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 betw...

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Detalles Bibliográficos
Autores: Diaz Coronado, RY, Mynarek, M, Koelsche, C, Mora Alferez, P, Casavilca, S, Wachtel Aptowitzer, A, Sahm, F, von Deimling, A, Schüller, U, Spohn, M, Sturm, D, Pfister, SM, Morales La Madrid, A, Sernaque Quintana, R, Sarria Bardales, G, Negreiros Chinchihuara, T, Ojeda Medina, L, Garcia-Corrochano Medina, P, Campos Sanchez, DA, Ponce Farfan, J, Rutkowski, S, Garcia Leon, JL
Tipo de recurso: artículo
Estado:Versión publicada
Fecha de publicación:2021
País:Perú
Institución:Instituto Nacional de Enfermedades Neoplásicas
Repositorio:INEN-Institucional
Idioma:inglés
OAI Identifier:oai:repositorio.inen.sld.pe:20.500.14703/87
Acceso en línea:https://hdl.handle.net/20.500.14703/87
Access Level:acceso abierto
Palabra clave:Peru
central nervous system (CNS)
pediatric
sarcoma
somatic DICER1 mutation
https://purl.org/pe-repo/ocde/ford#3.02.21
Descripción
Sumario: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.

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