Chapter 09: Research Focused on a Range of Body Areas
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Description
Dr. Cox summarizes the range of research he administered on fractionation while involved with the RTOG: lung cancer, head and neck cancers, cervix and brain. He also discusses the key importance of adding chemotherapy to patients’ treatment regimens to get the best results.
Dr. Cox next explains that while he was Chair of the RTOG he was able to move combined treatments forward in the NCI and other organizations. He explains why the NCI is biased toward chemotherapy. He also comments on NCI politics is influencing how gynecologic cancers will be investigated.
Dr. Cox next comments on other cancer studies he oversaw during the period when he was Vice President for Patient Care under Dr. Charles LeMaistre [Oral History Interview].
Identifier
CoxJ_02_20130412_C09
Publication Date
4-12-2013
City
Houston, Texas
Interview Session
Topics Covered
The Interview Subject's Story - The Researcher; The Administrator; The Researcher; Professional Practice; The Professional at Work; Overview; Definitions, Explanations, Translations; On Research and Researchers; The History of Health Care, Patient Care
Transcript
Tacey Ann Rosolowski, PhD:
Uh-hunh (affirmative). How did that focus [on patterns of failure in radiation treatments] evolve as you began to undertake your own studies that you can see from the beginning?
James D. Cox, MD:
Well the other area of interest—and they kind of went together—was the area that’s called fractionation. That is—you split up the dose of radiations that you give a patient to exploit the differences between the cancer cells ability to—the inability of the cancer cells to recover between doses of radiation and the ability of normal tissues to recover. And if you don’t give too big a dose at one time, you can exploit that difference. So I was working in that area.
Tacey Ann Rosolowski, PhD:
And what kind of cancer? James Cox MD That was primarily cancer of the lung, head and neck, cervix. It seems to me there was another—brain. This was in the context of the RTOG by that time, and we mounted a series of trials looking at fractionation and found that some fractionation experiments just didn’t seem to help. Others, and cancer of the lung, did seem to help.
Tacey Ann Rosolowski, PhD:
When I was looking at the array of body areas that you focused on, they’re so different. I’m wondering what—I’m sure this is a terribly naive question—but what are the unique challenges that each of these areas of the body presents to the radiation oncologist?
James D. Cox, MD:
Well the challenges are similar for each of the areas, and that is basically to improve the control of the tumor locally because radiation therapy is a local treatment means. And so that went together with the patterns of failure analyses. For many, there are disease sites where you’re trying to improve the tumor locally. As it turned out, a much more important approach, which did not come from our work—that came from the work of people in the Netherlands adding chemotherapy simultaneously with radiation therapy and then comparing that with radiation therapy alone. It turned out that that was a much more powerful way to approach controlling the disease than the altered fractionation. That’s proven to be true in many disease sites. One of the first ones was cancer of the esophagus and then cancer of the lung, head and neck, cervix, and all these areas where we did the chemotherapy and radiation therapy at the same time. The chemotherapy plus concurrent radiation therapy was better than radiation therapy alone, and that was measured by survival in every case.
Tacey Ann Rosolowski, PhD:
What were some of the figures that you came up with—the survivorship rates?
James D. Cox, MD:
Well for example, one of the biggest ones—and this didn’t come from the group in the Netherlands as a starter—was cancer of the esophagus, where the results with radiation therapy alone, with relatively high doses, were poor—very poor. Well, when we did the randomized trial, at three years no patient was alive that was treated with radiation therapy alone, and a lesser dose of radiation combined with chemotherapy led to a survival of about twenty-five percent, which is a long way from what you would like it to be, but it’s very different than zero. And so that was one of the ones. Later on we did head and neck, initially looking at preserving the larynx—preserving function and later on looking at survival.
Tacey Ann Rosolowski, PhD:
Now were these all accommodations with chemo, or did you also work with people in surgery on this?
James D. Cox, MD:
The one for head and neck was with the surgeons because if there wasn’t a very favorable response by a certain point in time, then they would go on to a laryngectomy.
Tacey Ann Rosolowski, PhD:
Uh-hunh (affirmative). I think I remember talking to Dr. [Kent] Gifford about this. James Cox MD Right. He was very much involved. Dr. [Kie Kian] Ang was very much involved. Tacey Ann Rosolowski PhD Tell me about that collaboration. When did that take place, and what exactly did you do for that study?
James D. Cox, MD:
Well, in the RTOG they had done a study in the Veterans Administration system where they compared chemoradiation—where they did chemoradiation for cancer of the larynx that otherwise would be completely removed—the larynx would be removed. So if they did chemoradiation and there was a favorable response, then they would go on to pursue chemoradiation and avoid surgery. If there was not a favorable response, they would proceed to surgery. So that was the study that was done largely by Dr. Ang and the Veterans Administration system. We took one step back from that and said, “Well, if we did chemotherapy and radiation therapy together, would it be better than radiation therapy alone?” And it did prove to be better. The chemoradiation was better primarily in larynx preservation because if that failed, they went on to laryngectomy, and the survival was pretty much the same in both groups. One of the interesting things that we did that involved very much the investigators at MD Anderson—and I will give you the expurgated view of that—was to look at concurrent chemoradiation for cancer of the cervix, and a disease that is pretty curable with radiation therapy of the lung. And it turned out that the chemoradiation was clearly superior. That has now become the standard throughout the world.
Tacey Ann Rosolowski, PhD:
When were those findings made?
James D. Cox, MD:
Oh I think that was published in—those findings were published in the early 1990s. And that’s become a standard ever since.
Tacey Ann Rosolowski, PhD:
Who were your collaborators on that project?
James D. Cox, MD:
Well actually I was chairing the RTOG, so officially I wasn’t a collaborator. Although Dr. Eifel would acknowledge that I did a huge amount of work in moving that forward, both within the RTOG and within the National Cancer Institute because all of those studies had to be approved by part of the NCI called the Cancer Therapy Evaluation Program and within that a branch called the Clinical Investigations Branch. They were not as sympathetic to what we were doing as we wanted them to be.
Tacey Ann Rosolowski, PhD:
Why was that?
James D. Cox, MD:
But eventually they came around.
Tacey Ann Rosolowski, PhD:
And was that—I think you mentioned last time that there was a bias in the NCI and maybe other organizations towards surgery and chemo. Am I remembering that correctly?
James D. Cox, MD:
Well, at the NCI it’s a bias primarily toward chemo because the cooperative groups were started to investigate leukemia. Tacey Ann Rosolowski PhD Oh, I see. Okay.
James D. Cox, MD:
Since the vast majority of the physicians at NCI are medical oncologists and a handful—a small handful are surgeons, and an even smaller group are radiation oncologists, the view of the chemotherapy lobby, if you will, is vastly stronger.
Tacey Ann Rosolowski, PhD:
Were the sources of resistance to the treatment you were proposing in this study different, or did that come from the same bias?
James D. Cox, MD:
They were different in one way. The RTOG didn’t have an NCI approved actual committee on gynecologic cancer. There was a separate cooperative group—the gynecology, oncology group—that was doing those studies. And from the NCI perspective, all of those studies ought to be done by that group and not by the RTOG. I had to lobby very hard to get it started by the RTOG and even to get it continued because in the middle of all this, we had a once-every-five-year review. There was a chance that they would make us close down the study. But they didn’t, fortunately. But it did require a lot of effort, both within the group and within NCI. It was highly successful. Another one that was done, which again, in this case, didn’t involve a big survival advantage because, like the larynx study, you could do surgery afterwards, and it would help correct the failure. That was for cancer of the anal canal, and there the goal was to avoid colostomy. There was a separate trial in cancer of the nasopharynx where surgery doesn’t come into the picture at all, but radiation therapy is quite effective. Perusing chemotherapy and radiation therapy at the same time led to a much better result with cancer of the nasopharynx. So we had all of these series of trials that were carried out—either started or came to fruition during the period that I chaired the group. A lot of them were published afterwards.
Tacey Ann Rosolowski, PhD:
So this sounds like a really, really fruitful time for MD Anderson work, certainly.
James D. Cox, MD:
It was. And the interesting part of that is going back to when I first came here, and the position I was in—vice president for patient care—I think I related to you that it turned out to be, from my view, not a very satisfactory position. The thing that kept me sane was the research efforts with the RTOG.
Tacey Ann Rosolowski, PhD:
Now tell me about setting up the connections with these different researchers during that unsatisfying period when you were VP, but nonetheless obviously helping to forward these collaborations and careers of other MD Anderson faculty.
James D. Cox, MD:
Well it was generated from the radiation oncologists and the surgeons. The medical oncologists were not the primary players during that time in these studies.
Tacey Ann Rosolowski, PhD:
Why do you think that was? Why do you think medical oncology was—
James D. Cox, MD:
Well, they were involved, but they were not testing new drugs, so it was not of paramount interest to them. Their goal, by and large, is to test new drugs and try to see if they get better results. Sometimes the results are only measured in the shrinkage of a tumor, then to have it return rather quickly. Or, in patients that have widespread disease, to improve survival by a matter of weeks or a few months. So the endpoints for drug studies are very different than the endpoints for radiation studies. We do not consider response an important endpoint. Local control of the tumor within the field of irradiation becomes the primary endpoint for radiation studies.
Tacey Ann Rosolowski, PhD:
So you were saying it was the radiation oncologists and the surgeons who were really the prime movers behind this. So who are some significant people that you (???)(inaudible, speaking at once) connections with.
James D. Cox, MD:
Well in the head and neck arena, it was Dr. Ang—Kian Ang—and Helmuth Geopfert [Oral History Interview]. The collaboration has always been—well almost always—it depends on far back you want to go. But in recent years, there’s always been a strong collaboration between the head and neck surgeons and the radiation oncologist. And so Geopfert was a champion with us along with Kian Ang, Moshe Maor. And then in the lung studies, it was Dr. [Wuan Ki] Hong [Oral History Interview] and as far as feeding into them, Dr. [Jack] Roth in surgery, and then Dr. [Ritsuko] Komaki. The three of them served as a resource for the implementation of these trials. There were a few other medical oncologists involved—Jin Soo Lee, who is now in a leadership position in a cancer center in South Korea. Then in the cervix area it was Patricia Eifel in radiation oncology and Mitch Morris who left the institution years ago to pursue a career. He was the gynecologic oncologist who was most involved with the cervix studies. In fact, the publication that came out, he was the first author. Then he went off in the field of information technology. That interested him. I don’t think he ever practiced after that, but I don’t know for sure. But he was very actively involved. And then—what else? Those were the main ones where positions from MD Anderson were very actively involved in these studies.
Recommended Citation
Cox, James D. MD and Rosolowski, Tacey A. PhD, "Chapter 09: Research Focused on a Range of Body Areas" (2013). Interview Chapters. 791.
https://openworks.mdanderson.org/mchv_interviewchapters/791
Conditions Governing Access
Open
