Impact of pathologic necrosis on clinical outcomes following neoadjuvant radiation for soft tissue sarcoma.

e23565 Background: Tumor necrosis is a common pathologic finding in soft tissue sarcomas (STS) following neoadjuvant therapy, yet its prognostic significance and associated factors remain incompletely understood within orthopedic oncology. This study examined the relationship between the extent of tumor necrosis and clinical outcomes and identified factors associated with necrosis percentage in patients with STS. Methods: We retrospectively analyzed 64 patients with STS who underwent surgical resection following neoadjuvant therapy (2020-2023). Patients were stratified into two groups based on pathologic tumor necrosis: high necrosis (≥75%, n = 32, mean 93.6%) vs minimal necrosis ( < 75%, n = 32, mean 26.8%). Demographics, tumor characteristics, radiation parameters, and surgical outcomes were compared between groups. Primary outcomes included local recurrence, distant metastasis, and mortality. Results: The two groups were similar in demographics, tumor characteristics, radiation therapy parameters, and surgical outcomes. Patients with high necrosis had statistically significantly higher rates of current/former smoking (46.9% vs 21.9%; p = 0.041). No significant correlations were found between necrosis percentage and age (p = 0.742), BMI (p = 0.241), comorbidity index (p = 0.757), tumor size (p = 0.295), or any radiation parameters (dose p = 0.911, fractions p = 0.625, timing between last radiation dose and surgery p = 0.960). A paradoxical pattern emerged in clinical outcomes: high necrosis was associated with lower local recurrence (12.5% vs 25.0%, p = 0.337) but higher distant metastasis (46.9% vs 25.0%, OR = 2.647, p = 0.117) and mortality (25.0% vs 12.5%, OR = 2.333, p = 0.337). While these outcome differences did not reach statistical significance, they represent clinically meaningful trends suggesting nearly 2-fold increased risk of systemic disease progression in high necrosis tumors. Conclusions: In this cohort of STS patients treated with neoadjuvant therapy, smoking history was significantly associated with tumor necrosis extent. Extensive necrosis demonstrated a paradoxical relationship with outcomes, associated with better local control but worse systemic disease progression. This suggests that while high necrosis may reflect effective local treatment response, it may also indicate more aggressive underlying tumor biology with a propensity for distant metastasis. These findings highlight that extensive necrosis should not provide false reassurance, and patients with high necrosis may benefit from continued surveillance for metastatic disease.