title: Effects of neoadjuvant chemotherapy on image-directed planning of surgical resection for distal femoral osteosarcoma.
abstract: BACKGROUND
  Standard therapy for localized osteosarcoma includes neoadjuvant chemotherapy preceding local control surgery, followed by adjuvant chemotherapy. When limb-salvage procedures were being developed, preoperative chemotherapy allowed a delay in definitive surgery to permit fabrication of custom endoprosthetic reconstruction implants. One rationale for its continuation as the care standard has been the perception that it renders surgery easier and safer. Our objective was to compare surgical procedures planned on the basis of magnetic resonance images (MRIs) of distal femoral osteosarcomas acquired before neoadjuvant chemotherapy with surgical procedures planned on the basis of MRIs acquired after neoadjuvant chemotherapy as a measure of the surgically critical anatomic effects of the chemotherapy.
  
  
  METHODS
  Twenty-four consecutive patients with distal femoral osteosarcoma had available digital MRIs preceding and following neoadjuvant chemotherapy. Thorough questionnaires were used to catalogue surgically critical anatomic details of MRI-directed surgical planning. Four faculty musculoskeletal oncologic surgeons and two musculoskeletal radiologists evaluated the blinded and randomly ordered MRIs. Interrater and intrarater reliabilities were calculated with intraclass correlation coefficients. The Student t test and chi-square test were used to compare pre-chemotherapy and post-chemotherapy continuous and categorical variables on the questionnaire. Mixed-effect regression models were employed to compare surgical procedures planned on the basis of pre-chemotherapy MRIs and with those planned on the basis of post-chemotherapy MRIs.
  
  
  RESULTS
  The blinded reviews generated strong intraclass correlation coefficients for both interrater (0.772) and mean intrarater (0.778) reliability. The MRI-planned resections for the majority of tumors changed meaningfully after chemotherapy, but in inconsistent directions. On the basis of mixed-effect regression modeling, it appeared that more amputations were planned on the basis of post-chemotherapy MRIs. No other parameters differed in a significant and clinically meaningful fashion. Surgeons demonstrated their expectation that neoadjuvant chemotherapy would improve resectability by planning more radical surgical procedures on the basis of scans that they predicted had been obtained pre-chemotherapy.
  
  
  CONCLUSIONS
  Surgeons can reliably record the anatomic details of a planned resection of an osteosarcoma. Such methods may be useful in future multi-institutional clinical trials or registries. The common belief that neoadjuvant chemotherapy increases the resectability of extremity osteosarcomas remains anecdotally based. Rigorous assessment of this phenomenon in larger cohorts and at other anatomic sites as well as re-evaluation of other arguments for neoadjuvant chemotherapy should be considered.
authors.affiliation: Department of Orthopaedics and the Center for Children's Cancer Research, Huntsman Cancer Institute, University of Utah, Salt Lake City, UT 84112, USA. kevin.jones@hci.utah.edu
authors.forename: Kevin B
authors.initials: KB
authors.lastname: Jones
authors.forename: Peter C
authors.initials: PC
authors.lastname: Ferguson
authors.forename: Brian
authors.initials: B
authors.lastname: Lam
authors.forename: David J
authors.initials: DJ
authors.lastname: Biau
authors.forename: Sevan
authors.initials: S
authors.lastname: Hopyan
authors.forename: Benjamin
authors.initials: B
authors.lastname: Deheshi
authors.forename: Anthony M
authors.initials: AM
authors.lastname: Griffin
authors.forename: Lawrence M
authors.initials: LM
authors.lastname: White
authors.forename: Jay S
authors.initials: JS
authors.lastname: Wunder
mesh_terms: D000671:Amputation, Surgical / Q000706:statistics & numerical data; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use; D017024:Chemotherapy, Adjuvant; D016009:Chi-Square Distribution; D005260:Female; D005266:Femoral Neoplasms / Q000188:drug therapy* / Q000473:pathology / Q000601:surgery*; D006801:Humans; D008279:Magnetic Resonance Imaging; D008297:Male; D020360:Neoadjuvant Therapy; D012516:Osteosarcoma / Q000188:drug therapy* / Q000473:pathology / Q000601:surgery*; D012044:Regression Analysis; D015203:Reproducibility of Results; D012189:Retrospective Studies; D025321:Surgery, Computer-Assisted / Q000379:methods*; D011795:Surveys and Questionnaires; D016896:Treatment Outcome