CHEMOTHERAPY-SURGERY INTERVAL EFFECTS ON TUMOR NECROSIS AND OUTCOME IN
CHILDREN AND YOUNG ADULTS WITH OSTEOSARCOMA
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.