Abstract 126P
Background
A desmoplastic colorectal tumor stroma, characterized by excess turnover of the fibroblast derived collagens type III and VI, can lead to reduced drug-uptake and poor treatment response. We investigated the association between blood-based biomarkers of collagen type III and VI and overall survival (OS) in patients with metastatic colorectal cancer (mCRC) treated with chemotherapy and bevacizumab.
Methods
Serum samples were collected from 252 patients with mCRC prior to treatment with bevacizumab and chemotherapy. Serum concentrations of biomarkers (collagen fragments) reflecting formation of collagen type III (PRO-C3) and VI (PRO-C6) and degradation of collagen type VI (C6Mand C6Mα3) were determined by ELISA. The collagen biomarkers were evaluated for associations with OS, individually, combined, and after adjusting for carcinoembryonic antigen (CEA), lactate dehydrogenase (LDH) and performance status (PS).
Results
High baseline levels (>median) of each collagen biomarker were significantly associated with shorter OS (PRO-C3: HR=2.0, 95%CI=1.54-2.63; PRO-C6: HR=1.6, 95%CI=1.24-2.11; C6M: HR=1.4, 95%CI=1.05-1.78; C6Mα3: HR=1.6, 95%CI=1.16-2.07). PRO-C3 and PRO-C6 remained significant after adjustment for CEA, LDH and PS. Weak correlations were seen between the collagen biomarkers (Spearman, r=0.03-0.59) and combining all improved prognostic capacity (HR=3.6, 95%CI=2.30-5.76).
Conclusions
Circulating collagen biomarkers were predictive of shorter OS in patients with mCRC and measuring different collagen epitopes were complementary compared to either alone. This supports that collagen composition and fibroblast biology is important in CRC. Collagen turnover measured non-invasively may assist in clinical decision making and help in guiding future treatment strategies for patients with mCRC.
Clinical trial identification
Editorial acknowledgement
Legal entity responsible for the study
Nordic Bioscience A/S.
Funding
Nordic Bioscience A/S.
Disclosure
S. Kehlet: Leadership role: Nordic Bioscience A/S. C. Jensen: Full/Part-time employment: Nordic Bioscience A/S. J. Erler: Shareholder/Stockholder/Stock options: LOXiPharm. M.A. Karsdal: Leadership role, Shareholder/Stockholder/Stock options, Full/Part-time employment: Nordic Bioscience A/S. J. Mortensen: Full/Part-time employment: Nordic Bioscience A/S. N. Willumsen: Leadership role, Full/Part-time employment: Nordic Bioscience A/S. All other authors have declared no conflicts of interest.