Preoperative Intensity-Modulated Radiation Therapy Compared to Three-Dimensional Conformal Radiation Therapy for High Grade Extremity Sarcomas in Children: An Analysis of Children's Oncology Group (COG) Study ARST 0332

Abstract

One of the potential disadvantages of neoadjuvant chemoradiation therapy for high grade extremity soft tissue sarcomas (STS) is an increased risk of peri-operative wound complications. In adults, studies have demonstrated reduced radiation dose to the skin and subcutaneous soft tissues may decrease the acute wound complication rate and lead to better limb function. Intensity modulated radiotherapy (IMRT) allows delivery of dose to the target volume with the potential advantage of highly conformal therapy to reduce dose to subcutaneous tissues thus limiting dose to the skin. The purpose of this study was to assess tumor coverage and skin dose in pediatric patients treated with IMRT vs. 3D conformal radiation therapy (3D-CRT) on ARST 0332. Of the 551 eligible patients, 200 were enrolled in Arm D of ARST 0332 in which patients <30 years of age were treated with neoadjuvant ifosfamide/doxorubicin chemotherapy and 45 Gy RT, then surgery, and an RT boost based on margins. A total of 121 RT plans of patients were available for review through remote access of the Imaging and Radiation Oncology Core (IROC) Rhode Island database. Of these, 56 RT plans for patients with extremity STS were reviewed to evaluate the dose delivered to the clinical target volume (CTV) and skin (contoured from the surface to a depth of 5 mm). Of the 56 pediatric patients with extremity STS with RT plans available for review, 38 (65%) were treated with 3D-CRT and 18 (32%) with IMRT. There was no difference in distribution of site treated with IMRT vs. 3D-CRT (upper leg: 53% vs. 50%; knee: 16% vs. 17%; lower leg: 11% vs. 17%; lower arm: 11% vs. 17%, IMRT vs. 3D-CRT, respectively) with the exception of 0% vs. 11% of patients treated with IMRT vs. 3D-CRT to the upper arm. There was no difference in CTV volume between groups of patients treated with IMRT (median 1027 cc, range 66-2867 cc) or 3D-CRT (median 647 cc, range 30-4854 cc) (P = 0.920); however, patients treated with IMRT had significantly improved CTV coverage with 100% of the prescription dose compared to those receiving 3D-CRT (median CTV coverage, 95% vs. 87% respectively, P = 0.011). In patients without skin bolus, the percentage of skin receiving 45 Gy or more was significantly lower in patients treated with IMRT compared to 3D-CRT (mean percentage, 3% vs. 8% respectively, P = 0.039). Pre-operative IMRT compared to 3D-CRT may result in improved RT target coverage with reduced dose to the skin. Future studies are important to assess if this lower skin dose translates to reduced wound complications and/or improved limb function.