Chapter 05: Developing Radiation to Address the ”Oxygen Effect” in Tumors

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Chapter 05: Developing Radiation to Address the ”Oxygen Effect” in Tumors

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Description

Dr. Almond describes the “oxygen effect” –the idea that anoxic cells are more resistant to radiation than those that are supplied oxygen—and discusses how researchers attempted to overcome it in this chapter. He describes MD Anderson’s collaboration with Texas A&M in the 1960s to build a Cyclotron that could use deuterons instead of cobalt-60 to provide radiation therapy and the eventual end of this treatment due to high complications.

Identifier

AlmondP_01_20040404_C05

Publication Date

4-4-2004

Publisher

The Historical Resources Center, Research Medical Library, The University of Texas Cancer Center

City

Houston, Texas

Topics Covered

The University of Texas MD Anderson Cancer Center - Overview; Portraits; Overview; Definitions, Explanations, Translations; MD Anderson History; MD Anderson Snapshot; Understanding Cancer, the History of Science, Cancer Research; The History of Health Care, Patient Care; Technology and R&D; The MD Anderson Brand, Reputation; Patients; Patients, Treatment, Survivors; MD Anderson Impact; MD Anderson Impact; Industry Partnerships

Creative Commons License

Creative Commons Attribution-Noncommercial-No Derivative Works 3.0 License
This work is licensed under a Creative Commons Attribution-Noncommercial-No Derivative Works 3.0 License.

Disciplines

History of Science, Technology, and Medicine | Oncology | Oral History

Transcript

Peter Almond, Ph.D.

Now, you wanted to know about neutrons and Cyclotrons.

James S. Olson, Ph.D.

Yes.

Peter Almond, Ph.D.

This goes back to Hermann’s suit and hyperbolic oxygen. I’m trying to think of the timescale for this. Anyhow, certainly in maybe the fifties, but probably the sixties, it was known that cells that were anoxic, that is they were not in an oxygen atmosphere, were about three times more radio resistant than cells that were in oxygen or had oxygen supplied to them. You could say that the other way. If you have oxygen there, the cells are more sensitive to radiation. Low oxygen, they’re resistant to radiation. It’s well known and was documented during that period that in the center of solid tumors where the blood vessels have been pushed out, the cells right in the middle will die due to lack of oxygen. There’s a necrotic center to tumors. They’re just unviable.

But right around the edge of that anoxic, necrotic center, if you have one, there are cells, which are starved from oxygen, but they’re still viable. You try and treat those with radiation. You may kill all of the tumor cells on the outside, which have a good oxygen supply, but you may not kill the cells right in the center that have no oxygen. It’s called the oxygen effect, and there’s a factor of about three round of radiation. So people started to think, “How can we get over the oxygen thing?” That’s why they put them in the hyperbolic oxygen chamber, pumped them up,

hoped the oxygen would get through and diffuse a little. There were reasons to think that it could work, but there a lot of reasons to think that it shouldn’t work, but it was tried and it didn’t work. But a number of people found that, in fact, if you were radiated with neutrons rather than electrons or X-rays, the cells and the oxygen effect disappeared. So the killing mechanism was a little different. With neutrons, instead of it being a factor of three, it’s a factor of 1.3. So it’s a slight difference, but not nearly as much of a difference. So the argument went if we could use neutrons, we could kill all of the cancer cells and maybe we could improve cure rates.

It was tried in the 1940s out in California by a man by the name of [ ] Stone. It was tried in England in Hammersmith Hospital. One of the difficulties is that neutrons are very damaging to tissue, and especially if there is any kind of fat content there, because they interact with the protons in the fat and you get a lot of solid fibrosis with neutrons, a lot of normal tissue damage, that you don’t want. An initial trial out in [University of California at] Berkeley had sort of come to a screeching halt because the complications are too high, there’s just too much fibrosis in normal tissues. But they were using low-energy neutrons, and one thought that maybe one should try that and see. This was in the late 1960s.

Then Texas A&M built a great big Cyclotron in the late 1960s, and we approached Texas A&M and said would they be interested in a joint project. If we could take a beam line off of their Cyclotron, very high energies, and make neutrons with it, we would get high-energy neutrons, much higher than the people at Berkeley had had, and we would like to see whether we could try neutron therapy. So we had a joint agreement with Texas A&M to develop the program out there, built one. One research area there we turned into a treatment area, and they sort of bused the patients up twice a week. It turns out with neutrons, the fractionation, how many times you give treatments, is not as critical as it is with X-rays. So you could go twice a week without sort of giving out.

James S. Olson, Ph.D.

Instead of every day?

Peter Almond, Ph.D.

Instead of every day. Eventually what we did, we mixed the neutrons with X-rays, which seemed to work very well. Anyhow, that trial, that program, seemed to work. We could certainly get rid of the tumors. The long-term event complications seemed to be less, and so it was decided we can’t continue to take patients up there and staff up there and run these two limousines. There was the day the wheel came off the limousine. We were driving along and the wheel took off down the road. Never knew what was going to happen, that was a fairly . . .

James S. Olson, Ph.D.

Who was in the limousine when that happened, which one of you?

Peter Almond, Ph.D.

I wasn’t there. Dave Fossiard [?] . I forget who was the physicist at that time. It wasn’t my day on.

Lesley W. Brunet, MA, CA

Was it a bus or a limousine that you went on?

Peter Almond, Ph.D.

Limousine.

James S. Olson, Ph.D.

With the patients.

Lesley W. Brunet, MA, CA

The patients went up on a limousine.

Peter Almond, Ph.D.

Yes, and so did the staff.

James S. Olson, Ph.D.

So did the physicists.

Peter Almond, Ph.D.

Physicists and radiography, we would cram into this limousine. We’d have a driver drive up. We eventually ended up with an apartment or two at A&M, and so several people stayed up there.

Anyhow, that pilot project seemed to work, so we decided we would see whether we would get a Cyclotron here at Anderson and went to NCI [National Cancer Institute] and got funding for one. A Cyclotron, instead of accelerating electrons, which all the other devices do, accelerates charged particles. We ended up accelerating deuterons, which is a proton and a neutron together. It’s the nucleus of a deuteron, take the electron off, because if deuterium at high energies hits a beryllium target, it will produce neutrons, and these are fairly high-energy neutrons, gives a nice sort of distribution like the distribution out of a linear accelerator for high-energy X-rays. So it was probably better than cobalt 60 in terms of the distribution and depth of penetration.

We went to the Cyclotron corporation in Berkeley that had built one or two sort of Cyclotrons, and they were willing to build us a Cyclotron to be housed in a hospital. Memorial had a Cyclotron up in New York for production of isotopes, but not for . . . The only other hospital

based Cyclotron was at Hammersmith Hospital in England where they were doing neutron therapy. They claimed a lot of success.

James S. Olson, Ph.D.

There’s so much hoopla about it when it happens, and then it seems to die off, to me.

Peter Almond, Ph.D.

Well, it did, and the problem. We eventually got the Cyclotron, we got it operational, we put it in the basement here, and treated a lot of patients with it. What we found out, I think, in the long run was what the initial study had found out, although we could cure patients, the long-term complications were just too high.

James S. Olson, Ph.D.

Because of the tissue damage?

Peter Almond, Ph.D.

Tissue damage, it just, just was not acceptable. As I say, we tried a regimen of part neutrons and part X-rays, which seemed to help. Some people continued a little longer than we did, and there may have been one or two sites that might have been useful and could have been treated by neutrons, but you really couldn’t justify the expense. It’s a fairly expensive process. The machine was expensive, keeping it operational was expensive, produces a lot of unwanted radioactivity, so health success-wise.

Anyhow, it was a project that needed to be tried. We did the pilot study. It seemed to work and got the Cyclotron here and then treated a lot of patients on it. But as those were followed out, [?] just disproved. I think also what’s happened, the other technologies and the other forms of radiation therapy have really sort of improved and improved so that you can get the dose to the tumors that you want. In some cases, with intensity-modulated radiation therapy, you can go up to doses half as high again as you used to be able to go. That’s a significant increase, and hopefully the tumor.

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Chapter 05: Developing Radiation to Address the ”Oxygen Effect” in Tumors

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