title: Development and external validation of nomograms predicting distant metastases and overall survival after neoadjuvant chemotherapy and surgery for patients with nonmetastatic osteosarcoma: A multi-institutional study.
abstract: BACKGROUND
  In this era of individualized cancer treatment, data that could be applied to predicting the survival of patients with osteosarcoma are still limited because of the rarity of the disease and the difficulty in accumulating a sufficient number of patients. Therefore, a multi-institutional collaboration was implemented to develop and externally validate nomograms that would predict metastasis-free survival (MFS) and overall survival (OAS) for patients with nonmetastatic osteosarcoma.
  
  
  METHODS
  This study retrospectively examined 1070 patients treated with neoadjuvant chemotherapy and surgery for nonmetastatic osteosarcoma. Data from Japanese patients (n = 557) were used to develop multivariate nomograms based on Cox regression. Six clinical and pathologic variables were built into nomograms estimating the probability of MFS and OAS 3 and 5 years after diagnosis. The model was internally validated for discrimination and calibration with bootstrap resampling and was externally validated with an independent patient cohort from Korea (n = 513).
  
  
  RESULTS
  A patient's age, tumor site, and histologic response were found to have a stronger influence on MFS and OAS in the model than sex, tumor size, or pathologic fracture. The nomograms and calibration plots based on these results well predicted the probability of MFS (concordance index, 0.631) and OAS (concordance index, 0.679). The concordance indices for external validation were 0.682 for MFS and 0.665 for OAS.
  
  
  CONCLUSIONS
  The nomograms were externally validated and verified to be useful for the prediction of MFS and OAS and for the assessment of the postoperative prognosis. They can be used for counseling patients and for establishing appropriate surveillance strategies after surgery.
authors.affiliation: Department of Musculoskeletal Oncology, National Cancer Center Hospital, Tokyo, Japan.|Department of Orthopedic Surgery, The University of Tokyo Hospital, Tokyo, Japan.
authors.forename: Koichi
authors.initials: K
authors.lastname: Ogura
authors.affiliation: Department of Musculoskeletal Oncology, National Cancer Center Hospital, Tokyo, Japan.|Department of Orthopedic Surgery, Okayama University, Okayama, Japan.
authors.forename: Tomohiro
authors.initials: T
authors.lastname: Fujiwara
authors.affiliation: Department of Health Economics and Epidemiology Research, School of Public Health, The University of Tokyo, Tokyo, Japan.
authors.forename: Hideo
authors.initials: H
authors.lastname: Yasunaga
authors.affiliation: Department of Health Economics and Epidemiology Research, School of Public Health, The University of Tokyo, Tokyo, Japan.
authors.forename: Hiroki
authors.initials: H
authors.lastname: Matsui
authors.affiliation: Department of Orthopedic Surgery, Korea Cancer Center Hospital, Seoul, Korea.
authors.forename: Dae-Geun
authors.initials: DG
authors.lastname: Jeon
authors.affiliation: Department of Orthopedic Surgery, Korea Cancer Center Hospital, Seoul, Korea.
authors.forename: Wan Hyeong
authors.initials: WH
authors.lastname: Cho
authors.affiliation: Department of Orthopedic Surgery, Hokkaido Cancer Center, Hokkaido, Japan.
authors.forename: Hiroaki
authors.initials: H
authors.lastname: Hiraga
authors.affiliation: Department of Orthopedic Surgery, Chiba Cancer Center, Chiba, Japan.
authors.forename: Takeshi
authors.initials: T
authors.lastname: Ishii
authors.affiliation: Department of Orthopedic Surgery, Chiba Cancer Center, Chiba, Japan.
authors.forename: Tsukasa
authors.initials: T
authors.lastname: Yonemoto
authors.affiliation: Department of Orthopedic Surgery, Chiba Cancer Center, Chiba, Japan.
authors.forename: Hiroto
authors.initials: H
authors.lastname: Kamoda
authors.affiliation: Department of Orthopedic Surgery, Okayama University, Okayama, Japan.
authors.forename: Toshifumi
authors.initials: T
authors.lastname: Ozaki
authors.affiliation: Department of Orthopedic Surgery, Nagoya University, Aichi, Japan.
authors.forename: Eiji
authors.initials: E
authors.lastname: Kozawa
authors.affiliation: Department of Orthopedic Surgery, Nagoya University, Aichi, Japan.
authors.forename: Yoshihiro
authors.initials: Y
authors.lastname: Nishida
authors.affiliation: Department of Orthopedic Surgery, Keio University, Tokyo, Japan.
authors.forename: Hideo
authors.initials: H
authors.lastname: Morioka
authors.affiliation: Department of Orthopedic Surgery, Kanagawa Cancer Center, Kanagawa, Japan.
authors.forename: Toru
authors.initials: T
authors.lastname: Hiruma
authors.affiliation: Department of Orthopedic Surgery, Osaka National Hospital, Osaka, Japan.
authors.forename: Shigeki
authors.initials: S
authors.lastname: Kakunaga
authors.affiliation: Department of Orthopedic Surgery, Osaka National Hospital, Osaka, Japan.
authors.forename: Takafumi
authors.initials: T
authors.lastname: Ueda
authors.affiliation: Department of Orthopedic Surgery, The University of Tokyo Hospital, Tokyo, Japan.
authors.forename: Yusuke
authors.initials: Y
authors.lastname: Tsuda
authors.affiliation: Department of Orthopedic Surgery, The University of Tokyo Hospital, Tokyo, Japan.
authors.forename: Hirotaka
authors.initials: H
authors.lastname: Kawano
authors.affiliation: Department of Musculoskeletal Oncology, National Cancer Center Hospital, Tokyo, Japan.
authors.forename: Akira
authors.initials: A
authors.lastname: Kawai
mesh_terms: D000293:Adolescent; D000328:Adult; D000367:Age Factors; D000465:Algorithms; D001859:Bone Neoplasms / Q000175:diagnosis / Q000401:mortality* / Q000628:therapy; D017024:Chemotherapy, Adjuvant; D002648:Child; D015331:Cohort Studies; D005260:Female; D006801:Humans; D007564:Japan; D008297:Male; D020360:Neoadjuvant Therapy; D009362:Neoplasm Metastasis; D049451:Nomograms; D009985:Orthopedics; D012516:Osteosarcoma / Q000175:diagnosis / Q000401:mortality* / Q000628:therapy; D011237:Predictive Value of Tests; D011379:Prognosis; D012189:Retrospective Studies; D012307:Risk Factors; D015996:Survival Rate; D016896:Treatment Outcome; D055815:Young Adult
keywords: external validation; nomogram; osteosarcoma; prognosis; survival