Background
Prospective randomized trial (NCI) evaluating adjuvant external beam radiation therapy (EBRT) after limb-sparing surgery for soft tissue sarcomas of the extremities. 141 patients randomized to adjuvant EBRT vs. no RT. High-grade (n=91) and low-grade (n=50) tumors analyzed separately. Surgery included wide local excision with or without adjuvant brachytherapy.
Interventions and follow up
Arm A: Limb-sparing surgery + adjuvant EBRT (45–50 Gy to the tumor bed with margins, 13 Gy boost = ~63 Gy total)
Arm B: Limb-sparing surgery alone (no RT)
Primary endpoint: Local recurrence, overall survival
mFollow up: 5 year
Arm B: Limb-sparing surgery alone (no RT)
Primary endpoint: Local recurrence, overall survival
mFollow up: 5 year
Results
5-Year LC (high-grade, EBRT): 96% vs. 69% (no RT), P<.0001
5-Year LC (low-grade, EBRT): 96% vs. 85% (no RT), P=.016
5-Year OS: No significant difference in either subgroup
Functional outcomes: EBRT associated with greater limb stiffness and edema vs. surgery alone
5-Year LC (low-grade, EBRT): 96% vs. 85% (no RT), P=.016
5-Year OS: No significant difference in either subgroup
Functional outcomes: EBRT associated with greater limb stiffness and edema vs. surgery alone
Adverse events
Main adverse events: EBRT arm: limb edema (36%), fibrosis, joint stiffness, pathological fracture risk with bone field involvement. Significant impact on limb function with high-dose EBRT. No treatment-related deaths.
Conclusions
Adjuvant EBRT significantly improves local control in both high- and low-grade extremity STS after limb-sparing surgery, but without OS benefit. Establishes RT as standard of care for local control in extremity STS.
Key Limitations
Key Limitations: Stratified analysis by tumor grade driven by relatively small sample per stratum; no OS benefit — questions whether improved LC justifies RT toxicity in all patients, particularly low-grade STS; EBRT doses used (63 Gy) higher than current practice (50 Gy pre-op or 66 Gy post-op); no modern imaging (MRI) for pre-treatment planning.
Clinical Context
Along with the Rosenberg NCI amputation trial and Pisters MSKCC brachytherapy trial, this establishes the three-part evidence base for RT in extremity STS. Current NCCN guidelines recommend RT for most high-grade, large (>5 cm), or margin-positive STS. The survival equivalence but LC advantage of RT supports its routine use to reduce morbid local recurrences.
References