Relevance of Molecular Groups in Children with Newly Diagnosed Atypical Teratoid Rhabdoid Tumor: Results from Prospective St. Jude Multi-institutional Trials

Clin Cancer Res. 2021 May 15;27(10):2879-2889. doi: 10.1158/1078-0432.CCR-20-4731. Epub 2021 Mar 18.


Purpose: Report relevance of molecular groups to clinicopathologic features, germline SMARCB1/SMARCA4 alterations (GLA), and survival of children with atypical teratoid rhabdoid tumor (ATRT) treated in two multi-institutional clinical trials.

Materials and methods: Seventy-four participants with newly diagnosed ATRT were treated in two trials: infants (SJYC07: age < 3 years; n = 52) and children (SJMB03: age 3-21 years; n = 22), using surgery, conventional chemotherapy (infants), or dose-dense chemotherapy with autologous stem cell rescue (children), and age- and risk-adapted radiotherapy [focal (infants) and craniospinal (CSI; children)]. Molecular groups ATRT-MYC (MYC), ATRT-SHH (SHH), and ATRT-TYR (TYR) were determined from tumor DNA methylation profiles.

Results: Twenty-four participants (32%) were alive at time of analysis at a median follow-up of 8.4 years (range, 3.1-14.1 years). Methylation profiling classified 64 ATRTs as TYR (n = 21), SHH (n = 30), and MYC (n = 13), SHH group being associated with metastatic disease. Among infants, TYR group had the best overall survival (OS; P = 0.02). However, outcomes did not differ by molecular groups among infants with nonmetastatic (M0) disease. Children with M0 disease and <1.5 cm2 residual tumor had a 5-year progression-free survival (PFS) of 72.7 ± 12.7% and OS of 81.8 ± 11%. Infants with M0 disease had a 5-year PFS of 39.1 ± 11.5% and OS of 51.8 ± 12%. Those with metastases fared poorly [5-year OS 25 ± 12.5% (children) and 0% (infants)]. SMARCB1 GLAs were not associated with PFS.

Conclusions: Among infants, those with ATRT-TYR had the best OS. ATRT-SHH was associated with metastases and consequently with inferior outcomes. Children with nonmetastatic ATRT benefit from postoperative CSI and adjuvant chemotherapy.

Publication types

  • Clinical Trial, Phase II
  • Multicenter Study
  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Antineoplastic Combined Chemotherapy Protocols / adverse effects
  • Antineoplastic Combined Chemotherapy Protocols / therapeutic use
  • Biomarkers, Tumor*
  • Child
  • Child, Preschool
  • DNA Copy Number Variations
  • DNA Methylation
  • Diagnosis, Differential
  • Disease Management
  • Disease Susceptibility
  • Female
  • Germ-Line Mutation
  • Humans
  • Infant
  • Male
  • Mutation
  • Prognosis
  • Rhabdoid Tumor / diagnosis*
  • Rhabdoid Tumor / etiology*
  • Rhabdoid Tumor / mortality
  • Rhabdoid Tumor / therapy
  • SMARCB1 Protein / genetics
  • Teratoma / diagnosis*
  • Teratoma / etiology*
  • Teratoma / mortality
  • Teratoma / therapy
  • Treatment Outcome


  • Biomarkers, Tumor
  • SMARCB1 Protein
  • SMARCB1 protein, human

Supplementary concepts

  • Typical Teratoid Rhabdoid Tumor