PMID- 33549705
OWN - NLM
STAT- MEDLINE
DCOM- 20210924
LR  - 20220716
IS  - 1879-355X (Electronic)
IS  - 0360-3016 (Print)
IS  - 0360-3016 (Linking)
VI  - 110
IP  - 4
DP  - 2021 Jul 15
TI  - Neoadjuvant SABR for Renal Cell Carcinoma Inferior Vena Cava Tumor 
      Thrombus-Safety Lead-in Results of a Phase 2 Trial.
PG  - 1135-1142
LID - S0360-3016(21)00163-2 [pii]
LID - 10.1016/j.ijrobp.2021.01.054 [doi]
AB  - 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.
CI  - Copyright (c) 2021 Elsevier Inc. All rights reserved.
FAU - Margulis, Vitaly
AU  - Margulis V
AD  - 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.
FAU - Freifeld, Yuval
AU  - Freifeld Y
AD  - Department of Urology, University of Texas Southwestern Medical Center, Dallas, 
      Texas; Department of Urology, Lady Davis Carmel Medical Center, Haifa, Israel.
FAU - Pop, Laurentiu M
AU  - Pop LM
AD  - Department of Radiation Oncology, University of Texas Southwestern Medical 
      Center, Dallas, Texas.
FAU - Manna, Subrata
AU  - Manna S
AD  - Department of Radiation Oncology, University of Texas Southwestern Medical 
      Center, Dallas, Texas.
FAU - Kapur, Payal
AU  - Kapur P
AD  - 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.
FAU - Pedrosa, Ivan
AU  - Pedrosa I
AD  - 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.
FAU - Christie, Alana
AU  - Christie A
AD  - Kidney Cancer Program, Simmons Comprehensive Cancer Center, University of Texas 
      Southwestern Medical Center, Dallas, Texas.
FAU - Mohamad, Osama
AU  - Mohamad O
AD  - Department of Radiation Oncology, University of California, San Francisco, 
      California.
FAU - Mannala, Samantha
AU  - Mannala S
AD  - Department of Radiation Oncology, University of Texas Southwestern Medical 
      Center, Dallas, Texas.
FAU - Singla, Nirmish
AU  - Singla N
AD  - Departments of Urology and Oncology, The James Buchanan Brady Urological 
      Institute, The Johns Hopkins University School of Medicine, Baltimore, Maryland.
FAU - Wait, Michael
AU  - Wait M
AD  - 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.
FAU - Bagrodia, Aditya
AU  - Bagrodia A
AD  - 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.
FAU - Woldu, Solomon L
AU  - Woldu SL
AD  - 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.
FAU - Gahan, Jeffrey
AU  - Gahan J
AD  - 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.
FAU - Brugarolas, James
AU  - Brugarolas J
AD  - 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.
FAU - Timmerman, Robert
AU  - Timmerman R
AD  - 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.
FAU - Hannan, Raquibul
AU  - Hannan R
AD  - 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.
LA  - eng
GR  - P50 CA196516/CA/NCI NIH HHS/United States
GR  - R01 CA154475/CA/NCI NIH HHS/United States
GR  - U01 CA207091/CA/NCI NIH HHS/United States
PT  - Clinical Trial, Phase II
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20210205
PL  - United States
TA  - Int J Radiat Oncol Biol Phys
JT  - International journal of radiation oncology, biology, physics
JID - 7603616
SB  - IM
MH  - Aged
MH  - Carcinoma, Renal Cell/complications/*radiotherapy
MH  - Female
MH  - Humans
MH  - Kidney Neoplasms/complications/*radiotherapy
MH  - Male
MH  - Middle Aged
MH  - Neoadjuvant Therapy/*adverse effects
MH  - Radiosurgery/*adverse effects
MH  - Retrospective Studies
MH  - *Safety
MH  - *Vena Cava, Inferior
MH  - Venous Thrombosis/*complications
PMC - PMC8856732
MID - NIHMS1681574
COIS- Conflicts of interest: none.
EDAT- 2021/02/08 06:00
MHDA- 2021/09/25 06:00
PMCR- 2022/07/15
CRDT- 2021/02/07 20:34
PHST- 2020/10/19 00:00 [received]
PHST- 2021/01/12 00:00 [revised]
PHST- 2021/01/30 00:00 [accepted]
PHST- 2021/02/08 06:00 [pubmed]
PHST- 2021/09/25 06:00 [medline]
PHST- 2021/02/07 20:34 [entrez]
PHST- 2022/07/15 00:00 [pmc-release]
AID - S0360-3016(21)00163-2 [pii]
AID - 10.1016/j.ijrobp.2021.01.054 [doi]
PST - ppublish
SO  - Int J Radiat Oncol Biol Phys. 2021 Jul 15;110(4):1135-1142. doi: 
      10.1016/j.ijrobp.2021.01.054. Epub 2021 Feb 5.