In an ongoing effort to develop cancer therapies that provide a better quality of life, Fred Hutchinson Cancer Center physicians are spearheading the next generation of cancer treatments that transform radiation therapy into precision medicine. This innovative strategy uses different types of radiation, such as X-rays, protons and neutrons, to trigger an immune response and enhance the effectiveness of immunotherapy.
By creating a vaccine effect, precision radiation oncology can provide long-term protection against a recurrence. It can also destroy cancer cells elsewhere in the body.
Precision oncology has traditionally included targeted therapy and immunotherapy. These treatments target the specific molecular characteristics of a person’s cancer or harness the power of a person’s own immune system against cancer.
“In the past, we treated cancer with the maximum dose we could safely deliver,” says Ramesh Rengan, MD, PhD, Professor and Chair of Radiation Oncology, Fred Hutch and UW Medicine. “The new frontier of cancer care is precision medicine — which now includes radiation oncology. Using this approach, we can deliver the right treatment to destroy cancer while minimizing harm to the patient.”
Radiation Therapy, Immunotherapy and the Abscopal Response
The immune system plays an important role in recognizing and ridding the body of cancer. “We think that about 10% to 30% of the time, the immune system identifies cancer as foreign and destroys it,” says Dr. Rengan.
Some cancers are visible to the immune system but shut down the immune response by applying a brake. Immunotherapy can be an effective treatment in this case because it releases the brake and allows the immune system to do its job.
Immunotherapy, however, is ineffective against other cancers that the immune system doesn’t recognize as foreign. When delivered in a specific way, radiation causes immunogenic death and makes cancer cells visible to the immune system and vulnerable to treatment.
Once the immune system can see the cancer, immunotherapy can release the brakes and accelerate the immune response. What’s more, this response is:
- Abscopal: An abscopal effect occurs when treatment of a tumor in one area leads to shrinkage of tumors elsewhere in the body.
- Long lasting: The immune system remembers the cancer and can quickly mount a response if it returns.
“In this way, radiation therapy and immunotherapy are synergistic partners and a powerful weapon in the precision drug arsenal,” says Dr. Rengan.
Determining the Right Type and Dose of Radiation
When finding the right type of radiation to deliver, Dr. Rengan has access to a wide range of tools at Fred Hutch, including:
- Neutron therapy
- Proton therapy
- Stereotactic body radiation therapy (SBRT)
Neutrons are particularly useful in treating poorly oxygenated tumors, such as some head and neck cancers. “There are other institutions doing this work, but we’re the only center in North America that offers neutron therapy,” he says.
Fred Hutch radiation oncology faculty recently published two case reports describing the use of neutron therapy in patients with Merkel cell carcinoma (MCC) who had progressed through multiple lines of immunotherapy. After treating the tumors with neutrons and continued immunotherapy, the cancer disappeared inside and outside the treatment field.
The radiation dose rate also affects its biological impact, so Dr. Rengan’s team is currently investigating the use of ultra-high dose rate (FLASH) radiation. FLASH radiation delivers the radiation treatment approximately 1000 times faster than regular radiation therapy, and preclinical results show this leads to less damage in healthy tissues. After testing FLASH radiation at the Fred Hutch Proton Center, physicians confirmed findings from other scientists.
Bringing Precision Radiation Oncology from the Bench to the Bedside
At the forefront of medicine, Fred Hutch is known for developing new technologies and treatments and improving standards of care. This bench-to-bedside transformation culminates in a robust portfolio of clinical trials, including those involving precision radiation oncology.
FLASH radiation is on the cusp of being ready for clinical trials, says Dr. Rengan: "Our goal is to open a clinical trial in 2024. We have many other trials that will be opening soon.”
Two clinical trials currently enrolling patients include:
- Phase 3 study of durvalumab with SBRT vs. placebo with SBRT in patients with unresected stage I/II, lymph node-negative non-small cell lung cancer (ClinicalTrials.gov Identifier: NCT03833154)
- Phase 2 study of hypofractionated radiation maintenance therapy after induction with platinum-based chemotherapy plus durvalumab in patients with stage IV small cell lung cancer (ClinicalTrials.gov Identifier: NCT05161533)
Partnering with Fred Hutch Radiation Oncologists
As part of a large academic department, Fred Hutch radiation oncologists are disease site specialists who participate in dedicated tumor boards and multidisciplinary clinics. They coordinate closely with medical oncologists, surgeons and other specialists to evaluate patients and determine the best treatment approach.
At Fred Hutch, radiation oncologists seek to complement the care patients receive from their community oncologists. By working together, patients can often receive some treatments close to home.
“If community oncologists reach a limit of what they're able to provide, we want to be a supplemental resource,” says Dr. Rengan. “If they think a patient can benefit from a type of radiation therapy we have available, we’re happy to partner with them to explore that option.”
To consult with Dr. Rengan or another radiation oncologist, call 1.800.4UW.DOCS.
For Patient Referrals, Contact:
Phone: 206.606.1024
Fax: 206.606.1025
