85IN - Innovative combination of targeted agents with radiotherapy

Date 29 September 2014
Event ESMO 2014
Session Controversies in the neo-adjuvant treatment of localised soft tissue sarcomas (STS)
Topics Anticancer Agents
Soft Tissue Sarcomas
Surgical Oncology
Biological Therapy
Radiation Oncology
Presenter Rick Haas
Citation Annals of Oncology (2014) 25 (suppl_4): iv31-iv32. 10.1093/annonc/mdu309
Authors R. Haas
  • Radiotherapy, The Netherlands Cancer Institute Antoni van Leeuwenhoek Hospital, 1066CX - Amsterdam/NL




Role of RT “in general” in STS: Radical surgery while maintaining function as much as possible is the cornerstone of extremity soft tissue sarcoma (ESTS) management. Several studies have shown that (neo-)adjuvant radiotherapy (RT) increases the probability of local control, be it at the cost of increased wound complication rates and fibrosis. Possibly only for high grade sarcomas, this gain in local control translates into a survival benefit.

When not to irradiate at all: Since small (<5cm) superficial low grade ESTS demonstrate a low local failure rate after surgery only and the metastatic potential is low for those that do recur, it is generally accepted not to irradiate these patients in first line treatment. Applying RT may, however, be considered for recurrent cases. In all other circumstances, the MSKCC nomogram (Ann Surg 2012; 255: 343-7.) may guide the individualized indication for RT.

Arguments for chemo-RT in ESTS: In many carcinomas, the addition of chemotherapy and/or smart molecules to RT has resulted in increased antitumor efficacy usually at the cost of temporary increased toxicity. The chemotherapy enhancement factor (CEF) published vary from 1.15-1.3 with conventional agents like cisplatin and 5-FU. The CEF for tyrosine kinase inhibitors is unknown. It is likely (but high levels of evidence still have to be produced) that chemo-RT in ESTS will result in comparable clinico-pathological phenomena. Ongoing and planned studies: Several sarcoma groups investigate the feasibility of combining angiogenesis inhibitors with preoperative RT. Some of these studies (Sorafenib and Bevacizumab) have already been published, others are ongoing. Given the fact, that local control after conservative surgery and RT is already high (85–93% range), it may well be that chemo-RT in ESTS offers the opportunity to lower the RT dose, while maintaining adequate local control and lowering the wound complication rate of subsequent surgery. By this means functionality of limb and quality of life after prolonged follow-up may increase.

In summary: Innovative combinations of targeted agents with RT in ESTS are currently being investigated. Their future perspectives are promising, but high levels of evidence still have to be produced.


The author has declared no conflicts of interest.