Mayo Clinic, Rochester, MN
Bahar Saberzadeh Ardestani , Nathan R. Foster , Hee Eun Lee , Qian Shi , Steven R Alberts , Thomas C. Smyrk , Frank A. Sinicrope
Background: Tumor-infiltrating lymphocytes (TILs) are significantly associated with clinical outcomes in patients with colon cancer. However, the potential for a differential effect of TILs on prognosis based on primary tumor sidedness has not been studied. We determined the interaction between TILs and tumor sidedness in relationship to disease-free survival (DFS). Methods: We analyzed data on TIL densities by primary tumor sidedness in 1532 stage III colon carcinomas from participants in a phase III trial of FOLFOX-based adjuvant chemotherapy (NCCTG N0147). TIL densities were dichotomized as low or high (≤3 /HPF) based on an optimized cutoff previously identified for DFS in this cohort. Right-sided tumors were defined as proximal to the splenic flexure. Analysis of TILs and sidedness with DFS were examined using Kaplan-Meier methodology and multivariable Cox regression. Results: Overall, tumors with high vs low TILs had the best DFS [HRadj: 0.58 (95%CI: 0.45-0.74); Padj<0.0001]. The association of TIL densities with 5-yr DFS differed significantly by primary tumor sidedness (Pinteraction (adj) = 0.045). Among right-sided tumors, high vs low TILs were significantly associated with improved DFS (Padj<0.0001)[Table]. Among left-sided tumors, however, DFS did not differ significantly for high vs low TILs (Padj =0.173)[Table]. Similar results for TILs and DFS by sidedness were found for pMMR cancers. We then analyzed our data in low risk (T1-3, N1) and high risk (T4 and/or N2) tumors. Among low risk tumors, high vs low TILs was significantly associated with improved 5-yr DFS only in right-sided tumors (Padj =0.006) [Table]. Among high risk tumors, high vs low TILs were significantly associated with better DFS in both right-sided (Padj<0.001) and left-sided (Padj =0.024) tumors. Conclusions: Overall, tumors with high TIL densities had significantly better DFS in right-sided but not left-sided cancers. Among low risk patients, the association of high TILs with better DFS was limited to right-sided tumors. These findings suggest that TILs should be interpreted by sidedness for prognostication. ClinicalTrials.gov Identifier: NCT00079274.
Population | Tumor sidedness | 5-year Free | Disease Survival | HR (95%CI) | P-value |
---|---|---|---|---|---|
High TILs | Low TILs | ||||
Overall | Right | 77% | 57% | 0.50 (0.36-0.69) | <0.0001 |
Left | 76% | 69% | 0.77 (0.52-1.13) | 0.173 | |
Low risk | Right | 84% | 70% | 0.48 (0.28-0.83) | 0.006 |
Left | 79% | 78% | 0.97 (0.57-1.66) | 0.914 | |
High risk | Right | 68% | 44% | 0.49 (0.32-0.75) | 0.0004 |
Left | 71% | 60% | 0.54 (0.30-0.96) | 0.024 |
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Abstract Disclosures
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