Local Control For High-Grade Nonrhabdomyosarcoma Soft Tissue Sarcoma Assigned to Radiation Therapy on ARST0332: A Report From the Childrens Oncology Group

Lynn Million, Andrea Hayes-Jordan, Yueh Yun Chi, Sarah S. Donaldson, Suzanne Wolden, Carol Morris, Stephanie Terezakis, Fran Laurie, Karen Morano, T. J. Fitzgerald, Torunn I. Yock, David A. Rodeberg, James R. Anderson, Rose Anne Speights, Jennifer O. Black, Cheryl Coffin, Mary Beth McCarville, Simon C. Kao, Douglas S. Hawkins, Sheri L. SpuntR. Lor Randall

Research output: Contribution to journalArticlepeer-review

Abstract

Purpose: The ARST0332 trial for pediatric and young adults with nonrhabdomyosarcoma soft tissue sarcoma (NRSTS) used risk-based treatment including primary resection with lower-than-standard radiation doses to optimize local control (LC) while minimizing long-term toxicity in those requiring radiation therapy (RT). RT for high-grade NRSTS was based on extent of resection (R0: negative margins, R1: microscopic margins, R2/U: gross disease/unresectable); those with >5 cm tumors received chemotherapy (CT; ifosfamide/doxorubicin). This analysis evaluates LC for patients assigned to RT and prognostic factors associated with local recurrence (LR). Methods and Materials: Patients aged <30 years with high-grade NRSTS received RT (55.8 Gy) for R1 ≤5 cm tumor (arm B); RT (55.8 Gy)/CT for R0/R1 >5 cm tumor (arm C); or neoadjuvant RT (45 Gy)/CT plus delayed surgery, CT, and postoperative boost to 10.8 Gy R0 <5 mm margins/R1 or 19.8 Gy for R2/unresected tumors (arm D). Results: One hundred ninety-three eligible patients had 24 LRs (arm B 1/15 [6.7%], arm C 7/65 [10.8%], arm D 16/113 [14.2%]) at median time to LR of 1.1 years (range, 0.11-5.27). Of 95 eligible for delayed surgery after neoadjuvant therapy, 89 (93.7%) achieved R0/R1 margins. Overall LC after RT were as follows: R0, 106 of 109 (97%); R1, 51 of 60 (85%); and R2/unresectable, 2 of 6 (33%). LR predictors include extent of delayed resection (P <.001), imaging response before delayed surgery (P <.001), histologic subtype (P <.001), and no RT (P =.046). The 5-year event-free survival was significantly lower (P =.0003) for patients unable to undergo R0/R1 resection. Conclusions: Risk-based treatment for young patients with high-grade NRSTS treated on ARST0332 produced very high LC, particularly after R0 resection (97%), despite lower-than-standard RT doses. Neoadjuvant CT/RT enabled delayed R0/R1 resection in most patients and is preferred over adjuvant therapy due to the lower RT dose delivered.

Original languageEnglish (US)
Pages (from-to)821-830
Number of pages10
JournalInternational Journal of Radiation Oncology Biology Physics
Volume110
Issue number3
DOIs
StateAccepted/In press - 2021

Bibliographical note

Funding Information:
This research was supported in part by grants from the National Institutes of Health to the Children’s Oncology Group ( U10CA180886 , U10CA180899 , U10CA098543 , U10CA098413 ), the Quality Assurance Review Center ( U10CA29511 ), the Imaging and Radiation Oncology Core ( U10CA180803 ), and St. Jude Children's Research Hospital ( P30CA21765 and CA23099 ), and by funding from the St. Baldrick’s Foundation, the Seattle Children’s Foundation (from Kat’s Crew Guild through the Sarcoma Research Fund), and the American Lebanese Syrian Associated Charities.

Funding Information:
Disclosures: S.T. received grants from ASELL and Elekta Industries outside the submitted work. F.L. received grants from the National Cancer Institute during the conduct of the study. T.I.Y. received nonfinancial support from MIM Corporation outside the submitted work. J.R.A. received grants from CTEP/ National Cancer Institute, during the conduct of the study; and other from Merck and Co, outside the submitted work. D.S.H. received clinical trial fees paid to Seattle Children’s to offset costs of study conduct; was reimbursed for or provided travel, housing, and food to attend medial advisory board meetings for Loxo Oncology, Bayer, Bristol Myers Squibb, Lilly, and Celgene; and had clinical trial fees paid to Seattle Children’s to offset costs of study conduct from Merck Sharpe Dohme, Eisai, Novartis, Glaxo Smith Kline, Sanofi, Amgen, Jazz Pharmaceuticals, Seattle Genetics, and Incyte. S.L.S. received grants from the National Cancer Institute/Children's Oncology Group, during the conduct of the study; received grants from F. Hoffman-LaRoche Ltd, Novartis, Alex's Lemonade Stand Foundation, Cookies for Kids' Cancer, Bayer Healthcare Phramaceuticals, Inc, Sanofi US Services, Inc, Loxo Oncology, Incyte Corporation, Bristol Myers Squibb, St. Baldrick's Foundation, Pfizer, Inc, and the University of California, Santa Cruz, outside the submitted work.

Funding Information:
This research was supported in part by grants from the National Institutes of Health to the Children's Oncology Group (U10CA180886, U10CA180899, U10CA098543, U10CA098413), the Quality Assurance Review Center (U10CA29511), the Imaging and Radiation Oncology Core (U10CA180803), and St. Jude Children's Research Hospital (P30CA21765 and CA23099), and by funding from the St. Baldrick's Foundation, the Seattle Children's Foundation (from Kat's Crew Guild through the Sarcoma Research Fund), and the American Lebanese Syrian Associated Charities.

Publisher Copyright:
© 2021 Elsevier Inc.

Fingerprint Dive into the research topics of 'Local Control For High-Grade Nonrhabdomyosarcoma Soft Tissue Sarcoma Assigned to Radiation Therapy on ARST0332: A Report From the Childrens Oncology Group'. Together they form a unique fingerprint.

Cite this