James Cox, MD, FASTRO
Question: I am Gustavo Montana, Chairman of the ASTRO History Committee, and with me is Dr. Herman Suit, also a member of the History Committee. We will be interviewing Dr. Jim Cox, a particularly accomplished member of our Society and our specialty. Today is June 17, 2011. First of all, I want to thank Jim for giving us the time to conduct this interview. This is really very important for the Society to document the history of our Society and our specialty.
Dr. Cox: It's my pleasure.
Question: Thank you. I would like to begin by asking you to tell us about your beginnings, where you were born, a bit about your family, if you have anybody who was influential in your career or how your career evolved, and where you went to school.
Dr. Cox: I was born in Steubenville, Ohio, but I grew up in Dayton, Ohio. Through connections there, actually through somebody who impressed my father very much, I applied and eventually was accepted to Kenyon College in Gambier, Ohio. I spent four years at Kenyon, initially in a combined curriculum of biology and chemistry. I wasn't committed to going to medical school until my junior year.
Question: Tell us a little bit about how you made this commitment to medical school.
Dr. Cox: Well, I was interested in science all the way through, and I did well in those courses. I had a couple of professors who I respected greatly who suggested, between my sophomore and junior years, that I consider medical school. I didn't have any physicians or scientists in my family.
Question: Nor did I.
Dr. Cox: but I had an older sister who was always critical of what I did. She didn't think I was very smart until she gave me an IQ test for part of her psychology course in college and then she said, well, maybe.
Question: So how did you select your medical school?
Dr. Cox: A professor of physiology from the University of Rochester came through Kenyon as a lecturer. He was also recruiting for the physiology laboratories at Rochester; he had some summer fellowships that he was prepared to offer, and I, and three of my colleagues from Kenyon, ended up going to the University of Rochester for eight weeks on that fellowship. That really sealed the deal. I knew that I wanted to do that and I ended up applying to the University of Rochester Medical School and was accepted.
Question: Now, here is one of the most interesting things in your CV and it is that you went to Penrose Cancer Center before graduating from medical school.
Dr. Cox: Yes. I became interested in cancer from the time I took pathology in my second year of med school. I mean, I was just fascinated by the disease and anything having to do with its presentation and the patients and the research possibilities and everything. It was common at the University of Rochester to take a year out of medical school to do research.
Question: Where had you heard about radiation therapy and did you meet anybody in the specialty? How did you hear about Penrose or Regato?
Dr. Cox: Well, at that time I wanted to apply to a cancer hospital for my year out of med school. I didn't want to do it in a laboratory, I wanted a clinical environment. So I wrote, I think, five letters to various places, and the most interested and interesting reply I got was from Juan del Regato, who said, "We've never had a student for a year and we kind of don't know what to do with that, but I'm interested and I'll see if I can find some funds." So, with some funds from his training grant and some funds made available by the American Cancer Society in New York, I went to Penrose for a year.
Question: How did you hear about del Regato, in the first place, to write a letter?
Dr. Cox: Well, the cancer coordinator at the University of Rochester was a surgeon, and he came up with a list of possibilities, including Jacob Furth. Del Regato was the only radiation oncologist on my list.
Question: Okay. That was very interesting. It's nice to have this on the record.
Question: So, Jim, del Regato already had a training grant. What year was that you went to Penrose?
Dr. Cox: In 1963.
Question: In 1963, so that was around the same time that Kligerman and Kaplan got their grants and their training programs established.
Dr. Cox: Right. But del Regato had been training people in what was then called therapeutic radiology since the 1950s, when everybody else was still training general radiologists. And so his program from way back then was totally geared toward training people for radiation oncology. And at some point, probably about 1969, one-third of all of the board-certified therapeutic radiologists in the United States had trained at Penrose.
Question: Sure.
Dr. Cox: He had a profound influence on me. He became like an intellectual father to me, and we had a wonderful relationship until he died, except when we had a fundamental political disagreement that was quite severe during the last two years of my residency.
Question: Can you tell us about that?
Dr. Cox: Well, del Regato considered himself to be a liberal of the mold of Hubert Humphrey and I think most of the rest of the world thought that had become old and conservative. And I was opposed to the Vietnam War, even though I volunteered for the draft in 1965 during my internship to become a candidate for the Berry Plan. And I was accepted into the Berry Plan. So I was actually an inactive reserve in the Army while I was a resident at Penrose. And then after my residency and a year of fellowship at the Gustave Roussy, I went on active duty in the military in July of 1970.
Question: Can you just comment a little bit about your time at the Gustave Roussy?
Dr. Cox: Well, I went there primarily to work with Bernard Pierquin, because we did not have very much in the way of brachytherapy experience at Penrose and Bernard at the time was considered the master . . .
Question: … the king….
Dr. Cox: Yes, the king of brachytherapy, right. And he was incredibly creative, and of course, Andrée Dutreix was there then, and the physics team at Gustave Roussy was really powerful. And, of course, Maurice Tubiana was chairman of that department, and later became director of the institute. And when Pierquin accepted the position to become head of the department at the Henri Mondor University Hospital in Créteil, Daniel Chassagne became the chairman of the radiation oncology department at Gustave Roussy.
Question: How long were you there with Pierquin?
Dr. Cox: A year.
Question: And did you enjoy it?
Dr. Cox: Oh, I had a fabulous time. I learned a great deal about brachytherapy, but it wasn't confined to that. I worked with Pierquin for only about five months and then I was involved in a project on lymphomas, and then I took a month and went to England and I went to the Royal Marsden, I went to Manchester and I learned a little bit about what was going on there. I went to Oxford and met Frank Ellis and so I got to meet a lot of the really, really big pioneers.
Question: Legendary figures.
Dr. Cox: Yes, legendary figures. Ritsuko [Komaki] just brought back news of several of them from the most recent ESTRO meeting. She spent a lot of time with Andrée Dutreix, who brought her up to date on a lot of people. Sadly, Pierquin had just died of carcinoma of the kidney at the age of 90. And Jean Dutreix is pretty frail. And Tubiana is frail. He's over 90, but very sharp. Mentally he's really very sharp. Just like del Regato was in his later years. He became frail physically, but he was mentally very sharp. Daniel Chassagne is still around and doing okay.
Question: After you had this year, did you do any projects, write a paper, anything of the sort?
Dr. Cox: Yes, I wrote a paper with Alain Laugier and the pathologist Gerard Morehand on what would now be called diffuse large-cell lymphomas arising in nodal or extranodal sites and the difference of behavior in those two groups.
Question: Okay. Well, then you then came back to the states.
Dr. Cox: I came back to the states and went on active duty in the Army and was stationed at Walter Reed in Chevy Chase in 1970-1972. I was fortunate to be able to practice radiation oncology during that time. Jack Maier was my commanding officer and then became head of the department of radiology. When Jack decided to retire from the Army and Walter Reed ran out of regular Army radiation oncologists during my second year there, I became the head of the radiotherapy service there by default. Although it didn’t involve much in the way of administrative responsibilities, that was my first job as leader of a section or anything like that. Then Jack was recruited to go to Georgetown, and he asked me to go along with him. However, about a month before we were due to leave, he changed his mind and decided to go to George Washington instead. Georgetown didn't have anybody, so they turned to me. And so at the age of 34, I became the head of the radiotherapy section in the department of radiology at Georgetown.
Question: So, Jim, were you with Jack Maier at Walter Reed when he did the work on seminomas?
Dr. Cox: No, he had already done that by that time. My contemporaries, who were also in the Berry Plan, were Leonard Shukovsky, who came from MD Anderson, and John Fazekas. We had a very interesting group—a lot of disagreements, a lot of excitement, a lot of fun. I learned a lot from them and from the whole environment. I wrote a couple of papers there with people at the Armed Forces Institute of Pathology in the hematopathology department, because I was primarily interested in lymphomas at that time.
Question: So from Georgetown you went to Wisconsin.
Dr. Cox: Yes, I went on to the Medical College of Wisconsin because—well, Jack Maier actually had suggested my name as a possible candidate for the head of radiation therapy. It wasn't a department yet, but they did have radiation oncology at the Medical College of Wisconsin. Georgetown clearly didn't have enough money to do the things that they needed to do to make it a top-flight place, so I went to Milwaukee. And then I recruited Frank Wilson to come with me, and we recruited Roger Byhardt, and that was the start of the department at the Medical College of Wisconsin.
Question: And from there then you went to Columbia.
Dr. Cox: Yes, largely through the influence of Eric Hall, with whom I had become very good friends, I went to Columbia Presbyterian Medical Center. As is usually the case in these things, they made a lot of promises. However, after I had been there a year or a year and a half, the head of the hospital called everybody in and said we're losing $2 million a month, we can't keep this up. Basically he said they couldn’t afford to meet any of the promises that they had made. At that time, Jerry Dodd, who was the head of radiology at MD Anderson, had suggested me for the position of physician in chief at MD Anderson. And so I interviewed with Charles LeMaistre, who was the president at the time, and with the heads of the various divisions at MD Anderson, and they offered me that position. It was, in a sentence, a great title and a bad position.
Question: So as physician in chief you were at the top of the administrative staff.
Dr. Cox: Well, I wasn't at the top. That was the problem, because LeMaistre could veto anything that I wanted to do, and the division heads—heads of pathology, surgery, medicine and so on—all had direct access to LeMaistre. So if I didn't do what they wanted, they went to him. So I wasn't able to accomplish anything, and I became very frustrated, and they became frustrated with me as well. That was arguably the worst four years of my career. The only thing that kept me sane during that time was the RTOG.
Question: Oh, I hadn’t known about that.
Dr. Cox: Yes, I was running the RTOG at that time and that was my sanity. It was like having a great research lab and I was responsible for it. I went to Philadelphia about three days out of every three weeks and spent time on the phone every morning with Tom Pajak, who was the statistical head. And so with Tom being sort of the scientist in residence at the RTOG and my being in Houston, we were really able to accomplish a lot.
Question: Well, that's for sure. How long did LeMaistre stay there at MD Anderson?
Dr. Cox: LeMaistre retired in late 1995 or early 1996 and was succeeded by John Mendelsohn. I had stepped down as physician-in-chief in 1992 and had gone back to taking care of patients and working with residents and so on. When Lester Peters decided to go back to Australia, I said, well, I do know how to lead a radiation oncology department, so I put my hat in the ring and was eventually selected to do so. I was head of the division of radiation oncology for 15 years until I stepped down in November 2011.
Question: I thought you were head of the department during your time with LeMaistre…?
Dr. Cox: No, I was not department head while I was physician-in-chief, which was part of the problem because Lester wasn't happy with my being in his department, on the one hand, and on the other hand being his boss. That was not a comfortable situation.
Question: Okay. Now we understand. Some of the difficulties for the physician in chief in that situation were that the department heads could go directly to the top administrator and bypass you.
Dr. Cox: Yes. You can read between the lines and imagine what that was like. So anyhow, once I gave up that job, I became much, much happier at MD Anderson. I came fully to realize what a great institution it was in terms of caring for patients and how it, and we, were turning the corner in clinical research. And I think I we influenced that turn a fair amount. We helped to influence both the department and the institution to look beyond the really good stuff, the fantastic stuff they were doing, though in a somewhat isolated way, and become leaders in the RTOG, especially in head and neck, lung, and GYN cancer.
Question: Well, since you mentioned Ritsuko several times, why don't you tell us how and when you first met...
Dr. Cox: Well, we met in Milwaukee. She was pursuing postgraduate training in the United States on the advice of a radiologist who worked at what was then called the Atomic Bomb Casualty Commission in Hiroshima, which was her home town. And through Walt Russell and his good friend Jim Youker, she got in a somewhat roundabout way to Milwaukee, and she was working at the VA. She was interested in leukemia because of her experiences in Hiroshima. And then she saw patients treated with radiation therapy for lymphomas and she became interested in radiation oncology and so she wanted a residency and so she became a resident.
Question: Very good.
Question: Excellent. Well, Herman and I understand your position and the different roles you have had at MD Anderson. I know that Herman would like to ask you some questions about proton therapy.
Question: Yes, I think it would be very interesting for us to hear something about the major roles that you've played and how, during your tenure as head of the department, the research developed in terms of laboratory research, clinical research including the proton. And any one of these that you'd like to start with would be fine. I saw on Google your very strongly enthusiastic statement about the proton therapy program that you now have up and running and doing all sorts of nice things. But whichever you'd like and in whatever sequence you want, I think we'd both be glad to hear you describe your biography in that area.
Dr. Cox: In terms of timelines, in December 1995 I took over as chairman of the department of radiation oncology and head of the division of radiation oncology. The division had, and has, two other departments, experimental radiation oncology and radiation physics.
Question: So the division of radiation oncology included physics and radiobiology. Is that correct?
Dr. Cox: Yes, they're part of the division, which is the superstructure over the three departments--clinical, physics and radiobiology. In other institutions, the nomenclature would be reversed -- the larger entity, the department, would have three component divisions. But here at Anderson, the departments are components of the division.
Question: Okay. So please step forward, then.
Dr. Cox: We had expanded the clinical operation a lot. We got a lot of new equipment. The department was behind as far as equipment was concerned and so we started very carefully expanding the equipment capabilities. The institution was wonderfully supportive as we went to advanced techniques, advanced accelerators, and we opened a separate department across the street from the main hospital in a new outpatient building that housed the offices of GYN, GU and breast, with associated faculty and trainees. So the department grew to include six accelerators, two simulators and various other equipment. In the clinical department, the department of radiation oncology, we went from a faculty of 17 to about 55 physicians. I don't know exactly how many physicists were on board when I took over, but now there are 50 to 55 physicists.
Question: Now these are PhD physicists?
Dr. Cox: I think 40 of them are PhD physicists and about 15 are masters-level physicists.
Question: Okay. And the patient load has gone up from what to what?
Dr. Cox: The patient load has gone up from about 225 patients a day to about 600 patients a day, not counting the patients treated at the satellite facilities. In 1999, we started a satellite program when one of our stellar trainees who was coming out of fulfilling her Air Force obligation wanted to practice in Houston. As luck would have it, a nearby facility was available that had fallen on really bad times and was really in a mess, and we could pick it up for not much. And so we started a satellite program with her as the lead figure, and she took it and grew it, and now we have six facilities, which are now called regional care centers because they now include medical oncology and, within the past year, they've added surgery. Each one of these regional care center started with a radiation oncology program. And now they're treating about 160 or 170 patients a day over and above the 600 I mentioned.
Question: And all the 600 are at the MD Anderson per se.
Dr. Cox: Yes, those 600 are all treated at the MD Anderson campus. But about 110 or 120 of them now are at the proton center.
Question: Well, is there any radiation oncology center in the world that's treating at the primary site more than 600 a day?
Dr. Cox: Yes, there are a couple, I think, Herman. And I'm not sure about that, but one of them is Princess Margaret.
Question: Oh, how many are they treating?
Dr. Cox: I think they're treating about the same number.
Question: Okay. Well now, then, do you want to go ahead and talk about your development of the proton center or...
Dr. Cox: Well, let me tell you just the evolution. When I was division head, I recruited Radhe Mohan, who was at the Medical College of Virginia and had previously been at Memorial as the head of physics. And he helped the development of this technology in an incredibly strong way. And he was very strongly interested in research. When I took over the division, we had no extramural funding in physics, no peer-reviewed extramural funding in physics. But after Radhe came on board, we competed for and won several R01s. And then the P01, which of course as you know is in collaboration with Mass General. And the P01 is focused entirely on protons. So that developed very, very well. We also recruited Mike Gillin from Milwaukee, we recruited Al Smith who helped work on the proton equipment development with Hitachi, and then several other people who are also really strong in physics. On the radiobiology side, we recruited two people during the early phase of my heading the division, both molecular biologists. One was Lei Li, whose main work is in DNA damage and repair; later we recruited Khandan Keyomarsi, who is working primarily in the area of cell cycle regulation.
Question: All right. Well, that sounds very good.
Dr. Cox: And of course Luka Milas joined us and chaired the radiobiology group (officially the department of experimental radiation oncology). He and Kian Ang did a great job with another very long running P01 here, which focused on head and neck cancer but involved many types of research as well.
Question: Did you know that I had recruited Luka when I was there?
Dr. Cox: Yes. Yes, I knew that.
Question: So I know him well.
Dr. Cox: Well, he did a really fantastic job. He, Kathy Mason, Lester Peters,while he was here, and Kian Ang really did an excellent job in doing research primarily related to tumors and normal tissues in mice. And that work ultimately came to be very important for the development of molecular-targeted work with the EGFR antibody erlotinib (Erbitux). The discovery that erlotinib and other molecular-targeting agents interacted favorably with radiation treatment then served as a basis for developing clinical trials, with the ensuing success of Erbitux combined with radiation therapy for head and neck cancer. That's been very successful. Ray Meyn took over after Luka retired. And then about two or three years ago Ray and I were working to recruit a new chairman of experimental radiation oncology, and we recruited Junjie Chen from Yale. Junjie he is a very successful scientist, a fundamental biologist working in the area of DNA damage and repair. And he's got a great publication record. He's doing a good job. It took a little while to go from running a big laboratory to running a department, but it's evolved nicely now.
Question: Okay, very good.
Dr. Cox: And so what else can I tell you about? Do you want to hear about protons.
Question: Do you have PhD students?
Dr. Cox: Yes we do, although I can’t tell you exactly how many we have right now. The institution was granted the right by the University of Texas Board of Regents to award degrees of various levels to students in physics and biology through the Graduate School of Biomedical Sciences, where MD Anderson faculty members teach about three-quarters of the courses.
That’s actually another area in which we have made great strides over the years—we now have a big educational component. When I took over, the residents were very nice people, but their orientation was not particularly academic, and usually when they left residency they went into private practice. It took a long time to change that, but for quite a few years now, we have been able to recruit outstanding physicians, in many cases budding physician-scientists, to join our faculty. Our MD-PhDs typically spend probably 75 percent of their time working in the laboratory. And so the residency program has evolved in a direction that I wanted to see when I took over, so I'm happy about that.
Question: Very good. Congratulations.
Dr. Cox: Okay, protons?
Question: All right.
Dr. Cox: I don't know if you'll recall, Herman, but I was part of a site visit team that was put together by the Board of Scientific Counselors of the Division of Cancer Treatment at NCI somewhere around 1989. A proposal had come in from Mass General to develop a proton center, essentially moving the work from the Harvard Cyclotron Laboratory to Mass General.
Question: Oh, yes. Of course. I remember that.
Dr. Cox: And the administrative people at NCI were not happy about that plan, for reasons dating back to Henry Kaplan, who had put in a proposal for a huge grant for pi mesons many years earlier. At that time the NCI group wasn’t going to consider any major developmental grants that would involve tens of millions of dollars for construction. I think the proposal for Mass General, which if I recall, Herman, you may have done, was the first one that they had come up against since then, and so they wrestled with that. And among the things that they did was have this site visit team go to Boston and investigate protons, to sort of say what was this all about and what could be done and so on. And I was on that site visit team and at that time, in the late 1980s, I must admit my shortsightedness, that I didn't see any particular value for proton therapy, but I turned out to be wrong. And what convinced me I was wrong was the evolution in radiation therapy techniques between the late 1980s and the late 1990s, first on 3-D conformal therapy and then later on IMRT, but especially going from 2-D to 3-D and 3-D conformal in being able to give higher doses to tumors and avoid normal tissues and avoid side effects and all of that. And then I realized, well, gosh, I mean, protons are a natural evolution of that progress, going from 2-D to 3-D to IMRT [intensity-modulated radiation therapy] and beyond, the natural progression of that I think is proton therapy and now IMPT.
Question: Well, anyway, eventually we did get the grant.
Dr. Cox: Yes, that's right, and I think it helped a lot with the development of your very nice facility there at MGH.
Question: Although we had the grant for the work at the Cyclotron Lab from '76 onward.
Dr. Cox: I know, I know.
Question: But having had that grant certainly facilitated putting the new facility on the campus here, no doubt about it.
Dr. Cox: Sure. And the work you all did with the development of proton dosimetry and advancement of the potential for proton therapy, I mean, was great.
Question: Yeah, well, let's hear more about you.
Dr. Cox: All right. In 1998 we said, okay, we ought to develop a proton capability at Anderson. And I went to the powers that be, primarily to John Mendelsohn and the financial team working with him and said we really need to do this, it would be really a great step forward. And I had a good relationship with John and those people, who felt I was credible as far as they were concerned, so they took the effort very seriously. We went to the UT system and said we would like to do this and the people at the UT system said that's all well and good, but we're not going to give you $125 million because it would mess up our bond rating. And so we had to go out and try to find a way to raise funds, and we did that through a public-private partnership with investors in the community. And when we came up with enough money, we looked for vendors. We were very impressed with Hitachi's program, especially at Tsukuba, what with their manufacturing capability and how deep they were and what engineering capability they had and so on. So we selected Hitachi as the vendor. During that time, Al Smith and others, including Wayne Newhauser and others from MGH, worked very closely with Hitachi and were very demanding about what we wanted to have done, including the development of a scanning beam technology. So we built the facility and installed the Hitachi equipment and started treating patients in May 2006. Rather a long time between 1998 and 2006, but as facilities of this type go, it's not too bad. . .
Question: Par for the course.
Dr. Cox: Yes indeed. So we've been treating patients since that time. We ramped up slowly. We had two gantries and one fixed-beam room. And in 2008 we brought the third gantry online, the one with the scanning beam. And we used the scanning beam, not in a pure IMPT mode, but for shaping and for efficiency. And we've treated, oh, I don't know, probably more than 500 patients with the scanning beam now.
Question: Oh, very good.
Dr. Cox: And over the course of the past year or so, we've slowly developed multifield optimization so that we are able to do IMPT. The problem on that is the QA [quality assurance], which our physicists are quite rightly compulsive about. The QA for every patient treated with IMPT takes about eight hours of physics time. So we can't treat very many patients yet, and we've got to become more efficient and we have to hire more physicists and we're working on that. But, we've treated probably 25 or 30 patients with IMPT or multifield optimization by this time. And we've also begun treating patients with cancer of the head and neck. In that sense we've finally turned a corner that leaders in treating head and neck cancer have come to realize the value of IMPT for head and neck lesions in terms of being able to avoid normal tissues. Kian Ang is increasingly enthusiastic about it, so much so that he thinks that we could open the floodgates by treating carcinoma of the oropharynx, but at this point the QA process is still too long and laborious, and we're not ready to do that quite yet.
Question: So besides head and neck tumors what are the other major groups of patients or tumors you are focusing on or exploring proton therapy for?
Dr. Cox: Our goal from the very beginning was to try to expand proton therapy into all disease sites where protons might have some benefit. And so beginning in January 2004, well over two years before we opened, we started having weekly meetings to develop protocols for the various disease sites. One week we would discuss GU, and the next week it would be thoracic, and the next week GI and the next week GYN and CNS and kids and so on. And the program itself has matured from those meetings. We are treating an especially large number of thoracic tumors, lung or esophageal cancer, with concurrent chemotherapy and proton therapy, something that has not been done very much. And of course in the process we’ve had to learn how to manage motion of the tumors in the chest, including the distal esophagus. We started working on motion management strategies around 2004 with the goal of being able to use them with IMRT. So we've had a group working on motion management research for at least seven years now. And our standard for every patient with thoracic tumors is to get 4-D CT scans and track the movement of the tumor and the normal tissues on those scans throughout the respiratory cycle, and account for that motion during treatment planning. Last year we treated 80 patients with cancer of the esophagus, a figure that just blew my mind. And we've treated probably three times as many patients with cancer of the lung.
Question: But I'm sure that you keep in mind that you expect to achieve a better outcome than with conventional treatment because there is the issue of cost. The cost differential is such that this needs to be factored in very seriously. The other thing is that the patterns of failure have to be primarily local to justify the more expensive proton therapy.
Dr. Cox: That’s a very good observation, and we are looking very closely at that. We just completed a project looking at the patterns of failure, detailed patterns of failure after proton therapy in 57 patients with lung cancer with a minimum follow-up time of two years. These patients received a total dose of 74 Gy-equivalents. And what we found was 10 failures within the high-dose area and 2 failures at the margin of the high-dose area. So 12 local-regional failures of 57 patients with locally advanced non-small-cell carcinoma of the lung—that’s pretty good. It's 80 percent thereabouts. And I don't know any proton experience that's been comparable to that.
Question: And you need to total up the cost of taking care of the failed patients; you talk about the cost of proton therapy, the cost if there's a difference in the failure rate or difference in the complication rate, both of those are expenses that need to be factored in as well.
Dr. Cox: Exactly. And there's no place where that is more true than the children. We've treated a lot of kids with medulloblastoma, and if we can avoid irradiating all of the structures anterior to the vertebral body by using protons . . .
Question: Well, we can. It's established. That’s not an opinion.
Dr. Cox: That's right, I agree, Herman. The group at the Karolinska has modeled the economics of that showing that it's cost-saving in the long run to treat those kids with proton therapy by virtue of what you can avoid in terms of taking care of side effects.
Question: At this point there is no disagreement with that. But with the enormous problem of the high cost of healthcare, it is extremely important to target the use of proton therapy for tumors or diseases that have a very high, or relatively high frequency of local failure and low distant metastatic disease failure rate.
Dr. Cox: I agree. However, if you want to put this in perspective, I've got a little talk that I gave recently called “Economic Considerations in Proton Therapy.” And one of those considerations was the total cost of proton therapy in 2008 in the United States, which was estimated to be $73 million. The cost of the top four drugs in the formulary of the MD Anderson Cancer Center for the same period—just the top four drugs—was $92 million. One institution, four drugs. So you put that in perspective, the cost of protons, I think, is really quite a small part of the cost of healthcare for patients with cancer.
Question: I’m certain you are very aware of this and I don't want to go into a economic debate, so we can move on. But I would love to talk more about this. So I think that looking at the overall issue of healthcare cost, I think that we have to be very cognizant of the cost that is transferred to society and to individuals.
Dr. Cox: Well, I agree. In my talk on economic considerations, I look at it from the point of view of the patients and from the point of view of society. And in both cases, proton therapy does not end up looking bad.
Question: Oh, no. But I think we'd better proceed to let you finish your discussion about proton therapy and how it's working out in your institution and then go to maybe to physics or whatever.
Dr. Cox: Okay. So we have now expanded our treatment capabilities, and we are treating on average somewhere between 115 and 120 patients a day. About 40 percent of those patients have cancer of the prostate. About 30 percent have thoracic tumors, either lung or esophagus or sometimes other tumors. About 15 percent are kids and another 15 percent or thereabouts have brain tumors, so that's the approximate breakdown. We're moving forward with treatment for tumors in the liver in conjunction with the work at Mass General, and we're also moving forward with the protocols for children.
Question: Now, is Kian going to get any slot for head and neck?
Dr. Cox: He is; he's quite interested. As I mentioned earlier, the problem there is that he feels that if we’re going to do better than IMRT, then we need IMPT, and we don't yet have efficient processes for quality assurance in IMPT yet. We're working on it, we're going to get there, but we’re not there yet. But he is very interested.
Question: Very good.
Question: This has been a wonderful and very illuminating discussion about your personal experience with the use of protons. So, Herman, do you have any other questions?
Dr. Cox: While you’re gathering your thoughts, I need to say something here. To be fair to Herman, when he first came and talked about this, he said there's not a photon plan that he could not improve upon with protons and he was absolutely right. So I have become convinced and am now at least as strong an advocate in support of his viewpoint as anybody.
Question: Well, thank you very much. Now, with respect to your plans, do you want to just say anything about any future developments that you're pushing in terms of 4-D this and 4-D that or making Monte Carlo available or...
Dr. Cox: Yes indeed, we are working on Monte Carlo. We’re using Monte Carlo calculations right now to assess the in-field and out-of-field failures in that group of 57 patients with lung cancer. That's ongoing work.
Question: Yes. Well, I imagine it won't be too long before practically -- you know, another few years as we get bigger computers that Monte Carlo will be routine and standard.
Dr. Cox: I think you're right.
Question: Oh, what about imaging? Are you doing any special, what would you want to say about your view of future developments?
Dr. Cox: Well, one of the things that we need desperately—and probably is a weakness at MD Anderson at the present time—is some capability for molecular imaging. I mean, we've got so much interest in molecular targeting agents, and we've got a whole department on targeted therapy, and we're very interested in the interaction of radiation therapy and chemoradiation with biologic agents, so we want to move forward with that clinically. This kind of work is moving forward in the laboratory with the xenograft mouse models. But what we don't have, I think, is the sophistication in molecular imaging that I wish we had. I think there are other institutions, including Mass General, are well ahead of us in molecular imaging. Duke, too, and Stanford have some really outstanding programs.
Question: Well, anyway, if you set your goal on it, you're going to catch up or pass.
Dr. Cox: So true. And we are working toward that. We have physicists and imaging experts.
Question: How wonderful it is to know that you have people advancing in the same area and that they're going to leapfrog over you unless you really get busy. And so this is a powerful stimulating thing.
Dr. Cox: Yes, right. I think that's the main area that we need to get going on. And to pursue the physical targeting with protons and all of the image management—all of the motion management stuff that goes with that, and the biological targeting, alone or in combination with chemotherapy, That's what we're working on in the immediate future, and the imaging, the molecular imaging part of it is a critical piece for the future.
Question: So you're doing that in part to determine in the actual patients…?
Dr. Cox: Yes, but we’re not doing the imaging of protons in real time.
Question: Well, I thought—well, that's another application of these imaging...
Dr. Cox: It is.
Question: But I don't know whether it's so -- what advantage it has over just plane calculations with good CTs.
Dr. Cox: I don't know either.
Question: Anyway, it's something that we're doing here, but it's very high-tech, but I don't know exactly what is the real gain. With very high-quality CT and density analysis, it gets pretty darn accurate with just the calculations, the pure physics.
Dr. Cox: Right.
Question: Now, do you have a lot of people coming in and spending time with you and doing fellowships, etcetera, in the particle therapy program?
Dr. Cox: Well, we certainly have had quite a few people who want to come and spend a month or two. We have one person this year who was a fellow in proton therapy and we're trying to work that into the residency training program more effectively than we have in the past. Right now the residents are exposed to the proton program mostly as a function of their following individual faculty members; so, for example, if they're on GYN they hardly ever see it, but if they’re on the CNS service, they're at the proton center all the time.
Question: Yes.
Dr. Cox: So we're working on that. One problem, of course, is funding.
Question: Of course. And what about the physics department? How is that progressing?
Dr. Cox: Recently, the chair of the physics department, Radhe Mohan, stepped down, and after an international search, Geoff Ibbott, who had previously headed of the Radiological Physics Center, was chosen as department chairman. And they have some wonderful research people, among the most creative of whom is Lei Dong.
Question: Okay.
Dr. Cox: So they are doing really good stuff. And despite the funding environment, they are continuing to apply for peer-reviewed funding and they're being reasonably successful.
Question: Well, there's one thing for sure. You're not going to get the funding if you don't ask for it.
Dr. Cox: Right, exactly.
Question: But anyway, you sound as though you're really very pleased with your physics program and its advancement. And are they having PhD students or postdoctoral fellows or...
Dr. Cox: They have a lot of postdoctoral fellows. It seems to me that they have two PhD students now, and they have several medical physics residents.
Question: Yeah, well, we have them also and driving the way in which the young people say they -- because I've been dealing with one that seems to be extremely bright and well-informed about nuclear physics and nuclear particles and, I mean, it seems like an exceptional person. But she says that the jobs are just not available unless you want to do another three or four years of postdoctoral fellowships. So this is one reason why the residency program is attracting a lot of real good talent.
Dr. Cox: Right.
Question: Well, Jim, when we review your career, which is simply outstanding to say the least, all the things you have done, the positions that you have occupied, the honors that you've received, and your experience at MD Anderson, you know, it takes me back to your having been trained by Dr. del Regato who was very, very, very clinically oriented.
Dr. Cox: Clinical in education. Remember, del Regato and Ackerman wrote the first textbook on cancer in English.
Question: Right. But we don't know how del Regato would have evolved in this era of highly sophisticated technological developments. You know? Maybe he wouldn't have not embraced all of them as much. But in your opinion how are we practicing now? How we are handling patients now? Do you think that there is something, should we be re-emphasizing something? Any thoughts along those lines?
Dr. Cox: Well, I'm sure there are things happening in the field that are not what we would like, and some things that could be better. I think there's a group out there that thinks we should be functioning more like medical oncologists. I don't share that opinion. Having grown up in an environment where I did all of the chemotherapy and the radiation therapy and did a lot of surgical procedures as well, I don't think it's necessary or desirable if you've got a good multidisciplinary team. But I do think we need to train our residents and trainees to have a broad view of oncology and a broad understanding of the capabilities of the other disciplines. That's a training issue.
Question: Do you think they should have rotations, formal rotations in medical oncology?
Dr. Cox: Actually, we have an internship now in which they spend six months in medicine and six months in surgery before they do radiation oncology.
Question: Because of time, let me take you to a point I have in mind. I think that we, radiation oncologists, have at our disposal phenomenal technological tools, and we are also creating a greater distance between ourselves and the patients to the point where, in my opinion, we are less clinically skilled, we take less good histories, do less thorough and careful physical exams, sometimes don't examine the patients at all. In the training programs I see people "in the practice" of the specialty. I see people who don't touch the patients, don't come close to that, and I think we are missing a lot.
Dr. Cox: I see your point, and I think that distance is a big mistake. It's totally a hands-on thing as far as I'm concerned. We examine the patients regularly. I've got a couple of physicians who come to me for follow-up and have told me the reason they do so is that I'm the only one who examines them.
Question: But I don't think this is limited to radiation oncology.
Dr. Cox: No, it's not limited to radiation oncology.
Question: You had a very important role for quite a long time as editor-in-chief of the Red Journal. How did you get into that? Did you enjoy it?
Dr. Cox: I've done 15 years of it, and I'm going to give it up at the end of this year [2011]. It's grown like crazy.
Question: It's wonderful. I think this ought to be in your biographical sketch.
Dr. Cox: Yeah, well, it's an important thing and I think I've served a good role there, helping to bring the journal to a position of prominence, certainly prominence within the field and prominence in oncology. But because it's a journal of physics and biology as well, the readership is maybe more targeted and more… you know, it's a different readership than you would find, let's say, in medical oncology.
Question: It seems to me like you've done an extraordinary good job.
Dr. Cox: I think it's gone well and I'm very pleased with it. I've worked hard at it, and I'm happy about what I've done.
Question: Well, I think you also are going to wind up with a very energetic successor.
Dr. Cox: I think so, too. Anthony [Zietman] is coming to Houston in July 2011 to meet with us and staff members to crystallize the transition. But I'm sure it will be fine. Anthony has great energy and he's got good ideas. As I understand it, he's going to try to spread out the senior editor's responsibility more.
Question: You just deserve a lot of very high credit marks.
Question: Indeed, a lot of credit. But while we are on the phone, we as members of the History Committee would like for the journal to consider publishing a few key papers dealing with the history of our specialty. In this year's educational session, in fact, we have presentations by three distinguished people on important subjects, and we very much hope that the journal will consider publishing these presentations. One will be on Hodgkin disease by Richard Hoppe, another on the history of breast cancer by Barbara Fowble, and another offering an overview of the history of radiation biology by Mark Dewhirst.
Dr. Cox: I think the journal is quite open to that idea; in fact, we just published or are in the process of publishing a paper by Florence Chu on the evolution of radiation oncology at Memorial Sloan-Kettering.
Question: Anything you would like to say about your involvement/participation with ASTRO? Needless to say the Society is in good shape but should the society do anything different? Anything the society is not doing that the society should be doing? Just any comments you would like to make about the society would be welcome.
Dr. Cox: ASTRO is flourishing. It has tended to become less ecumenical over time, with the public thrust representing the current leadership interests rather than advocacy for radiation oncology and its biologists and physicists in the broader medical community. The recent name change has resulted in confusion in some quarters such as Japan where I am at the moment.
Question: Looking back over your distinguished career, what has given you the most reward and satisfaction?
Dr. Cox: I have been fortunate to have many satisfactions: ASTRO, ACR, RTOG, and others. On reflecting, my greatest satisfaction has come from leading the division of radiation oncology for 15 years and helping it to become what it is today. The faculty, residents, collaborations with other departments and institutions have been fun and rewarding. The rapid technologic advances and the way they help our patients is truly gratifying and fun, with protons being one of the most recent ones. We are only at the beginning of wedding these advances with molecular targeted agents, so there is much excitement in the future.
Question: Well, listen, thank you very much.
Question: Yes, thank you very much.
Dr. Cox: It's been a pleasure. I love talking with you all and if you wish to follow up in any way, I'll try to be available.
Dr. Cox: It's my pleasure.
Question: Thank you. I would like to begin by asking you to tell us about your beginnings, where you were born, a bit about your family, if you have anybody who was influential in your career or how your career evolved, and where you went to school.
Dr. Cox: I was born in Steubenville, Ohio, but I grew up in Dayton, Ohio. Through connections there, actually through somebody who impressed my father very much, I applied and eventually was accepted to Kenyon College in Gambier, Ohio. I spent four years at Kenyon, initially in a combined curriculum of biology and chemistry. I wasn't committed to going to medical school until my junior year.
Question: Tell us a little bit about how you made this commitment to medical school.
Dr. Cox: Well, I was interested in science all the way through, and I did well in those courses. I had a couple of professors who I respected greatly who suggested, between my sophomore and junior years, that I consider medical school. I didn't have any physicians or scientists in my family.
Question: Nor did I.
Dr. Cox: but I had an older sister who was always critical of what I did. She didn't think I was very smart until she gave me an IQ test for part of her psychology course in college and then she said, well, maybe.
Question: So how did you select your medical school?
Dr. Cox: A professor of physiology from the University of Rochester came through Kenyon as a lecturer. He was also recruiting for the physiology laboratories at Rochester; he had some summer fellowships that he was prepared to offer, and I, and three of my colleagues from Kenyon, ended up going to the University of Rochester for eight weeks on that fellowship. That really sealed the deal. I knew that I wanted to do that and I ended up applying to the University of Rochester Medical School and was accepted.
Question: Now, here is one of the most interesting things in your CV and it is that you went to Penrose Cancer Center before graduating from medical school.
Dr. Cox: Yes. I became interested in cancer from the time I took pathology in my second year of med school. I mean, I was just fascinated by the disease and anything having to do with its presentation and the patients and the research possibilities and everything. It was common at the University of Rochester to take a year out of medical school to do research.
Question: Where had you heard about radiation therapy and did you meet anybody in the specialty? How did you hear about Penrose or Regato?
Dr. Cox: Well, at that time I wanted to apply to a cancer hospital for my year out of med school. I didn't want to do it in a laboratory, I wanted a clinical environment. So I wrote, I think, five letters to various places, and the most interested and interesting reply I got was from Juan del Regato, who said, "We've never had a student for a year and we kind of don't know what to do with that, but I'm interested and I'll see if I can find some funds." So, with some funds from his training grant and some funds made available by the American Cancer Society in New York, I went to Penrose for a year.
Question: How did you hear about del Regato, in the first place, to write a letter?
Dr. Cox: Well, the cancer coordinator at the University of Rochester was a surgeon, and he came up with a list of possibilities, including Jacob Furth. Del Regato was the only radiation oncologist on my list.
Question: Okay. That was very interesting. It's nice to have this on the record.
Question: So, Jim, del Regato already had a training grant. What year was that you went to Penrose?
Dr. Cox: In 1963.
Question: In 1963, so that was around the same time that Kligerman and Kaplan got their grants and their training programs established.
Dr. Cox: Right. But del Regato had been training people in what was then called therapeutic radiology since the 1950s, when everybody else was still training general radiologists. And so his program from way back then was totally geared toward training people for radiation oncology. And at some point, probably about 1969, one-third of all of the board-certified therapeutic radiologists in the United States had trained at Penrose.
Question: Sure.
Dr. Cox: He had a profound influence on me. He became like an intellectual father to me, and we had a wonderful relationship until he died, except when we had a fundamental political disagreement that was quite severe during the last two years of my residency.
Question: Can you tell us about that?
Dr. Cox: Well, del Regato considered himself to be a liberal of the mold of Hubert Humphrey and I think most of the rest of the world thought that had become old and conservative. And I was opposed to the Vietnam War, even though I volunteered for the draft in 1965 during my internship to become a candidate for the Berry Plan. And I was accepted into the Berry Plan. So I was actually an inactive reserve in the Army while I was a resident at Penrose. And then after my residency and a year of fellowship at the Gustave Roussy, I went on active duty in the military in July of 1970.
Question: Can you just comment a little bit about your time at the Gustave Roussy?
Dr. Cox: Well, I went there primarily to work with Bernard Pierquin, because we did not have very much in the way of brachytherapy experience at Penrose and Bernard at the time was considered the master . . .
Question: … the king….
Dr. Cox: Yes, the king of brachytherapy, right. And he was incredibly creative, and of course, Andrée Dutreix was there then, and the physics team at Gustave Roussy was really powerful. And, of course, Maurice Tubiana was chairman of that department, and later became director of the institute. And when Pierquin accepted the position to become head of the department at the Henri Mondor University Hospital in Créteil, Daniel Chassagne became the chairman of the radiation oncology department at Gustave Roussy.
Question: How long were you there with Pierquin?
Dr. Cox: A year.
Question: And did you enjoy it?
Dr. Cox: Oh, I had a fabulous time. I learned a great deal about brachytherapy, but it wasn't confined to that. I worked with Pierquin for only about five months and then I was involved in a project on lymphomas, and then I took a month and went to England and I went to the Royal Marsden, I went to Manchester and I learned a little bit about what was going on there. I went to Oxford and met Frank Ellis and so I got to meet a lot of the really, really big pioneers.
Question: Legendary figures.
Dr. Cox: Yes, legendary figures. Ritsuko [Komaki] just brought back news of several of them from the most recent ESTRO meeting. She spent a lot of time with Andrée Dutreix, who brought her up to date on a lot of people. Sadly, Pierquin had just died of carcinoma of the kidney at the age of 90. And Jean Dutreix is pretty frail. And Tubiana is frail. He's over 90, but very sharp. Mentally he's really very sharp. Just like del Regato was in his later years. He became frail physically, but he was mentally very sharp. Daniel Chassagne is still around and doing okay.
Question: After you had this year, did you do any projects, write a paper, anything of the sort?
Dr. Cox: Yes, I wrote a paper with Alain Laugier and the pathologist Gerard Morehand on what would now be called diffuse large-cell lymphomas arising in nodal or extranodal sites and the difference of behavior in those two groups.
Question: Okay. Well, then you then came back to the states.
Dr. Cox: I came back to the states and went on active duty in the Army and was stationed at Walter Reed in Chevy Chase in 1970-1972. I was fortunate to be able to practice radiation oncology during that time. Jack Maier was my commanding officer and then became head of the department of radiology. When Jack decided to retire from the Army and Walter Reed ran out of regular Army radiation oncologists during my second year there, I became the head of the radiotherapy service there by default. Although it didn’t involve much in the way of administrative responsibilities, that was my first job as leader of a section or anything like that. Then Jack was recruited to go to Georgetown, and he asked me to go along with him. However, about a month before we were due to leave, he changed his mind and decided to go to George Washington instead. Georgetown didn't have anybody, so they turned to me. And so at the age of 34, I became the head of the radiotherapy section in the department of radiology at Georgetown.
Question: So, Jim, were you with Jack Maier at Walter Reed when he did the work on seminomas?
Dr. Cox: No, he had already done that by that time. My contemporaries, who were also in the Berry Plan, were Leonard Shukovsky, who came from MD Anderson, and John Fazekas. We had a very interesting group—a lot of disagreements, a lot of excitement, a lot of fun. I learned a lot from them and from the whole environment. I wrote a couple of papers there with people at the Armed Forces Institute of Pathology in the hematopathology department, because I was primarily interested in lymphomas at that time.
Question: So from Georgetown you went to Wisconsin.
Dr. Cox: Yes, I went on to the Medical College of Wisconsin because—well, Jack Maier actually had suggested my name as a possible candidate for the head of radiation therapy. It wasn't a department yet, but they did have radiation oncology at the Medical College of Wisconsin. Georgetown clearly didn't have enough money to do the things that they needed to do to make it a top-flight place, so I went to Milwaukee. And then I recruited Frank Wilson to come with me, and we recruited Roger Byhardt, and that was the start of the department at the Medical College of Wisconsin.
Question: And from there then you went to Columbia.
Dr. Cox: Yes, largely through the influence of Eric Hall, with whom I had become very good friends, I went to Columbia Presbyterian Medical Center. As is usually the case in these things, they made a lot of promises. However, after I had been there a year or a year and a half, the head of the hospital called everybody in and said we're losing $2 million a month, we can't keep this up. Basically he said they couldn’t afford to meet any of the promises that they had made. At that time, Jerry Dodd, who was the head of radiology at MD Anderson, had suggested me for the position of physician in chief at MD Anderson. And so I interviewed with Charles LeMaistre, who was the president at the time, and with the heads of the various divisions at MD Anderson, and they offered me that position. It was, in a sentence, a great title and a bad position.
Question: So as physician in chief you were at the top of the administrative staff.
Dr. Cox: Well, I wasn't at the top. That was the problem, because LeMaistre could veto anything that I wanted to do, and the division heads—heads of pathology, surgery, medicine and so on—all had direct access to LeMaistre. So if I didn't do what they wanted, they went to him. So I wasn't able to accomplish anything, and I became very frustrated, and they became frustrated with me as well. That was arguably the worst four years of my career. The only thing that kept me sane during that time was the RTOG.
Question: Oh, I hadn’t known about that.
Dr. Cox: Yes, I was running the RTOG at that time and that was my sanity. It was like having a great research lab and I was responsible for it. I went to Philadelphia about three days out of every three weeks and spent time on the phone every morning with Tom Pajak, who was the statistical head. And so with Tom being sort of the scientist in residence at the RTOG and my being in Houston, we were really able to accomplish a lot.
Question: Well, that's for sure. How long did LeMaistre stay there at MD Anderson?
Dr. Cox: LeMaistre retired in late 1995 or early 1996 and was succeeded by John Mendelsohn. I had stepped down as physician-in-chief in 1992 and had gone back to taking care of patients and working with residents and so on. When Lester Peters decided to go back to Australia, I said, well, I do know how to lead a radiation oncology department, so I put my hat in the ring and was eventually selected to do so. I was head of the division of radiation oncology for 15 years until I stepped down in November 2011.
Question: I thought you were head of the department during your time with LeMaistre…?
Dr. Cox: No, I was not department head while I was physician-in-chief, which was part of the problem because Lester wasn't happy with my being in his department, on the one hand, and on the other hand being his boss. That was not a comfortable situation.
Question: Okay. Now we understand. Some of the difficulties for the physician in chief in that situation were that the department heads could go directly to the top administrator and bypass you.
Dr. Cox: Yes. You can read between the lines and imagine what that was like. So anyhow, once I gave up that job, I became much, much happier at MD Anderson. I came fully to realize what a great institution it was in terms of caring for patients and how it, and we, were turning the corner in clinical research. And I think I we influenced that turn a fair amount. We helped to influence both the department and the institution to look beyond the really good stuff, the fantastic stuff they were doing, though in a somewhat isolated way, and become leaders in the RTOG, especially in head and neck, lung, and GYN cancer.
Question: Well, since you mentioned Ritsuko several times, why don't you tell us how and when you first met...
Dr. Cox: Well, we met in Milwaukee. She was pursuing postgraduate training in the United States on the advice of a radiologist who worked at what was then called the Atomic Bomb Casualty Commission in Hiroshima, which was her home town. And through Walt Russell and his good friend Jim Youker, she got in a somewhat roundabout way to Milwaukee, and she was working at the VA. She was interested in leukemia because of her experiences in Hiroshima. And then she saw patients treated with radiation therapy for lymphomas and she became interested in radiation oncology and so she wanted a residency and so she became a resident.
Question: Very good.
Question: Excellent. Well, Herman and I understand your position and the different roles you have had at MD Anderson. I know that Herman would like to ask you some questions about proton therapy.
Question: Yes, I think it would be very interesting for us to hear something about the major roles that you've played and how, during your tenure as head of the department, the research developed in terms of laboratory research, clinical research including the proton. And any one of these that you'd like to start with would be fine. I saw on Google your very strongly enthusiastic statement about the proton therapy program that you now have up and running and doing all sorts of nice things. But whichever you'd like and in whatever sequence you want, I think we'd both be glad to hear you describe your biography in that area.
Dr. Cox: In terms of timelines, in December 1995 I took over as chairman of the department of radiation oncology and head of the division of radiation oncology. The division had, and has, two other departments, experimental radiation oncology and radiation physics.
Question: So the division of radiation oncology included physics and radiobiology. Is that correct?
Dr. Cox: Yes, they're part of the division, which is the superstructure over the three departments--clinical, physics and radiobiology. In other institutions, the nomenclature would be reversed -- the larger entity, the department, would have three component divisions. But here at Anderson, the departments are components of the division.
Question: Okay. So please step forward, then.
Dr. Cox: We had expanded the clinical operation a lot. We got a lot of new equipment. The department was behind as far as equipment was concerned and so we started very carefully expanding the equipment capabilities. The institution was wonderfully supportive as we went to advanced techniques, advanced accelerators, and we opened a separate department across the street from the main hospital in a new outpatient building that housed the offices of GYN, GU and breast, with associated faculty and trainees. So the department grew to include six accelerators, two simulators and various other equipment. In the clinical department, the department of radiation oncology, we went from a faculty of 17 to about 55 physicians. I don't know exactly how many physicists were on board when I took over, but now there are 50 to 55 physicists.
Question: Now these are PhD physicists?
Dr. Cox: I think 40 of them are PhD physicists and about 15 are masters-level physicists.
Question: Okay. And the patient load has gone up from what to what?
Dr. Cox: The patient load has gone up from about 225 patients a day to about 600 patients a day, not counting the patients treated at the satellite facilities. In 1999, we started a satellite program when one of our stellar trainees who was coming out of fulfilling her Air Force obligation wanted to practice in Houston. As luck would have it, a nearby facility was available that had fallen on really bad times and was really in a mess, and we could pick it up for not much. And so we started a satellite program with her as the lead figure, and she took it and grew it, and now we have six facilities, which are now called regional care centers because they now include medical oncology and, within the past year, they've added surgery. Each one of these regional care center started with a radiation oncology program. And now they're treating about 160 or 170 patients a day over and above the 600 I mentioned.
Question: And all the 600 are at the MD Anderson per se.
Dr. Cox: Yes, those 600 are all treated at the MD Anderson campus. But about 110 or 120 of them now are at the proton center.
Question: Well, is there any radiation oncology center in the world that's treating at the primary site more than 600 a day?
Dr. Cox: Yes, there are a couple, I think, Herman. And I'm not sure about that, but one of them is Princess Margaret.
Question: Oh, how many are they treating?
Dr. Cox: I think they're treating about the same number.
Question: Okay. Well now, then, do you want to go ahead and talk about your development of the proton center or...
Dr. Cox: Well, let me tell you just the evolution. When I was division head, I recruited Radhe Mohan, who was at the Medical College of Virginia and had previously been at Memorial as the head of physics. And he helped the development of this technology in an incredibly strong way. And he was very strongly interested in research. When I took over the division, we had no extramural funding in physics, no peer-reviewed extramural funding in physics. But after Radhe came on board, we competed for and won several R01s. And then the P01, which of course as you know is in collaboration with Mass General. And the P01 is focused entirely on protons. So that developed very, very well. We also recruited Mike Gillin from Milwaukee, we recruited Al Smith who helped work on the proton equipment development with Hitachi, and then several other people who are also really strong in physics. On the radiobiology side, we recruited two people during the early phase of my heading the division, both molecular biologists. One was Lei Li, whose main work is in DNA damage and repair; later we recruited Khandan Keyomarsi, who is working primarily in the area of cell cycle regulation.
Question: All right. Well, that sounds very good.
Dr. Cox: And of course Luka Milas joined us and chaired the radiobiology group (officially the department of experimental radiation oncology). He and Kian Ang did a great job with another very long running P01 here, which focused on head and neck cancer but involved many types of research as well.
Question: Did you know that I had recruited Luka when I was there?
Dr. Cox: Yes. Yes, I knew that.
Question: So I know him well.
Dr. Cox: Well, he did a really fantastic job. He, Kathy Mason, Lester Peters,while he was here, and Kian Ang really did an excellent job in doing research primarily related to tumors and normal tissues in mice. And that work ultimately came to be very important for the development of molecular-targeted work with the EGFR antibody erlotinib (Erbitux). The discovery that erlotinib and other molecular-targeting agents interacted favorably with radiation treatment then served as a basis for developing clinical trials, with the ensuing success of Erbitux combined with radiation therapy for head and neck cancer. That's been very successful. Ray Meyn took over after Luka retired. And then about two or three years ago Ray and I were working to recruit a new chairman of experimental radiation oncology, and we recruited Junjie Chen from Yale. Junjie he is a very successful scientist, a fundamental biologist working in the area of DNA damage and repair. And he's got a great publication record. He's doing a good job. It took a little while to go from running a big laboratory to running a department, but it's evolved nicely now.
Question: Okay, very good.
Dr. Cox: And so what else can I tell you about? Do you want to hear about protons.
Question: Do you have PhD students?
Dr. Cox: Yes we do, although I can’t tell you exactly how many we have right now. The institution was granted the right by the University of Texas Board of Regents to award degrees of various levels to students in physics and biology through the Graduate School of Biomedical Sciences, where MD Anderson faculty members teach about three-quarters of the courses.
That’s actually another area in which we have made great strides over the years—we now have a big educational component. When I took over, the residents were very nice people, but their orientation was not particularly academic, and usually when they left residency they went into private practice. It took a long time to change that, but for quite a few years now, we have been able to recruit outstanding physicians, in many cases budding physician-scientists, to join our faculty. Our MD-PhDs typically spend probably 75 percent of their time working in the laboratory. And so the residency program has evolved in a direction that I wanted to see when I took over, so I'm happy about that.
Question: Very good. Congratulations.
Dr. Cox: Okay, protons?
Question: All right.
Dr. Cox: I don't know if you'll recall, Herman, but I was part of a site visit team that was put together by the Board of Scientific Counselors of the Division of Cancer Treatment at NCI somewhere around 1989. A proposal had come in from Mass General to develop a proton center, essentially moving the work from the Harvard Cyclotron Laboratory to Mass General.
Question: Oh, yes. Of course. I remember that.
Dr. Cox: And the administrative people at NCI were not happy about that plan, for reasons dating back to Henry Kaplan, who had put in a proposal for a huge grant for pi mesons many years earlier. At that time the NCI group wasn’t going to consider any major developmental grants that would involve tens of millions of dollars for construction. I think the proposal for Mass General, which if I recall, Herman, you may have done, was the first one that they had come up against since then, and so they wrestled with that. And among the things that they did was have this site visit team go to Boston and investigate protons, to sort of say what was this all about and what could be done and so on. And I was on that site visit team and at that time, in the late 1980s, I must admit my shortsightedness, that I didn't see any particular value for proton therapy, but I turned out to be wrong. And what convinced me I was wrong was the evolution in radiation therapy techniques between the late 1980s and the late 1990s, first on 3-D conformal therapy and then later on IMRT, but especially going from 2-D to 3-D and 3-D conformal in being able to give higher doses to tumors and avoid normal tissues and avoid side effects and all of that. And then I realized, well, gosh, I mean, protons are a natural evolution of that progress, going from 2-D to 3-D to IMRT [intensity-modulated radiation therapy] and beyond, the natural progression of that I think is proton therapy and now IMPT.
Question: Well, anyway, eventually we did get the grant.
Dr. Cox: Yes, that's right, and I think it helped a lot with the development of your very nice facility there at MGH.
Question: Although we had the grant for the work at the Cyclotron Lab from '76 onward.
Dr. Cox: I know, I know.
Question: But having had that grant certainly facilitated putting the new facility on the campus here, no doubt about it.
Dr. Cox: Sure. And the work you all did with the development of proton dosimetry and advancement of the potential for proton therapy, I mean, was great.
Question: Yeah, well, let's hear more about you.
Dr. Cox: All right. In 1998 we said, okay, we ought to develop a proton capability at Anderson. And I went to the powers that be, primarily to John Mendelsohn and the financial team working with him and said we really need to do this, it would be really a great step forward. And I had a good relationship with John and those people, who felt I was credible as far as they were concerned, so they took the effort very seriously. We went to the UT system and said we would like to do this and the people at the UT system said that's all well and good, but we're not going to give you $125 million because it would mess up our bond rating. And so we had to go out and try to find a way to raise funds, and we did that through a public-private partnership with investors in the community. And when we came up with enough money, we looked for vendors. We were very impressed with Hitachi's program, especially at Tsukuba, what with their manufacturing capability and how deep they were and what engineering capability they had and so on. So we selected Hitachi as the vendor. During that time, Al Smith and others, including Wayne Newhauser and others from MGH, worked very closely with Hitachi and were very demanding about what we wanted to have done, including the development of a scanning beam technology. So we built the facility and installed the Hitachi equipment and started treating patients in May 2006. Rather a long time between 1998 and 2006, but as facilities of this type go, it's not too bad. . .
Question: Par for the course.
Dr. Cox: Yes indeed. So we've been treating patients since that time. We ramped up slowly. We had two gantries and one fixed-beam room. And in 2008 we brought the third gantry online, the one with the scanning beam. And we used the scanning beam, not in a pure IMPT mode, but for shaping and for efficiency. And we've treated, oh, I don't know, probably more than 500 patients with the scanning beam now.
Question: Oh, very good.
Dr. Cox: And over the course of the past year or so, we've slowly developed multifield optimization so that we are able to do IMPT. The problem on that is the QA [quality assurance], which our physicists are quite rightly compulsive about. The QA for every patient treated with IMPT takes about eight hours of physics time. So we can't treat very many patients yet, and we've got to become more efficient and we have to hire more physicists and we're working on that. But, we've treated probably 25 or 30 patients with IMPT or multifield optimization by this time. And we've also begun treating patients with cancer of the head and neck. In that sense we've finally turned a corner that leaders in treating head and neck cancer have come to realize the value of IMPT for head and neck lesions in terms of being able to avoid normal tissues. Kian Ang is increasingly enthusiastic about it, so much so that he thinks that we could open the floodgates by treating carcinoma of the oropharynx, but at this point the QA process is still too long and laborious, and we're not ready to do that quite yet.
Question: So besides head and neck tumors what are the other major groups of patients or tumors you are focusing on or exploring proton therapy for?
Dr. Cox: Our goal from the very beginning was to try to expand proton therapy into all disease sites where protons might have some benefit. And so beginning in January 2004, well over two years before we opened, we started having weekly meetings to develop protocols for the various disease sites. One week we would discuss GU, and the next week it would be thoracic, and the next week GI and the next week GYN and CNS and kids and so on. And the program itself has matured from those meetings. We are treating an especially large number of thoracic tumors, lung or esophageal cancer, with concurrent chemotherapy and proton therapy, something that has not been done very much. And of course in the process we’ve had to learn how to manage motion of the tumors in the chest, including the distal esophagus. We started working on motion management strategies around 2004 with the goal of being able to use them with IMRT. So we've had a group working on motion management research for at least seven years now. And our standard for every patient with thoracic tumors is to get 4-D CT scans and track the movement of the tumor and the normal tissues on those scans throughout the respiratory cycle, and account for that motion during treatment planning. Last year we treated 80 patients with cancer of the esophagus, a figure that just blew my mind. And we've treated probably three times as many patients with cancer of the lung.
Question: But I'm sure that you keep in mind that you expect to achieve a better outcome than with conventional treatment because there is the issue of cost. The cost differential is such that this needs to be factored in very seriously. The other thing is that the patterns of failure have to be primarily local to justify the more expensive proton therapy.
Dr. Cox: That’s a very good observation, and we are looking very closely at that. We just completed a project looking at the patterns of failure, detailed patterns of failure after proton therapy in 57 patients with lung cancer with a minimum follow-up time of two years. These patients received a total dose of 74 Gy-equivalents. And what we found was 10 failures within the high-dose area and 2 failures at the margin of the high-dose area. So 12 local-regional failures of 57 patients with locally advanced non-small-cell carcinoma of the lung—that’s pretty good. It's 80 percent thereabouts. And I don't know any proton experience that's been comparable to that.
Question: And you need to total up the cost of taking care of the failed patients; you talk about the cost of proton therapy, the cost if there's a difference in the failure rate or difference in the complication rate, both of those are expenses that need to be factored in as well.
Dr. Cox: Exactly. And there's no place where that is more true than the children. We've treated a lot of kids with medulloblastoma, and if we can avoid irradiating all of the structures anterior to the vertebral body by using protons . . .
Question: Well, we can. It's established. That’s not an opinion.
Dr. Cox: That's right, I agree, Herman. The group at the Karolinska has modeled the economics of that showing that it's cost-saving in the long run to treat those kids with proton therapy by virtue of what you can avoid in terms of taking care of side effects.
Question: At this point there is no disagreement with that. But with the enormous problem of the high cost of healthcare, it is extremely important to target the use of proton therapy for tumors or diseases that have a very high, or relatively high frequency of local failure and low distant metastatic disease failure rate.
Dr. Cox: I agree. However, if you want to put this in perspective, I've got a little talk that I gave recently called “Economic Considerations in Proton Therapy.” And one of those considerations was the total cost of proton therapy in 2008 in the United States, which was estimated to be $73 million. The cost of the top four drugs in the formulary of the MD Anderson Cancer Center for the same period—just the top four drugs—was $92 million. One institution, four drugs. So you put that in perspective, the cost of protons, I think, is really quite a small part of the cost of healthcare for patients with cancer.
Question: I’m certain you are very aware of this and I don't want to go into a economic debate, so we can move on. But I would love to talk more about this. So I think that looking at the overall issue of healthcare cost, I think that we have to be very cognizant of the cost that is transferred to society and to individuals.
Dr. Cox: Well, I agree. In my talk on economic considerations, I look at it from the point of view of the patients and from the point of view of society. And in both cases, proton therapy does not end up looking bad.
Question: Oh, no. But I think we'd better proceed to let you finish your discussion about proton therapy and how it's working out in your institution and then go to maybe to physics or whatever.
Dr. Cox: Okay. So we have now expanded our treatment capabilities, and we are treating on average somewhere between 115 and 120 patients a day. About 40 percent of those patients have cancer of the prostate. About 30 percent have thoracic tumors, either lung or esophagus or sometimes other tumors. About 15 percent are kids and another 15 percent or thereabouts have brain tumors, so that's the approximate breakdown. We're moving forward with treatment for tumors in the liver in conjunction with the work at Mass General, and we're also moving forward with the protocols for children.
Question: Now, is Kian going to get any slot for head and neck?
Dr. Cox: He is; he's quite interested. As I mentioned earlier, the problem there is that he feels that if we’re going to do better than IMRT, then we need IMPT, and we don't yet have efficient processes for quality assurance in IMPT yet. We're working on it, we're going to get there, but we’re not there yet. But he is very interested.
Question: Very good.
Question: This has been a wonderful and very illuminating discussion about your personal experience with the use of protons. So, Herman, do you have any other questions?
Dr. Cox: While you’re gathering your thoughts, I need to say something here. To be fair to Herman, when he first came and talked about this, he said there's not a photon plan that he could not improve upon with protons and he was absolutely right. So I have become convinced and am now at least as strong an advocate in support of his viewpoint as anybody.
Question: Well, thank you very much. Now, with respect to your plans, do you want to just say anything about any future developments that you're pushing in terms of 4-D this and 4-D that or making Monte Carlo available or...
Dr. Cox: Yes indeed, we are working on Monte Carlo. We’re using Monte Carlo calculations right now to assess the in-field and out-of-field failures in that group of 57 patients with lung cancer. That's ongoing work.
Question: Yes. Well, I imagine it won't be too long before practically -- you know, another few years as we get bigger computers that Monte Carlo will be routine and standard.
Dr. Cox: I think you're right.
Question: Oh, what about imaging? Are you doing any special, what would you want to say about your view of future developments?
Dr. Cox: Well, one of the things that we need desperately—and probably is a weakness at MD Anderson at the present time—is some capability for molecular imaging. I mean, we've got so much interest in molecular targeting agents, and we've got a whole department on targeted therapy, and we're very interested in the interaction of radiation therapy and chemoradiation with biologic agents, so we want to move forward with that clinically. This kind of work is moving forward in the laboratory with the xenograft mouse models. But what we don't have, I think, is the sophistication in molecular imaging that I wish we had. I think there are other institutions, including Mass General, are well ahead of us in molecular imaging. Duke, too, and Stanford have some really outstanding programs.
Question: Well, anyway, if you set your goal on it, you're going to catch up or pass.
Dr. Cox: So true. And we are working toward that. We have physicists and imaging experts.
Question: How wonderful it is to know that you have people advancing in the same area and that they're going to leapfrog over you unless you really get busy. And so this is a powerful stimulating thing.
Dr. Cox: Yes, right. I think that's the main area that we need to get going on. And to pursue the physical targeting with protons and all of the image management—all of the motion management stuff that goes with that, and the biological targeting, alone or in combination with chemotherapy, That's what we're working on in the immediate future, and the imaging, the molecular imaging part of it is a critical piece for the future.
Question: So you're doing that in part to determine in the actual patients…?
Dr. Cox: Yes, but we’re not doing the imaging of protons in real time.
Question: Well, I thought—well, that's another application of these imaging...
Dr. Cox: It is.
Question: But I don't know whether it's so -- what advantage it has over just plane calculations with good CTs.
Dr. Cox: I don't know either.
Question: Anyway, it's something that we're doing here, but it's very high-tech, but I don't know exactly what is the real gain. With very high-quality CT and density analysis, it gets pretty darn accurate with just the calculations, the pure physics.
Dr. Cox: Right.
Question: Now, do you have a lot of people coming in and spending time with you and doing fellowships, etcetera, in the particle therapy program?
Dr. Cox: Well, we certainly have had quite a few people who want to come and spend a month or two. We have one person this year who was a fellow in proton therapy and we're trying to work that into the residency training program more effectively than we have in the past. Right now the residents are exposed to the proton program mostly as a function of their following individual faculty members; so, for example, if they're on GYN they hardly ever see it, but if they’re on the CNS service, they're at the proton center all the time.
Question: Yes.
Dr. Cox: So we're working on that. One problem, of course, is funding.
Question: Of course. And what about the physics department? How is that progressing?
Dr. Cox: Recently, the chair of the physics department, Radhe Mohan, stepped down, and after an international search, Geoff Ibbott, who had previously headed of the Radiological Physics Center, was chosen as department chairman. And they have some wonderful research people, among the most creative of whom is Lei Dong.
Question: Okay.
Dr. Cox: So they are doing really good stuff. And despite the funding environment, they are continuing to apply for peer-reviewed funding and they're being reasonably successful.
Question: Well, there's one thing for sure. You're not going to get the funding if you don't ask for it.
Dr. Cox: Right, exactly.
Question: But anyway, you sound as though you're really very pleased with your physics program and its advancement. And are they having PhD students or postdoctoral fellows or...
Dr. Cox: They have a lot of postdoctoral fellows. It seems to me that they have two PhD students now, and they have several medical physics residents.
Question: Yeah, well, we have them also and driving the way in which the young people say they -- because I've been dealing with one that seems to be extremely bright and well-informed about nuclear physics and nuclear particles and, I mean, it seems like an exceptional person. But she says that the jobs are just not available unless you want to do another three or four years of postdoctoral fellowships. So this is one reason why the residency program is attracting a lot of real good talent.
Dr. Cox: Right.
Question: Well, Jim, when we review your career, which is simply outstanding to say the least, all the things you have done, the positions that you have occupied, the honors that you've received, and your experience at MD Anderson, you know, it takes me back to your having been trained by Dr. del Regato who was very, very, very clinically oriented.
Dr. Cox: Clinical in education. Remember, del Regato and Ackerman wrote the first textbook on cancer in English.
Question: Right. But we don't know how del Regato would have evolved in this era of highly sophisticated technological developments. You know? Maybe he wouldn't have not embraced all of them as much. But in your opinion how are we practicing now? How we are handling patients now? Do you think that there is something, should we be re-emphasizing something? Any thoughts along those lines?
Dr. Cox: Well, I'm sure there are things happening in the field that are not what we would like, and some things that could be better. I think there's a group out there that thinks we should be functioning more like medical oncologists. I don't share that opinion. Having grown up in an environment where I did all of the chemotherapy and the radiation therapy and did a lot of surgical procedures as well, I don't think it's necessary or desirable if you've got a good multidisciplinary team. But I do think we need to train our residents and trainees to have a broad view of oncology and a broad understanding of the capabilities of the other disciplines. That's a training issue.
Question: Do you think they should have rotations, formal rotations in medical oncology?
Dr. Cox: Actually, we have an internship now in which they spend six months in medicine and six months in surgery before they do radiation oncology.
Question: Because of time, let me take you to a point I have in mind. I think that we, radiation oncologists, have at our disposal phenomenal technological tools, and we are also creating a greater distance between ourselves and the patients to the point where, in my opinion, we are less clinically skilled, we take less good histories, do less thorough and careful physical exams, sometimes don't examine the patients at all. In the training programs I see people "in the practice" of the specialty. I see people who don't touch the patients, don't come close to that, and I think we are missing a lot.
Dr. Cox: I see your point, and I think that distance is a big mistake. It's totally a hands-on thing as far as I'm concerned. We examine the patients regularly. I've got a couple of physicians who come to me for follow-up and have told me the reason they do so is that I'm the only one who examines them.
Question: But I don't think this is limited to radiation oncology.
Dr. Cox: No, it's not limited to radiation oncology.
Question: You had a very important role for quite a long time as editor-in-chief of the Red Journal. How did you get into that? Did you enjoy it?
Dr. Cox: I've done 15 years of it, and I'm going to give it up at the end of this year [2011]. It's grown like crazy.
Question: It's wonderful. I think this ought to be in your biographical sketch.
Dr. Cox: Yeah, well, it's an important thing and I think I've served a good role there, helping to bring the journal to a position of prominence, certainly prominence within the field and prominence in oncology. But because it's a journal of physics and biology as well, the readership is maybe more targeted and more… you know, it's a different readership than you would find, let's say, in medical oncology.
Question: It seems to me like you've done an extraordinary good job.
Dr. Cox: I think it's gone well and I'm very pleased with it. I've worked hard at it, and I'm happy about what I've done.
Question: Well, I think you also are going to wind up with a very energetic successor.
Dr. Cox: I think so, too. Anthony [Zietman] is coming to Houston in July 2011 to meet with us and staff members to crystallize the transition. But I'm sure it will be fine. Anthony has great energy and he's got good ideas. As I understand it, he's going to try to spread out the senior editor's responsibility more.
Question: You just deserve a lot of very high credit marks.
Question: Indeed, a lot of credit. But while we are on the phone, we as members of the History Committee would like for the journal to consider publishing a few key papers dealing with the history of our specialty. In this year's educational session, in fact, we have presentations by three distinguished people on important subjects, and we very much hope that the journal will consider publishing these presentations. One will be on Hodgkin disease by Richard Hoppe, another on the history of breast cancer by Barbara Fowble, and another offering an overview of the history of radiation biology by Mark Dewhirst.
Dr. Cox: I think the journal is quite open to that idea; in fact, we just published or are in the process of publishing a paper by Florence Chu on the evolution of radiation oncology at Memorial Sloan-Kettering.
Question: Anything you would like to say about your involvement/participation with ASTRO? Needless to say the Society is in good shape but should the society do anything different? Anything the society is not doing that the society should be doing? Just any comments you would like to make about the society would be welcome.
Dr. Cox: ASTRO is flourishing. It has tended to become less ecumenical over time, with the public thrust representing the current leadership interests rather than advocacy for radiation oncology and its biologists and physicists in the broader medical community. The recent name change has resulted in confusion in some quarters such as Japan where I am at the moment.
Question: Looking back over your distinguished career, what has given you the most reward and satisfaction?
Dr. Cox: I have been fortunate to have many satisfactions: ASTRO, ACR, RTOG, and others. On reflecting, my greatest satisfaction has come from leading the division of radiation oncology for 15 years and helping it to become what it is today. The faculty, residents, collaborations with other departments and institutions have been fun and rewarding. The rapid technologic advances and the way they help our patients is truly gratifying and fun, with protons being one of the most recent ones. We are only at the beginning of wedding these advances with molecular targeted agents, so there is much excitement in the future.
Question: Well, listen, thank you very much.
Question: Yes, thank you very much.
Dr. Cox: It's been a pleasure. I love talking with you all and if you wish to follow up in any way, I'll try to be available.
