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OBJECTIVES: To determine the hearing status of survivors treated for head and neck rhabdomyosarcoma (HNRMS) at long-term follow-up. DESIGN: Cross-sectional long-term follow-up study. SETTING: Tertiary comprehensive cancer centre. PARTICIPANTS: Survivors treated for HNRMS during childhood in two concurrent cohorts; survivors in London had been treated with external beam radiotherapy (EBRT-based local therapy); survivors in Amsterdam were treated with AMORE (Ablative surgery, MOuld technique afterloading brachytherapy and surgical REconstruction) if feasible, otherwise EBRT (AMORE-based local therapy). MAIN OUTCOME MEASURES: We assessed hearing status of HNRMS survivors at long-term follow-up. Hearing thresholds were obtained by pure-tone audiometry. METHODS: We assessed the hearing thresholds, the number of patients with clinically relevant hearing loss and hearing impairment graded according to the Common Terminology Criteria for Adverse Events version 4.0 (CTCAEv4) and Boston criteria. Furthermore, we compared hearing loss between survivors treated with EBRT-based local therapy (London) and AMORE-based local therapy (Amsterdam). RESULTS: Seventy-three survivors were included (median follow-up 11 years). We found clinically relevant hearing loss at speech frequencies in 19% of survivors. Multivariable analysis showed that survivors treated with EBRT-based treatment and those with parameningeal tumours had significantly more hearing impairment, compared to survivors treated with AMORE-based treatment and non-parameningeal tumours. CONCLUSIONS: One in five survivors of HNRMS developed clinically relevant hearing loss. AMORE-based treatment resulted in less hearing loss compared to EBRT-based treatment. As hearing loss was highly prevalent and also occurred in survivors with orbital primaries, we recommend systematic audiological follow-up in all HNRMS survivors.
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Neoplasias de Cabeza y Cuello/terapia , Pérdida Auditiva/etiología , Rabdomiosarcoma/terapia , Adolescente , Adulto , Audiometría de Tonos Puros , Niño , Preescolar , Estudios Transversales , Femenino , Estudios de Seguimiento , Humanos , Lactante , Londres , Masculino , Países Bajos , SobrevivientesRESUMEN
PURPOSE: Treatment with (131)I-MIBG is associated with significant thyroid damage. This study was undertaken to investigate the long-term efficacy of current thyroid prophylaxis, to explore the relationship between thyroid dysfunction and thyroid volume after exposure to (131)I-MIBG and to evaluate the possible negative effects of (131)I(-) on the parathyroid glands. METHODS: Of 81 long-term surviving patients with neuroblastoma treated with (131)I-MIBG during the period 1999-2012, 24 were finally evaluated. Patients received thyroxine (T4), methimazole and potassium iodide as thyroid protection. In all patients (para)thyroid function was evaluated and ultrasound investigation of the (para)thyroid gland(s) was performed. Thyroid dysfunction was defined as a plasma thyrotropin concentration >5.0 mU/L (thyrotropin elevation, TE) or as the use of T4 at the time of follow-up. Hyperparathyroidism was defined as a serum calcium concentration above the age-related reference range in combination with an inappropriately high parathyroid hormone level. RESULTS: At a median follow-up of 9.0 years after (131)I-MIBG treatment, thyroid disorders were seen in 12 patients (50 %; 9 with TE, 5 with a thyroid nodule and 1 patient was subsequently diagnosed with differentiated thyroid carcinoma). No significant risk factors for the occurrence of thyroid damage could be identified. In 14 of 21 patients (67 %) in whom thyroid volume could be determined, the volume was considered small (<-2SD) for age and gender. Patients treated with T4 at the time of follow-up had significantly smaller thyroid volumes for age than patients without T4 treatment (p = 0.014). None of the patients was diagnosed with hyperparathyroidism. CONCLUSION: Thyroid protection during treatment with (131)I-MIBG needs attention and must be further improved, as thyroid disorders are still frequently seen despite current thyroid prophylaxis. Reduced thyroid volume in neuroblastoma survivors may be related to previous (131)I-MIBG therapy or current T4 treatment. No deleterious effects of (131)I-MIBG on the parathyroid glands could be found.
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3-Yodobencilguanidina/efectos adversos , Hipotiroidismo/prevención & control , Neoplasias Inducidas por Radiación/prevención & control , Neuroblastoma/radioterapia , Radiofármacos/efectos adversos , Radioterapia/efectos adversos , Neoplasias de la Tiroides/prevención & control , 3-Yodobencilguanidina/uso terapéutico , Niño , Preescolar , Femenino , Humanos , Hipotiroidismo/etiología , Lactante , Masculino , Neoplasias Inducidas por Radiación/etiología , Radiofármacos/uso terapéutico , Neoplasias de la Tiroides/etiologíaRESUMEN
Several studies in adults have shown patient reported outcomes (PROs) to be effective in enhancing patient-physician communication and discussion of Health Related Quality of Life outcomes. Although less studied, positive results have been demonstrated in children. A PRO-intervention needs to be feasible in clinical practice to be successful. In the current study, 74 parents of children who successfully completed their cancer treatment and 21 pediatric oncologists (POs) evaluated a PRO-intervention and gave recommendations for future use in their practice. Most parents and POs suggested PROs to be an important part of standard care, starting during treatment, with an assessment frequency of every 3 months.
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Oncología Médica , Padres/psicología , Evaluación del Resultado de la Atención al Paciente , Médicos/psicología , Pautas de la Práctica en Medicina , Adolescente , Adulto , Niño , Preescolar , Femenino , Estudios de Seguimiento , Humanos , Lactante , Recién Nacido , Masculino , Atención al Paciente , Pronóstico , Calidad de VidaRESUMEN
BACKGROUND: For several adult cancer types, there is evidence that treatment in high volume hospitals, high case volume providers, or in specialised hospitals leads to a better outcome. The aim of this study is to give an overview of the existing evidence regarding the volume effect in paediatric oncology related to the quality of care or survival. MATERIALS AND METHODS: An extensive search was carried out for studies on the effect of provider case volume on the quality of care or survival in childhood cancer. Information about study characteristics, comparisons, results, and quality assessment were abstracted. RESULTS: In total, 14 studies were included in this systematic review. Studies with a low risk of bias provide evidence that treatment of children with brain tumours, acute lymphoblastic leukaemia, osteosarcoma, Ewing's sarcoma, or children receiving treatment with allogenic bone marrow transplantation in higher volume hospitals, specialised hospitals, or by high case volume providers, is related with a better outcome. CONCLUSIONS: This systematic review provides support for the statement that higher volume hospitals, higher case volume providers, and specialised hospitals are related to the better outcome in paediatric oncology. No studies reported a negative effect of a higher volume.
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Instituciones Oncológicas/normas , Neoplasias/terapia , Calidad de la Atención de Salud , Niño , Hospitales Pediátricos , Humanos , Oncología Médica , Neoplasias/mortalidad , Resultado del TratamientoRESUMEN
BACKGROUND: Our study aimed to evaluate final height in a cohort of Dutch childhood cancer survivors (CCS) and assess possible determinants of final height, including height at diagnosis. PATIENTS AND METHODS: We calculated standard deviation scores (SDS) for height at initial cancer diagnosis and height in adulthood in a cohort of 573 CCS. Multivariable regression analyses were carried out to estimate the influence of different determinants on height SDS at follow-up. RESULTS: Overall, survivors had a normal height SDS at cancer diagnosis. However, at follow-up in adulthood, 8.9% had a height ≤-2 SDS. Height SDS at diagnosis was an important determinant for adult height SDS. Children treated with (higher doses of) radiotherapy showed significantly reduced final height SDS. Survivors treated with total body irradiation (TBI) and craniospinal radiation had the greatest loss in height (-1.56 and -1.37 SDS, respectively). Younger age at diagnosis contributed negatively to final height. CONCLUSION: Height at diagnosis was an important determinant for height SDS at follow-up. Survivors treated with TBI, cranial and craniospinal irradiation should be monitored periodically for adequate linear growth, to enable treatment on time if necessary. For correct interpretation of treatment-related late effects studies in CCS, pre-treatment data should always be included.
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Estatura/efectos de la radiación , Irradiación Craneana/efectos adversos , Neoplasias/radioterapia , Sobrevivientes , Irradiación Corporal Total/efectos adversos , Adolescente , Adulto , Factores de Edad , Niño , Preescolar , Femenino , Humanos , Lactante , Recién Nacido , Masculino , Neoplasias/patología , Factores SexualesRESUMEN
BACKGROUND: The aim of this study was to investigate whether an unfavourable psychosocial developmental trajectory while growing up with childhood cancer is related to a smaller likelihood of labour participation in adult life. METHODS: A total of 53 childhood cancer survivors (CCS) with and 313 CCS without disability benefits, and 508 peers from the general Dutch population (reference group) completed the Course of Life Questionnaire (CoLQ) about the achievement of psychosocial developmental milestones. Differences between the three groups were tested by conducting analysis of variance with contrasts (scale scores CoLQ) and logistic regression analysis (individual milestones). Effect sizes and odds ratios were calculated. RESULTS: Compared with the reference group, both CCS with and CCS without benefits reported lower scale scores with respect to social and psychosexual development. CCS with disability benefits had lower social (d = - 0.6; p < 0.001) and psychosexual (d = -0.4; p < 0.01) scale scores than the CCS without disability benefits. CCS with disability benefits scored less favourably (p < 0.01) than peers from the general population on 14 out of 22 psychosocial milestones whereas the number was only six for those without disability benefits. CONCLUSIONS: CCS with an unfavourable developmental trajectory while growing up were more likely to apply for disability benefits in adulthood than CCS with a more favourable development. Early recognition and support are warranted. Further research is needed on risk factors of application for disability benefits. In addition, research should show whether stimulating the achievement of developmental milestones while growing up will create conditions for a better labour market position.
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Desarrollo del Adolescente , Desarrollo Infantil , Seguro por Discapacidad/estadística & datos numéricos , Neoplasias/psicología , Sobrevivientes/psicología , Adolescente , Adulto , Estudios de Casos y Controles , Preescolar , Estudios Transversales , Femenino , Humanos , Masculino , Autonomía Personal , Desarrollo Psicosexual , Conducta Social , Encuestas y Cuestionarios , Adulto JovenRESUMEN
BACKGROUND: The use of anthracyclines as effective antineoplastic drugs is limited by the occurrence of cardiotoxicity. Multiple genetic variants predictive of anthracycline-induced cardiotoxicity (ACT) in children were recently identified. The current study was aimed to assess replication of these findings in an independent cohort of children. PROCEDURE: . Twenty-three variants were tested for association with ACT in an independent cohort of 218 patients. Predictive models including genetic and clinical risk factors were constructed in the original cohort and assessed in the current replication cohort. RESULTS: . We confirmed the association of rs17863783 in UGT1A6 and ACT in the replication cohort (P = 0.0062, odds ratio (OR) 7.98). Additional evidence for association of rs7853758 (P = 0.058, OR 0.46) and rs885004 (P = 0.058, OR 0.42) in SLC28A3 was found (combined P = 1.6 × 10(-5) and P = 3.0 × 10(-5), respectively). A previously constructed prediction model did not significantly improve risk prediction in the replication cohort over clinical factors alone. However, an improved prediction model constructed using replicated genetic variants as well as clinical factors discriminated significantly better between cases and controls than clinical factors alone in both original (AUC 0.77 vs. 0.68, P = 0.0031) and replication cohort (AUC 0.77 vs. 0.69, P = 0.060). CONCLUSIONS: . We validated genetic variants in two genes predictive of ACT in an independent cohort. A prediction model combining replicated genetic variants as well as clinical risk factors might be able to identify high- and low-risk patients who could benefit from alternative treatment options.
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Antraciclinas/efectos adversos , Antineoplásicos/efectos adversos , Cardiotoxinas/efectos adversos , Enfermedades Cardiovasculares/genética , Glucuronosiltransferasa/genética , Proteínas de Transporte de Membrana/genética , Modelos Biológicos , Polimorfismo de Nucleótido Simple , Adolescente , Antraciclinas/administración & dosificación , Antineoplásicos/administración & dosificación , Cardiotoxinas/administración & dosificación , Enfermedades Cardiovasculares/inducido químicamente , Niño , Preescolar , Estudios de Cohortes , Femenino , Marcadores Genéticos , Humanos , Lactante , Masculino , Neoplasias/tratamiento farmacológico , Neoplasias/genética , Valor Predictivo de las PruebasRESUMEN
Neuroblastomas frequently have deletions of chromosome 1p and amplification of the N-myc oncogene. We analysed 53 neuroblastomas for the N-myc copy number, loss of heterozygosity (LOH) of chromosome 1p36 and the parental origin of the lost alleles. Allelic loss of 1p36 was found in 15 tumours. All N-myc amplified tumours belonged to this subset. In 13/15 tumours with LOH of 1p36 the lost allele was of maternal origin. This non-random distribution implies that the two alleles of the putative neuroblastoma suppressor gene on chromosome 1p36 are functionally different, depending on their parental origin. This is the first evidence as far as we know for genomic imprinting on chromosome 1p.
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Alelos , Cromosomas Humanos Par 1 , Amplificación de Genes , Eliminación de Gen , Regulación Neoplásica de la Expresión Génica , Genes Supresores de Tumor , Genes myc , Neuroblastoma/genética , Polimorfismo de Longitud del Fragmento de Restricción , Adulto , Preescolar , ADN de Neoplasias/genética , Femenino , Marcadores Genéticos , Humanos , Técnicas In Vitro , Lactante , Modelos Genéticos , Neoplasias Primarias Múltiples/genéticaRESUMEN
BACKGROUND: Providing high-quality care for children with cancer could improve treatment outcomes, survival and quality of life of the children and parents. The aim of this study is to select high-quality care recommendations for all children with cancer based on literature and consensus for future development of quality indicators. MATERIALS AND METHODS: We performed an extensive search in databases for scientific literature and in websites of international health care and guideline development organizations to create an inventory of recommendations for the care for all children with cancer. The RAND modified Delphi method was used to grade and select recommendations for high-quality care. RESULTS: Our search resulted in a list of 131 recommendations on care for all children with cancer. The expert panel graded, discussed and prioritized these recommendations. Analysis of these ratings resulted ultimately in a list of 109 high-quality care recommendations for all children with cancer, including 31 prioritized recommendations. CONCLUSIONS: This study defines a set of high-quality care recommendations based on literature and consensus. These recommendations provide a basis for the development of a comprehensive set of quality indicators to evaluate care in paediatric oncology.
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Neoplasias/terapia , Calidad de la Atención de Salud , Niño , Humanos , Guías de Práctica Clínica como Asunto , Encuestas y CuestionariosRESUMEN
BACKGROUND: The Late Effects of Childhood Cancer task force of the Dutch Childhood Oncology Group (DCOG LATER) developed a guideline for follow-up of asymptomatic cardiac dysfunction in childhood cancer survivors (CCS). In this paper, we present the methods, available evidence and final recommendations of our guideline. MATERIALS AND METHODS: A multidisciplinary working group specified clinical questions that should be answered to get to recommendations for the guideline. We carried out short or extensive evidence summaries and determined methodological quality of studies and levels of evidence in order to answer all clinical questions. When evidence was lacking for CCS, we carefully extrapolated evidence from other populations. Final recommendations were based on evidence and consensus. RESULTS: There was high-level evidence for the increased risk of cardiac dysfunction in CCS and its main risk factors. Evidence was lacking regarding the prognosis, diagnosis and treatment of cardiac dysfunction in CCS. We recommended echocardiographic screening for asymptomatic cardiac dysfunction in CCS treated with cardiotoxic treatments and counseling about potential advantages and disadvantages of our screening recommendations. CONCLUSION: The DCOG LATER guideline recommends risk-based screening for asymptomatic cardiac dysfunction in CCS, but it should be noted that recommendations are not completely supported by evidence in CCS.
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Corazón/fisiopatología , Neoplasias/fisiopatología , Niño , Ecocardiografía , Estudios de Seguimiento , Cardiopatías/diagnóstico por imagen , Cardiopatías/etiología , Humanos , SobrevivientesRESUMEN
PURPOSE: Treatment protocols in pediatric oncology have historically known high accrual rates, up to 94 %. Accrual for supportive care studies on the other hand appears to be a challenge. The aim of this study was to search for reasons explaining this poor accrual and for possible interventions to improve patient enrolment. METHODS: The failure screen log of our supportive care study (the Aristocaths study) was analyzed, and subsequently, a literature search was performed. RESULTS: The literature search (1985-2011) revealed three factors that can influence accrual. Firstly, study implementation and patient enrolment can be facilitated by appointing a dedicated clinical investigator in all participating centers and by facilitating clinical research nurses. Furthermore, adequate and tailor-made information is required for families to make a well-informed decision regarding study participation. Lastly, sufficient time should be assured for the process of decision making, especially since the number of eligible studies is increasing rapidly. Concerning our study, all three elements were met, but the most striking finding was the presumed burden of study participation by the majority of parents (82 %) as the main argument against randomization. CONCLUSIONS: Accrual of pediatric oncology patients in supportive care studies is challenging. Nevertheless, well-designed randomized controlled trials in supportive care will be essential for the improvement of pediatric cancer care. Therefore, we will need to increase awareness through (inter)national supportive care working groups regarding the need for supportive care trials and stimulate accrual when such trials are open.
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Ensayos Clínicos como Asunto , Neoplasias/terapia , Selección de Paciente , Actitud del Personal de Salud , Niño , Conocimientos, Actitudes y Práctica en Salud , HumanosRESUMEN
Deficiency of mannose-binding lectin (MBL) has been suggested to influence duration of febrile neutropenia and prognosis in paediatric oncology patients. However, there is no consensus on the definition of MBL deficiency. In a cohort of children with cancer, we investigated (i) how to determine MBL deficiency and (ii) whether MBL is a prognostic factor for disease severity. In 222 paediatric oncology patients, 92 healthy children and 194 healthy adults, MBL plasma levels and MBL2 genotype (wild-type: A, variant: O) were determined. Event-free survival (EFS), overall survival (OS) and paediatric intensive care unit (PICU) admissions were recorded prospectively. In febrile neutropenic patients admitted to the PICU, disease severity was assessed by clinical, microbiological and laboratory parameters. An optimal cut-off value for MBL deficiency was determined to be < 0·20 µg/ml. Wild-type MBL2 genotype patients, including the XA/XA haplotype, had increased MBL levels compared to healthy individuals. MBL deficiency was associated with decreased EFS (P = 0·03), but not with need for PICU admission. A trend for a twice increased frequency of septic shock (80% versus 38%, P = 0·14), multiple organ failure (40% versus 17%, P = 0·27) and death (40% versus 21%, P = 0·27) was observed in the absence of microbiological findings. MBL deficiency was associated with decreased EFS and possibly with an increased severity of disease during PICU admission after febrile neutropenia in the absence of any association with microbiological findings. These findings suggest prognosis to be worse in MBL-deficient compared to MBL-sufficient paediatric oncology patients.
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Neoplasias Hematológicas/diagnóstico , Neoplasias Hematológicas/genética , Lectina de Unión a Manosa/genética , Lectina de Unión a Manosa/inmunología , Adulto , Niño , Preescolar , Progresión de la Enfermedad , Servicios Médicos de Urgencia , Predisposición Genética a la Enfermedad , Neoplasias Hematológicas/mortalidad , Neoplasias Hematológicas/fisiopatología , Humanos , Lactante , Recién Nacido , Masculino , Lectina de Unión a Manosa/sangre , Neutropenia , Servicio de Oncología en Hospital , Polimorfismo Genético , Pronóstico , Índice de Severidad de la Enfermedad , Análisis de SupervivenciaRESUMEN
BACKGROUND: This study assessed the long-term effects of cancer therapies on reproductive status in adult male childhood cancer survivors, evaluated the treatment-related risk factors for hypergonadotropic hypogonadism and assessed the association between the FSH levels and the later need for assisted reproductive techniques (ART). METHODS: The study cohort included adult male 5-year survivors of childhood cancer who were treated in our institution between 1966 and 2003. Data concerning patient and treatment characteristics, FSH, LH and testosterone levels and pregnancy outcome were collected. Multivariate regression analyses were performed to evaluate the treatment-related risk factors for disturbances in reproductive endocrine status. The diagnostic and predictive values of FSH and later need for ART were evaluated. RESULTS: Data on reproductive endocrine status were available for 488 survivors (86.4%) of the 565 male survivors who visited the outpatient clinic in adulthood. The median follow-up time from initiation of treatment to first visit to the outpatient clinic in adulthood was 15 years. The prevalence rates of elevated FSH levels and decreased testosterone levels were 33 and 12%, respectively. The use of procarbazine, cyclophosphamide, vinca-alkaloids, other alkylating agents, pelvic/abdominal irradiation, total body irradiation and testicular surgery were identified as treatment-related risk factors for elevated FSH levels. During the follow-up period, 73 men reported 120 conceptions, which resulted in 103 live births. Of these men, 56 (77%) were able to achieve conception naturally. All men whose partners conceived by assisted reproductive techniques (n = 13) had elevated FSH levels at their first visit after their 18th birthday (sensitivity: 100%; 95% CI: 71-100%) and all male survivors with a normal FSH level did not need assisted reproductive techniques (negative predictive value: 100%; 95% CI: 89-100%). CONCLUSIONS: One-third of young adult male survivors of childhood cancer has elevated FSH levels. FSH appears to be a very sensitive marker for the need of assisted reproductive techniques in male childhood cancer survivors.
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Infertilidad Masculina/complicaciones , Neoplasias/complicaciones , Reproducción/fisiología , Sobrevivientes , Adulto , Antineoplásicos/efectos adversos , Estudios de Cohortes , Femenino , Hormona Folículo Estimulante/sangre , Estudios de Seguimiento , Humanos , Hipogonadismo/inducido químicamente , Hipogonadismo/epidemiología , Infertilidad Masculina/epidemiología , Masculino , Análisis Multivariante , Neoplasias/tratamiento farmacológico , Neoplasias/radioterapia , Embarazo , Resultado del Embarazo , Prevalencia , Reproducción/efectos de los fármacos , Reproducción/efectos de la radiación , Técnicas Reproductivas Asistidas , Medición de Riesgo , Factores de Riesgo , Resultado del TratamientoRESUMEN
BACKGROUND: We determined whether mannose-binding lectin (MBL) deficiency is associated with an increased risk of febrile neutropenia (FN) and/or infection in pediatric oncology patients. PROCEDURE: We systematically searched and reviewed all the literature on MBL and infections in children with cancer, identified from a literature search of Medline, Embase, and Central (1966-April 2010). We extracted information on the type of study, patient characteristics, definition of MBL deficiency, definition of infection and method of detection, follow-up period and the results of the outcome in different groups. The validity of each study was assessed. RESULTS: Six cohort studies were retrieved, consisting of 581 children with leukemia (n = 2) or varying types of cancer (n = 4). Many different outcome definitions were used. In only one out of three genotype studies, variant MBL2 genotypes, as well as MBL levels < 1,000 µg/L, were associated with an increased duration of FN. In one additional MBL level study the number of FN episodes, bacteremia and severe bacterial infection were increased in patients with MBL levels < 100 µg/L as compared to those with MBL levels of 100-999 µg/L. Sepsis, pneumonia, viral infection, and fungal infection were not associated with either MBL levels or genotypes in any of the studies. CONCLUSIONS: MBL deficiency could not be identified as an independent risk factor for FN or infection in pediatric oncology patients. A multicenter study of children with comparable chemotherapy regimens, relevant and equal outcome definitions and measuring both MBL levels and genotypes, will be required to avoid clinical and methodological inconsistencies.
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Bacteriemia/sangre , Lectina de Unión a Manosa/sangre , Micosis/sangre , Neoplasias/tratamiento farmacológico , Neutropenia/sangre , Virosis/sangre , Adolescente , Bacteriemia/inducido químicamente , Bacteriemia/genética , Niño , Preescolar , Femenino , Genotipo , Humanos , MEDLINE , Masculino , Lectina de Unión a Manosa/genética , Micosis/inducido químicamente , Micosis/genética , Neoplasias/sangre , Neoplasias/genética , Neutropenia/inducido químicamente , Factores de Riesgo , Virosis/inducido químicamente , Virosis/genéticaRESUMEN
The chromosomal position of human genes is rapidly being established. We integrated these mapping data with genome-wide messenger RNA expression profiles as provided by SAGE (serial analysis of gene expression). Over 2.45 million SAGE transcript tags, including 160,000 tags of neuroblastomas, are presently known for 12 tissue types. We developed algorithms to assign these tags to UniGene clusters and their chromosomal position. The resulting Human Transcriptome Map generates gene expression profiles for any chromosomal region in 12 normal and pathologic tissue types. The map reveals a clustering of highly expressed genes to specific chromosomal regions. It provides a tool to search for genes that are overexpressed or silenced in cancer.
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Cromosomas Humanos/genética , Expresión Génica , Genoma Humano , Neoplasias/genética , Mapeo Físico de Cromosoma , ARN Mensajero/genética , Algoritmos , Bases de Datos Factuales , Perfilación de la Expresión Génica , Biblioteca de Genes , Silenciador del Gen , Humanos , Familia de Multigenes , Programas Informáticos , Transcripción GenéticaRESUMEN
BACKGROUND: The interest in evidence-based medicine (EBM) is still increasing throughout medicine, but the precise role of EBM in the field of pediatric oncology remains unclear. We undertook this survey to evaluate the attitude of Dutch pediatric oncologists and pediatric oncologists in training towards EBM and their views on how to move from opinion-based medicine to EBM. PROCEDURE: A questionnaire was sent to all pediatric oncologists (n = 44) and pediatric oncologists in training (n = 13) of the 8 university medical centers in the Netherlands. RESULTS: The questionnaire was returned by 71% of the pediatric oncologists and pediatric oncologists in training. The majority had a positive attitude towards EBM, but at the moment only approximately 50% of their clinical practice was thought to be evidence-based. The most important barrier to practicing EBM in pediatric oncology was a lack of time. However, only a minority of the respondents thought that more time was an appropriate method to facilitate the use of EBM in pediatric oncology. The majority of pediatric oncologists and pediatric oncologists in training would prefer to be able to use EBM summaries, guidelines and protocols. CONCLUSIONS: Despite the positive attitude of the majority of pediatric oncologists and pediatric oncologists in training towards EBM, only half of clinical practice is currently believed to be evidence-based. By using EBM summaries, guidelines and protocols as time-saving methods the use of EBM in pediatric oncology practice may be improved.
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Medicina Basada en la Evidencia , Oncología Médica/métodos , Pediatría/métodos , Pautas de la Práctica en Medicina , Actitud del Personal de Salud , Niño , Recolección de Datos , Humanos , Países Bajos , MédicosRESUMEN
The aim of the study was to investigate: (1) health-related quality of life (HRQoL) and anxiety in school-aged cancer survivors during the first 4 years of continuous remission after the end of treatment; and (2) correlations of disease-related coping with HRQoL and anxiety. A total of 76 survivors aged 8-15 years completed questionnaires about HRQoL, anxiety and disease-related cognitive coping at one to five measurement occasions. Their HRQoL was compared with norm data, 2 months (n = 49) and 1 year (n = 41), 2 years (n = 41), 3 years (n = 42) and 4 years (n = 27) after treatment. Through longitudinal mixed models analyses it was investigated to what extent disease-related cognitive coping was associated with HRQoL and anxiety over time, independent of the impact of demographic and medical variables. Survivors reported worse Motor Functioning (HRQoL) 2 months after the end of treatment, but from 1 year after treatment they did no longer differ from the norm population. Lower levels of anxiety were associated with male gender, being more optimistic about the further course of the disease (predictive control) and less searching for information about the disease (interpretative control). Stronger reliance on the physician (vicarious control) was associated with better mental HRQoL. As a group, survivors regained good HRQoL from 1 year after treatment. Monitoring and screening survivors are necessary to be able to trace the survivors at risk of worse HRQoL.
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Adaptación Psicológica , Ansiedad/epidemiología , Estado de Salud , Neoplasias/psicología , Calidad de Vida , Sobrevivientes/psicología , Niño , Cognición/fisiología , Femenino , Humanos , Estudios Longitudinales , Masculino , Destreza Motora/fisiología , Neoplasias/fisiopatología , Neoplasias/terapia , Países Bajos/epidemiología , Factores SexualesRESUMEN
BACKGROUND: Anthracyclines are among the most effective chemotherapeutic agents in the treatment of numerous malignancies. Unfortunately, their use is limited by a dose-dependent cardiotoxicity. In an effort to prevent this cardiotoxicity, different cardioprotective agents have been studied. OBJECTIVES: The objective of this review was to assess the efficacy of different cardioprotective agents in preventing heart damage in cancer patients treated with anthracyclines. SEARCH STRATEGY: We searched the databases of the Cochrane Central Register of Controlled Trials (CENTRAL, Issue 2, 2007), MEDLINE (1966 to April 2007) and EMBASE (1980 to April 2007). In addition, we handsearched reference lists and conference proceedings of the SIOP and ASCO meetings (1998 to 2006). SELECTION CRITERIA: Randomised controlled trials (RCTs) in which any cardioprotective agent was compared to no additional or placebo therapy in cancer patients (children and adults) receiving anthracyclines. DATA COLLECTION AND ANALYSIS: Two review authors independently performed the study selection, quality assessment and data-extraction including adverse effects. MAIN RESULTS: We identified RCTs for seven cardioprotective agents: N-acetylcysteine, phenetylamines, coenzyme Q10, combination of vitamins E and C and N-acetylcysteine, L-carnitine, carvedilol and dexrazoxane (mostly adults with advanced breast cancer). All studies had methodological limitations. For the first six agents, there were too few studies to allow pooling of results. None of the individual studies showed a cardioprotective effect. The nine included studies of dexrazoxane enrolled 1403 patients. The meta-analysis of dexrazoxane showed a statistically significant benefit in favour of dexrazoxane for the occurrence of heart failure (Relative Risk (RR) 0.29, 95% CI 0.20 to 0.41). No evidence was found for a difference in response rate or survival between the dexrazoxane and control group. Only for one adverse effect (abnormal white blood cell count at nadir) a difference in favour of the control group was identified. AUTHORS' CONCLUSIONS: For cardioprotective agents for which pooling was impossible, no definitive conclusions can be made about their efficacy. Dexrazoxane prevents heart damage and no evidence for a difference in response rate or survival between the dexrazoxane and control group was identified. Only for an abnormal white blood cell count at nadir a clearly significant difference in favour of the control group was identified. We conclude that if the risk of cardiac damage is expected to be high, it might be justified to use dexrazoxane in patients with cancer treated with anthracyclines. However, for each individual patient clinicians should weigh the cardioprotective effect of dexrazoxane against the possible risk of adverse effects.
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Antraciclinas/efectos adversos , Antibióticos Antineoplásicos/efectos adversos , Cardiopatías/prevención & control , Neoplasias/tratamiento farmacológico , Cardiotónicos/uso terapéutico , Citoprotección , Cardiopatías/inducido químicamente , Humanos , Ensayos Clínicos Controlados Aleatorios como AsuntoRESUMEN
Oncological treatment has been associated with an increased risk of infection, most often related to therapy-induced pancytopenia. However, limited research has been conducted on the effect of oncological therapy on the complement system, being part of the non-cellular innate immune system. This became the rationale for an observational clinical study (C2012) in which we have investigated the prevalence of transient complement defects. Once we had observed such defects, a correlation of the complement defects to specific clinical parameters or to specific therapeutic regimens was investigated. A prominent defect observed in C2012 was the inhibition of the lectin pathway (LP) of complement activation during the treatment of acute lymphoblastic leukemia (ALL), which we could directly associate to the use of asparaginase (ASNase). Ex-vivo experiments confirmed a direct dose-dependent inhibitory effect of ASNase on the LP functionality.
Asunto(s)
Asparaginasa/farmacología , Lectina de Unión a Manosa de la Vía del Complemento/efectos de los fármacos , Polietilenglicoles/farmacología , Asparaginasa/administración & dosificación , Asparaginasa/uso terapéutico , Niño , Depresión Química , Relación Dosis-Respuesta a Droga , Humanos , Lectina de Unión a Manosa/sangre , Serina Proteasas Asociadas a la Proteína de Unión a la Manosa/antagonistas & inhibidores , Polietilenglicoles/administración & dosificación , Polietilenglicoles/uso terapéutico , Leucemia-Linfoma Linfoblástico de Células Precursoras/tratamiento farmacológico , Unión Proteica/efectos de los fármacosRESUMEN
INTRODUCTION: Prognosis of neuroblastoma patients is very diverse, indicating the need for more accurate prognostic parameters. The excretion of catecholamine metabolites by most neuroblastomas is used for diagnostic purposes, but their correlation with prognosis has hardly been investigated. Therefore, we performed an in-depth analysis of a panel of elevated urinary catecholamine metabolites at diagnosis and their correlation with prognosis. PATIENTS AND METHODS: Retrospective study of eight urinary catecholamine metabolites in a test (n = 96) and validation (n = 205) cohort of patients with neuroblastoma (all stages) at diagnosis. RESULTS: Multivariate analyses, including risk factors such as stage and MYCN amplification, revealed that 3-methoxytyramine (3MT) was an independent risk factor for event-free survival (EFS) and overall survival (OS). Furthermore, only 3MT appeared to be an independent risk factor for both EFS and OS in high-risk patients, which was independent of modern high-risk therapy and immunotherapy. Among high-risk patients, those with elevated 3MT and older than 18 months had an extremely poor prognosis compared to patients with non-elevated 3MT and younger than 18 months (5-year EFS of 14.3% ± 4% and 66.7% ± 18%, respectively, p = 0.001; 5-year OS of 21.8% ± 5% and 87.5% ± 12%, respectively, p < 0.001). CONCLUSIONS: Elevated 3MT at diagnosis was associated with high-risk disease and poor prognosis. For high-risk patients, elevated 3MT at diagnosis was the only significant risk factor for EFS and OS. 3MT was also able to identify subgroups of high-risk patients with favourable and extremely poor prognosis.