ESTRO 2010, 12-16 September, Barcelona

Professor Jordi Giralt - Vall D'Hebron University Hospital, Barcelona, Spain

The importance of good practice in radiotherapy

You have ten abstracts in posters in this session, so you’re obviously a very, very busy man and you’re really doing a lot of very good translational research as well. You were wanting to tell us a little bit about the head and neck work that you’re doing here?

Yes, this is an outstanding trial because in this trial we address the question of quality controlled radiotherapy and its impact on outcome. For the first time we were able to prove that those patients that were not properly treated according to quality assurance, they have a reduction in survival, a 20% reduction in overall survival. So it’s important information we need to address and we need to share with other people to know that.

So just tell me what you did. You showed that if the quality of the radiotherapy was not optimal, up to the proper standards, there was a 20% reduction in survival?

Yes.

That’s massive.

Yes. In fact we conducted an international trial for head and neck addressing tirapazamine, which is hypoxic radiosensitizer, in combination with a concurrent radiotherapy may improve survival. So indeed it was an international randomised trial, we recruited 850 patients all over the world and the trial was negative for survival, the main aim of the trial, but in this trial the procedures of quality assurance or radiotherapy were very well established. Every patient in the trial, investigators were required to submit all their documentation just in the first week of treatment to an external review centre. It was called QART – quality assurance radiotherapy, and they performed a rapid review to follow if the investigator had followed the guidelines of the protocols.

With fields and doses?

Yes, fields and doses. And those non-compliant plans, QART said to the investigator it was not compliant and they made some suggestions for corrections. So at the end of the treatment members of the trial managed a committee that were all radiation oncologists, we went to QART for the final evaluation. We performed blindly, without knowing which patient was, and we found that in 12% of the treatment plans there is a risk of both reducing the tumour control probability because of a lower dose on the tumour or plans in corrections. So we looked at the survival, according to these criteria and we found that those patients that were treated badly, incorrectly, that their reduction in survival at two years was 20%. It was also very interesting, it’s an important data also, is that then we looked at those patients treated properly according to the protocol and in those patients treated according to the protocol we compared those treated with tirapazamine and without. Interestingly, in the patients who were treated tirapazamine produced an additive effect, an improvement in local regional control. The question, because of the number, is not significant. There is a clear trend, the p value is 0.06, so a really good trial. Excellent local regional control at two years, 80% in patients treated with radiotherapy and cisplatinum and 85% in patients treated with radiotherapy, cisplatinum and tirapazamine.

So what we could show is that randomisation was not a saviour for treatment incorrection. So in the future, all the trials addressing a question where radiotherapy is there need to have a quality control procedure.

From the beginning?

Yes, because if not, probably the conclusions of the trial will be disturbed by the effect of the poor quality radiotherapy.

That’s very, very important and I congratulate you on doing that. You do a lot of clinical trials, you’re also planning a big European trial on radiotherapy in children’s cancers?

Yes, this year at Barcelona we are also presenting, in fact Rolf Kortmann who is the German investigator, will present the data of a trial for treatment of hyperfractionation radiotherapy in medulloblastoma. In Europe we have all the paediatric radiation oncology and paediatric medical oncology working together, because of the numbers we need international collaborations. So we include 350 patients and we randomise the patients in medulloblastoma. It’s a brain tumour and it’s a tumour that can relapse in the whole CNS so it needs to be treated with craniospinal radiation and then we ask whether hyperfractionation craniospinal irradiation may improve outcome and also make decreased toxicity. In this trial the trial was negative for the primary input so the survival groups were the same for children treated with standard radiotherapy or with hyperfractionation radiotherapy but we proved that with hyperfractionation there is a reduction in toxicity especially in autotoxicity. Also we found that in the intermediate risk group the use of hyperfractionation may improve local regional control. The problem is because it’s a subgroup analysis the number is not enough to show differences but there is a clear trend and now for the future trial we are considering in these patients the use of investigating again the advantage of hyperfractionation radiotherapy in these patients.

You’re a busy man. Thank you very much indeed.