Neoadjuvant stereotactic ablative radiation (Neo-SABR) followed by radical nephrectomy and thrombectomy (RN-IVCT) was safe and showed signs of positive clinical activity in patients with renal cell carcinoma (RCC) and inferior vena cava (IVC) tumor thrombus (TT), according to findings from a phase 1/2 trial published in the International Journal of Radiation Oncology, Biology, Physics.1,2
“There have been no improvements in outcomes for kidney cancer patients with tumor extensions in the past 50 years,” first author Vitaly Margulis, MD, stated in a press release.1 “This new combination of radiation with surgery could offer new hope for these patients,” added Margulis, professor of urology, Department of Urology, University of Texas Southwestern Medical Center.
When kidney cancers infiltrate the renal vein, they can then spread into the IVC, which provides the cancers with open passage to the heart.1 Surgical procedures for these tumors are difficult because they necessitate “not only opening the abdomen but often also the chest and placing patients on bypass circulation,” the researchers explained in a press release.1
“It is a difficult surgery that should be performed only by teams with expertise,” stated Margulis.
Exploring options for more efficient and effective outcomes in this setting, researchers at the Harold C. Simmons Comprehensive Cancer Center’s kidney cancer program, radiation oncology, and urology departments developed a novel approach using SABR, which can deliver high radiation doses to tumor vein extensions.
The preliminary research, which was conducted in 2015, had positive outcomes. “SABR was a success,” lead author of the subsequent phase 1/2 study, Raquibul Hannan, MD, PhD, stated in the press release. “SABR stopped tumor growth and in some cases induced regression,” added Hannan, associate professor of radiation oncology and immunology at Kidney Cancer Program, Simmons Comprehensive Cancer Center, University of Texas Southwestern Medical Center.
The success of this exploratory research led to the phase 1/2 study. The published results are from the safety lead-in portion of the single-arm trial. In the study, patients with RCC and IVC tumor thrombus received Neo-SABR (40 Gy in 5 fractions) to the IVC-TT followed by open RN-IVCT. The primary end point was the absence of grade 4/5 adverse events (AEs) <90 days of RN-IVCT.
The final analysis included 6 patients, none of whom had grade 4/5 AEs. Overall, there were 81 AEs reported within 90 days of surgery. Nearly three-fourths (73%) were grade 1, about one-fourth (23%) were grade 2, and the remaining 4% (n = 3) were grade 3.
All patients were alive at the median follow-up of 24 months. One patient on the trial had developed de novo metastatic disease. There were 3 patients with metastatic disease at diagnosis. According to the researchers, “1 [of these patients] had a complete and another had a partial abscopal response without the concurrent use of systemic therapy.” Further, Neo-SABR led to a reduction in Ki-67 and raised PD-L1 expression in the IVC-TT. “Inflammatory cytokines and autoantibody titers reflecting better host immune status were observed in patients with nonprogressive disease,” the authors wrote.
Looking ahead to potential next steps with the research, Hannan stated “SABR is likely to have applications beyond the presurgical setting.”
1. UT Southwestern investigators report first analysis of pioneering kidney cancer radiation approach in clinical trial. UT Southwestern Medicine. Published online June 24, 2021. Accessed June 30, 2021. https://bit.ly/2TlTklA.
2. Margulis V, Freifeld Y, Pop LM, et al. Neoadjuvant SABR for renal cell carcinoma inferior vena cava tumor thrombus-safety lead-in results of a phase 2 trial. Int J Radiat Oncol Biol Phys. 2021;110(4):1135-1142. doi:10.1016/j.ijrobp.2021.01.054