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 Spunt; R Lor Randall

doi:10.1016/j.ijrobp.2021.01.051

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

Int J Radiat Oncol Biol Phys. 2021 Jul 1;110(3):821-830. doi: 10.1016/j.ijrobp.2021.01.051. Epub 2021 Feb 3.

Authors

Lynn Million¹, Andrea Hayes-Jordan², Yueh-Yun Chi³, Sarah S Donaldson⁴, Suzanne Wolden⁵, Carol Morris⁶, Stephanie Terezakis⁷, Fran Laurie⁸, Karen Morano⁸, T J Fitzgerald⁹, Torunn I Yock¹⁰, David A Rodeberg¹¹, James R Anderson¹², Rose Anne Speights¹³, Jennifer O Black¹⁴, Cheryl Coffin¹⁵, Mary Beth McCarville¹³, Simon C Kao¹⁶, Douglas S Hawkins¹⁷, Sheri L Spunt⁴, R Lor Randall¹⁸

Affiliations

¹ Department of Radiation Oncology (LM, SSD) and Department of Pediatrics (SS), Stanford University, Stanford, California. Electronic address: lmillion@stanford.edu.
² Department of Surgery, University of North Carolina, Chapel Hill, North Carolina.
³ Department of Biostatistics, University of Southern California, Los Angeles, California.
⁴ Department of Radiation Oncology (LM, SSD) and Department of Pediatrics (SS), Stanford University, Stanford, California.
⁵ Department of Radiation Oncology, Memorial Sloan Cancer Center, New York, New York.
⁶ Department of Orthopedic Surgery, Johns Hopkins University, Baltimore Maryland.
⁷ Department of Radiation Oncology, University of Minnesota, Minneapolis, Minnesota.
⁸ Imaging and Radiation Oncology Core (IROC), Lincoln, Rhode Island.
⁹ Department of Radiation Oncology, University of Massachusetts, Worcester, Massachusetts.
¹⁰ Department of Radiation Oncology, Massachusetts General Hospital, Boston Massachusetts.
¹¹ Department of Surgery, East Carolina University, Greenville, North Carolina.
¹² MERCK Research Laboratories, North Wales, Pennsylvania.
¹³ St. Jude Children's Research Hospital, Memphis, Tennessee.
¹⁴ Department of Pathology, Children's Hospital Colorado, Aurora, Colorado.
¹⁵ Department of Pathology, Vanderbilt University, Nashville, Tennessee.
¹⁶ Department of Radiology, University of Iowa, Iowa City, Iowa.
¹⁷ Department of Pediatrics, Seattle Children's Hospital, Seattle, Washington.
¹⁸ Department of Orthopedics, University of California Davis, Sacramento, California.

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.

Trial registration: ClinicalTrials.gov NCT00346164.

Publication types

Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't

MeSH terms

Adolescent
Child
Child, Preschool
Female
Humans
Male
Neoplasm Grading
Research Design*
Soft Tissue Neoplasms / pathology*
Soft Tissue Neoplasms / radiotherapy*
Young Adult

Associated data

ClinicalTrials.gov/NCT00346164

Abstract

Publication types

MeSH terms

Associated data

Grants and funding