Abstract
Simple SummaryThe immune response to colon cancer (CC) is highly variable among patients and is clinically relevant. In this study, we compared the immune response assessment for early-stage CC, as measured by Immunoscore (IS), to pathologist visual scoring of the CD3+ and CD8+ T-cell densities at the tumor site (T-score). The objectives were to determine the inter-observer agreement between pathologists and the concordance between the two methods. Agreement between pathologists was minimal to weak. Moreover, a weak concordance between the two methods was observed, leading to misclassification of 48% of cases by pathologist scoring. Due to the high level of immune infiltrate heterogeneity resulting in disagreement of interpretation among pathologists, IS is unlikely to be reproduced via non-standardized methods.Adjunction of immune response into the TNM classification system improves the prediction of colon cancer (CC) prognosis. However, immune response measurements have not been used as robust biomarkers of pathology in clinical practice until the introduction of Immunoscore (IS), a standardized assay based on automated artificial intelligence assisted digital pathology. The strong prognostic impact of the immune response, as assessed by IS, has been widely validated and IS can help to refine treatment decision making in early CC. In this study, we compared pathologist visual scoring to IS. Four pathologists evaluated tumor specimens from 50 early-stage CC patients and classified the CD3+ and CD8+ T-cell densities at the tumor site (T-score) into 2 (High/Low) categories. Individual and overall pathologist scoring of immune response (before and after training for immune response assessment) were compared to the reference IS (High/Low). Pathologists’ disagreement with the reference IS was observed in almost half of the cases (48%) and training only slightly improved the accuracy of pathologists’ classification. Agreement among pathologists was minimal with a Kappa of 0.34 and 0.57 before and after training, respectively. The standardized IS assay outperformed expert pathologist assessment in the clinical setting.
Highlights
The important role of immune response to the tumor has been demonstrated in numerous solid cancers [1–7], including Colon Cancer (CC) [8–16], with a high-level of tumor-infiltrating lymphocytes (TILs) being consistently associated with a favorable prognosis
We previously showed that of all immune cells involved in the in situ immune reaction, CD3+ and CD8+ T-lymphocyte cells provided the optimal combination for prognostic purpose
A predefined two-level classification (2 groups of recurrence risk) uses predefined cutoffs corresponding to IS-Low with a mean percentile of 0–25% (IS 0–1) and IS-Low to highly infiltrated tumors (IS-High) with a mean percentile of >25–100% (IS 2–4), consistent with the validated assay cutoffs determined in the Society for Immunotherapy of Cancer (SITC) study [6], with
Summary
The important role of immune response to the tumor has been demonstrated in numerous solid cancers [1–7], including Colon Cancer (CC) [8–16], with a high-level of tumor-infiltrating lymphocytes (TILs) being consistently associated with a favorable prognosis. Immunoscore® values are reported based on predefined cutoffs and given one of five category scores (IS 0 to IS 4) that are combined into two relevant clinical risk categories: IS Low (IS 0–1) and IS High (IS 2–4) These distinguish tumors with low versus high immune infiltration that are associated with high versus low risk of recurrence, respectively. Whose risk for recurrence was similar to that of low-risk stage II patients when not treated with chemotherapy [3,23,24] This strongly suggests a clinical utility for the IS assay to identify patients having a low biological recurrence risk despite the presence of pathologic high-risk features that might otherwise trigger adjuvant chemotherapy. These patients may avoid unnecessary treatment and its attendant toxicities. The performance of each of the two Cancers 2022, 14, 1170 methods in assessing the immune response status and the impact of misclassifications of the risk of recurrence on patient management and treatment decisions was evaluated
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