI (Magnetic resonance imaging)] and blood investigations for LDH (Lactate dehydrogenase), TLS (Tumor lysis syndrome) and organ functions. Life threatening complications like SVCS (Superior vena cava syndrome)/Mediastinal syndrome and TLS need to pre-empted and promptly managed. All children with poor general condition, co-morbidities, metabolic or obstructive complications should receive a steroid or chemotherapy pro-phase first. For mature B-NHL (B cell - Non-Hodgkin lymphoma), in centres with good infrastructure and methotrexate levels, FAB-LMB-96 (French-American-British/Lymphomes Malins B) or BFM (Berlin-Frankfurt-Münster)-NHL-95 protocols may be used. In centres with limited infrastructure and/or no methotrexate levels; CHOP (Cyclophosphamide-hydroxydaunomycin-oncovin-prednisolone) (early stage) or MCP (Multi-centre protocol)-842 [all stages except CNS (Central nervous system) disease] may be used. Patients with poor early response should have escalated therapy. High-Risk B-NHL will benefit with addition of Rituximab to standard chemotherapy. Radiotherapy (RT) is not warranted. For lymphoblastic lymphoma, in centres with good infrastructure and methotrexate levels, BFM-95 protocol may be used. In centres with limited infrastructure and/or no methotrexate levels; modified MCP-841 with cytarabine, modified BFM-90 protocol with reduced-dose methotrexate or I-BFM 2009 protocol using Capizzi methotrexate may be considered. For ALCL (Anaplastic large cell lymphoma), in centres with good infrastructure and methotrexate levels, ALCL-99 protocol may be considered. In centres with limited infrastructure and/or no methotrexate levels; CHOP (limited-stage only), modified MCP-842 protocol or APO (Adriamycin-prednisolone-oncovin) regimen may be used.
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Linfoma no Hodgkin/terapia , Niño , Humanos , India , Linfoma no Hodgkin/diagnóstico , Linfoma no Hodgkin/patologíaRESUMEN
The prevalence of people affected by cancer has been steadily increasing. More and more people are being offered the chance of increased longevity. This has been possible due to advances not only in medicines and techniques but also because of the gain in understanding of cancer biology through Translational Cancer Medicine. A significant step towards obtaining this success was the establishment of successful biobanking practise. In this review we discuss about the importance of a Biobank and the various impacts that a biobank can have not only in the field of cancer but also on many other aspects. Later we discuss a method of quantitative evaluation of these impacts of a biobank.