Tumors constantly evolve, and that evolution creates opportunities for cancer to elude the ongoing therapy. No single strategy will work. We must have a treatment to uniquely fit the particular patient’s situation.

Robert Timmerman, Chair of Radiation Oncology

 

UT Southwestern’s new Department of Radiation Oncology Chair, Robert Timmerman, M.D., is best known for his groundbreaking work in developing a treatment called stereotactic ablative radiotherapy (SAbR) that delivers high, very precise doses of radiation to kill cancer. The study he published in JAMA in 2010 showed such dramatic results in treating lung cancer that it quickly changed the standard of care.

Now, Dr. Timmerman, who became the Department’s Chair in March after serving six months as Interim Chair, has plans for revolutionizing cancer care again. As part of an overall effort to adapt treatment to the patient rather than rely on established standards, UT Southwestern has already begun using a new strategy called personalized ultrafractionated stereotactic adaptive radiotherapy, or PULSAR.

Dr. Timmerman joined UT Southwestern and the Harold C. Simmons Comprehensive Cancer Center in 2004 as Professor and Vice Chair for Clinical Affairs in Radiation Oncology, as well as Director of the Annette Simmons Stereotactic Treatment Center. He later became Clinical Director and Director of Clinical Research in the Department, adding an appointment in Neurological Surgery in 2008. 

He had previously worked as an Associate Professor of Radiation Oncology at the Indiana University School of Medicine. Dr. Timmerman holds a Bachelor of Science in nuclear engineering from Iowa State University and a master’s in reactor physics from the University of Tennessee in Knoxville. He received his medical degree from the University of South Dakota and completed a residency in radiation oncology at the Johns Hopkins Hospital.

Dr. Timmerman shared with Center Times his ambitious goals for Radiation Oncology, one of the University’s largest departments.

What are your goals for the Department?

Big changes are planned. After Professor Emeritus Hak Choy, M.D., stepped down as Chair of Radiation Oncology last year, faculty and staff collaborated on a new strategic plan that aims to treat each patient with an appropriately unique therapy. This personalization is a big departure from drawn-out conventional radiotherapy, even from our previous emphasis on short-course SAbR. While conventional radiotherapy and SAbR are different in many ways, they both are class solutions, in which patients of a certain type all get the same therapy. This prior paradigm might be called “one size fits all.” It is likely that some patients are overtreated, with no added benefit, while others are undertreated. We are moving toward a personalized, unique therapy for each patient.

How will you achieve this?

Much is in place, but more is required. We have installed a number of new “adaptive” treatment machines that can perform sophisticated imaging just before a treatment, as the patient waits on the treatment table. This allows us to recognize any changes in the patient and their cancer. Sophisticated computer software can then use this information to create a plan adapted to the imaging in minutes. UT Southwestern acquired the world’s second RefleXion PET-LINAC machine last summer, along with two Elekta Unity MR-LINACs. We are the only center in the world with two.

Yet these machines alone are not enough. We need to study the individual patient’s biology, including the treated tumor’s reaction to prior therapies, to determine if the treatment is performing adequately. Tumors constantly evolve, and that evolution creates opportunities for cancer to elude the ongoing therapy. No single strategy will work. We must have a treatment to uniquely fit the particular patient’s situation, whether it’s going well or poorly.

How does your shift to PULSAR factor into this strategy?

We started moving to PULSAR-style treatment about two years ago. With PULSAR, you put in purposeful pauses between treatments. You don’t want to reach a point where you wish you had given more or less treatment, but you’ve used all your ammo – treated to patient tolerance – before you’ve figured out whether you’re on the right course.

This style of treatment may also have the advantage of increasing the chances that the patient’s body will launch an immune response to the irradiated and destroyed cancer cells – something adjacent healthy cells might not be strong enough to do if stressed from frequent radiation treatments. SAbR by itself, while likely “vaccinating” the patient against their own cancer, rarely independently leads to an effective immune challenge to the cancer. However, using radiation plus other immune therapy modulators, like checkpoint-inhibiting drugs, shows tremendous promise to more elegantly fight cancer, even when strongly established. 

Tell me about new research using artificial intelligence, or AI, to tailor treatments to individual patients.

For the next several years, we’ll be collecting large volumes of patient-specific features as the patient and tumor react to therapy. We will also, of course, be following these patients’ outcomes. The plan is to then use AI computer technology to store, mine, and analyze patient-specific information – genetics, patient tolerance to imaging, what their tumor looked like, blood tests, and cancer cell and tumor markers. Eventually, through AI, we will start to recognize patterns that will help us personalize treatment for individual patients.

You developed SAbR, sometimes called SBRT, which delivers higher levels of more focused radiation to treat cancers. How did you get started on this?

I was originally trained to carry out the more drawn-out conventional radiotherapy that had been standard for nearly 100 years. In my personal view, the field was in a rut and needed to be reinvented. I, along with a few others around the world, introduced the SAbR paradigm, which exploited a number of technologies to direct radiation toward a tumor and away from normal, uninvolved tissues. Importantly, we used this technology to give very short courses of intense, highly focused radiation.

This radiation, unlike the previous type, was ablative – meaning highly potent – and caused dramatic tumor eradication. But because of the technological sparing, it was well tolerated. Such ablative radiation had been tried prior to the availability of the advanced technology, though it was very toxic at the time. But as opportunities and resources change, even old ideas can be re-examined and work much better. SAbR was such an example.