Chapter 11:  Documenting the Benefits of Proton Therapy

Chapter 11: Documenting the Benefits of Proton Therapy



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Dr. Cox explains a difficulty with proton therapy: the advantages can be seen on paper and modeled by computer, but “we don’t yet have the evidence that people want.” He describes the kinds of treatment advantages that proton therapy provides, particularly the reduction of toxicity.

Dr. Cox explains a study showing that proton therapy avoided toxicity in treatment of 15 patients with cancer of the tongue, then describes the next step of this research: to demonstrate the differences between two dimensional and three dimensional, conformational therapy. He explains that proton therapy offers these advantages because the beam can be targeted to hit very isolated structures.



Publication Date



Houston, Texas

Topics Covered

The Interview Subject's Story - The Researcher; The Researcher; Overview; Definitions, Explanations, Translations; Devices, Drugs, Procedures; Healing, Hope, and the Promise of Research; Discovery and Success; On Research and Researchers


Uh-hunh (affirmative). Now when you said surprised or that you weren’t surprised, it sounds to me that you weren’t surprised because you really believe in the ability of radiation to do this. Am I interpreting that correctly? James Cox MD Well, I don’t know if I believe it. I take it back, you’re probably quite right. (laughter) I’m in a situation now—and you’re going to want to come to that eventually—where proton therapy, because we can see the advantages on paper or in the computer, we can see that the dose distributions that avoid normal tissues have to decrease the risk of complications because it avoids the tissues where complications occur. But we don’t have the evidence that people want and they’re in a great hurry for—comparing protons versus x-rays. Tacey Ann Rosolowski PhD Uh-hunh (affirmative). Talk to me about what you are seeing on paper and on computer that creates these advantages.

James D. Cox, MD:

Well, you’re seeing that you’re able to spare normal structures. For lung we’re able to spare the lung, the normal lung—and the heart and the esophagus better than we can with even the most sophisticated x-rays, which would be IMRT or intensity-modulated radiation therapy. Is that going to play out in the advantage of either reducing toxicity or improving tumor control? I think the main difference there is going to be a difference in survival because I think it’s going to be a combination of controlling the tumor and avoiding toxic effects on the lung. But in head and neck, Steven Frank, one of my colleagues, is taking the lead in treating patients with cancer of the oropharynx—that’s tonsil and base of tongue, mostly tonsil and base of tongue—tonsillar fossa and base of tongue, showing that by using protons with the scanning beam, he’s able to avoid toxicity in the tongue. When they treat such patients with IMRT, they have to spread the dose out, so a lot of the dose goes into the oral cavity. That is incredibly adverse in terms of altering people’s lives—interfering with the quality of life. He has shown with just a handful of patients—15 patients—that there’s an ability to avoid that toxicity in the oral cavity that is very striking.

Tacey Ann Rosolowski, PhD:

And his name again?

James D. Cox, MD:

Steven Frank.

Tacey Ann Rosolowski, PhD:

Thank you. What was the research that you did after the lung studies in the ’90s or continuing with them into the 2000s that brought you to the interest in the proton center or in proton therapy?

James D. Cox, MD:

Well, I’m not sure that the lung studies brought me into the interest in the proton center. Actually the study—that I didn’t do, it was done by other people at MD Anderson—that shed the greatest light on showing the difference between the older kind of 2D treatment versus a 3-dimensional conformal therapy to a higher total dose showed that the patients who were treated to the higher total dose did better in terms of biochemical freedom from progression, and that was one of the earliest studies that showed that difference. Then it seemed obvious that by avoiding the normal structures that caused toxicity when treating cancer to the prostate and giving a higher dose, you can improve survival. Then on paper or in the computer, proton therapy is the ultimate way to do it—maybe not the ultimate way, but a way very different than anything that can be done with x-rays because protons stop and can be made to stop wherever you want them to stop in the body. And so that was the genesis in my interest in proton therapy because I knew that in the future so much more could be done. And then, when we started developing the portfolio of clinical investigations for proton therapy, cancer of the lung was at the top of my list because I thought we could make a lot of progress there, and we have, but we don’t have enough patients treated in comparison with IMRT that have been followed long enough to say anything.

Tacey Ann Rosolowski, PhD:

How would you like to proceed next? Because obviously there’s lots going on with the Proton Therapy Center and the research in the different studies, but I want to make sure that we fill in the blanks so that we know how you moved up to working with that. Do you feel we’ve covered the research that you’ve done prior to the Proton Center adequately? Or are there some other studies you’d like to mention?

James D. Cox, MD:

Well, we could talk for a long time about all of those studies. I think we’ve covered it generally. It was a mix. If you look at the overlap if you were to try a Venn diagram, you would see the studies that were being done in the RTOG overlapping that were being done at MD Anderson. In lymphoma there was no overlap, but with lung there was a great deal of overlap. Then I got directed into studies also of cancer of the esophagus, which really is a story of putting all modalities together of the surgery and the radiation therapy and the chemotherapy—chemotherapy and radiation therapy being given at the beginning, and then following that was surgery.

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Chapter 11:  Documenting the Benefits of Proton Therapy