TY - JOUR
T1 - Efficacy of high-dose chemotherapy and three-dimensional conformal radiation for atypical teratoid/rhabdoid tumor
T2 - A report from the Children’s Oncology Group trial ACNS0333
AU - Reddy, Alyssa T.
AU - Strother, Douglas R.
AU - Judkins, Alexander R.
AU - Burger, Peter C.
AU - Pollack, Ian F.
AU - Krailo, Mark D.
AU - Buxton, Allen B.
AU - Williams-Hughes, Chris
AU - Fouladi, Maryam
AU - Mahajan, Anita
AU - Merchant, Thomas E.
AU - Ho, Ben
AU - Mazewski, Claire M.
AU - Lewis, Victor A.
AU - Gajjar, Amar
AU - Vezina, Louis Gilbert
AU - Booth, Timothy N.
AU - Parsons, Kerry W.
AU - Poss, Vicky L.
AU - Zhou, Tianni
AU - Biegel, Jaclyn A.
AU - Huang, Annie
N1 - Funding Information:
Supported by the Children’s Oncology Group and the National Cancer Institute of the National Institutes of Health (NIH) under the National Clinical Trials Network (NCTN) Operations Center Grant No. U10CA180886, the NCTN Statistics & Data Center Grant No. U10CA180899, and the St Baldrick’s Foundation. Tumor biology studies were also supported by NIH Grant No. CA46274, Canadian Cancer Society Research Grant No. 705056, and the Children’s of Alabama Kaul Pediatric Research Institute. The content is solely the responsibility of the authors and does not necessarily represent the official views of the NIH.
Publisher Copyright:
Copyright © 2020 American Society of Clinical Oncology. All rights reserved.
PY - 2020/4/10
Y1 - 2020/4/10
N2 - PURPOSE Atypical teratoid/rhabdoid tumor (AT/RT) is an aggressive, early-childhood brain tumor without standard effective treatment. To our knowledge, we conducted the first AT/RT-specific cooperative group trial, ACNS0333, to examine the efficacy and safety of intensive postoperative chemotherapy and focal radiation to treat AT/RT. PATIENTS AND METHODS Patients from birth to 22 years of age with AT/RT were eligible. After surgery, they received 2 courses of multiagent chemotherapy, followed by 3 courses of high-dose chemotherapy with peripheral blood stem cell rescue and involved-field radiation therapy. Timing of radiation was based on patient age and disease location and extent. Central testing of tumor and blood for SMARCB1 status was mandated. Tumor molecular subclassification was performed retrospectively. The primary analysis was event-free survival (EFS) for patients, 36 months of age compared with a cooperative groups’ historical cohort. Although accrual was based on the therapeutic question, potential prognostic factors, including age, tumor location, M stage, surgical resection, order of therapy, germline status, and molecular subtype, were explored. RESULTS Of 65 evaluable patients, 54 were, 36 months of age. ACNS0333 therapy significantly reduced the risk of EFS events in patients, 36 months of age compared with the historical cohort (P, .0005; hazard rate, 0.43; 95% CI, 0.28 to 0.66). Four-year EFS and overall survival for the entire cohort were 37% (95% CI, 25% to 49%) and 43% (95% CI, 31% to 55%), respectively. Timing of radiation did not affect survival, and 91% of relapses occurred by 2 years from enrollment. Treatment-related deaths occurred in 4 patients. CONCLUSION The ACNS0333 regimen dramatically improved survival compared with historical therapies for patients with AT/RT. Clinical characteristics and molecular subgrouping suggest prognostic differences. ACNS0333 results lay a foundation on which to build future studies and incorporate testing of new therapeutic agents.
AB - PURPOSE Atypical teratoid/rhabdoid tumor (AT/RT) is an aggressive, early-childhood brain tumor without standard effective treatment. To our knowledge, we conducted the first AT/RT-specific cooperative group trial, ACNS0333, to examine the efficacy and safety of intensive postoperative chemotherapy and focal radiation to treat AT/RT. PATIENTS AND METHODS Patients from birth to 22 years of age with AT/RT were eligible. After surgery, they received 2 courses of multiagent chemotherapy, followed by 3 courses of high-dose chemotherapy with peripheral blood stem cell rescue and involved-field radiation therapy. Timing of radiation was based on patient age and disease location and extent. Central testing of tumor and blood for SMARCB1 status was mandated. Tumor molecular subclassification was performed retrospectively. The primary analysis was event-free survival (EFS) for patients, 36 months of age compared with a cooperative groups’ historical cohort. Although accrual was based on the therapeutic question, potential prognostic factors, including age, tumor location, M stage, surgical resection, order of therapy, germline status, and molecular subtype, were explored. RESULTS Of 65 evaluable patients, 54 were, 36 months of age. ACNS0333 therapy significantly reduced the risk of EFS events in patients, 36 months of age compared with the historical cohort (P, .0005; hazard rate, 0.43; 95% CI, 0.28 to 0.66). Four-year EFS and overall survival for the entire cohort were 37% (95% CI, 25% to 49%) and 43% (95% CI, 31% to 55%), respectively. Timing of radiation did not affect survival, and 91% of relapses occurred by 2 years from enrollment. Treatment-related deaths occurred in 4 patients. CONCLUSION The ACNS0333 regimen dramatically improved survival compared with historical therapies for patients with AT/RT. Clinical characteristics and molecular subgrouping suggest prognostic differences. ACNS0333 results lay a foundation on which to build future studies and incorporate testing of new therapeutic agents.
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U2 - 10.1200/JCO.19.01776
DO - 10.1200/JCO.19.01776
M3 - Article
C2 - 32105509
AN - SCOPUS:85083003110
SN - 0732-183X
VL - 38
SP - 1175
EP - 1185
JO - Journal of Clinical Oncology
JF - Journal of Clinical Oncology
IS - 11
ER -