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 poorerfor patients who had had a delay of greater than twenty-one days before the resumption of chemotherapy compared with those who had had a shorterdelay (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.
Bibliographical noteFunding Information:
Limited funding for statistical support was provided by discretionary funds from the Mayo Clinic Department of Pediatric and Adolescent Medicine. The Children's Oncology Group (COG) trial INT-0133, from which the majority of the patients analyzed in this trial originated, was supported by COG Grant CA 98543. A complete listing of grant support for research conducted by COG and POG before initiation of the COG grant in 2003 is available online at: http://www.childrensoncologygroup.org/admin/grantinfo.htm .