Fundamental Considerations in Radiation Oncology With Charles Simone, MD, FACRO

At the recent Oncology Nursing Society (ONS) Congress in Anaheim, California, Charles B. Simone, II, MD, FACRO, explained the concepts underlying the treatment of cancer with radiation therapy. In this interview with Oncology Data Advisor, Dr. Simone discusses the different types of radiation treatments and some considerations in choosing treatment. He also shares current evidence from his research about synergy between radiation therapy and checkpoint inhibitors or chemotherapy. 

Oncology Data Advisor: Welcome to Oncology Data Advisor. Today, I am here with Dr. Charles Simone, an internationally recognized expert in thoracic and radiation oncology and Research Professor and Chief Medical Officer of the New York Proton Center and a member of the Department of Radiation Oncology at Memorial Sloan Kettering Cancer Center. Thanks so much for doing this interview, Dr. Simone.

Charles Simone, MD, FACRO: My pleasure. Thank you very much for having me.

Oncology Data Advisor: Can you tell us a little bit about yourself and what your research interests are?

Dr. Charles Simone: Sure. I’m a radiation oncologist. I focus on thoracic malignancies, including lung cancer, mesothelioma and thymic tumors. Most of my research has been to determine ways and novel approaches to mitigate normal tissue toxicity or to give treatment options to patients who don’t have good conventional treatment options. That has covered everything from looking at drugs to give during radiation to help protect from side effects or different approaches in technology, such as proton therapy or intensity-modulated radiation therapy. I also have a particular interest in combining radiation with immunotherapy, and then, lastly, re-irradiation, as well—giving radiation a second time to the same area.

Oncology Data Advisor: That’s a lot of great stuff. What are important considerations in determining which type of radiation treatment to choose for a patient?

Dr. Charles Simone: Great question. It really comes down to the tumor location and type and the expected outcomes with that treatment. Some treatments that are very superficial may warrant a type of radiation called electron therapy, but most treatments are delivered with proton or photon radiation therapy. About 97% of all external beam radiation treatments in the US are delivered with photons, and there are many different flavors of photon therapy, the most modern of which being intensity-modulated radiation therapy or arc-based, volumetric arc-based treatment. Those are very, very well suited for most tumors, but there are several tumors that potentially have high expected risks of side effects or limited chance of controlling the tumor long term. Those are tumors that probably are most suited for proton therapy treatment.

Oncology Data Advisor: What’s the difference between proton versus photon therapy?

Dr. Charles Simone: With photon therapy, it is x-ray radiation. So, you can think of it almost like if you are projecting a flashlight. The radiation will keep going. As you get further from the flashlight, it’s less intense. But the radiation essentially leaves the head of the treatment machine, travels to the body, hits the area that you want to hit, but then it keeps going out other side, so it goes through and through patients. Now the energy decreases, just like that flashlight example, as you travel further into the body, and that’s because the radiation is being absorbed by the normal tissues. And that’s where you get side effects from radiation, in the normal tissues both before and after the tumor that you intend to treat.

With proton therapy, because it’s a heavy charged particle, we can send the radiation in, we hit the area we want to hit, and then we can deposit all the radiation at that exact depth, so there’s no radiation beyond the tumor. So, all the normal tissues beyond the tumor are spared of any risk of side effects from radiation therapy. That can allow protons to have decrease in overall side effect profile and better preservation of quality of life for patients.

Oncology Data Advisor: When should patients consider traveling to get proton therapy?

Dr. Charles Simone: Right. There are only 39 proton centers in the country. They tend to be aggregated in large metropolitan areas. Much of the rural part of the United States is more than 50 miles away from a proton center. Our governing body and society projects that around 20 to 30% of tumors could significantly benefit from proton therapy, but it really depends on the tumor type. For many early-stage cancers that have high tumor control rates and low toxicity risks, there really isn’t much appreciable benefit to traveling to get proton therapy. For more difficult to treat tumors that are very invasive, very large, spread to many lymph nodes in the area, those are tumors that may be more likely to benefit from proton therapy.

Oncology Data Advisor: Thanks. And then my last question is based a bit on your research, which is what is the current evidence for synergy between radiation therapy and checkpoint inhibitors or chemotherapy?

Dr. Charles Simone: There is certainly increasing evidence. We’ve long realized that many tumors are immunogenic in nature, whether your own body’s immune system is helping to address the tumor or giving a specific drug or agent to address the tumor itself. Historically, there have been many approaches to that, such as strong immune stimulants, and, more recently, vaccine treatments and chimeric antigen receptor (CAR) T-cell therapy, natural killer (NK), and T-cell therapy. But we’re seeing more and more use of inhibitory check blocking, such as immune checkpoint inhibitors, and most ubiquitous throughout the different malignancies is programmed cell death-1 (PD-1) and PD-ligand-1 (PD-L1) agents. Those agents are very good at increasing immune response to tumors, and in patients that have responses, the responses are pretty significant and can be quite durable. But, unfortunately, with those agents, in almost every cancer, it’s a minority of patients who will actually respond to an immune checkpoint inhibitor.

Combining immune checkpoint inhibitors with other immune checkpoint inhibitors or with chemotherapy or other targeted agents may improve their response rates, but there’s more and more interest in using radiation therapy as a way to increase the response rates of the immune checkpoint inhibitors. And there are two ways that can happen: one is with radiation essentially working in an additive approach with the immune checkpoint inhibitor, so radiation controlling an area locally and using the immune checkpoint inhibitor to control regional and distant disease. But radiation can also upregulate the immune system and even turn some tumors that would not have likely responded to immune checkpoint inhibitors to be more likely to respond to immune checkpoint inhibitors.

So, it’s certainly an exciting area of research, it’s really blossomed in the last two or three years. And there are several studies that have shown we can even achieve abscopal effects, meaning patients that are progressing on an immune checkpoint inhibitor get radiation to one area, and areas outside of that radiation field respond significantly to the immune checkpoint inhibitor combined with radiation. Many early trials are showing this is a potential. Certainly, we’re far from understanding how we harness this most appropriately, what radiation fractionation should we use, how do we time the radiation with the immunotherapy, but there are more and more studies looking at that combination. I’m leading a large phase 3 NCI-funded trial now, looking at immune checkpoint inhibitor in combination with radiation therapy for early-stage non-small cell lung cancer as one of the trials.

Oncology Data Advisor: That’s really interesting and thank you so much for your time.

Dr. Charles Simone: My pleasure. Thank you so much for inviting me.

About Charles Simone

Charles B. Simone, II, MD, FACRO is a Research Professor and the Chief Medical Officer of the New York Proton Center and a Full Member in the Department of Radiation Oncology at Memorial Sloan Kettering Cancer Center. He is internationally recognized as a proton therapy expert specializing in the treatment of thoracic malignancies. His research into the development of new clinical strategies in radiation oncology include studies in reirradiation of previously irradiated sites, clinical trial development in thoracic radiation oncology, stereotactic body radiation therapy, proton therapy, and traditional therapy as part of multi-modality therapy for thoracic malignancies. He has received funding through the National Science Foundation, the National Institutes of Health, and the Department of Defense. Dr. Simone has published over 465 peer-reviewed scientific articles and book chapters, given hundreds of scientific lectures to national and international audiences, and is the national Principal Investigator or Co-Chair of eight NIH-funded cooperative group trials. He is a three-time winner of the Association of Residents in Radiation Oncology (ARRO) Educator of the Year Award, and he is a Fellow in the American College of Radiation Oncology (FACRO). Dr. Simone Chairs or Co-Chairs multiple committees involved with radiation oncology. He is the Editor-in-Chief of Annals of Palliative Medicine and on the Editorial Boards of several other peer-reviewed journals.

For More Information

Simone C, VanDuren J, Farley-McDonnell B & Mead-Smith S (2022). Deciphering the specialty of oncology radiation. Presented at: 47th Annual ONS Congress.

Transcript edited for clarity. Any views expressed above are the speaker’s own and do not necessarily reflect those of Oncology Data Advisor. 

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