Writing | Wei Jiabin Editor | Zhou Yebin
Classification of rare embryonal tumors of the central nervous system (CNS) has been a difficult problem and has been revised over the past few years. “Central nervous system-primitive neuroectodermal tumor” (CNS-PNET) was removed from the classification of CNS tumors (2016 revision) by WHO due to the limited specificity of the diagnostic criteria and the high rate of misdiagnosis.
In a previous cohort study of CNS-PNET, reassessed by DNA methylation analysis, many tumors can be epigenetically classified into specific tumor classes, many of which are known Layer rosette’s embryonal tumor (ETMR), high-grade glioma (HGG), etc. Based on specific DNA methylation signatures and genetic alterations, the researchers identified four additional specific types of CNS-PNETs, one of which was morphologically similar to central neuroblastoma and contained chromosomal rearrangements that led to FOXR2 gene expression increased, and named it CNS NB-FOXR2 accordingly.
September 2021, co-published in Neuro-Oncology titled Neuro-Oncology by Katja von Hoff and other children’s cancer research centers strong>Therapeutic implications of improved molecular diagnostics for rare CNS embryonal tumor entities: results of an international, retrospective studyThe article, Analysis of tumor samples diagnosed as CNS-PNET by DNA methylation arrays, It was found that the prognosis of CNS-PNET patients could be further differentiated by novel molecular typing, revealing the importance of molecular diagnostic identification of rare CNS embryonal tumors.
From the 307 samples collected, the researchers screened 108 CNS NB-FOXR2 samples and 58 ETMR samples for study. Among them, CNS NB-FOXR2 patients have improved overall survival after combined cranial irradiation (CSI) and chemotherapy (CT), but have an increased risk of recurrence and disease-related death.
CNS NB-FOXR2 copy number profile, sex ratio, age distribution at first diagnosis, tumor location, treatment and outcome
The majority of ETMR patients are highly aggressive and resistant to treatment, while prolonged survival has also been observed in some ETMR patients. Based on the analysis performed here, no molecular signatures associated with favorable outcomes were detected.
Copy number profile, sex ratio, age distribution at 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) rates were 40%±3% and 51%±3%, respectively . Patients with different molecularly informative diagnoses had significantly different survival rates.
CNS NB-FOXR2 patients had the highest survival rates (5-year PFS and OS were 69% ± 9% and 86% ± 7%, respectively) (see Figures C, D). Similar survival was observed in the expansion cohort of CNS NB-FOXR2 patients (5-year PFS and OS: 57% ± 10%; 85% ± 5%). Combining the two CNS NB-FOXR2 cohorts, 5-year PFS and OS were 63% ± 7% and 85% ± 5%, respectively. In this cohort, no statistically significant differences in survival according to initial stage were observed.
In the CNS-PNET reassessment cohort, patients with ETMR (5-year PFS and OS: 18% ± 6%; 24% ± 6%) and HGG patients (5-year PFS and OS: 22%±7%; 25%±7%) had the lowest survival rate. 5-year PFS and OS were 25% ± 10% and 34% ± 11%, respectively, in ETMR patients with metastases (no residual tumor after surgery) and 34% ± 11% in 20 completely resected non-metastatic patients , while the PFS and OS of the 13 patients with metastases were both 8% ± 7%.
Survival results of patients with different molecular types
In summary, this retrospective study of a rare CNSComprehensive analysis of clinical behavior and treatment-related outcomes in patients with embryonal tumors, and pooled and structured analysis of clinical data based on DNA methylation classification. The study data showed that, in addition to high-grade gliomas, ETMR was also listed as the cause of poor prognosis of “CNS-PNET” for the first time. 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 spinal irradiation is likely to be an important prerequisite for good survival in CNS NB-FOXR2 patients. Patients with ETMR were younger at onset, and the majority of patients had treatment-refractory progression regardless of treatment modality.
Data from this study demonstrate the importance of developing molecular diagnostic differentiation and entity-specific prospective trials of CNS NB-FOXR2 and ETMR for the clinical treatment of rare CNS embryonal tumors Offer new ideas.
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