DICER1-associated central nervous system sarcoma: A comprehensive clinical and genomic characterization of case series of young adult patients.

BACKGROUND

alterations are associated with intracranial tumors in the pediatric population, including pineoblastoma, pituitary blastoma, and the recently described "primary -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 variants were present in two patients, 75% of cases had more than one somatic alteration in , and the most frequent commutation was . 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 and . 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 , , and and most alterations at progression were related to , and signaling pathways.