Elsevier

The Lancet

Volume 359, Issue 9325, 29 June 2002, Pages 2235-2241
The Lancet

Articles
Preoperative versus postoperative radiotherapy in soft-tissue sarcoma of the limbs: a randomised trial

https://doi.org/10.1016/S0140-6736(02)09292-9Get rights and content

Summary

Background

External-beam radiotherapy (delivered either preoperatively or postoperatively) is frequently used in local management of sarcomas in the soft tissue of limbs, but the two approaches differ substantially in their potential toxic effects. We aimed to determine whether the timing of external-beam radiotherapy affected the number of wound healing complications in soft-tissue sarcoma in the limbs of adults.

Methods

After stratification by tumour size (≤ 10 cm or > 10 cm), we randomly allocated 94 patients to preoperative radiotherapy (50 Gy in 25 fractions) and 96 to postoperative radiotherapy (66 Gy in 33 fractions). The primary endpoint was rate of wound complications within 120 days of surgery. Analyses were per protocol for primary outcomes and by intention to treat for secondary outcomes.

Findings

Median follow-up was 3·3 years (range 0·27–5·6). Four patients, all in the preoperative group, did not undergo protocol surgery and were not evaluable for the primary outcome. Of those patients who were eligible and evaluable, wound complications were recorded in 31 (35%) of 88 in the preoperative group and 16 (17%) of 94 in the postoperative group (difference 18% [95% CI 5–30], p=0·01). Tumour size and anatomical site were also significant risk factors in multivariate analysis. Overall survival was slightly better in patients who had preoperative radiotherapy than in those who had postoperative treatment (p=0·0481).

Interpretation

Because preoperative radiotherapy is associated with a greater risk of wound complications than postoperative radiotherapy, the choice of regimen for patients with soft-tissue sarcoma should take into account the timing of surgery and radiotherapy, and the size and anatomical site of the tumour.

Published online June 11, 2002 http://image.thelancet.com/extras/01art4373web.pdf

Introduction

Local management of adult soft-tissue sarcoma generally requires surgery combined with radiotherapy. The usual radiation protocols are preoperative or postoperative external-beam treatment, or brachytherapy.1, 2, 3, 4, 5 The aim of every strategy is to have maximum control of local tumours while preserving function. For external-beam treatment, however, preoperative radiotherapy requires smaller field sizes6 and lower doses.7, 8 Lower doses are usually preferred because higher doses result in worse functional outcome.9 Features such as tumour size and grade and depth of origin are associated with worse prognosis,10 and preoperative radiotherapy is more likely to be chosen in such lesions than postoperative radiotherapy.2

Despite potential advantages of preoperative radiotherapy, the higher rates of wound complication cause concern.11, 12, 13, 14, 15 However, high rates of surgical complications have also been reported without radiation, especially in complicated resections.16 Therefore, use of preoperative radiation for more advanced lesions could contribute to the reported increase in wound complication rates in patients with soft-tissue sarcoma.

We did a multicentre randomised controlled trial to determine whether scheduling of external beam radiotherapy (preoperative vs postoperative) affected the rate of wound complications.

Section snippets

Patients

The trial opened to accrual in October, 1994, and closed in December, 1997, after 190 patients had been randomised. We closed the trial before completion of planned accrual (266 cases) because a planned, preliminary analysis by a data-monitoring committee determined that the primary outcome showed a significant difference. Randomisation was by computer-generated block design issued through a telephone call by which the participating centre confirmed the patient's eligibility. The people who did

Results

We randomly assigned 94 patients to preoperative and 96 to postoperative radiotherapy (figure 1). Quality assurance was done in 161 (88%) of 184 patients planned for radiotherapy (two patients planned for radiotherapy did not receive it). Of these, 153 (95%) met phase I protocol requirements, including five who had their plans modified because of the quality assurance review. Four of 88 patients in the preoperative group had negative resection margins, but received a postoperative boost (phase

Discussion

Our results show that the number of severe wound complications is related to timing of external-beam radiotherapy. The result confirms retrospective reports over the past decade, even though these reports could have been biased by selection of patients.13, 14, 15 The finding is relevant to decision making in management of soft-tissue sarcoma because outcome, especially quality of life, is significantly associated with wound complication after limb conservation management for soft-tissue sarcoma.

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