OCCLUDES Study

Ovarian cancer and capillary density of the skin

Chief Investigator	Dates	Funding Stream	Amount
Dr Gemma Cass	Apr-18 to Jun 2019	A&B Autumn 2017	£14,415

Introduction

Ovarian cancer is the seventh most common cancer in women.  The majority of cases present with advanced disease and survival is poor with only 15-20% of women living beyond 5 years.  However, trials are emerging to test new drugs which prevent the formation of new blood vessels (angiogenesis).  The hope is that these drugs will stop cancers, as growth and spread of cancer depends on angiogenesis, but there is a reluctance to use these drugs due to side effects and cost effectiveness.  At present it is not clear who may benefit from them and when it is best to use them in the current treatment regime of chemotherapy and surgery.

The number of small blood vessels in the skin (skin capillary density) and in the tumour, may be a marker of angiogenesis.  I have been measuring this capillary density and have noticed changes during the course of treatment.  Markers in the blood that are linked with angiogenesis may also change, and I collected 110 blood samples on ovarian cancer patients to be analysed.  To date this grant has been fundamental to enable me to analyse over 250 serum samples as part of the OCCLUDES study. 

Summary of work carried out

This research project recruited and followed up 64 patients with ovarian cancer (original target was 50) and measuring skin capillary density, blood vessels in the tumour and blood samples.  The tests and blood sampling are carried out five times for each participant, at diagnosis, after 3 cycles of chemotherapy, at 48 hrs and 2 weeks post-surgery and again 6 weeks after the last chemotherapy.  This grant has enabled me to conduct ELISAs for various angiogenic markers to ascertain a biomarker of disease response in ovarian cancer.  All laboratory tests have been concluded and tissue samples and microvessel density has also been completed.  Reduction in skin capillary density occurs in women on Bevacizumab and I am currently conducting statistical analysis on the results of the serum ELISAs to ascertain any trends in angiogenic markers and whether any similarly fall on Bevacizumab treatment.  From analysis of micro vessel density in the tumour, it appears that CD34 affectively stains the tissue to measure vessels at high magnification.  A high microvessel density appears to be associated with a higher stage of disease at initial analysis but more statistical analysis is ongoing.

In the long term we aim to have impact in the design of the future ICON trials which are part of a national programme of trials into the treatment for ovarian cancer.  It is our hypothesis that not all ovarian cancers are the same and that some will respond better to drugs that prevent angiogenesis than others.  We hope to provide proof of concept of how screening for patients with high angiogenesis could take place.  This could then be incorporated into the baseline and screening data to allow a more targeted approach to ovarian cancer treatment.

Main findings and impact to date

Skin capillary density and angiogenic markers in the blood are useful in predicting response and outcomes in ovarian cancer.

This study has validated a foundation for further research into the use of biomarkers in ovarian cancer to enable a personalised approach to care to ensure the best outcome for patients.

Project outputs

The project is currently in the completion stages of analysis of results.  By one year post the end date I will have submitted my higher degree and peer review articles

Further funding applications

The work has contributed to a Cancer Research Fund grant award of £5000.

Once analysis of results has been completed I would hope to develop a proposal for an NIHR EME grant.

Other project outcomes

This project is part of my higher degree and developed my skills in managing a research project, patient consent, ethical considerations and basic science techniques.  I feel fully capable to manage other studies and lead as a principal or chief investigator on other projects which is already invaluable in my new role for UHBT as a subspecialist registrar.  These skills will also enhance my work as future NHS Consultant and therefore improve patient care.  This project has resulted in established links with the University of Bristol which are ongoing and this project has also formed part of a proposal for a BSC student.

Updated by R&I 17.07.2019