Influence of Urethra Sparing on Tumor Control Probability and Normal Tissue Complication Probability in Focal Dose Escalated Hypofractionated Radiotherapy: A Planning Study Based on Histopathology Reference
PurposeMultiparametric magnetic resonance tomography (mpMRI) and prostate specific membrane antigen positron emission tomography (PSMA-PET/CT) are used to guide focal radiotherapy (RT) dose escalation concepts. Besides improvements of treatment effectiveness, maintenance of a good quality of life is...
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Frontiers Media S.A.
2021-05-01
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Online Access: | https://www.frontiersin.org/articles/10.3389/fonc.2021.652678/full |
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Article |
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DOAJ |
language |
English |
format |
Article |
sources |
DOAJ |
author |
Simon K. B. Spohn Simon K. B. Spohn Simon K. B. Spohn Ilias Sachpazidis Rolf Wiehle Benedikt Thomann August Sigle Peter Bronsert Juri Ruf Matthias Benndorf Nils H. Nicolay Nils H. Nicolay Tanja Sprave Tanja Sprave Anca L. Grosu Anca L. Grosu Dimos Baltas Dimos Baltas Constantinos Zamboglou Constantinos Zamboglou Constantinos Zamboglou |
spellingShingle |
Simon K. B. Spohn Simon K. B. Spohn Simon K. B. Spohn Ilias Sachpazidis Rolf Wiehle Benedikt Thomann August Sigle Peter Bronsert Juri Ruf Matthias Benndorf Nils H. Nicolay Nils H. Nicolay Tanja Sprave Tanja Sprave Anca L. Grosu Anca L. Grosu Dimos Baltas Dimos Baltas Constantinos Zamboglou Constantinos Zamboglou Constantinos Zamboglou Influence of Urethra Sparing on Tumor Control Probability and Normal Tissue Complication Probability in Focal Dose Escalated Hypofractionated Radiotherapy: A Planning Study Based on Histopathology Reference Frontiers in Oncology hypofractionated radiotherapy PSMA - prostate specific membrane antigen focal dose escalation tumor control probability (TCP) NTCP (normal tissue complication probability) model mpMRI |
author_facet |
Simon K. B. Spohn Simon K. B. Spohn Simon K. B. Spohn Ilias Sachpazidis Rolf Wiehle Benedikt Thomann August Sigle Peter Bronsert Juri Ruf Matthias Benndorf Nils H. Nicolay Nils H. Nicolay Tanja Sprave Tanja Sprave Anca L. Grosu Anca L. Grosu Dimos Baltas Dimos Baltas Constantinos Zamboglou Constantinos Zamboglou Constantinos Zamboglou |
author_sort |
Simon K. B. Spohn |
title |
Influence of Urethra Sparing on Tumor Control Probability and Normal Tissue Complication Probability in Focal Dose Escalated Hypofractionated Radiotherapy: A Planning Study Based on Histopathology Reference |
title_short |
Influence of Urethra Sparing on Tumor Control Probability and Normal Tissue Complication Probability in Focal Dose Escalated Hypofractionated Radiotherapy: A Planning Study Based on Histopathology Reference |
title_full |
Influence of Urethra Sparing on Tumor Control Probability and Normal Tissue Complication Probability in Focal Dose Escalated Hypofractionated Radiotherapy: A Planning Study Based on Histopathology Reference |
title_fullStr |
Influence of Urethra Sparing on Tumor Control Probability and Normal Tissue Complication Probability in Focal Dose Escalated Hypofractionated Radiotherapy: A Planning Study Based on Histopathology Reference |
title_full_unstemmed |
Influence of Urethra Sparing on Tumor Control Probability and Normal Tissue Complication Probability in Focal Dose Escalated Hypofractionated Radiotherapy: A Planning Study Based on Histopathology Reference |
title_sort |
influence of urethra sparing on tumor control probability and normal tissue complication probability in focal dose escalated hypofractionated radiotherapy: a planning study based on histopathology reference |
publisher |
Frontiers Media S.A. |
series |
Frontiers in Oncology |
issn |
2234-943X |
publishDate |
2021-05-01 |
description |
PurposeMultiparametric magnetic resonance tomography (mpMRI) and prostate specific membrane antigen positron emission tomography (PSMA-PET/CT) are used to guide focal radiotherapy (RT) dose escalation concepts. Besides improvements of treatment effectiveness, maintenance of a good quality of life is essential. Therefore, this planning study investigates whether urethral sparing in moderately hypofractionated RT with focal RT dose escalation influences tumour control probability (TCP) and normal tissue complication probability (NTCP).Patients and Methods10 patients with primary prostate cancer (PCa), who underwent 68Ga PSMA-PET/CT and mpMRI followed by radical prostatectomy were enrolled. Intraprostatic tumour volumes (gross tumor volume, GTV) based on both imaging techniques (GTV-MRI and -PET) were contoured manually using validated contouring techniques and GTV-Union was created by summing both. For each patient three IMRT plans were generated with 60 Gy to the whole prostate and a simultaneous integrated boost up to 70 Gy to GTV-Union in 20 fractions by (Plan 1) not respecting and (Plan 2) respecting dose constraints for urethra as well as (Plan 3) respecting dose constraints for planning organ at risk volume for urethra (PRV = urethra + 2mm expansion). NTCP for urethra was calculated applying a Lyman-Kutcher-Burman model. TCP-Histo was calculated based on PCa distribution in co-registered histology (GTV-Histo). Complication free tumour control probability (P+) was calculated. Furthermore, the intrafractional movement was considered.ResultsMedian overlap of GTV-Union and PRV-Urethra was 1.6% (IQR 0-7%). Median minimum distance of GTV-Histo to urethra was 3.6 mm (IQR 2 – 7 mm) and of GTV-Union to urethra was 1.8 mm (IQR 0.0 – 5.0 mm). The respective prescription doses and dose constraints were reached in all plans. Urethra-sparing in Plans 2 and 3 reached significantly lower NTCP-Urethra (p = 0.002) without significantly affecting TCP-GTV-Histo (p = p > 0.28), NTCP-Bladder (p > 0.85) or NTCP-Rectum (p = 0.85), resulting in better P+ (p = 0.006). Simulation of intrafractional movement yielded even higher P+ values for Plans 2 and 3 compared to Plan 1.ConclusionUrethral sparing may increase the therapeutic ratio and should be implemented in focal RT dose escalation concepts. |
topic |
hypofractionated radiotherapy PSMA - prostate specific membrane antigen focal dose escalation tumor control probability (TCP) NTCP (normal tissue complication probability) model mpMRI |
url |
https://www.frontiersin.org/articles/10.3389/fonc.2021.652678/full |
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doaj-a97761b46d5243758ea160b6aaa7dafd2021-05-14T06:08:07ZengFrontiers Media S.A.Frontiers in Oncology2234-943X2021-05-011110.3389/fonc.2021.652678652678Influence of Urethra Sparing on Tumor Control Probability and Normal Tissue Complication Probability in Focal Dose Escalated Hypofractionated Radiotherapy: A Planning Study Based on Histopathology ReferenceSimon K. B. Spohn0Simon K. B. Spohn1Simon K. B. Spohn2Ilias Sachpazidis3Rolf Wiehle4Benedikt Thomann5August Sigle6Peter Bronsert7Juri Ruf8Matthias Benndorf9Nils H. Nicolay10Nils H. Nicolay11Tanja Sprave12Tanja Sprave13Anca L. Grosu14Anca L. Grosu15Dimos Baltas16Dimos Baltas17Constantinos Zamboglou18Constantinos Zamboglou19Constantinos Zamboglou20Department of Radiation Oncology, Medical Center – University of Freiburg, Faculty of Medicine, University of Freiburg, Freiburg, GermanyGerman Cancer Consortium (DKTK). Partner Site Freiburg, Freiburg, GermanyBerta-Ottenstein-Programme, Faculty of Medicine, University of Freiburg, Freiburg, GermanyDivision of Medical Physics, Department of Radiation Oncology, Medical Center - University of Freiburg, Faculty of Medicine, University of Freiburg, Freiburg, GermanyDivision of Medical Physics, Department of Radiation Oncology, Medical Center - University of Freiburg, Faculty of Medicine, University of Freiburg, Freiburg, GermanyDivision of Medical Physics, Department of Radiation Oncology, Medical Center - University of Freiburg, Faculty of Medicine, University of Freiburg, Freiburg, GermanyDepartment of Urology, Medical Center – University of Freiburg, Faculty of Medicine, University of Freiburg, Freiburg, GermanyInstitute for Surgical Pathology, Medical Center – University of Freiburg, Faculty of Medicine, University of Freiburg, Freiburg, GermanyDepartment of Nuclear Medicine, Medical Center – University of Freiburg, Faculty of Medicine, University of Freiburg, Freiburg, GermanyDepartment of Radiology, Medical Center – University of Freiburg, Faculty of Medicine, University of Freiburg, Freiburg, GermanyDepartment of Radiation Oncology, Medical Center – University of Freiburg, Faculty of Medicine, University of Freiburg, Freiburg, GermanyGerman Cancer Consortium (DKTK). Partner Site Freiburg, Freiburg, GermanyDepartment of Radiation Oncology, Medical Center – University of Freiburg, Faculty of Medicine, University of Freiburg, Freiburg, GermanyGerman Cancer Consortium (DKTK). Partner Site Freiburg, Freiburg, GermanyDepartment of Radiation Oncology, Medical Center – University of Freiburg, Faculty of Medicine, University of Freiburg, Freiburg, GermanyGerman Cancer Consortium (DKTK). Partner Site Freiburg, Freiburg, GermanyGerman Cancer Consortium (DKTK). Partner Site Freiburg, Freiburg, GermanyDivision of Medical Physics, Department of Radiation Oncology, Medical Center - University of Freiburg, Faculty of Medicine, University of Freiburg, Freiburg, GermanyDepartment of Radiation Oncology, Medical Center – University of Freiburg, Faculty of Medicine, University of Freiburg, Freiburg, GermanyGerman Cancer Consortium (DKTK). Partner Site Freiburg, Freiburg, GermanyBerta-Ottenstein-Programme, Faculty of Medicine, University of Freiburg, Freiburg, GermanyPurposeMultiparametric magnetic resonance tomography (mpMRI) and prostate specific membrane antigen positron emission tomography (PSMA-PET/CT) are used to guide focal radiotherapy (RT) dose escalation concepts. Besides improvements of treatment effectiveness, maintenance of a good quality of life is essential. Therefore, this planning study investigates whether urethral sparing in moderately hypofractionated RT with focal RT dose escalation influences tumour control probability (TCP) and normal tissue complication probability (NTCP).Patients and Methods10 patients with primary prostate cancer (PCa), who underwent 68Ga PSMA-PET/CT and mpMRI followed by radical prostatectomy were enrolled. Intraprostatic tumour volumes (gross tumor volume, GTV) based on both imaging techniques (GTV-MRI and -PET) were contoured manually using validated contouring techniques and GTV-Union was created by summing both. For each patient three IMRT plans were generated with 60 Gy to the whole prostate and a simultaneous integrated boost up to 70 Gy to GTV-Union in 20 fractions by (Plan 1) not respecting and (Plan 2) respecting dose constraints for urethra as well as (Plan 3) respecting dose constraints for planning organ at risk volume for urethra (PRV = urethra + 2mm expansion). NTCP for urethra was calculated applying a Lyman-Kutcher-Burman model. TCP-Histo was calculated based on PCa distribution in co-registered histology (GTV-Histo). Complication free tumour control probability (P+) was calculated. Furthermore, the intrafractional movement was considered.ResultsMedian overlap of GTV-Union and PRV-Urethra was 1.6% (IQR 0-7%). Median minimum distance of GTV-Histo to urethra was 3.6 mm (IQR 2 – 7 mm) and of GTV-Union to urethra was 1.8 mm (IQR 0.0 – 5.0 mm). The respective prescription doses and dose constraints were reached in all plans. Urethra-sparing in Plans 2 and 3 reached significantly lower NTCP-Urethra (p = 0.002) without significantly affecting TCP-GTV-Histo (p = p > 0.28), NTCP-Bladder (p > 0.85) or NTCP-Rectum (p = 0.85), resulting in better P+ (p = 0.006). Simulation of intrafractional movement yielded even higher P+ values for Plans 2 and 3 compared to Plan 1.ConclusionUrethral sparing may increase the therapeutic ratio and should be implemented in focal RT dose escalation concepts.https://www.frontiersin.org/articles/10.3389/fonc.2021.652678/fullhypofractionated radiotherapyPSMA - prostate specific membrane antigenfocal dose escalationtumor control probability (TCP)NTCP (normal tissue complication probability) modelmpMRI |