ASTRO Interview with Dr. Eric Ford
A few months ago, I received the opportunity to sit down with notable physicist, professor, and experimental radiobiology researcher, Dr. Eric Ford. As one of the masterminds behind the Precision Proton Radiotherapy Platform, which uses particle beams to precisely target tissue, Dr. Ford helps us understand how particle beams interact with tumors and normal tissue. With his focus on improving the quality of patient treatments, capturing his motivation and outlook behind the image guided proton irradiator seemed fitting at the 2017 American Society for Radiation Oncology Conference.
With the idea in mind of treating cancer, was there a particular type of cancer that fueled your passion for creating the Precision Proton Radiotherapy Platform?
Proton therapy can be used for a lot of different types of cancer. But one of the cancers that fueled my passion was pediatric cancer, because of the tissue sparing that happens and the long life that patients will have after they survive this cancer. So, to me it is highly motivating to further understand the biology of those pediatric cancers; those cancers that largely present in the CNS. Overall, it’s important to understand the normal tissue toxicities that are different in a proton beam verses a photon beam. There are discussions here at ASTRO about this very issue. So, it is kind of an unknown area.
How would you explain to an immunologist the benefits of using proton beam therapy?
There is very little known about the differential effects of protons verses other radiation in the immune context. There are some data out there that suggest that it is different. The upregulation of genes appears to be different, the “eat-me” signal that is given out appears to be different with particle beams, but it is really a work in progress. So, I would say that it is unknown and that there are lots of experiments that need to be done. You really need focused radiation to be able to do these types of experiments. Because if you dose a whole organism, there are big effects on the different cellular components of the immune system; which will really affect the experiments.
Based on the science and development behind the Precision Proton Radiotherapy Platform, do you foresee a cancer type that your platform would be most effective at treating?
It’s hard to make a prediction about it having an impact for one type of cancer. Jim Deye and I recently wrote a review article that looked at all the literature that has been published in the last 5 or 6 years on this, and there are not many papers in the realm of particle beam experimentation, because there hasn’t really been a platform to investigate this in vivo. But if you look at the photon experiments, there are interesting results in lung cancer, brain cancer, pancreatic cancer, and prostate cancer. So, it spans a broad spectrum of things and I believe that it may be similar with proton beam therapy.
Would you say that this platform will be just as beneficial for investigating benign conditions?
Currently, proton therapy is used for benign conditions; but that is relatively less common right now. For example, radiosurgery is done for trigeminal neuralgia, which is a condition that affects the 5th cranial nerve. We can treat this with radiation but that is not so much treated with protons.
Do you believe that your platform can bring treatment for benign conditions to the next level?
We have done some work with non-cancers with the platform. There has been some innovative work in neurodevelopment looking at stem cell niches in the brain where you can use the beam to ablate stem cells regions very specifically. For example, Blackwell’s group at John Hopkins, found a population of stem cells in the 4th ventricle of the brain; in which they didn’t know what its function was. So, they did an ablative procedure where they radiated just that region; a region right near the pituitary gland. That is very challenging to do, but they found that those cells were involved with metabolism and this spun a whole new area of research. It’s an example that shows what can be done within non-cancerous conditions using this type of platform.
Looking at more basic biology, there is another experiment we did looking at an SSRI, selective serotonin reuptake inhibitor. The question was about the mechanism and how it works. This is outside the realm of cancer research, but we could show that part of the mechanism had to do with a neuroprogenitor cell component in the brain. This information was actually important for understanding the effects of associated drugs.
So, I think this is way beyond cancer and the awareness needs to be out there for labs to know about the technology. If you look at the difference between protons verses photons and you are delivering an ablative dose, it doesn’t matter how you do that; whether X-rays or protons. But you might argue that you can do something more localized with protons, or something that may be more targeted and have less of an effect on the rest of the organism. So that might be an area where we might see some benefit. But there is a lot more needed to look at that.
I think the key thing here is that you can do these experiments in vivo, and that has not been something that was possible very much until now. Being able to target the beam enough so that you do not disturb the surrounding tissues is important. If you are looking at cancer, then you only treat the tumor and you do not want to irradiate the normal tissue because this can have an undesired effect. So, you need image guidance and a localized beam to do that. We have had this with X-rays for a while, but we really didn’t have this for particle beams; until now.
Using a recently read research paper, has there been anything that made you say, “This is why my proton beam technology will be so useful.”
When you look at new experiments coming out and you see intriguing data that are not thoroughly explained, that is an exciting thing. We are seeing some experiments looking at particular beams where a differential effect of particle beam verses X-rays, may have something to do with the way the dose is deposited. Generally, much of what will come in the next few years is still unknown. When there is something new that has yet to be explained, and now we have a tool to go and look at it, that is a good thing.
How would you describe your feelings about bringing this platform to the industry?
It’s exciting! But it also brings many uncertainties. Because it’s biology; and biology is the land of the unknown.
Speaking of biology, how is it to be a physicist and deal with the different aspect of uncertainty associated with biology?
As a physicist, we like to control and measure things, just like all scientists. Physics is on the extreme spectrum of that. But when you look at a biological system, there are so many more variables. You just don’t have that level of control. So, it’s a little bit intimidating. I think that is the word that I was looking for… intimidating. It’s exciting, but also intimidating.
Viewing myself from the physics point of view, I often feel like a translator; translating across disciplines. Giving ideas about what we can do technically, while understanding bits and pieces of the biology. Not being an expert in it, but knowing enough to talk to people.
What made you so interested in combining your technology with the Small Animal Radiation Research Platform (SARRP)?
For me, it was my long history in the development of SARRP. I was involved in the early days in its development back at Hopkins. Back in 2005, we built this prototype actually taking images with a film plate. So, it’s a history that goes way back. And for me, it’s more of familiarity with the technology. When we got the unit, we were able to adopt it very easily to the prototype proton beam line. And that was not trivial because the beam line is a fixed beam coming out of the wall; and so, it’s under some strong geometrical constraints. It’s good that we were able to do this as a partnership.
How has this partnership bettered your outlook for the Precision Proton Radiotherapy Platform?
It has opened us up to new experiments that we might do with different labs that are interested.
A statement was made at ASTRO by Dr. Silvia Formenti, in which she referred to you regarding dose fractionation and blood circulation, can you tell me more about this?
She was referring to a mathematical model that I helped developed. This model looks at the radiation dose delivered to the blood pool of a patient that is being treated.
With the idea that the blood flows through the portal as the beam is on, you are delivering a nonsignificant dose to the entire blood pool of the patient; and over time that accumulates. It does depend on fractionation and the way that the radiation is delivered. This is a model that we worked on about 7 years ago. It has actually shown to have an effect in clinical data now; which is really exciting.
In relation to radiation oncology, what is your opinion about the following statement made at ASTRO?
“People will live with cancer as a chronic condition, not as a terminal condition.”
A lot of that is outside of what I am an expert on. But one thing that I can say, if this is true, and cancer patients are going to be living with a chronic condition, then the research is more important. It’s important that we get the right agents, reduce the toxicity, and reduce the cost.
Where do you see the Precision Proton Radiotherapy Platform and the field of research in 5 years?
I think that combined agents have not been fully explored. When you look at an agent, it is interesting to know what it does in combination with other agents. Part of the reason that it has not been explored is because the technology to investigate it is not widely available.
You will see this in the clinic as well. If you have a technology that is available like 4D CT suddenly you can treat patients with a new technique, like SBRT. So, when you have a technology that enables a new area of clinical treatment or a new area of research it can lead to fruitful avenues.
What’s next for you?
Well we just need to do more experiments. I have tried to focus less on the technical development and more on the science because as a physicist with a technical background it is easy to become addicted to the gadgets; which are important. But then you must think about what is next…what does this gadget really allow you to do.
