Radiographic and histologic response to neoadjuvant radiotherapy in patients with soft tissue sarcoma

Abstract

Background: Limited data exist regarding the radiographic and histologic response of soft tissue sarcoma (STS) to neoadjuvant radiotherapy (RT).

Methods: Between February 2000 and January 2009, a total of 25 patients aged >16 years with intermediate- or high-grade primary STS of all sites were treated with neoadjuvant RT followed by definitive resection. Patients receiving chemoradiotherapy were excluded. Cross-sectional images obtained before and after RT as well as pathologic specimens were reviewed for maximal change in tumor diameter and percentage tumor necrosis, respectively. Clinicopathologic variables were analyzed for their association with pathologic and radiographic response.

Results: There were 18 extremity (72%) and 7 retroperitoneal (28%) tumors. Median maximal tumor size was 9 cm (range, 3.3-35 cm), and 88% were of high grade. There were 21 R0 resections (84%) and 4 R1 resections (16%). Radiographically, the median percentage change in tumor diameter was 0% (range, -25 to +86%). By Response Evaluation Criteria in Solid Tumors (RECIST), 5 patients demonstrated progressive disease, 20 demonstrated stable disease, and 0 demonstrated partial/complete response. The median pathologic percentage tumor necrosis was 30% (range, 5-100%). Two tumors (8%) demonstrated near-complete pathologic response (≥95% necrosis). Near-complete pathologic response was associated with favorable oncologic outcomes, although these associations were not statistically significant.

Conclusions: Radiologic and near-complete pathologic responses are rare events after preoperative RT for STS. Near-complete pathologic response may be a potentially meaningful surrogate marker for disease outcome and is not predicted by RECIST response. Knowledge of these historical response rates is important for the evaluation of novel neoadjuvant therapies for patients with STS.

Fig. 1

Kaplan–Meier curve depicting local recurrence-free survival, overall survival, and distant recurrence-free survival for the entire cohort of soft tissue sarcoma patients treated with preoperative radiotherapy followed by resection with curative intent

Fig. 2

a Waterfall plot of radiographic percentage change in maximal tumor diameter (RECIST response) from initial diagnosis to restaging after preoperative radiotherapy. RECIST, Response Evaluation Criteria in Solid Tumors (http://ctep.cancer.gov/protocolDevelopment/docs/recist_guideline.pdf). (b) Waterfall plot of percentage tumor necrosis in resected surgical specimens after preoperative radiotherapy for soft tissue sarcoma

Fig. 3

Kaplan–Meier curve depicting distant recurrence-free survival grouped by presence or absence of near-complete pathologic necrosis in resected surgical specimen (≥95% tumor necrosis). Log rank test P value is shown

Fig. 4

Bar graph comparing mean percentage tumor necrosis stratified by various clinicopathologic characteristics. ** P = 0.003 by Mann–Whitney U-test. RECIST Response Evaluation Criteria in Solid Tumors; SD stable disease; PD progressive disease. Myxoid histology includes 5 myxoid/round liposarcoma and 2 myxofibrosarcoma