In a VarianVision webinar held in early 2021 and moderated by Ricky Sharma, MD, PhD, Vice President of Clinical Affairs at Varian (pictured above), expert oncologists from the University of California at San Diego Moores Cancer Center discussed how advances in combining immunotherapy with stereotactic radiotherapy may be leading to a paradigm shift in the treatment of metastatic cancers. In 2020, almost half of the anti-cancer agents approved by the FDA involve the immune system1 —a key indicator of how cancer treatment is evolving.
Furthermore, advances in radiosurgery, sometimes referred to as stereotactic body radiotherapy (SBRT), have broadened its applicability beyond the treatment of brain cancer to encompass treatment for many other cancer indications throughout the body. Panelist Andrew Sharabi, MD, radiation oncologist at UC San Diego, indicated that, when treating prostate cancer bone metastases with SBRT, the local control rate is typically upward of 90%, and Phase II clinical trials indicate that treating prostate cancer metastases with SBRT improves survival outcomes when there are only a few sites of metastatic disease (oligometastases).2,3
Immunotherapy—in particular checkpoint blockade drugs, which are monoclonal antibodies infused intravenously—is designed to stimulate a patient’s immune cells to fight the cancer, according to panelist Sandip Patel, MD, medical oncologist at UC San Diego. Dr. Patel has seen improvements in outcomes for lung cancer treatment in particular. The clinical factors currently considered for selecting patients for immunotherapy are largely based on the presence of PDL1 biomarkers and tumor mutation burden and may also depend on the type of tumor.
For patients to be treated with a combination of immunotherapy and SBRT, the clinicians look at a wide range of factors, such as the stability of the metastatic disease, the level of control with systemic therapy, the risk of spread, and whether there are already immune cells infiltrating the tumor (a so-called “hot” tumor).
Patients receiving this type of combination treatment receive care from a multidisciplinary team that includes relevant medical specialties, such as a gastroenterologist, pulmonologist, endocrinologist, and radiologist, who can monitor for toxicities, autoimmune conditions, and endocrinopathies.
Both of the panelists agreed that, together, immunotherapy and SBRT have great promise. Several clinical trials on this topic are underway at UCSD, including trials into the abscopal effect, where radiation treatment not only shrinks the target tumor but induces immune responses to trigger the shrinking of oligometastatic tumors. Multiple groups have shown in preclinical studies that, 7 to 14 days post treatment with SBRT, there’s an influx of immune cells to the treatment site. 4,5
The UC San Diego oncologists are also involved in a phase two study examining the effectiveness of immunotherapy with SBRT in a large population. Moving forward, this research will be vital to understanding how to interpolate all cancer therapies—surgery, radiation, immunotherapy—and how treatment is driven not only by the type of therapy, but by the patient’s characteristics.
1 Mullard A. 2020 FDA Drug Approvals. Nature Reviews Drug Discovery 20, 85-90 (2021). doi
2 Palma DA, Olson, R, Harrow S et al. Stereotactic Ablative Radiotherapy for the Comprehensive Treatment of Oligometastatic Cancers: Long-Term Results of the SABR-COMET Phase II Randomized Trial. Journal of Clinical Oncology 2020;38(25):2830-2838.
3 Phillips R, Shi WY, Deek M, et al. Outcomes of Observation vs Stereotactic Ablative Radiation for Oligometastatic Prostate Cancer: The ORIOLE Phase 2 Randomized Clinical Trial. JAMA Oncol. 2020;6(5):650–659.
4 Dagoglu N, Karaman S, Caglar HB, Oral EN. Abscopal Effect of Radiotherapy in the Immunotherapy Era: Systematic Review of Reported Cases. Cureus. 2019;11(2):e4103. Published 2019 Feb 20. doi:10.7759/cureus.4103
5 Daguenet, E., Louati, S., Wozny, AS. et al. Radiation-induced bystander and abscopal effects: important lessons from preclinical models. Br J Cancer 123, 339–348 (2020).