Late radiation morbidity following randomization to preoperative versus postoperative radiotherapy in extremity soft tissue sarcoma

Background and Purpose: This study compared late radiation morbidity in patients with extremity soft tissue sarcoma randomized to treatment by pre- (50 Gy) or postoperative (66 Gy) radiotherapy in combination with surgery. The morbidities evaluated included fibrosis, joint stiffness and edema at 2 years following treatment. The impact of morbidity on patient function as measured by the Musculoskeletal Tumor Rating Scale (MSTS) and the Toronto Extremity Salvage Score (TESS) was also evaluated. Patients and methods: 129 patients were evaluated. Toxicity rates were compared by treatment arm using the Fisher's exact test. Function scores by toxicity were analyzed using the Wilcoxon rank sum test. Multivariate logistic regression was used to evaluate the joint effect of treatment arm, field size, and dose on subcutaneous tissue fibrosis, joint stiffness and edema. Results: 27 of 56 patients (48.2%) in the postoperative arm compared to 23 of 73 (31.5%) in the preoperative arm had grade 2 or greater fibrosis (P=0.07). Although not statistically significant, edema was more frequent in the postoperative arm, 13 of 56 (23.2%) versus 11 of 73 (15.1%) in the preoperative arm, as was joint stiffness, 13 of 56 (23.2%) versus 13 of 73 (17.8%). Patients with significant fibrosis, joint stiffness or edema had significantly lower function scores on both measures (all P-values <0.01). Field size was predictive of greater rates of fibrosis (P=0.002) and joint stiffness (P=0.006) and marginally predictive of edema (P=0.06). Conclusions: Patients treated with postoperative radiotherapy tended to have greater fibrosis. Fibrosis, joint stiffness and edema adversely affect patient function