Is dose de-escalation possible in sarcoma patients treated with enlarged limb sparing resection?

Purpose: To evaluate the impact of dose de-escalation in a large series of resected limbs soft tissue sarcomas (STS). Methods: Data were retrospectively analysed from 414 consecutive patients treated for limb STS by enlarged surgery and radiotherapy at Gustave Roussy from 05/1993 to 05/2012. Radiotherapy (RT) dose level was decided by the multidisciplinary staff and depended upon the quality of surgery and margins size. Results: RT was delivered prior (13%) or after (87%) surgery. Seven patients (2%) had pre- and a postoperative RT boost. Median delivered RT dose was 50 Gy (36–70 Gy), and 33% received ≥55 Gy. At a median follow-up of 6.8 years, the 5-year actuarial local relapse (LR) rate was 7% (95% CI: 4.4–10%). The median time to the first LR was 2.7 years (range: 0.6–11.2 years). The LR was most often located within the irradiated field (26/32; 81%), where the median total applied dose was 56 Gy (range, 40–60 Gy). The 5-year LR rates were 4%, and 15% in patients receiving <55 Gy, and in those who had ≥55 Gy (p < 0.001), respectively. In the multivariate analysis, dose ≥55 Gy (HR [hazard ratio]: 2.9; p = 0.02), certain histological subtypes (HR: 7.8; p < 0.001), and minimal surgical margins <1 mm (HR: 2.9; p = 0.02) were associated to higher LR rates. In the subgroup of patients with “positive” margins <1 mm (n = 102), these histological subtypes (HR: 4.4; p = 0.03), and inadequate initial surgery justifying re-excision (HR: 3; p = 0.048) predicted for an increased LR, whereas dose of irradiation did not (p = 0.2). Patients who had late complications (n = 64; 15%) received higher doses of irradiation as compared with other patients (median: 55 Gy vs. 50 Gy, respectively; p < 0.001). Conclusion: In this retrospective analysis of patients having enlarged surgery and RT, histological subtype is the strongest predictor of LR, whereas dose de-escalation did not lead to worse outcomes. A dose of 50 Gy may be recommended in case of planned enlarged surgery with R0 margins.