Taking biopsies in clinical trials: The WINTHER laboratory experience
Dr Paolo Nuciforo - Vall d'Hebron Institute of Oncology, Barcelona, Spain
Biopsies now for personalised medicine trials is something critical. Most of the trials usually take only tumour biopsies and assess alterations or differences in gene expression on tumour biopsy. In the WINTHER trials what we did is something different, it was an innovative study because we wanted to see how the tumours compare to the normal tissue and the normal gene expression and decide the treatment based on this difference and distance between tumour and normal.
What was the rationale for comparing tumour and matched normal biopsy samples in the WINTHER trial?
The rationale was that although this is very challenging because you have to do two biopsies in two different sites, the rationale was that each patient has its own genetic background. It’s important to take this into consideration and exclude this from a possible treatment decision. We want to see the tumour, we don’t want to see the genetic background, that is noise in this case.
How were dual biopsies taken and handled in the WINTHER trial?
Usually each centre in the study created a circuit with surgeon, radiologist, pathologist involved in this and a biologist that then process the samples. So samples were collected by the radiologist and then a technician or the pathology itself goes to take the samples, evaluate the samples for the quality and if the samples pass the quality correctly for the study these are analysed.
What results have been obtained so far?
As I said, this was an innovative trial and we recruited more than 200 patients. We managed to treat, at least to take a decision, for about half of the patients. We observed a big attrition rate here due to these dual biopsy procedures because of many reasons: that one of the two sites is not biopsiable, either the tumour or the normal site, or the biopsy was not correctly performed because the content in the tumour cellularity was not sufficient for analytical purposes, or the quality of the biopsy was not good enough to perform downstream analysis.
Could you comment on the overall success of taking dual biopsies over time?
We struggled a lot before finding the right way to do it. At the beginning of the study, during the first month, we had a failure rate that was close to 40% correlated to the biopsy failure. We now, after two years, we are now below 10% failure rate. So this is a great improvement.
What lessons can be learned from the WINTER lab experience for future trials?
There are a few lessons that can be learned from these studies. First that collecting fresh biopsies, the circuits need to be very well studied, very well defined. There needs to be a lot of communication between the people involved in the biopsy collection. Also it could be important, this is what WINTHER can tell us, to shift from a fresh frozen biopsy collection that is more logistically complex to do it to a formal and fixed processing of the sample; it is easier to handle for the different laboratories that are involved in the study.
Should dual biopsy become standard practice in personalised medicine cancer trials?
We can’t say that at the present moment. I think WINTHER will tell us if dual biopsies is the right way to go but we can’t say now.
What’s the take-home message regarding the WINTHER lab experience?
We’ll learn a lot with the WINTHER study. This learning curve that we had now makes the study easier to run because the failure rate is decreasing significantly. We saw that by addressing the different failure steps, that means developing better standard operating procedures, increasing the communication with radiologists, so with the people that take the biopsy and training of the person, all the people involved in this process, can really increase the success of the standard personalised medicine studies.
