Written by | Wei Jiabin is responsible for editing | Zhou Yebin
The classification of rare embryonic tumors of the central nervous system (CNS) has been a conundrum and has been modified in the past few years. Due to the limited specificity of diagnostic criteria and the high rate of misdiagnosis, "central nervous system-primitive neuroectodermal tumors" (CNS-PNET) were removed from the WHO classification of CNS tumors (revised 2016).
In previous cohort studies of CNS-PNET, by re-evaluation by DNA methylation analysis, many tumors can be classified into specific types of tumors according to epigenetics, known embryonic tumors with multiple layers of garlands (ETMR), high-grade gliomas (HGG), etc. Based on specific DNA methylation characteristics and genetic alterations, the researchers found 4 specific types of CNS-PNET, one of which is morphologically similar to central neuroblastoma and contains chromosomal rearks, resulting in increased expression of the FOXR2 gene, according to which it was named CNS NB-FOXR2.
In September 2021, a joint publication by Katja von Hoff and several other pediatric oncology research centers titled Theraeutic implications of improved molecular diagnostics for rare CNS embryonal tumor entities: results of an international, The retrospective study article, which analyzed tumor samples diagnosed as CNS-PNET through DNA methylation arrays, found that the prognosis of CNS-PNET patients can be further differentiated by new molecular typing, revealing the importance of molecular differential diagnosis of rare central nervous system embryonic tumors.
From the 307 samples collected, the researchers screened 108 CNS NB-FOXR2 samples and 58 ETMR samples for study. Overall survival of patients with CNS NB-FOXR2 after combination of cranial cord irradiation (CSI) and chemotherapy (CT) was increased, but the risk of recurrence and disease-related death was increased.
Copy number profile, sex ratio, age distribution of first diagnosis, tumor location, treatment, and outcome of CNS NB-FOXR2
Most ETMR patients are highly aggressive and tolerant to treatment, while prolonged survival has been observed in some ETMR patients. According to the analysis carried out here, no molecular features associated with favorable results were detected.
Copy number profile, sex ratio, age distribution of first diagnosis, tumor location, treatment, and outcome
In the CNS-PNET reassessment cohort, the overall 5-year progression-free survival (PFS) and overall survival (OS) were 40% ±3%, and 51% ±3%, respectively. Survival rates for patients with different molecular information diagnoses vary significantly.
Patients with CNS NB-FOXR2 had the highest survival rates (69% ±9% and 86% ±7% for 5-year PFS and OS, respectively) (see Figures C, D below). Similar survival rates were observed in the expanded cohort of patients with CNS NB-FOXR2 (5 year PFS and OS: 57% ± 10%; 85% ±5%). Combining the two CNS NB-FOXR2 queues, 5-year PFS and OS were 63% ± 7% and 85% ±5%, respectively. In this cohort, no statistically significant difference in survival rates was observed based on initial staging.
In the CNS-PNET reassessment cohort, ETMR patients (5-year PFS and OS: 18% ±6%; 24% ±6%), and HDG patients (5-year PFS and OS: 22% ±7%; 25% ±7%)had the lowest survival rates. 5-year PFS and OS in ETMR patients with metastases (no residual tumors after surgery) were 25% ± 10% and 34% ± 11%, respectively, 20 completely resected non-metastatic patients were 34% ± 11%, and PFS and OS were 8% ±7% in 13 patients with metastases.
Outcome of survival rates in patients under different molecular typings
In summary, this retrospective study is a comprehensive analysis of clinical behavior and treatment-related outcomes in patients with rare central nervous system embryonic tumors, and a pooled and structured analysis of clinical data based on the classification of DNA methylation. In addition to high-grade gliomas, ETMR was also the first to be listed as the cause of a poor prognosis for "CNS-PNET," according to the research data. Compared with ETMR, the 5-year overall survival rate of CNS NB-FOXR2 patients was significantly better, up to 85%. The data suggest that the use of cranial pulp irradiation is likely to be an important prerequisite for good survival in patients with CNS NB-FOXR2. Patients with ETMR are younger in age of onset and most patients experience refractory progression regardless of treatment modalities.
The data from this study demonstrate the importance of developing molecular diagnostic differentiation and entity-specific prospective trials for CNS NB-FOXR2 and ETMR, providing new ideas for the clinical treatment of rare CNS embryonic tumors.
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