Factors influencing outcomes of older children with medulloblastoma over 15 years in Peru, a resource-limited setting.

BACKGROUND: Medulloblastoma is the most common malignant brain tumor in children. While survival has improved in high-income countries (HIC), the outcomes for patients in low-to-middle-income countries (LMIC) are unclear. Therefore, we sought to determine the survival of children with medulloblastoma at the Instituto Nacional de Enfermedades Neoplasicas (INEN) between 1997 and 2013 in Peru. METHODS: Between 1997 and 2013, data from 103 children older than 3 years with medulloblastoma were analyzed. Fourteen patients were excluded. The patients were split into two distinct cohorts, 1997-2008 and 2009-2013, corresponding with chemotherapy regimen changes. Event-free (EFS) and overall survival (OS) were calculated using the Kaplan-Meier method, whereas prognostic factors were determined by univariate analysis (log-rank test). RESULTS: Eighty-nine patients were included; median age was 8.1 years (range: 3-13.9 years). The 5-year OS was 62% (95% CI: 53%-74%), while EFS was 57% (95% CI: 48%-69%). The variables adversely affecting survival were anaplastic histology (compared to desmoplastic; OS: HR = 3.4, p = .03), metastasis (OS: HR = 3.5, p = .01; EFS: HR = 4.3, p = .004), delay in radiation therapy of 31-60 days (compared to ≤30 days; EFS: HR = 2.1, p = .04), and treatment 2009-2013 cohort (OS: HR = 2.2, p = .02; EFS: HR = 2.0, p = .03). CONCLUSIONS: Outcomes for medulloblastoma at INEN were low compared with HIC. Anaplastic subtype, metastasis at diagnosis, delay in radiation therapy, and treatment in the period 2009-2013 negatively affected the outcomes in our study. Multidisciplinary teamwork, timely delivery of treatment, and partnerships with loco-regional groups and colleagues in HIC is likely beneficial.

Primary central nervous system sarcoma with DICER1 mutation-treatment results of a novel molecular entity in pediatric Peruvian patients.

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.

Características radiológicas de los tumores malignos intracraneales mediante resonancia magnética y espectroscopia en el Instituto Nacional de Enfermedades Neoplásicas, durante el periodo Setiembre 2008 - Julio 2010 / Radiologic characteristics of intracranial malignant tumors using magnetic resonance and spectroscopy at the National Institute of Neoplasic Diseases, in the period September 2008 - July 2010

OBJETIVO; Determinar las características de los tumores intracraneales malignos por Resonancia Magnética y Espectroscopía en pacientes del Instituto Nacional de Enfermedades Neoplásicas, durante el periodo Setiembre 2008 - Agosto 2010. MATERIAL Y METODOS: El tipo de estudio es no experimental, descriptivo y transversal. La población en estudio son pacientes con tumores cerebrales malignos, con estudio de resonancia magnética cerebral y espectroscopía y con estudio anatomopatológico confirmado, admitidos al INEN entre setiembre 2008 y agosto 2010, siendo una muestra no probabilística por elección, la muestra estuvo conformada por 51 pacientes con características similares a la población. Se utilizó una ficha de datos validados por expertos para consolidar lo encontrado producto de la revisión de historia clínica y estudio de resonancia magnética cerebral con espectroscopía. El procesamiento estadístico se realizó con las aplicaciones de Tabla Dinámica de MS Excel, donde se procedió a realizar el análisis y la descripción estadísticos, como la obtención de frecuencias, porcentajes, sensibilidad y especificidad. La significancia estadística se analizó con la prueba Chi cuadrado. RESULTADOS: La mayoría de tumores malignos intracraneales de alto grado fueron de localización supratentorial, de bordes mal definidos, con realce intenso, con restricción en las secuencias de difusión, de baja señal en secuencias morfológicas ponderadas en T1 y alta señal en secuencias ponderadas en T2, la mayoría de tumores malignos presentaron índices Colina/Creatina elevados, índice N-Acetil Aspartato/Creatinina disminuidos, el índice Colina/N-Acetil Aspartato presenta una relación directa para tumores malignos de alto y bajo grado con un punto de corte de 1.8. Con buena sensibilidad, especificidad y exactitud del método. CONCLUSIONES: Espectroscopía por resonancia magnética puede sustancialmente mejorar en forma no invasiva la exactitud diagnóstica y la clasificación de estos tumores de alto y bajo grado con buena sensibilidad especificidad exactitud del método. La espectroscopía también nos ayuda a diferenciar tumores de bajo y alto grado de malignidad, según el índice de Colina/N-Acetil Aspartato. El software de espectroscopía a color de la institución permite observar los voxel de mayor concentración de colina, pudiendo llegar a constituir un mejor método para la guía de biopsias cerebrales. El índice colina/N acetil aspartato puede ayudar a diferenciar recurrencia del tumor versus injuria por radiación. Como método de diagnóstico presenta algunas limitaciones como presencia de sangrado por lo que siempre es conveniente apoyar el método con las secuencias morfológicas y de difusión