5-fluoro-deoxyglucose PET/CT response after neoadjuvant chemotherapy predicts long-term outcomes in soft tissue sarcomas: Results from a prospective trial.

BACKGROUND: Only 30%-40% of high-grade sarcomas respond to initial chemotherapy, which can have significant toxicities. Computed tomography imaging alone has limitations in evaluating treatment response. Imaging with 5-fluoro-deoxyglucose-positron emission tomography/computed tomography (FDG-PET/CT), which evaluates tumor metabolism, offers an alternative. This study examined whether early changes in the maximum standardized uptake value (SUVmax) after neoadjuvant chemotherapy can be used to predict outcomes in high-grade sarcomas. METHODS: This prospective trial assessed whether changes in the SUVmax after one or four cycles of pegylated-liposomal doxorubicin plus ifosfamide could predict progression-free survival (PFS), overall survival (OS), and histologic response. Fifty-six patients were required for 90% power. Metabolic response was defined as a reduction ≥40% in the SUVmax from baseline after either cycle 1 (delta 1) or cycle 4 (delta 2). RESULTS: Sixty-nine patients were enrolled (2006-2013) with a median follow-up of 8.1 years. The 10-year PFS rate was 74% versus 42% for delta 1 responders versus nonresponders (p = .0082), respectively; and 69% versus 33% for delta 2 responders versus nonresponder (p = .0015), respectively. The 10-year OS rate was 73% versus 58% for delta 1 responders versus nonresponder (p = .28), respectively; and 81% versus 37% for delta 2 responders versus nonresponder (p = .00026), respectively. Of 46 delta 1 nonresponders, 23 met criteria at delta 2. A positron emission tomography response was correlated with histologic necrosis. At last follow-up, 31 patients (44.9%) were alive and disease free, and 10 (14.5%) were alive with sarcoma. Five patients developed secondary malignancies. CONCLUSIONS: An SUVmax reduction verified on FDG-PET/CT imaging after neoadjuvant chemotherapy was a strong predictor of long-term outcomes. Metabolic imaging at treatment completion identified responders, supporting continued therapy in initially nonresponsive patients and guiding personalized treatment strategies.