Patients with an increased time to treatment initiation have a poorer overall survival after definitive surgery for localized high-grade soft-tissue sarcoma in the extremity or trunk

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Abstract
Aims: Time to treatment initiation (TTI) is generally defined as the time from the histological diagnosis of malignancy to the initiation of first definitive treatment. There is no consensus on the impact of TTI on the overall survival in patients with a soft-tissue sarcoma. The purpose of this study was to determine if an increased TTI is associated with overall survival in patients with a soft-tissue sarcoma, and to identify the factors associated with a prolonged TTI. Methods: We identified 23,786 patients from the National Cancer Database who had undergone definitive surgery between 2004 and 2015 for a localized high-grade soft-tissue sarcoma of the limbs or trunk. A Cox proportional hazards model was used to examine the relationship between a number of factors and overall survival. We calculated the incidence rate ratio (IRR) using negative binomial regression models to identify the factors that affected TTI. Results: Patients in whom the time to treatment initiation was prolonged had poorer overall survival than those with a TTI of 0 to 30 days. These were: 31 to 60 days (hazard ratio (HR) 1.08, p = 0.011); 61 to 90 days (HR 1.11, p = 0.044); and 91 days (HR 1.22; p = 0.003). The restricted cubic spline showed that the hazard ratio increased substantially with a TTI longer than 50 days. Non-academic centres (vs academic centres; IRR ranging from 0.64 to 0.86; p < 0.001) had a shorter TTI. Those insured by Medicaid (vs private insurance; IRR 1.34), were uninsured (vs private insurance; IRR 1.17), or underwent a transition in care (IRR 1.62) had a longer TTI. Conclusion: A time to treatment initiation of more than 30 days after diagnosis was independently associated with poorer survival. The hazard ratio showed linear increase, especially if the TTI was more than 50 days. We recommend starting treatment within 30 days of diagnosis to achieve the highest likelihood of cure for localized high-grade soft-tissue sarcomas in the limbs and trunk, even when a patient needs to be referred to a specialist centre. Cite this article: Bone Joint J 2021;103-B(6):1142–1149.

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