A prognostic and predictive computational pathology immune signature for ductal carcinoma in situ: retrospective results from a cohort within the UK/ANZ DCIS trial

作者：Haojia Li, Arpit Aggarwal, Paula Toro, Pingfu Fu, Sunil Badve, Jack M. Cuzick, Anant Madabhushi, Mangesh A. Thorat · 发表于：The Lancet Digital Health · 年份：2024 · DOI：10.1016/s2589-7500(24)00116-x · 被引用次数：15 · 研究领域：Cancer Immunotherapy and Biomarkers、Breast Cancer Treatment Studies、Inflammatory Biomarkers in Disease Prognosis

BackgroundThe density of tumour-infiltrating lymphocytes (TILs) could be prognostic in ductal carcinoma in situ (DCIS). However, manual TIL quantification is time-consuming and suffers from interobserver and intraobserver variability. In this study, we developed a TIL-based computational pathology biomarker and evaluated its association with the risk of recurrence and benefit of adjuvant treatment in a clinical trial cohort.MethodsIn this retrospective cohort study, a computational pathology pipeline was developed to generate a TIL-based biomarker (CPath TIL categories). Subsequently, the signature underwent a masked independent validation on H&E-stained whole-section images of 755 patients with DCIS from the UK/ANZ DCIS randomised controlled trial. Specifically, continuous biomarker CPath TIL score was calculated as the average TIL density in the DCIS microenvironment and dichotomised into binary biomarker CPath TIL categories (CPath TIL-high vs CPath TIL-low) using the median value as a cutoff. The primary outcome was ipsilateral breast event (IBE; either recurrence of DCIS [DCIS-IBE] or invasive progression [I-IBE]). The Cox proportional hazards model was used to estimate the hazard ratio (HR).FindingsCPath TIL-score was evaluable in 718 (95%) of 755 patients (151 IBEs). Patients with CPath TIL-high DCIS had a greater risk of IBE than those with CPath TIL-low DCIS (HR 2·10 [95% CI 1·39–3·18]; p=0·0004). The risk of I-IBE was greater in patients with CPath TIL-high DCIS tha...