Proton Therapy vs. X-Ray Radiation for Prostate Cancer Treatment

Brian McCloskey, Allen Morris, and Brad Power May 15, 2023 “The cancer cells could care less what you're hitting them with. They don't know protons versus X-rays.

Advanced cancer patients face enormous challenges in eradicating their metastatic lesions, especially when their cancer has spread to several different locations in the body, hard to reach locations due to proximity to vital organs, and tough body parts like bones or the brain. They can consider surgical removal and various kinds of radiation. , they must have minimal medical problems, good lung function, and not be on certain medications).

Traditional radiation delivers X-rays, or beams of photons, to the tumor and beyond it. This can damage nearby healthy tissues and can cause significant side effects. By contrast, proton therapy delivers a beam of subatomic particles that stops at the tumor, so it's less likely to damage nearby healthy tissues.

Most commonly, proton beam therapy is used to treat tumors near critical organs or structures, such as head and neck cancers, and increasingly in spine, breast, sarcoma, brain, and prostate cancers. This is particularly beneficial to those who are vulnerable to radiation or have received prior radiation either to or immediately adjacent to the area that needs to be treated.

Proton beam radiation therapy may be safer and just as effective as traditional radiation therapy for adults with advanced cancer. Proton therapy is generally more expensive than traditional radiation, and not all insurance companies cover the cost of the treatment, given the limited evidence of its benefits.

Nevertheless, over 40 medical centers, including such NCI flagship institutions as Memorial Sloan-Kettering, Mayo Clinic, and Johns Hopkins have spent millions of dollars building proton therapy centers, and many advertise the potential, but unproven, advantages of the treatment. Carl Rossi, MD, and Medical Director at California Protons, is uniquely qualified to discuss the issues and solutions in proton radiation. Dr.

Rossi has personally treated more than 13,000 prostate cancer patients with proton radiation over the last 31 years—more than any other physician in the world. Internationally recognized for his achievements in cancer treatment, Dr. Rossi is a radiation oncologist with a research focus on the quality of life and cure rate in prostate cancer and lymphoma.

Specializing in proton beam therapy, he has been treating prostate cancer patients with proton therapy since 1991. Prior to serving as the Medical Director of California Protons, he was the Medical Director of the Scripps Proton Therapy Center and was an Associate Professor in the Department of Radiation Medicine at the Loma Linda University Medical Center.

He is currently also a professor of radiation medicine on the UCSD Radiation Medicine faculty. Dr. Rossi gave an overview of proton therapy for prostate cancer and a summary of recent papers. He discussed success stories in prostate cancer, why to choose proton therapy vs. alternative radiation approaches, and when proton therapy works/doesn't work.

Brian McCloskey 0:00 I am happy to announce that Dr. Carl Rossi is here with us today. I just met with him last week regarding my own case, and the use of proton therapy, in my particular disease setting. Dr. I've valued his counsel not only in radiation, but on how to navigate some of the challenges that I've had with my disease. Dr.

Rossi came from Loma Linda University Medical Center, which is where I believe proton therapy was invented back in the 70s if memory serves me correctly, and he mentored with the best. Dr. Rossi, If you want to add some more context, I think it would be helpful. But before you do that, the main point for our patients is that when they're considering local therapy, it's often just a decision between doing surgery or radiation. Dr.

Rossi is going to help us understand when that makes sense, and what is the difference between proton therapy and various other forms of local radiation? Carl Rossi 2:12 Dr. Rossi’s history as a Radiation Oncologist I got into all this entirely by accident. I just happened to do my radiation oncology residency at Loma Linda, when they were starting construction of what was and is the world's first medical proton center.

So I was there really by accident when everything was going at that place, and ended up staying there for almost 25 years. Then I came down here to San Diego when this facility was being built because of the technology differences, which are true now of all the newer centers, and I'll be touching on that again in this presentation. Carl Rossi 2:56 There is going to be a fair number of slides.

I'm going to go through them fairly quickly, though, because I want to save a lot of time for Q and A. I'm going to talk about the use of protons near the end, both in primary therapy, it's one of the many ways to cure prostate cancer that's localized, and also in what we're doing more and more of now, which is treatment of oligometastatic disease.

That's because we're becoming somewhat not victims, but it's a consequence of our success at controlling prostate cancer and other cancers. This idea of treating solitary metastasis, or a few metastases, really came about because the primary therapies and the systemic therapies have gotten better and that people live long enough to develop these problems which wasn’t as much of an issue even 10 or 15 years ago.

So, it's in some respects a good problem to have until we get to the point that we can eliminate this stuff by radiotherapy and current therapies entirely. Molecular target of action for Radiotherapy: DNA Just to remind folks, the target for radiotherapy is DNA. That's what we do with any type of radiation. What we're doing is we're causing DNA breaks.

And that's why when you talk about radiotherapy, we've done a lot of things to try to be more target specific because the more dose we can put in the bad stuff, the greater we can crack that window open. Unfortunately, the fact is the repair difference between bad tissue and good tissue is small. We've had radiotherapy for a really long time. The most toxic mechanism of action of radiotherapy is double stranded DNA breaks.

[Comment from Allen Morris: One does not want to create double stranded DNA breaks in normal tissue or a genomically stable indolent cancer because of the side effect: secondary cancers of normal tissue or genomic evolution of a stable cancer, barring “nuclear bomb”, ablative effect to the latter.

] History of Radiation Oncology It's been well over 100 years since it was first used in a very rudimentary way before the beginning of the 20th century. Within a year of the discovery of X-rays and natural radioactivity, people were using it to treat all sorts of stuff. They learned a lot of things the hard way.

To illustrate, here is a picture of a monument in Hamburg, Germany to the radium martyrs, the several 100 people, clinicians, and other folks who died because of radiation induced diseases they developed. We learned the hard way, like so many things in medicine and in science. ] So we have some basic tenets in radiotherapy. The first is that nothing that we know of is radiation-resistant. Some things are more resistant than others.

But if you give a high enough dose, you can kill anything with radiation that we know of. In general, the malignant cells, as I mentioned earlier, are less able to repair that damage, but that difference can be relatively modest. And the other is this idea that, learned empirically, radiation is a toxin, and that there probably is no dose below which toxicity does not occur.

Off Target Toxicity (Organs at Risk/OARs) Certainly the higher doses are more toxic, but it doesn't mean that lower doses are non toxic. We have this concept called ALARA, an acronym for “As Low As Reasonably Achievable”, that underlies all radiation protection. Whether you're working in a nuclear power plant, or whether you're doing radiation therapy, or diagnostic work, we try to keep the dose to people as low as we can.

And this is underlying all of our modern radiotherapy delivery technologies; this desire to spare people from unnecessary radiation. We’ve had a lot of advances. “Intensity modulated X-ray therapy”, “IMRT”, is probably the standard way (standard of care) of doing great X-ray therapy. We have protons, brachytherapy, or implants, and radioimmunotherapy, as many of you have experienced personally. These are all different variations on the same theme.

That is, let's limit toxicity by being as careful as we can. Using whatever technology we have to maximize target dose and minimize normal tissue dose. The reason we all pull on the physics lever is because we understand it better. We do not have as nearly an accurate grasp of Radiation Biology, despite having studied this now for a long time, as we do on radiation physics. So we use the tool that we can exploit and that's the physics tool.

I mentioned a minute ago that IMRT is the standard radiation tool (standard of care). In IMRT you're using different X-rays, either in what's called a step and shoot fashion or arc, you're doing a volumetric arc, and you're varying the intensity of the beam as you deliver it so that you're stacking the dose, the highest dose to whatever target you want to hit.

IMRT works great compared to three dimensional X-ray therapy of 10 to 15 to 20 years ago. But the problem is you're using X-ray beams and you have to dose on the way in and dose on the way out. So the compromise you have to make, if you're doing say IMRT to the prostate, is that they get this beautiful high dose to the prostate, but you're gonna give a bath of dose to everything else [Off target dose - Organs at Risk/OARS].