Evaluating the median p-value method for assessing the statistical significance of tests when using multiple imputation
Austin PC, Eekhout I, van Buuren S. J Appl Stat. 2025; 52(6):1161-1176. Epub 2024; Oct 25.
Purpose — The impact of Ductal Carcinoma in Situ (DCIS) with multiple foci of microinvasion (MI) (≤ 1 mm) on the risks of local recurrence (LR) and invasive LR is unknown, leading to uncertainty if DCIS with multiple foci of MI requires more aggressive treatment. We report a population-based analysis of the impact of multiple foci of MI, confirmed by pathology review, on the 15-year risks of LR and invasive LR treated with breast-conserving surgery (BCS) ± radiotherapy (RT).
Methods — Cohort includes all women diagnosed with DCIS ± MI from 1994 to 2003 treated with BCS ± RT. Cox proportional hazards model was used to evaluate the impact of multiple foci of MI on the risks of LR and invasive LR, adjusting for covariates. The 15-year local and invasive local recurrence-free survival rates were calculated using the Kaplan–Meier method with differences compared by log-rank test.
Results — The cohort includes 2988 women treated by BCS; 2721 had pure DCIS (51% received RT), 267 had DCIS with one or more foci of MI (58% had RT). Median follow-up was 13 years. Median age at diagnosis was 58 years. On multivariable analyses, the presence of multiple foci of MI was associated with an increased risk of invasive LR (HR = 1.59, 95% CI 1.01–2.49, p = 0.04) but not DCIS LR (HR = 0.89, 95% CI 0.46, 1.76, p = 0.7). The 15-year invasive LRFS risks for cases with pure DCIS, with 1 focus or multiple foci of MI were 85.7%, 85.6%, 74.7% following treatment by BCS alone, 87.2%, 89.9%, and 77% for those treated with BCS + RT without boost and 89.2%, 91.3%, and 95% for women treated with BCS + RT and boost.
Conclusions — The presence of multiple foci of MI in DCIS is associated with higher 15-year risks of invasive LR after breast-conserving therapy compared to women with pure DCIS but treatment with whole breast and boost RT can mitigate this risk.
Rakovitch E, Sutradhar R, Lalani N, Nofech-Mozes S, Gu S, Goldberg M, Hanna W, Fong C, Paszat L. Breast Cancer Res Treat. 2019; 178(1):169-76. Epub 2019 Jul 19.
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