Proximal tumor location and fluid-fluid levels on MRI predict resistance to chemotherapy in stage IIB osteosarcoma.

Background: Primary tumor growth during neoadjuvant chemotherapy is believed to be a sign of resistance to chemotherapy (chemoresistance), and often is associated with poor histologic response, local recurrence, and poorer survival. Currently there are no proven indicators to predict poor response to chemotherapy at the time of diagnosis.

Questions/purposes: We asked (1) what clinicopathologic factors present at diagnosis predict primary tumor growth during neoadjuvant chemotherapy, (2) what factors at presentation predict survival, and (3) when the factors at presentation and the treatment-related factors are considered, what factors independently correlate with survival.

Methods: We studied 567 patients with Stage IIB osteosarcomas. The factors assessed included age, sex, location, pattern on plain radiographs (radiodense, radiolucent, mixed), MRI findings, pathologic subtype, initial tumor volume determined by MRI, tumor volume change after chemotherapy, surgical margin, and histologic response to preoperative chemotherapy. Logistic modeling was used to identify risk factors.

Results: Independent risk factors associated with primary tumor growth after neoadjuvant chemotherapy were proximal tumor location (p < 0.01; relative risk [RR], 2.41; 95% CI, 1.5-3.86) and fluid-fluid level on initial MRI (p < 0.01; RR, 5.56; 95% CI, 3.48-8.87). Among factors at presentation, large initial tumor volume (p < 0.01; RR, 1.58; 95% CI, 1.22-2.04), proximal tumor site (p < 0.01; RR, 1.61; 95% CI, 1.19-2.19), and presence of fluid-fluid level (p < 0.01; RR, 1.83; 95% CI, 1.37-2.5) independently predicted reduced event-free survival. When we consider the factors at presentation and treatment-related factors, large initial tumor volume (p < 0.01; RR, 1.54), tumor growth after neoadjuvant chemotherapy (p < 0.01; RR, 3.88), inadequate surgical margin (p < 0.01; RR, 2.42), and poor histologic response (p = 0.03; RR, 1.43) were independent poor prognostic factors of event-free survival.

Conclusions: Proximal tumor location and the presence of the fluid-fluid level on initial MRI were predictors of tumor progression and poor survival in patients presenting with Stage IIB osteosarcomas. If confirmed in other studies, patients with these risk factors should be considered for trials of other treatment strategy.

Level Of Evidence: Level III, prognostic study. See the Instructions for Authors for a complete description of levels of evidence.