Vitaly Margulis1, Yuval Freifeld2, Laurentiu M Pop3, Subrata Manna3, Payal Kapur4, Ivan Pedrosa5, Alana Christie6, Osama Mohamad7, Samantha Mannala3, Nirmish Singla8, Michael Wait9, Aditya Bagrodia1, Solomon L Woldu1, Jeffrey Gahan1, James Brugarolas10, Robert Timmerman11, Raquibul Hannan12. 1. Department of Urology, University of Texas Southwestern Medical Center, Dallas, Texas; Kidney Cancer Program, Simmons Comprehensive Cancer Center, University of Texas Southwestern Medical Center, Dallas, Texas. 2. Department of Urology, University of Texas Southwestern Medical Center, Dallas, Texas; Department of Urology, Lady Davis Carmel Medical Center, Haifa, Israel. 3. Department of Radiation Oncology, University of Texas Southwestern Medical Center, Dallas, Texas. 4. Kidney Cancer Program, Simmons Comprehensive Cancer Center, University of Texas Southwestern Medical Center, Dallas, Texas; Department of Pathology, University of Texas Southwestern Medical Center, Dallas, Texas. 5. Department of Urology, University of Texas Southwestern Medical Center, Dallas, Texas; Kidney Cancer Program, Simmons Comprehensive Cancer Center, University of Texas Southwestern Medical Center, Dallas, Texas; Department of Radiology, University of Texas Southwestern Medical Center, Dallas, Texas. 6. Kidney Cancer Program, Simmons Comprehensive Cancer Center, University of Texas Southwestern Medical Center, Dallas, Texas. 7. Department of Radiation Oncology, University of California, San Francisco, California. 8. Departments of Urology and Oncology, The James Buchanan Brady Urological Institute, The Johns Hopkins University School of Medicine, Baltimore, Maryland. 9. Kidney Cancer Program, Simmons Comprehensive Cancer Center, University of Texas Southwestern Medical Center, Dallas, Texas; Department of Cardiovascular and Thoracic Surgery, University of Texas Southwestern Medical Center, Dallas, Texas. 10. Kidney Cancer Program, Simmons Comprehensive Cancer Center, University of Texas Southwestern Medical Center, Dallas, Texas; Division of Hematology/Oncology, Department of Internal Medicine, University of Texas Southwestern Medical Center, Dallas, Texas. 11. Kidney Cancer Program, Simmons Comprehensive Cancer Center, University of Texas Southwestern Medical Center, Dallas, Texas; Department of Radiation Oncology, University of Texas Southwestern Medical Center, Dallas, Texas. 12. Kidney Cancer Program, Simmons Comprehensive Cancer Center, University of Texas Southwestern Medical Center, Dallas, Texas; Department of Radiation Oncology, University of Texas Southwestern Medical Center, Dallas, Texas. Electronic address: raquibul.hannan@utsouthwestern.edu.
Abstract
PURPOSE: To evaluate the feasibility, safety, oncologic 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 1 and 2 trial. Patients with kidney cancer (renal cell carcinoma [RCC]) and inferior vena cava (IVC) tumor thrombus (TT) underwent Neo-SAbR (40 Gy in 5 fractions) to the IVC-TT followed by open RN-IVCT. Absence of grade 4 to 5 adverse events (AEs) within 90 days of RN-IVCT was the primary endpoint. Exploratory studies included pathologic and immunologic alterations attributable to SAbR. RESULTS: Six patients were included in the final analysis. No grade 4 to 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 3 patients with metastasis at diagnosis, 1 had a complete and another had a partial abscopal response without the concurrent use of systemic therapy. 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 nonprogressive disease. CONCLUSIONS: Neo-SAbR followed by RN-IVCT for RCC IVC-TT is feasible and safe. Favorable host immune environment correlated with abscopal response to SABR and RCC relapse-free survival, though direct causal relation to SABR has yet to be established.
PURPOSE: To evaluate the feasibility, safety, oncologic 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 1 and 2 trial. Patients with kidney cancer (renal cell carcinoma [RCC]) and inferior vena cava (IVC) tumor thrombus (TT) underwent Neo-SAbR (40 Gy in 5 fractions) to the IVC-TT followed by open RN-IVCT. Absence of grade 4 to 5 adverse events (AEs) within 90 days of RN-IVCT was the primary endpoint. Exploratory studies included pathologic and immunologic alterations attributable to SAbR. RESULTS: Six patients were included in the final analysis. No grade 4 to 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 3 patients with metastasis at diagnosis, 1 had a complete and another had a partial abscopal response without the concurrent use of systemic therapy. 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 nonprogressive disease. CONCLUSIONS: Neo-SAbR followed by RN-IVCT for RCC IVC-TT is feasible and safe. Favorable host immune environment correlated with abscopal response to SABR and RCC relapse-free survival, though direct causal relation to SABR has yet to be established.
Authors: Liufu Deng; Hua Liang; Byron Burnette; Michael Beckett; Thomas Darga; Ralph R Weichselbaum; Yang-Xin Fu Journal: J Clin Invest Date: 2014-01-02 Impact factor: 14.808
Authors: Ahmed Q Haddad; Christopher G Wood; E Jason Abel; Laura-Maria Krabbe; Oussama M Darwish; R Houston Thompson; Jennifer E Heckman; Megan M Merril; Bishoy A Gayed; Arthur I Sagalowsky; Stephen A Boorjian; Vitaly Margulis; Bradley C Leibovich Journal: J Urol Date: 2014-04-02 Impact factor: 7.450
Authors: Silvia C Formenti; Nils-Petter Rudqvist; Encouse Golden; Benjamin Cooper; Erik Wennerberg; Claire Lhuillier; Claire Vanpouille-Box; Kent Friedman; Lucas Ferrari de Andrade; Kai W Wucherpfennig; Adriana Heguy; Naoko Imai; Sacha Gnjatic; Ryan O Emerson; Xi Kathy Zhou; Tuo Zhang; Abraham Chachoua; Sandra Demaria Journal: Nat Med Date: 2018-11-05 Impact factor: 53.440
Authors: E Jason Abel; R Houston Thompson; Vitaly Margulis; Jennifer E Heckman; Megan M Merril; Oussama M Darwish; Laura-Maria Krabbe; Stephen A Boorjian; Bradley C Leibovich; Christopher G Wood Journal: Eur Urol Date: 2013-11-07 Impact factor: 20.096
Authors: Kirtesh R Patel; Anthony Martinez; John M Stahl; Suzanna J Logan; Adam J Perricone; Matthew J Ferris; Zachary S Buchwald; Mudit Chowdhary; Keith A Delman; David K Monson; Shervin V Oskouei; Nicholas B Reimer; Kenneth Cardona; Mark A Edgar; Karen D Godette Journal: Oncoimmunology Date: 2018-03-15 Impact factor: 8.110