FUNCTION AND QUALITY OF LIFE OUTCOMES IN A RANDOMIZED TRIAL COMPARING PRE-OPERATIVE vs POST-OPERATIVE RADIOTHERAPY IN EXTREMITY SOFT TISSUE SARCOMA

AM Davis, B O’Sullivan, RS Bell, CN Catton, R Turcotte, JS Wunder, P Chabot, A Hammond, V Benk, M Isler, C Freeman, K Goddard, A Bezjak, A Sadura, A Day, K James, B Zee, Canadian Sarcoma Group and NCI Canada Clinical Trials Group, Canada

Introduction and Purpose: Morbidity based on increased incidence of wound complications may translate into disability and quality of life disadvantages for patients treated with pre-operative radiotherapy (RT). This report describes the functional outcome and quality of life of patients with extremity soft tissue sarcoma randomized in a phase III trail comparing pre vs. post-operative RT.

Materials and Methods: One hundred and ninety adult patients with extremity STS were randomized to pre- or post-operative RT from October 1994 to December 1997. Study eligibility included the need for combined surgery and RT for local management; stratification was 21by tumor size (dichotomized at 10 cm). The trial end-points included the incidence of wound complications, local and metastatic outcomes, survival, functional outcome and quality of life and late RT effects. Functional measures consisted of two disease-specific measures, the Musculoskeletal Tumor Society Rating Scale (MSTS) and the Toronto Extremity Salvage Score (TESS), and a generic measure, the Shortform-36 (SF-36). Data were collected at randomization, 6 weeks, 3, 6 and 12 months post surgery.

Results: The study arms were balanced with respect to age, gender, tumor size, depth of tumor, and co-morbidity. For all 187 patients with function data, the patients treated with post-operative RT had higher MSTS (25 vs 21, p=0.00), TESS (69 vs 60, p=0.01) and SF-36 bodily pain (67 vs 58, p=0.03) scores at 6 weeks post-surgery. There were no differences between the treatment arms at later time points. After controlling for treatment arm, adverse change scores of the MSTS were predicted by having a lower extremity tumor, large resection specimen and motor nerve sacrifice; TESS change scores were predicted by lower extremity tumor, prior incomplete excision with a trend towards lower scores for those with motor nerve sacrifice. Wound complications were more common with pre-op RT (31 of 88 evaluable patients - 35%) compared to post-op RT (16 of 94 cases - 17%) (p=0.01).

Conclusion: There is a statistically significant disadvantage to pre-operative RT in the very early stages of recovery from treatment. However, as follow-up increases the MSTS, TESS and SF-36 scores for patients treated by either pre-op or post-op RT are identical. While pre-op RT predisposes to higher rates of wound morbidity, local anatomic factors must be considered in the choice of RT scheduling. Long-term RT effects and important local control outcomes remain to be analyzed in this study.