Evidence map›Paper›PMID 30850209›Full record

ArticleRadiotherapy and oncology : journal of the European Society for Therapeutic Radiology and Oncology2019

Biological effects in normal cells exposed to FLASH dose rate protons.

Manuela Buonanno, Veljko Grilj, David J Brenner

Abstract read
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In one paragraph

Article in Radiotherapy and oncology : journal of the European Society for Therapeutic Radiology and Oncology, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 127 papers, 5 of them syntheses that pooled it.

0numbers the graph read from it
0cells of the map it votes in
127citing papers in PubMed, 5 pooled it
–field-weighted citation impact
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

127 citing papers in PubMed, 5 syntheses or guidelines pooled it.

  1. Pooled it
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  4. The current status of FLASH particle therapy: a systematic review.Physical and engineering sciences in medicine · 2023
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  13. Use of apertures in single-energy pristine Bragg peak FLASH radiotherapy.Journal of applied clinical medical physics · 2026
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67 more citing papers are in PubMed but not listed here.

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

3 authors.

Manuela BuonannoRadiological Research Accelerator Facility (RARAF), New York, United States. Electronic address: mb3591@cumc.columbia.edu.
Veljko GriljRadiological Research Accelerator Facility (RARAF), New York, United States. Electronic address: vg2400@cumc.columbia.edu.
David J BrennerRadiological Research Accelerator Facility (RARAF), New York, United States. Electronic address: djb3@cumc.columbia.edu.

Funding

TR&D 3P41EB002033 · NIBIB · COLUMBIA UNIVERSITY HEALTH SCIENCES · PI BRENNER, DAVID JONATHAN · 2003 to 2018
$17.0M
NIBIB NIH HHS P41 EB002033
6 · The paper itself

Abstract

backgroundRadiotherapy outcomes are limited by toxicity in the healthy tissues surrounding the irradiated tumor. Recent pre-clinical studies have shown that irradiations with electrons or photons delivered at so called FLASH dose rates (i.e. >40 Gy/s) dramatically reduce adverse side effects in the normal tissues while being equally efficient for tumor control as irradiations at conventional dose rates (3-5 cGy/s). In the case of protons however, FLASH effects have not been investigated partially because of the limited availability of facilities that can achieve such high dose rates.

methodsUsing a novel irradiation platform, we measured acute and long-term biological effects in normal human lung fibroblasts (IMR90) exposed to therapeutically relevant doses of 4.5 MeV protons (LET = 10 keV/µm) delivered at dose rates spanning four orders of magnitude. Endpoints included clonogenic cell survival, γH2AX foci formation, induction of premature senescence (β-gal), and the expression of the pro-inflammatory marker TGFβ.

resultsProton dose rate had no influence on the cell survival, but for the highest dose rate used (i.e. 1000 Gy/s) foci formation saturated beyond 10 Gy. In the progeny of irradiated cells, an increase in dose (20 Gy vs. 10 Gy) and dose rate (1000 Gy/s vs. 0.05 Gy/s) positively affected the number of senescence cells and the expression of TGFβ1.

conclusionsIn normal lung fibroblasts proton dose rate had little impact on acute effects, but significantly influenced the expression of long-term biological responses in vitro. Compared to conventional dose rates, protons delivered at FLASH dose rates mitigated such delayed detrimental effects.

Indexed as

ProtonsCell SurvivalElectronsFibroblastsHumansLungNeoplasmsPhotonsProton TherapyRadiation DosageProtonsProton dose rate effectsProton FLASH dose rateProton FLASH irradiationProton FLASH therapyProton radiotherapy

Identifiers

PMID30850209
PMCPMC6728238

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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.