Abstract:
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Use of optimal methods for addressing immortal time bias (ITB) arising from the variation in timing of initiation of radiotherapy is lacking in radiation oncology literature. The objective of the study is to illustrate ITB by using an oncology outcomes database and quantify through simulations the magnitude and direction of ITB when different analytic techniques are used. A cohort of 9,300 women who received neoadjuvant chemotherapy and underwent mastectomy with pathologically positive lymph nodes were accrued from the National Cancer Database (2004-2008). Multivariable Cox regression models comparing overall survival in patients receiving post-mastectomy radiation therapy with those who did not receive radiation showed a borderline significant treatment effect (HR: 0.94; 95% CI 0.87,1.00). Time-dependent (TD) and landmark (LM) methods estimated no treatment effect with HR: 0.98; 95%CI 0.91,1.05 and HR range: 0.90,1.25, respectively, with LM time from diagnosis ranging from 6-24 months. Simulation study based recommendation will be presented to reduce effect of ITB indicating that TD exposures need to be included as TD variables in hazard-based analyses.
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