AI Article Synopsis
- Tumor-infiltrating lymphocytes (TILs) play a significant role in predicting patient survival in stage III colon cancer, with variations based on whether the tumor is right- or left-sided.
- Lower TIL densities are found in left-sided tumors, and their impact on disease-free survival (DFS) is notably evident in right-sided tumors, particularly among patients considered at high clinical risk.
- The study highlights that TILs have a much greater contribution to DFS in right-sided tumors, making them an important factor in understanding cancer prognosis and guiding treatment strategies.
Article Abstract
Background: 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- (T, N) and high-risk (T and/or N) groups.
Patients And Methods: 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.
Results: 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 (P = 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; P < 0.0001), but not left-sided tumors (P = 0.1731). Among clinical low-risk patients, low (versus high) TILs were adversely prognostic only in right-sided tumors (P = 0.0058). Among high-risk patients, low TILs were prognostic independent of sidedness (P < 0.025). The relative contribution of TILs to DFS was substantially greater in right- versus left-sided tumors (24% versus 1.5%). In high-risk tumors, TILs had the highest relative contribution to DFS (42%) of all variables. In low-risk tumors, the contribution of TILs (16%) to DFS was second to KRAS.
Conclusions: The association of TIL densities with patient survival differed by primary tumor sidedness and clinical risk group, suggesting that TILs should be interpreted in this context among stage III colon cancers.
Gov Identifier: NCT00079274; https://clinicaltrials.gov/ct2/show/NCT00079274.
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| http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9882989 | PMC |
| http://dx.doi.org/10.1016/j.annonc.2022.07.1942 | DOI Listing |
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