Abstract
BackgroundIdentification of biomarkers associated with benefit of adjuvant chemotherapy in stage II/III colon cancer is an important task.MethodsVessel density (VD) and tumour stroma were analysed in a randomised-trial-derived discovery cohort (n = 312) and in a stage II/III group of a population-based validation cohort (n = 85). VD was scored separately in the tumour centre, invasive margin and peritumoral stroma compartments and quantitated as VD/total analysed tissue area or VD/stroma area.ResultsHigh stroma-normalised VD in the invasive margin was associated with significantly longer time to recurrence and overall survival (OS) (p = 0.002 and p = 0.006, respectively) in adjuvant-treated patients of the discovery cohort, but not in surgery-only patients. Stroma-normalised VD in the invasive margin and treatment effect were significantly associated according to a formal interaction test (p = 0.009). Similarly, in the validation cohort, high stroma-normalised VD was associated with OS in adjuvant-treated patients, although statistical significance was not reached (p = 0.051).ConclusionThrough the use of novel digitally scored vessel-density-related metrics, this exploratory study identifies stroma-normalised VD in the invasive margin as a candidate marker for benefit of adjuvant 5-FU-based chemotherapy in stage II/III colon cancer. The findings, indicating particular importance of vessels in the invasive margin, also suggest biological mechanisms for further exploration.
Highlights
Identification of biomarkers associated with benefit of adjuvant chemotherapy in stage II/III colon cancer is an important task
No statistically significant differences were found in Time to recurrence (TTR) or overall survival (OS) between the surgeryalone group and the group having surgery followed by adjuvant chemotherapy (Supplementary Fig. 2)
This study identifies high stroma-normalised Vessel density (VD) in the invasive margin as a candidate marker for identification of patients benefiting of adjuvant chemotherapy in stage II–III colon cancer
Summary
Identification of biomarkers associated with benefit of adjuvant chemotherapy in stage II/III colon cancer is an important task. METHODS: Vessel density (VD) and tumour stroma were analysed in a randomised-trial-derived discovery cohort (n = 312) and in a stage II/III group of a population-based validation cohort (n = 85). RESULTS: High stroma-normalised VD in the invasive margin was associated with significantly longer time to recurrence and overall survival (OS) (p = 0.002 and p = 0.006, respectively) in adjuvant-treated patients of the discovery cohort, but not in surgery-only patients. CONCLUSION: Through the use of novel digitally scored vessel-density-related metrics, this exploratory study identifies stromanormalised VD in the invasive margin as a candidate marker for benefit of adjuvant 5-FU-based chemotherapy in stage II/III colon cancer. Criteria for high risk of recurrence include a low number of sampled lymph nodes (
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