Beyond Clinical Trials: Understanding Neurotrophic Tropomyosin Receptor Kinase Inhibitor Challenges and Efficacy in Real-World Pediatric Oncology.

PURPOSE: Our study aimed to explore real-world treatment scenarios for children and adolescents with neurotrophic tropomyosin receptor kinase (NTRK)-fused tumors, emphasizing access, responses, side effects, and outcomes. PATIENTS AND METHODS: Pooled clinical data from 17 pediatric cases (11 soft-tissue sarcomas, five brain tumors, and one neuroblastoma) treated with larotrectinib and radiologic images for 14 patients were centrally reviewed. Testing for gene fusions was prompted by poor response to treatment, tumor progression, or aggressiveness. RESULTS: Six different NTRK fusion subtypes were detected, and various payment sources for testing and medication were reported. Radiologic review revealed objective tumor responses (OR) in 11 of 14 patients: Complete responses: two; partial responses: nine; and stable disease: three cases. Grades 1 or 2 Common Terminology Criteria for Adverse Events adverse effects were reported in five patients. Regarding the entire cohort's clinical information, 15 of 17 patients remain alive (median observation time: 25 months): four with no evidence of disease and 11 alive with disease (10 without progression). One patient developed resistance to the NTRK inhibitor and died from disease progression while another patient died due to an unrelated cause. CONCLUSION: This real-world study confirms favorable agnostic tumor OR rates to larotrectinib in children with NTRK-fused tumors. Better coordination to facilitate access to medication remains a challenge, particularly in middle-income countries like Brazil.

Neck Circumference for Identification of Excess Adiposity in Adolescents with Cancer: A Better Parameter for Use in Clinical Practice?

Purpose: Excess weight in adolescents with cancer during treatment does affect cancer outcomes. Neck circumference (NC), an easygoing anthropometric measure, may present greater metabolic risk, and is associated with excess adiposity. The aim of this study was to identify the prevalence of elevated NC in adolescents with cancer and associated factors. Methods: Cross-sectional study with adolescents aged 10-19 years, under antineoplastic treatment, evaluated from 2015 to 2017, at a Pediatric Oncology Institute's outpatient clinic. Anthropometric parameters were collected, besides diagnosis, sex, and age. The classification of elevated NC was carried out considering cutoff values for adolescents, according to sex and age group. A binary logistic regression was used to determine relationships between NC and associated factors. Results: Among 496 eligible cases, most were male (n = 299, 60.3%). A total of 31.9% of cases had high NC. There is significant and moderate correlation between skinfold thickness (TS) and NC (ρ = 0.6; p = 0.000), and a significant but weak correlation between TS and body mass index (ρ = 0.267; p = 0.000). The adjusted analysis for sex, age group, and type of tumor showed that females are more likely to belong to the high NC category, to have excess adiposity. The age group between 10 and 12 years was the most associated with this outcome (2.795 [0.979-7.977]; p < 0.05). TS is also associated with high NC (1.114 [1.050-1.182]; p < 0.05). Conclusion: It was concluded that there is high prevalence of elevated NC and higher risks for this outcome considering type of tumor, sex, age group, besides being an easy and simple measure for use in clinical practice.

Comparison between whole-body magnetic resonance imaging and whole-body metaiodobenzylguanidine scintigraphy in the evaluation of primary tumor and metastases in neuroblastoma.

BACKGROUND: Whole-body metaiodobenzylguanidine (131 I-MIBG) scintigraphy is the gold standard method to detect neuroblastoma; however, it depends on radioactive material and is expensive. In contrast, whole-body magnetic resonance imaging (WB-MRI) is affordable in developing countries and has been shown to be effective in the evaluation of solid tumors. This study aimed to compare the sensitivity and specificity of WB-MRI with MIBG in the detection of primary tumors and neuroblastoma metastases. PROCEDURE: This retrospective study enrolled patients with neuroblastoma between 2013 and 2020. All patients underwent WB-MRI and MIBG at intervals of up to 15 days. The results were marked in a table that discriminated anatomical regions for each patient. Two experts evaluated, independently and in anonymity, the WB-MRI images, and two others evaluated MIBG. The results were compared in terms of sensitivity and specificity, for each patient, considering MIBG as the gold standard. This study was approved by the UNIFESP Ethics Committee. RESULTS: Thirty patients with neuroblastoma were enrolled in this study. The age ranged from 1 to 15 years, with a mean of 5.7 years. The interval between exams (WB-MRI and MIBG) ranged from 1 to 13 days, with an average of 6.67 days. Compared to MIBG, WB-MRI presented a sensitivity and specificity greater than or equal to 90% for the detection of primary neuroblastoma in bones and lymph nodes. When we consider the patient without individualizing the anatomical regions, WB-MRI presented sensitivity of 90% and specificity of 73.33%. CONCLUSION: In conclusion, WB-MRI is a sensitive and specific method to detect neuroblastoma in bone and lymph nodes and highly sensible to primary tumor diagnosis, suggesting that this test is a viable alternative in places where MIBG is difficult to access. Studies with a larger number of cases are necessary for definitive conclusions.

The risks of the new morbidities acquired during pediatric onco-critical care and their life-shortening effects.

OBJECTIVE: The authors investigated the functional status at ICU admission and at hospital discharge, and the impact of dysfunctions on survivors' lifespan. METHOD: Single-center retrospective cohort. The FSS (Functional Status Scale) was calculated at ICU admission and at hospital discharge. A new morbidity was defined as an increase in FSS ≥ 3. RESULTS: Among 1002 patients, there were 855 survivors. Of these, 194 (22.6%) had died by the end of the study; 45 (5.3%) had a new morbidity. Means in the motor domain at admission and discharge were 1.37 (SD: 0.82) and 1.53 (SD 0.95, p = 0.002). In the feeding domain, the means were 1.19 (SD 0.63) and 1.30 (SD 0.76), p = 0.002; global means were 6.93 (SD 2.45) and 7.2 (SD 2.94), p = 0.007.  Acute respiratory failure requiring mechanical ventilation, the score PRISM IV, age < 5 years, and central nervous system tumors were independent predictors of new morbidity. New morbidity correlated with lower odds of survival after hospital discharge, considering all causes of death (p = 0.014), and was independently predictive of death (Cox hazard ratio = 1.98). In Weibull models, shortening in the life span of 14.2% (p = 0.014) was estimated as a new morbidity. CONCLUSIONS: New morbidities are related to age, disease severity at admission, and SNC tumors. New morbidities, in turn, correlate with lower probabilities of survival and shortening of the remaining life span. Physical rehabilitation interventions in this population of children may have the potential to provide an increase in lifespan.

The risks of the new morbidities acquired during pediatric onco-critical care and their life-shortening effects

Abstract Objective: The authors investigated the functional status at ICU admission and at hospital discharge, and the impact of dysfunctions on survivors' lifespan. Method: Single-center retrospective cohort. The FSS (Functional Status Scale) was calculated at ICU admission and at hospital discharge. A new morbidity was defined as an increase in FSS ≥ 3. Results: Among 1002 patients, there were 855 survivors. Of these, 194 (22.6%) had died by the end of the study; 45 (5.3%) had a new morbidity. Means in the motor domain at admission and discharge were 1.37 (SD: 0.82) and 1.53 (SD 0.95, p = 0.002). In the feeding domain, the means were 1.19 (SD 0.63) and 1.30 (SD 0.76), p = 0.002; global means were 6.93 (SD 2.45) and 7.2 (SD 2.94), p = 0.007. Acute respiratory failure requiring mechanical ventilation, the score PRISM IV, age < 5 years, and central nervous system tumors were independent predictors of new morbidity. New morbidity correlated with lower odds of survival after hospital discharge, considering all causes of death (p = 0.014), and was independently predictive of death (Cox hazard ratio = 1.98). In Weibull models, shortening in the life span of 14.2% (p = 0.014) was estimated as a new morbidity. Conclusions: New morbidities are related to age, disease severity at admission, and SNC tumors. New morbidities, in turn, correlate with lower probabilities of survival and shortening of the remaining life span. Physical rehabilitation interventions in this population of children may have the potential to provide an increase in lifespan.

Diagnostic Errors in Wilms' Tumors: Learning From Our Mistakes.

Aim: This study aimed to analyze clinical characteristics and image findings in patients initially diagnosed with renal masses and treated on the Société Internationale d'Oncologie Pédiatrique (SIOP) 2001 protocol for Wilms tumor (WT) that eventually were diagnosed with different pathologies. Methods: We reviewed the preoperative symptoms, laboratory tests, and images of patients who were initially treated for WT and proved to have other diagnoses. Data from these patients were compared to those of the last 10 patients with WT and the last 10 patients with neuroblastoma (NBL) treated at a single institution. Results: From June 2001 to December 2020, we treated 299 patients with NBL and 194 with WT. Five patients treated with preoperative chemotherapy for WT were postoperatively diagnosed with NBL (one patient had bilateral renal masses and one with multifocal xanthogranulomatous pyelonephritis). Three underwent nephrectomy, two biopsies only, and one adrenalectomy due to intraoperative characteristics. Regarding clinical presentation, abdominal mass or swelling was very suggestive of WT (p = 0.011); pain, although very prevalent in the study group (67%), was not statistically significant, as well as intratumoral calcifications on computed tomography (CT) (67%). Urinary catecholamines were elevated in all patients mistreated for WT with the exception of the patient with pyelonephritis in which it was not collected. Conclusion: Some pathologies can be misdiagnosed as WT, especially when they present unspecified symptoms and dubious images. Diagnostic accuracy was 98.1%, which highlights the quality of the multidisciplinary team. Abdominal mass or swelling is highly suggestive of WT, especially in the absence of intratumoral calcifications on CT. If possible, urinary catecholamines should be collected at presentation as they help in the differential diagnosis of NBL.

Management of Pediatric Tumors With Vascular Extension.

Background: Pediatric tumors can present with vascular extension to the inferior vena cava and right atrium, which impacts the surgical strategy and can be challenging during surgical treatment. Wilms tumor (WT) is the most common retroperitoneal tumor that can present with vascular extension, but also adrenal tumors, clear cell tumors from the kidney, and hepatoblastomas can present with this situation. Surgical aims include obtaining complete tumor resection without risk for patients, to avoid severe bleeding, cardiac arrest, and embolization, and to avoid cardiac bypass if possible. Objective: To describe and discuss the surgical strategies to deal with pediatric tumors with vascular extension and propose a protocol. Method: Retrospectivly review the experience of treating patients with vascular extension in a single institution, describing different scenarios and a decision making fluxogram based on the preoperative evaluation regarding the surgical techniques and the need for cardiac bypass that are adequate for each situation. Image studies are important to guide the surgical strategy. Depending on the quality of image available, computerized tomography (CT) or magnetic resonance imaging (MRI) can be enough to give the information needed for surgical decisions. Ultrasonography (US) with Doppler is helpful to confirm diagnosis and describes factors to guide the adequate surgical strategy, like the upper level extension and presence or absence of blood flow around the thrombus. Neoadjuvant chemotherapy is indicated in most cases, in order to reduce the upper level of extension (and avoid the need for cardiac bypass) and to lower the risk of embolization. The approach is based on the upper level of the thrombus and can include cavotomy or cavectomy, sometimes with cardiac bypass and cardiac arrest with hypothermia, when the thrombus reaches the diaphragmatic level or above. Pathology analysis of the thrombus can guide staging and the need for radiotherapy postoperatively. Results: A decision making fluxogram protocol is presented focusing on the surgical treatment of such condition. Conclusion: Surgery strategy is highly impacted by the presence of vascular extension in pediatric tumors. Surgeons should be aware of potential complications and how to prevent them. Such cases should be treated in reference centers.

Effects of Glycine on Collagen, PDGF, and EGF Expression in Model of Oral Mucositis.

Oral mucositis is frequently a toxic effect of chemotherapeutic and/or radiotherapeutic treatment, resulting from complex multifaceted biological events involving DNA damage. The clinical manifestations have a negative impact on the life quality of cancer patients. Preventive measures and curative treatment of mucositis are still not well established. The glycine has anti-inflammatory, immunomodulatory, and cytoprotective actions, being a potential therapeutic in mucositis. The objective was to evaluate the effects of glycine on the expression of collagen and growth factors, platelet and epidermal in a hamster model oral mucositis. The mucositis was induced by the protocol of Sonis. There were 40 hamsters used, divided into two groups: Group I-control; Group II-supplemented with 5% intraperitoneal glycine, 2.0 mg/g diluted in hepes. Histopathological sections were used to perform the immune-histochemical method, the evaluation of collagen expression, and the growth factors: Epidermal growth factor (EGF) and platelet (PDGF). It was observed that the group supplemented with glycine experienced higher amounts of collagen expression and predominance type of collagen I. The glycine group presented lower immunoexpression of the growth factors, EGF and PDGF. The group supplemented with glycine showed a marked healing process of the oral mucosite, demonstrated by the predominance of collagen type I and reduction of growth factors, EGF and PDGF.

Aspectos clínicos, epidemiológicos e sobrevida de crianças com neuroblastoma: 21 anos de experiência do instituto de oncologia pediátrica, são paulo / Clinical and epidemiological characteristics and survival outcomes of children with neuroblastoma: 21 years of experience at the instituto de oncologia pediátrica, in são paulo, brazil

RESUMO Objetivo: Descrever as características clínicas e epidemiológicas e a sobrevida de crianças com neuroblastoma (NB) atendidas em centro de oncologia pediátrica, no período de 1991 a 2012. Métodos: Estudo retrospectivo, com análise de dados clínicos e epidemiológicos de 258 pacientes com NB atendidos em centro de oncologia pediátrica, no período de 1991 a 2012, por meio de consulta a prontuários médicos. Resultados: A idade média das crianças foi de 40,5±46,4 meses, e a mediana, de 28,9 meses (intervalo interquartil 42,2); relação masculino:feminino 1,3:1, sendo 1% dos pacientes assintomáticos. As manifestações mais frequentes foram: febre (25%), dor abdominal (22%), massa abdominal (19%) e dor óssea (19%). O tempo médio do início dos sintomas até a realização do diagnóstico foi de 3,0±4,8 meses. A localização do tumor mais frequente foi o abdome (63%). As metástases ocorreram na medula óssea (37%) e nos ossos (33%). A sobrevida global (SG) e a sobrevida livre de eventos (SLE) em cinco anos foram de 62 e 52%, respectivamente. A principal causa de óbito foi a progressão da doença (72%). Conclusões: As características clínicas das crianças com NB são variáveis e, em sua maioria, inespecíficas, o que torna o reconhecimento clínico difícil e, em geral, tardio. Em crianças com idade inferior a 5 anos, massa abdominal e/ou dor óssea, irritabilidade e febre de origem indeterminada, o diagnóstico de NB deve ser considerado.

ABSTRACT Objective: To describe the clinical and epidemiological characteristics and survival outcomes of children with neuroblastoma (NB) treated at a pediatric oncology center from 1991 to 2012. Methods: A retrospective study with clinical and epidemiological data from 258 patients with neuroblastoma treated at a pediatric oncology center from 1991 to 2012, using medical records. Results: The average age of the children at diagnosis was 40.5±46.4 months with a median age of 28.9 months (interquartile range 42.2). The male:female ratio was 1.3:1, and 1% of the patients were asymptomatic. The most frequent manifestations were: fever (25%), abdominal pain (22%), abdominal mass (19%), and bone pain (19%). The mean time from symptom onset to diagnosis was 3.0±4.8 months. The most common location of the tumor was the abdomen (63%). Metastases occurred in the bone marrow (37%) and in the bone (33%). Overall survival (OS) and event-free survival (EFS) in five years were 62 and 52%, respectively. The main cause of death was the progression of the disease (72%). Conclusions: The clinical features of children with neuroblastoma are variable and mostly nonspecific, which makes clinical recognition difficult and, in general, too late. In children less than 5 years old, with an abdominal mass and/or bone pain, irritability, and a fever from an unknown cause, neuroblastoma should be considered as a possible diagnosis.

CLINICAL AND EPIDEMIOLOGICAL CHARACTERISTICS AND SURVIVAL OUTCOMES OF CHILDREN WITH NEUROBLASTOMA: 21 YEARS OF EXPERIENCE AT THE INSTITUTO DE ONCOLOGIA PEDIÁTRICA, IN SÃO PAULO, BRAZIL. / ASPECTOS CLÍNICOS, EPIDEMIOLÓGICOS E SOBREVIDA DE CRIANÇAS COM NEUROBLASTOMA: 21 ANOS DE EXPERIÊNCIA DO INSTITUTO DE ONCOLOGIA PEDIÁTRICA, SÃO PAULO.

OBJECTIVE: To describe the clinical and epidemiological characteristics and survival outcomes of children with neuroblastoma (NB) treated at a pediatric oncology center from 1991 to 2012. METHODS: A retrospective study with clinical and epidemiological data from 258 patients with neuroblastoma treated at a pediatric oncology center from 1991 to 2012, using medical records. RESULTS: The average age of the children at diagnosis was 40.5±46.4 months with a median age of 28.9 months (interquartile range 42.2). The male:female ratio was 1.3:1, and 1% of the patients were asymptomatic. The most frequent manifestations were: fever (25%), abdominal pain (22%), abdominal mass (19%), and bone pain (19%). The mean time from symptom onset to diagnosis was 3.0±4.8 months. The most common location of the tumor was the abdomen (63%). Metastases occurred in the bone marrow (37%) and in the bone (33%). Overall survival (OS) and event-free survival (EFS) in five years were 62 and 52%, respectively. The main cause of death was the progression of the disease (72%). CONCLUSIONS: The clinical features of children with neuroblastoma are variable and mostly nonspecific, which makes clinical recognition difficult and, in general, too late. In children less than 5 years old, with an abdominal mass and/or bone pain, irritability, and a fever from an unknown cause, neuroblastoma should be considered as a possible diagnosis.

OBJETIVO: Descrever as características clínicas e epidemiológicas e a sobrevida de crianças com neuroblastoma (NB) atendidas em centro de oncologia pediátrica, no período de 1991 a 2012. MÉTODOS: Estudo retrospectivo, com análise de dados clínicos e epidemiológicos de 258 pacientes com NB atendidos em centro de oncologia pediátrica, no período de 1991 a 2012, por meio de consulta a prontuários médicos. RESULTADOS: A idade média das crianças foi de 40,5±46,4 meses, e a mediana, de 28,9 meses (intervalo interquartil 42,2); relação masculino:feminino 1,3:1, sendo 1% dos pacientes assintomáticos. As manifestações mais frequentes foram: febre (25%), dor abdominal (22%), massa abdominal (19%) e dor óssea (19%). O tempo médio do início dos sintomas até a realização do diagnóstico foi de 3,0±4,8 meses. A localização do tumor mais frequente foi o abdome (63%). As metástases ocorreram na medula óssea (37%) e nos ossos (33%). A sobrevida global (SG) e a sobrevida livre de eventos (SLE) em cinco anos foram de 62 e 52%, respectivamente. A principal causa de óbito foi a progressão da doença (72%). CONCLUSÕES: As características clínicas das crianças com NB são variáveis e, em sua maioria, inespecíficas, o que torna o reconhecimento clínico difícil e, em geral, tardio. Em crianças com idade inferior a 5 anos, massa abdominal e/ou dor óssea, irritabilidade e febre de origem indeterminada, o diagnóstico de NB deve ser considerado.

DO THE RADIOLOGICAL CRITERIA WITH THE USE OF RISK FACTORS IMPACT THE FORECASTING OF ABDOMINAL NEUROBLASTIC TUMOR RESECTION IN CHILDREN?

BACKGROUND: The treatment of neuroblastoma is dependent on exquisite staging; is performed postoperatively and is dependent on the surgeon's expertise. The use of risk factors through imaging on diagnosis appears as predictive of resectability, complications and homogeneity in staging. AIM: To evaluate the traditional resectability criteria with the risk factors for resectability, through the radiological images, in two moments: on diagnosis and in pre-surgical phase. Were analyzed the resectability, surgical complications and relapse rate. METHODS: Retrospective study of 27 children with abdominal and pelvic neuroblastoma stage 3 and 4, with tomography and/or resonance on the diagnosis and pre-surgical, identifying the presence of risk factors. RESULTS: The mean age of the children was 2.5 years at diagnosis, where 55.6% were older than 18 months, 51.9% were girls and 66.7% were in stage 4. There was concordance on resectability of the tumor by both methods (INSS and IDRFs) at both moments of the evaluation, at diagnosis (p=0.007) and post-chemotherapy (p=0.019); In this way, all resectable patients by IDRFs in the post-chemotherapy had complete resection, and the unresectable ones, 87.5% incomplete. There was remission in 77.8%, 18.5% relapsed and 33.3% died. CONCLUSIONS: Resectability was similar in both methods at both pre-surgical and preoperative chemotherapy; preoperative chemotherapy increased resectability and decreased number of risk factors, where the presence of at least one IDRF was associated with incomplete resections and surgical complications; relapses were irrelevant.

ASSESSMENT OF THE LATE EFFECTS ON BONES AND ON BODY COMPOSITION OF CHILDREN AND ADOLESCENTS TREATED FOR ACUTE LYMPHOCYTIC LEUKEMIA ACCORDING TO BRAZILIAN PROTOCOLS. / AVALIAÇÃO DOS EFEITOS ÓSSEOS TARDIOS E COMPOSIÇÃO CORPORAL DE CRIANÇAS E ADOLESCENTES TRATADOS DE LEUCEMIA LINFOIDE AGUDA SEGUNDO PROTOCOLOS BRASILEIROS.

OBJECTIVE: To evaluate the impact of therapy on bone mineral density (BMD) and body composition in survivors of acute lymphoblastic leukemia (ALL) treated in accordance with Brazilian protocols by the Brazilian Cooperative Group of Treatment of Lymphoblastic Leukemia in Childhood (GBTLI) LLA-93 and LLA-99. METHODS: A cross-sectional study with 101 patients was performed. BMD and body composition were evaluated using bone densitometry and were interpreted according to the age group and the reference population. Values between -1.1 and -1.9 in the group of children under 20 years were considered as risk group for low BMD z-scores. BMD values were compared to clinical characteristics, treatment received and body composition. A chi-square test, Fisher's exact test, likelihood ratio and Student's t-test were applied, with a 5% significance level. RESULTS: The patients presented a frequency of fractures of 2%, of osteonecrosis, 2%, and of low BMD, 2.9%. In the group of 79 patients under 20 years of age, three had low BMD. The 16 that presented risk for low BMD, demonstrated lower valutes in lumbar vertebrae L1-L4 (p=0.01) and whole body (p=0.005), and smaller values of lean body mass (p=0.03). In the group of 22 patients over 20 years of age, ten had osteopenia. CONCLUSIONS: The low impact of treatment on BMD of this study confirms the concept that the bone mass gain occurs with increasing age and that the treatment does not influence the process. The population at risk for low BMD values presented lower bone mass values and could benefit from a long-term monitoring for possible bone toxicity.

OBJETIVO: Avaliar o impacto da terapia sobre a densidade mineral óssea (DMO) e composição corporal em sobreviventes da leucemia linfoide aguda (LLA), tratados de acordo com os protocolos brasileiros do Grupo Cooperativo Brasileiro de Tratamento de Leucemia Linfoide Aguda na Infância (GBTLI), LLA-93 e LLA-99. MÉTODOS: Em estudo transversal com 101 pacientes, avaliaram-se a composição corporal e a DMO por meio da densitometria óssea, interpretando-a conforme a faixa etária e a população de referência. Foi considerado grupo de risco para baixa DMO valores de z-escore entre -1,1 e -1,9 no grupo dos menores de 20 anos. Compararam-se os valores da DMO com características clínicas, tratamento recebido e composição corporal. Foram utilizados os testes qui-quadrado, exato de Fisher, razão de verossimilhança e t de Student, com nível de significância de 5%. RESULTADOS: Foram encontradas 2% de fraturas, 2% de osteonecrose e 2,9% de baixa DMO. No grupo de pacientes com menos de 20 anos, três apresentaram baixa DMO. Os 16 pacientes com risco para baixa DMO exibiram menores valores em vértebras lombares L1-L4 (p=0,01), corpo total (p=0,005) e valores mais baixos de massa magra (p=0,03). No grupo de 22 pacientes com mais de 20 anos, dez demonstraram osteopenia. CONCLUSÕES: O baixo impacto do tratamento sobre a DMO neste estudo ratifica o conceito de que o ganho de massa óssea ocorre com o aumento da idade e que o tratamento não influencia tal processo. A população de risco para baixa DMO demonstrou valores menores de massa óssea, podendo beneficiar-se de um acompanhamento em longo prazo para uma possível toxicidade óssea.

Do the radiological criteria with the use of risk factors impact the forecasting of abdominal neuroblastic tumor resection in children? / Critérios radiológicos impactam a previsão de ressecabilidade em neuroblastomas abdominais na criança com o uso de fatores de risco?

ABSTRACT Background: The treatment of neuroblastoma is dependent on exquisite staging; is performed postoperatively and is dependent on the surgeon's expertise. The use of risk factors through imaging on diagnosis appears as predictive of resectability, complications and homogeneity in staging. Aim: To evaluate the traditional resectability criteria with the risk factors for resectability, through the radiological images, in two moments: on diagnosis and in pre-surgical phase. Were analyzed the resectability, surgical complications and relapse rate. Methods: Retrospective study of 27 children with abdominal and pelvic neuroblastoma stage 3 and 4, with tomography and/or resonance on the diagnosis and pre-surgical, identifying the presence of risk factors. Results: The mean age of the children was 2.5 years at diagnosis, where 55.6% were older than 18 months, 51.9% were girls and 66.7% were in stage 4. There was concordance on resectability of the tumor by both methods (INSS and IDRFs) at both moments of the evaluation, at diagnosis (p=0.007) and post-chemotherapy (p=0.019); In this way, all resectable patients by IDRFs in the post-chemotherapy had complete resection, and the unresectable ones, 87.5% incomplete. There was remission in 77.8%, 18.5% relapsed and 33.3% died. Conclusions: Resectability was similar in both methods at both pre-surgical and preoperative chemotherapy; preoperative chemotherapy increased resectability and decreased number of risk factors, where the presence of at least one IDRF was associated with incomplete resections and surgical complications; relapses were irrelevant.

RESUMO Racional: O tratamento do neuroblastoma é dependente de estadiamento primoroso, realizado no pós-cirúrgico e dependente da expertise do cirurgião. O uso de fatores de risco através da imagem ao diagnóstico surge como preditivo de ressecabilidade, complicações e homogeneidade no estadiamento. Objetivos: Avaliar o critério de ressecabilidade tradicional com os fatores de risco para ressecabilidade, através das imagens radiológicas, em dois momentos no diagnóstico e no pré-cirúrgico analisando a ressecabilidade, complicações cirúrgicas e índice de recidiva. Métodos: Estudo retrospectivo em 27 crianças com neuroblastoma estádios 3 e 4 em abdome e pelve, e com tomografia e/ou ressonância no diagnóstico e pré-cirúrgico, identificando-se a presença de fatores de risco. Resultados: A idade média das crianças foi de 2,5 anos ao diagnóstico, onde 55,6% estavam acima dos 18 meses, 51,9% eram meninas e 66,7% tinham estádio 4. Houve concordância da ressecabilidade do tumor pelos dois métodos avaliados (INSS e IDRFs) e em ambos os momentos da avaliação, ao diagnóstico (p=0,007) e pós-quimioterapia (p=0,019). Desta forma todos pacientes ressecáveis por IDRFs no pós-quimioterapia tiveram ressecção completa; já nos irressecáveis, 87,5% tiveram ressecção incompleta. Houve remissão em 77,8%, 18,5% recaíram e 33,3% morreram. Conclusões: Aressecabilidade foi semelhante em ambos os métodos tanto no diagnóstico como no pré-cirúrgico. A quimioterapia pré-operatória aumentou a ressecabilidade e diminuição do número de fatores de risco, onde a presença de ao menos um IDRF associou-se às ressecções incompletas e complicações cirúrgicas. As recidivas foram irrelevantes.

AVALIAÇÃO DOS EFEITOS ÓSSEOS TARDIOS E COMPOSIÇÃO CORPORAL DE CRIANÇAS E ADOLESCENTES TRATADOS DE LEUCEMIA LINFOIDE AGUDA SEGUNDO PROTOCOLOS BRASILEIROS / ASSESSMENT OF THE LATE EFFECTS ON BONES AND ON BODY COMPOSITION OF CHILDREN AND ADOLESCENTS TREATED FOR ACUTE LYMPHOCYTIC LEUKEMIA ACCORDING TO BRAZILIAN PROTOCOLS

RESUMO Objetivo: Avaliar o impacto da terapia sobre a densidade mineral óssea (DMO) e composição corporal em sobreviventes da leucemia linfoide aguda (LLA), tratados de acordo com os protocolos brasileiros do Grupo Cooperativo Brasileiro de Tratamento de Leucemia Linfoide Aguda na Infância (GBTLI), LLA-93 e LLA-99. Métodos: Em estudo transversal com 101 pacientes, avaliaram-se a composição corporal e a DMO por meio da densitometria óssea, interpretando-a conforme a faixa etária e a população de referência. Foi considerado grupo de risco para baixa DMO valores de z-escore entre -1,1 e -1,9 no grupo dos menores de 20 anos. Compararam-se os valores da DMO com características clínicas, tratamento recebido e composição corporal. Foram utilizados os testes qui-quadrado, exato de Fisher, razão de verossimilhança e t de Student, com nível de significância de 5%. Resultados: Foram encontradas 2% de fraturas, 2% de osteonecrose e 2,9% de baixa DMO. No grupo de pacientes com menos de 20 anos, três apresentaram baixa DMO. Os 16 pacientes com risco para baixa DMO exibiram menores valores em vértebras lombares L1-L4 (p=0,01), corpo total (p=0,005) e valores mais baixos de massa magra (p=0,03). No grupo de 22 pacientes com mais de 20 anos, dez demonstraram osteopenia. Conclusões: O baixo impacto do tratamento sobre a DMO neste estudo ratifica o conceito de que o ganho de massa óssea ocorre com o aumento da idade e que o tratamento não influencia tal processo. A população de risco para baixa DMO demonstrou valores menores de massa óssea, podendo beneficiar-se de um acompanhamento em longo prazo para uma possível toxicidade óssea.

ABSTRACT Objective: To evaluate the impact of therapy on bone mineral density (BMD) and body composition in survivors of acute lymphoblastic leukemia (ALL) treated in accordance with Brazilian protocols by the Brazilian Cooperative Group of Treatment of Lymphoblastic Leukemia in Childhood (GBTLI) LLA-93 and LLA-99. Methods: A cross-sectional study with 101 patients was performed. BMD and body composition were evaluated using bone densitometry and were interpreted according to the age group and the reference population. Values between -1.1 and -1.9 in the group of children under 20 years were considered as risk group for low BMD z-scores. BMD values were compared to clinical characteristics, treatment received and body composition. A chi-square test, Fisher’s exact test, likelihood ratio and Student’s t-test were applied, with a 5% significance level. Results: The patients presented a frequency of fractures of 2%, of osteonecrosis, 2%, and of low BMD, 2.9%. In the group of 79 patients under 20 years of age, three had low BMD. The 16 that presented risk for low BMD, demonstrated lower valutes in lumbar vertebrae L1-L4 (p=0.01) and whole body (p=0.005), and smaller values of lean body mass (p=0.03). In the group of 22 patients over 20 years of age, ten had osteopenia. Conclusions: The low impact of treatment on BMD of this study confirms the concept that the bone mass gain occurs with increasing age and that the treatment does not influence the process. The population at risk for low BMD values presented lower bone mass values and could benefit from a long-term monitoring for possible bone toxicity.

The value of anterior displacement of the abdominal aorta in diagnosing neuroblastoma in children / O valor do deslocamento anterior da aorta abdominal para o diagnóstico de neuroblastoma em crianças

Abstract Objective: To determine the value of anterior displacement of the abdominal aorta, when present at any level or only at the level of the adrenal gland, contralateral to the mass, in diagnosing neuroblastoma on computed tomography or magnetic resonance imaging in children up to 7 years of age. Materials and Methods: Imaging examinations of 66 patients were classified by consensus as for the presence of anterior aorta displacement and were compared with the pathology report. Results: We found anterior abdominal aorta displacement in 26 (39.39%) of the 66 patients evaluated. Among those 26 patients, we identified neuroblastoma in 22 (84.62%), nephroblastoma in 3 (11.54%), and Burkitt lymphoma in 1 (3.85%). The positive predictive value was 84.62%, and the specificity was 88.24%. The displacement of the aorta was at the adrenal level, contralateral to the mass, in 14 cases, all of which were attributed to neuroblastoma. Conclusion: When the abdominal aorta is displaced at the level of the adrenal gland, contralateral to the mass, it can be said that the diagnosis is neuroblastoma, whereas abdominal aorta displacement occurring at other abdominal levels has a positive predictive value for neuroblastoma of approximately 85%.

Resumo Objetivo: Determinar o valor do deslocamento tumoral anterior da aorta abdominal, quando presente em qualquer nível abdominal e quando presente somente ao nível da suprarrenal contralateral, na tomografia computadorizada e/ou ressonância magnética, para o diagnóstico de neuroblastoma, em crianças com até 7 anos de idade. Materiais e Métodos: Imagens de exames de 66 pacientes foram classificadas em consenso quanto à presença do deslocamento anterior da aorta e confrontadas com o anatomopatológico. Resultados: Observou-se deslocamento anterior da aorta abdominal, em qualquer nível abdominal, em 26 (39,39%) dos 66 pacientes. Desses 26 pacientes, 22 (84,62%) apresentaram neuroblastoma e os outros 4 (15,38%) representaram 3 casos de nefroblastomas e 1 de linfoma de Burkitt. O valor preditivo positivo foi 84,62% e a especificidade, 88,24%. Considerando o deslocamento da aorta somente presente quando ocorreu ao nível da suprarrenal contralateral à massa, observou-se que 14 casos eram neuroblastomas e nenhum outro tumor que não o neuroblastoma deslocava a aorta neste nível. Conclusão: Quando o deslocamento anterior da aorta abdominal é presente ao nível da suprarrenal contralateral à massa, pode-se afirmar que o diagnóstico é de neuroblastoma, ao passo que, quando presente nos demais níveis abdominais, sua capacidade em predizer neuroblastoma será de aproximadamente 85% nesta população.

The value of anterior displacement of the abdominal aorta in diagnosing neuroblastoma in children.

OBJECTIVE: To determine the value of anterior displacement of the abdominal aorta, when present at any level or only at the level of the adrenal gland, contralateral to the mass, in diagnosing neuroblastoma on computed tomography or magnetic resonance imaging in children up to 7 years of age. MATERIALS AND METHODS: Imaging examinations of 66 patients were classified by consensus as for the presence of anterior aorta displacement and were compared with the pathology report. RESULTS: We found anterior abdominal aorta displacement in 26 (39.39%) of the 66 patients evaluated. Among those 26 patients, we identified neuroblastoma in 22 (84.62%), nephroblastoma in 3 (11.54%), and Burkitt lymphoma in 1 (3.85%). The positive predictive value was 84.62%, and the specificity was 88.24%. The displacement of the aorta was at the adrenal level, contralateral to the mass, in 14 cases, all of which were attributed to neuroblastoma. CONCLUSION: When the abdominal aorta is displaced at the level of the adrenal gland, contralateral to the mass, it can be said that the diagnosis is neuroblastoma, whereas abdominal aorta displacement occurring at other abdominal levels has a positive predictive value for neuroblastoma of approximately 85%.

OBJETIVO: Determinar o valor do deslocamento tumoral anterior da aorta abdominal, quando presente em qualquer nível abdominal e quando presente somente ao nível da suprarrenal contralateral, na tomografia computadorizada e/ou ressonância magnética, para o diagnóstico de neuroblastoma, em crianças com até 7 anos de idade. MATERIAIS E MÉTODOS: Imagens de exames de 66 pacientes foram classificadas em consenso quanto à presença do deslocamento anterior da aorta e confrontadas com o anatomopatológico. RESULTADOS: Observou-se deslocamento anterior da aorta abdominal, em qualquer nível abdominal, em 26 (39,39%) dos 66 pacientes. Desses 26 pacientes, 22 (84,62%) apresentaram neuroblastoma e os outros 4 (15,38%) representaram 3 casos de nefroblastomas e 1 de linfoma de Burkitt. O valor preditivo positivo foi 84,62% e a especificidade, 88,24%. Considerando o deslocamento da aorta somente presente quando ocorreu ao nível da suprarrenal contralateral à massa, observou-se que 14 casos eram neuroblastomas e nenhum outro tumor que não o neuroblastoma deslocava a aorta neste nível. CONCLUSÃO: Quando o deslocamento anterior da aorta abdominal é presente ao nível da suprarrenal contralateral à massa, pode-se afirmar que o diagnóstico é de neuroblastoma, ao passo que, quando presente nos demais níveis abdominais, sua capacidade em predizer neuroblastoma será de aproximadamente 85% nesta população.

Nutritional status of children and adolescents at diagnosis of hematological and solid malignancies.

OBJECTIVE: To assess the nutritional status of child and adolescent patients with cancer at diagnosis. METHODS: A total of 1154 patients were included and divided into two groups: solid and hematological malignancies. The parameters used for nutritional assessment were weight, height, triceps skinfold thickness, mid-upper arm circumference, arm muscle circumference, body mass index and percentage weight loss. RESULTS: At diagnosis, below adequate body mass index was observed by anthropometric analysis in 10.85% of the patients - 12.2% in the solid tumor group and 9.52% in the hematologic group. The average weight loss adjusted for a period of 7 days was -2.82% in the hematologic group and -2.9% in the solid tumor group. CONCLUSIONS: The prevalence of malnutrition is higher among patients with malignancies than in the general population, even though no difference was observed between the two groups.

Nutritional status of children and adolescents at diagnosis of hematological and solid malignancies

Objective: To assess the nutritional status of child and adolescent patients with cancer at diagnosis. Methods: A total of 1154 patients were included and divided into two groups: solid and hematological malignancies. The parameters used for nutritional assessment were weight, height, triceps skinfold thickness, mid-upper arm circumference, arm muscle circumference, body mass index and percentage weight loss. Results: At diagnosis, below adequate body mass index was observed by anthropometric analysis in 10.85% of the patients – 12.2% in the solid tumor group and 9.52% in the hematologic group. The average weight loss adjusted for a period of 7 days was −2.82% in the hematologic group and −2.9% in the solid tumor group. Conclusions: The prevalence of malnutrition is higher among patients with malignancies than in the general population, even though no difference was observed between the two groups...

Migraine is frequent in children and adolescents with neurofibromatosis type 1.

BACKGROUND: Despite the high prevalence of headache in patients with neurofibromatosis type 1 (NF1), little data exist regarding the classification and characterization of headaches experienced by these patients. This paper describes a study of headache in patients with NF1 compared with healthy controls. METHODS: In this transversal study, participants (aged 4-19 years) were classified into two groups: NF1 patients or control subjects. The diagnosis of NF1 was performed according to the diagnostic criteria of the National Institutes of Health Consensus Conference, and the headache diagnosis was performed according to the diagnostic criteria of the International Classification of Headache Disorders, Second Edition. All participants underwent physical and neurologic evaluation and completed a detailed headache questionnaire. RESULTS: The comparison of 50 patients with NF1 and 50 age-matched controls revealed that the complaint of headache was significantly more frequent in the NF1 group than in the control group (CG) (62% vs 14%, χ(2)(1) = 22.4; P < 0.001). Migraine was significantly more frequent in patients with NF1 than in the CG (54% vs 14%, χ(2)(1) = 17.82; P < 0.001). No differences were found between the two groups regarding the use of simple analgesics (NF1: 14% vs CG: 5%, χ(2)(1) = 1.18; P = 0.276). CONCLUSIONS: Children and adolescents with NF1 are prone to migraines. Complaints of headache are very frequent in this population.

Facial reconstruction surgery 10 years after treatment for hemangiopericytoma: planning considerations and clinical outcomes.

This paper describes the surgical correction of ankylosis of the right temporomandibular joint and reconstruction of the middle and lower thirds of the right side of the face in a young man who had undergone treatment for hemangiopericytoma 10 years earlier, which led to serious functional, esthetic, and psychological problems and diminished his quality of life. The results of reconstruction surgery with alloplastic material (Medopor®) and surgical planning with fibrotic tissue due to radiation and the risk of osteoradionecrosis are discussed.