F. F. Xu1, S. F. Zheng2, L. Cao1, C. Wang3, and J. Y. Chen1; 1Department of Radiation Oncology, Ruijin Hospital, Shanghai Jiaotong University School of Medicine, Shanghai, China, 2Department of Pathology, Ruijin Hospital, Shanghai Jiaotong University School of Medicine, Shanghai, China, 3Department of Pathology, Ruijin Hospital, Shanghai Jiaotong University School of Medicine, shanghai, China
Purpose/Objective(s): This study aims to identify the role of tumor immune microenvironment in ductal carcinoma in situ (DCIS) in predicting risk of recurrence and benefit of whole breast irradiation (WBI). Materials/
Methods: Different subtypes of tumor infiltrating lymphocytes (TILs), tumor associated macrophages (TAMs) and tertiary lymphoid structures (TLSs) were determined in tumor tissues of DCIS cohort who received breast-conserving surgery (BCS). All the TILs and TAMs subtypes were evaluated by the average numbers of touching-TILs/TAMs which defined as TILs/ TAMs touching or within one lymphocyte/macrophage cell thickness from the malignant ducts’ basement membrane. Results: In total, 165 patients were enrolled in this analysis with 113 patients received WBI. After a median follow-up of 73.7 months, 15 ipsilateral breast tumor recurrence (IBTR) events occurred with 6 invasive-IBTRs. Nine out of 15 IBTRs occurred outside of the original quadrant (elsewhere failure event, EFE). The univariate analyses showed that dense TILs subtype, TAMs and TLS were significantly associated with higher IBTR (all p <0.05). High ratios of CD4+/CD8+, Treg/CD4+ and Treg/CD8+ were also found to be prognostic factors for higher IBTR (all p<0.01). We then performed least absolute shrinkage and selection operator (LASSO) and multivariate Cox regression analyses to identify the variables associated with IBTR. The ER negative status, high ratios of CD4+/CD8+, dense CD68+ TAMs, sparse CD8+ T cell and dense mature TLS remained independent risk factors of IBTR (all p<0.05) to develop a nomogram. Points of nomogram were defined as immune microenvironment score (IMS) which divided all patients into low-, intermediate- and high-risk groups. Significant differences in IBTR existed among these three risk subgroups (5y-rate: 0.0% vs. 11.4% vs. 72.2%, p<0.01). For the whole cohort, the benefit of WBI was found only in the intermediate-risk subgroup (5y-rate of IBTR: 7.0% vs. 22.0%, p=0.04). With respect to EFE, WBI also significantly reduced the rate from 16.4% to 2.3% (p=0.01) in the intermediate-risk group while not in the low- and high-risk group. Conclusion: Assessment of overall immune cells subtypes provides a tool for comprehensive evaluation of the DCIS immune microenvironment. The benefit of WBI was only observed in the intermediate-risk group. Patients in the high-risk group showed an increased risk of IBTR regardless of the receipt of WBI.
