(P 418) INTEGRATING SARCULATOR AND PET RESPONSE TO GUIDE NEOADJUVANT TREATMENT DECISIONS IN HIGH-RISK SOFT TISSUE SARCOMA

Objective: The benefit of perioperative chemotherapy in high-grade soft tissue sarcomas (STS) remains controversial . Meta-analyses and trials have shown improved progression-free survival (PFS), but overall survival (OS) benefits are inconsistent. The objective of this study was to determine how Positron Emission Tomography (PET) response to neoadjuvant chemotherapy outcomes compare to baseline risk estimates using SARCULATOR.

Methods: Sixty-nine patients with high-grade STS received preoperative pegylated liposomal doxorubicin and ifosfamide. PET scans were performed after cycles 1 and 4. Responders were defined as having ≥40% reduction in SUVmax from baseline. PFS and OS were analyzed by PET response and compared to SARCULATOR-predicted risk. Number needed to treat (NNT) was calculated to estimate clinical impact.

Results: Of the 69 patients, 38 (55%) were PET responders at the completion of four cycles of neoadjuvant chemotherapy. The mean SARCULATOR-predicted 5-year OS was 70.1% in responders compared to 71.9% in non-responders; 10-year OS was 58.9% and 60.1%, respectively. In contrast, the observed 5-year OS was 87% (95% CI, 77–99) in responders versus 37% (95% CI, 21–64) in non-responders; observed 10-year OS was 81% vs. 37%. Predicted 5-year distant metastasis (DM) was 38.7% in responders versus 37.2% in non-responders; the 10-year DM was 42.8% and 41.2%. Observed PFS at 5 and 10 years was 72% and 69% in responders, respectively, versus 33% at both time points in non-responders. The absolute OS benefit (87% vs. 37% at 5 years and 81% vs. 37% at 10 years) corresponds to NNT of 2.0 and 2.3, respectively.

Conclusion: Metabolic response assessed by PET provides significantly stronger prognostic stratification than SARCULATOR alone. As predictive models evolve to incorporate dynamic, real-time data throughout the treatment course, PET response should be recognized as a critical factor. In this study, patients with a metabolic response had substantial improvements in long-term OS and PFS. In contrast, non-responders appeared to derive no benefit from chemotherapy, with outcomes comparable or worse than those expected with local therapy alone. Approximately 50% of patients benefited from chemotherapy. These findings support the use of neoadjuvant chemotherapy in high-risk STS and highlight PET response as a valuable tool to guide treatment stratification and future trial design—particularly for tailoring therapy in PET non-responders.