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Cardiac-sparing radiotherapy for locally advanced non-small cell lung cancer

BACKGROUND: We have carried out a study to determine the scope for reducing heart doses in photon beam radiotherapy of locally advanced non-small cell lung cancer (LA-NSCLC). MATERIALS AND METHODS: Baseline VMAT plans were created for 20 LA-NSCLC patients following the IDEAL-CRT isotoxic protocol, a...

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Autores principales: Turtle, Louise, Bhalla, Neeraj, Willett, Andrew, Biggar, Robert, Leadbetter, Jonathan, Georgiou, Georgios, Wilson, James M., Vivekanandan, Sindu, Hawkins, Maria A., Brada, Michael, Fenwick, John D.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: BioMed Central 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8176693/
https://www.ncbi.nlm.nih.gov/pubmed/34082782
http://dx.doi.org/10.1186/s13014-021-01824-3
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author Turtle, Louise
Bhalla, Neeraj
Willett, Andrew
Biggar, Robert
Leadbetter, Jonathan
Georgiou, Georgios
Wilson, James M.
Vivekanandan, Sindu
Hawkins, Maria A.
Brada, Michael
Fenwick, John D.
author_facet Turtle, Louise
Bhalla, Neeraj
Willett, Andrew
Biggar, Robert
Leadbetter, Jonathan
Georgiou, Georgios
Wilson, James M.
Vivekanandan, Sindu
Hawkins, Maria A.
Brada, Michael
Fenwick, John D.
author_sort Turtle, Louise
collection PubMed
description BACKGROUND: We have carried out a study to determine the scope for reducing heart doses in photon beam radiotherapy of locally advanced non-small cell lung cancer (LA-NSCLC). MATERIALS AND METHODS: Baseline VMAT plans were created for 20 LA-NSCLC patients following the IDEAL-CRT isotoxic protocol, and were re-optimized after adding an objective limiting heart mean dose (MD(Heart)). Reductions in MD(Heart) achievable without breaching limits on target coverage or normal tissue irradiation were determined. The process was repeated for objectives limiting the heart volume receiving ≥ 50 Gy (V(Heart-50-Gy)) and left atrial wall volume receiving ≥ 63 Gy (V(LAwall-63-Gy)). RESULTS: Following re-optimization, mean MD(Heart), V(Heart-50-Gy) and V(LAwall-63-Gy) values fell by 4.8 Gy and 2.2% and 2.4% absolute respectively. On the basis of associations observed between survival and cardiac irradiation in an independent dataset, the purposefully-achieved reduction in MD(Heart) is expected to lead to the largest improvement in overall survival. It also led to useful knock-on reductions in many measures of cardiac irradiation including V(Heart-50-Gy) and V(LAwall-63-Gy), providing some insurance against survival being more strongly related to these measures than to MD(Heart). The predicted hazard ratio (HR) for death corresponding to the purposefully-achieved mean reduction in MD(Heart) was 0.806, according to which a randomized trial would require 1140 patients to test improved survival with 0.05 significance and 80% power. In patients whose baseline MD(Heart) values exceeded the median value in a published series, the average MD(Heart) reduction was particularly large, 8.8 Gy. The corresponding predicted HR is potentially testable in trials recruiting 359 patients enriched for greater MD(Heart) values. CONCLUSIONS: Cardiac irradiation in RT of LA-NSCLC can be reduced substantially. Of the measures studied, reduction of MD(Heart) led to the greatest predicted increase in survival, and to useful knock-on reductions in other cardiac irradiation measures reported to be associated with survival. Potential improvements in survival can be trialled more efficiently in a population enriched for patients with greater baseline MD(Heart) levels, for whom larger reductions in heart doses can be achieved. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1186/s13014-021-01824-3.
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spelling pubmed-81766932021-06-04 Cardiac-sparing radiotherapy for locally advanced non-small cell lung cancer Turtle, Louise Bhalla, Neeraj Willett, Andrew Biggar, Robert Leadbetter, Jonathan Georgiou, Georgios Wilson, James M. Vivekanandan, Sindu Hawkins, Maria A. Brada, Michael Fenwick, John D. Radiat Oncol Research BACKGROUND: We have carried out a study to determine the scope for reducing heart doses in photon beam radiotherapy of locally advanced non-small cell lung cancer (LA-NSCLC). MATERIALS AND METHODS: Baseline VMAT plans were created for 20 LA-NSCLC patients following the IDEAL-CRT isotoxic protocol, and were re-optimized after adding an objective limiting heart mean dose (MD(Heart)). Reductions in MD(Heart) achievable without breaching limits on target coverage or normal tissue irradiation were determined. The process was repeated for objectives limiting the heart volume receiving ≥ 50 Gy (V(Heart-50-Gy)) and left atrial wall volume receiving ≥ 63 Gy (V(LAwall-63-Gy)). RESULTS: Following re-optimization, mean MD(Heart), V(Heart-50-Gy) and V(LAwall-63-Gy) values fell by 4.8 Gy and 2.2% and 2.4% absolute respectively. On the basis of associations observed between survival and cardiac irradiation in an independent dataset, the purposefully-achieved reduction in MD(Heart) is expected to lead to the largest improvement in overall survival. It also led to useful knock-on reductions in many measures of cardiac irradiation including V(Heart-50-Gy) and V(LAwall-63-Gy), providing some insurance against survival being more strongly related to these measures than to MD(Heart). The predicted hazard ratio (HR) for death corresponding to the purposefully-achieved mean reduction in MD(Heart) was 0.806, according to which a randomized trial would require 1140 patients to test improved survival with 0.05 significance and 80% power. In patients whose baseline MD(Heart) values exceeded the median value in a published series, the average MD(Heart) reduction was particularly large, 8.8 Gy. The corresponding predicted HR is potentially testable in trials recruiting 359 patients enriched for greater MD(Heart) values. CONCLUSIONS: Cardiac irradiation in RT of LA-NSCLC can be reduced substantially. Of the measures studied, reduction of MD(Heart) led to the greatest predicted increase in survival, and to useful knock-on reductions in other cardiac irradiation measures reported to be associated with survival. Potential improvements in survival can be trialled more efficiently in a population enriched for patients with greater baseline MD(Heart) levels, for whom larger reductions in heart doses can be achieved. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1186/s13014-021-01824-3. BioMed Central 2021-06-03 /pmc/articles/PMC8176693/ /pubmed/34082782 http://dx.doi.org/10.1186/s13014-021-01824-3 Text en © The Author(s) 2021 https://creativecommons.org/licenses/by/4.0/Open AccessThis article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/ (https://creativecommons.org/licenses/by/4.0/) . The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/ (https://creativecommons.org/publicdomain/zero/1.0/) ) applies to the data made available in this article, unless otherwise stated in a credit line to the data.
spellingShingle Research
Turtle, Louise
Bhalla, Neeraj
Willett, Andrew
Biggar, Robert
Leadbetter, Jonathan
Georgiou, Georgios
Wilson, James M.
Vivekanandan, Sindu
Hawkins, Maria A.
Brada, Michael
Fenwick, John D.
Cardiac-sparing radiotherapy for locally advanced non-small cell lung cancer
title Cardiac-sparing radiotherapy for locally advanced non-small cell lung cancer
title_full Cardiac-sparing radiotherapy for locally advanced non-small cell lung cancer
title_fullStr Cardiac-sparing radiotherapy for locally advanced non-small cell lung cancer
title_full_unstemmed Cardiac-sparing radiotherapy for locally advanced non-small cell lung cancer
title_short Cardiac-sparing radiotherapy for locally advanced non-small cell lung cancer
title_sort cardiac-sparing radiotherapy for locally advanced non-small cell lung cancer
topic Research
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8176693/
https://www.ncbi.nlm.nih.gov/pubmed/34082782
http://dx.doi.org/10.1186/s13014-021-01824-3
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