Alain Fourquet, MD
By Beryl McCormick, MD, FASTRO and David Morgan, MB
The following interview of Alain Fourquet, MD, was conducted on September 15, 2020, by Beryl McCormick, MD and David Morgan, MB.
Beryl McCormick: What got you into medicine and more specifically in oncology, and then breast oncology, which is what we're going to really focus on this morning.
Alain Fourquet: Yeah. Okay. So first it came by chance and opportunities. I started to go into hematology. And then I had the opportunity to go to the Curie Institute and meet with Robert Calle, Bob Calle, that you know?
Beryl McCormick: Uh-hmm, I do.
David Morgan: Uh-hmm, very much, yeah.
Alain Fourquet: And eventually, I, you know, did my residency at the Curie in radiation oncology. And it was something that was not very well-known in the medical schools. I mean, it was a bit: Radiation what's that? and this and that. And so --
David Morgan: I think that was the same everywhere.
Alain Fourquet: Yeah. So I discovered the whole picture. And because it was the Curie, and Bob Calle and everyone there, so I rapidly went into breast cancer management and breast conserving treatment, et cetera, et cetera. So that's it. That's how, you know it went, I guess. It's often the case, opportunities and meeting the nice people, mentors, and then getting to the field.
David Morgan: So what year did you start at Curie, Alain?
Alain Fourquet: I started residency in -- well, I did a sort of pre-residency year in 1980. And then I really started in 1981. Then I trained there for two years. At the time, the residency program in radiation oncology was only three years.
David Morgan: You stayed there?
Alain Fourquet: Yeah. I trained for two years at the Curie and then one year at Necker Hospital, a University Hospital in Paris. And then I went to Memorial Sloan Kettering in New York where I had the pleasure of meeting with Beryl.
Beryl McCormick: I remember that. That was a good year.
Alain Fourquet: So at the time the idea was to get elsewhere, to go abroad and see what's going on, yeah, the general picture.
David Morgan: Yeah. That's why I came to Paris at that time. Yeah.
Alain Fourquet: Yeah, I think, at the Gustave Roussy, right?
David Morgan: Yes.
Alain Fourquet: And so, so it was very enriching, and the year at Memorial was great for me, really. I've seen different thinking and a different way of just figuring the same problems with – different approaches.
David Morgan: Yeah, yeah, very much so.
Beryl McCormick: Was Dr. Baclesse ever alive when you were there or not?
Alain Fourquet: No, I never, I never met him. I think, I'm not sure, but I think he died in 1969 or something. I'm not sure if that's when. So I never met with him. But Bob Calle was director here.
David Morgan: Yeah. I've been thinking, thinking back to that time in preparation for this interview. And I'm trying to remember the state of breast cancer radiotherapy back then, because breast conservation was still relatively controversial, wasn't it?
Alain Fourquet: It was very much because there were no clinical trials in the sense that we are conducting trials now. But as a matter of fact, they had at the Curie. I mean, they had started breast conservation treatments. Well, I came on a paper that was published, I think, in 1939. It was signed by a radiation oncologist who practiced at the time, a pathologist, and a surgeon. And I think the title was in French, but it was radiation therapy for locally advanced breast cancer. It wasn't on radiation therapy; it was roentgen therapy. In this paper they delivered 5,000 roentgens in protracted courses - up to six, eight, or even ten weeks - to patients who were having inflammatory locally advanced huge tumors and all this thing. But the interesting thing is that they looked at the pathological response and they classified the response in terms of complete response, partial response, minor response, and no response from the pathologic point of view. So, yeah, it was very interesting because they continued in this afterwards.
And in the '40s and '50s Baclesse had published a large series of 400-500 patients treated with radiation therapy for breast cancer. And then, they continue the group of surgeons, radiation oncologists, pathologists. They continue and they continue with breast conserving surgery, and radiotherapy and et cetera, et cetera.
And so, I came on a book published in 1972, reporting articles from a meeting in Strasbourg, in France. And there were people from the Curie, and from other centers in France (such as Dr Bernard Pierquin, from Henri Mondor University Hospital.
David Morgan: Yeah, I know very well.
Alain Fourquet: Mustakallio from Sweden, I think, and Vera Peters from Canada. And they all presented their data on breast conserving treatment of breast cancer. And the total amount was almost more than 2,000 patients treated with five years follow up. And so from that time on, it really became breast conserving surgery and radiotherapy, the reference treatment for early breast cancer, at least at the Curie in the early '70s.
David Morgan: I remember we look to the Curie in those days as sort of pioneering the -- as you say, that lots of people were involved. The Curie Institut sort of stood out as one where it was taking it forward.
Alain Fourquet: And so when I came to the Curie, it was the reference treatment. Many patients were treated that way.
Beryl McCormick: And certainly, for me in the United States, although, I think, unfortunately, for many breast radiation oncologists who really think primarily of Samuel Hellman as the person that really started breast conservation surgery in this country in Boston, just because of the relationship of a radiation oncologist called Nem Ghossein who I worked with for about a year and a half up at Albert Einstein in New York and his very strong relationship at the Curie. I really learned about this very rich, long-standing experience in France, and Canada, in Scandinavia, that's far, far came before, anything that Hellman did in Boston. And I think that's important to go into the ASTRO history books because it really did start there not in Boston.
David Morgan: Thus speaks the lady from New York.
Alain Fourquet: Beryl, you eventually came to Memorial Sloan Kettering, right?
Beryl McCormick: Yes.
Alain Fourquet: No, but I think, you know, I don't know if there is any at least transmission or a message that could be sent to the younger people. But I think it came out in a sort of an orderly way because some people were working together, and that means surgeons, pathologists, and radiation oncologists at the time.
I remember when I was a young resident at the Curie and I attended the clinics of the Head of the surgical department and this and that. He was seeing patients and he was examining them. And he would say, "Well, this is going to be radio resistant. So let's do mastectomy." Or he would say, "Okay, I could remove the breast, lady, but if I could preserve your breast and then you have the radiation and this young man here, will take you in charge." And it was already -- I remember at that time that there were exchanges every day. I mean, we were calling the surgeon in the clinics to see whether these patients were amenable to breast conservation surgery and vice versa. So it was a very endless discussion, case by case.
David Morgan: I have to say multidisciplinary treatment is of course recognized everywhere now, but my impression is that it was developing in France before other places because I only saw selected places. What you're telling me confirms this.
Alain Fourquet: I think it was mostly for breast cancer. And one of the reasons is that breast cancer, unlike other surgical or other specialties is not a specialty per se. So to take breast cancer patients in charge in a comprehensive center, like the Curie, you had to work together with other disciplines. Otherwise, there was no way you could do it, so --
David Morgan: People are seeing that for all sorts of situations now, but yeah. You were ahead of us, I think, in many ways.
Alain Fourquet: It was the case in other centers also in France. But I guess it was also helped by the fact that we have this system created in, I think, it was 1947, what we call the cancer centers. There were 20 cancer centers in France that were created just after the war.
David Morgan: 1947. Yeah. Wow.
Alain Fourquet: And the idea was to have everywhere in France centers that could allow treatment to patients at short distances. And the setting so that any patient in the country was less than 40 kilometers from the center. And so it helped us. It obliged people to work together.
David Morgan: Yes, yes. Yeah.
Alain Fourquet: That was interesting.
David Morgan: Sontre d'élude faire au Les Centres de Lutte contre le Cancer.
Alain Fourquet: Exactly. Yeah.
David Morgan: Yeah.
Alain Fourquet: And of course it goes back, if you wanted, to Marie Curie. Because at the time they created the Foundation Curie and even before, Marie Curie, along with and a clinician (Dr Claudius Regaud), were working together really to try to understand, to develop the use of radiation therapy in treating cancers, and to understand the radiobiology of the whole thing. So, really historically, it really started in the early '20s and then, yeah.
Beryl McCormick: So Alain, we've talked a lot about the history of what you inherited when you became the department chairman, but tell us now with some of your best achievements with the rest of department.
Alain Fourquet: Well, I'm not sure it's mine to say.
David Morgan: Yes, it is. Go on.
Alain Fourquet: But more seriously, what I've tried to is to continue this, especially through teaching residents bedside. One of the things nowadays that I'm not very pleased with is the fact that you have so much technology that the clinical involvement is decreasing in the young radiation oncologist in a way. I mean, they're fascinated by all this technology, but they still have to put their fingers in, if you see what I mean.
So, I try always to have them involved into this, to go into the operating rooms, to go in the pathology labs, and to understand how the disease was evolving. And to get involved also in understanding the effects of chemotherapies, and also of systemic treatments that we are using now. I mean, to have a general picture to being an oncologist, not to be a radiation whatever. I think this is a difficult task and I think that's very important these days.
So what we did also, we tried to develop, of course, clinical research. And we've done clinical research to trying to measure the effects of radiation in the neoadjuvant setting, because up until the end of the 1980s, when we started to do neoadjuvant chemotherapy, we were doing neoadjuvant radiotherapy, and we're doing exclusive radiotherapy. Many patients treated without surgery.
And so what we have, a series of almost 2,000 patients treated with radiotherapy first, and with surgery following radiotherapy or without surgery at all in the case of good response. So we had large cohorts and understanding of clinical effects of radiation therapy as it was used at the time, of course, which is a bit different now. We're more precise.
So it remains rather vivid in the sense that it has -- I think, at least in my institution, and I hope it is the same elsewhere, but it remains an important part of the treatment. It remains a way of research. We have started to do radiotherapy and immunotherapy in breast cancer, and the combination of various targeted treatments in radiotherapy, et cetera, et cetera. And one of my regrets is that we were not able to push and stronger the research in clinical radiobiology. I mean, that's specifically in breast cancer. And I think that's something that really is the future in that particular field.
Beryl McCormick: What about your involvement with the internal mammary node trial?
Alain Fourquet: Okay. Yeah. So, we’ve participated in several European trials. The first one was the EORTC “Boost trial”, testing an additional dose to the tumor bed to patients. And then I was one of the writers and designers of the EORTC internal mammary node trial with Harry Bartelink and others in Europe. I was involved also in the Young Boost trial where we tested the effects of an increased dosage to the tumor bed in young patients-- I've always been interested in the outcome of breast cancer in varying patients. Local recurrence following breast conserving treatments was mostly determined by the age of the patient at the time of diagnosis.
David Morgan: Yeah.
Alain Fourquet: So we tried to understand that. We tried with multiple studies, multivariate analysis to trying to determine what would explain that. And every time it was a bit disappointing because every time we came up with the results, it was always young age that came as the main predicting factor for local recurrence.
So we went to this and then went to genetic studies, of course, and et cetera, et cetera. So the Young Boost trial was aimed at trying to see whether increasing the dose of the tumor bed in young patients could improve the results further. The problem is in a sense - but it's a good problem - is that the overall rate of local recurrence is so low in this group of young patients, that we haven't reached the number of events that allow us to analyze the trial. And we're now seven years of follow-up, so I'm not sure.
Beryl McCormick: Oh, my goodness.
Alain Fourquet: So the rate in this group of patients is, I don’t know. I think it's like 3 percent at seven years or something in patients below 50. Right.
David Morgan: That’s powerful. I’m wondering if the extra boost will be bad for the cosmesis.
Alain Fourquet: Yeah, it is in a sense. It is, of course. It's not so bad, but it's worse than the conventional 16 Gray boost that we're using. So we will probably come up with, okay no need to increase the dose but at least it's interesting because we are able to carry out biological studies with-- the group in Amsterdam Dr Marc van de Vijver, the pathologist that's been working at NKI with Harry Bartelink is analyzing the whole population. We have tumor samples and we’re doing –-
David Morgan: How many patients now?
Alain Fourquet: Well, in the trial, there were 2,400 patients altogether. So, in roughly probably a bit more than half of them we have frozen samples, and of course the histological blocks and everything. So we were able to do this large genomic studies and the whole thing. Yeah.
Beryl McCormick: So when are you expecting to report on more of this?
Alain Fourquet: Well, probably at the ten years endpoint, we should have enough number according to the stats plan to analyze the comparison and see whether we have something. For the biological studies altogether, I don't know. It's ongoing. It might take maybe one or two years, hopefully.
Beryl McCormick: Now that will be fascinating information.
Alain Fourquet: Yeah, I hope so.
Beryl McCormick: No. I remember I was chairing a session of ASTRO the year that Anne de la Rochefordière talked about, I guess, probably your first study of pre-menopausal women, with mastectomy or with lumpectomy. I had a lot of trouble pronouncing her name and I always remember that. But that's a study I still send my residents to look at because it's so well done looking at actual age - very good.
Alain Fourquet: Yeah, she presented that well, Anne de la Rochefordière.
Beryl McCormick: Yeah, I didn't even come close to saying it correctly.
Alain Fourquet: Don't worry.
Beryl McCormick: Where do you see yourself, what do you see yourself doing in the next three to four years?
Alain Fourquet: Well, first of all, in a very practical way I will start to decrease the overall activity in terms of clinical - seeing patients, treatment and everything - starting this January. So, I will reduce. I'm still doing consultations in the clinics, but reducing the overall thing.
I've started a trial last year in DCIS, Beryl. So that sounds familiar to you. And so we're doing an de-escalation trial. We started to, you know, we've published a paper in 1983, I think, in the breast conserving treatment of DCIS. It was 52 patients at the time. And we just picked up in the database patients who had non-infiltrating disease. So we went through the whole database and picked up these small numbers, and we just looked at the outcome. And we saw that these patients who were treated with radiation - they didn't have more local recurrences -, than patients with invasive cancer. So we were interested in that.
And this, it was at the same time that the large screening programs started and then the rate of DCIS was increasing. So, we had more and more patients treated. So, last year, I started a trial in trying to identify patients with extremely low risk. So, we started with the criteria that you used in the RTOG trial. We wanted to be practical and simple so we asked the centers to do an immunohistochemical study, the IHC signature, you know, David, people from London. And so, they have to have a luminal A so-called subtype to be included in the trial, in addition to the other criteria that were used in the RTOG trial. And so we randomize them 2:1 radiation or no radiation, and so --
Beryl McCormick: That's interesting.
Alain Fourquet: So, and of course we'll have a centralized post-trial review. And we have plenty of ancillary studies, biological studies, looking at the disease itself, but also at the environment of the tumors.
David Morgan: Will the patients be getting endocrine therapy?
Alain Fourquet: No, they won't.
David Morgan: Good.
Alain Fourquet: We’re not so fascinated by endocrine therapy in DCIS.
David Morgan: Well, it is a difficult one to fight off sometimes, isn't it?
Alain Fourquet: Yeah, I know. In England, I guess, particularly. So, no, they won’t. They won’t. They won't.
Beryl McCormick: Alain, you'll be happy to know, we finally are circulating the 15-year results of the manuscript from the RTOG trial to the co-authors, after many, many back and forth. So you will hear more from us.
Alain Fourquet: I'm longing for it. That was the understanding.
Beryl McCormick: But we do have a paragraph or two discussing luminal A, although we didn't have the specimen, so I’m really excited to hear about your trial.
Alain Fourquet: Okay. So I'll let you know. So I will compile this and have a young radiation oncologist who was our resident. She's in and she's working with me and she will continue the trials when I get to retire then. So it's in good hands.
Beryl McCormick: Is there an age in France where you have to retire, like there is in the Netherlands or not really?
Alain Fourquet: Well, in medicine, now you can work, you can retire starting at 65, but you can go up to 70. But then you have to retire after 70. Well, at least in the public or equivalent system. Now if you want to go in private practice, you can go up to 80 if you want. But I'm not sure it's a good thing.
David Morgan: As long as the insurers are happy.
Alain Fourquet: So that's it, otherwise, I'm involved in the National League against Cancer, which is the fundraising body in France that have been existing for almost 60 years.
David Morgan: Tell us the full name of that, Alain.
Alain Fourquet: It’s Ligue Nationale Contre Le Cancer.
David Morgan: Okay. We probably want that for the record only. Yeah.
Alain Fourquet: Uh-hmm. So they're raising funds, and they are helping patients. A large part of it is to help patients, you know, and particularly to cope with the disease and the after disease, the going back to social and professional lives. And also they finance the clinical research programs and all this kind of thing.
David Morgan: This is charitable. This isn't publicly funded. This is true - for charity work?
Alain Fourquet: Yeah, it's charity. Yeah. So I’m quite involved in that. And I'm also very much involved in the French society for breast diseases, which is quite active. I mean, it has its own meeting. It's the only meeting, which can gather multidisciplinary participants around breast cancer as a matter of fact. Let's say it's a bit like the San Antonio in a much smaller scale, of course. But the general idea is to have people from all disciplines being together for two or three days and have a single session, a single session meeting.
David Morgan: A national meeting?
Alain Fourquet: It's a national meeting.
David Morgan: The francophone Belgians and Swiss come along.
Alain Fourquet: Right, right, and from Canada also sometimes and people from Northern Africa also.
David Morgan: What about the other organizations you've been involved with, Alain, in the past? There must be a long list.
Alain Fourquet: Yeah, well, not so long. I've been very much involved in the clinics and everything. So you have to find the proper balance, I would say.
David Morgan: Of course.
Alain Fourquet: So I've been involved in ASTRO a bit. I was involved in the EORTC maybe the first 10 or 15 years of my career. I was --
David Morgan: Well, I think that's where we met, wasn't it? Yeah.
Alain Fourquet: We met there, absolutely. This is what I'm wanting to say. And I was involved in the Curie. I was, for almost ten years at the board of the administrators of the whole institute, you know, both the research center and the hospital. So I was involved in a number of things. I was involved in ASTRO a little bit. I was in ASCO also, so these kind of things but -- yeah.
David Morgan: Yeah. Going on, what, Alain, do you think was the work that came out of the -- what would you highlight from your time in those various organizations that you think has been important developments? What stands out for you?
Alain Fourquet: Well, I think, again, one thing in the early years was really to - it was both things - set the breast conservation as really the reference when it, of course, met the criteria for it. So I guess, quite frankly, the people adopted it, and really now, everywhere in the country. And it has been the case for quite a long time now - a very large percentage of the patients that can be treated with breast conserving treatment actually receive breast conserving treatment. And this has been the case since, I would say, maybe the mid '90s or even earlier--
David Morgan: It most certainly wasn't the case when you were starting at Curie. It might have been there but it wasn't accepted everywhere else by any means, was it? I can’t remember.
Alain Fourquet: Yeah. Right, exactly. So I think we pushed very much for that. Second, it was for DCIS because, really, at the time, DCIS was considered to be a radio resistant tumor coming from nowhere. And, really, we were able, through the communications, papers, meeting, whatever, to improve that and to have it. Now, really breast conserving surgeries is carried out.
I have been involved from the very beginning also in designing and writing the guidelines for breast cancer management in France. So I started this in 1994, I think. So it helped though, you know, I'm very modest about the whole thing. But I guess it helped to sort of homogenize the practice in the country, and to help people to refer to something, to be more confident in what they are doing.
David Morgan: Now, you're being very modest about this, Alain. We know it's very important.
Alain Fourquet: No. I think it is. The guidelines per se really depends on how people are using them. But the general idea, I think, that's really an improvement to -- what do I say? To have people be confident about the decision they're taking of preserving the breast, choosing for radiation, and also helping them to more precisely define their indication. And also be able to somehow resist other disciplines. Why are you still doing this radiation, et cetera, et cetera.? So I think that --
Beryl McCormick: Alain?
Alain Fourquet: Yeah.
Beryl McCormick: Do you have a set of those guidelines also oriented towards patients like the American NCCN guideline? Or are they mostly for physicians?
Alain Fourquet: Well, at the beginning they were for physicians, of course. And that's with the evolution of the mentalities and experience. Now, for the past ten years maybe both in the institutional guidelines and the national guidelines through the National Cancer Institute in France (Institut National du Cancer), we always have patients involved. And when the guidelines are reviewed before being released, they're reviewed by groups of patients. They give their point of view. So it's much more, there's a much larger implications of patients to be present than when I started, of course.
But we try to keep, to design the guidelines based as much as possible on the evidence, which is not -- of course, you don't have the evidence for anything. But at least trying to keep a rigorous and orderly way to design these guidelines and to really mention if: this we know; this we don't know. So there are options and then we can choose.
But the way patients are involved is probably quite different though maybe not so much in France, at least, in the States. We know that sometimes patients are completely lost when they're asked to choose and to decide because they are sort of drowning in the sea of information coming from everywhere all the time. So sometimes, I still have quite a large number of patients after a while that says, "Okay, I'll let you decide," because they're lost. They're simply lost. It's too much information to swallow in a short period of time.
Beryl McCormick: I think that's a good point anywhere. Okay.
David Morgan: What thoughts for the future, Alain?
Alain Fourquet: Yeah. Okay. Well, one point I didn't mention is that I think one thing for the future in terms of pure radiation oncology technology is the use -- at least is some development of proton therapy in breast cancer. Not every patient, of course, but some patients particularly those very young patients, those patients who have a family or genetic breast cancer predisposition. In a sense that using protons helps to really target better, and to avoid the contralateral breast when treating the ipsilateral breast. You know, IMRT and VMAT and TomoTherapy or whatever are very nice tools, but in very young patients, I don't choose them because the dose to the contralateral breast --
David Morgan: Yes. You know, they splash the dose around everywhere. Yeah.
Alain Fourquet: And patients that have BRCA1 or 2 or other mutations you really don't know that - what's the impact of increasing the rate of contralateral breast if a patient does not choose to have a mastectomy. So protons can be helpful with breast cancer, you know. Comparative studies in that and then we started to include patients in the study for proton in this particular group of patients at risk, I would say.
And, again, the future, as to my opinion, is really -- of course, it's personalized medicine, which means radiation therapy to be able to really identify the patients who may need or may not need radiation; to identify the type of patients who may benefit from certain type of fractionation versus not, et cetera, et cetera, et cetera; and patients who may need to be given concurrent targeted therapies whether it be targeted antibodies or immunotherapy in breast cancer. There's a lot to do there. It's a nice study we have then. So we started trial with the anti-PD-L1 and anti-CTLA-4 in patients with breast cancer concurrently with radiation too really to test for the response, the tolerance et cetera, et cetera.
David Morgan: I imagine that like everywhere else, this pandemic has had a big impact upon what you're doing. How do you think that will affect a lot of things going forward? Do you have any views on that?
Alain Fourquet: Yeah. We started in March and the lockdown was in March 16, so we had to very rapidly, very quickly reconsider the whole picture and for all patients. You know, we treat 5,000 patients per year in radiation therapy. And almost 60 percent of them are breast cancer. And so --
David Morgan: Do you think the changes you had to make will be carried on if and when the pandemic recedes? What are your thoughts on that?
Alain Fourquet: Well, we know what to do in terms of adaptation because we were able to reduce the treatment time because we used, reduced fractionation scheme and this and that. So if it goes up again we know at least what to do. We probably tried to learn from that, of course, and see what we can keep or not for routine practice afterwards so we may learn from it.
But I would say it's probably a bit early. We got to analyze the whole thing at least one year after and to see how the patients that were treated within this period of time - two months with altered fractionation schemes and delay in initiating radiation, what was the outcome a year after. So we're gathering the information and see.
But, yeah, we're probably, like always, under pressure and this way you're pushed to innovate and to learn from what you've done and see how we can try to apply in practice afterwards.
Beryl McCormick: Any words of wisdom for the historical committee.
Alain Fourquet: Okay. Well, I guess, at least a word of wisdom, I don't know but easy words. But I think towards the young people, I think it's a nice discipline because it's common sense. But you're doing clinics but you still have to do the clinical work and that's very important in radiation oncology. Again, I repeat this but I think it's essential, particularly vis-à-vis the other disciplines. It's important to appear as a clinical discipline. It's very large. You're doing physics. You're doing biology. You're doing a lot of things that's quite fascinating. And it really is something that should attract the young people.
And maybe to conclude but, I guess, it's not new. And you went through this yourself at different times because when I started radiation and met with a surgeon and afterward with the medical oncologist. You know, Bernie Fisher was one of the guys who said this kind of thing says that, well, ten years from now, radiation therapy will have disappeared and this and that. Forty years after it's still here and it's very dynamic and, I guess, it's very important.
I would say it's regaining and that's particularly true in breast cancer. It's regaining importance in terms of local control, of the impact of local control and survival, and also, now, of course, treatment of resistant oligometastases and polymetastases that really may improve the overall survival of the patient. So it's a never ending story. And I'm very glad to have went through that part of this history.
David Morgan: I agree.
Beryl McCormick: Okay. And wonderful to speak to everybody, I hope we get to see you in Paris personally very soon, Alain.
Alain Fourquet: And in Brittany, Beryl, I spent the summer in different places in Brittany, it was great. So next time, let me know.
Beryl McCormick: Yeah. No. I'll catch up with you because that's definitely on my list of things to do.
Alain Fourquet: Okay. Okay. And thanks very much. And David, I hope I'll see you soon.
David Morgan: Great to talk to you.
The following interview of Alain Fourquet, MD, was conducted on September 15, 2020, by Beryl McCormick, MD and David Morgan, MB.
Beryl McCormick: What got you into medicine and more specifically in oncology, and then breast oncology, which is what we're going to really focus on this morning.
Alain Fourquet: Yeah. Okay. So first it came by chance and opportunities. I started to go into hematology. And then I had the opportunity to go to the Curie Institute and meet with Robert Calle, Bob Calle, that you know?
Beryl McCormick: Uh-hmm, I do.
David Morgan: Uh-hmm, very much, yeah.
Alain Fourquet: And eventually, I, you know, did my residency at the Curie in radiation oncology. And it was something that was not very well-known in the medical schools. I mean, it was a bit: Radiation what's that? and this and that. And so --
David Morgan: I think that was the same everywhere.
Alain Fourquet: Yeah. So I discovered the whole picture. And because it was the Curie, and Bob Calle and everyone there, so I rapidly went into breast cancer management and breast conserving treatment, et cetera, et cetera. So that's it. That's how, you know it went, I guess. It's often the case, opportunities and meeting the nice people, mentors, and then getting to the field.
David Morgan: So what year did you start at Curie, Alain?
Alain Fourquet: I started residency in -- well, I did a sort of pre-residency year in 1980. And then I really started in 1981. Then I trained there for two years. At the time, the residency program in radiation oncology was only three years.
David Morgan: You stayed there?
Alain Fourquet: Yeah. I trained for two years at the Curie and then one year at Necker Hospital, a University Hospital in Paris. And then I went to Memorial Sloan Kettering in New York where I had the pleasure of meeting with Beryl.
Beryl McCormick: I remember that. That was a good year.
Alain Fourquet: So at the time the idea was to get elsewhere, to go abroad and see what's going on, yeah, the general picture.
David Morgan: Yeah. That's why I came to Paris at that time. Yeah.
Alain Fourquet: Yeah, I think, at the Gustave Roussy, right?
David Morgan: Yes.
Alain Fourquet: And so, so it was very enriching, and the year at Memorial was great for me, really. I've seen different thinking and a different way of just figuring the same problems with – different approaches.
David Morgan: Yeah, yeah, very much so.
Beryl McCormick: Was Dr. Baclesse ever alive when you were there or not?
Alain Fourquet: No, I never, I never met him. I think, I'm not sure, but I think he died in 1969 or something. I'm not sure if that's when. So I never met with him. But Bob Calle was director here.
David Morgan: Yeah. I've been thinking, thinking back to that time in preparation for this interview. And I'm trying to remember the state of breast cancer radiotherapy back then, because breast conservation was still relatively controversial, wasn't it?
Alain Fourquet: It was very much because there were no clinical trials in the sense that we are conducting trials now. But as a matter of fact, they had at the Curie. I mean, they had started breast conservation treatments. Well, I came on a paper that was published, I think, in 1939. It was signed by a radiation oncologist who practiced at the time, a pathologist, and a surgeon. And I think the title was in French, but it was radiation therapy for locally advanced breast cancer. It wasn't on radiation therapy; it was roentgen therapy. In this paper they delivered 5,000 roentgens in protracted courses - up to six, eight, or even ten weeks - to patients who were having inflammatory locally advanced huge tumors and all this thing. But the interesting thing is that they looked at the pathological response and they classified the response in terms of complete response, partial response, minor response, and no response from the pathologic point of view. So, yeah, it was very interesting because they continued in this afterwards.
And in the '40s and '50s Baclesse had published a large series of 400-500 patients treated with radiation therapy for breast cancer. And then, they continue the group of surgeons, radiation oncologists, pathologists. They continue and they continue with breast conserving surgery, and radiotherapy and et cetera, et cetera.
And so, I came on a book published in 1972, reporting articles from a meeting in Strasbourg, in France. And there were people from the Curie, and from other centers in France (such as Dr Bernard Pierquin, from Henri Mondor University Hospital.
David Morgan: Yeah, I know very well.
Alain Fourquet: Mustakallio from Sweden, I think, and Vera Peters from Canada. And they all presented their data on breast conserving treatment of breast cancer. And the total amount was almost more than 2,000 patients treated with five years follow up. And so from that time on, it really became breast conserving surgery and radiotherapy, the reference treatment for early breast cancer, at least at the Curie in the early '70s.
David Morgan: I remember we look to the Curie in those days as sort of pioneering the -- as you say, that lots of people were involved. The Curie Institut sort of stood out as one where it was taking it forward.
Alain Fourquet: And so when I came to the Curie, it was the reference treatment. Many patients were treated that way.
Beryl McCormick: And certainly, for me in the United States, although, I think, unfortunately, for many breast radiation oncologists who really think primarily of Samuel Hellman as the person that really started breast conservation surgery in this country in Boston, just because of the relationship of a radiation oncologist called Nem Ghossein who I worked with for about a year and a half up at Albert Einstein in New York and his very strong relationship at the Curie. I really learned about this very rich, long-standing experience in France, and Canada, in Scandinavia, that's far, far came before, anything that Hellman did in Boston. And I think that's important to go into the ASTRO history books because it really did start there not in Boston.
David Morgan: Thus speaks the lady from New York.
Alain Fourquet: Beryl, you eventually came to Memorial Sloan Kettering, right?
Beryl McCormick: Yes.
Alain Fourquet: No, but I think, you know, I don't know if there is any at least transmission or a message that could be sent to the younger people. But I think it came out in a sort of an orderly way because some people were working together, and that means surgeons, pathologists, and radiation oncologists at the time.
I remember when I was a young resident at the Curie and I attended the clinics of the Head of the surgical department and this and that. He was seeing patients and he was examining them. And he would say, "Well, this is going to be radio resistant. So let's do mastectomy." Or he would say, "Okay, I could remove the breast, lady, but if I could preserve your breast and then you have the radiation and this young man here, will take you in charge." And it was already -- I remember at that time that there were exchanges every day. I mean, we were calling the surgeon in the clinics to see whether these patients were amenable to breast conservation surgery and vice versa. So it was a very endless discussion, case by case.
David Morgan: I have to say multidisciplinary treatment is of course recognized everywhere now, but my impression is that it was developing in France before other places because I only saw selected places. What you're telling me confirms this.
Alain Fourquet: I think it was mostly for breast cancer. And one of the reasons is that breast cancer, unlike other surgical or other specialties is not a specialty per se. So to take breast cancer patients in charge in a comprehensive center, like the Curie, you had to work together with other disciplines. Otherwise, there was no way you could do it, so --
David Morgan: People are seeing that for all sorts of situations now, but yeah. You were ahead of us, I think, in many ways.
Alain Fourquet: It was the case in other centers also in France. But I guess it was also helped by the fact that we have this system created in, I think, it was 1947, what we call the cancer centers. There were 20 cancer centers in France that were created just after the war.
David Morgan: 1947. Yeah. Wow.
Alain Fourquet: And the idea was to have everywhere in France centers that could allow treatment to patients at short distances. And the setting so that any patient in the country was less than 40 kilometers from the center. And so it helped us. It obliged people to work together.
David Morgan: Yes, yes. Yeah.
Alain Fourquet: That was interesting.
David Morgan: Sontre d'élude faire au Les Centres de Lutte contre le Cancer.
Alain Fourquet: Exactly. Yeah.
David Morgan: Yeah.
Alain Fourquet: And of course it goes back, if you wanted, to Marie Curie. Because at the time they created the Foundation Curie and even before, Marie Curie, along with and a clinician (Dr Claudius Regaud), were working together really to try to understand, to develop the use of radiation therapy in treating cancers, and to understand the radiobiology of the whole thing. So, really historically, it really started in the early '20s and then, yeah.
Beryl McCormick: So Alain, we've talked a lot about the history of what you inherited when you became the department chairman, but tell us now with some of your best achievements with the rest of department.
Alain Fourquet: Well, I'm not sure it's mine to say.
David Morgan: Yes, it is. Go on.
Alain Fourquet: But more seriously, what I've tried to is to continue this, especially through teaching residents bedside. One of the things nowadays that I'm not very pleased with is the fact that you have so much technology that the clinical involvement is decreasing in the young radiation oncologist in a way. I mean, they're fascinated by all this technology, but they still have to put their fingers in, if you see what I mean.
So, I try always to have them involved into this, to go into the operating rooms, to go in the pathology labs, and to understand how the disease was evolving. And to get involved also in understanding the effects of chemotherapies, and also of systemic treatments that we are using now. I mean, to have a general picture to being an oncologist, not to be a radiation whatever. I think this is a difficult task and I think that's very important these days.
So what we did also, we tried to develop, of course, clinical research. And we've done clinical research to trying to measure the effects of radiation in the neoadjuvant setting, because up until the end of the 1980s, when we started to do neoadjuvant chemotherapy, we were doing neoadjuvant radiotherapy, and we're doing exclusive radiotherapy. Many patients treated without surgery.
And so what we have, a series of almost 2,000 patients treated with radiotherapy first, and with surgery following radiotherapy or without surgery at all in the case of good response. So we had large cohorts and understanding of clinical effects of radiation therapy as it was used at the time, of course, which is a bit different now. We're more precise.
So it remains rather vivid in the sense that it has -- I think, at least in my institution, and I hope it is the same elsewhere, but it remains an important part of the treatment. It remains a way of research. We have started to do radiotherapy and immunotherapy in breast cancer, and the combination of various targeted treatments in radiotherapy, et cetera, et cetera. And one of my regrets is that we were not able to push and stronger the research in clinical radiobiology. I mean, that's specifically in breast cancer. And I think that's something that really is the future in that particular field.
Beryl McCormick: What about your involvement with the internal mammary node trial?
Alain Fourquet: Okay. Yeah. So, we’ve participated in several European trials. The first one was the EORTC “Boost trial”, testing an additional dose to the tumor bed to patients. And then I was one of the writers and designers of the EORTC internal mammary node trial with Harry Bartelink and others in Europe. I was involved also in the Young Boost trial where we tested the effects of an increased dosage to the tumor bed in young patients-- I've always been interested in the outcome of breast cancer in varying patients. Local recurrence following breast conserving treatments was mostly determined by the age of the patient at the time of diagnosis.
David Morgan: Yeah.
Alain Fourquet: So we tried to understand that. We tried with multiple studies, multivariate analysis to trying to determine what would explain that. And every time it was a bit disappointing because every time we came up with the results, it was always young age that came as the main predicting factor for local recurrence.
So we went to this and then went to genetic studies, of course, and et cetera, et cetera. So the Young Boost trial was aimed at trying to see whether increasing the dose of the tumor bed in young patients could improve the results further. The problem is in a sense - but it's a good problem - is that the overall rate of local recurrence is so low in this group of young patients, that we haven't reached the number of events that allow us to analyze the trial. And we're now seven years of follow-up, so I'm not sure.
Beryl McCormick: Oh, my goodness.
Alain Fourquet: So the rate in this group of patients is, I don’t know. I think it's like 3 percent at seven years or something in patients below 50. Right.
David Morgan: That’s powerful. I’m wondering if the extra boost will be bad for the cosmesis.
Alain Fourquet: Yeah, it is in a sense. It is, of course. It's not so bad, but it's worse than the conventional 16 Gray boost that we're using. So we will probably come up with, okay no need to increase the dose but at least it's interesting because we are able to carry out biological studies with-- the group in Amsterdam Dr Marc van de Vijver, the pathologist that's been working at NKI with Harry Bartelink is analyzing the whole population. We have tumor samples and we’re doing –-
David Morgan: How many patients now?
Alain Fourquet: Well, in the trial, there were 2,400 patients altogether. So, in roughly probably a bit more than half of them we have frozen samples, and of course the histological blocks and everything. So we were able to do this large genomic studies and the whole thing. Yeah.
Beryl McCormick: So when are you expecting to report on more of this?
Alain Fourquet: Well, probably at the ten years endpoint, we should have enough number according to the stats plan to analyze the comparison and see whether we have something. For the biological studies altogether, I don't know. It's ongoing. It might take maybe one or two years, hopefully.
Beryl McCormick: Now that will be fascinating information.
Alain Fourquet: Yeah, I hope so.
Beryl McCormick: No. I remember I was chairing a session of ASTRO the year that Anne de la Rochefordière talked about, I guess, probably your first study of pre-menopausal women, with mastectomy or with lumpectomy. I had a lot of trouble pronouncing her name and I always remember that. But that's a study I still send my residents to look at because it's so well done looking at actual age - very good.
Alain Fourquet: Yeah, she presented that well, Anne de la Rochefordière.
Beryl McCormick: Yeah, I didn't even come close to saying it correctly.
Alain Fourquet: Don't worry.
Beryl McCormick: Where do you see yourself, what do you see yourself doing in the next three to four years?
Alain Fourquet: Well, first of all, in a very practical way I will start to decrease the overall activity in terms of clinical - seeing patients, treatment and everything - starting this January. So, I will reduce. I'm still doing consultations in the clinics, but reducing the overall thing.
I've started a trial last year in DCIS, Beryl. So that sounds familiar to you. And so we're doing an de-escalation trial. We started to, you know, we've published a paper in 1983, I think, in the breast conserving treatment of DCIS. It was 52 patients at the time. And we just picked up in the database patients who had non-infiltrating disease. So we went through the whole database and picked up these small numbers, and we just looked at the outcome. And we saw that these patients who were treated with radiation - they didn't have more local recurrences -, than patients with invasive cancer. So we were interested in that.
And this, it was at the same time that the large screening programs started and then the rate of DCIS was increasing. So, we had more and more patients treated. So, last year, I started a trial in trying to identify patients with extremely low risk. So, we started with the criteria that you used in the RTOG trial. We wanted to be practical and simple so we asked the centers to do an immunohistochemical study, the IHC signature, you know, David, people from London. And so, they have to have a luminal A so-called subtype to be included in the trial, in addition to the other criteria that were used in the RTOG trial. And so we randomize them 2:1 radiation or no radiation, and so --
Beryl McCormick: That's interesting.
Alain Fourquet: So, and of course we'll have a centralized post-trial review. And we have plenty of ancillary studies, biological studies, looking at the disease itself, but also at the environment of the tumors.
David Morgan: Will the patients be getting endocrine therapy?
Alain Fourquet: No, they won't.
David Morgan: Good.
Alain Fourquet: We’re not so fascinated by endocrine therapy in DCIS.
David Morgan: Well, it is a difficult one to fight off sometimes, isn't it?
Alain Fourquet: Yeah, I know. In England, I guess, particularly. So, no, they won’t. They won’t. They won't.
Beryl McCormick: Alain, you'll be happy to know, we finally are circulating the 15-year results of the manuscript from the RTOG trial to the co-authors, after many, many back and forth. So you will hear more from us.
Alain Fourquet: I'm longing for it. That was the understanding.
Beryl McCormick: But we do have a paragraph or two discussing luminal A, although we didn't have the specimen, so I’m really excited to hear about your trial.
Alain Fourquet: Okay. So I'll let you know. So I will compile this and have a young radiation oncologist who was our resident. She's in and she's working with me and she will continue the trials when I get to retire then. So it's in good hands.
Beryl McCormick: Is there an age in France where you have to retire, like there is in the Netherlands or not really?
Alain Fourquet: Well, in medicine, now you can work, you can retire starting at 65, but you can go up to 70. But then you have to retire after 70. Well, at least in the public or equivalent system. Now if you want to go in private practice, you can go up to 80 if you want. But I'm not sure it's a good thing.
David Morgan: As long as the insurers are happy.
Alain Fourquet: So that's it, otherwise, I'm involved in the National League against Cancer, which is the fundraising body in France that have been existing for almost 60 years.
David Morgan: Tell us the full name of that, Alain.
Alain Fourquet: It’s Ligue Nationale Contre Le Cancer.
David Morgan: Okay. We probably want that for the record only. Yeah.
Alain Fourquet: Uh-hmm. So they're raising funds, and they are helping patients. A large part of it is to help patients, you know, and particularly to cope with the disease and the after disease, the going back to social and professional lives. And also they finance the clinical research programs and all this kind of thing.
David Morgan: This is charitable. This isn't publicly funded. This is true - for charity work?
Alain Fourquet: Yeah, it's charity. Yeah. So I’m quite involved in that. And I'm also very much involved in the French society for breast diseases, which is quite active. I mean, it has its own meeting. It's the only meeting, which can gather multidisciplinary participants around breast cancer as a matter of fact. Let's say it's a bit like the San Antonio in a much smaller scale, of course. But the general idea is to have people from all disciplines being together for two or three days and have a single session, a single session meeting.
David Morgan: A national meeting?
Alain Fourquet: It's a national meeting.
David Morgan: The francophone Belgians and Swiss come along.
Alain Fourquet: Right, right, and from Canada also sometimes and people from Northern Africa also.
David Morgan: What about the other organizations you've been involved with, Alain, in the past? There must be a long list.
Alain Fourquet: Yeah, well, not so long. I've been very much involved in the clinics and everything. So you have to find the proper balance, I would say.
David Morgan: Of course.
Alain Fourquet: So I've been involved in ASTRO a bit. I was involved in the EORTC maybe the first 10 or 15 years of my career. I was --
David Morgan: Well, I think that's where we met, wasn't it? Yeah.
Alain Fourquet: We met there, absolutely. This is what I'm wanting to say. And I was involved in the Curie. I was, for almost ten years at the board of the administrators of the whole institute, you know, both the research center and the hospital. So I was involved in a number of things. I was involved in ASTRO a little bit. I was in ASCO also, so these kind of things but -- yeah.
David Morgan: Yeah. Going on, what, Alain, do you think was the work that came out of the -- what would you highlight from your time in those various organizations that you think has been important developments? What stands out for you?
Alain Fourquet: Well, I think, again, one thing in the early years was really to - it was both things - set the breast conservation as really the reference when it, of course, met the criteria for it. So I guess, quite frankly, the people adopted it, and really now, everywhere in the country. And it has been the case for quite a long time now - a very large percentage of the patients that can be treated with breast conserving treatment actually receive breast conserving treatment. And this has been the case since, I would say, maybe the mid '90s or even earlier--
David Morgan: It most certainly wasn't the case when you were starting at Curie. It might have been there but it wasn't accepted everywhere else by any means, was it? I can’t remember.
Alain Fourquet: Yeah. Right, exactly. So I think we pushed very much for that. Second, it was for DCIS because, really, at the time, DCIS was considered to be a radio resistant tumor coming from nowhere. And, really, we were able, through the communications, papers, meeting, whatever, to improve that and to have it. Now, really breast conserving surgeries is carried out.
I have been involved from the very beginning also in designing and writing the guidelines for breast cancer management in France. So I started this in 1994, I think. So it helped though, you know, I'm very modest about the whole thing. But I guess it helped to sort of homogenize the practice in the country, and to help people to refer to something, to be more confident in what they are doing.
David Morgan: Now, you're being very modest about this, Alain. We know it's very important.
Alain Fourquet: No. I think it is. The guidelines per se really depends on how people are using them. But the general idea, I think, that's really an improvement to -- what do I say? To have people be confident about the decision they're taking of preserving the breast, choosing for radiation, and also helping them to more precisely define their indication. And also be able to somehow resist other disciplines. Why are you still doing this radiation, et cetera, et cetera.? So I think that --
Beryl McCormick: Alain?
Alain Fourquet: Yeah.
Beryl McCormick: Do you have a set of those guidelines also oriented towards patients like the American NCCN guideline? Or are they mostly for physicians?
Alain Fourquet: Well, at the beginning they were for physicians, of course. And that's with the evolution of the mentalities and experience. Now, for the past ten years maybe both in the institutional guidelines and the national guidelines through the National Cancer Institute in France (Institut National du Cancer), we always have patients involved. And when the guidelines are reviewed before being released, they're reviewed by groups of patients. They give their point of view. So it's much more, there's a much larger implications of patients to be present than when I started, of course.
But we try to keep, to design the guidelines based as much as possible on the evidence, which is not -- of course, you don't have the evidence for anything. But at least trying to keep a rigorous and orderly way to design these guidelines and to really mention if: this we know; this we don't know. So there are options and then we can choose.
But the way patients are involved is probably quite different though maybe not so much in France, at least, in the States. We know that sometimes patients are completely lost when they're asked to choose and to decide because they are sort of drowning in the sea of information coming from everywhere all the time. So sometimes, I still have quite a large number of patients after a while that says, "Okay, I'll let you decide," because they're lost. They're simply lost. It's too much information to swallow in a short period of time.
Beryl McCormick: I think that's a good point anywhere. Okay.
David Morgan: What thoughts for the future, Alain?
Alain Fourquet: Yeah. Okay. Well, one point I didn't mention is that I think one thing for the future in terms of pure radiation oncology technology is the use -- at least is some development of proton therapy in breast cancer. Not every patient, of course, but some patients particularly those very young patients, those patients who have a family or genetic breast cancer predisposition. In a sense that using protons helps to really target better, and to avoid the contralateral breast when treating the ipsilateral breast. You know, IMRT and VMAT and TomoTherapy or whatever are very nice tools, but in very young patients, I don't choose them because the dose to the contralateral breast --
David Morgan: Yes. You know, they splash the dose around everywhere. Yeah.
Alain Fourquet: And patients that have BRCA1 or 2 or other mutations you really don't know that - what's the impact of increasing the rate of contralateral breast if a patient does not choose to have a mastectomy. So protons can be helpful with breast cancer, you know. Comparative studies in that and then we started to include patients in the study for proton in this particular group of patients at risk, I would say.
And, again, the future, as to my opinion, is really -- of course, it's personalized medicine, which means radiation therapy to be able to really identify the patients who may need or may not need radiation; to identify the type of patients who may benefit from certain type of fractionation versus not, et cetera, et cetera, et cetera; and patients who may need to be given concurrent targeted therapies whether it be targeted antibodies or immunotherapy in breast cancer. There's a lot to do there. It's a nice study we have then. So we started trial with the anti-PD-L1 and anti-CTLA-4 in patients with breast cancer concurrently with radiation too really to test for the response, the tolerance et cetera, et cetera.
David Morgan: I imagine that like everywhere else, this pandemic has had a big impact upon what you're doing. How do you think that will affect a lot of things going forward? Do you have any views on that?
Alain Fourquet: Yeah. We started in March and the lockdown was in March 16, so we had to very rapidly, very quickly reconsider the whole picture and for all patients. You know, we treat 5,000 patients per year in radiation therapy. And almost 60 percent of them are breast cancer. And so --
David Morgan: Do you think the changes you had to make will be carried on if and when the pandemic recedes? What are your thoughts on that?
Alain Fourquet: Well, we know what to do in terms of adaptation because we were able to reduce the treatment time because we used, reduced fractionation scheme and this and that. So if it goes up again we know at least what to do. We probably tried to learn from that, of course, and see what we can keep or not for routine practice afterwards so we may learn from it.
But I would say it's probably a bit early. We got to analyze the whole thing at least one year after and to see how the patients that were treated within this period of time - two months with altered fractionation schemes and delay in initiating radiation, what was the outcome a year after. So we're gathering the information and see.
But, yeah, we're probably, like always, under pressure and this way you're pushed to innovate and to learn from what you've done and see how we can try to apply in practice afterwards.
Beryl McCormick: Any words of wisdom for the historical committee.
Alain Fourquet: Okay. Well, I guess, at least a word of wisdom, I don't know but easy words. But I think towards the young people, I think it's a nice discipline because it's common sense. But you're doing clinics but you still have to do the clinical work and that's very important in radiation oncology. Again, I repeat this but I think it's essential, particularly vis-à-vis the other disciplines. It's important to appear as a clinical discipline. It's very large. You're doing physics. You're doing biology. You're doing a lot of things that's quite fascinating. And it really is something that should attract the young people.
And maybe to conclude but, I guess, it's not new. And you went through this yourself at different times because when I started radiation and met with a surgeon and afterward with the medical oncologist. You know, Bernie Fisher was one of the guys who said this kind of thing says that, well, ten years from now, radiation therapy will have disappeared and this and that. Forty years after it's still here and it's very dynamic and, I guess, it's very important.
I would say it's regaining and that's particularly true in breast cancer. It's regaining importance in terms of local control, of the impact of local control and survival, and also, now, of course, treatment of resistant oligometastases and polymetastases that really may improve the overall survival of the patient. So it's a never ending story. And I'm very glad to have went through that part of this history.
David Morgan: I agree.
Beryl McCormick: Okay. And wonderful to speak to everybody, I hope we get to see you in Paris personally very soon, Alain.
Alain Fourquet: And in Brittany, Beryl, I spent the summer in different places in Brittany, it was great. So next time, let me know.
Beryl McCormick: Yeah. No. I'll catch up with you because that's definitely on my list of things to do.
Alain Fourquet: Okay. Okay. And thanks very much. And David, I hope I'll see you soon.
David Morgan: Great to talk to you.
