PMID- 34246048
OWN - NLM
STAT- PubMed-not-MEDLINE
LR  - 20210816
IS  - 1936-5233 (Print)
IS  - 1936-5233 (Electronic)
IS  - 1936-5233 (Linking)
VI  - 14
IP  - 10
DP  - 2021 Oct
TI  - Genomic identification of sarcoma radiosensitivity and the clinical implications 
      for radiation dose personalization.
PG  - 101165
LID - S1936-5233(21)00157-1 [pii]
LID - 10.1016/j.tranon.2021.101165 [doi]
LID - 101165
AB  - BACKGROUND: Soft-tissue sarcomas (STS) are heterogeneous with variable response 
      to radiation therapy (RT). Utilizing the radiosensitivity index (RSI) we 
      estimated the radiobiologic ratio of lethal to sublethal damage (alpha/beta), 
      genomic-adjusted radiation dose(GARD), and in-turn a biological effective 
      radiation dose (BED). METHODS: Two independent cohorts of patients with 
      soft-tissue sarcoma were identified. The first cohort included 217 
      genomically-profiled samples from our institutional prospective tissue collection 
      protocol; RSI was calculated for these samples, which were then used to 
      dichotomize the population as either highly radioresistant (HRR) or 
      conventionally radioresistant (CRR). In addition, RSI was used to calculate alpha/beta 
      ratio and GARD, providing ideal dosing based on sarcoma genomic radiosensitivity. 
      A second cohort comprising 399 non-metastatic-STS patients treated with 
      neoadjuvant RT and surgery was used to validate our findings. RESULTS: Based on 
      the RSI of the sample cohort, 84% would historically be considered 
      radioresistant. We identified a HRR subset that had a significant difference in 
      the RSI, and clinically a lower tumor response to radiation (2.4% vs. 19.4%), 
      5-year locoregional-control (76.5% vs. 90.8%), and lower estimated alpha/beta (3.29 vs. 
      5.98), when compared to CRR sarcoma. Using GARD, the dose required to optimize 
      outcome in the HRR subset is a BED(alpha/beta=)(3.29) of 97 Gy. CONCLUSIONS: We 
      demonstrate that on a genomic scale, that although STS is radioresistant overall, 
      they are heterogeneous in terms of radiosensitivity. We validated this clinically 
      and estimated an alpha/beta ratio and dosing that would optimize outcome, personalizing 
      dose.
CI  - Copyright (c) 2021. Published by Elsevier Inc.
FAU - Yang, George
AU  - Yang G
AD  - H. Lee Moffitt Cancer Center and Research Institute, Department of Radiation 
      Oncology, United States.
FAU - Yuan, Zhigang
AU  - Yuan Z
AD  - H. Lee Moffitt Cancer Center and Research Institute, Department of Radiation 
      Oncology, United States.
FAU - Ahmed, Kamran
AU  - Ahmed K
AD  - H. Lee Moffitt Cancer Center and Research Institute, Department of Radiation 
      Oncology, United States.
FAU - Welsh, Eric A
AU  - Welsh EA
AD  - Biostatistics, United States.
FAU - Fulp, William J
AU  - Fulp WJ
AD  - Fred Hutchinson Research Institute, United States.
FAU - Gonzalez, Ricardo J
AU  - Gonzalez RJ
AD  - Sarcoma, United States.
FAU - Mullinax, John E
AU  - Mullinax JE
AD  - Sarcoma, United States.
FAU - Letson, Douglas
AU  - Letson D
AD  - Sarcoma, United States.
FAU - Bui, Marilyn
AU  - Bui M
AD  - Sarcoma, United States; Pathology, United States.
FAU - Harrison, Louis B
AU  - Harrison LB
AD  - H. Lee Moffitt Cancer Center and Research Institute, Department of Radiation 
      Oncology, United States.
FAU - Scott, Jacob G
AU  - Scott JG
AD  - Cleveland Clinic, Translational Hematology and Oncology Research, United States.
FAU - Torres-Roca, Javier F
AU  - Torres-Roca JF
AD  - H. Lee Moffitt Cancer Center and Research Institute, Department of Radiation 
      Oncology, United States.
FAU - Naghavi, Arash O
AU  - Naghavi AO
AD  - H. Lee Moffitt Cancer Center and Research Institute, Department of Radiation 
      Oncology, United States. Electronic address: Arash.Naghavi@moffitt.org.
LA  - eng
GR  - R21 CA101355/CA/NCI NIH HHS/United States
GR  - R21 CA135620/CA/NCI NIH HHS/United States
PT  - Journal Article
DEP - 20210707
PL  - United States
TA  - Transl Oncol
JT  - Translational oncology
JID - 101472619
PMC - PMC8274330
OTO - NOTNLM
OT  - Genomic-adjusted radiation dose
OT  - Radiation therapy
OT  - Radiosensitivity
COIS- Javier F. Torres-Roca MD reports stock and leadership in Cvergenx, Inc. and 
      royalty and patents on RSI. Jacob G. Scott MD PhD reports a patent in GARD and 
      stock in Cvergenx, Inc. All remaining authors have declared no conflicts of 
      interest.
EDAT- 2021/07/11 06:00
MHDA- 2021/07/11 06:01
PMCR- 2021/07/07
CRDT- 2021/07/10 20:18
PHST- 2021/05/25 00:00 [received]
PHST- 2021/06/14 00:00 [revised]
PHST- 2021/06/22 00:00 [accepted]
PHST- 2021/07/11 06:00 [pubmed]
PHST- 2021/07/11 06:01 [medline]
PHST- 2021/07/10 20:18 [entrez]
PHST- 2021/07/07 00:00 [pmc-release]
AID - S1936-5233(21)00157-1 [pii]
AID - 101165 [pii]
AID - 10.1016/j.tranon.2021.101165 [doi]
PST - ppublish
SO  - Transl Oncol. 2021 Oct;14(10):101165. doi: 10.1016/j.tranon.2021.101165. Epub 
      2021 Jul 7.