Contribution Of Tumor Stroma Ratio To A Better Selection Of Stage Ii Colon Cancer Patients Into High And Low Risk Groups: A Population Based Study.

Journal of Clinical Oncology(2016)

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3582 Background: Despite the well-known uncertainty on efficiency, adjuvant chemotherapy is today offered to a subgroup of stage II colon cancer patients with high risk of recurrence, currently based on T-stage, lymphovascular invasion, malignancy grade, perforation and inadequate lymph node sampling. Recent research has focused on the stroma in epithelial tumors as a prognostic biomarker in various malignant epithelial neoplasms, including colon cancer. Patients with a high percentage of stroma within the tumor, determined by the Tumor-Stroma-Ratio (TSR), show a poor prognosis. Methods: The study included all patients diagnosed with stage II colon cancer in Denmark in 2003. Patients receiving adjuvant chemotherapy were excluded. The TSR was scored on routine H&E tissue sections. Stroma-high (> 50% stroma) and stroma-low (≤ 50% stroma) groups were evaluated regarding Overall Survival (OS) and Recurrence-Free Cancer Specific Survival (RF-CSS). The currently defined risk groups were stratified according to TSR, and a prognostic index was created using the coefficients obtained from a collective multiple Cox regression, based on RF-CSS data. Results: Of 580 patients, 107 (18.4%) were scored as stroma-high and 473 (81.6%) as stroma-low. TSR showed prognostic impact in both univariate (OS: p= 0.0075, HR = 1.58 (1.14-2.20), RF-CSS: p< 10-5, HR = 2.47 (1.53-3.98)) and multiple COX analyses (OS: p= 0.0007, HR = 1.66 (1.24-2.22), RF-CSS: p= 0.0001, HR = 2.22 (1.58-3.27)). When comparing the generated RF-CSS risk index based on traditional high-risk, and including the TSR, the TSR contributed significantly to the index, p= 0.0001. When stratifying according to TSR, stroma high patients showed significantly poorer 5 years RF-CSS in both low (stroma high: 76%, stroma low; 89%; p < 10-5) and high (stroma high: 49%, stroma low: 71%; p = 0.01) risk groups. Conclusions: This population based study confirms the prognostic importance of TSR in both uni- and multivariate analyses. Furthermore, including TSR in the current risk assessment of patients with stage II colon cancer, may contribute to a more appropriate definition of high and low risk groups than todays practice.
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