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219 Skin capillary density as a novel biomarker of cytotoxic and bevacizumab treatment in ovarian cancer: a prospective clinical trial
  1. G Cass1,
  2. R Lewes2,
  3. J Pawade3 and
  4. C Newton1
  1. 1University Hospitals Bristol NHS Foundation Trust Headquarters, UK
  2. 2University of Bristol, UK
  3. 3North Bristol NHS Trust, UK


Introduction/Background*The role of angiogenesis in ovarian cancer progression is well established. Bevacizumab has been demonstrated to have a survival advantage for a subgroup of women with stage 4 disease and those who have suboptimal debulking surgery. The search for a biomarker of Bevacizumab efficacy is elusive. Skin capillary density (SCD) is a dynamic marker that may provide a surrogate indicator of angiogenic activity and alter in response to treatment in cancer patients.

Methodology A cohort of 50 women with stage 3 and 4 high grade serous cancer were enrolled over 2 years at University Hospitals Bristol, UK. Written informed consent was obtained from each participant. SCD was measured at baseline and at specified time points during treatment. Serum angiogenic markers (VEGF and Ang 1) and tissue micro vessel density and proliferation (ki67) were also measured and correlated with SCD. Longitudinal and survival analysis was conducted to ascertain changes in SCD during treatment and association with cancer outcomes including surgical resection, overall survival (OS) and progression free survival (PFS). Correlations were investigated between SCD and tumour vascularity.

Result(s)*Capillary rarefaction occurred in all patients during cytotoxic treatment (p=<0.001). This correlated with a decline in VEGF and Ang 1 (p=0.02, p=<0.001). Rarefaction was greater in the subgroup of patients who received Bevacizumab and was strongly correlated with a rise in blood pressure. Baseline SCD was strongly associated with the outcome of debulking surgery (p=0.001). Patients who had a smaller reduction in skin capillary density during treatment had a worse PFS (p=0.01). Vessel density in the tumour reduced after treatment and was more significant in patients who received Bevacizumab. There was no correlation between SCD and tumour vascularity.

Conclusion*Skin capillary rarefaction occurs during both cytotoxic and anti angiogenic treatment in women with ovarian cancer. SCD could be useful as a biomarker of response to treatment and cancer outcomes and act as a surrogate marker of angiogenesis in cancer. It is a reproducible, cheap and non-invasive investigation that is acceptable to patients and shows promise in helping to guide treatment and prognostic information in the era of personalised medicine.

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