High dose (54 Gy) Pre-operative Tomotherapy for Retroperitoneal Liposarcoma: Results of a Phase 2 Multicenter Study

Abstract

To evaluate efficacy and feasibility of intensity-modulated radiotherapy (IMRT) with tomotherapy followed by surgery, especially concerning the high-level of radiotherapy (RT) prescribed dose (54 Gy/30 fractions/6 weeks). Helical tomotherapy was used for pre-operative RT. Inclusion criteria were operable, biopsy-proven, retroperitoneal liposarcomas. Clinical Target Volume (CTV) and mains organs at risk (contralateral kidney, bowel bag) were systematically discussed with the surgeon. Prescribed dose was 54 Gy at the median of PTV) Main dosimetric constraints concerned contralateral kidney (Dmax ≤ 12 Gy mean dose ≤ 8 Gy) and bowel bag (V45 Gy ≤ 33% and V30 Gy ≤ 50%). Surgery was planned 4 to 8 weeks after RT. Toxicity was graded according to CTCAE V3.0. Overall survival (OS) was estimated using Kaplan-Meier method. Due to competing risks, we estimated the cumulative incidence of loco-regional relapse; 95% confidence intervals are reported [95% CI]. From 04/2009 to 09/2013, 48 patients were included. Mean age: 62 years (y) (36 to 82). All but 1 patient were OMS ≤ 2. Histological types were 20 well differentiated (WDLS) and 28 dedifferentiated liposarcomas. Mean CTV was 2954 cc (920-4989). Treatment: All patients but1completed the radiosurgical schedule. Monobloc exerese was always achieved. Surgical margins were R0 (16; 34%), R1 (28; 60%), R2 (2; 4%) or missing (1; 2%). Twenty-nine patients underwent bowel resection, including large bowel (28/29), small bowel (4/29) and duodenum (1/29). Oncological outcomes: Median follow-up was 4.7years. Cumulative incidence of loco-regional relapse at3 and 5 years was 17% [8%; 29%] and 31% [16%; 47%], respectively. Estimates were 5% and 35% for dedifferentiated liposarcoma and 26% and 26% for well differentiated liposarcoma. OS at 3 and 5 years was 81% [66%; 89%]) and 78% ([63%; 88%] respectively. Toxicity within the first 6 months was higher than expected: mean weight loss during RT was 5.4 kg (about 8% of mean body weight) and 8.9 kg at the first visit after surgery. At 2 months, grade 3 toxicities included duodenal stenosis (1/46), intestinal fistula (1/46) and enterocolitis (1/46) and grade 4 toxicity included GI fistula (1/46). At 6 months and 1 year, no further severe toxicities were observed. Five cases of second cancers were reported: 1 myeloid leukemia, 2 pancreatic, and 2 breast carcinomas. This trial highlights the feasibility of preoperative 54 Gy RT. Although efficacy data (local control and OS) are encouraging, high incidence rates of acute toxicities and second cancers should be considered. Preoperative RT for WDLS remains questionable. Results from ongoing EORTC phase III Strass trial may provide further level of evidence for this approach.