ABSTRACT
Background: DICER1 alterations are associated with intracranial tumors in the pediatric population, including pineoblastoma, pituitary blastoma, and the recently described "primary DICER1-associated CNS sarcoma" (DCS). DCS is an extremely aggressive tumor with a distinct methylation signature and a high frequency of co-occurring mutations. However, little is known about its treatment approach and the genomic changes occurring after exposure to chemoradiotherapy. Methods: We collected clinical, histological, and molecular data from eight young adults with DCS. Genomic analysis was performed by Next-generation Sequencing (NGS). Subsequently, an additional germline variants analysis was completed. In addition, an NGS analysis on post-progression tumor tissue or liquid biopsy was performed when available. Multiple clinicopathological characteristics, treatment variables, and survival outcomes were assessed. Results: Median age was 20 years. Most lesions were supratentorial. Histology was classified as fusiform cell sarcomas (50%), undifferentiated (unclassified) sarcoma (37.5%), and chondrosarcoma (12.5%). Germline pathogenic DICER1 variants were present in two patients, 75% of cases had more than one somatic alteration in DICER1, and the most frequent commutation was TP53. Seven patients were treated with surgery, Ifosfamide, Cisplatin, and Etoposide (ICE) chemotherapy and radiotherapy. The objective response was 75%, and the median time to progression (TTP) was 14.5 months. At progression, the most common mutations were in KRAS and NF1. Overall survival was 30.8 months. Conclusions: DCS is an aggressive tumor with limited therapeutic options that requires a comprehensive diagnostic approach, including molecular characterization. Most cases had mutations in TP53, NF1, and PTEN, and most alterations at progression were related to MAPK, RAS and PI3K signaling pathways.
ABSTRACT
El trastorno del estrés postraumático (TSPT) es una entidad nosológica clasificada desde 1980 por el DSM III, asociado a eventos traumáticos extraordinarios para el paciente y se presenta al cabo de mínimo 6 horas. El estudio abarca una muestra de 31 pacientes, seleccionados por haber sufrido herida por arma de fuego o cortopunzante en tórax y/o abdomen, de los cuales 16 cumplieron los criterios para el DSM III-R para el TSPT. Se encontró que el criterio que mas se cumplía en la población estudiada era el criterio referente a revivir el evento (26 pacientes) (criterio B). El item que más cumplieron los 31 pacientes fué el referido a alteración psicológica ante situaciones similares al evento (criterio B4) correspondiendo al 100 por ciento de población estudiada; de los pacientes que desarrollaron el TSPT todos presentaron hipervigilancia con una significancia estadística (p<0.0001). El estudio permite mostrar que el TSPT si se presenta en nuestra población además permite sugerir que los pacientes con las características establecidas para el presente estudio ameritan un control psicológico a mediano plazo como mínimo
