title: Location of residual viable tumor cells after neoadjuvant chemotherapy: A new concept with high prognostic performance in osteosarcoma.
abstract: OBJECTIVE
  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.
authors.affiliation: Department of Orthopaedic Surgery, Yonsei University College of Medicine, Seoul, Korea.
authors.forename: Seung Hyun
authors.identifier: http://orcid.org/0000-0002-3878-1944
authors.initials: SH
authors.lastname: Kim
authors.affiliation: Department of Orthopaedic Surgery, Yonsei University College of Medicine, Seoul, Korea.
authors.forename: Kyoo-Ho
authors.initials: KH
authors.lastname: Shin
authors.affiliation: Department of Orthopaedic Surgery, Yonsei University College of Medicine, Seoul, Korea.
authors.forename: Seong-Hwan
authors.initials: SH
authors.lastname: Moon
authors.affiliation: Department of Orthopaedic Surgery, Yonsei University College of Medicine, Seoul, Korea.
authors.forename: Youngho
authors.initials: Y
authors.lastname: Kong
authors.affiliation: Department of Radiology and Research Institute of Radiological Science, Yonsei University College of Medicine, Seoul, Korea.
authors.forename: Jin-Suck
authors.initials: JS
authors.lastname: Suh
authors.affiliation: Department of Pathology, Yonsei University College of Medicine, Seoul, Korea.
authors.forename: Woo-Ick
authors.initials: WI
authors.lastname: Yang
mesh_terms: D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use; D001859:Bone Neoplasms / Q000188:drug therapy* / Q000473:pathology* / Q000601:surgery; D017024:Chemotherapy, Adjuvant; D002945:Cisplatin / Q000008:administration & dosage; D004317:Doxorubicin / Q000008:administration & dosage; D005260:Female; D006801:Humans; D007069:Ifosfamide / Q000008:administration & dosage; D008297:Male; D020360:Neoadjuvant Therapy; D060787:Neoplasm Grading; D012516:Osteosarcoma / Q000188:drug therapy* / Q000473:pathology* / Q000601:surgery; D011379:Prognosis; D012189:Retrospective Studies
chemical_list: D004317:Doxorubicin; D002945:Cisplatin; D007069:Ifosfamide
keywords: locations of residual viable tumor cells (LRVTC); osteosarcoma; prognosis