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
Next-generation medicine encompasses different concepts related to healthcare models and technological developments. In Latin America and the Caribbean, healthcare systems are quite different between countries, and cancer control is known to be insufficient and inefficient considering socioeconomically discrepancies. Despite advancements in knowledge about the biology of different oncological diseases, the disease remains a challenge in terms of diagnosis, treatment, and prognosis for clinicians and researchers. With the development of molecular biology, better diagnosis methods, and therapeutic tools in the last years, artificial intelligence (AI) has become important, because it could improve different clinical scenarios: predicting clinically relevant parameters, cancer diagnosis, cancer research, and accelerating the growth of personalized medicine. The incorporation of AI represents an important challenge in terms of diagnosis, treatment, and prognosis for clinicians and researchers in cancer care. Therefore, some studies about AI in Latin America and the Caribbean are being conducted with the aim to improve the performance of AI in those countries. This review introduces AI in cancer care in Latin America and the Caribbean, and the advantages and promising results that it has shown in this socio-demographic context.
ABSTRACT
Immunotherapy has redefined the treatment of cancer patients and it is constantly generating new advances and approaches. Among the multiple options of immunotherapy, bispecific antibodies (bsAbs) represent a novel thoughtful approach. These drugs integrate the action of the immune system in a strategy to redirect the activation of innate and adaptive immunity toward specific antigens and specific tumor locations. Here we discussed some basic aspects of the design and function of bsAbs, their main challenges and the state-of-the-art of these molecules in the treatment of hematological and solid malignancies and future perspectives.