To evaluate the feasibility, safety, oncological outcomes and immune effect of neoadjuvant stereotactic radiation (Neo-SAbR) followed by radical nephrectomy and thrombectomy (RN-IVCT).
These are results from the safety lead-in portion of a single arm phase I-II trial. Patients with kidney cancer (RCC) and IVC tumor thrombus (IVC-TT) underwent Neo-SAbR (40 Gy in 5 fractions) of the IVC-TT followed by open RN-IVCT. Absence of grade 4-5 adverse events (AEs) within 90 days of RN-IVCT was the primary endpoint. Exploratory studies included pathological and immunological alterations attributable to SAbR.
6 patients were included in the final analysis. No grade 4-5 AEs were observed. A total of 81 AEs were reported within 90 days of surgery: 73% (59/81) were grade 1, 23% (19/81) were grade 2, and 4%(3/81) were grade 3. After a median follow-up of 24 months, all patients are alive. One patient developed de novo metastatic disease. Of the 3 patients with metastasis at diagnosis, 1 had a complete and another partial abscopal response without the concurrent use of systemic therpay. Neo-SAbR led to decreased Ki-67 and increased PD-L1 expression in the IVC-TT. Inflammatory cytokines and autoantibody titers reflecting better host immune status were observed in patients with non-progressive disease.
Neo-SAbR followed by RN-IVCT for RCC IVC-TT is feasible and safe. Favorable host immune environment may predict SAbR's abscopal response and RCC relapse-free survival although direct causal relation to SAbR is yet to be established.
International journal of radiation oncology, biology, physics. 2021 Feb 04 [Epub ahead of print]
Vitaly Margulis, Yuval Freifeld, Laurentiu M Pop, Subrata Manna, Payal Kapur, Ivan Pedrosa, Alana Christie, Osama Mohamad, Samantha Mannala, Nirmish Singla, Michael Wait, Aditya Bagrodia, Solomon L Woldu, Jeffrey Gahan, James Brugarolas, Robert Timmerman, Raquibul Hannan
Department of Urology, University of Texas Southwestern Medical Center, Dallas, TX 75390, USA;; Kidney Cancer Program, Simmons Comprehensive Cancer Center, University of Texas Southwestern Medical Center, Dallas, TX 75390, USA., Department of Urology, University of Texas Southwestern Medical Center, Dallas, TX 75390, USA;; Department of Urology, Lady Davis Carmel Medical Center, Haifa, 3436212, Israel., Department of Radiation Oncology, University of Texas Southwestern Medical Center, Dallas, TX 75390, USA., Kidney Cancer Program, Simmons Comprehensive Cancer Center, University of Texas Southwestern Medical Center, Dallas, TX 75390, USA;; Department of Pathology, University of Texas Southwestern Medical Center, Dallas, TX 75390, USA., Department of Urology, University of Texas Southwestern Medical Center, Dallas, TX 75390, USA;; Kidney Cancer Program, Simmons Comprehensive Cancer Center, University of Texas Southwestern Medical Center, Dallas, TX 75390, USA;; Department of Radiology, University of Texas Southwestern Medical Center, Dallas, TX 75390, USA., Kidney Cancer Program, Simmons Comprehensive Cancer Center, University of Texas Southwestern Medical Center, Dallas, TX 75390, USA., Department of Radiation Oncology, University of California, San Francisco, CA, 94115, USA., Departments of Urology and Oncology, The James Buchanan Brady Urological Institute, The Johns Hopkins University School of Medicine, Baltimore, MD, 21205, USA., Kidney Cancer Program, Simmons Comprehensive Cancer Center, University of Texas Southwestern Medical Center, Dallas, TX 75390, USA;; Department of Cardiovascular and Thoracic Surgery, University of Texas Southwestern Medical Center, Dallas, TX 75390, USA., Kidney Cancer Program, Simmons Comprehensive Cancer Center, University of Texas Southwestern Medical Center, Dallas, TX 75390, USA;; Division of Hematology/Oncology, Department of Internal Medicine, University of Texas Southwestern Medical Center, Dallas, TX 75390, USA., Kidney Cancer Program, Simmons Comprehensive Cancer Center, University of Texas Southwestern Medical Center, Dallas, TX 75390, USA;; Department of Radiation Oncology, University of Texas Southwestern Medical Center, Dallas, TX 75390, USA., Kidney Cancer Program, Simmons Comprehensive Cancer Center, University of Texas Southwestern Medical Center, Dallas, TX 75390, USA;; Department of Radiation Oncology, University of Texas Southwestern Medical Center, Dallas, TX 75390, USA. Electronic address: .