Early response to neoadjuvant chemotherapy (NAC) in combination with regional hyperthermia (RHT) to predict long-term survival for adult-type high-risk soft tissue sarcoma (HR-STS): Results of the EORTC-ESHO intergroup phase III study.
10054 Background: A randomized phase III completed trial showed that RHT added to NAC was beneficial in terms of local progression-free (LPFS), and disease-free (DFS) survival. Overall survival (OS) was improved in patients (pts) who completed the preoperative induction therapy with RHT (Lancet Oncol 2010). Here we analyzed both the radiographic (RR) and histopathologic (HR) response as early predictors for survival. Methods: 341 pts were randomized to receive 4 cycles of NAC + RHT (169 pts) or NAC alone (172 pts) as induction therapy. RR (CR/PR vs NC/PD) and HR (>75% vs <75% necrosis) were used to define responder vs non-responder. Predictive impact of response on LPFS, DFS, DDFS (distant disease-free survival) and OS was evaluated by intention-to-treat using Kaplan-Meier estimates and the log-rank test. Stratified (surgery before study entry yes/no; extremity vs non-extremity tumors) multivariate analyses were carried out by Cox regression. Results: Early response in pts with measurable disease was performed in 238 pts (103 pts not evaluable because of surgery before study entry). In the NAC+RHT group (114 pts) response rate was 49.1% (56 responders: RR: 18; HR: 22; RR + HR: 16) and substantially higher (p<0.001) compared to the NAC alone group (124 pts) which was 26,6% (33 responders: RR: 7; HR: 17; RR + HR: 9). In the NAC + RHT group, tumor response was associated with improved DFS (HR 0.58 CI 0.36-0.95; p=0.031) and OS (HR 0.50 CI 0.27-0.90; p=0.020) but not LPFS (HR 0.91 CI 0.49-1.71; p=0.78). For responders, OS median time was > 120 months vs 33 months for non-responders. For the entire NAC + RHT group (169 pts, including pts with surgery before study entry) response remained predictive for better OS (HR 0.54 CI 0.32-0.94; p=0.028) and was also associated with better DDFS (HR 0.47 CI 0.27-0.83; p=0.009). Conclusions: Adding RHT to NAC as induction therapy compared to NAC alone leads to significantly higher early response in almost half of the pts classified as responders which translates in better OS and prevention of distant metastases.