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.

Factores predictores del desarrollo de vasoespasmo cerebral en pacientes con hemorragia subaracnoidea aneurismática atendidos en el Hospital Nacional Edgardo Rebagliati Martins durante el periodo 2010-2011 / Factors predictors of the development of cerebral vasospasm in patients with aneurysmal subarachnoid hemorrhage treated at the National Hospital Edgardo Rebagliati Martins during the period 2010 - 2011

La Hemorragia Subaracnoidea (HSA) es una condición devastadora producto de la ruptura de un aneurisma cerebral. A pesar de avances en su diagnóstico y tratamiento el pronóstico continúa siendo pobre. Su principal complicación es el vasoespasmo, una condición potencialmente tratable. El presente tuvo por finalidad identificar, ¿Cuáles son los factores predictores del desarrollo de Vasoespasmo Cerebral en pacientes con HSA aneurismática atendidos en el "Hospital Nacional Edgardo Rebagliati Martins" durante el periodo 2010 - 2011? La población fue de 127 pacientes admitidos con diagnóstico definido de HSA aneurismática entre el 1ero de Junio del 2010 y el 31 de Diciembre del 2011 y seleccionados mediante criterios. Todo paciente tuvo una evaluación clínica y tomográfica inicial y seguido en su evolución mediante una ficha durante 20 días. Se les aplicó, además, la escala de valoración de riesgo de vasoespasmo e isquemia cerebral tardía (ERVI). Se realizó una TAC cerebral a las 72 horas, a los 7 días, ya los 14 días o cuando la condición clínica lo ameritaba. Concluido el seguimiento clínico y no habiendo evidencia clínico-imagenológica de vasoespasmo el paciente terminó su participación. La edad media fue 57.5 años ± DS 18.38. Del total, 63.78 por ciento tenía una edad <=50 años. La hipertensión arterial fue el antecedente más frecuente en 48.82 por ciento. Los estadios I y II de las escalas de la WFNS y Hunt and Huss (HH) fueron los predominantes en 66.93 por ciento. Contrariamente, los estadios III y IV lo fueron en la escala de Fisher en 64.56 por ciento. La incidencia de vasoespasmo cerebral/DCI fue de 47.24 por ciento, siendo solo vasoespasmo 33.07 por ciento, con una media de 7.3 días DS ± 3.37. Hubo un incremento progresivo de vasoespasmo/DCI a medida que incrementaba el grado de la ERVI, con incidencias de 22.73 por ciento, 64.44 por ciento y 100 por ciento para los grados I, II y III, respectivamente. La hidrocefalia fue la segunda complicación en...

Revascularización cerebral en el tratamiento de aneurismas cerebrales complejos / Cerebral revascularization for the treatment of complex intracranial aneurysms

Los procedimientos de revascularización cerebral se utilizan en el manejo quirúrgico de aneurismas en los que hay gran riesgo de generar isquemia al intentar el tratamiento quirúrgico o endovascular. Además se usan en el tratamiento de tumores de base craneal que engloban e infiltran la pared de la arteria carótida interna o sus ramas principales, en la enfermedad oclusiva vascular con riesgo de producir infarto de tipo hemodinámico y en la enfermedad de moyamoya.

Cerebral revascularization procedures are used in the surgical management of cerebral aneurysms in which there is agreat risk of generating ischemia, in the attempt for surgical or endovascular treatment. Besides this, these procedures are utilized en the treatment of cranial base tumors that encase and infiltrate the trunk of the internal carotid artery orits main branches, in the vascular occlusive disease with risk of producing hemodynamic type stroke and, in the moyamoya disease. These techniques have the aim of restoring the blood supply of the brain and with it, the nutrient loading in order to avoid ischemia in territories already affected or in risk. To obtain an effective revascularization, with good clinical outcome , the patient should be chosen adequately with cerebral blood flow studies and vascular reserve, to perform a meticulous technique and the correct graft should be elected.