RESUMEN
Amino acids (AAs) play a crucial role in cancer cell metabolism. Levels of 22 plasma AAs at the time of diagnosis and after treatment were established among 39 pediatric cancer patients and 33 healthy children. Glutamic acid levels decreased and tryptophan levels increased during treatment. Cancer patients presented significantly lower levels of glutamine and leucine post-treatment while levels of 12 other AAs were higher comparing to controls. Results suggest that plasma free AA profile may serve as a prognostic biomarker.
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Aminoácidos/sangre , Neoplasias/sangre , Adolescente , Biomarcadores de Tumor/sangre , Niño , Preescolar , Femenino , Estudios de Seguimiento , Humanos , Lactante , Masculino , Metabolómica , Neoplasias/diagnóstico , Neoplasias/terapia , PronósticoRESUMEN
Thymic tumors are epithelial tumors arising from the anterior mediastinum and constitute 0.2-1.5% of all adult malignancies but are exceptional in pediatric population. Thymic epithelial tumors (TETs) encompass a variety of histologic subtypes associated with different clinical outcomes. Due to its rarity in children, TETs' management requires a multidisciplinary approach. However, prognosis remains still poor, especially among patients with thymic carcinoma. This study presents the internationally recognized recommendations for the diagnosis and treatment of thymic tumors in children and adolescents, established by the European Cooperative Study Group for Pediatric Rare Tumors (EXPeRT) group within the EU-funded project Paediatric Rare Tumours Network - European Registry (PARTNER).
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Neoplasias Glandulares y Epiteliales , Timoma , Neoplasias del Timo , Adolescente , Adulto , Niño , Humanos , Pronóstico , Timoma/diagnóstico , Timoma/patología , Timoma/terapia , Neoplasias del Timo/diagnóstico , Neoplasias del Timo/patología , Neoplasias del Timo/terapiaRESUMEN
The PARTNER project (Paediatric Rare Tumours Network - European Registry) was launched in 2016. PARTNER aims to create a European Registry dedicated to children and adolescents with very rare tumors (VRT). It links existing national registries and provides a registry for those countries in which a VRT registry has not yet been created. This consortium is composed of the various national cooperative groups and their respective member institutions. The strategic value of this project is based on the Europe-wide data collection concerning the treatment of VRTs. These data are provided to experts and constitute the basis for new clinical practice guidelines for use by ERN (European Reference Network) and non-ERN institutions. The proposed tasks and milestones will increase collaboration in the field of pediatric oncology among member states and will also facilitate the inclusion of low health expenditure average rate (LHEAR) countries in this process. In addition, this project creates a platform for VRTs that may represent a model on how to elaborate a comprehensive approach (case registration, international case consultation and treatment recommendations, and website to provide information for parents/patients) for rare diseases.
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Neoplasias , Adolescente , Niño , Europa (Continente)/epidemiología , Humanos , Oncología Médica , Neoplasias/terapia , Enfermedades Raras/epidemiología , Enfermedades Raras/terapia , Sistema de RegistrosRESUMEN
As part of the European Union-funded project designated Paediatric Rare Tumours Network - European Registry (PARTNER), the European Cooperative Study Group for Pediatric Rare Tumors (EXPeRT) is continuously developing consensus recommendations in order to harmonize standard care for very rare solid tumors of children and adolescents. This paper presents the internationally recognized recommendations for the diagnosis and treatment of sex cord stromal tumors (SCST). The clinical approach to sex cord stromal tumors of the testis (TSCST) and ovary (OSCST) depends on histological differentiation and tumor stage. Virtually all TSCSTs present as localized nonmetastatic tumors, with excellent prognosis after complete resection. In contrast, the prognosis of OSCSTs may be adversely affected by tumor spillage during surgery or presence of metastases. In these cases, cisplatin-based chemotherapy is recommended. Of note, some SCSTs may develop in the context of tumor predisposition syndromes, for example, DICER-1, so that specific follow-up is indicated. SCSTs should be diagnosed and treated according to standardized recommendations that include reference pathology, genetic testing for tumor predisposition syndromes in selected cases, and stratified adjuvant chemotherapy in patients with unfavorable risk profile. To ensure high quality of diagnosis and therapy, patients should be enrolled into prospective registries.
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Neoplasias Ováricas , Tumores de los Cordones Sexuales y Estroma de las Gónadas , Adolescente , Niño , Consenso , Femenino , Humanos , Masculino , Neoplasias Ováricas/diagnóstico , Neoplasias Ováricas/genética , Neoplasias Ováricas/terapia , Estudios Prospectivos , Tumores de los Cordones Sexuales y Estroma de las Gónadas/diagnóstico , Tumores de los Cordones Sexuales y Estroma de las Gónadas/genética , Tumores de los Cordones Sexuales y Estroma de las Gónadas/terapia , SíndromeRESUMEN
Pancreatoblastoma (PBL) is a rare malignant epithelial neoplasm that affects typically young children. Signs related to advanced upper-abdominal tumor accompanied by elevated serum α-fetoprotein levels in a young child suggest PBL, however histopathological confirmation is mandatory. The mainstay of the treatment is a complete surgical resection. Unresectable and/or metastatic PBL may become amenable to complete delayed surgery after neoadjuvant chemotherapy. This manuscript presents the international consensus recommendations for the diagnosis and treatment of children with PBL, established by the European Cooperative Study Group for Pediatric Rare Tumors (EXPeRT) within the EU-funded PARTNER (Paediatric Rare Tumors Network - European Registry) project.
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Neoplasias Pancreáticas , Quimioterapia Adyuvante , Niño , Preescolar , Humanos , Terapia Neoadyuvante , Pancreatectomía , Neoplasias Pancreáticas/diagnóstico , Neoplasias Pancreáticas/patología , Neoplasias Pancreáticas/terapia , Enfermedades RarasRESUMEN
It has become increasingly clear in recent years that we need to develop ad hoc strategies to combat very rare tumors (VRT) of pediatric age. In 2008, several schemes being run in different countries were pooled together to create the European Cooperative Study Group for Pediatric Rare Tumors (EXPeRT) project: a cooperative study group that aimed to promote research in the relatively uncharted territory of rare tumors of pediatric age. EXPeRT members were able to activate different levels of cooperation to achieve their goals, and to obtain dedicated funding by participating in EU-financed projects. Their experiences emphasize the merits of networking, seeking new partnerships, joining forces, and pooling resources to extend the reach of research efforts, and ultimately improve the quality of patient care. Between 2018 and 2021, the EXPeRT has been active in establishing the Pediatric Rare Tumors Network - European Registry (PARTNER). This project had the main purposes of building a European common registry of pediatric VRT, but also the major task of developing diagnostic and treatment guidelines for VRT (or at least part of them). These clinical recommendations are the subject of a series of papers on Pediatric Blood and Cancer.
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Objetivos , Neoplasias , Niño , Humanos , Sistemas de Información , Neoplasias/terapia , Sistema de RegistrosRESUMEN
Cutaneous melanoma is rare in children and, like other very rare pediatric tumors, it suffers from a shortage of knowledge and clinical expertise. The clinical management of pediatric melanoma is often challenging. Its clinical and pathological diagnosis may be difficult, and there is no standard treatment. In the absence of specific treatment guidelines, young patients are generally treated following the same principle as for adults, but concern remains about their access to clinical trials and new drugs, which have been shown to dramatically change the natural history of advanced melanoma. This paper presents the internationally recognized recommendations for the diagnosis and treatment of children and adolescents with cutaneous melanoma, established by the European Cooperative Study Group for Pediatric Rare Tumors (EXPeRT) within the EU-funded project called PARTNER (Paediatric Rare Tumours Network - European Registry). Main recommendations for melanoma are to discuss pediatric patients in multidisciplinary teams that include both pediatric oncologists and specialists in adult melanoma; to enroll patients in prospective trials, if available; to collect data in national-international databases; and to develop an effective international collaboration between pediatric and adult melanoma groups in order to facilitate the transfer of potentially effective new agents from the adult to the pediatric setting.
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Melanoma , Neoplasias Cutáneas , Adolescente , Adulto , Niño , Humanos , Melanoma/diagnóstico , Melanoma/patología , Melanoma/terapia , Estudios Prospectivos , Sistema de Registros , Neoplasias Cutáneas/diagnóstico , Neoplasias Cutáneas/terapia , Melanoma Cutáneo MalignoRESUMEN
Salivary gland carcinomas (SGCs) are rare during childhood and adolescence. Consequently, no standardized recommendations for the diagnosis and therapeutic management of pediatric SGC are available, and pediatric oncologists and surgeons generally follow adult guidelines. Complete surgical resection with adequate margins constitutes the cornerstone of treatment. However, the indications and modalities of adjuvant therapy remain controversial and may be challenging in view of the potential long-term toxicities in the pediatric population. This paper presents the consensus recommendations for the diagnosis and treatment of children and adolescents with SGCs, established by the European Cooperative Study Group for Pediatric Rare Tumors (EXPeRT) within the EU-funded PARTNER project (Paediatric Rare Tumours Network - European Registry).
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Carcinoma , Neoplasias de las Glándulas Salivales , Adolescente , Adulto , Carcinoma/patología , Niño , Humanos , Neoplasias de las Glándulas Salivales/diagnóstico , Neoplasias de las Glándulas Salivales/patología , Neoplasias de las Glándulas Salivales/terapia , Glándulas Salivales/patologíaRESUMEN
Adrenocortical tumours (ACTs) are rare during childhood. A complete surgical resection provides the best chance of cure, but the role and efficacy of the adjuvant therapy are still controversial. Various histologic criteria of malignancy for ACTs adopted in children do not facilitate comparative studies and are not completely shared. Therefore, a sharp demarcation between benign and malignant lesions has not been recognised, making it difficult to identify who potentially needs perioperative therapy. This manuscript presents the internationally harmonised recommendations for the diagnosis and treatment of ACTs in children and adolescents, established by the European Cooperative Study Group for Paediatric Rare Tumours (EXPeRT) group within the EU-funded project PARTNER (Paediatric Rare Tumours Network - European Registry).
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Neoplasias , Adolescente , Niño , Terapia Combinada , Humanos , Sistema de RegistrosRESUMEN
Pleuropulmonary blastoma (PPB) is a rare cancer occurring mainly during early childhood and often associated with germline DICER1 mutations. It is classified by the macroscopic appearance into three interrelated clinico-pathologic entities on a developmental continuum. Complete tumor resection is a main prognostic factor and can be performed at diagnosis or after neoadjuvant treatment that includes chemotherapy and in some cases radiotherapy. Optimal modalities of neo- or adjuvant treatments can be challenging taking into account potential long-term toxicities in this young population. This paper presents the recommendations for diagnosis and treatment of children and adolescents with PPB elaborated by the European Cooperative Study Group for Pediatric Rare Tumors (EXPeRT) within the European Union-funded project PARTNER (Paediatric Rare Tumours Network - European Registry).
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Neoplasias Pulmonares , Blastoma Pulmonar , Adolescente , Niño , Preescolar , ARN Helicasas DEAD-box/genética , Humanos , Neoplasias Pulmonares/diagnóstico , Neoplasias Pulmonares/genética , Neoplasias Pulmonares/terapia , Terapia Neoadyuvante , Blastoma Pulmonar/diagnóstico , Blastoma Pulmonar/genética , Blastoma Pulmonar/terapia , Sistema de Registros , Ribonucleasa IIIRESUMEN
Nasopharyngeal carcinoma (NPC) is a rare pediatric tumor. Collaborative studies performed over the last decades showed improved results compared to historical data, but standardized guidelines for diagnosis and management of pediatric NPC are still unavailable. This study presents a European consensus guideline for the diagnosis and treatment of pediatric NPC developed by the European Cooperative Study Group for Pediatric Rare Tumors (EXPeRT). Main recommendations include induction chemotherapy with cisplatin and 5-flurouracil, concomitant chemoradiotherapy in advanced disease, and to consider maintenance treatment with interferon beta (IFN-ß) for selected high-risk patients. Dose adjustments of radiotherapy based on response to induction chemotherapy may decrease the rates of long-term treatment-related complications that affect most of the survivors.
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Carcinoma , Neoplasias Nasofaríngeas , Adolescente , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Carcinoma/patología , Quimioradioterapia , Niño , Cisplatino , Fluorouracilo , Humanos , Quimioterapia de Inducción , Carcinoma Nasofaríngeo/tratamiento farmacológico , Carcinoma Nasofaríngeo/terapia , Neoplasias Nasofaríngeas/tratamiento farmacológico , Neoplasias Nasofaríngeas/terapia , Estadificación de NeoplasiasRESUMEN
Nodular Lymphocyte Predominant Hodgkin Lymphoma (NLPHL) is a rare clinical entity. To investigate NLPHL clinical course and treatment a survey was performed within Polish Pediatric Leukaemia/Lymphoma Study Group (PPLLSG) participating centers. A questionnaire was sent to all participating centers and analysis of clinical data was performed. From 2010 to 2019, 19 pediatric patients with confirmed NLPHL were registered in Poland. Median age of patients was 12.2 (5.5 - 17.8) years. NLPHL occurred mainly in males (n = 17). Most of the patients (n = 16) had early stage disease - Stage I (n = 6) and stage II (n = 10). Four of the six patients with stage I disease (I A, n = 5; I B, n = 1) underwent complete primary resection. One of these relapsed and was treated with CVP (cyclophosphamide, vinblastine, prednisone) chemotherapy. Two other patients who were not resected completely received CVP chemotherapy and no relapses were observed. Thirteen patients presented with unresectable disease. Of these, eight received three CVP chemotherapy cycles, and five were treated with other chemotherapy regimens. Three relapses were observed and these patients were further treated with chemotherapy and rituximab. One patient underwent autologous stem cell transplantation (auto-SCT). All patients remain alive. Five-year progression-free survival and overall survival for the entire group of patients was 81.6% and 100%, respectively. NLPHL treatment results are consistent with results noted in other countries. Early stage patients have very good outcomes with surgery and observation or low intensity chemotherapy, but this approach may be insufficient in advanced disease.
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Trasplante de Células Madre Hematopoyéticas , Enfermedad de Hodgkin , Adolescente , Niño , Preescolar , Femenino , Enfermedad de Hodgkin/clasificación , Enfermedad de Hodgkin/terapia , Humanos , Linfocitos , Masculino , Polonia , Recurrencia , Trasplante AutólogoRESUMEN
Anti-cancer treatment in children can deteriorate gonadal function and affect future fertility. We analyzed the hormonal markers of gonadal function in adolescent leukemia survivors, treated in childhood with different levels of aggressiveness. We analyzed hormone levels in 69 adolescents and young adults, leukemia survivors stratified into standard (SR), intermediate (IR), and high (HR) risk groups, and in 80 healthy controls (38 men) at a similar age. We assessed follicular stimulating hormone (FSH), luteinizing hormone (LH), and inhibin B in the whole group, testosterone in males, and E2 and anti-Müllerian hormone (AMH) in females. Males classified into HR group presented, in comparison to control, higher levels of FSH, LH, lower inhibin B, and normal testosterone, whereas in SR and IR group, the hormonal values were comparable to the control. In females, in all risk groups, the levels of FSH, LH, E2, and inhibin B were comparable with the control, but the mean AMH levels were slightly lowered. We did not observe the effect of prophylactic cranial irradiation (12 or 18 Gy) or the time of treatment (before vs. during puberty) on hormone levels. In females, a positive correlation was found between the time interval after the end of treatment and AMH levels. Male leukemia survivors having undergone more intensive chemotherapy show the symptoms of disturbed spermatogenesis and need to be followed-up in the future. Women, irrespective of the risk group, can develop the signs of preterm ovarian insufficiency. They should be informed about the impact of the treatment on gonadal function.
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Biomarcadores , Supervivientes de Cáncer , Hormonas Esteroides Gonadales/sangre , Leucemia-Linfoma Linfoblástico de Células Precursoras/sangre , Adolescente , Niño , Preescolar , Terapia Combinada/efectos adversos , Terapia Combinada/métodos , Femenino , Fertilidad , Estudios de Seguimiento , Gónadas/metabolismo , Humanos , Masculino , Leucemia-Linfoma Linfoblástico de Células Precursoras/diagnóstico , Leucemia-Linfoma Linfoblástico de Células Precursoras/terapiaRESUMEN
INTRODUCTION: Cutaneous melanoma is rare in childhood and published studies have mainly been retrospective single-institution series or small case series. Given the absence of clinical protocols dedicated to pediatric melanoma, the treatment approach is generally extrapolated from the ones applied to adults. METHODS: Coordinated by the European Cooperative Study Group for Pediatric Rare Tumors (EXPeRT), this study collected patients prospectively registered between 2002 and 2012 under national cooperative projects dedicated to rare pediatric tumors in Italy, Poland, Germany, and France. Additional cases were collected from dermatology registries in Germany and Israel. RESULTS: A total of 219 patients aged 0-18 years (median 14.4) were included in the analysis. Sentinel lymph node biopsy was performed in 112 patients (76% of those with Breslow thickness > 0.75 mm) and was positive in 37.5%. Systemic therapy was used in 33 cases. In stage III cases, survival rates were similar for patients who received (23 cases) or not (21 cases) adjuvant therapy. For the whole series, 3-year overall and disease-free survival rates were 91.4% and 84.0%, respectively (median follow-up 41.8 months). Tumor site, tumor stage, and ulceration influenced survival rates. Patients treated by pediatric oncologists (n = 140) were more likely to have advanced disease than those treated by dermatologists (n = 79). DISCUSSION: This study would suggest that the clinical history of melanoma in children and adolescents might resemble that of adult counterpart. Cooperative efforts are needed to make new drugs more readily available to pediatric patients to increase the outcome of patient with advanced disease.
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Melanoma/mortalidad , Melanoma/terapia , Neoplasias Cutáneas/mortalidad , Neoplasias Cutáneas/terapia , Adolescente , Adulto , Niño , Preescolar , Terapia Combinada , Europa (Continente) , Femenino , Estudios de Seguimiento , Humanos , Lactante , Recién Nacido , Masculino , Melanoma/diagnóstico , Pronóstico , Estudios Prospectivos , Neoplasias Cutáneas/diagnóstico , Tasa de Supervivencia , Adulto Joven , Melanoma Cutáneo MalignoRESUMEN
In the last 40 years, considerable progress was made in the treatment of childhood cancer. Nearly 80% of children achieve long-term clinical remission or are permanently cured. This improvement is however not without sacrifice. This is the first Polish study analyzing the general health status and epidemiology of organ late effects in the cohort of Polish childhood and adolescent cancer survivors monitored by doctors and registered in the on-line national database for late effects (N = 1761). This tool collects information on previous therapy and current health status (medical history, physical examination, laboratory tests) of cancer survivors. The survivors are invited to take part in the follow-up examination 5 years after the end of treatment. In the study group, 207 survivors (11.75%) had no complaints; whereas in 1554 cases (88.25%), one or more symptoms/complaints suggesting organ dysfunction were reported. In the whole group, the circulatory problems were most common (31.7%); more than 20% of survivors presented complaints or abnormal function of the urinary tract and had skin, dental, skeletal/muscular problems, or difficulty with chewing. Obesity or short stature alone (21.4%) and a variety of endocrine problems (short stature, obesity, thyroid dysfunction, and gonads toxicity) were present in 323 patients (118 females 15.0% and 205 males 21.0%). Gonadal dysfunction, as the only problem, occurred in 75 girls (9.6%) and 131 boys (13.4%). In our cohort, severe or life-threatening health conditions (3 and 4 grade according to toxicity criteria) were present in low percentage, i.e., 0.2% in the circulatory system, 0.3% in the respiratory tract and, 0.7% in kidney insufficiency. CONCLUSION: Our findings indicate that many childhood cancer survivors demonstrate numerous complaints, even a short time after treatment, suggesting the importance of regular follow-up examinations in subsequent years. What is Known: ⢠Contemporary studies indicate that a significant number of childhood cancer survivors present different long-term side effects which influence their quality of life. What is New: ⢠This is the first nationwide study performed in the largest cohort of Polish childhood cancer survivors concerning general health status and frequency of organ dysfunction.
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Supervivientes de Cáncer , Estado de Salud , Neoplasias/complicaciones , Neoplasias/terapia , Adolescente , Niño , Preescolar , Femenino , Estudios de Seguimiento , Humanos , Lactante , Masculino , Polonia , Adulto JovenRESUMEN
The first and family names of the authors were interchanged. The correct author names are now correctly presented in this article.
RESUMEN
The aim of this review is to specify new potential reliable and non-invasive methods for the diagnosis of biliary atresia (BA) that could shorten the way to diagnose BA, and finally the surgical treatment. Apart from the biomarkers that have been proven helpful and are used nowadays in neonatal wards, there are several new potential biomarkers that researchers have found to be helpful in the diagnosis of biliary atresia. Circulating microRNAs, matrix metalloproteinase-7, stool proteins, interleukin-33, Th17-associated cytokines, urinary metabolomics, anti-smooth muscle antibodies, heat shock proteins 90 and positive biliary epithelial cells CD56 are among those presented in this summary. These markers may play a new significant role in BA diagnosis. The described methods include Nomogram, Circulating microRNAs (miRNAs), Matrix metalloproteinase-7 (MMP-7), Stool proteins, Interleukin-33 (IL-33), Th17-associated cytokines, Alpha-aminoadipic acid and N-acetyl-d-mannosamine in urine, Anti-smooth muscle antibodies (ASMA), Heat shock proteins 90 (HSP90), Positive biliary epithelial cells CD56.
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Atresia Biliar , MicroARNs , Recién Nacido , Humanos , Atresia Biliar/diagnóstico , Proteínas HSP90 de Choque Térmico , Interleucina-33 , Metaloproteinasa 7 de la Matriz , Autoanticuerpos , Biomarcadores , CitocinasRESUMEN
Pheochromocytoma (PPC) and paraganglioma (PGL) are the tumors that rarely occur in the pediatric population (PPGL). Both originate from chromaffin cells, pheochromocytoma is localized in the adrenal gland, whereas paragangliomas are regarded as the tumors present in other localizations, from head to the pelvis. The clinical image is characterized by the presence of the sustained hypertension, headaches, sweating, palpitations. The symptoms are caused by the catecholamine secretion or are related to tumor mass pressure on different organs. The catecholamines and their metabolites levels in urine collection or plasma are necessary for further evaluation of the diagnosis. In pediatric population the tumors occur in multiple familial syndromes such as Multiple Endocrine type 2, Neurofibromatosis type 1, Von Hippel-Lindau syndrome, Familial Paraganglioma syndrome are related to specific mutations (SDHx, RET, VHL, NF1) leading to the characteristic phenotype. The radiological and nuclear imaging are an important part of the examination. Although CT and MR are reported to have overall good sensitivity for the tumor detection, further analysis with nuclear imaging is recommended for the specified diagnosis. Right now 68GA-DOTATATE is regarded as the tracer of choice, leading to the complex evaluation of patients with different mutations and metastatic disease. The treatment of choice is the tumor excision. Also, lately new therapeutic approaches including genetically targeted therapies are under investigation for more complex treatment of tumors with underlying genetic cause or metastatic disease. Long term follow-up after treatment to avoid recurrence or to detect it in early stadium must be performed.
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Neoplasias de las Glándulas Suprarrenales , Paraganglioma , Feocromocitoma , Niño , Humanos , Adolescente , Feocromocitoma/diagnóstico , Feocromocitoma/genética , Feocromocitoma/terapia , Paraganglioma/diagnóstico , Paraganglioma/genética , Paraganglioma/terapia , Transporte Biológico , Catecolaminas , Neoplasias de las Glándulas Suprarrenales/diagnóstico , Neoplasias de las Glándulas Suprarrenales/genética , Neoplasias de las Glándulas Suprarrenales/terapiaRESUMEN
Cytokines are responsible for maintaining homeostasis as cell growth, differentiation, migration and apoptosis mediators. They play a pivotal role in immune responses to inflammatory reactions. In oncological diseases, the cross-talk between cells of the immunological system and cells of the tumour microenvironment is led by cytokines. Also, the overproduction of cytokines may change the tumour microenvironment and stimulate tumour development and growth. To test whether pro-inflammatory cytokines or associated with them transcription factor levels are changed in a group of 53 paediatric cancer patients, serum levels of IL-1ß, IL-6, TNF-α and NF-κB were assessed and compared to measures in 25 healthy controls. Increased levels of IL-6 were found among patients in active oncological treatment (P=0.002) but not among patients whose treatment was completed. Our data suggest that IL6, but not IL-1ß, TNF-α and NF-κB, is elevated as a result of the immune response in the microenvironment around the tumour and in blood cancers, among patients who were not infected at the time of blood collection. Thus, IL6 levels might serve as a potential biomarker of oncohematological diseases.