Relevance of Molecular Groups in Children with Newly Diagnosed Atypical Teratoid Rhabdoid Tumor: Results from Prospective St. Jude Multi-Institutional Trials. Clinical cancer research : an official journal of the American Association for Cancer Research Upadhyaya, S. A., Robinson, G., Onar-Thomas, A., Orr, B. A., Johann, P., Wu, G., Billups, C. A., Tatevossian, R. G., Dhanda, S. K., Srinivasan, A., Broniscer, A., Qaddoumi, I., Vinitsky, A., Armstrong, G. T., Bendel, A., Hassall, T. E., Partap, S., Fisher, P. G., Crawford, J. R., Chintagumpala, M. M., Bouffet, E., Gururangan, S., Mostafavi, R., Sanders, R. P., Klimo, P., Patay, Z., Indelicato, D. J., Nichols, K. E., Boop, F. A., Merchant, T. E., Kool, M., Ellison, D. W., Gajjar, A. 2021


PURPOSE: Report relevance of molecular groups to clinico-pathologic features, germline SMARCB1/SMARCA4 alterations (GLA), and survival of children with atypical teratoid rhabdoid tumor (ATRT) treated in two multi-institutional clinical trials.PATIENTS 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 radiation therapy [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 non-metastatic (M0) disease. Children with M0 disease and <1.5 cm2 residual tumor had a 5-year progression-free survival (PFS) of 72.7{plus minus}12.7% and OS of 81.8{plus minus}11%. Infants with M0 disease had a 5-year PFS of 39.1{plus minus}11.5% and OS of 51.8{plus minus}12%. Those with metastases fared poorly [5-year OS 25{plus minus}12.5% (children) and 0% (infants)]. SMARCB1 GLAs were not associated with PFS.CONCLUSION: Among infants, those with ATRT-TYR had the best OS. ATRT-SHH was associated with metastases and consequently with inferior outcomes. Children with non-metastatic ATRT benefit from post-operative CSI and adjuvant chemotherapy.

View details for DOI 10.1158/1078-0432.CCR-20-4731

View details for PubMedID 33737307