Intensity-modulated radiation therapy (IMRT) has been used to deliver preRX or PORT to patients with extremity soft tissue sarcomas in an effort to spare the femur, joints, and selected other normal tissues from the full prescription dose and to maintain local control while potentially reducing radiation therapy-related morbidity. Initial single-institution reports suggest that high rates of local control with some reduction in morbidity are possible with this technique.[18,19]
In some tumors of the extremities or trunk, surgery alone can be performed without the use of radiation. Evidence for this approach is limited to single-institution, relatively small, case series [1,20,21] or analysis of outcomes in the National Cancer Institute's Surveillance, Epidemiology, and End Results (SEER) tumor registry. However, these comparisons suffer from low statistical power and differential evaluability rates that could have introduced bias. Patient selection factors may vary among surgeons. In general, this approach is considered in patients with low-grade tumors of the extremity or superficial trunk that are less than or equal to 5 cm in diameter (T1) and have microscopically negative surgical margins; long-term local tumor control is about 90% in such patients.
On occasion, surgical excision cannot be performed in the initial management of soft tissue sarcomas because the morbidity would be unacceptable or nearby critical organs make complete resection impossible. In such circumstances, radiation has been used as the primary therapy. However, this must be considered a treatment of last resort. Experience is limited to retrospective case series from single centers.[Level of evidence 3iiiDiv]
Role of Adjuvant or Neoadjuvant Chemotherapy for Clinically Localized Tumors
The role of adjuvant chemotherapy is not completely clear. The investigation of its use falls into two categories or generations—pre- and postifosfamide regimens. In discussions with a patient, any potential benefits should be considered in the context of the short- and long-term toxicities of the chemotherapy.
First-generation trials (preifosfamide)
Several prospective, randomized trials were unable to determine conclusively whether doxorubicin-based adjuvant chemotherapy benefits adults with resectable soft tissue sarcomas. The majority of these studies accrued small numbers of patients and did not demonstrate a metastasis-free survival or an OS benefit for adjuvant chemotherapy. A small study of adjuvant chemotherapy showed a positive effect on both disease-free survival (DFS) and OS in patients treated with postoperative chemotherapy. There was wide interstudy variability among the reported trials, including differences in therapeutic regimens, drug doses, sample size, tumor site, and histologic grade.
A quantitative meta-analysis of updated data from 1,568 individual patients in 14 trials of doxorubicin-based adjuvant therapy showed an absolute benefit from adjuvant therapy of 6% for local relapse-free interval (95% confidence interval [CI], 1%–10%), 10% for distant relapse-free interval (95% CI, 5%–15%), and 10% for recurrence-free survival (95% CI, 5%–15%). A statistically significant OS benefit at 10 years was not detected: absolute difference 4% (95% CI, -1%–+9%).[26,27][Level of evidence: 1iiDii] However, only a small proportion of patients in this meta-analysis were treated with ifosfamide, an agent with demonstrated activity against soft tissue sarcoma. In addition, a subset analysis suggested that patients with sarcomas of the extremities may have benefited from adjuvant chemotherapy (hazard ratio [HR] for death, 0.8, P = .029), but there was no clear evidence that patients with extremity sarcomas had outcomes that were statistically significantly different from the outcomes of patients with tumors at other sites (P = .58).