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Effects of Neoadjuvant Chemotherapy on Image-Directed Planning of Surgical Resection for Distal Femoral Osteosarcoma

Jones, Kevin B. MD; Ferguson, Peter C. MD; Lam, Brian MD; Biau, David J. MD, PhD; Hopyan, Sevan MD, PhD; Deheshi, Benjamin MD; Griffin, Anthony M. MS; White, Lawrence M. MD; Wunder, Jay S. MD

Journal of Bone & Joint Surgery - American Volume: 1 August 2012 - Volume 94 - Issue 15 - p 1399–1405
doi: 10.2106/JBJS.K.00971
Scientific Articles
Supplementary Content

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.

1Department of Orthopaedics and the Center for Children’s Cancer Research, Huntsman Cancer Institute, University of Utah, 2000 Circle of Hope Drive, Room 4263, Salt Lake City, UT 84112. E-mail address: kevin.jones@hci.utah.edu

2University Musculoskeletal Oncology Unit (P.C.F., D.J.B., B.D., A.M.G., and J.S.W.) and the Department of Medical Imaging (B.L. and L.M.W.), Mount Sinai Hospital, 600 University Avenue, Toronto, ON M5G 1X5, Canada

3Division of Orthopaedics, The Hospital for Sick Children, 555 University Avenue, Toronto, ON M5G 1X8, Canada

Copyright 2012 by The Journal of Bone and Joint Surgery, Incorporated
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