Chapter 05: The Radiation Therapy Oncology Group
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Description
Dr. Cox begins this segment with a brief history of the ROTG, founded in the late sixties, after several individuals running clinical trials created centers to gather statistics and manage trial operations. In the late sixties, the NCI gave instructions and funds to draws the disparate centers together. Dr. Cox became involved in 1978 or ’79 and soon became vice chair for research strategy. He lists the areas of research the ROTG followed: hypoxic desensitizers and hypothermia; chemotherapy; and fractionization. He explains that he evaluated the results of studies. He speaks about an MD Anderson study treating cancer of the cervix with a combination of radiation and chemo.
Dr. Cox describes how technologies of radiation therapy have evolved and how this evolution has been influenced by the NCI’s interest. (Dr. Cox feels the NCI has a prejudice in favor of chemotherapy, thus making less money available for radiation and surgery, even today.)
Identifier
CoxJ_01_20130103_C05
Publication Date
1-3-2013
City
Houston, Texas
Interview Session
Topics Covered
The Interview Subject's Story - The Administrator; The Researcher; Overview; Definitions, Explanations, Translations; Understanding Cancer, the History of Science, Cancer Research; Devices, Drugs, Procedures; Activities Outside Institution; Beyond the Institution; Understanding Cancer, the History of Science, Cancer Research; The History of Health Care, Patient Care; Business of Research
Transcript
Tacey Ann Rosolowski, PhD:
It sounds really interesting. I was wondering if you would tell me more about the involvement with the Radiation Therapy Oncology Group? You talked about how that was established in the late ‘60s you said?
James D. Cox, MD:
Uh-hunh (affirmative).
Tacey Ann Rosolowski, PhD:
And who was involved in founding that organization? When did you really get involved?
James D. Cox, MD:
It was a guy named Simon Kramer, and he was actually—he was a—not a contemporary. He was a bit younger than Dr. del Regado, but they were on many national committees together. Simon Kramer, Gilbert Fletcher from Anderson, Henry Kaplan from Stanford, Morton Kligerman from Yale—they were all sort of contemporaries in the sense that they were frequently involved at the National Cancer Institute in the treatment and evaluation of policy. And so Kaplan had started a trial on Hodgkin’s disease in about ’65 and pulled together a unique set of individuals who were interested in doing it, a statistical setter, an operations setter and so on—a whole self-contained construct. Del Regado did the same thing with cancer of the prostate, but Kaplan’s was with Hodgkin’s. Del Regado did the same thing with cancer of the prostate a couple years later—pulled together—you know—had its own statistician, its own operations setter. And Simon Kramer went to the National Cancer Institute to get funding for yet another study that involved actually chemotherapy and radiation therapy for cancer of the head and neck, and the leadership at NCI said wait a minute—we cannot just do this for every idea that comes along from somebody who is notable, form a national group—and by that time there were a few national groups. They had come out of the recognition at the National Cancer Institute that you could not address questions with just the patients in a single institution—not even NCI. And so they pushed for the formation of cooperative groups. And I think NSABP was one of the earliest with Bernie Fisher.
Tacey Ann Rosolowski, PhD:
NSABP stands for? James Cox. MD National Surgical Adjuvant Breast Project. That was one of the earliest. And the Eastern Cooperative Oncology Group or ECOG was a little later than that. And then there was the Southwest Oncology Group. So there was some experience with these groups developing, and the NCI leadership at the time said form one of these groups. So Kramer did.
Tacey Ann Rosolowski, PhD:
So the idea—just to pick up a little piece—the idea of bringing together multiple institutions was simply that you needed the patient numbers?
James D. Cox, MD:
Yes.
Tacey Ann Rosolowski, PhD:
Okay.
James D. Cox, MD:
It was.
Tacey Ann Rosolowski, PhD:
So when did you become involved with the group?
James D. Cox, MD:
I became involved with the group in I think 1978 or ’79 when I was in the Medical College of Wisconsin. Actually we were developing a good strong department at that time, and they encouraged us to join. And we joined, and to this day the Medical College of Wisconsin is one of the leading institutions in the RTOG. But I was involved, and relatively soon after that I became one of the—I forget what it was called—vice chair for research strategy or something like that.
Tacey Ann Rosolowski, PhD:
And what did that entail?
James D. Cox, MD:
It entailed interacting with the various disease site areas. So there was the group treating tumors of the central nervous system, head and neck, lung, cervix, esophagus—anyhow so there was—oh and prostate. So there was brain, head and neck, thorax, GI, GU, and GYN. And so it was interacting with each of those groups to sort of stimulate the evolution of the research questions. After that experience I was elected to chair of the group in 1987, and with it went a big grant, and I have forgotten how much money it was. It would have been a lot more now, but it is probably four or five million dollars, and that was to be distributed throughout the institutions for participation in these clinical trials.
Tacey Ann Rosolowski, PhD:
So what were some of the most significant initiatives and findings that were taking place while you were there at that time?
James D. Cox, MD:
Well in—and they were mostly in the area of chemotherapy and radiation therapy together. There was a big interest—oh there were some blind alleys of course—so there was a big interest in drugs that were called hypoxic sensitizers, and oxygen—the lack of oxygen is what makes tumors resistant to radiation therapy. So if you had drugs that would counteract that—that would work in the tumors to make them more sensitive to radiation, tumors would be controlled better. So there are several years of work on hypoxic cell sensitizers.
Tacey Ann Rosolowski, PhD:
And was this one of the blind alleys?
James D. Cox, MD:
This was one of the blind alleys. It just never went anywhere. Another one was hypothermia. You know—the biology was really incredibly strong. The ability to monitor heat distribution and delivery was very poor. It just did not work. But adding chemotherapy together with radiation therapy did work. And so it became one of the areas of considerable interest. The other thing that was of great interest was what was called fractionation, which is splitting the dose that is delivered into large doses each time or small doses each time, giving it once a week or giving it two or three times a day, and there was a lot of interest in that. And that has continued to go, but that has sort of reached a plateau and took a background place to the work with chemotherapy and radiation therapy together. So—I mean—I was involved in all of those and also involved in shutting them down and stopping them when they weren’t going anywhere, which was not a very popular thing to do.
Tacey Ann Rosolowski, PhD:
So you were reviewing all the research—
James D. Cox, MD:
Yeah.
Tacey Ann Rosolowski, PhD:
—and the results, and then deciding who got money and (both speaking at once)?
James D. Cox, MD:
Deciding—you know—sort of coming to the group—we met semi-annually—coming to the group and saying we cannot afford to do this anymore. We are going nowhere with this strategy, and we’ve got limited resources. We’ve got to use those resources otherwise. So we shut down the hypothermia program. We shut down the hypoxic sensitizer program, and we moved more into fractionation and into chemoradiation. The first big success was in cancer of the esophagus. The second big success was in cancer of the nasopharynx. And then the one that really got MD Anderson turned on more than any others was actually cancer of the cervix. Patricia Eifel and Mitch Morris, who was here—I don’t know if you still know that name—but Mitch Morris was a gynecological oncologist, very active in GYN oncology, and he and Patricia actually were the lead people in the nation in pushing the concept of chemoradiation versus radiation therapy alone for cancer of the cervix. Chemoradiation was clearly superior. And so that was another winner for that particular approach. Then they were doing one for cancer of the anal canal where the end point they were looking at was avoiding colostomy. They did one for cancer of the larynxcancer where it was avoiding laryngectomy. There were others.
Tacey Ann Rosolowski, PhD:
Was there—so on the one hand, you have the trials going on, which is thinking about how to most effectively use what was available either with radiation technology and then with chemotherapy—was there something happening at the same time with the technology of radiation therapy that was adding complexity to this mix or adding other factors?
James D. Cox, MD:
Yeah. There was, but it was not really being addressed as—I mean aside from hypothermia—it was not being addressed as a technology assessment approach, but hypothermia was being added to standard radiation therapy.
Tacey Ann Rosolowski, PhD:
Now is just hypothermia meaning you chilled the patient, or was there something else going on?
James D. Cox, MD:
No. You tried to heat the tumor.
Tacey Ann Rosolowski, PhD:
Okay. Got it.
James D. Cox, MD:
Now you could try to heat the patient, and actually Joan Bull, who is over at the UT Health Science Center, she was one of the leading people in the country in doing total body hyperthermia. The goal was that if you got the tumor up to a certain temperature, then radiation therapy and even chemotherapy were more effective.
Tacey Ann Rosolowski, PhD:
Meaning that with the increase in temperature the processes would take place faster? Or what would make the tumor more sensitive with more temperature?
James D. Cox, MD:
Well there were a lot of biologic studies trying to address that question. There were a lot of biochemical changes that took place when the temperature got a little higher and radiation or chemotherapy was added. Some of those biologic processes are still considered pretty important—the whole idea of heat shock proteins and—
Tacey Ann Rosolowski, PhD:
What are those?
James D. Cox, MD:
Well they supposedly develop when you get to a certain temperature, and they have various interactions in the tumor, and they are still being studied. So, but back to your question about technology evolution and technology assessment, there were advances in technology going on in the field primarily with external radiation therapy—with treatment from the outside. But they were never—I mean there were simulators that came in, and there were imaging modalities that came in, but they were not formally evaluated. One of the reasons for it was that there was no interest at the National Cancer Institute in having them evaluated at that time. And the funding came for the RTOG and these other cooperative groups came from the National Cancer Institute. And—you want some water?
Tacey Ann Rosolowski, PhD:
I’ve got some down here.
James D. Cox, MD:
And so the ideas had to go through the Cancer Therapy Evaluation Program—CTEP. And if the people who were leading CTEP were not interested in the question that you wanted to address, then they were not going to approve funding for it. So it wasn’t just—the decisions about research strategy were not confined or limited to the RTOG. They had to be sold—if you will—to the leaders at CTEP. Now the leaders at CTEP were all medical oncologists. They did not know anything about radiation oncology. There were usually one or two very good, very prominent radiation oncologists that were there as consultants, but they did not participate much in making those decisions. And that is still true to today, that the somewhat grim statement about NCI is that it is a National Chemotherapy Institute. There is some interest in surgery, some interest in radiation therapy—not very much—and very little money that is allocated to either one. There is just a huge desire to hit another or hit some home runs with drug therapy. And now the drug therapy of course has multiplied many fold with the availability of biologic agents. And we have tried with the proton work—we have tried to see if there was any interest in clinical investigations of proton therapy. There is interest, but the interest is split among various agencies of the federal government. The National Cancer Institute is only one agency that has any interest in it, and they do not have a huge interest in it—again—for the same reason that it is not a drug.
Tacey Ann Rosolowski, PhD:
And why is there this prejudice towards drugs? I mean—is it a money thing? Or is it simply the history of who has been in power there?
James D. Cox, MD:
Yeah. It is strictly who has been in power at NCI. Yeah.
Tacey Ann Rosolowski, PhD:
Interesting. I hadn’t heard that before.
James D. Cox, MD:
No?
Tacey Ann Rosolowski, PhD:
No. Uh-hunh (negative).
James D. Cox, MD:
I was on the board of scientific counselors of the Division of Cancer Treatment, and CTEP—the Cancer Therapy Evaluation Program—is under that division. We would spend tens of millions of dollars looking for a new exciting drug in some—you know—forest in Thailand, and it was harder than hell to get any money to do any kind of research involving radiation therapy. They just were not—that was not what they wanted to do. They wanted the next—I don’t know—vincristine or vinblastine—they wanted the next drug that would be—that would hit a home run and take care of cancer. They have become a lot more sober about that possibility I think, but I think the interest is still the same. The people who work there in the sort of radiation research program are having to struggle with that internally all the time. So the people that are in the radiation research program would like us to investigate proton therapy, but there’s—they don’t have a good handle on the funds which stimulates such research.
Tacey Ann Rosolowski, PhD:
Let alone in the strategic kind of way. Interesting.
James D. Cox, MD:
Right.
Recommended Citation
Cox, James D. MD and Rosolowski, Tacey A. PhD, "Chapter 05: The Radiation Therapy Oncology Group" (2013). Interview Chapters. 787.
https://openworks.mdanderson.org/mchv_interviewchapters/787
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