Annals of Oncology | VOL. 33

Association of tumor-infiltrating lymphocytes with survival depends on primary tumor sidedness in stage III colon cancers (NCCTG N0147) [Alliance]

Publication Date Nov 1, 2022


Tumor-infiltrating lymphocytes (TILs) are a robust and independent prognostic variable in localized colon cancer. Given reported differences in molecular features and prognosis of right- versus left-sided tumors, we examined the association of TIL densities with patient survival by primary tumor sidedness in stage III cancers, including clinical low- (T1-3, N1) and high-risk (T4 and/or N2) groups. In a phase III trial of FOLFOX-based adjuvant chemotherapy, TIL densities were analyzed and dichotomized in colon carcinomas (N= 1532) based on a previously determined cut point optimized for disease-free survival (DFS). Right-sided tumors were defined as proximal to the splenic flexure. Associations of TILs and sidedness with 5-year DFS were examined using Kaplan-Meier methodology along with multivariable modeling and relative contribution analysis by Cox regression. Lower TIL densities were found in left- versus right-sided tumors (P < 0.0001). The association of TIL densities with DFS differed significantly by tumor sidedness (Pinteraction= 0.045). Overall, patient tumors with low (versus high) TILs had significantly poorer DFS in right-sided (hazard ratio 2.02, 95% confidence interval 1.45-2.82; Padj < 0.0001), but not left-sided tumors (Padj= 0.1731). Among clinical low-risk patients, low (versus high) TILs were adversely prognostic only in right-sided tumors (Padj= 0.0058). Among high-risk patients, low TILs were prognostic independent of sidedness (Padj < 0.025). The relative contribution of TILs to DFS was substantially gre...


Low Tumor-infiltrating Lymphocytes Tumor-infiltrating Lymphocytes Primary Tumor Sidedness Tumor-infiltrating Lymphocytes Densities Association Of Tumor-infiltrating Lymphocytes High Tumor-infiltrating Lymphocytes Localized Colon Cancer Disease-free Survival NCCTG N0147 Clinical Risk Group

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