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The alfa and beta of tumours: a review of parameters of the linear-quadratic model, derived from clinical radiotherapy studies

BACKGROUND: Prediction of radiobiological response is a major challenge in radiotherapy. Of several radiobiological models, the linear-quadratic (LQ) model has been best validated by experimental and clinical data. Clinically, the LQ model is mainly used to estimate equivalent radiotherapy schedules...

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Autores principales: van Leeuwen, C. M., Oei, A. L., Crezee, J., Bel, A., Franken, N. A. P., Stalpers, L. J. A., Kok, H. P.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: BioMed Central 2018
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5956964/
https://www.ncbi.nlm.nih.gov/pubmed/29769103
http://dx.doi.org/10.1186/s13014-018-1040-z
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author van Leeuwen, C. M.
Oei, A. L.
Crezee, J.
Bel, A.
Franken, N. A. P.
Stalpers, L. J. A.
Kok, H. P.
author_facet van Leeuwen, C. M.
Oei, A. L.
Crezee, J.
Bel, A.
Franken, N. A. P.
Stalpers, L. J. A.
Kok, H. P.
author_sort van Leeuwen, C. M.
collection PubMed
description BACKGROUND: Prediction of radiobiological response is a major challenge in radiotherapy. Of several radiobiological models, the linear-quadratic (LQ) model has been best validated by experimental and clinical data. Clinically, the LQ model is mainly used to estimate equivalent radiotherapy schedules (e.g. calculate the equivalent dose in 2 Gy fractions, EQD(2)), but increasingly also to predict tumour control probability (TCP) and normal tissue complication probability (NTCP) using logistic models. The selection of accurate LQ parameters α, β and α/β is pivotal for a reliable estimate of radiation response. The aim of this review is to provide an overview of published values for the LQ parameters of human tumours as a guideline for radiation oncologists and radiation researchers to select appropriate radiobiological parameter values for LQ modelling in clinical radiotherapy. METHODS AND MATERIALS: We performed a systematic literature search and found sixty-four clinical studies reporting α, β and α/β for tumours. Tumour site, histology, stage, number of patients, type of LQ model, radiation type, TCP model, clinical endpoint and radiobiological parameter estimates were extracted. Next, we stratified by tumour site and by tumour histology. Study heterogeneity was expressed by the I(2) statistic, i.e. the percentage of variance in reported values not explained by chance. RESULTS: A large heterogeneity in LQ parameters was found within and between studies (I(2) > 75%). For the same tumour site, differences in histology partially explain differences in the LQ parameters: epithelial tumours have higher α/β values than adenocarcinomas. For tumour sites with different histologies, such as in oesophageal cancer, the α/β estimates correlate well with histology. However, many other factors contribute to the study heterogeneity of LQ parameters, e.g. tumour stage, type of LQ model, TCP model and clinical endpoint (i.e. survival, tumour control and biochemical control). CONCLUSIONS: The value of LQ parameters for tumours as published in clinical radiotherapy studies depends on many clinical and methodological factors. Therefore, for clinical use of the LQ model, LQ parameters for tumour should be selected carefully, based on tumour site, histology and the applied LQ model. To account for uncertainties in LQ parameter estimates, exploring a range of values is recommended. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (10.1186/s13014-018-1040-z) contains supplementary material, which is available to authorized users.
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spelling pubmed-59569642018-05-24 The alfa and beta of tumours: a review of parameters of the linear-quadratic model, derived from clinical radiotherapy studies van Leeuwen, C. M. Oei, A. L. Crezee, J. Bel, A. Franken, N. A. P. Stalpers, L. J. A. Kok, H. P. Radiat Oncol Review BACKGROUND: Prediction of radiobiological response is a major challenge in radiotherapy. Of several radiobiological models, the linear-quadratic (LQ) model has been best validated by experimental and clinical data. Clinically, the LQ model is mainly used to estimate equivalent radiotherapy schedules (e.g. calculate the equivalent dose in 2 Gy fractions, EQD(2)), but increasingly also to predict tumour control probability (TCP) and normal tissue complication probability (NTCP) using logistic models. The selection of accurate LQ parameters α, β and α/β is pivotal for a reliable estimate of radiation response. The aim of this review is to provide an overview of published values for the LQ parameters of human tumours as a guideline for radiation oncologists and radiation researchers to select appropriate radiobiological parameter values for LQ modelling in clinical radiotherapy. METHODS AND MATERIALS: We performed a systematic literature search and found sixty-four clinical studies reporting α, β and α/β for tumours. Tumour site, histology, stage, number of patients, type of LQ model, radiation type, TCP model, clinical endpoint and radiobiological parameter estimates were extracted. Next, we stratified by tumour site and by tumour histology. Study heterogeneity was expressed by the I(2) statistic, i.e. the percentage of variance in reported values not explained by chance. RESULTS: A large heterogeneity in LQ parameters was found within and between studies (I(2) > 75%). For the same tumour site, differences in histology partially explain differences in the LQ parameters: epithelial tumours have higher α/β values than adenocarcinomas. For tumour sites with different histologies, such as in oesophageal cancer, the α/β estimates correlate well with histology. However, many other factors contribute to the study heterogeneity of LQ parameters, e.g. tumour stage, type of LQ model, TCP model and clinical endpoint (i.e. survival, tumour control and biochemical control). CONCLUSIONS: The value of LQ parameters for tumours as published in clinical radiotherapy studies depends on many clinical and methodological factors. Therefore, for clinical use of the LQ model, LQ parameters for tumour should be selected carefully, based on tumour site, histology and the applied LQ model. To account for uncertainties in LQ parameter estimates, exploring a range of values is recommended. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (10.1186/s13014-018-1040-z) contains supplementary material, which is available to authorized users. BioMed Central 2018-05-16 /pmc/articles/PMC5956964/ /pubmed/29769103 http://dx.doi.org/10.1186/s13014-018-1040-z Text en © The Author(s). 2018 Open AccessThis article is distributed under the terms of the Creative Commons Attribution 4.0 International License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated.
spellingShingle Review
van Leeuwen, C. M.
Oei, A. L.
Crezee, J.
Bel, A.
Franken, N. A. P.
Stalpers, L. J. A.
Kok, H. P.
The alfa and beta of tumours: a review of parameters of the linear-quadratic model, derived from clinical radiotherapy studies
title The alfa and beta of tumours: a review of parameters of the linear-quadratic model, derived from clinical radiotherapy studies
title_full The alfa and beta of tumours: a review of parameters of the linear-quadratic model, derived from clinical radiotherapy studies
title_fullStr The alfa and beta of tumours: a review of parameters of the linear-quadratic model, derived from clinical radiotherapy studies
title_full_unstemmed The alfa and beta of tumours: a review of parameters of the linear-quadratic model, derived from clinical radiotherapy studies
title_short The alfa and beta of tumours: a review of parameters of the linear-quadratic model, derived from clinical radiotherapy studies
title_sort alfa and beta of tumours: a review of parameters of the linear-quadratic model, derived from clinical radiotherapy studies
topic Review
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5956964/
https://www.ncbi.nlm.nih.gov/pubmed/29769103
http://dx.doi.org/10.1186/s13014-018-1040-z
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