Influence of site on the therapeutic ratio of adjuvant radiotherapy in soft-tissue sarcoma of the extremity

Purpose: The ultimate goal of adjuvant radiotherapy (RT) in soft-tissue sarcoma of the extremity is to improve the therapeutic ratio by increasing local control while minimizing morbidity. Most efforts in trying to improve this ratio have focused on the sequencing of RT and surgery, with little attention to the potential influence of the tumor site. The purpose of this study was to determine the influence of tumor site on local control and complications in a group of patients with primary high-grade soft-tissue sarcoma of the extremity treated at a single institution with postoperative RT. Methods and Materials: Between July 1982 and December 2000, 369 adult patients with primary high-grade soft-tissue sarcoma of the extremity were treated with limb-sparing surgery and postoperative RT. Patients who underwent surgery or RT outside our institution were excluded. The tumor site was the upper extremity (UE) in 103 (28%) and the lower extremity (LE) in 266 (72%). The tumor was ≤5 cm in 98 patients (27%), and the microscopic margins were positive in 44 (12%). Of the 369 patients, 104 (28%) underwent postoperative external beam RT (EBRT), 233 (63%) postoperative brachytherapy (BRT), and 32 underwent a combination (9%); 325 (88%) received a “conventional” radiation dose, defined as 60–70 Gy for EBRT, 45 Gy for BRT, and 45–50 Gy plus 15–20 Gy for EBRT plus BRT. Complications were assessed in terms of wound complications requiring repeat surgery, fracture, joint stiffness, edema, and Grade 3 or worse peripheral nerve damage. Results: The UE and LE groups were balanced with regard to age, depth, margin status, and type of RT (EBRT vs. BRT ± EBRT). However, more patients in the UE group had tumors ≤5 cm and more received a conventional radiation dose ( p = 0.01 and P = 0.03, respectively). With a median follow-up of 50 months, the 5-year actuarial rate of local control, distant relapse-free survival, and overall survival for the whole population was 82% (95% confidence interval [CI], 77–86%), 61% (95% CI, 56–66%), and 71% (95% CI, 66–76%), respectively. The 5-year local control rate in patients with UE STS was 70% (95% CI, 60–80%) compared with 86% (95% CI, 81–91%) for LE STS ( p = 0.0004). On multivariate analysis, an UE site ( p = 0.001; relative risk [RR], 3; 95% CI, 2–5) and positive resection margins ( p = 0.02; RR, 2; 95% CI, 1–4) were significant predictors of poor local control. The RT type or radiation dose, age, tumor depth, and size were not significant predictors of local control. The 5-year wound reoperation rate was 1% (95% CI, 0–3) in the UE compared with 11% (95% CI, 7–15) in the LE ( p = 0.002). On multivariate analysis, the UE site retained its significance as a predictor of low wound complications ( p = 0.001; RR, 0.08; 95% CI, 0.01–0.7). The site did not significantly influence the incidence of fracture ( p = 0.7), joint stiffness ( p = 0.2), edema ( p = 0.5), or Grade 3 or worse peripheral nerve damage ( p = 0.3). Conclusion: The UE site is associated with a greater rate of local recurrence compared with the LE. This difference was independent of other variables and could not be accounted for by an imbalance between the two groups. With a lower wound complication rate associated with an UE site, it would be of interest to determine whether preoperative RT and/or intensity-modulated RT can increase the local control in UE sarcomas, thus improving the therapeutic ratio.