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Effect of Time to Resumption of Chemotherapy After Definitive Surgery on Prognosis for Non-Metastatic Osteosarcoma
Hamayun Imran, MD, MSc1; Felicity Enders, PhD, MPH2; Mark Krailo, PhD3; Franklin Sim, MD2; Scott Okuno, MD2; Douglas Hawkins, MD4; Joseph Neglia, MD, MPH5; R. Lor Randall, MD6; Richard Womer, MD7; Leo Mascarenhas, MD, MS8; Carola A.S. Arndt, MD2
1 University of South Alabama, 1504 Springhill Avenue, Room 5231, Mobile, AL 36604
2 Mayo Clinic, 200 First Street S.W., Rochester, MN 55905. E-mail address for C.A.S. Arndt: carndt@mayo.edu
3 Children's Oncology Group-Operations Center, Statistics, 440 East Huntington Drive, 4th Floor, Arcadia, CA 91006
4 Children's Hospital and Regional Medical Center, 4800 Sand Point Way, Mail Stop B6553, Seattle, WA 98105
5 Division of Pediatric Hematology/Oncology, University of Minnesota Cancer Center, Room D-557 Mayo Building, Mayo Mail Code 484, 420 Delaware Street, S.E., Minneapolis, MN 55455
6 Department of Orthopedic Surgery, Primary Children's Hospital, University of Utah, 100 North Medical Drive, Salt Lake City, UT 84113-1100
7 Division of Oncology, Children's Hospital of Philadelphia, 324 South 34th Street, Philadelphia, PA 19104
8 Childrens Hospital Los Angeles, University of Southern California Keck School of Medicine at University of Southern California, 4650 Sunset Boulevard, Mail Stop 54, Los Angeles, CA 90027
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Presented, in part, at the Annual Meeting of the Musculoskeletal Tumor Society, St. Louis, Missouri, May 11, 2007.
Disclosure: The authors did not receive any outside funding or grants in support of their research for or preparation of this work. Neither they nor a member of their immediate families received payments or other benefits or a commitment or agreement to provide such benefits from a commercial entity. No commercial entity paid or directed, or agreed to pay or direct, any benefits to any research fund, foundation, division, center, clinical practice, or other charitable or nonprofit organization with which the authors, or a member of their immediate families, are affiliated or associated.

The Journal of Bone and Joint Surgery, Inc.
J Bone Joint Surg Am, 2009 Mar 01;91(3):604-612. doi: 10.2106/JBJS.H.00449
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Background: The dose intensity of chemotherapy has been described as affecting the outcome of the treatment of a number of different types of tumors. A delay in the resumption of chemotherapy after definitive surgery for the treatment of osteosarcoma can decrease the overall dose intensity. The goal of this study was to assess the prognostic significance of the time to resumption of chemotherapy after definitive surgery in patients with localized osteosarcoma in an extremity.

Methods: The relationships of the time between definitive surgery and resumption of chemotherapy with death and adverse events in 703 patients with a localized resectable osteosarcoma in an extremity (556 treated in the Children's Oncology Group [COG] Study [INT 0133] and 147 treated at five tertiary care cancer centers) were assessed with use of Cox proportional hazards models.

Results: The twenty-fifth, fiftieth, and seventy-fifth percentiles of time from definitive surgery to resumption of chemotherapy were twelve, sixteen, and twenty-one days, respectively. Overall survival was poorer for patients who had had a delay of greater than twenty-one days before the resumption of chemotherapy compared with those who had had a shorter delay (hazard ratio = 1.57 [95% confidence interval = 1.04 to 2.36]; p = 0.03). Of seventy-one COG-study patients with postoperative complications, 32% (twenty-three) had a delay of more than twenty-one days before resumption of chemotherapy, but 20% (eighty-nine) of 444 patients with no complications had a similar delay.

Conclusions: In this retrospective analysis, increased time from the definitive surgery to the resumption of chemotherapy was found to be associated with an increased risk of death of patients with localized osteosarcoma in an extremity. Within the limitations of a retrospective study, the data indicate that it is best to resume chemotherapy within twenty-one days after definitive surgery. Surgeons, oncologists, patients, and those responsible for scheduling need to work together to ensure timely resumption of chemotherapy after surgery.

Level of Evidence: Prognostic Level II. See Instructions to Authors for a complete description of levels of evidence.

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    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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