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Background: The evaluation of existing resources and services is key to identify gaps and prioritize interventions to expand care capacity for children with central nervous system (CNS) tumors. We sought to evaluate the resources for pediatric neuro-oncology (PNO) in Mexico. Methods: A cross-sectional online survey with 35 questions was designed to assess PNO resources and services, covering aspects including number of patients, infrastructure, human resources, and diagnostic and treatment time intervals. The survey was distributed to the members of the Mexican Association of Pediatric Oncology and Hematology (AMOHP) who belong to the nation's many different health systems. Results: Responses were obtained from 33 institutions, distributed throughout the country and part of the many health systems that exist in Mexico. Twenty-one (64%) institutions had less than 10 new cases of pediatric CNS tumors per year. Although 30 (91%) institutions saw pediatric patients up to the age of 18 years, 2 (6%) had a cutoff of 15 years. Twenty-four (73%) institutions had between 1 and 3 pediatric oncologists providing care for children with CNS tumors. Six (18%) institutions did not have a neurosurgeon, while 19 (57%) institutions had a pediatric neurosurgeon. All centers had a pathology department, but 13 (39%) institutions only had access to basic histopathology. Eleven (33%) institutions reported histopathological diagnoses within one week, but 3 (9%) took more than 4 weeks. Radiotherapy for pediatric CNS tumors was referred to outside centers at 18 (55%) institutions. All centers had access to conventional cytotoxic chemotherapy, but only 6 (18%) had access to targeted therapy. Eighteen (55%) respondents estimated a survival rate of less than 60%. Fifteen (45%) centers attributed the main cause of mortality to non-tumor related factors, including infection and post-surgical complications. Conclusions: This is the first national assessment of the resources available in Mexico for the treatment of CNS tumors. It shows disparities in resource capacity and a lack of the specific and efficient diagnoses that allow timely initiation of treatment. These data will enable the prioritization of collaborative interventions in the future.
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BACKGROUND: A high frequency of primary central nervous system (CNS) sarcomas was observed in Peru. This article describes the clinical characteristics, biological characteristics, and outcome of 70 pediatric patients. METHODS: Data from 70 pediatric patients with primary CNS sarcomas diagnosed between January 2005 and June 2018 were analyzed. DNA methylation profiling from 28 tumors and gene panel sequencing from 27 tumors were available. RESULTS: The median age of the patients was 6 years (range, 2-17.5 years), and 66 of 70 patients had supratentorial tumors. DNA methylation profiling classified 28 of 28 tumors as primary CNS sarcoma, DICER1 mutant. DICER1 mutations were found in 26 of 27 cases, TP53 mutations were found in 22 of 27 cases, and RAS-pathway gene mutations (NF1, KRAS, and NRAS) were found in 19 of 27 tumors, all of which were somatic (germline control available in 19 cases). The estimated incidence in Peru was 0.19 cases per 100,000 children (<18 years old) per year, which is significantly higher than the estimated incidence in Germany (0.007 cases per 100,000 children [<18 years] per year; P < .001). Patients with nonmetastatic disease (n = 46) that were treated with a combination therapy had a 2-year progression-free survival (PFS) rate of 58% (95% CI, 44%-76%) and a 2-year overall survival rate of 71% (95% CI, 57%-87%). PFS was the highest in patients treated with chemotherapy with ifosfamide, carboplatin, and etoposide (ICE) after upfront surgery followed by radiotherapy and ICE (2-year PFS, 79% [59%-100%], n = 18). CONCLUSIONS: Primary CNS sarcoma with DICER1 mutation has an aggressive clinical course. A combination of surgery, chemotherapy, and radiotherapy seems beneficial. An underlying cancer predisposition syndrome explaining the increased incidence in Peruvian patients has not been identified so far. LAY SUMMARY: A high incidence of primary pediatric central nervous system sarcomas in the Peruvian population is described. Using sequencing technologies and DNA methylation profiling, it is confirmed that these tumors molecularly belong to the recently proposed entity "primary central nervous system sarcomas, DICER1 mutant." Unexpectedly, DICER1 mutations as well as all other defining tumor mutations (TP53 mutations and RAS-pathway mutations) were not inherited in all 19 patients where analyzation was possible. These tumors have an aggressive clinical course. Multimodal combination therapy based on surgery, ifosfamide, carboplatin, and etoposide chemotherapy, and local radiotherapy leads to superior outcomes.
Assuntos
Neoplasias do Sistema Nervoso Central , Sarcoma , Adolescente , Sistema Nervoso Central/patologia , Neoplasias do Sistema Nervoso Central/tratamento farmacológico , Neoplasias do Sistema Nervoso Central/genética , Criança , Pré-Escolar , RNA Helicases DEAD-box/genética , Humanos , Mutação , Peru/epidemiologia , Ribonuclease III/genética , Sarcoma/tratamento farmacológico , Sarcoma/genéticaRESUMO
PURPOSE: Pediatric neuro-oncology resources are mostly unknown in Chile. We report the human and material resources available in Chilean hospitals providing pediatric neuro-oncology services. METHODS: A cross-sectional survey was distributed to 17 hospitals providing pediatric neuro-oncology services (Programa Infantil Nacional de Drogas Antineoplásicas [PINDA] hospitals, 11; private, 6). RESULTS: Response rate was 71% (PINDA, 8; private, 4). Pediatric neuro-oncology services were mainly provided within general hospitals (67%). Registries for pediatric CNS tumors and chemotherapy-related toxicities were available in 100% and 67% of hospitals, respectively. CNS tumors were treated by pediatric oncologists in 92% of hospitals; none were formally trained in neuro-oncology. The most used treatment protocols were the national PINDA protocols. All WHO essential medicines for childhood cancer were available in more than 80% of the hospitals except for gemcitabine, oxaliplatin, paclitaxel, and procarbazine. The median number of pediatric neurosurgeons per hospital was two (range, 2-6). General neuroradiologists were available in 83% of the centers. Pathology specimens were sent to neuropathologists (58%), adult pathologists (25%), and pediatric pathologists (17%). Intensity-modulated radiotherapy, conformal radiotherapy, and cobalt radiotherapy were used by 67%, 58%, and 42% of hospitals, respectively. Only one private hospital performed autologous hematopoietic cell transplant for children with CNS tumors. CONCLUSION: A wide range of up-to-date treatment modalities are available for children with CNS tumors. Our survey highlights future directions to improve the pediatric neuro-oncology services available in Chile such as the expansion of multidisciplinary clinics, palliative care services, long-term cancer survivorship programs, dedicated clinical research support teams, establishing standardized mechanism for sending pathologic specimen for second opinion to international specialized centers, and establishing specialized neuro-oncology training program.