Volumetric Regression in Brain Metastases After Stereotactic Radiotherapy: Time Course, Predictors, and Significance
BackgroundThere is insufficient understanding of the natural course of volumetric regression in brain metastases after stereotactic radiotherapy (SRT) and optimal volumetric criteria for the assessment of response and progression in radiotherapy clinical trials for brain metastases are currently unk...
Main Authors: | , , , , , , , , , , , |
---|---|
Format: | Article |
Language: | English |
Published: |
Frontiers Media S.A.
2021-01-01
|
Series: | Frontiers in Oncology |
Subjects: | |
Online Access: | https://www.frontiersin.org/articles/10.3389/fonc.2020.590980/full |
id |
doaj-4a0c3a57092e40e8943e8811dc45cbd0 |
---|---|
record_format |
Article |
collection |
DOAJ |
language |
English |
format |
Article |
sources |
DOAJ |
author |
Dominik Oft Manuel Alexander Schmidt Thomas Weissmann Johannes Roesch Veit Mengling Siti Masitho Christoph Bert Sebastian Lettmaier Benjamin Frey Luitpold Valentin Distel Rainer Fietkau Florian Putz |
spellingShingle |
Dominik Oft Manuel Alexander Schmidt Thomas Weissmann Johannes Roesch Veit Mengling Siti Masitho Christoph Bert Sebastian Lettmaier Benjamin Frey Luitpold Valentin Distel Rainer Fietkau Florian Putz Volumetric Regression in Brain Metastases After Stereotactic Radiotherapy: Time Course, Predictors, and Significance Frontiers in Oncology brain metastases stereotactic radiotherapy stereotactic radiosurgery volumetric analysis MRI longitudinal analysis |
author_facet |
Dominik Oft Manuel Alexander Schmidt Thomas Weissmann Johannes Roesch Veit Mengling Siti Masitho Christoph Bert Sebastian Lettmaier Benjamin Frey Luitpold Valentin Distel Rainer Fietkau Florian Putz |
author_sort |
Dominik Oft |
title |
Volumetric Regression in Brain Metastases After Stereotactic Radiotherapy: Time Course, Predictors, and Significance |
title_short |
Volumetric Regression in Brain Metastases After Stereotactic Radiotherapy: Time Course, Predictors, and Significance |
title_full |
Volumetric Regression in Brain Metastases After Stereotactic Radiotherapy: Time Course, Predictors, and Significance |
title_fullStr |
Volumetric Regression in Brain Metastases After Stereotactic Radiotherapy: Time Course, Predictors, and Significance |
title_full_unstemmed |
Volumetric Regression in Brain Metastases After Stereotactic Radiotherapy: Time Course, Predictors, and Significance |
title_sort |
volumetric regression in brain metastases after stereotactic radiotherapy: time course, predictors, and significance |
publisher |
Frontiers Media S.A. |
series |
Frontiers in Oncology |
issn |
2234-943X |
publishDate |
2021-01-01 |
description |
BackgroundThere is insufficient understanding of the natural course of volumetric regression in brain metastases after stereotactic radiotherapy (SRT) and optimal volumetric criteria for the assessment of response and progression in radiotherapy clinical trials for brain metastases are currently unknown.MethodsVolumetric analysis via whole-tumor segmentation in contrast-enhanced 1 mm³-isotropic T1-Mprage sequences before SRT and during follow-up. A total of 3,145 MRI studies of 419 brain metastases from 189 patients were segmented. Progression was defined using a volumetric extension of the RANO-BM criteria. A subset of 205 metastases without progression/radionecrosis during their entire follow-up of at least 3 months was used to study the natural course of volumetric regression after SRT. Predictors for volumetric regression were investigated. A second subset of 179 metastases was used to investigate the prognostic significance of volumetric response at 3 months (defined as ≥20% and ≥65% volume reduction, respectively) for subsequent local control.ResultsMedian relative metastasis volume post-SRT was 66.9% at 6 weeks, 38.6% at 3 months, 17.7% at 6 months, 2.7% at 12 months and 0.0% at 24 months. Radioresistant histology and FSRT vs. SRS were associated with reduced tumor regression for all time points. In multivariate linear regression, radiosensitive histology (p=0.006) was the only significant predictor for metastasis regression at 3 months. Volumetric regression ≥20% at 3 months post-SRT was the only significant prognostic factor for subsequent control in multivariate analysis (HR 0.63, p=0.023), whereas regression ≥65% was no significant predictor.ConclusionsVolumetric regression post-SRT does not occur at a constant rate but is most pronounced in the first 6 weeks to 3 months. Despite decreasing over time, volumetric regression continues beyond 6 months post-radiotherapy and may lead to complete resolution of controlled lesions by 24 months. Radioresistant histology is associated with slower regression. We found that a cutoff of ≥20% regression for the volumetric definition of response at 3 months post-SRT was predictive for subsequent control whereas the currently proposed definition of ≥65% was not. These results have implications for standardized volumetric criteria in future radiotherapy trials for brain metastases. |
topic |
brain metastases stereotactic radiotherapy stereotactic radiosurgery volumetric analysis MRI longitudinal analysis |
url |
https://www.frontiersin.org/articles/10.3389/fonc.2020.590980/full |
work_keys_str_mv |
AT dominikoft volumetricregressioninbrainmetastasesafterstereotacticradiotherapytimecoursepredictorsandsignificance AT manuelalexanderschmidt volumetricregressioninbrainmetastasesafterstereotacticradiotherapytimecoursepredictorsandsignificance AT thomasweissmann volumetricregressioninbrainmetastasesafterstereotacticradiotherapytimecoursepredictorsandsignificance AT johannesroesch volumetricregressioninbrainmetastasesafterstereotacticradiotherapytimecoursepredictorsandsignificance AT veitmengling volumetricregressioninbrainmetastasesafterstereotacticradiotherapytimecoursepredictorsandsignificance AT sitimasitho volumetricregressioninbrainmetastasesafterstereotacticradiotherapytimecoursepredictorsandsignificance AT christophbert volumetricregressioninbrainmetastasesafterstereotacticradiotherapytimecoursepredictorsandsignificance AT sebastianlettmaier volumetricregressioninbrainmetastasesafterstereotacticradiotherapytimecoursepredictorsandsignificance AT benjaminfrey volumetricregressioninbrainmetastasesafterstereotacticradiotherapytimecoursepredictorsandsignificance AT luitpoldvalentindistel volumetricregressioninbrainmetastasesafterstereotacticradiotherapytimecoursepredictorsandsignificance AT rainerfietkau volumetricregressioninbrainmetastasesafterstereotacticradiotherapytimecoursepredictorsandsignificance AT florianputz volumetricregressioninbrainmetastasesafterstereotacticradiotherapytimecoursepredictorsandsignificance |
_version_ |
1724344638063509504 |
spelling |
doaj-4a0c3a57092e40e8943e8811dc45cbd02021-01-08T06:56:34ZengFrontiers Media S.A.Frontiers in Oncology2234-943X2021-01-011010.3389/fonc.2020.590980590980Volumetric Regression in Brain Metastases After Stereotactic Radiotherapy: Time Course, Predictors, and SignificanceDominik Oft0Manuel Alexander Schmidt1Thomas Weissmann2Johannes Roesch3Veit Mengling4Siti Masitho5Christoph Bert6Sebastian Lettmaier7Benjamin Frey8Luitpold Valentin Distel9Rainer Fietkau10Florian Putz11Department of Radiation Oncology, Universitätsklinikum Erlangen, Friedrich-Alexander-Universität Erlangen-Nürnberg, Erlangen, GermanyDepartment of Neuroradiology, Universitätsklinikum Erlangen, Friedrich-Alexander-Universität Erlangen-Nürnberg, Erlangen, GermanyDepartment of Radiation Oncology, Universitätsklinikum Erlangen, Friedrich-Alexander-Universität Erlangen-Nürnberg, Erlangen, GermanyDepartment of Radiation Oncology, Universitätsklinikum Erlangen, Friedrich-Alexander-Universität Erlangen-Nürnberg, Erlangen, GermanyDepartment of Radiation Oncology, Universitätsklinikum Erlangen, Friedrich-Alexander-Universität Erlangen-Nürnberg, Erlangen, GermanyDepartment of Radiation Oncology, Universitätsklinikum Erlangen, Friedrich-Alexander-Universität Erlangen-Nürnberg, Erlangen, GermanyDepartment of Radiation Oncology, Universitätsklinikum Erlangen, Friedrich-Alexander-Universität Erlangen-Nürnberg, Erlangen, GermanyDepartment of Radiation Oncology, Universitätsklinikum Erlangen, Friedrich-Alexander-Universität Erlangen-Nürnberg, Erlangen, GermanyDepartment of Radiation Oncology, Universitätsklinikum Erlangen, Friedrich-Alexander-Universität Erlangen-Nürnberg, Erlangen, GermanyDepartment of Radiation Oncology, Universitätsklinikum Erlangen, Friedrich-Alexander-Universität Erlangen-Nürnberg, Erlangen, GermanyDepartment of Radiation Oncology, Universitätsklinikum Erlangen, Friedrich-Alexander-Universität Erlangen-Nürnberg, Erlangen, GermanyDepartment of Radiation Oncology, Universitätsklinikum Erlangen, Friedrich-Alexander-Universität Erlangen-Nürnberg, Erlangen, GermanyBackgroundThere is insufficient understanding of the natural course of volumetric regression in brain metastases after stereotactic radiotherapy (SRT) and optimal volumetric criteria for the assessment of response and progression in radiotherapy clinical trials for brain metastases are currently unknown.MethodsVolumetric analysis via whole-tumor segmentation in contrast-enhanced 1 mm³-isotropic T1-Mprage sequences before SRT and during follow-up. A total of 3,145 MRI studies of 419 brain metastases from 189 patients were segmented. Progression was defined using a volumetric extension of the RANO-BM criteria. A subset of 205 metastases without progression/radionecrosis during their entire follow-up of at least 3 months was used to study the natural course of volumetric regression after SRT. Predictors for volumetric regression were investigated. A second subset of 179 metastases was used to investigate the prognostic significance of volumetric response at 3 months (defined as ≥20% and ≥65% volume reduction, respectively) for subsequent local control.ResultsMedian relative metastasis volume post-SRT was 66.9% at 6 weeks, 38.6% at 3 months, 17.7% at 6 months, 2.7% at 12 months and 0.0% at 24 months. Radioresistant histology and FSRT vs. SRS were associated with reduced tumor regression for all time points. In multivariate linear regression, radiosensitive histology (p=0.006) was the only significant predictor for metastasis regression at 3 months. Volumetric regression ≥20% at 3 months post-SRT was the only significant prognostic factor for subsequent control in multivariate analysis (HR 0.63, p=0.023), whereas regression ≥65% was no significant predictor.ConclusionsVolumetric regression post-SRT does not occur at a constant rate but is most pronounced in the first 6 weeks to 3 months. Despite decreasing over time, volumetric regression continues beyond 6 months post-radiotherapy and may lead to complete resolution of controlled lesions by 24 months. Radioresistant histology is associated with slower regression. We found that a cutoff of ≥20% regression for the volumetric definition of response at 3 months post-SRT was predictive for subsequent control whereas the currently proposed definition of ≥65% was not. These results have implications for standardized volumetric criteria in future radiotherapy trials for brain metastases.https://www.frontiersin.org/articles/10.3389/fonc.2020.590980/fullbrain metastasesstereotactic radiotherapystereotactic radiosurgeryvolumetric analysisMRIlongitudinal analysis |