PMID- 34607037
OWN - NLM
STAT- MEDLINE
DCOM- 20220110
LR  - 20220110
IS  - 1879-8519 (Electronic)
IS  - 1879-8500 (Linking)
VI  - 12
IP  - 1
DP  - 2022 Jan-Feb
TI  - Evaluation of Dose Distribution to Organs-at-Risk in a Prospective Phase 1 Trial 
      of Pembrolizumab and Multisite Stereotactic Body Radiation Therapy (SBRT).
PG  - 68-77
LID - S1879-8500(21)00234-4 [pii]
LID - 10.1016/j.prro.2021.09.005 [doi]
AB  - PURPOSE: Our purpose was to characterize the radiation doses to organs-at-risk 
      (OAR) in the phase I trial (NCT02608385) that established safety/efficacy of 
      stereotactic body radiation therapy (SBRT) using NRG-BR001 dose constraints 
      combined with programmed cell death protein 1 blockade for metastatic disease. 
      METHODS AND MATERIALS: Between January 2016 and May 2018, 73 patients with 
      advanced solid tumors were treated with SBRT followed by pembrolizumab. Tumor 
      volumes (gross tumor volume/internal tumor volume) were delineated for each 
      metastasis, with planning target volume contraction to limit OAR dose per 
      protocol (n = 54) or when gross tumor volume/internal tumor volume > 65 cm(3) 
      (n = 19). For 20 OAR, doses were compared with NRG-BR001 constraints. Protocol 
      constraints were considered challenged when the minimum of the highest dose 
      received by >/=6 patients without dose-limiting toxicities (DLTs) (D(max)(6th)) was 
      >/=70% of the protocol constraint. RESULTS: A total of 151 metastases were 
      irradiated including 32 peripheral lung, 23 central lung, 13 
      mediastinal/cervical, 24 liver, 28 abdominal-pelvic, 16 osseous, and 15 spinal 
      metastases. A median of 2 metastases (range, 2-4) with mean volumes of 33.5 cm(3) 
      (range, 0.4-391 cm(3)) were treated using average planning target volumes of 50.7 
      cm(3) (range, 3.2-161 cm(3)). At least 1 dose constraint from NRG-BR001 was 
      exceeded in 38 of 73 (52%) patients. OAR constraints were challenged in 10 serial 
      organs (gastrointestinal, cardio-pulmonary, musculoskeletal, and nervous systems) 
      and 1 parallel OAR (lung). Grade 3 DLTs occurred in 6 patients, including 
      pneumonitis (n = 3), colitis (n = 2), and hepatic failure (n = 1). In 4 patients, 
      the toxicity could be directly attributed to the planned dose to OAR (ie, 
      pneumonitis due to high lung dose or colitis due to high bowel dose). 
      CONCLUSIONS: Multisite SBRT in combination with programmed cell death protein 1 
      blockade was safely tolerated when treating critical central, abdominal-pelvic, 
      and peripheral OAR nearing NRG-BR001 constraints with clinically acceptable 
      toxicity in the corresponding organ systems. The observed relationship between 
      dose and DLTs in 4 of 6 patients indicates that NRG-BR001 dose constraints should 
      be respected in subsequent trials to maintain clinical safety.
CI  - Copyright (c) 2021 American Society for Radiation Oncology. Published by Elsevier 
      Inc. All rights reserved.
FAU - Xiao, Annie
AU  - Xiao A
AD  - The University of Chicago Pritzker School of Medicine, Chicago, Illinois.
FAU - Luke, Jason J
AU  - Luke JJ
AD  - Division of Hematology/Oncology, University of Pittsburgh Medical Center, 
      Pittsburgh, Pennsylvania.
FAU - Partouche, Julien
AU  - Partouche J
AD  - Departments of Radiation & Cellular Oncology.
FAU - Karrison, Ted
AU  - Karrison T
AD  - Public Health Sciences, University of Chicago, Chicago, Illinois.
FAU - Chmura, Steven J
AU  - Chmura SJ
AD  - Departments of Radiation & Cellular Oncology.
FAU - Al-Hallaq, Hania A
AU  - Al-Hallaq HA
AD  - Departments of Radiation & Cellular Oncology. Electronic address: 
      halhallaq@radonc.uchicago.edu.
LA  - eng
PT  - Clinical Trial, Phase I
PT  - Journal Article
DEP - 20211001
PL  - United States
TA  - Pract Radiat Oncol
JT  - Practical radiation oncology
JID - 101558279
RN  - 0 (Antibodies, Monoclonal, Humanized)
RN  - DPT0O3T46P (pembrolizumab)
SB  - IM
MH  - Antibodies, Monoclonal, Humanized
MH  - Humans
MH  - *Lung Neoplasms/surgery
MH  - Organs at Risk
MH  - Prospective Studies
MH  - *Radiosurgery/adverse effects
MH  - Radiotherapy Dosage
MH  - Radiotherapy Planning, Computer-Assisted
EDAT- 2021/10/05 06:00
MHDA- 2022/01/11 06:00
CRDT- 2021/10/04 20:17
PHST- 2021/06/18 00:00 [received]
PHST- 2021/09/02 00:00 [accepted]
PHST- 2021/10/05 06:00 [pubmed]
PHST- 2022/01/11 06:00 [medline]
PHST- 2021/10/04 20:17 [entrez]
AID - S1879-8500(21)00234-4 [pii]
AID - 10.1016/j.prro.2021.09.005 [doi]
PST - ppublish
SO  - Pract Radiat Oncol. 2022 Jan-Feb;12(1):68-77. doi: 10.1016/j.prro.2021.09.005. 
      Epub 2021 Oct 1.