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.

International Society of Paediatric Oncology (SIOP) Global Mapping Programme: Latin American Society of Pediatric Oncology (SLAOP) country-level report.

BACKGROUND: Latin American countries are improving childhood cancer care, showing strong commitment to implement the Global Initiative for Childhood Cancer, but there are scant publications of the situation at a continental level. METHODS: As part of the International Society of Paediatric Oncology Global Mapping project, delegates of each country participating in the Latin American Society of Pediatric Oncology (SLAOP) and chairs of national pediatric oncology societies and cooperative groups were invited to provide information regarding availability of national pediatric cancer control programs (NPCCP), pediatric oncology laws, pediatric oncology tumor registries, and training programs and support to diagnosis and treatment. RESULTS: Nineteen of the 20 countries participating in SLAOP responded. National delegates reported nine countries with NPCCP and four of them were launched in the past 5 years. National pediatric tumor registries are available in eight countries, and three provided published survival results. Fellowship programs for training pediatric oncologists are available in 12 countries. National delegates reported that eight countries provide support to most essential diagnosis and treatments and 11 provide partial or minimal support that is supplemented by civil society organizations. Seven countries have a pediatric oncology law. There are three international cooperative groups and four national societies for pediatric oncology. CONCLUSION: Despite many challenges, there were dramatic advances in survivorship, access to treatment, and availability of NPCCP in Latin America. Countries with highest social development scores in general provide more complete support and are more likely to have NPCCP, training programs, and reported survival results.

Evolução do diagnóstico virológico de raiva humana no Instituto Pasteur de São Paulo, Brasil (1970-2020): análise de dados / Evolution of the virological diagnosis of human rabies at the Pasteur Institute of São Paulo, Brazil (1970-2020): data analysis

O diagnóstico laboratorial precoce de raiva humana deve ser realizado por testes apropriados, visto que a aplicação de protocolos de tratamento médico em indivíduos internados depende dos resultados laboratoriais. O presente estudo analisou os dados referentes aos 560 casos suspeitos de raiva humana submetidos ao diagnóstico virológico no IP-SP entre os anos de 1970 e 2020. Houve um avanço das metodologias laboratoriais, especialmente as moleculares, que passaram a ser essenciais, possibilitando o tratamento de indivíduos expostos, bem como a determinação da fonte de infecção dos casos, fato fundamental para a efetividade de ações de controle em regiões vulneráveis à disseminação da doença. Intervenções no ciclo urbano da raiva, por meio de vacinação de cães e gatos e encaminhamento de amostras para diagnóstico, diminuiram os casos transmitidos por cães, principalmente no Sudeste. Em contrapartida, no mesmo período foi observado um aumento exponencial de casos relacionados ao ciclo silvestre nas regiões Norte (32%) e Nordeste (53,3%), tendo os morcegos como principais transmissores (72%), seguidos dos primatas não humanos (6%) e dos canídeos silvestres (1%). Esses resultados demonstraram a importância do aprimoramento do diagnóstico laboratorial, que é parte essencial na condução de estratégias de controle, bem como de tratamento de indivíduos expostos.

Early laboratory diagnosis of human rabies should be performed by appropriate tests, since the application of medical treatment protocols in hospitalized individuals depends on laboratory results. The present study analyzed the data referring to the 560 suspected cases of human rabies submitted to virological diagnosis in the IP-SP from 1970 to 2020. There has been an advance in laboratory methodologies, especially molecular ones, which have become essential, enabling the treatment of exposed individuals, as well as allowing the determination of the source of infection of cases, a fundamental fact for the effectiveness of control actions in regions vulnerable to the spread of the disease. Interventions in the urban cycle of rabies, through vaccination of dogs and cats and referral of samples for diagnosis decreased the cases transmitted by dogs, especially in the Southeast, on the other hand, an exponential increase of cases was observed in the same period, in the North (32%) and Northeast (53.3%) regions, with cases related to the wild cycle, with bats as the main transmitters (72%), followed by non-human primates (6%), and wild canids (1%). Our results demonstrated the importance of improving laboratory diagnosis, which is an essential part of conducting control strategies as well as the treatment of exposed individuals.

Diffusion-weighted imaging in pediatric extracranial germ cell tumors.

BACKGROUND: Germ cell tumors (GCTs) comprise a rare and heterogeneous group of neoplasms presenting different clinical and histological characteristics, leading to a challenging scenario in clinical practice. Diffusion-weighted imaging (DWI) has been suggested as an indirect marker of tumor density and cellularity and could be used to monitor therapeutic response. However, its role in pediatric GCTs needs to be clarified. PURPOSE: Here, we evaluated the features of DWI in pediatric extracranial GCTs in a reference Brazilian institution. MATERIAL AND METHODS: We included 43 pediatric patients with primary GCTs treated between 2008 and 2022 in Hospital de Amor de Barretos. The patients' MRI images included T1-weighted without contrast, T2-weighted, DWI and apparent diffusion coefficient (ADC) maps. DWI was evaluated in the section that exhibited the greatest restricted diffusion in the largest hypersignal area of the image. The lowest ADC value was determined to define the region of interest (ROI). We used a small ROI, avoiding necrotic, adipose tissue, noisy or nonenhancing lesion voxels as recommended. ROI determination was established by visual inspection by two radiologists in accordance. We used two values of b (b = 50 mm2/s or b = 800) for ADC values. RESULTS: The highest mean ADC (mADC) value was observed in pure teratomas (1,403.50 ± 161.76 x10-3 mm2/s; mean ± SD) compared to other histologies (yolk sac, mixed teratoma, dysgerminoma and mixed GCT) of GCT (p<0.001). Furthermore, ROC analysis determined a cutoff mADC value of 1,179.00 x 10-3 mm2/s that differentiated pure teratomas from the other GCT histologies with a sensitivity of 95.8% and a specificity of 92.9% (AUC = 0.979; p<0.01). A significant increase in mADC was observed for malignant GCTs in treatment (1,197.00 ± 372.00 mm2/s; p<0.001) compared to that exhibited at the time of diagnosis (780.00 ± 168.00 mm2/s; mean ± SD. Our findings suggest that mADC assessment could be used as a tool to distinguish pure teratomas from malignant CGT histologies at diagnosis. Additionally, we demonstrated reasonable evidence that it could be used as a complementary tool to monitor treatment response in patients with malignant GCT.

Molecular Biology of Pediatric and Adult Ovarian Germ Cell Tumors: A Review.

Ovarian germ cell tumors (OGCTs) are rare in adults; indeed, they occur predominantly in children, adolescents, and young adults, and they account for approximately 11% of cancer diagnoses in these groups. Because OGCTs are rare tumors, our current understanding of them is sparse; this is because few studies have investigated the molecular basis of pediatric and adult cancers. Here, we review the etiopathogenesis of OGCTs in children and adults, and we address the molecular landscape of these tumors, including integrated genomic analysis, microRNAs, DNA methylation, the molecular implications of treatment resistance, and the development of in vitro and in vivo models. An elucidation of potential molecular alterations may provide a novel field for understanding the pathogenesis, tumorigenesis, diagnostic markers, and genetic peculiarity of the rarity and complexity of OGCTs.

How we approach conservative treatment of retinoblastoma in South America in the era of local ocular treatments: A consensus of the Grupo America Latina de Oncologia Pediatrica (GALOP).

Local therapies are increasingly used for ocular preservation in retinoblastoma. In middle-income countries, these techniques pose specific challenges mostly related to more advanced disease at diagnosis. The Grupo de America Latina de Oncología Pediátrica (GALOP) developed a consensus document for the management of conservative therapy for retinoblastoma. Intra-arterial chemotherapy (OAC) is the preferred therapy, except for those with less advanced disease or age younger than 6 months. OAC allowed for a reduction in the use of external beam radiotherapy in our setting. Intravitreal chemotherapy is the preferred treatment for vitreous seeding. Enucleation is the treatment of choice for eyes with advanced disease.

High-dose chemotherapy with autologous stem cell transplantation for patients with extracranial germ cell tumors - experience of two Brazilian pediatric centers.

Malignant extracranial germ cell tumors (GCTs) are rare in pediatric patients and are usually extremely sensitive to chemotherapy. Relapsed or refractory tumors, although rare, established the need for second-line therapies, including high-dose chemotherapy with autologous stem cell transplantation (HDCT/ASCT). However, there are few data on its use in children with GCTs. We present a retrospective analysis of all patients diagnosed with extracranial GCTs who received HDCT/ASCT at two Brazilian pediatric cancer centers from May 1999 to December 2019. We identified a total of 34 patients with a median age at diagnosis of 2.8 years (range, 0 to 18.8), who received HDCT/ASCT. Most patients (73%) received carboplatin, etoposide and melphalan (CEM) as a HDCT regimen. Fourteen patients received a second-line conventional dose chemotherapy (CDCT), 14 received a third-line CDCT and five received even a fourth-line CDCT prior to HDCT/ASCT. After a median follow-up of 22.7 months (range, 0.3 to 198.1), 16 patients had died after tumor relapse/progression and 2 patients died from HDCT/ASCT toxicity. We observed a 5-year OS of 47.1% and 5-year EFS of 44.1%. The 5-year OS for patients referred for HDCT/ASCT with progressive disease was 10% compared to 62.5% for those who achieved disease control before HDCT/ASCT (p = 0.001). In our experience, heavily pretreated children and adolescents with extracranial GCTs achieved considerable survival rates with HDCT/ASCT since, at least, partial control of their disease was possible before starting HDCT/ASCT. The role of HDCT/ASCT in pediatric patients with GCTs should be investigated in prospective trials.

Ocorrência de florações de cianobactérias e consequências para a saúde pública no Nordeste do Brasil / Ocurrence of cyanobacterial bloom and consequences for public health in Northeastern Brazil / Ocurrencia de las floraciones de cianobacterias y consecuencias para la salud pública en el Nordeste de Brasil

As florações são resultado de interações entre fatores físicos, químicos e biológicos, sendo caracterizadas pelo crescimento massivo de microrganismos. As proliferações de cianobactérias indicam a deterioração na qualidade da água e podem ser consideradas problemas de saúde pública, devido à capacidade de produção e liberação de toxinas pelas cianobactérias nos ambientes aquáticos, especialmente nos reservatórios de abastecimento. Assim, este trabalho teve como objetivo verificar, a partir de uma revisão de literatura, a ocorrência de florações de cianobactérias e cianotoxinas e os efeitos especialmente para saúde pública. A metodologia utilizada foi revisão narrativa de trabalhos selecionados seguindo os critérios de inclusão. Foi verificada a ocorrência de 74 espécies de cianobactérias, sendo Microcystis aeruginosa e Raphidiopsis raciborskii as predominantes. Espécies potencialmente tóxicas foram encontradas em todas as florações relatadas nos trabalhos realizados na região Nordeste. As florações de cianobactérias ocorreram principalmente em reservatórios da região Nordeste, juntamente com cianotoxinas (microcistinas, cilindrospermopiscina e saxitoxina). Têm sido frequentes florações com cianotoxinas em sistemas aquáticos, ocasionando alterações no ambiente aquático. Essas modificações alcançam diversos níveis tróficos e podem alcançar o homem, sendo problema de saúde pública.

The blooms are the result of interactions between physical, chemical, and biological factors, and are characterized by the explosive growth of microorganisms. The proliferations of cyanobacteria indicate deterioration in quality and can be considered public health problems due to the ability of cyanobacteria to produce and release toxins in aquatic environments, especially in supply reservoirs. Thus, this study aimed to review the literature to verify the occurrence of cyanobacteria and cyanotoxin blooms and the effects especially for public health. The methodology used was narrative review of selected papers according to the inclusion criteria. The occurrence of 74 cyanobacteria species was verified, with Microcystis aeruginosa and Raphidiopsis raciborskii being the predominant ones. Potentially toxic species were found in all blooms studies carried out in the Northeast region. Cyanobacterial blooms were found mainly in reservoirs in the Northeast region, along with cyanotoxins (microcystins, cylindrospermopsin, and saxitoxin). Blooms with cyanotoxins have been frequent in aquatic systems, causing changes in the aquatic environment. These changes reach several trophic levels, and can reach man, being a public health problem.

Las floraciones son el resultado de interacciones entre factores físicos, químicos y biológicos, caracterizadas por el crecimiento explosivo de microorganismos. La proliferación de cianobacterias indica un deterioro de la calidad y puede considerarse un problema de salud pública debido a la capacidad de las cianobacterias de producir y liberar toxinas en ambientes acuáticos, especialmente en los embalses de abastecimiento. Así, este estudio tenía como objetivo revisar la literatura para verificar la ocurrencia de floraciones de cianobacterias y cianotoxina, así como sus efectos especialmente en la salud pública. La metodología utilizada fue la revisión narrativa de los documentos seleccionados de acuerdo con los criterios de inclusión. Se verificó la aparición de 74 especies de cianobacterias, de las cuales Microcystis aeruginosa y Raphidiopsis raciborskii fueron las más predominantes. Se encontraron especies potencialmente tóxicas en todos los estudios de floración realizados en los estados de la región Nordeste de Brasil. Las floraciones de cianobacterias se encontraron principalmente en embalses en la región Nordeste, junto con cianotoxinas (microcistinas, cilindrospermopsinas y saxitoxinas). Ha habido frecuentes floraciones con cianotoxinas en los sistemas acuáticos, causando cambios en el medio acuático. Estos cambios alcanzan varios niveles tróficos y pueden llegar al hombre, siendo un problema de salud pública.

A consensus document for the clinical management of invasive fungal diseases in pediatric patients with hematologic cancer and/or undergoing hematopoietic stem cell transplantation in Brazilian medical centers

ABSTRACT In the present paper we summarize the suggestions of a multidisciplinary group including experts in pediatric oncology and infectious diseases who reviewed the medical literature to elaborate a consensus document (CD) for the diagnosis and clinical management of invasive fungal diseases (IFDs) in children with hematologic cancer and those who underwent hematopoietic stem-cell transplantation. All major multicenter studies designed to characterize the epidemiology of IFDs in children with cancer, as well as all randomized clinical trials addressing empirical and targeted antifungal therapy were reviewed. In the absence of randomized clinical trials, the best evidence available to support the recommendations were selected. Algorithms for early diagnosis and best clinical management of IFDs are also presented. This document summarizes practical recommendations that will certainly help pediatricians to best treat their patients suffering of invasive fungal diseases.

A consensus document for the clinical management of invasive fungal diseases in pediatric patients with hematologic cancer and/or undergoing hematopoietic stem cell transplantation in Brazilian medical centers.

In the present paper we summarize the suggestions of a multidisciplinary group including experts in pediatric oncology and infectious diseases who reviewed the medical literature to elaborate a consensus document (CD) for the diagnosis and clinical management of invasive fungal diseases (IFDs) in children with hematologic cancer and those who underwent hematopoietic stem-cell transplantation. All major multicenter studies designed to characterize the epidemiology of IFDs in children with cancer, as well as all randomized clinical trials addressing empirical and targeted antifungal therapy were reviewed. In the absence of randomized clinical trials, the best evidence available to support the recommendations were selected. Algorithms for early diagnosis and best clinical management of IFDs are also presented. This document summarizes practical recommendations that will certainly help pediatricians to best treat their patients suffering of invasive fungal diseases.

Results of a randomized, prospective clinical trial evaluating metronomic chemotherapy in nonmetastatic patients with high-grade, operable osteosarcomas of the extremities: A report from the Latin American Group of Osteosarcoma Treatment.

BACKGROUND: Metronomic chemotherapy (MC) consists of the administration of a low dose of chemotherapy on a daily or weekly basis without a long break to achieve an antitumoral effect through an antiangiogenic effect or stimulation of the immune system. The potential effect of MC with continuous oral cyclophosphamide and methotrexate in patients with high-grade operable osteosarcomas (OSTs) of the extremities was investigated. METHODS: Patients with high-grade OSTs who were 30 years old or younger were eligible for registration at diagnosis. Eligibility for randomization included 1) nonmetastatic disease and 2) complete resection of the primary tumor. The study design included a backbone of 10 weeks of preoperative therapy with methotrexate, adriamycin, and platinum (MAP). After surgery, patients were randomized between 2 arms to complete 31 weeks of MAP or receive 73 weeks of MC after MAP. The primary endpoint was event-free survival (EFS) from randomization. RESULTS: There were 422 nonmetastatic patients registered (May 2006 to July 2013) from 27 sites in 3 countries (Brazil, Argentina and Uruguay), and 296 were randomized to MAP plus MC (n = 139) or MAP alone (n = 157). At 5 years, the EFS cumulative proportions surviving in the MAP-MC group and the MAP-alone group were 61% (standard error [SE], 0.5%) and 64% (SE, 0.5%), respectively, and they were not statistically different (Wilcoxon [Gehan] statistic = 0.724; P =.395). The multivariate analysis showed that necrosis grades 1 and 2, tumor size, and amputation were associated with shorter EFS. CONCLUSIONS: According to the current follow-up, EFS with MAP plus MC is not statistically superior to EFS with MAP alone in patients with high-grade, resectable OSTs of the extremities. Cancer 2017;123:1003-10. © 2016 American Cancer Society.

Lowered Cisplatin Dose and No Bleomycin in the Treatment of Pediatric Germ Cell Tumors: Results of the GCT-99 Protocol From the Brazilian Germ Cell Pediatric Oncology Cooperative Group.

PURPOSE: We describe the results of a risk-adapted, response-based therapeutic approach from the Brazilian GCT-99 study on germ cell tumors. PATIENTS AND METHODS: From May 1999 to October 2009, 579 participants were enrolled in the Brazilian GCT-99 study. Treatment, defined as specific chemotherapy regimen and number of cycles, was allocated by means of risk-group assignment at diagnosis with consideration for stage and primary tumor site. Patients at low risk received no chemotherapy. Patients at intermediate risk (IR) with a good response (GR) received four cycles of platinum and etoposide (PE), for total doses of platinum 420 mg/m(2) and etoposide 2,040 mg/m(2). Patients at IR with a partial response (PR) received three cycles of PE plus three cycles of ifosfamide, vinblastine, and bleomycin. Patients at high risk (HR) with a GR received four cycles of PE and ifosfamide (PEI) at total doses of platinum 420 mg/m(2), etoposide 1,200 mg/m(2), and ifosfamide 30 g/m(2). Patients at HR with a PR received six cycles of PEI. RESULTS: The risk-group distribution was 213 LR, 138 IR, and 129 HR for 480 evaluable patients. Overall survival (OS) and event-free survival (EFS) rates at 10 years were, respectively, 90% and 88.6% in the IR-GR group (n = 126) and 74.1% and 74.1% in the IR-PR group (n = 12). Ten-year rates for the HR-GR group (n = 86) were an OS of 66.8% and an EFS of 62.5%. The HR-PR group (n = 43) had an OS of 74.8% and an EFS of 73.4%. In univariable and multivariable analysis, increased serum lactate dehydrogenase level and histology for a metastatic immature teratoma were prognostic of a worsened outcome. CONCLUSION: Reduction of therapy to two drugs did not compromise survival outcomes for patients in the IR-GR group, and escalation of therapy with PEI did not significantly improve OS and EFS in patients at HR.

Carboplatin in the treatment of Ewing sarcoma: Results of the first Brazilian collaborative study group for Ewing sarcoma family tumors-EWING1.

BACKGROUND: Large cooperative group studies have shown the efficacy of risk-adapted treatment for Ewing sarcoma. However, validation and local adaptation by National cooperative groups is needed. A multicenter protocol to determine the efficacy and safety of a risk-adapted intensive regimen was developed by the Brazilian cooperative group. PROCEDURE: Patients <30 years old with Ewing sarcoma were eligible. Induction chemotherapy consisted of two cycles of ICE (ifosfamide, carboplatin, and etoposide) followed by two cycles of VDC (vincristine, doxorubicin, and cyclophosphamide), followed by local control. Patients with low risk (LR) disease (localized resectable with normal LDH) received 10 additional alternating courses of IE with VDC. For patients with high-risk (HR) disease (unresectable, pelvic, metastatic, or high LDH), two additional cycles of ICE were given. RESULTS: One-hundred seventy five patients (39% metastatic) were enrolled. Fifty-two patients (29.7%) were LR and 123 (70.3%) were HR. Overall response rate at end of induction was 27.4%. Five-year event-free survival (EFS) and overall survival (OS) estimates were 51.4% and 54.4%, respectively. Patients with localized disease had better outcomes than patients with metastases (5-year EFS 67.9% vs. 25.5%, and 5-year OS 70.3% vs. 29.1%, respectively). On multivariate analysis, the presence of metastatic disease was the only prognostic factor (P < 0.01). CONCLUSION: The VDC/ICE protocol was feasible, and considering the high tumor burden in our population, resulted in comparable results to those reported by cooperative groups in high-income countries. Further adaptation to maximize efficacy and minimize toxicity will be required.

Osteosarcoma in patients younger than 12 years old without metastases have similar prognosis as adolescent and young adults.

BACKGROUND: Childhood cancer is relatively rare and tends to present specific age distribution, as a prognostic factor for some of these diseases. Information on how young age affects prognosis, response to chemotherapy, and local control options in children versus AYA with osteosarcoma (OST) is minimal. METHODS: In order to identify the main differences in clinical pathologic features, surgical approaches and survival rates of primary high grade OST of the extremity between children (n = 156; <12 years old) and AYA (n = 397; 12-30 years old), the institutional database with 553 patients treated by BOTG studies over 15 years were reviewed. RESULTS: There were no differences in metastases at diagnosis, tumor size, and grade of necrosis between the two age groups. The rate of amputation was 30% higher in the children group (P = 0.018). The rate of limb salvage surgery using reconstruction with allograft or autograft was 70% higher in the children group (P = 0.018) while endoprosthesis rate was 40% higher in the AYA group (P = 0.018). The log rank test revealed that survival is similar between the two age groups for non-metastatic patients (P = 0.424 for OS and P = 0.393 for EFS). Metastatic patients of both ages group had higher risk of dying compared to non-metastatic (HR 3.283 95% CI 2.581-4.177; P < 0.001). Children with metastases at diagnosis had less OS time (P = 0.049) and EFS time (P = 0.032) than adolescents. CONCLUSION: Non-metastatic OST in preadolescent patients does not appear to be significantly different from those seen in AYA patients, but has local control challenges. Children presenting with metastases should be considered an ultra-high-risk group.

Investigation of IGF2, Hedgehog and fusion gene expression profiles in pediatric sarcomas.

UNLABELLED: The childhood sarcomas are malignant tumors with high mortality rates. They are divided into two genetic categories: a category without distinct pattern karyotypic changes and the other category showing unique translocations that originate gene rearrangements. This category includes rhabdomyosarcoma (RMS), Ewing's sarcoma (ES) and synovial sarcoma (SS). Diverse studies have related development genes, such as; IGF2, IHH, PTCH1 and GLI1 and sarcomatogenesis. OBJECTIVE: To characterize the RMS, ES and SS rearrangements, we quantify the expression of IGF2 IHH, PTCH1 and GLI1 genes and correlate molecular data with clinical parameters of patients. DESIGN: We analyzed 29 RMS, 10 SS and 60 ES tumor samples by RT-PCR (polymerase chain reaction-reverse transcription) and qPCR (quantitative PCR). RESULTS: Among the samples of ARMS, 50% had rearrangements of PAX3/7-FOXO1, 60% of ES samples were EWS-FLI1 positive and 90% of SS samples were positive for SS18-SSX1/2. In relation to the control reference samples (QPCR Human Reference Total RNA-Stratagene, Human Skeletal Muscle Total RNA-Ambion, Universal RNA Human Normal Tissues-Ambion), RMS samples showed a high IGF2 gene expression (p<0.0001). Moreover, ES samples showed a low IGF2 gene expression (p<0.0001) and high IHH (p<0.0001), PTCH1 (p=0.0173) and GLI1 (p=0.0113) gene expressions. CONCLUSIONS: The molecular characterization of IGF and Hedgehog pathway in these pediatric sarcomas may collaborate to enable a better understanding of the biological behavior of these neoplasms.