A systematic overview of radiation therapy effects in soft tissue sarcomas

Abstract

A systematic review of radiation therapy trials in several tumour types was performed by The Swedish Council of Technology Assessment in Health Care (SBU). The procedures for evaluation of the scientific literature are described separately (Acta Oncol 2003; 42: 357-365). This synthesis of the literature on radiation therapy for soft tissue sarcomas (STS) is based on data from five randomized trials. Moreover, data from 6 prospective studies, 25 retrospective studies and 3 other articles were used. In total, 39 scientific articles are included, involving 4 579 patients. The results were compared with those of a similar overview from 1996 which included 3 344 patients. The conclusions reached can be summarized as follows: The well-established prognostic factors for tumour-related death from STS-histological grade, tumour size and age-are well documented. The importance of superficial versus deep site as well as the anatomic site is also reaffirmed to some extent. There is strong evidence that adjuvant radiotherapy improves the local control rate in combination with conservative surgery in the treatment of STS of extremities and trunk in patients with negative, marginal or minimal microscopic positive surgical margins. A local control rate of 90% has been achieved. Improvement is obtained with radiotherapy added in the case of intralesional surgery, but the local control rate is somewhat lower. More studies are needed on this issue. For STS in other anatomic sites, retroperitoneum, head and neck, breast and uterus, there is only weak indication of a benefit for the local control rate, with the use of adjuvant radiotherapy. There is still insufficient data to establish that preoperative radiotherapy is favourable compared to postoperative radiotherapy for local control in patients presenting primarily with large tumours. One small study has shown a possible survival benefit for preoperative radiotherapy. There is fairly good evidence to suggest that the preoperative setting results in more wound complications. There is no randomized study comparing external beam radiotherapy and brachytherapy. The data suggest that external beam radiotherapy and low dose rate brachytherapy result in comparable local control for high-grade tumours. Some patients with low-grade soft tissue sarcomas benefit from external beam radiotherapy in terms of local control. Brachytherapy with low dose rate for low-grade tumours seems to be of no benefit, but data are sparse. The available data are inconclusive concerning the effect of intraoperative high dose rate radiotherapy for retroperitoneal STS. Further studies are needed. Neutron radiotherapy might be beneficial for patients with low- and intermediate-grade tumours considered inoperable and for those operated with intralesional margins. More severe side effects for neutrons have been registered. In two small studies investigating hyperfractionation schedules there was no indication of improvements compared to daily fractions of 2 Gy. Further studies should be encouraged. One small study using preoperative limb perfusion with TNF alpha melphalan and +/- interferon gamma combined with postoperative radiotherapy in the case of marginal or positive surgical margin has shown excellent local control without enhanced morbidity.