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BACKGROUND: More than 50% children with high-risk neuroblastoma (HR-NBL) experience disease progression, which we hypothesise is due to non-response of primary tumour to treatment. Current imaging techniques are unable to characterise response in primary tumour (necrotic versus viable tissue) at diagnosis or follow-up. OBJECTIVES: Compare clinico-histological characteristics between primary 123ImIBG-avid tumours that became entirely 123ImIBG-non-avid (responders) after induction chemotherapy (IC) versus primary 123ImIBG-avid tumour that remained 123ImIBG-avid (non-responders). METHODS: Retrospective review of clinico-radiological data of children diagnosed with 123ImIBG-avid HR-NBL at our centre (2005-2016). Patients received Rapid COJEC IC and two additional courses of TVD if metastatic response was inadequate. Primary tumour 123ImIBG response was assessed qualitatively as positive, negative or intermediate at diagnosis and after IC. Post-surgical histopathology slices were marked considering percentage of viable tissue. RESULTS: Sixteen of 61 patients showed complete primary tumour 123ImIBG response, 20 partial response, while 25 no response. There was no statistically significant difference between clinical demographics of complete responders and group of non- or partial responders. Mean percentage of viable tumour cells was higher in non-responders than in complete responders (44.6% vs 20.6%; p = 0.05). Five-year EFS was significantly higher in complete responders than non-responders (43 ± 15% vs 7 ± 6%; p < 0.005). CONCLUSIONS: 123ImIBG response in primary HR-NBL correlates with amount of necrotic tissue, skeletal metastatic 123ImIBG response and outcome. An entirely 123ImIBG non-avid tumour can still harbour viable tumour cells. Therefore, our findings do not support utility of primary tumour 123ImIBG response in decision making regarding residual tumour surgery. Combining both, primary and metastatic 123ImIBG response will improve interpretability of clinical trial results.
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Quimioterapia de Indução , Neuroblastoma , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Humanos , Lactente , Neuroblastoma/tratamento farmacológico , Estudos RetrospectivosRESUMO
In this study, we report three paediatric cases of Diffuse Glioneuronal Tumours with Oligodendroglioma-like features and Nuclear Clusters (DGONC).
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Neoplasias Encefálicas/patologia , Ganglioglioma/patologia , Oligodendroglioma/patologia , Criança , Humanos , MasculinoRESUMO
PURPOSE: Effective treatment of diffuse intrinsic pontine glioma (DIPG) remains a formidable challenge due to inadequate penetration of the blood-brain barrier (BBB) by systemically administered chemotherapies. The BBB can be overcome by directly infusing drugs into pons using method of convection-enhanced delivery (CED). We describe our clinical experience and what we have learned about the safety and feasibility of treating DIPG with intermittent CED of carboplatin and sodium valproate to the pons through the Renishaw Drug Delivery System (RDDS). METHODS: Retrospective review (2017-2020) of children with DIPG, who following radiotherapy, received compassionate treatment commencing 3.3-10 months post-diagnosis (median 4.9 months). They received up to 7 cycles of 3-6 weekly pontine infusions of carboplatin (0.12-0.18 mg/ml) and sodium valproate (14.4-28.8 mg/ml). RESULTS: 13 children 3-19 years (mean 6.9 years) were treated. There were no surgical complications. With the exception of infusion channels blocking in one device, there were no adverse device effects. Two patients developed persistent 6th nerve palsies, which led to drug concentration reduction in the combination therapy. Subsequently infusion/ drug-related toxicities were transient. Tumour was controlled in pons in 10/13 patients. Median progression-free survival (PFS) was 13.0 months, while median overall survival (OS) was 15.3 months. CONCLUSIONS: Use of the RDDS was safe and well tolerated in all 13 patients. Treatment improved control of pontine disease resulting in longer PFS and OS and merits further evaluation in a clinical trial.
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Antineoplásicos , Glioma Pontino Intrínseco Difuso , Glioma , Antineoplásicos/uso terapêutico , Carboplatina/efeitos adversos , Criança , Convecção , Glioma/tratamento farmacológico , Glioma/radioterapia , Humanos , Ponte , Estudos Retrospectivos , Ácido Valproico/efeitos adversos , Adulto JovemRESUMO
BACKGROUND: Diffuse midline gliomas (DMG) are aggressive brain tumours, previously known as diffuse intrinsic pontine gliomas (DIPG), with 10% overall survival (OS) at 18 months. Predicting OS will help refine treatment strategy in this patient group. MRI based texture analysis (MRTA) is novel image analysis technique that provides objective information about spatial arrangement of MRI signal intensity (heterogeneity) and has potential to be imaging biomarker. OBJECTIVES: To investigate MRTA in predicting OS in childhood DMG. METHODS: Retrospective study of patients diagnosed with DMG, based on radiological features, treated at our institution 2007-2017. MRIs were acquired at diagnosis and 6 weeks after radiotherapy (54Gy in 30 fractions). MRTA was performed using commercial available TexRAD research software on T2W sequence and Apparent Diffusion Coefficient (ADC) maps encapsulating tumour in the largest single axial plane. MRTA comprised filtration-histogram technique using statistical and histogram metrics for quantification of texture. Kaplan-Meier survival analysis determined association of MRI texture parameters with OS. RESULTS: In all, 32 children 2-14 years (median 7 years) were included. MRTA was undertaken on T2W (n=32) and ADC (n=22). T2W-MRTA parameters were better at prognosticating than ADC-MRTA. Children with homogenous tumour texture, at medium scale on diagnostic T2W MRI, had worse prognosis (Mean of Positive Pixels (MPP): P=0.005, mean: P=0.009, SD: P=0.011, kurtosis: P=0.037, entropy: P=0.042). Best predictor MPP was able to stratify patients into poor and good prognostic groups with median survival of 7.5 months versus 17.5 months, respectively. CONCLUSIONS: DMG with more homogeneous texture on diagnostic MRI is associated with worse prognosis. Texture parameter MPP is the most predictive marker of OS in childhood DMG.
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Neoplasias do Tronco Encefálico , Glioma , Criança , Imagem de Difusão por Ressonância Magnética , Glioma/diagnóstico por imagem , Humanos , Imageamento por Ressonância Magnética , Estudos RetrospectivosRESUMO
Primary tumours of the meninges are rare accounting for only 0.4-4.6% of all paediatric tumours of the central nervous system. Due to the rarity of these tumours in children, and the consequent absence of collaborative prospective trials, there is no clear consensus on how the unique characteristics of paediatric meningiomas impact clinical status, management approach, and survival. Much of the evidence and treatment recommendations for paediatric meningiomas are extrapolated from adult data. Translating and adapting adult treatment recommendations into paediatric practice can be challenging and might inadvertently lead to inappropriate management. In 2009, Traunecker et al. published guidelines for the management of intracranial meningioma in children and young people on behalf of UK Children's Cancer and Leukaemia Group (CCLG). Ten years later we have developed the updated guidelines following a comprehensive appraisal of the literature. Complete surgical resection is the treatment of choice for symptomatic meningiomas, while radiotherapy remains the only available adjuvant therapy and may be necessary for those tumours that cannot be completely removed. However, significant advances have been made in the identification of the genetic and molecular alterations of meningioma, which has not only a potential value in the development of therapeutic agents but also in surveillance of childhood meningioma survivors. This guideline builds upon the CCLG 2009 guideline. We summarise recommendations for the diagnosis, treatment, surveillance and long-term follow-up of children and adolescents with meningioma.
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Leucemia , Neoplasias Meníngeas , Meningioma , Adolescente , Criança , Humanos , Neoplasias Meníngeas/diagnóstico , Neoplasias Meníngeas/terapia , Meningioma/diagnóstico , Meningioma/terapia , Estudos Prospectivos , Sobreviventes , Adulto JovemRESUMO
Wilms tumour (WT) is the commonest primary malignant renal tumour of childhood. Acquired von Willebrand syndrome (avWS) is a well-described paraneoplastic phenomenon, but it is uncommon and may not be detected until clinically significant bleeding is encountered during interventional procedures. Previous studies on small cohorts of patients have determined an incidence of between 4 and 8%. We have performed a retrospective study on cases of WT presenting over an 11.5-year period to a paediatric haematology/oncology unit in a tertiary referral centre to review the incidence of avWS, bleeding phenotype, management, and response to treatment of the primary pathology.
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Neoplasias Renais/fisiopatologia , Tumor de Wilms/fisiopatologia , Doenças de von Willebrand/epidemiologia , Criança , Pré-Escolar , Feminino , Seguimentos , Hemorragia/epidemiologia , Humanos , Incidência , Lactente , Masculino , Prognóstico , Estudos Retrospectivos , Centros de Atenção Terciária , Reino Unido/epidemiologia , Doenças de von Willebrand/diagnósticoRESUMO
BACKGROUND: The introduction of aggressive chemo-radiotherapy regimens has improved overall survival in children with primitive neuroectodermal tumours (PNET). However, these combinations may result in neurotoxicity. Previously reported magnetic resonance imaging abnormalities in children receiving intensive sequential chemotherapy, hyperfractionated accelerated radiotherapy (HART) and high-dose thiotepa prompted us to investigate the degree of brain volume loss and patients' functional status after therapy. METHODS: We retrospectively reviewed clinico-radiological data of children with PNET treated in this way at our centre. RESULTS: We studied 14 children treated between December 2009 and April 2013. Data were not complete for one child. Performance status was severely restricted in four children, and mildly to moderately impaired in 7 of the 13 children. Eleven of 13 children showed mild-to-severe generalised neuroparenchymal atrophy, in 7 of whom neuroparenchymal volume loss was moderate to severe. Of these seven, six had received high-dose thiotepa. There was no correlation between brain volume loss and Lansky performance status. However, unexpected neurotoxicities, such as symptoms of transverse myelitis, were observed. CONCLUSION: Measurement of brain volume loss in patients treated with HART and high-dose thiotepa may not be sufficient to predict function. However, correlation of brain volume loss due to late neurotoxicity with performance decline may be more obvious over longer period of follow-up. The combination of HART and myeloablative courses of thiotepa is associated with severe neurotoxicity and subsequent decline in performance status in a significant proportion of patients.
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Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Neoplasias Encefálicas/patologia , Quimiorradioterapia , Quimioterapia de Indução , Tumores Neuroectodérmicos Primitivos/patologia , Adolescente , Neoplasias Encefálicas/terapia , Carboplatina/administração & dosagem , Criança , Pré-Escolar , Ciclofosfamida/administração & dosagem , Fracionamento da Dose de Radiação , Etoposídeo/administração & dosagem , Feminino , Seguimentos , Humanos , Masculino , Estadiamento de Neoplasias , Tumores Neuroectodérmicos Primitivos/terapia , Prognóstico , Estudos Retrospectivos , Taxa de Sobrevida , Tiotepa/administração & dosagem , Carga TumoralRESUMO
Neuroblastoma is the most common extra-cranial malignancy of childhood, with the highest incidence in children younger than 4 years. The prognosis depends on many factors, such as age at diagnosis, stage of disease and molecular genetic subtype. More than 50% of children who present with the disease are deemed to have high-risk neuroblastoma. The standard therapy for children with high-risk neuroblastoma consists of intensive chemotherapy, surgery, radiotherapy, myeloablative consolidation with autologous haematopoietic stem cell rescue followed by the treatment of minimal residual disease with 13-cis-retinoic acid. Unfortunately, more than half of the patients relapse regardless of the treatment intensity. Combined therapy with monoclonal antibodies (anti-GD2), intravenous interleukin-2 (Il-2), intravenous granulocyte-macrophage colony-stimulating factor (GM-CSF) and oral 13-cis-retinoic acid have been proved to be effective in some randomised trials. A better understanding of the underlying immunological processes in therapy with anti-GD2 antibodies will allow its success to be evaluated more accurately and direct future endeavours. Nevertheless, the long-term benefit of this treatment approach needs to be established.
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Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Imunoterapia , Recidiva Local de Neoplasia , Neuroblastoma/terapia , Adolescente , Anticorpos Monoclonais/uso terapêutico , Criança , Pré-Escolar , Fator Estimulador de Colônias de Granulócitos e Macrófagos/uso terapêutico , Humanos , Lactente , Interleucina-2/uso terapêutico , Isotretinoína/uso terapêutico , Neuroblastoma/tratamento farmacológico , Neuroblastoma/patologia , Ensaios Clínicos Controlados Aleatórios como Assunto , Índice de Gravidade de Doença , Resultado do TratamentoAssuntos
Protocolos de Quimioterapia Combinada Antineoplásica/administração & dosagem , Doença de Hodgkin/tratamento farmacológico , Doença de Hodgkin/patologia , Linfonodos/patologia , Linfócitos/patologia , Pré-Escolar , Ciclofosfamida/administração & dosagem , Humanos , Masculino , Prednisolona/administração & dosagem , Vimblastina/administração & dosagemRESUMO
Aims: To determine an imaging protocol that can be used to assess the distribution of infusate in children with DIPG treated with CED. Methods: 13 children diagnosed with DIPG received between 3.8 and 5.7 ml of infusate, through two pairs of catheters to encompass tumor volume on day 1 of cycle one of treatment. Volumetric T2-weighted (T2W) and diffusion-weighted MRI imaging (DWI) were performed before and after day 1 of CED. Apparent diffusion coefficient (ADC) maps were calculated. The tumor volume pre and post CED was automatically segmented on T2W and ADC on the basis of signal intensity. The ADC maps pre and post infusion were aligned and subtracted to visualize the infusate distribution. Results: There was a significant increase (p < 0.001) in mean ADC and T2W signal intensity (SI) ratio and a significant (p < 0.001) increase in mean tumor volume defined by ADC and T2W SI post infusion (mean ADC volume pre: 19.8 ml, post: 24.4 ml; mean T2W volume pre: 19.4 ml, post: 23.4 ml). A significant correlation (p < 0.001) between infusate volume and difference in ADC/T2W SI defined tumor volume was observed (ADC, r = 0.76; T2W, r = 0.70). Finally, pixel-by-pixel subtraction of the ADC maps pre and post infusion demonstrated a volume of high signal intensity, presumed infusate distribution. Conclusions: ADC and T2W MRI are proposed as a combined parameter method for evaluation of CED infusate distribution in brainstem tumors in future clinical trials.
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In this paper, the authors present a clinical picture of the diagnosis and current treatment regimens of optic pathway glioma in the pediatric population, with an emphasis on the role of an ophthalmic diagnosis in the differentiation and monitoring of lesions. Glioma is the most common optic nerve tumor in children. MATERIAL: Articles in PubMed, Scholar and Website were reviewed, taking into account current standards of management related to sporadic or NF1-related optic glioma, epidemiology, location, course of the disease, clinical manifestations, histological types of the tumor, genetic predisposition, diagnostic ophthalmic tests currently applicable in therapeutic monitoring of the tumor, neurological diagnosis, therapeutic management and prognosis. The importance of current screening recommendations, in line with standards, was emphasized. RESULTS: Glioma occurs in children most often in the first decade of life. Initially, they may be asymptomatic, and clinically ophthalmic changes are associated with the organ of vision or with systemic changes. Gliomas associated with the NF1 mutation have a better prognosis for sporadic gliomas. Diagnosis includes radiological imaging methods/MRI/ophthalmology/OCT and visual acuity log MAR assessment. The basis of treatment is clinical observation. In the case of disease progression, surgical treatment, chemotherapy and targeted therapy are used. CONCLUSION: Further research into novel techniques for detecting gliomas would allow for early monitoring of the disease.
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OBJECTIVE: Clinical diagnostic sequencing of circulating tumour DNA (ctDNA) is well advanced for adult patients, but application to paediatric cancer patients lags behind. METHODS: To address this, we have developed a clinically relevant (67 gene) NGS capture panel and accompanying workflow that enables sensitive and reliable detection of low-frequency genetic variants in cell-free DNA (cfDNA) from children with solid tumours. We combined gene panel sequencing with low pass whole-genome sequencing of the same library to inform on genome-wide copy number changes in the blood. RESULTS: Analytical validity was evaluated using control materials, and the method was found to be highly sensitive (0.96 for SNVs and 0.97 for INDEL), specific (0.82 for SNVs and 0.978 for INDEL), repeatable (>0.93 [95% CI: 0.89-0.95]) and reproducible (>0.87 [95% CI: 0.87-0.95]). Potential for clinical application was demonstrated in 39 childhood cancer patients with a spectrum of solid tumours in which the single nucleotide variants expected from tumour sequencing were detected in cfDNA in 94.4% (17/18) of cases with active extracranial disease. In 13 patients, where serial samples were available, we show a close correlation between events detected in cfDNA and treatment response, demonstrate that cfDNA analysis could be a useful tool to monitor disease progression, and show cfDNA sequencing has the potential to identify targetable variants that were not detected in tumour samples. CONCLUSIONS: This is the first pan-cancer DNA sequencing panel that we know to be optimised for cfDNA in children for blood-based molecular diagnostics in paediatric solid tumours.
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Ácidos Nucleicos Livres , DNA Tumoral Circulante , Neoplasias , Adulto , Biomarcadores Tumorais/genética , Ácidos Nucleicos Livres/genética , Criança , Sequenciamento de Nucleotídeos em Larga Escala/métodos , Humanos , Mutação , Neoplasias/diagnóstico , Neoplasias/genética , Neoplasias/patologia , Sequenciamento Completo do Genoma/métodosRESUMO
AIM: Differentiated thyroid cancer (DTC) in children and adolescents is rare and data about its presentation and management are not well known. The aim of this study was to provide evidence of the current practice in the United Kingdom before the launch of the Rare National Paediatric Endocrine Tumours Guidelines (to be published in 2020). METHODS: Seventy-two children and adolescents with DTC (<18 years) who were treated at our institution between 2003 and 2018 were identified and their presentation, treatment and outcomes were reviewed. RESULTS: Median age at presentation was 12.7 years [range: 1-18] and fifty-two (72%) were girls. Fifty (69.4%) children and adolescents presented with a thyroid nodule. Thirteen (18%) had cervical adenopathy and seven of them (54%) underwent an excision biopsy under GA. Eight patients (11%) had evidence of lung metastases at presentation. Twenty-four patients (33%) underwent a hemithyroidectomy and 22 of those had a completion thyroidectomy subsequently, ten (14%) a total thyroidectomy alone and 37 (51%) a total thyroidectomy with lymph nodes dissection. Seventy patients (97%) underwent adjuvant RAI at our institution. The median number of children and adolescents managed per year was five [range: 0-10]. After an overall median follow-up of 40 months, eight patients (11%) had developed recurrent disease. The 1- and 5-year recurrence-free-survival-rates were 93% and 87%, respectively. Overall survival was 100%, with eight children and adolescents (11%) being alive with disease. CONCLUSION: This study confirms that DTC in children and adolescents is uncommon, is frequently advanced at presentation and has considerable recurrence rates. Despite this, overall survival is excellent. Although the work-up was generally appropriate (image-guided cytology), open biopsy for the diagnosis of lymph node involvement was still employed. The introduction of a specific UK guideline for this age-group will likely result in more tailored-made treatment-pathways and thereby hopefully improve quality and outcomes even further. TYPE OF STUDY: Prognosis study. LEVEL OF EVIDENCE: Level IV.
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Adenocarcinoma Folicular , Carcinoma Papilar , Neoplasias da Glândula Tireoide , Adenocarcinoma Folicular/cirurgia , Adolescente , Carcinoma Papilar/cirurgia , Criança , Feminino , Humanos , Recidiva Local de Neoplasia/cirurgia , Prognóstico , Estudos Retrospectivos , Neoplasias da Glândula Tireoide/cirurgia , Tireoidectomia , Reino Unido/epidemiologiaRESUMO
BACKGROUND: More than half of pediatric tumors of central nervous system (CNS) primarily originate in the posterior fossa and are conventionally treated with radiation therapy (RT). OBJECTIVES: The objective of this study was to establish whether corpus callosum volumes (CCV) and whole brain volumes (WBV) are correlated and to determine the impact of whole-brain lowvs high-dose RT on brain parenchymal volume loss as assessed using each technique. MATERIAL AND METHODS: Of the 30 identified children (6-12 years) with newly diagnosed posterior fossa tumors treated with cranial RT, including focal and whole-brain RT, suitable imaging was obtained for 23. Radiotherapy regimens were the following: no whole-brain RT (Group 1, n = 7), low-dose whole-brain RT (<30 Gy, Group 2, n = 9) and high-dose whole-brain RT (>30 Gy, Group 3, n = 7) in addition to focal boost. Magnetic resonance images (MRIs) were analyzed at baseline and follow-up (median 14 months). The CCVs were manually segmented on midline sagittal slice (n = 23), while WBVs were segmented semi-automatically using Freesurfer (n = 15). This was done twice (6-month interval) for all baseline CCV measurements and 5 randomly selected WBV measurements to establish measurement reproducibility. Correlations between CCV and WBV were investigated and percentage of children demonstrating reduction in CCV or WBV noted. RESULTS: Correlation between baseline CCV and WBV was not significant (p = 0.37). Measurement reproducibility was from 6% to -9% for CCV and from 4.8% to -1.2% for WBV. Among the children studied, 30.4% (7/23) had >9% reduction in CCV at follow-up, while 33.3% (5/15) had >1.2% reduction in WBV. Five of 7 patients with CCV loss were not picked up by WBV measurements. Similarly, 3 of 5 patients with WBV loss were not picked up by CCV measurements. CONCLUSIONS: The CCV and the WBV are unrelated and may indicate different brain parenchymal losses following RT. Up to a third of posterior fossa tumors treated with RT have measurable CCV or WBV loss; incidence was equivalent in lowvs high-dose whole-brain RT.
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Neoplasias Encefálicas/radioterapia , Encéfalo/efeitos da radiação , Corpo Caloso/efeitos da radiação , Neoplasias Infratentoriais/radioterapia , Radioterapia/efeitos adversos , Criança , Humanos , Tamanho do Órgão/efeitos da radiação , Reprodutibilidade dos TestesRESUMO
The authors would like to point out a possibility of immune system disturbances (especially lymphocyte T), severe infection occurring in patients following splenectomy. Five children following splenectomy due to severe spherocytosis were studied. In all children serum level of IgA, IgG, IgM immunoglobulins, phagocytic index, Hamburger count and lymphocyte antigen surface expression CD3, CD4 CD10, CD19, CD20, CD29, CD45RA, CD56 were evaluated. In comparison to control group, median numbers of lymphocyte T CD3 (p < 0.05), lymphocyte CD4 (p < 0.05), lymphocyte T CD4CD29 (p < 0.001) and percentage of cells reacting with z CD4CD45RA (p < 0.001) were significantly lower in splenectomized children, whereas number of NK cells occurred to be noticeable higher (p < 0.001). Immunoglobulins' levels, Hamburger count, phagocytic index and percentage of lymphocyte CD8, CD19 and CD20 did not differ between groups. On the basis of the results, the authors recommend the necessity of routine vaccination in this group of patients against most common pathogens.
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Antígenos CD/imunologia , Doenças Transmissíveis/epidemiologia , Doenças Transmissíveis/imunologia , Imunoglobulinas/imunologia , Esplenectomia/estatística & dados numéricos , Criança , Feminino , Fluorometria , Humanos , MasculinoRESUMO
Wilms' tumor is the commonest renal tumor of childhood affecting one in 10,000 children. It is also one of the successes of paediatric oncology with long term survival above 90% for localised disease and 75% for metastatic disease. Successful management of Wilms' tumor necessitates meticulous attention to correct staging of the tumor and a collaborative effort between paediatric oncologists, specialist surgeons, radiologists, pathologists, and radiation oncologists. Although current treatment protocols are based on risk assignment to minimise toxicity for low risk patients and improve outcomes for those with high risk disease, challenges remain in identifying novel molecular, histological and clinical risk factors for stratification of treatment intensity. Knowledge about Wilms' tumor biology and treatment is evolving rapidly and remains a paradigm for multimodal malignancy treatment. Future efforts will focus on the use of biomarkers to improve risk stratification and the introduction of newer molecularly targeted therapies that will minimise toxicity and improve the outcomes for patients with unfavourable histology and recurrent disease. The aim of this article is to summarise advances in our understanding of the biology of Wilms' tumor and to describe the current approaches to clinical management of patients.
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The term "leukaemia" refers to a large and heterogenous group of diseases, with treatment response and outcome dependent on the specific type of malignancy. New molecular methods allow us to specifically evaluate the type of disorder, and provide treatment of necessary intensity. The aim of this review is to provide insight into the progress in leukaemia treatment that had been possible due to advances in molecular genetics over the last few decades. Those new sophisticated diagnostic methods have allowed us not only to predict patients' prognosis but also to provide a specific therapy depending on the molecular and genetic characteristics of patients. Our review is based on 25 articles regarding novel diagnostic and therapeutic methods as well as prognostic factors, released between 1992 and 2011. Those articles focus mostly on molecular and cytogenetic testing allowing revolutionary methods of patient classification and individual therapy for this highly heterogeneous group of disorders. Implementation of molecular genetic testing to evaluate the type of leukaemia allowed paediatric oncologists and haematologists to adjust the intensity of treatment, improve outcome, minimize toxicity of therapies and considerably lower the risk of side effects. In the last few decades there has been a great improvement in survival among children suffering from haematopoietic malignancies. Progress made in molecular genetics allowed the creation of new treatment protocols that are designed to maintain a high cure rate for children with leukaemia while reducing toxicity.
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Antineoplásicos/uso terapêutico , Biomarcadores Tumorais/genética , Leucemia/tratamento farmacológico , Leucemia/genética , Terapia de Alvo Molecular , Transdução de Sinais/efeitos dos fármacos , Animais , Antineoplásicos/efeitos adversos , Criança , Predisposição Genética para Doença , Humanos , Leucemia/metabolismo , Técnicas de Diagnóstico Molecular , Terapia de Alvo Molecular/efeitos adversos , Fenótipo , Medicina de Precisão , Valor Preditivo dos Testes , Indução de Remissão , Fatores de Tempo , Resultado do TratamentoRESUMO
Human cancers represent one of the biggest challenges for modern societies. By 2020, cancer deaths worldwide could reach 10 million. Therefore, one of the important aims of science research is the improvement of anti-malignant treatment options to mitigate cancer-related morbidity and mortality. This essay summarises current trends and future directions of target tumour suppressor genes therapies based on an example of one of the most promising targets, p53.
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Genes Supressores , Neoplasias/terapia , Proteína Supressora de Tumor p53/antagonistas & inibidores , Animais , Quimiorradioterapia , Genes p53 , Humanos , Mutação , Neoplasias/genéticaRESUMO
The use of improved technology has fostered increasing interest in hypofractionated radiation therapy for prostate cancer. There also is convincing evidence that an unusual aspect of prostate cancer radiobiology allow a different approach to dose escalation that is radiobiological in nature. The aim of this paper is to explain the rationale behind hypofractionated high-dose intensity-modulated radiotherapy in patients with localized prostate cancer.
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Neoplasias da Próstata/radioterapia , Radioterapia de Intensidade Modulada , Humanos , Masculino , Dosagem RadioterapêuticaRESUMO
INTRODUCTION: Acute lymphoblastic leukemia (ALL) and its treatment may lead to impairment of kidney function. The aim of the present study was to evaluate kidney function in children after treatment of ALL. We used our 99mTc-DTPA (diethylene triamine pentaacetic acid labeled with 99mTc) dynamic scintigraphy protocol. MATERIAL AND METHODS: The study group consisted of 48 ALL patients, aged 79-275 months, in complete remission (mean duration 51 months). Treatment was according to the guidelines of the Berlin Frankfurt Münster (BFM) BFM 86 and BFM 90 protocols in 36 (75%) and 12 (25%) children, respectively. Follow-up after treatment was up to 12 months in 10 (21%) children (group I), 12-60 months in 21 (44%) children (group II), and more than 60 months in 17 (35%) children (group III). 99mTc-DTPA dynamic renal scintigraphy was done in all patients. The glomerular filtration rate (GFR) was determined according to Gates and the diuretic test was done after 18 minutes of the examination. RESULTS: The glomerular filtration rate at the end of the 5-year follow-up was less than 80 mL/min/1.73 m2 (p < 0.002) in 3 (25%) children treated with the BFM 86 protocol. In the remaining 45 (94%) patients, GFR exceeded 80 mL/ min/1.73 m2. Normal renogram curves were obtained in 40 (83%) patients. Eight (17%) children had cumulative curves with normal clearance. This finding was interpreted as non-obstructive uropathy. There was no statistical correlation between outflow disorders seen during dynamic scintigraphy, type of chemotherapy protocol, and assignment to risks group. CONCLUSIONS: 1. There was no clinically significant kidney function impairment in children after treatment of ALL. 2. Dynamic renal scintigraphy can be a valuable and non-invasive method for the assessment of kidney function in patients with a risk factor in the form of previous potentially nephrotoxic antitumor treatment.