Chemotherapy-Surgery Interval Effects on Tumor Necrosis and Outcome in Children and Young Adults With Osteosarcoma

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.

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 and 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.

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: 1.0-1.2; p = 0.016).

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.