Artificial intelligence, along with an expansion of radiation oncology services, is allowing UT Southwestern (UTSW) Medical Center cancer physicians to pioneer a new PULSAR radiation therapy strategy that improves tumor control compared with traditional daily therapy.
Personalized ultra-fractionated stereotactic adaptive radiotherapy, or PULSAR-detailed in the International Journal of Radiation Oncology, Biology, Physics-achieved better tumor control by giving [alpha]-PD-L1 therapy during or after radiation, and spacing fractions 10 days apart rather than traditional daily fractions (2021; https://doi.org/10.1016/j.ijrobp.2021.03.047).
In the PULSAR paradigm, patients receive only a few large dose "pulses" delivered with sophisticated, image-guided precision at least a week and perhaps months apart. These split treatments are a radical break from the daily, long-course, conventional radiation treatments lasting 6-9 weeks. They are less toxic and give oncologists time to fine-tune treatment after the new machines' imaging shows the tumor's changed shape, size, position, and its reaction to radiation.
"We unexpectedly found in these experiments that the time split between large, focused doses of radiotherapy will predict whether a certain class of immunotherapy drugs will work," said Robert Timmerman, MD, Professor of Radiation Oncology and Neurological Surgery, and member of the Harold C. Simmons Comprehensive Cancer Center at UT Southwestern.
"If they are 10 days apart, the drug therapy helps a lot for this model. If they are 1-4 days, it doesn't help. Yet many of the clinical trials that are being done right now with radiotherapy and immunotherapy are using radiation schedules a day apart or every other day apart-perhaps the exact wrong timing."
By allowing more time to assess changes for meaningful adaptation of an individual patient's course, the PULSAR paradigm fulfills the promise of personalized cancer care. Instead of marching through a course of stand-alone, daily radiotherapy without interruption, PULSAR can be spaced out to more thoughtfully integrate with surgery and drug therapy.
"Using artificial intelligence, the team can replan cancer treatment in 30 minutes instead of the typical 5-7 days," said Timmerman, who is also Vice Chair and Medical Director of Radiation Oncology and holds the Effie Marie Cain Distinguished Chair in Cancer Therapy Research. "The equipment and expertise under one roof should break new ground in fighting cancer."
Collaborating on the PULSAR project are faculty from the departments of Radiation Oncology, Immunology, Pathology, and Neurological Surgery, and members of UT Southwestern's Peter O'Donnell Jr. Brain Institute and Simmons Cancer Center. UTSW Radiation Oncology is pioneering PULSAR in a new expansion of radiation oncology services with seven new machines that image tumors and treat them with radiation.
Artificial intelligence experts from Radiation Oncology and the Lyda Hill Department of Bioinformatics developed machine-learning algorithms, while radiation oncologists use the machines' combined radiation and imaging abilities to make treatments as precise as possible, hitting the tumors and sparing healthy tissue. Plans are underway to share expertise and data with other academic institutions, including Massachusetts General Hospital in Boston.
Timmerman and his colleagues discovered PULSAR radiation could bolster systemic immunotherapy benefit, even in situations where immunotherapy alone was not effective. They tested one of the most common classes of immunotherapy, a PD-L1 checkpoint inhibitor, along with the PULSAR radiation, which, in this combination, acts like a vaccination against the implanted tumors. The team found that splitting two pulses of radiation by 10 days was much more effective in combination with the checkpoint drug than the typical daily radiation schedule commonly used in radiotherapy clinics.