The following is the summary of “Association of tumor-infiltrating lymphocytes with survival depends on primary tumor sidedness in stage III colon cancers (NCCTG N0147) [Alliance]” published in the november 2022 issue of Oncology by Ardestani, et al.

The presence of tumor-infiltrating lymphocytes (TILs) is a strong and independent predictive predictor in patients with stage I colon cancer. We investigated the relationship between TIL densities and patient survival by primary tumor sidedness in stage III cancers, including clinical low- (T1-3, N1) and high-risk (T4 and/or N4) groups, because of previously reported differences in molecular features and prognosis between right- and left-sided tumors.

TIL densities were evaluated and dichotomized in colon carcinomas (N=1532) using a previously determined cut point optimized for disease-free survival in a phase III study of FOLFOX-based adjuvant chemotherapy (DFS). Tumors on the patient’s right side were classified as being located above the splenic flexure. Kaplan-Meier analysis, multivariate modeling, and relative contribution analysis using Cox regression were used to investigate the links between TILs and 5-year DFS. TIL densities were significantly lower in left-sided tumors than right-sided tumors (P<0.0001). TIL densities were found to have a significantly different relationship with DFS depending on the sidedness of the tumor (Pinteraction =0.045). Overall, right-sided (hazard ratio 2.02, 95% confidence interval 1.45-2.82; Padj <0.0001) but not left-sided (Padj =0.1731) tumors from patients with low (vs. high) TILs had significantly lower DFS. Low (vs high) TILs were only adversely predictive in right-sided tumors among clinical low-risk patients (Padj =0.0058). 

Low TILs were predictive regardless of sidedness in high-risk patients (Padj <0.025). TILs had a far larger impact on DFS in right-sided tumors (24% vs. 1.5%) than in left-sided tumors (6%). TILs contributed to DFS in high-risk tumors more than any other variable (42%). TILs contributed to DFS in low-risk tumors by a smaller percentage (16%) than KRAS (23%) in these cases. The TIL density-survival correlation varied by initial tumor sidedness and clinical risk group, indicating that TILs need to be interpreted in this setting for stage III colon malignancies.