Relevance of Molecular Groups in Children with Newly Diagnosed Atypical Teratoid Rhabdoid Tumor: Results from...

Area of Science:

• Pediatric Oncology
• Molecular Pathology
• Neuro-oncology

Background:

• Atypical teratoid rhabdoid tumor (ATRT) is a rare and aggressive pediatric brain tumor.
• Understanding the molecular heterogeneity of ATRT is crucial for improving treatment strategies and patient outcomes.
• Previous studies have identified distinct molecular subgroups, but their clinical relevance requires further investigation.

Purpose of the Study:

• To investigate the association between molecular subgroups of ATRT and clinicopathologic features.
• To determine the relevance of germline SMARCB1/SMARCA4 alterations (GLA) in ATRT.
• To evaluate the impact of molecular groups on the survival of children with ATRT treated in multi-institutional clinical trials.

Main Methods:

• Seventy-four newly diagnosed ATRT patients were enrolled in two clinical trials (SJYC07 for infants, SJMB03 for children).
• Tumor DNA methylation profiling was used to classify ATRTs into molecular groups: ATRT-MYC (MYC), ATRT-SHH (SHH), and ATRT-TYR (TYR).
• Treatment included surgery, chemotherapy, and age/risk-adapted radiotherapy (focal or craniospinal irradiation).

Main Results:

• Methylation profiling classified 64 ATRTs into TYR (n=21), SHH (n=30), and MYC (n=13).
• The ATRT-SHH group was significantly associated with metastatic disease and inferior outcomes.
• Among infants, the ATRT-TYR group demonstrated the best overall survival (OS), while outcomes did not differ for nonmetastatic infants.
• Children with nonmetastatic ATRT and minimal residual tumor (<1.5 cm²) had a 5-year PFS of 72.7% and OS of 81.8%.

Conclusions:

• ATRT-TYR subgroup is associated with favorable outcomes in infants.
• ATRT-SHH subgroup is linked to metastasis and poorer survival in pediatric patients.
• Nonmetastatic ATRT in children benefits from postoperative craniospinal irradiation and adjuvant chemotherapy.