Stereotactic Ablative Radiotherapy (SABR)

Incubating Progress: Talent + Technology + Teamwork

UT Southwestern is helping redefine lung cancer care through innovations in stereotactic body radiation therapy

Background

Stereotactic radiotherapy, originally piloted for treating tumors situated in important functional parts of the brain, operates on a converging-beam principle in which dozens of highly focused yet relatively weak radiation beams from different directions travel through normal tissues on their way to a tumor target deep within the body. The intentionally weak beams cause little entry damage, but at the point of convergence, they add up to deliver a very potent tumor treatment.

For decades, its use was confined to the cranium. Precise but also extremely powerful, stereotactic radiotherapy was not possible elsewhere in the body, where breathing and other functions could cause the target to move, potentially resulting in disastrous side effects.

However, recognition that new image-guidance technology could address that challenge has fueled development of stereotactic body radiation therapy (SBRT), also known as stereotactic ablative radiotherapy (SABR). For the past decade, UT Southwestern has been on the leading edge of SABR innovations.

Drs. Choy and Timmerman at control panel
Radiation oncologists Hak Choy, M.D., and Robert Timmerman, M.D., oversee the image guidance features of the VERO linac as it precisely directs stereotactic radiation toward a patient’s lung tumor.

The Foundations

2003: Hak Choy, M.D., is named Chairman of Radiation Oncology at UT Southwestern, with the goal of developing a department that deploys the most promising technologies against cancer.

2003: At a national meeting of radiation oncologists, Robert Timmerman, M.D., then a faculty member at Indiana University and a renowned expert in stereotactic radiosurgery, is met with skepticism when he presents early results of a clinical trial indicating SABR appears effective in patients with early-stage, non-small cell lung cancer (NSCLC).

2004: Dr. Timmerman is recruited to join the radiation oncology faculty at UT Southwestern in a practice focused on stereotactic radiation. The lung — the most mobile and difficult site to work with — is the subject of the first wave of SABR research because proof-of-principle in that location would translate readily to cancers in other locations.

2011: UT Southwestern becomes the first North American institution to install Vero SBRT, an advanced system for imaging tumors and delivering treatment. Vero joins Simmons Cancer Center’s formidable arsenal of stereotactic radiotherapy technology, including cutting-edge Gamma Knife, CyberKnife, Agility, and TrueBeam technology.

The Translation

2010: In a study of 55 early-stage lung cancer patients too frail to withstand traditional surgery, Drs. Timmerman, Choy, and colleagues report SABR has achieved control of 98 percent of the primary tumors, a rate comparable with surgical resection. Previously, for early-stage patients unable to withstand surgery, standard radiation had achieved only a 30 to 40 percent rate of tumor control. The publication changes the standard of care for so-called medically inoperable patients.

News release: Precision radiation therapy may improve survival rates of patients with inoperable early-stage lung cancer

2011: A $3.5 million grant from the Cancer Prevention and Research Institute of Texas (CPRIT) funds a five-year, multi-institution effort to develop advanced radiotherapy technology for lung cancer with the aim of also reducing toxicity. The program is led by Dr. Choy and includes Cancer Center members Dr. Timmerman, Chul Ahn, Ph.D., and Puneeth Iyengar, M.D., Ph.D.

2012: Cancer Center scientists receive a $4.1 million multi-investigator research award from CPRIT to explore in lung cancer how best to exploit the radiobiological effects of SABR, whose cancer-killing properties at the cellular level appear different than those of standard radiation. Dr. Timmerman heads the project, which also involves Cancer Center members Drs. Ralph Mason, Rolf Brekken, Chul Ahn, Debu Saha, and others, along with the work of the late Dr. Phil Thorpe.

2014: Cancer Center researchers led by Drs. Timmerman and Choy potentially extend the use of SABR to patients with stage IV limited metastatic NSCLC. In a phase II, multi-institution trial combining lowered doses of SABR with the drug erlotinib, the treatment is well-tolerated and patients markedly surpass the time periods they otherwise would be expected to survive without disease progression. Tissue analyses suggest the SABR is primarily responsible for the benefit.

News release: Stereotactic body radiation therapy plus chemotherapy improves survival among stage 4 lung cancer patients

The Impact

2008-2015: As stereotactic radiotherapy research flourishes, new studies indicate its effectiveness on various cancers that have spread to a limited number of sites in organs such as the liver and lungs. SABR also appears promising in classically “radio-resistant” tumors such as renal cancer and melanoma.

2009: UT Southwestern’s Department of Radiation Oncology begins hosting quarterly, hands-on courses to train peers interested in implementing SABR in their clinical practice. As of 2015, more than 300 practitioners from all over the world had been trained through the initiative.

2014: A team led by Dr. Timmerman reports on five-year follow-up results among the patients, too frail for surgery, who received SABR for early-stage lung cancer. The rate of recurrence at primary tumor sites is low, and the powerful therapy is not associated with any surge of late ill effects — demonstrating SABR’s long-term efficacy and safety in early lung cancer.

2015: Investigation of SABR continues at UT Southwestern for cancers in sites including the prostate, breast, and larynx, and a range of clinical trials of the therapy are open at Simmons Cancer Center.

The Future

Drs. Timmerman, Choy, and Ahn are leading an ambitious phase III study, expected to encompass more than two dozen sites, directly comparing the benefits of surgery versus SABR in lung cancer patients healthy enough to choose surgery. The trial aims to collect evidence from 258 patients with high-risk stage 1 NSCLC.

UT Southwestern scientists continue to reveal other possible uses for SABR — for instance, treating inferior vena cava tumor thrombus, an often-deadly kidney cancer complication — while medical physicists are advancing imaging techniques to more precisely predict motion, further improving treatment safety and accuracy.
News release: Physicians pioneer the use of stereotactic body radiation for deadly kidney cancer complication 

Simmons researchers also aim to develop SABR using heavy particles instead of photons — lowering radiation dose to healthy tissues. And with a $1 million planning grant from the National Cancer Institute, as well as state funding, UT Southwestern is leading a Texas consortium to plan for the first National Heavy Ion Radiation Therapy and Research Center, with the goal of researching and providing innovative cancer treatments that leverage the potency and precision of heavy particles.

Significant Publications

Timmerman, R. et al. Stereotactic body radiation therapy for inoperable early stage lung cancer.  JAMA 303, 1070-76. (2010).
Iyengar, P. et al. Phase II trial of stereotactic body radiation therapy combined with erlotinib for patients with limited but progressive metastatic non-small-cell lung cancer. J Clin Oncol 32, 3824-30 (2014).
Timmerman, R.D. et al. Emergence of stereotactic body radiation therapy and its impact on current and future clinical practice. J Clin Oncol 32, 2847-54 (2014).
Westover, K.D. et al. SABR for aggressive local therapy of metastatic cancer: A new paradigm for metastatic non-small cell lung cancer. Lung Cancer 89, 87-93 (2015).

The new Harold C. Simmons Comprehensive Cancer Center Radiation Oncology Building is North Texas' largest and most comprehensive individual facility for radiation oncology.