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Scientific Articles   |    
Effects of Neoadjuvant Chemotherapy on Image-Directed Planning of Surgical Resection for Distal Femoral Osteosarcoma
Kevin B. Jones, MD1; Peter C. Ferguson, MD2; Brian Lam, MD2; David J. Biau, MD, PhD2; Sevan Hopyan, MD, PhD3; Benjamin Deheshi, MD2; Anthony M. Griffin, MS2; Lawrence M. White, MD2; Jay S. Wunder, MD2
1 Department 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
2 University 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
3 Division of Orthopaedics, The Hospital for Sick Children, 555 University Avenue, Toronto, ON M5G 1X8, Canada
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Investigation performed at the University of Toronto, Toronto, Ontario, Canada



Disclosure: None of the authors received payments or services, either directly or indirectly (i.e., via his or her institution), from a third party in support of any aspect of this work. None of the authors, or their institution(s), have had any financial relationship, in the thirty-six months prior to submission of this work, with any entity in the biomedical arena that could be perceived to influence or have the potential to influence what is written in this work. Also, no author has had any other relationships, or has engaged in any other activities, that could be perceived to influence or have the potential to influence what is written in this work. The complete Disclosures of Potential Conflicts of Interest submitted by authors are always provided with the online version of the article.

Copyright © 2012 by The Journal of Bone and Joint Surgery, Inc.
J Bone Joint Surg Am, 2012 Aug 01;94(15):1399-1405. doi: 10.2106/JBJS.K.00971
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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.

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    Accreditation Statement
    These activities have been planned and implemented in accordance with the Essential Areas and policies of the Accreditation Council for Continuing Medical Education (ACCME) through the joint sponsorship of the American Academy of Orthopaedic Surgeons and The Journal of Bone and Joint Surgery, Inc. The American Academy of Orthopaedic Surgeons is accredited by the ACCME to provide continuing medical education for physicians.
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