Location of residual viable tumor cells after neoadjuvant chemotherapy: A new concept with high prognostic performance in osteosarcoma

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Abstract
BACKGROUND AND OBJECTIVES: The purpose of this study was to establish a new concept for evaluating responses to neoadjuvant chemotherapy in osteosarcoma.METHODS: A total of 56 high‐grade extremity osteosarcoma patients were retrospectively reviewed. A new conceptual method was derived from locations of residual viable tumor cells (LRVTC) after chemotherapy, whether extracompartmental or intracompartmental, rather than quantitative measurements of necrosis rates of tumor cells.RESULTS: LRVTC after chemotherapy was independently associated with overall survival ([OS]hazard ratio [HR] = 6.502, P = 0.008) after adjustment for Huvos grade (HR = 3.694, P = 0.045), alkaline phosphatase ([ALP] HR = 2.140, P = 0.226), size (HR = 0.318, P = 0.133), joint extension (HR = 2.309, P = 0.162), and metastasis at diagnosis (HR = 8.228, P = 0.009). LRVTC was also independently associated with metastasis (HR = 5.096, P = 0.002) after adjustment for Huvos grade (HR = 2.261, P = 0.101), ALP (HR = 2.558, P = 0.053), size (HR = 1.280, P = 0.641), and joint extension (HR = 1.800, P = 0.254). AUC values of LRVTC for OS and metastasis were superior to those of Huvos grade: AUCs for OS (LRVTC: 0.757, Confidence Interval [CI] = 0.618 to 0.865 vs Huvos grade: 0.590, [CI] = 0.445 to 0.725; AUC = 0.167, P = 0.086) and metastasis (LRVTC: 0.769, CI = 0.631 to 0.874 vs Huvos grade: 0.606, [CI] = 0.461 to 0.739; AUC = 0.163, P = 0.046).CONCLUSIONS: LRVTC after chemotherapy may be useful as a new method with high performance for evaluating chemo‐responses in osteosarcoma.

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