A new study from Roswell Park Cancer Institute reporting the findings of the first clinical trial to evaluate the immune effects of high-dose radiation therapy followed by surgery in patients with advanced kidney cancer may also set the stage for combination treatments with immunotherapy. The research, published in Clinical Cancer Research, a journal of the American Association for Cancer Research (AACR), shows that nephrectomy can be effectively paired with stereotactic body radiation therapy (SBRT), and also provides strong evidence that immunotherapy may be an effective third element to incorporate into this combination therapy strategy.
Drs. Thomas Schwaab, Anurag Singh and Jason Muhitch, from left, lead authors on a new study showing that it is possible to combine stereotactic body radiation therapy and surgery as treatment for advanced kidney cancer.
In a pilot clinical study, 14 patients with metastatic renal cell carcinoma (mRCC) were treated with SBRT in a single administration, or fraction, followed four weeks later by cytoreductive nephrectomy, or surgery to remove or reduce the size of their tumors. The team set out to assess the safety and feasibility of this approach and analyze the immunological impact of high-dose radiation. Based on their preliminary studies in the lab, the team monitored patients’ tumors for expression of immunomodulatory molecules and tumor-associated antigens.
They found that nephrectomy paired with high-dose stereotactic radiation is a feasible and well-tolerated treatment approach. They also demonstrated that tumors treated with SBRT evidenced increased expression of the immunomodulatory molecule calreticulin and the tumor-associated antigens CA9, 5T4, NY-ESO-1 and MUC-1. The determination that SBRT appears to trigger immunomodulation in the tumors of patients with metastatic kidney cancer — the first demonstration of this effect in any cancer type — has important implications for cancer immunotherapy.
“Patients with kidney cancer are not normally treated with both high-dose radiation and surgery. This trial afforded us the unique opportunity to evaluate the intratumoral immune landscape in patients following radiation. We were able to show that tumors from patients treated with radiation had higher levels of the immunomodulatory molecule calreticulin, tumor-associated antigens and proliferating T cells compared to archived samples,” notes co-last author Jason Muhitch, PhD, Assistant Professor of Oncology in the Department of Urology at Roswell Park.
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“We saw a significant increase in calreticulin and other molecules that stimulate T cells,” says the paper’s first author, Anurag Singh, MD, Professor of Oncology and Director of Radiation Research with the Department of Radiation Medicine at Roswell Park. “This suggests that it may be possible to improve the effectiveness of immunotherapies by first priming the pump with high-dose radiation.”
“Our findings provide a striking rationale for looking into even broader combination treatment strategies incorporating not just radiation and surgery but also immunotherapy,” says co-last author Thomas Schwaab, MD, PhD, Professor in the Departments of Urology and Immunology at Roswell Park, where he is also Chief of Strategy, Business Development and Outreach. “We will be eager to see if we can improve the effectiveness of therapy for patients with advanced kidney cancer, and those are the next directions we’re pursuing.”
The authors include a contributor from the Department of Radiation Oncology at the Medical University of South Carolina. The study, “A Pilot Study of Stereotactic Body Radiation Therapy Combined with Cytoreductive
Nephrectomy for Metastatic Renal Cell Carcinoma,” is available at clincancerres.aacrjournals.org
Findings from this research will also be presented at the American Society for Radiation Oncology (ASTRO) Annual Meeting in San Diego Sept. 24-27, where Dr. Singh will receive a Basic/Translational Science Abstract Award for his role in this work. The research was supported by grants from the National Center for Advancing Translational Sciences (project no. UL1TR001412), National Cancer Institute (project nos. P30CA016056 and R01CA140622), the Sklarow Foundation, Elsa Kreiner Memorial Fund, Fraternal Order of Eagles and RPCI Friends of Urology.
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