Value of functional in-vivo endpoints in preclinical radiation research

Berit Kummer; Steffen Loeck; Kristin Gurtner; Nadine Hermann; Ala Yaromina; Wolfgang Eicheler; Michael Baumann; Mechthild Krause; Christina Jentsch

doi:10.1016/j.radonc.2021.02.024

Value of functional in-vivo endpoints in preclinical radiation research

Berit Kummer, Steffen Loeck, Kristin Gurtner, Nadine Hermann, Ala Yaromina, Wolfgang Eicheler, Michael Baumann, Mechthild Krause^*, Christina Jentsch

^*Corresponding author for this work

Research output: Contribution to journal › Article › Academic › peer-review

Abstract

Background: Cancer research faces the problem of high rates of clinical failure of new treatment approaches after positive preclinical data. We hypothesize that a major confounding factor to this problem in radiooncology is the choice of the preclinical endpoint. Methods: We present a comprehensive re-evaluation of large-scale preclinical in-vivo data on fractionated irradiation alone or simultaneously with Epidermal Growth Factor Receptor inhibition. Taking the permanent local tumour control assay as a gold standard, we evaluated different tumour volume dependent endpoints that are widely used for preclinical experiments. Results: The analysis showed the highest correlations between volume related and local tumour control endpoints after irradiation alone. For combined treatments, wide inter-tumoural variations were observed with reduced correlation between the endpoints. Evaluation of growth delay per Gray (GD/Gy) based on two or more dose levels showed closest correlation with local tumour control dose 50% (TCD50).

Conclusions: GD/Gy with at least two dose groups correlates with TCD50, but cannot replace the latter as the goldstandard.

(c) 2021 The Author(s). Published by Elsevier B.V. Radiotherapy and Oncology 158 (2021) 155-161 This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/).

Original language	English
Pages (from-to)	155-161
Number of pages	7
Journal	Radiotherapy and Oncology
Volume	158
DOIs	https://doi.org/10.1016/j.radonc.2021.02.024
Publication status	Published - May 2021

Keywords

Neoplasms
Irradiation
Combined modality therapy
Preclinical research
Xenografts
EGFR
SQUAMOUS-CELL CARCINOMA
CANCER STEM-CELLS
LOCAL TUMOR-CONTROL
FRACTIONATED-IRRADIATION
RADIOTHERAPY
INHIBITION
EXPRESSION
LINES
RADIOSENSITIVITY

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10.1016/j.radonc.2021.02.024Licence: CC BY-NC-ND

Cite this

@article{57efa64184a94aafb8c71bf3a5518b69,

title = "Value of functional in-vivo endpoints in preclinical radiation research",

abstract = "Background: Cancer research faces the problem of high rates of clinical failure of new treatment approaches after positive preclinical data. We hypothesize that a major confounding factor to this problem in radiooncology is the choice of the preclinical endpoint. Methods: We present a comprehensive re-evaluation of large-scale preclinical in-vivo data on fractionated irradiation alone or simultaneously with Epidermal Growth Factor Receptor inhibition. Taking the permanent local tumour control assay as a gold standard, we evaluated different tumour volume dependent endpoints that are widely used for preclinical experiments. Results: The analysis showed the highest correlations between volume related and local tumour control endpoints after irradiation alone. For combined treatments, wide inter-tumoural variations were observed with reduced correlation between the endpoints. Evaluation of growth delay per Gray (GD/Gy) based on two or more dose levels showed closest correlation with local tumour control dose 50% (TCD50).Conclusions: GD/Gy with at least two dose groups correlates with TCD50, but cannot replace the latter as the goldstandard.(c) 2021 The Author(s). Published by Elsevier B.V. Radiotherapy and Oncology 158 (2021) 155-161 This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/).",

keywords = "Neoplasms, Irradiation, Combined modality therapy, Preclinical research, Xenografts, EGFR, SQUAMOUS-CELL CARCINOMA, CANCER STEM-CELLS, LOCAL TUMOR-CONTROL, FRACTIONATED-IRRADIATION, RADIOTHERAPY, INHIBITION, EXPRESSION, LINES, RADIOSENSITIVITY",

author = "Berit Kummer and Steffen Loeck and Kristin Gurtner and Nadine Hermann and Ala Yaromina and Wolfgang Eicheler and Michael Baumann and Mechthild Krause and Christina Jentsch",

year = "2021",

month = may,

doi = "10.1016/j.radonc.2021.02.024",

language = "English",

volume = "158",

pages = "155--161",

journal = "Radiotherapy and Oncology",

issn = "0167-8140",

publisher = "Elsevier Ireland Ltd",

}

TY - JOUR

T1 - Value of functional in-vivo endpoints in preclinical radiation research

AU - Kummer, Berit

AU - Loeck, Steffen

AU - Gurtner, Kristin

AU - Hermann, Nadine

AU - Yaromina, Ala

AU - Eicheler, Wolfgang

AU - Baumann, Michael

AU - Krause, Mechthild

AU - Jentsch, Christina

PY - 2021/5

Y1 - 2021/5

N2 - Background: Cancer research faces the problem of high rates of clinical failure of new treatment approaches after positive preclinical data. We hypothesize that a major confounding factor to this problem in radiooncology is the choice of the preclinical endpoint. Methods: We present a comprehensive re-evaluation of large-scale preclinical in-vivo data on fractionated irradiation alone or simultaneously with Epidermal Growth Factor Receptor inhibition. Taking the permanent local tumour control assay as a gold standard, we evaluated different tumour volume dependent endpoints that are widely used for preclinical experiments. Results: The analysis showed the highest correlations between volume related and local tumour control endpoints after irradiation alone. For combined treatments, wide inter-tumoural variations were observed with reduced correlation between the endpoints. Evaluation of growth delay per Gray (GD/Gy) based on two or more dose levels showed closest correlation with local tumour control dose 50% (TCD50).Conclusions: GD/Gy with at least two dose groups correlates with TCD50, but cannot replace the latter as the goldstandard.(c) 2021 The Author(s). Published by Elsevier B.V. Radiotherapy and Oncology 158 (2021) 155-161 This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/).

AB - Background: Cancer research faces the problem of high rates of clinical failure of new treatment approaches after positive preclinical data. We hypothesize that a major confounding factor to this problem in radiooncology is the choice of the preclinical endpoint. Methods: We present a comprehensive re-evaluation of large-scale preclinical in-vivo data on fractionated irradiation alone or simultaneously with Epidermal Growth Factor Receptor inhibition. Taking the permanent local tumour control assay as a gold standard, we evaluated different tumour volume dependent endpoints that are widely used for preclinical experiments. Results: The analysis showed the highest correlations between volume related and local tumour control endpoints after irradiation alone. For combined treatments, wide inter-tumoural variations were observed with reduced correlation between the endpoints. Evaluation of growth delay per Gray (GD/Gy) based on two or more dose levels showed closest correlation with local tumour control dose 50% (TCD50).Conclusions: GD/Gy with at least two dose groups correlates with TCD50, but cannot replace the latter as the goldstandard.(c) 2021 The Author(s). Published by Elsevier B.V. Radiotherapy and Oncology 158 (2021) 155-161 This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/).

KW - Neoplasms

KW - Irradiation

KW - Combined modality therapy

KW - Preclinical research

KW - Xenografts

KW - EGFR

KW - SQUAMOUS-CELL CARCINOMA

KW - CANCER STEM-CELLS

KW - LOCAL TUMOR-CONTROL

KW - FRACTIONATED-IRRADIATION

KW - RADIOTHERAPY

KW - INHIBITION

KW - EXPRESSION

KW - LINES

KW - RADIOSENSITIVITY

U2 - 10.1016/j.radonc.2021.02.024

DO - 10.1016/j.radonc.2021.02.024

M3 - Article

C2 - 33639191

SN - 0167-8140

VL - 158

SP - 155

EP - 161

JO - Radiotherapy and Oncology

JF - Radiotherapy and Oncology

ER -