title: Proximal tumor location and fluid-fluid levels on MRI predict resistance to chemotherapy in stage IIB osteosarcoma.
abstract: BACKGROUND
  Primary tumor growth during neoadjuvant chemotherapy is believed to be a sign of resistance to chemotherapy (chemoresistance), and often is associated with poor histologic response, local recurrence, and poorer survival. Currently there are no proven indicators to predict poor response to chemotherapy at the time of diagnosis.
  
  
  OBJECTIVE
  We asked (1) what clinicopathologic factors present at diagnosis predict primary tumor growth during neoadjuvant chemotherapy, (2) what factors at presentation predict survival, and (3) when the factors at presentation and the treatment-related factors are considered, what factors independently correlate with survival.
  
  
  METHODS
  We studied 567 patients with Stage IIB osteosarcomas. The factors assessed included age, sex, location, pattern on plain radiographs (radiodense, radiolucent, mixed), MRI findings, pathologic subtype, initial tumor volume determined by MRI, tumor volume change after chemotherapy, surgical margin, and histologic response to preoperative chemotherapy. Logistic modeling was used to identify risk factors.
  
  
  RESULTS
  Independent risk factors associated with primary tumor growth after neoadjuvant chemotherapy were proximal tumor location (p < 0.01; relative risk [RR], 2.41; 95% CI, 1.5-3.86) and fluid-fluid level on initial MRI (p < 0.01; RR, 5.56; 95% CI, 3.48-8.87). Among factors at presentation, large initial tumor volume (p < 0.01; RR, 1.58; 95% CI, 1.22-2.04), proximal tumor site (p < 0.01; RR, 1.61; 95% CI, 1.19-2.19), and presence of fluid-fluid level (p < 0.01; RR, 1.83; 95% CI, 1.37-2.5) independently predicted reduced event-free survival. When we consider the factors at presentation and treatment-related factors, large initial tumor volume (p < 0.01; RR, 1.54), tumor growth after neoadjuvant chemotherapy (p < 0.01; RR, 3.88), inadequate surgical margin (p < 0.01; RR, 2.42), and poor histologic response (p = 0.03; RR, 1.43) were independent poor prognostic factors of event-free survival.
  
  
  CONCLUSIONS
  Proximal tumor location and the presence of the fluid-fluid level on initial MRI were predictors of tumor progression and poor survival in patients presenting with Stage IIB osteosarcomas. If confirmed in other studies, patients with these risk factors should be considered for trials of other treatment strategy.
  
  
  METHODS
  Level III, prognostic study. See the Instructions for Authors for a complete description of levels of evidence.
authors.affiliation: Department of Orthopedic Surgery, Korea Cancer Center Hospital, 215-4, Gongneung-dong, Nowon-gu (75, Nowon-Ro, Nowon-Gu), Seoul, 139-706, Korea, dgjeon@kcch.re.kr.
authors.forename: Dae-Geun
authors.initials: DG
authors.lastname: Jeon
authors.forename: Won Seok
authors.initials: WS
authors.lastname: Song
authors.forename: Wan Hyeong
authors.initials: WH
authors.lastname: Cho
authors.forename: Chang-Bae
authors.initials: CB
authors.lastname: Kong
authors.forename: Sang Hyun
authors.initials: SH
authors.lastname: Cho
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000970:Antineoplastic Agents / Q000627:therapeutic use*; D001859:Bone Neoplasms / Q000188:drug therapy* / Q000401:mortality / Q000473:pathology; D017024:Chemotherapy, Adjuvant; D002648:Child; D002675:Child, Preschool; D018572:Disease-Free Survival; D019008:Drug Resistance, Neoplasm; D005260:Female; D006801:Humans; D053208:Kaplan-Meier Estimate; D016015:Logistic Models; D008279:Magnetic Resonance Imaging; D008297:Male; D008875:Middle Aged; D015999:Multivariate Analysis; D020360:Neoadjuvant Therapy; D009367:Neoplasm Staging; D016017:Odds Ratio; D012516:Osteosarcoma / Q000188:drug therapy* / Q000401:mortality / Q000473:pathology; D011237:Predictive Value of Tests; D016016:Proportional Hazards Models; D012189:Retrospective Studies; D012307:Risk Factors; D013997:Time Factors; D017211:Treatment Failure; D047368:Tumor Burden; D055815:Young Adult
chemical_list: D000970:Antineoplastic Agents