Prevalence of Café-au-Lait Spots in children with solid tumors.

Cafe-au-lait maculae (CALM) are frequently observed in humans, and usually are present as a solitary spot. Multiple CALMs are present in a smaller fraction of the population and are usually associated with other congenital anomalies as part of many syndromes. Most of these syndromes carry an increased risk of cancer development. Previous studies have indicated that minor congenital anomalies may be more prevalent in children with cancer. We investigated the prevalence of CALMs in two samples of Brazilian patients with childhood solid tumors, totaling 307 individuals. Additionally, 176 school children without diagnosis of cancer, or of a cancer predisposing syndrome, were investigated for the presence of CALMs. The prevalence of solitary CALM was similar in both study groups (18% and 19%) and also in the group of children without cancer. Multiple CALMs were more frequently observed in one of the study groups (Z = 2.1). However, when both groups were analyzed together, the significance disappeared (Z = 1.5). The additional morphological abnormalities in children with multiple CALMs were analyzed and compared to the findings observed in the literature. The nosologic entities associated with CALMs are reviewed.

Efficacy of irinotecan single drug treatment in children with refractory or recurrent hepatoblastoma – A phase II trial of the childhood liver tumour strategy group (SIOPEL)

Abstract Purpose:To assess the clinical activity of irinotecan as single drug in children with refractory or recurrent hepatoblastoma. Patients and methods: Four cycles of irinotecan were administered (20 mg/m2/day intravenous (i.v.) infusion on days 1–5 and 8–12, every 21 days) unless tumour progression occurred or resectability was achieved earlier. Tumour response was assessed according to modified SIOPEL and Response Evaluation Criteria In Solid Tumours (RECIST) criteria. Main end-points were best overall response rate (RR), early progression rate (EPR) and progression free survival (PFS). Results: Twenty-four eligible patients (median age 58.0 months; 19 boys) were enrolled in the study (11 relapses, 13 refractory diseases). Of the 23 evaluable patients six had an overall partial response, 11 stable disease and six progressive disease, of which four were early progression (RR: 26%, EPR: 17%). In eight patients the residual tumour could be completely resected; seven patients became tumour free. At last follow-up 12 patients were alive (six with no evidence of disease, six with disease). PFS at 1 year was 24%. Patients with relapse had a higher RR than patients with refractory disease (46% versus 8%) and patients with isolated lung lesions showed a better response than patients with other tumour localisations (50% versus 13%). The main grade 3–4 toxicities, diarrhoea and neutropenia, occurred in half of the patients. Conclusion: Irinotecan has a significant anti-tumour activity and acceptable toxicity in patients with relapsed hepatoblastoma and therefore should be considered for the treatment of these patients. Exploration of the role of irinotecan in the initial treatment of hepatoblastoma is warranted. (AU)

Prognostic stratification for children with hepatoblastoma: the SIOPEL experience

Purpose: To identify factors relevant to long-term outcome in newly diagnosedhepatoblastoma, and define subgroups for clinical research on tailoring treatment to the individual patient. Patients and methods: Between 1995 and 2006 the SIOPEL group conducted two clinical trials which established risk-adapted therapy for hepatoblastoma patients. Patients were stratified into high-risk (AFP < 100 ng/mL and/or PRETEXT IV and/or vascular invasion and/or extra-hepatic intra-abdominal disease (V+/P+/E+) and/or metastases) and standard-risk(all others). The hierarchy of these factors plus multifocality, PRETEXT III,AFP > 1,200,000 ng/mL, patient age, platelet count and histology were further explored.The outcome measure was event-free survival (EFS).Results: In 541 patients, reduced EFS correlated significantly with AFP < 100 ng/ml (hazardratio [HR] 4.09, 95% confidence interval 2.16–7.75), AFPP 1.2 _ 106 ng/mL (2.48, 1.47–4.17), metastatic disease (3.02, 2.05–4.44), PRETEXT IV (2.15, 1.19–3.87), multifocality(1.59, 1.01–2.50), age>5 years (2.76, 1.68–4.53); borderline with small cell undifferentiated(SCU) histology (2.29, 95% confidence interval 0.91–5.77); but not with PRETEXT III, age30–60 months, platelet count or V+/P+/E+. By using the significant factors and SCU to stratifythe population, we have identified three distinct prognostic groups: PRETEXT I/II/III,and no other factors, have 3 year EFS of 90%, PRETEXT IV and/or multifocal tumourand/or age > 5 years and/or AFP > 1.2 _ 106 have 3 year EFS of 71% and SCU and/orAFP < 100 ng/mL and/or metastatic have a 3 year EFS of 49%.Conclusion: Prognostic stratification for clinical research on newly diagnosed hepatoblastomashould take into consideration PRETEXT, metastatic disease, AFP, multifocality, age andSCU histology. (AU)

Low prevalence of HPV in Brazilian children with retinoblastoma

Retinoblastoma is the most frequent intra-ocular malignant tumor of the childhood, occurring in 1 of 18,000–30,000 live births. Little is known about the causes of sporadic retinoblastoma and only a few authors have investigated the etiologic role of human papillomavirus (HPV), with controversial results. Formalin-fixed, paraffin-embedded tissue blocks containing retinoblastoma were retrieved from the archives of the Department of Pathology at Hospital A C Camargo, SÆo Paulo, Brazil. All patients were treated with enucleation (21 children had both eyes enucleated). Retinoblastoma and, when possible, normal retina of each specimen, were micro-dissected under direct light microscopic visualization by using a PixCell II Laser Capture Micro-dissection System. The DNA quality was evaluated by polymerase chain reaction (PCR) amplification of 110 base pairs fragment of the human β-globin gene using primers PCO3 +/PCO4+. All globin positive specimens were analyzed by PCR for the presence of HPV DNA using consensus primers GP5+/GP6+. A total of 154 specimens were evaluated. Forty-four patients also had normal retinal specimens available for analysis of DNA HPV. The DNA HPV prevalence among all tumor specimens was 4.6% (95% CI 2.0; 8.8) (7 positive specimens/153 adequate specimens). Among normal retinal specimens, the DNA HPV prevalence was 9.1% (95% CI 2.9; 20.5) (4 positive specimens/44 specimens). There was no statistically significant difference between these rates (P = 0.318). Excluding any experimental failure, our results indicate a low prevalence of HPV DNA in retinoblastomas. We were therefore unable to conclude about the association between these oncogenic viruses and this rare pediatric neoplasm (AU)

Socioeconomic status and the incidence of non-central nervous system childhood embryonic tumours in Brazil

BACKGROUND: Childhood cancer differs from most common adult cancers, suggesting a distinct aetiology for some types of childhood cancer. Our objective in this study was to test the difference in incidence rates of 4 non-CNS embryonic tumours and their correlation with socioeconomic status (SES) in Brazil.METHODS: Data was obtained from 13 Brazilian population-based cancer registries (PBCRs) of neuroblastoma (NB), Wilms'tumour (WT), retinoblastoma (RB), and hepatoblastoma (HB). Incidence rates by tumour type, age, and gender were calculated per one million children. Correlations between social exclusion index (SEI) as an indicator of socioeconomic status (SES) and incidence rates was investigated using the Spearman's test. RESULTS: WT, RB, and HB presented with the highest age-adjusted incidence rates (AAIRs) in 1 to 4 year old of both genders, whereas NB presented the highest AAIR in ­š11 month-olds. However, differences in the incidence rates among PBCRs were observed. Higher incidence rates were found for WT and RB, whereas lower incidence rates were observed for NB. Higher SEI was correlated with higher incidences of NB (0.731; p = 0.0117), whereas no SEI correlation was observed between incidence rates for WT, RB, and HB. In two Brazilian cities, the incidence rates of NB and RB were directly correlated with SEI; NB had the highest incidence rates (14.2, 95% CI, 8.6-19.7), and RB the lowest (3.5, 95% CI, 0.7-6.3) in Curitiba (SEI, 0.730). In Natal (SEI, 0.595), we observed just the opposite; the highest incidence rate was for RB and the lowest was for NB (4.6, 95% CI, 0.1-9.1). CONCLUSION: Regional variations of SES and the incidence of embryonal tumours were observed, particularly incidence rates for NB and RB. Further studies are necessary to investigate risk factors for embryonic tumours in Brazil (AU)

A palliative prognostic score for terminally ill children and adolescents with cancer.

BACKGROUND: The loss of a child is considered the hardest moment in a parent's life. Studies addressing length of survival under pediatric palliative care are rare. The aim of this study was to improve a survival prediction model for children in palliative care, as accurate information positively impacts parent and child preparation for palliative care. PROCEDURE: Sixty-five children referred to a pediatric palliative care team were followed from August 2003 until December 2006. Variables investigated (also included in previous studies) were: diagnosis, home care provider, presence of anemia, and performance status score given by the home care provider. Clinical variables such as symptom number were also used to test the score's ability to predict survival. RESULTS: The length of survival prognostic score was validated using the above variables. The number of symptoms at transition to palliative care does not improve the score's predictive ability. The sum of the single scores gives an overall score for each patient, dividing the population into three groups by probability of 60-day survival: Group A 80.0%, Group B 38.0%, and Group C 28.5% (P < 0.001). CONCLUSION: A pediatric palliative care score based on easily accessible variables is statistically significant in multivariate analysis. Factors that increase accuracy of life expectancy prediction enable adequate information to be given to patients and families, contributing to therapeutic decision-making issues.

Challenges on participation in a cooperative group of childhood renal tumors in Brasil.

OBJECTIVE: Children with renal tumors included in clinical trials have significantly better outcomes. In Brasil, the enrollment of patients in clinical trials remains challenging. Here we aimed to describe participation accrual in the Brazilian Wilms Tumor Study Group (BWTSG) and to identify barriers to trial registration of children with renal tumors. METHODS: We determined the numbers of renal tumor diagnoses in 105 hospital-based cancer registries from 2001-2009. We then compared these totals with the numbers of renal tumor cases registered in the BWTSG from the same hospitals during the same time period. We also invited members of the Brazilian Pediatric Oncology Society to complete a 5-point Likert-type scale questionnaire regarding their opinions of the importance of participation in cooperative group trials. RESULTS: The accrual rate of patient participation per hospital varied from 25% to 76%, and was highest in the South region. The accrual rate of hospital participation also varied according to the region (20-31%) and was highest in the Southeast region. For the questionnaire regarding the importance of participation in cooperative groups, the responses showed an agreement of >75% on 10 of the 13 statements. CONCLUSION: Our results demonstrated low accrual of participation in a cooperative group trial in Brasil. We identified variations in registration rates according to geographic region and hospital, which may help targeted efforts to increase registration rates. The survey responses demonstrated that colleagues understand the importance of trial participation.

Incidence and mortality of bone cancer among children, adolescents and young adults of Brazil.

OBJECTIVES: Bone cancers occur frequently in children, adolescents, and young adults aging 15 to 29 years. Osteosarcoma and Ewing sarcoma are the most frequent subtypes in this population. The aim of this study was to describe incidence and mortality trends of bone cancers among Brazilian children, adolescents and young adults. METHODS: Incidence information was obtained from 23 population-based cancer registries. Mortality data were extracted from the Atlas of Cancer Mortality from 1979 to 2013. Specific and adjusted rates per million were analyzed according to gender, morphology and age at diagnosis. Median rates were used as a measure of central tendency. Joinpoint regression was applied to analyze trends. RESULTS: Median incidence rates were 5.74 and 11.25 cases per million in children and young adults respectively. Osteosarcoma in the 15-19 years aged group had the highest incidence rates. Stable incidence rates were observed among five registries in 0-14 year's age group. Four registries had a decreased incidence trend among adolescents and young adults. Median mortality rates were 1.22 and 5.07 deaths per million in children and young adults respectively. Increased mortality was observed on the North and Northeast regions. Decreased mortality trends were seen in the South (children) and Southeast (adolescents and young adults). CONCLUSION: Osteosarcoma and Ewing Sarcoma are the most incident bone cancers in all Brazilian regions. Bone cancers showed incidence and mortality patterns variation within the geographic regions and across age groups, although not significant. Despite limitations, it is crucial to monitor cancer epidemiology trends across geographic Brazilian regions.

Intra-tumor genetic heterogeneity in Wilms tumor samples.

Childhood renal tumors account for ~7% of all childhood cancers, and most cases are embryonic Wilms' tumors (WT). Children with WT are usually treated by either COG or SIOP. The later treats the children using preoperative chemotherapy, but both have around 90% of overall survival in five years. WT is a genetically heterogeneous group with a low prevalence of known somatic alterations. Only around 30% of the cases present mutation in known genes, and there is a relatively high degree of intra-tumor genetic heterogeneity (ITGH). Besides potentially having an impact on the clinical outcome of patients, ITGH may interfere with the search for molecular markers that are prospectively being tested by COG and SIOP. In this review, we present the proposal of the current UMBRELLA SIOP Study 2017/Brazilian Renal Tumor Group that requires the multi-sampling collection of each tumor to better evaluate possible molecular markers, as well as to understand WT biology.

Histiocitose de c‚lulas de Langerhans com envolvimento ungueal em crian‡a: relato de caso / Langerhans cell histiocytosis with nail involvement in childhood: a case report

A histiocitose de c‚lulas de Langerhans pode apresentar-se de diversas formas cl¡nicas. Neste trabalho, os autores relatam caso de menino de trˆs anos de idade com queixa de otite m‚dia cr“nca e tumora‡Æo na regiÆo da mast¢ide direita. O exame anatomopatol¢gico revelou histiocitose. O paciente apresentava dermatite importante no couro cabeludo e altera‡äes distr¢ficas com onic¢lise, p£stulas e deformidades ungueais nos dedos das mÆos e p‚s. As lesäes responderam … terapia antineopl sica. O aparecimento de lesäes distr¢ficas ungueais na histiocitose de c‚lulas de Langerhans ‚ raro em crian‡as. Esse caso cl¡nico sugere que o tratamento com terapia antineopl sica pode ser eficaz.(AU)

Langerhans cell histiocytosis may appear in a variety of ways. The authors present the case report of a 3-year-old white boy with a main complaint about chronic media otitis and a tumor lesion in right mastoid bone. Pathology revealed histiocytosis. The patient had severe dermatitis on the scalp and dystrophic changes with onycholysis, pustules, and nail plate deformity underneath all fingernails and toenails. These lesions responded to antineoplastic therapy. Development of nail dystrophics in Langerhans cell histiocytosis is unusual in children. This case suggests that treatment with antineoplastic therapy might be effective.(AU)

Pan-cytokeratin immunoexpression in Wilms' tumors: a simple approach for understanding tumor epithelial differentiation

Os tumores de Wilms sÆo alguns dos mais freqentes tumores s¢lidos da infƒncia e reconhecidamente um modelo para a compreensÆo da patogˆnese dos tumores embrion rios. As citoqueratinas sÆo prote¡nas intracelulares presentes em tecidos de origem epitelial. Estudamos a imunoexpressÆo da pan-citoqueratina AE1AE3 em 24 tumores de Wilms, dentre ao quais 15 continham tamb‚m tecidos renais nÆo-neopl sicos e 12 apresentavam restos nefrogˆnicos em blocos de parafina, para avaliar a diferencia‡Æo epitelial no desenvolvimento dos tumores de Wilms. Observamos aumento na intensidade de expressÆo de AE1AE3 no componente epitelial dos tumores de Wilms diretamente relacionado ao grau de matura‡Æo das estruturas epiteliais correspondentes aos ductos coletores. (AU)

Atraso diagn¢stico do retinoblastoma / Delayed diagnosis in retinoblastoma

OBJETIVOS: Identificar os principais sinais e sintomas do retinoblastoma e determinar o tempo m‚dio entre o in¡cio dos sintomas e o diagn¢stico. MTODOS: Estudo retrospectivo, com revisÆo dos prontu rios das crian‡as diagnosticadas com retinoblastoma entre janeiro de 1991 e junho de 2000 no Departamento de Pediatria do Hospital do Cƒncer de SÆo Paulo. An lise estat¡stica: teste t de Student, an lise e variƒncia, teste de Tukey-HSD (honest significant differences), teste de Levene, an lise de regressÆo linear, curva ROC, regressÆo log¡stica e an lise de sobrevida pelo m‚todo de Kaplan-Meier. RESULTADOS: Foram revisados 327 prontu rios, sendo 171 pacientes do sexo masculino. A idade m‚dia foi de 25 meses. Doen‡a localizada foi verificada em 269 pacientes. Os sintomas mais freqentes foram leucocoria (79 por cento), estrabismo (10,7 por cento) e tumora‡Æo (3,4 por cento). O tempo m‚dio de queixa foi de 5,8 meses. Pacientes maiores de 2 anos de idade apresentaram maior tempo de queixa em rela‡Æo aos lactentes (7,2 meses versus 4,7 meses; p = 0,001).

Pacientes com estrabismo tiveram maior tempo de queixa (8,8 meses) em compara‡Æo com pacientes com tumora‡Æo (2,3 meses) ou leucocoria (5,6 meses) (p = 0,014). Pacientes com doen‡a metast tica apresentaram maior tempo de queixa (10,6 meses; p < 0,001). O tempo de queixa foi influenciado por doen‡a avan‡ada (OR = 3,25/IC = 1,61:6,55), metast tica (OR = 3,52/IC = 1,21:10,21) e estrabismo (OR = 2,84/IC = 1,36:5,92). A sobrevida global em 5 anos foi maior entre os pacientes com doen‡a localizada (94,6 por cento; p < 0,001) e entre os pacientes com tempo de queixa menor que 6 meses (91 por cento) em compara‡Æo com os pacientes com tempo de queixa maior que 6 meses (78 por cento) (p < 0,001). CONCLUSÇO: Os sinais e sintomas mais freqentes de retinoblastoma foram leucocoria, estrabismo e tumora‡Æo. O tempo m‚dio de queixa foi de 5,8 meses. Estrabismo e doen‡a avan‡ada foram associados a maior tempo de queixa. Pacientes com doen‡a avan‡ada e com tempo de queixa maior que 6 meses tiveram pior progn¢stico. (AU)

Atraso diagn¢stico do retinoblastoma / Delayed diagnosis in retinoblastoma

To identify the main symptoms of retinoblastoma and to determine the mean time between symptom onset and diagnosis(lag time). We carried out a retrospective analysis of the patients diagnosed with retinoblastoma between January 1991 and June 2000, at the Pediatric Department of the Hospital do Cƒncer, SÆo Paulo, Brazil. Statistical analyses performed were: Student.s t test, ANOVA, Tukey-HSD test (honest significant differences), Levene.s test, multiple regression, ROC curve, logistic regression, Kaplan-Meier, and log rank. 327 medical records (171 males) were reviewed. The mean age was 25 months. Localized disease was identified in 269 patients. The most frequent symptoms were leukocoria (79%), strabismus (10.7%) and tumor mass (3.4%). Mean lag time was 5.8 months. Patients older than 2 years old had longer lag time in comparison to infants (7.2 vs 4.7 months; p = 0.001). Lag time was longer among patients with strabismus (8.8 months) in comparison to patients with tumor mass (2.3 months) and leukocoria (5.6 months); p = 0.014. Patients with metastatic disease had longer lag time (10.6 months; p < 0.001). Lag time was influenced by advanced disease (OR = 3.25/CI = 1.61:6.55), metastatic disease (OR=3.52/CI = 1.21:10.21) and strabismus (OR = 2.84/IC = 1.36:5.92). Fiveyear overall survival rates were higher among patients with localized disease (94.6% ) and among patients with lag time less than 6 months (91%), in comparison to patients with longer lag time (78%;p < 0.001). Most frequent symptoms of retinoblastoma were leukocoria, strabismus and tumor mass. Mean lag time was 5.8 months. Strabismus and advanced disease were associated to longer lag time. Patients with advanced disease and lag time longer than 6 months had worse prognosis.(AU)

Sepse grave e choque s‚ptico em crian‡as com cƒncer: fatores preditores de ¢bito

Descrever as caracter¡sticas cl¡nicas das crian‡as e adolescentes portadores de doen‡as oncol¢gicas que foram admitidos na UTIP apresentando sepse grave ou choque s‚ptico. E determinar os fatores preditores de ¢bito e uso de ventila‡Æo pulmonar mecƒnica (VPM). Foram analisadas prospectivamente 33 crian‡as com diagn¢stico de sepse grave ou choque s‚ptico, na UTIP do Hospital do Cƒncer, entre junho e dezembro de 2001. Durante o per¡odo houve 33 interna‡äes, cuja idade variou entre 1 e 23 anos; 16 (48%) eram do sexo masculino e 17 (52%) do sexo feminino. Vinte pacientes eram portadores de leucemia ou linfoma e 13 pacientes de tumores s¢lidos. Vinte e oito pacientes apresentaram quadro infeccioso documentado. Houve crescimento de pat¢genos em 73%, sendo que as infec‡äes por germes gram-negativos foram respons veis por 67% das amostras. Suporte respirat¢rio foi necess rio em 18 casos (54%), a administra‡Æo de drogas inotr¢picas em 22 casos (67%) e em quatro casos a di lise foi indicada. A taxa de mortalidade foi de 41% para os pacientes que necessitaram de drogas inotr¢picas, 69% para os que utilizaram VPM e 100% para aqueles submetidos … di lise. A taxa de mortalidade foi de 27%. Nossos dados sugerem que o in¡cio precoce de tratamento intensivo para crian‡as com cƒncer apresentando sepse grave e choque s‚ptico pode ser um fator capaz de influenciar a mortalidade desses pacientes. E a utiliza‡Æo da ventila‡Æo pulmonar mecƒnica nÆo invasiva demonstrou ser um procedimento capaz de reduzir a necessidade de intuba‡Æo orotraqueal e ventila‡Æo pulmonar mecƒnica invasiva.(AU)

Sepse grave e choque s‚ptico em crian‡as com cƒncer: fatores preditores de ¢bito / Severe sepsis and septic shock in children with cancer

OBJETIVO: Descrever as caracter¡sticas cl¡nicas das crian‡as e adolescentes portadores de doen‡as oncol¢gicas que foram admitidos na UTIP apresentando sepse grave ou choque s‚ptico. E determinar os fatores preditores de ¢bito e uso de ventila‡Æo pulmonar mecƒnica (VPM). MTODOS: Foram analisadas prospectivamente 33 crian‡as com diagn¢stico de sepse grave ou choque s‚ptico, na UTIP do Hospital do Cƒncer, entre junho e dezembro de 2001. RESULTADOS: Durante o per¡odo houve 33 interna‡äes, cuja idade variou entre 1 e 23 anos; 16 (48 por cento) eram do sexo masculino e 17 (52 por cento) do sexo feminino. Vinte pacientes eram portadores de leucemia ou linfoma e 13 pacientes de tumores s¢lidos. Vinte e oito pacientes apresentaram quadro infeccioso documentado. Houve crescimento de pat¢genos em 73 por cento, sendo que as infec‡äes por germes gram-negativos foram respons veis por 67 por cento das amostras. Suporte respirat¢rio foi necess rio em 18 casos (54 por cento), a administra‡Æo de drogas inotr¢picas em 22 casos (67 por cento) e em quatro casos a di lise foi indicada. A taxa de mortalidade foi de 41 por cento para os pacientes que necessitaram de drogas inotr¢picas, 69 por cento para os que utilizaram VPM e 100 por cento para aqueles submetidos … di lise. A taxa de mortalidade foi de 27 por cento. CONCLUSåES: Nossos dados sugerem que o in¡cio precoce de tratamento intensivo para crian‡as com cƒncer apresentando sepse grave e choque s‚ptico pode ser um fator capaz de influenciar a mortalidade desses pacientes. E a utiliza‡Æo da ventila‡Æo pulmonar mecƒnica nÆo invasiva demonstrou ser um procedimento capaz de reduzir a necessidade de intuba‡Æo orotraqueal e ventila‡Æo pulmonar mecƒnica invasiva. (AU)

Long-term survival rates in young patients with thyroid carcinoma

Thyroid carcinoma in patients younger than 18 years is rare. It is associated with a greater risk of metastases. However, the prognosis for these patients is better when compared with that of adults.To present the experience of a single institution in the treatment of patients with thyroid carcinoma during childhood and adolescence.Thirty-eight patients, ranging in age from 4 to 18 years, were diagnosed as having thyroid carcinoma. Pathologic types of carcinoma included 29 papillary, 4 follicular, 1 Hrthle cell, and 4 medullary cases. Hypocalcemia was the main complication, being transitory in 9 patients (24%) and permanent in 6 patients (16%). Vocal cord palsy occurred in 2 patients (5%). Two patients (5%) had a surgical site infection. After a mean follow-up of 9.5 years (range, 1-40 years), 28 patients (74%) were alive and had no evidence of disease, 3 (8%) were alive and had recurrent disease, 4 (11%) died (2 of the disease and 2 of non-cancer-related causes), and 3 (8%) were lost to follow-up. The survival rates at 10 years for the patients with papillary, follicular, and medullary carcinoma were 93%, 100%, and 50%, respectively. Thyroid carcinoma in patients younger than 18 years has a good prognosis even in the presence of neck or distant metastasis. Total thyroidectomy, associated with adjuvant radioactive iodine therapy and thyroidal suppression or not, is effective in patients with a well-differentiated thyroid carcinoma.(AU)

Challenges on participation in a cooperative group of childhood renal tumors in Brasil

SUMMARY OBJECTIVE Children with renal tumors included in clinical trials have significantly better outcomes. In Brasil, the enrollment of patients in clinical trials remains challenging. Here we aimed to describe participation accrual in the Brazilian Wilms Tumor Study Group (BWTSG) and to identify barriers to trial registration of children with renal tumors. METHODS We determined the numbers of renal tumor diagnoses in 105 hospital-based cancer registries from 2001-2009. We then compared these totals with the numbers of renal tumor cases registered in the BWTSG from the same hospitals during the same time period. We also invited members of the Brazilian Pediatric Oncology Society to complete a 5-point Likert-type scale questionnaire regarding their opinions of the importance of participation in cooperative group trials. RESULTS The accrual rate of patient participation per hospital varied from 25% to 76%, and was highest in the South region. The accrual rate of hospital participation also varied according to the region (20-31%) and was highest in the Southeast region. For the questionnaire regarding the importance of participation in cooperative groups, the responses showed an agreement of >75% on 10 of the 13 statements. CONCLUSION Our results demonstrated low accrual of participation in a cooperative group trial in Brasil. We identified variations in registration rates according to geographic region and hospital, which may help targeted efforts to increase registration rates. The survey responses demonstrated that colleagues understand the importance of trial participation.

RESUMO OBJETIVO Crianças com tumores renais incluídas em ensaios clínicos apresentam melhora significativa na sobrevida. No entanto, o envolvimento desses pacientes em ensaios clínicos continua sendo um desafio no Brasil. Nosso objetivo neste estudo é descrever a taxa de aderência e adesão no Grupo Cooperativo Brasileiro para tratamento de Tumor de Wilms (GCBTTW) e identificar barreiras na participação ao protocolo. MÉTODOS Identificamos o número de casos de tumores renais diagnosticados em 105 registros hospitalares de câncer no período de 2001 a 2009. O número total desses casos foi então comparado ao número de casos de tumores renais registrados no GCBTTW provenientes das mesmas unidades hospitalares e durante o mesmo período. Os membros da Sociedade Brasileira de Oncologia Pediátrica foram convidados para completar um questionário com escala do tipo likert com o objetivo de conhecer suas opiniões sobre a importância e as dificuldades na participação em ensaios clínicos de grupos cooperativos. RESULTADOS A aderência de pacientes por hospital variou de 25% a 76% e foi maior na região Sul. A adesão da participação do hospital também variou de acordo com a região (20-31%) e foi maior na região Sudeste. Com relação ao questionário referente à importância da participação em grupos cooperativos, as respostas mostraram concordância de mais de 75% em 10 das 13 afirmações. CONCLUSÃO Nossos resultados demonstraram uma baixa participação em grupos cooperativos no Brasil. Houve variações nas taxas de adesão e aderência de acordo com a região geográfica e unidade hospitalar, o que pode auxiliar em futuros esforços para a melhora dessas taxas. As respostas ao questionário demonstraram que os profissionais entendem a importância da participação em grupos cooperativos.

Association of CYP3A4 genotype with detection of Vgamma/Jbeta trans-rearrangements in the peripheral blood leukocytes of pediatric cancer patients undergoing chemotherapy for ALL.

Cancer patients receiving chemotherapy are exposed to high doses of cytotoxic and genotoxic drugs which, in some cases, can lead to treatment related leukemia. Since this only occurs in a minority of patients, however, it is possible some individuals are predisposed due to genetic polymorphisms in genes for enzymes that mediate drug metabolism. To address this possibility we measured the genotoxicity of chemotherapeutic agents in patients receiving treatment for ALL by the frequency of the Vgamma/Jbeta trans-rearrangement in their peripheral blood leukocytes and compared this with CYP3A4 genotype. CYP3A4 is the most abundant of the cytochrome P450 (CYP) enzyme in the liver and intestine which contains a common -392A>G substitution in the promoter region (CYP3A4*1B allele). We found a significant increase in the frequency of rearrangements during chemotherapy only in patients homozygous for the wild type CYP3A4*1A allele. This provides a direct link between CYP3A4 genotype and susceptibility to drug genotoxicity thus strengthening the possibility that predisposition to treatment related leukemia may be measurable by simple genetic testing.

[Severe sepsis and septic shock in children with cancer]. / Sepse grave e choque séptico em crianças com câncer: fatores preditores de óbito.

BACKGROUND: This report describes the clinical characteristics of children and adolescents bearers of oncological disease who were admitted to PICU with severe sepsis and septic shock. The predicting factors for mortality and for need of pulmonary mechanical ventilation were also determined. METHODS: Thirty-three children diagnosed with severe sepsis and septic shock were evaluated prospectively at the PICU of Hospital do Câncer between June and December of 2001. RESULTS: Thirty-three admissions were analyzed during this period; ages ranged from 1 to 23 years; 16 (48%) were boys and 17 (52%) were girls. Twenty patients had leukemia/lymphoma and 13 patients had solid tumors. Twenty-eight patients had a diagnosis of infectious diseases. In 73% of the patients, infection germs were isolated and gram negative organisms were responsible for 67% of the samples. Respiratory support was necessary for 18 patients (54%), inotropic support for 22 (67%) and dialysis for four patients. The mortality rate was of 41% for patients who needed inotropic support, of 69% for those requiring respiratory support and of 100% for those with an indication for dialysis. The overall mortality rate was of 27%. CONCLUSIONS: This research suggests that early intensive treatment for children with cancer exhibiting severe sepsis and/or septic shock could be an important factor to influence the mortality rate of these patients. Moreover, that noninvasive ventilation could be an option to reduce endotracheal intubation and invasive ventilation.

Incidence and mortality of bone cancer among children, adolescents and young adults of Brazil

OBJECTIVES: Bone cancers occur frequently in children, adolescents, and young adults aging 15 to 29 years. Osteosarcoma and Ewing sarcoma are the most frequent subtypes in this population. The aim of this study was to describe incidence and mortality trends of bone cancers among Brazilian children, adolescents and young adults. METHODS: Incidence information was obtained from 23 population-based cancer registries. Mortality data were extracted from the Atlas of Cancer Mortality from 1979 to 2013. Specific and adjusted rates per million were analyzed according to gender, morphology and age at diagnosis. Median rates were used as a measure of central tendency. Joinpoint regression was applied to analyze trends. RESULTS: Median incidence rates were 5.74 and 11.25 cases per million in children and young adults respectively. Osteosarcoma in the 15-19 years aged group had the highest incidence rates. Stable incidence rates were observed among five registries in 0-14 year's age group. Four registries had a decreased incidence trend among adolescents and young adults. Median mortality rates were 1.22 and 5.07 deaths per million in children and young adults respectively. Increased mortality was observed on the North and Northeast regions. Decreased mortality trends were seen in the South (children) and Southeast (adolescents and young adults). CONCLUSION: Osteosarcoma and Ewing Sarcoma are the most incident bone cancers in all Brazilian regions. Bone cancers showed incidence and mortality patterns variation within the geographic regions and across age groups, although not significant. Despite limitations, it is crucial to monitor cancer epidemiology trends across geographic Brazilian regions.