ABSTRACT
Background/Objective: Osteosarcoma treatment incorporates
chemotherapy and surgery. Resection of the primary tumor usually occurs
after induction chemotherapy. Occasionally, scheduling challenges and
medical complications result in delay. The goal of this study is to
determine if an increased interval between completion of neoadjuvant
therapy and surgical resection correlates with decreased tumor necrosis
and inferior outcomes in children and young adults with osteosarcoma.Design/Method: We conducted a retrospective chart review of 121
patients age less than 40 years diagnosed with osteosarcoma treated at a
single tertiary medical center between 2000-2022. Inclusion criteria
included receipt of two cycles of neoadjuvant methotrexate, cisplatin,
and doxorubicin. Association of the interval from completion of
induction chemotherapy to resection with tumor necrosis (Spearman’s
correlation) and outcomes (multivariable Cox hazard regression) were
analyzed.Results: There was no significant correlation between interval
length and tumor necrosis. However, patients with an interval greater
than 16 days had lower 5-year event free survival (p=0.019).
Multivariable adjusted analysis of patients with initially localized
disease revealed that each day increase in interval length corresponds
with a 1.1 times greater hazard of having an event (95% CI: 1.02 to
1.19; p=0.016).Conclusion: Delays in local control were not associated with
tumor necrosis. This is consistent with the hypothesis that tumor
necrosis is a biologic marker of a tumor’s sensitivity to chemotherapy
and may not be affected by minor regimen aberrations. However, surgical
delay from completion of induction chemotherapy may confer worse
outcomes. Longer intervals generally confer worse outcomes in patients
with initially localized disease.