New PULSAR radiotherapy strategy enables better tumor control

Artificial intelligence, along with a $ 71 million expansion of radiation oncology services, enables oncologists at UT Southwestern Medical Center to launch new PULSAR radiation therapy strategy that improves tumor control over traditional daily therapy.

Personalized Ultra-Fractional Stereotaxic Adaptive Radiation Therapy, or PULSAR – detailed in International Journal of Radiation Oncology, Biology, Physics – achieved better tumor control by administering α-PD-L1 therapy during or after radiation therapy, and spacing out 10-day fractions rather than traditional daily fractions.

In the PULSAR paradigm, patients receive only a few high-dose “pulses”, delivered with sophisticated, image-guided precision, at least a week or even months apart. These “fractional treatments” are a radical departure from conventional long-term daily radiotherapy treatments that last six to nine weeks. They are less toxic and give oncologists time to refine treatment once the new machines’ imaging shows the tumor shape, size, position and response to radiation.

“We unexpectedly found in these experiments that the time-split between large and targeted doses of radiation therapy will predict whether a certain class of immunotherapy drugs will work,” said Robert Timmerman, MD, professor of radiation oncology and surgery neurologist and member of the Harold C. Simmons Comprehensive Cancer Center at UT Southwestern. “If they are 10 days apart, drug treatment helps a lot for this model. If they last one to four days, it does not help. Yet many ongoing clinical trials with radiation and immunotherapy use radiation programs one day apart or every other day apart – maybe exactly the wrong time. “

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 taking a daily stand-alone course of radiation therapy without interruption, PULSAR can be spaced out to more thoughtfully fit into surgery and drug therapy.

“Using artificial intelligence, the team can reschedule cancer treatment in 30 minutes instead of the usual five to seven days,” said Dr. Timmerman, vice president and medical director of radiation oncology and incumbent. the Effie Marie Cain Chair in Cancer Therapy Research. “Equipment and expertise brought together under one roof should innovate in the fight against cancer.

Professors from the departments of Radiation Oncology, Immunology, Pathology and Neurological Surgery collaborate on the PULSAR project, as do members of the Peter O’Donnell Jr. Brain Institute and the Simmons Cancer Center at UT Southwestern, the one of 51 designated comprehensive cancer centers in the United States. by the National Cancer Institute, a member of the elite 30 members of the National Comprehensive Cancer Network, with its cancer program ranked in the top 25 by American News and World Report.

UTSW Radiation Oncology is pioneering PULSAR in a new 71,000 square foot extension of radiation oncology departments with seven new machines that image tumors and treat them with radiation.

The new adaptive radiotherapy devices of the Radiation Oncology extension are:

• Two Varian Ethos machines, which integrate CT scans and artificial intelligence with radiotherapy.
• Two Elekta Unity machines, which integrate MRI imaging with radiotherapy.
• Two Varian Halcyon machines, which integrate cone beam computed tomography with radiotherapy.
• One RefleXion, which integrates PET imaging with radiotherapy.

Artificial intelligence experts from radiation oncology and Lyda Hill’s bioinformatics department have developed machine learning algorithms, while radiation oncologists use the combined radiation and imaging capabilities of machines to make treatments too as precise as possible, hitting tumors and sparing healthy tissue.

Plans are underway to share expertise and data with other academic institutions, including Massachusetts General Hospital in Boston.

Results

Dr. Timmerman and his colleagues found that PULSAR radiation could enhance the benefits of systemic immunotherapy, even in situations where immunotherapy alone was not effective.

They tested one of the most common classes of immunotherapy, a PD-L1 checkpoint inhibitor, as well as PULSAR radiation, which in this combination acts as a vaccine against implanted tumors. The team found that splitting two 10-day pulses of radiation was much more effective in combination with the checkpoint medication than the typical daily radiation schedule commonly used in radiation therapy clinics.

In the PULSAR paradigm, patients receive only a few high-dose “pulses”, delivered with sophisticated, image-guided precision, at least a week or even months apart. These “fractional treatments” are a radical departure from conventional long-term daily radiotherapy treatments that last six to nine weeks. They are less toxic and give oncologists time to refine treatment after imaging from the new machines shows the tumor shape, size, position and response to radiation.