Radiotherapy Between or During Chemotherapy Cycles Reduces the Risk of Breast Cancer
Prof. Indrajit (Indy) Fernando discusses his EMCC 2011 talk on how radiotherapy between or during chemotherapy cycles reduces risk of breast cancer recurrence.
The Group Room at the 2011 European Multidisciplinary Cancer Conference was made possible, in part, by:
VIDEO TRANSCRIPT
Selma Schimmel, Founder & CEO, Vital Options International:
This is Selma Schimmel at the Multidisciplinary Cancer Congress 2011 in Stockholm, where I’m happy to be joined by Doctor Indy Fernando. Hello Doctor Fernando.
Prof. Indrajit Fernando, MD, Queen Elizabeth Hospital, Birmingham, UK:
Hello.
Selma Schimmel:
And I’m most interested in your work because you’ve done an interesting study in the UK involving radiation therapy – or you call it radiotherapy – between or during chemotherapy cycles and the impact that this has on breast cancer recurrence. Talk to us about it.
Prof. Indrajit Fernando:
Well, the standard way of giving chemotherapy and radiotherapy in the world is to give your chemotherapy first, and then follow that up with radiation treatment. That’s been the standard of care everywhere, and what we were concerned about is this was delaying the radiotherapy for quite a long time. Therefore was it possible to give you radiotherapy actually in between the chemotherapy cycles, or in between one cycle and then through to another? And if we did that, we could avoid delaying the radiotherapy, we might also see sort of a combined effect of chemotherapy and radiotherapy together. And that combined affect is what we call synchronous treatment. It’s something we’ve seen in several other tumor types, and we’ve shown that we can actually improve local tumor control rates above and beyond what we normally see if you gave the treatment in the end. That’s what the trial was about, and what the trial showed was that you could reduce your chances of the cancer coming back locally in the breast, or if you’d had the mastectomy on the chest wall by 35%. That extent of benefit was as much as you see in sort of giving this chemo-radiation combination in lots of other different houses. And that was quite a surprising effect, and larger than we were expecting.
Selma Schimmel:
This is a sort of thing with further research could change standard of care.
Prof. Indrajit Fernando:
It could indeed. It does involve using a CMF-type chemotherapy schedule, which is probably used far less frequently in the United States than in Europe and in the United Kingdom. Nevertheless the benefits are seen, and benefits are quite substantial, especially when you take into account that for every four local occurrences that you prevent you can also actually save the lives of one patient.
Selma Schimmel:
When you say psytoxifiamuetoxisamethatrextate, which was commonly used in the 80s in the US, now this could become… this would be the protocol that would have to be used?
Prof. Indrajit Fernando:
Our data is based on this particular combination either used by itself or with Anthracyline, what we call Adriamycin or Epirubicin given before the CMF.
Selma Schimmel:
What stage of disease were these patients?
Prof. Indrajit Fernando:
These patients were all early stage breast cancers, but they all required both chemotherapy and radiotherapy. And what was interesting was using this particular combination of drugs and radiation we didn’t see any very significant side effects, apart from the fact that the skin did certainly become more sore. We got more skin reactions but for the trial as a whole, over 96% of the patients at the end of six weeks, all the skin reactions had completely settled, and what patients particularly liked – even more than… I mean they didn’t know if their cancer was going to come back or not, but what patients particularly liked – was the fact it shortened their treatment. If you think that people have to go through six, seven months of chemotherapy then have to wait, then have to have five or six weeks of radiotherapy by doing it in this combination it meant that once they finished their last chemotherapy, they finished all their treatment. They particularly liked that because it’s a long haul for a patient, it’s quite nice to say you’ve finished your last chemotherapy, you could book your holiday, you could get back to work.
Selma Schimmel:
What about side effects such as fatigue because this is a big burden of treatment on a patient at one time?
Prof. Indrajit Fernando:
That’s why we did a very detailed quality of life analysis. And that we have also presented in fact this after on our poster. But what was very interesting is that we didn’t in any way impact on quality of life. Quality of life on patients who have the chemotherapy followed by radiation, and those patients who had the combined treatment was almost identical. There was no significant statistical difference. So we weren’t giving them miserable time during their treatment. As I said they did get a slightly worse skin reaction, and in the long term you did get a very, very slight effect on a condition called Telangiectasia. What I mean by that is the skin pigmentation looks slightly different. It doesn’t cause any physical harm but the appearances of the skin are slightly different. That was very small, it was like 1.5% more, it was a very small affect.
Selma Schimmel:
What happens now with the research because obviously this is a significant outcome of study?
Prof. Indrajit Fernando:
Well our next step is obviously we’ll be writing up the paper formally. We are looking at all the different chemotherapy and radiotherapy schedules that we used to see which ones will be suitable for this program, which ones aren’t, and we may have to go forward and consider further research trial to see if the same benefit is seen in other types of chemotherapy treatments that are used, using combinations such as Anthracyline followed by Taxid. This would clearly involve completely new research projects and new research trials to see the same benefit that we’ve seen now, and the same minimal toxicity profile is carried on with other treatment schedules.
Selma Schimmel:
And the patients in the trials, for how long did you follow them?
Prof. Indrajit Fernando:
We had a long follow-up of over 8.8 years. So we know these are long term results. These results are not going to change.
Selma Schimmel:
Are you still following these patients?
Prof. Indrajit Fernando:
All the patients had to be followed up for ten years. So we have already followed up. Median follow up is already 8.8 years but every patient will have to be followed up for ten years.
Selma Schimmel:
So Doctor Fernando, just out of curiosity, what inspired the study, the research? How did you come to think about what would happen if we delivered radiotherapy differently than in the classic way that we’ve done it thus far?
Prof. Indrajit Fernando:
I was sitting in a room, listening to a talk, and somebody happened to mention that they’ve done an audit and it looked as if thirty or forty percent of oncologists gave their radiation at the end, and it looked like twenty to thirty percent of oncologists were already giving it in between cycles. I thought to myself nobody’s actually looked at this to see if it really is beneficial, nobody’s actually looked to see if the side effects are worse. And this is clearly a very important clinical trial that needs to be undertaken, and it’s extraordinary if you think that we have been using chemotherapy and radiotherapy for over 30 years, and until today we’ve not had any really good data to show which is the best way of sequencing the tumor. But today we do have some data suggesting probably the way we need to go.
Selma Schimmel:
I can only imagine how excited you must be.
Prof. Indrajit Fernando:
Well, I’ll say if you had asked me to predict the result when we set up the trial, I would have said it may probably show slight benefit, but I was concerned about long term side effects would be worse. In fact long term side effects were much better than any of us were expecting.
Selma Schimmel:
Doctor Fernando, what made you suspect that there could be any therapeutic benefit?
Prof. Indrajit Fernando:
It’s a very interesting question. What I thought was we’re delaying radiation therapy for a long time. You usually do chemotherapy for six or seven months, you’re giving your radiation treatment at the end, that’s a long delay. I thought ‘let’s try and bring the radiotherapy earlier to avoid the delay’. I didn’t want to give the radiotherapy first because that delays the chemotherapy, and we knew from a study that had been done in the United States that there was a suggestion that if you gave the radiotherapy first and followed it with the chemo you’re delaying your chemotherapy and that probably wasn’t the best way of doing it. So what made me think is I said ‘if we do it this way, we won’t be delaying either treatment’. But in fact since I thought of the study we’ve had more and more data from lots of other cancer sites showing that this chemo-radiation, which I’m sure you’ve seen in many other cancer, there’s has an extra additional effect. It’s used in head-and-neck cancer, it’s used in lung cancer, it’s used in survival cancer, it’s used in rectal cancer and all these sites given the chemo and radiation together seems to give it an enhanced effect. We didn’t have any data to suggest that when we set up the trial in 1998. The main thing I was looking at was trying not to delay either treatment.
Selma Schimmel:
How do you successfully do radiation on a fresh surgical site that’s still trying to heal?
Prof. Indrajit Fernando:
By the time the patients come to me the operative scar has healed. So patients will usually start their chemotherapy approximately four weeks after their surgery. So our surgeons are pretty good, by then they will have healed.
Selma Schimmel:
Well, I think this is a really fascinating study and I want to congratulate you on being so innovative and thinking out of the box. And wouldn’t that be something if you realize that your work is a practice changing event?
Prof. Indrajit Fernando:
Well, we think it is. We think it will practice change for people… if people using the sort of chemotherapy that we’ve used in the trial there really can be marginal argument for not using this. It wins on every score – you shorten your treatment time for your patient, your side effects are minimal, and they’re controllable – and we did the study, it was set up in 1998 finished in 2004. Radiotherapy techniques have advanced enormously so even the soreness of the skin problems that we did find are now very much less because of our improved technology. We can use that technology to probably reduce the side effects to what we’ve actually seen in this study. So it is important that we select patients carefully, if you think somebody’s going to develop a very nasty sore, skin reaction, this treatment may not be suitable for every single patient. But for the vast majority of patients it will be, and it’s wonderful if you can think you may have reduced the chances of that cancer coming back by a third. That’s a big benefit locally. It means a lot of ladies who might have gone on to have a mastectomy will not need to do so. Lot of ladies who get a recount on the chest wall after reconstruction, the reconstruction will not have to be removed.
Selma Schimmel:
And I especially like the idea that you can consolidate everything, and shorten the time that a patient needs treatment.
Prof. Indrajit Fernando:
Oh yeah, it’s a long haul, isn’t it?
Selma Schimmel:
Yes, it’s a very long haul.
Prof. Indrajit Fernando:
And it’s nice to finish a bit early – about two months earlier.
Selma Schimmel:
Congratulations and thank you, Doctor Indy Fernando.
Prof. Indrajit Fernando, MD:
Thank you.
END OF VIDEO