RESUMEN
PURPOSE: Central nervous system (CNS) embryonal tumors are a diverse group of malignant tumors typically affecting pediatric patients that recently have been better defined, and this paper describes evolution of a unique type of embryonal tumor at relapse. METHODS: Two pediatric patients with CNS embryonal tumors with EWSR1-PLAGL1 rearrangements treated at Arkansas Children's Hospital with histopathologic and molecular data are described. RESULTS: These two patients at diagnosis were classified as CNS embryonal tumors with EWSR1-PLAGL1 rearrangements based on histologic appearance and molecular data. At relapse both patient's disease was reclassified as atypical teratoid rhabdoid tumor (ATRT) based on loss of INI-1, presence of SMARCB1 alterations, and methylation profiling results. CONCLUSION: CNS embryonal tumors with EWSR1-PLAGL1 rearrangements acquire or include a population of cells with SMARCB1 alterations that are the component that predominate at relapse, suggesting treatment aimed at this disease component at diagnosis should be considered.
Asunto(s)
Neoplasias del Sistema Nervioso Central , Recurrencia Local de Neoplasia , Neoplasias de Células Germinales y Embrionarias , Proteína EWS de Unión a ARN , Proteína SMARCB1 , Femenino , Humanos , Masculino , Neoplasias del Sistema Nervioso Central/genética , Neoplasias del Sistema Nervioso Central/patología , Reordenamiento Génico , Recurrencia Local de Neoplasia/genética , Recurrencia Local de Neoplasia/patología , Neoplasias de Células Germinales y Embrionarias/genética , Neoplasias de Células Germinales y Embrionarias/patología , Tumor Rabdoide/genética , Tumor Rabdoide/patología , Proteína EWS de Unión a ARN/genética , Proteína SMARCB1/genética , LactanteRESUMEN
Individuals diagnosed with cancer as adolescents and young adults (AYAs; ages 15-39 years) face unique vulnerabilities. Compared with individuals diagnosed when younger (≤14 years) or older (≥40 years), AYAs have not seen the same improvement in survival. Furthermore, they sit at a complex moment of social, emotional, and cognitive development, and have a unique interface with the healthcare system. With these observations, NCI prioritized addressing the unique vulnerabilities among AYAs with cancer, and NCCN developed guidelines regarding optimal AYA cancer care. Improvements in certain locales have been seen in the wake of this focus on AYAs, suggesting that continuing to consider AYA outcomes in the context of their specific needs is critical as we strive toward additional improvements. However, it is key to consider the drivers of these outcomes to continue this trajectory. This review presents a holistic conceptual model that includes factors that influence outcomes among AYAs with cancer, including domains in these levels that influence both clinical outcomes (such as relapse and survival) and health-related quality of life (HRQoL). These include domains at the patient level, such as social constructs (race/ethnicity, socioeconomic status), behavior (adherence, risk-taking), biologic characteristics (cancer biology, host genetics), medical treatment (treatment regimen, risk-based survivorship care), and treatment-related toxicities. The model also includes domains at the system level, which include treatment location (NCI designation, facility model, AYA program presence), clinical trial enrollment, transdisciplinary communication, fertility preservation, and psychosocial support. Recognizing these multiple factors at the level of the individual and the healthcare system influence AYA outcomes (from HRQoL to survival), it is key not only to consider patient-level interventions and development of novel cancer agents but also to develop systems-level interventions that can be executed in parallel. In this way, the impact can be expanded to a vast number of AYAs.