Evidence map›Paper›PMID 33395747›Full record

ArticleTranslational oncology2021

TNFR1 and the TNFα axis as a targetable mediator of liver injury from stereotactic body radiation therapy.

Matthew M Cousins, Emily Morris, Christopher Maurino, Theresa P Devasia, David Karnak, Dipankar Ray, Neehar D Parikh, Dawn Owen, Randall K Ten Haken, Matthew J Schipper and 2 more

Open access · goldAbstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Translational oncology, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 11 papers.

0numbers the graph read from it
0cells of the map it votes in
11citing papers in PubMed
1.8field-weighted citation impact, top 14% of its field
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

11 citing papers in PubMed, 17 citations in OpenAlex.

  1. A Phase II Study of Optimized Individualized Adaptive Radiotherapy for Hepatocellular Carcinoma.Clinical cancer research : an official journal of the American Association for Cancer Research · 2023
    Trial
  2. Article
  3. Radiation-Induced Liver Injury: An Overview.Journal of hepatocellular carcinoma · 2025
    Review
  4. Review
  5. Article
  6. Article
  7. Review
  8. Article
  9. Article
  10. Article
  11. Review
4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

12 authors at 1 institution in 1 country.

Matthew M CousinsDepartment of Radiation Oncology, University of Michigan, UH B2C490, 1500 E Medical Center Dr, Ann Arbor, MI 48109-5010, USA.
Emily MorrisDepartment of Radiation Oncology, University of Michigan, UH B2C490, 1500 E Medical Center Dr, Ann Arbor, MI 48109-5010, USA.
Christopher MaurinoDepartment of Radiation Oncology, University of Michigan, UH B2C490, 1500 E Medical Center Dr, Ann Arbor, MI 48109-5010, USA.
Theresa P DevasiaDepartment of Radiation Oncology, University of Michigan, UH B2C490, 1500 E Medical Center Dr, Ann Arbor, MI 48109-5010, USA.
David KarnakDepartment of Radiation Oncology, University of Michigan, UH B2C490, 1500 E Medical Center Dr, Ann Arbor, MI 48109-5010, USA.
Dipankar RayDepartment of Radiation Oncology, University of Michigan, UH B2C490, 1500 E Medical Center Dr, Ann Arbor, MI 48109-5010, USA.
Neehar D ParikhDepartment of Internal Medicine, University of Michigan, 3110 Taubman Center, SPC 5368, 1500 E Medical Center Dr, Ann Arbor, MI 48109-5368, USA.
Dawn OwenDepartment of Radiation Oncology, University of Michigan, UH B2C490, 1500 E Medical Center Dr, Ann Arbor, MI 48109-5010, USA.
Randall K Ten HakenDepartment of Radiation Oncology, University of Michigan, UH B2C490, 1500 E Medical Center Dr, Ann Arbor, MI 48109-5010, USA.
Matthew J SchipperDepartment of Radiation Oncology, University of Michigan, UH B2C490, 1500 E Medical Center Dr, Ann Arbor, MI 48109-5010, USA.
Theodore S LawrenceDepartment of Radiation Oncology, University of Michigan, UH B2C490, 1500 E Medical Center Dr, Ann Arbor, MI 48109-5010, USA.
Kyle C CuneoDepartment of Radiation Oncology, University of Michigan, UH B2C490, 1500 E Medical Center Dr, Ann Arbor, MI 48109-5010, USA. Electronic address: kcuneo@med.umich.edu.
University of Michigan · US

Funding

XenograftP30CA046592 · NCI · UNIVERSITY OF MICHIGAN AT ANN ARBOR · PI THEODORE S LAWRENCE · 1988 to 2026
$178.2M
TREATMENT VERIFICATION AND TREATMENT PLAN REFINEMENTP01CA059827 · NCI · UNIVERSITY OF MICHIGAN AT ANN ARBOR · PI KESSLER, MARC LEWIS, LAWRENCE, THEODORE S · 1993 to 2018
$37.9M
NCI NIH HHS P01 CA059827NCI NIH HHS P30 CA046592
6 · The paper itself

Abstract

introductionRadiation therapy for the management of intrahepatic malignancies can adversely affect liver function. Liver damage has been associated with increased levels of inflammatory cytokines, including tumor necrosis factor alpha (TNFα). We hypothesized that an inflammatory state, characterized by increased soluble TNFα receptor (sTNFR1), mediates sensitivity of the liver to radiation. MATERIALS/

methodsPlasma samples collected during 3 trials of liver radiation for liver malignancies were assayed for sTNFR1 level via enzyme-linked immunosorbent assay (ELISA). Univariate and multivariate logistic regression and longitudinal models were used to characterize associations between liver toxicity (defined as a ≥2-point increase in Child-Pugh [CP] score within 6 months of radiation treatment) and sTNFR1 levels, ALBI score, biocorrected mean liver dose (MLD), age, and baseline laboratory values.

resultsSamples from 78 patients given liver stereotactic body radiation therapy [SBRT] (92%) or hypofractionated radiation were examined. There was a significant association between liver toxicity and sTNFR1 levels, and higher values were associated with increased toxicity over a range of mean liver doses. When ALBI score and biocorrected dose were included in the model with sTNFR1, baseline ALBI score and change in ALBI (ΔALBI) were significantly associated with toxicity, but sTNFR1 was not. Baseline aminotransferase levels also predicted toxicity but not independently of ALBI score.

conclusionsElevated plasma sTNFR1 levels are associated with liver injury after liver radiation, suggesting that elevated inflammatory cytokine activity is a predictor of radiation-induced liver dysfunction. Future studies should determine whether administration of agents that decrease inflammation prior to treatment is warranted.

Indexed as

Hepatocellular cancerInflammationRadiation therapySoluble tumor necrosis factor receptor 1TNFR1TNFα

Identifiers

PMID33395747
PMCPMC7744766
OpenAlexW3111533001

What OpenQuestion holds

Textmetadata
LicenceCC BY-NC-ND
Read underepoch 390

Registered trials

None linked

Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.