Examination of biomarkers in prostate biopsies from patients in two radiotherapy trials

Institute of Cancer Research and Royal Marsden HospitalDr Chris Parker£126,8012009 - 2011

Why we funded it

Dr Parker's previous research identified two tumour markers (VEGF and HIF-1 alpha) that seemed to identify men at higher risk of cancer recurrence after radiotherapy treatment. If confirmed in this larger study, these markers could help identify men for whom standard radiotherapy is likely to be less successful and who would be suitable for trials of more intensive treatment.

 

Scientific title

Evaluating tissue biomarkers of outcome: secondary analyses of MRC RT01 and PR07.

 

Research project summary

At present, all patients receiving radiotherapy are given the same dose. This research project aims to find better ways to predict prostate cancer treatment outcome so that in future, specific molecules referred to as 'markers' in the prostate cancer biopsy tissue could be identified to determine the most appropriate dose for each individual patient. Additionally, given that higher doses of radiotherapy improve disease control but also increase treatment side effects, there is a need to find markers that predict which patients will benefit from higher doses. Markers such as these could also identify patients who are unlikely to be cured by radiotherapy, and who would therefore be suitable for other treatment strategies.

Dr Chris Parker and his research team will begin by identifying patients for whom standard treatment has a poor outcome, and thus would be suitable for clinical trials of more aggressive treatments. For this, they will use prostate biopsy samples following ethical consent (further info below), taken between 1995 and 2005, from 1400 men who took part in two national prostate cancer radiotherapy trials. Information will be available regarding what has happened to these 1400 men, so it will be known in each case whether or not treatment was successful.

To enable best use of the tissue samples, the researchers will construct a 'tissue microarray' (TMA) - this is a technique which involves putting many tissue samples on one slide so they can be further investigated with different tests simultaneously.  Using the TMA, the team will test three promising markers (used in previous studies), to determine whether or not they can predict treatment outcome. These markers are associated either with tumour oxygen levels and blood supply, or with the mechanism of cell death.

The research team have based these studies on their previous findings from 200 prostate cancer cases in which they identified two markers which were associated with recurrence of cancer after treatment. They also identified a third marker that determined whether patients were more likely to benefit from higher doses of radiotherapy (further info below). The confirmation of their previous findings in another 1400 tissue samples would further validate these markers towards a method for individualising treatments for patients.

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Further info...

The 1400 biopsy samples, which were taken up to 13 years ago, are currently stored in pathology departments around the UK. With ethical approval, we will contact these departments, in writing and, if necessary, by telephone, to collect the samples. We anticipate that it will take approximately six months to collect the samples, six months to make the TMAs, six months to score the markers, and six months to analyse and disseminate the results.

We expect to confirm or refute our previous findings based on a study of around 200 cases. We found two markers (VEGF and HIF−1 alpha) that identified patients at high risk of recurrence after treatment. If confirmed in this larger study, these markers could identify patients who would be suitable for trials of more intensive treatment. We also found that a third marker, Bcl-2, identified patients more likely to benefit from higher doses of radiotherapy. If confirmed, patients with Bcl-2 positive tumours could receive high dose treatment, whereas patients with Bcl−2 negative tumours could choose to receive standard dose treatment which has a lower risk of side-effects.