Atypical aggressiveness.

Top Line: What is the standard approach to treating atypical teratoid/rhabdoid tumors (ATRT)..?

The Study: Remember, ATRTs are primary CNS tumors that occur in young children. They are rare (even in the pediatric tumor world) and highly aggressive with poor outcomes with no clear consensus on effective treatment. ACNS0333 is the first cooperative group trial to establish a standard approach for ATRT, and it includes pretty much everything but the kitchen sink. 65 patients underwent resection followed by induction chemo of 2 cycles of vincristine, methotrexate, etoposide, cyclophosphamide, and cisplatin +/- second look surgery, then high-dose chemo of 3 cycles of carboplatin and thiotepa with stem cell rescue. Patients 6 months or older with infratentorial tumors and 12 months or older with supratentorial tumors received involved-field radiation after induction chemo and before consolidation. Even younger(!) patients received delayed radiation given at the end. The dose was 50.4 Gy for kids < 3 years and 54 Gy for all others. At 4-years, event-free survival was 37%—significantly better than historical controls—and OS was 43%. ACNS0333 specifically demonstrates the importance of methotrexate, radiation therapy, and high-dose chemo. Of note, protocol amendments were necessary to reduce treatment toxicity as treatment-related deaths (6%) were slightly higher than anticipated (4%). 

TBL: ACNS0333 establishes the standard treatment regimen for ATRT on which to build future regimens with less toxicity, targeted pathways, and improved survival outcomes. | Reddy, J Clin Oncol 2020