Abstract 1528P
Background
To examine whether concomitant chemotherapy (CXT) and radiation (RXT) achieves sufficient DFS rates.
Methods
We included only pts with histopathologically confirmed (size > 5cm, G2/3, deep located) STS, at least 18 yrs of age, normal BM, renal, heart, liver function, no evidence of distant mets at 40 german and austrian centers. They were assigned to either (arm 1) adjuvant or (arm 3) neoadjuvant IFO-DOXO x 3 - IFO x 2 + RXT 50.4 Gy* – IFO-DOXO x 1 (*if indicated/applicable, otherwise IFO-DOXO x 5) consisted of DOX 60 mg/sqm i.v., on day 1, and IFO 3 g/sqm i.v., d1-3, qd22 (d1-2, qd22 concomitant to RXT). Protocol amendment in 4/2013 included the limitation to 3 neo cyc and to 4-5 adj cyc if RTX was not applicable. Primary aim was DFS. Sample size was 274 (power 80%, hazard ratio 1.388, corresponds to DFS of 65% vs. 55% compared to historical controls. Secondary aims: ORR (in arm B), OS, prognostic factors, dose intensity.
Results
Between 6/09 and 10/16 292 pts were either assigned to arm 1 (n=109) or arm 2 (n=183) depending on local tumor board decision; 275 pts have been treated per protocol; median age 50 yrs (18-70); m/f 56/44%; ECOG 0/1/2, 67/21/3%; location, extr/rp/centr/HNO/girdle, 53/21/12/6/4%; histo, pleoNOS/LS/other/SS/LMS, 28/20/15/11/11%; G 2/3, 29/70%; deep, 100%; med. Size, 9.5 cm; resection, n.d. 3.6%; R-status, R0/1/2/unknown, 80/12/1/3%. 91 resp. 90% of pts underwent at least 3 cyc of CXT with higher dose reduction necessary due to IFO toxicity. Discontinuation rate was 5.5%. RXT was applicable in 71% of pts, median dose 59.4 Gy (arm 1) vs. 50.4 (arm 2). Only 1 pt. had RXT prior to CXT. Med. f/u duration was 26.3 mos (0.9-165.6). 29.8% pts relapsed. Projected 5-yr DFS was 61.7% (95% CI: 49.6-73.9%) in arm 1 and 53.1% (95% CI: 41.3-64.9%) in arm 2 with less events being observed during yrs 5-10. Proj. 5-yr OS was 79.2% (95% CI: 68.9-89.6%) in arm 1 and 68.2% (95% CI: 57.4-78.6%) in arm 2. Tumor reduction was seen in 52% of pts in arm 2.
Conclusions
CXT in close conjunction with RXT is an effective and feasible approach in STS population when limited to high risk pts. Lower survival rates have been seen in the neoadjuvant arm, obviously reflecting further adverse tumor features, e.g. grade, size, local invasion.
Clinical trial identification
Editorial acknowledgement
Legal entity responsible for the study
IAWS, AIO, ARO, CAO.
Funding
H.W. & J. Hector Stiftung zu Weinheim, Germany.
Disclosure
All authors have declared no conflicts of interest.