Clinical Investigation
Radiotherapy to Improve Local Control Regardless of Surgical Margin and Malignancy Grade in Extremity and Trunk Wall Soft Tissue Sarcoma: A Scandinavian Sarcoma Group Study

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Purpose

Adjuvant radiotherapy has during the past decades become increasingly used in the treatment of localized soft tissue sarcoma. We evaluated the effect of radiotherapy (RT) on local recurrence rates (LRRs) in Scandinavia between 1986 and 2005.

Methods and Materials

A total of 1,093 adult patients with extremity or trunk wall soft tissue sarcoma treated at four Scandinavian sarcoma centers were stratified according to the treatment period (1986–1991, 1992–1997, and 1998–2005). The use of adjuvant RT, quality of the surgical margin, interval between surgery and RT, and LRR were analyzed. The median follow-up was 5 years.

Results

The use of RT (77% treated postoperatively) increased from 28% to 53%, and the 5-year LRR decreased from 27% to 15%. The rate of wide surgical margins did not increase. The risk factors for local recurrence were histologic high-grade malignancy (hazard ratio [HR], 5), an intralesional (HR, 6) or marginal (HR, 3) surgical margin, and no RT (HR, 3). The effect of RT on the LRR was also significant after a wide margin resection and in low-grade malignant tumors. The LRR was the same after preoperative and postoperative RT. The median interval from surgery to the start of RT was 7 weeks, and 98% started RT within 4 months. The LRR was the same in patients who started treatment before and after 7 weeks.

Conclusion

The results of our study have shown that adjuvant RT effectively prevents local recurrence in soft tissue sarcoma, irrespective of the tumor depth, malignancy grade, and surgical margin status. The effect was most pronounced in deep-seated, high-grade tumors, even when removed with a wide surgical margin.

Introduction

A high malignancy grade and the quality of the surgical margin are the two most important risk factors for local recurrence (LR) of soft tissue sarcomas (STSs) 1, 2, 3, 4, 5, 6, 7. STSs were formerly regarded as relatively radioresistant tumors. In the past two decades, however, mounting evidence has shown an effect of radiotherapy (RT) on STS. Two randomized studies and several retrospective reports have indicated improved local control when surgical removal of high-grade STS was combined with RT 2, 8, 9, 10, 11, 12, 13, 14. The effect of RT has mainly been demonstrated after intralesional or marginal surgery, but improvements in local control after adding RT to wide margin surgery has also been reported 15, 16, 17. The effect of RT on low-grade malignant sarcomas is still controversial 9, 17, 18.

When the Scandinavian Sarcoma Group (SSG) was started in 1979, surgery with a wide margin was considered sufficient treatment of STS, and RT was used only for those with an intralesional or marginal margin. Because of the positive international experience of adjuvant RT, its use also increased in Scandinavia. In 1998, adjuvant RT was formally recommended by the SSG for intralesional and marginal margins, regardless of tumor depth, and for deep-seated, high-grade sarcoma, regardless of margin status (Clinical Protocol SSG XIII) (19). RT was recommended to begin as soon as the wound had healed. The only study on the importance of an early start of RT for STS found a better local recurrence-free survival rate (88%) in patients starting RT <4 months after surgery than in patients who started >4 months after surgery (62%) (20).

In 1986, the SSG established a register of soft tissue and bone sarcomas, including registration of detailed patient, tumor, treatment, and follow-up data. This register and the gradually increased use of RT gave us an opportunity to assess the effect of RT in relation to the surgical margins and histologic malignancy grade in STS patients treated at Scandinavian sarcoma centers between 1986 and 2005.

Section snippets

Patients and referral

The study was conducted in accordance with the Helsinki Declaration of 1975 (revised in 2000) and was approved by the Regional Committee for Medical Research Ethics and the Ombudsman for Privacy in Research, Norwegian Social Science Data Service.

The SSG Register currently contains information on >5,000 patients. It includes data on about 90% of all sarcomas treated in Sweden and Norway and is considered representative of the population. The remaining 10% of STSs not reported are mainly small

Results

The annual number of patients referred (before any surgery) increased with time. The fraction of wide surgical margin (including myectomy and compartmental margins) was similar, and the amputation rate did not change over time (Table 2).

Discussion

This study was of a large, prospective series of STSs treated at four sarcoma centers according to common guidelines and with complete follow-up. The LRRs decreased as the use of adjuvant RT increased. Our findings are in concordance with previous publications on the effect of RT for localized STS 2, 8, 9, 10, 11, 12, 13, 14. When we examined other treatment-related factors (surgical margin type, interval from surgery to the start of RT, use of adjuvant chemotherapy), we could not demonstrate

Conclusion

Adjuvant RT decreased the LRR of STSs, irrespective of surgical margin type, tumor depth, and malignancy grade. Tumor resection with an intralesional or a marginal margin necessitates RT. The effect of RT was small on low-grade tumors, irrespective of depth, after resection with a wide margin. The effect was moderate in high-grade, subcutaneous tumors resected with a wide margin. Whether this risk requires RT depends on the expected morbidity caused by surgical treatment of LR. RT had a

Acknowledgments

We are grateful to Tore Wenzel-Larsen, statistician, Center for Clinical Research, Haukeland University Hospital, Bergen, Norway; Anne-Lise Salbu, coordinator, Center for Bone and Soft Tissue Tumors, Haukeland University Hospital, Bergen, Norway; and Eva-Marie Olofsson, SSG-secretariat, Department of Cancer Epidemiology, Lund University Hospital, Lund, Sweden.

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    Supported in part by the Swedish Children Cancer Society, Swedish Cancer Society, and Nordic Cancer Union.

    N. L. Jebsen received funding from the National Competence Center for Sarcoma and from Rikshospitalet-Radiumhospitalet Medical Center, Oslo, Norway.

    Conflict of interest: none.

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