Neoadjuvant SABR for Renal Cell Carcinoma Inferior Vena Cava Tumor Thrombus-Safety Lead-in Results of a Phase 2 Trial.

Abstract Purpose To evaluate the feasibility, safety, oncological outcomes and immune effect of neoadjuvant stereotactic radiation (Neo-SAbR) followed by radical nephrectomy and thrombectomy (RN-IVCT). Methods and Materials 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. Results 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. Conclusions 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.