Increased Dose to Organs in Urinary Tract Associates With Measures of Genitourinary Toxicity in Pooled Voxel-Based Analysis of 3 Randomized Phase III Trials
Purpose: Dose information from organ sub-regions has been shown to be more predictive of genitourinary toxicity than whole organ dose volume histogram information. This study aimed to identify anatomically-localized regions where 3D dose is associated with genitourinary toxicities in healthy tissues...
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Frontiers Media S.A.
2020-07-01
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| Series: | Frontiers in Oncology |
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| Online Access: | https://www.frontiersin.org/article/10.3389/fonc.2020.01174/full |
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| author | Marco Marcello Marco Marcello James W. Denham Angel Kennedy Annette Haworth Allison Steigler Peter B. Greer Peter B. Greer Lois C. Holloway Lois C. Holloway Lois C. Holloway Jason A. Dowling Jason A. Dowling Michael G. Jameson Michael G. Jameson Michael G. Jameson Michael G. Jameson Dale Roach Dale Roach Dale Roach David J. Joseph David J. Joseph David J. Joseph Sarah L. Gulliford Sarah L. Gulliford David P. Dearnaley Matthew R. Sydes Emma Hall Martin A. Ebert Martin A. Ebert Martin A. Ebert |
| author_facet | Marco Marcello Marco Marcello James W. Denham Angel Kennedy Annette Haworth Allison Steigler Peter B. Greer Peter B. Greer Lois C. Holloway Lois C. Holloway Lois C. Holloway Jason A. Dowling Jason A. Dowling Michael G. Jameson Michael G. Jameson Michael G. Jameson Michael G. Jameson Dale Roach Dale Roach Dale Roach David J. Joseph David J. Joseph David J. Joseph Sarah L. Gulliford Sarah L. Gulliford David P. Dearnaley Matthew R. Sydes Emma Hall Martin A. Ebert Martin A. Ebert Martin A. Ebert |
| author_sort | Marco Marcello |
| collection | DOAJ |
| description | Purpose: Dose information from organ sub-regions has been shown to be more predictive of genitourinary toxicity than whole organ dose volume histogram information. This study aimed to identify anatomically-localized regions where 3D dose is associated with genitourinary toxicities in healthy tissues throughout the pelvic anatomy.Methods and Materials: Dose distributions for up to 656 patients of the Trans-Tasman Radiation Oncology Group 03.04 RADAR trial were deformably registered onto a single exemplar CT dataset. Voxel- based multiple comparison permutation dose difference testing, Cox regression modeling and LASSO feature selection were used to identify regions where 3D dose-increase was associated with late grade ≥ 2 genitourinary dysuria, incontinence and frequency, and late grade ≥ 1 haematuria. This was externally validated by registering dose distributions from the RT01 (up to n = 388) and CHHiP (up to n = 247) trials onto the same exemplar and repeating the voxel-based tests on each of these data sets. All three datasets were then combined, and the tests repeated.Results: Voxel-based Cox regression and multiple comparison permutation dose difference testing revealed regions where increased dose was correlated with genitourinary toxicity. Increased dose in the vicinity of the membranous and spongy urethra was associated with dysuria for all datasets. Haematuria was similarly correlated with increased dose at the membranous and spongy urethra, for the RADAR, CHHiP, and combined datasets. Some evidence was found for the association between incontinence and increased dose at the internal and external urethral sphincter for RADAR and the internal sphincter alone for the combined dataset. Incontinence was also strongly correlated with dose from posterior oblique beams. Patients with fields extending inferiorly and posteriorly to the CTV, adjacent to the membranous and spongy urethra, were found to experience increased frequency.Conclusions: Anatomically-localized dose-toxicity relationships were determined for late genitourinary symptoms in the urethra and urinary sphincters. Low-intermediate doses to the extraprostatic urethra were associated with risk of late dysuria and haematuria, while dose to the urinary sphincters was associated with incontinence. |
| first_indexed | 2024-12-12T03:52:22Z |
| format | Article |
| id | doaj.art-320ab27893814288a577a1000c3e012a |
| institution | Directory Open Access Journal |
| issn | 2234-943X |
| language | English |
| last_indexed | 2024-12-12T03:52:22Z |
| publishDate | 2020-07-01 |
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| record_format | Article |
| series | Frontiers in Oncology |
| spelling | doaj.art-320ab27893814288a577a1000c3e012a2022-12-22T00:39:20ZengFrontiers Media S.A.Frontiers in Oncology2234-943X2020-07-011010.3389/fonc.2020.01174523969Increased Dose to Organs in Urinary Tract Associates With Measures of Genitourinary Toxicity in Pooled Voxel-Based Analysis of 3 Randomized Phase III TrialsMarco Marcello0Marco Marcello1James W. Denham2Angel Kennedy3Annette Haworth4Allison Steigler5Peter B. Greer6Peter B. Greer7Lois C. Holloway8Lois C. Holloway9Lois C. Holloway10Jason A. Dowling11Jason A. Dowling12Michael G. Jameson13Michael G. Jameson14Michael G. Jameson15Michael G. Jameson16Dale Roach17Dale Roach18Dale Roach19David J. Joseph20David J. Joseph21David J. Joseph22Sarah L. Gulliford23Sarah L. Gulliford24David P. Dearnaley25Matthew R. Sydes26Emma Hall27Martin A. Ebert28Martin A. Ebert29Martin A. Ebert30Department of Radiation Oncology, Sir Charles Gairdner Hospital, Nedlands, WA, AustraliaDepartment of Physics, University of Western Australia, Perth, WA, AustraliaSchool of Medicine and Public Health, University of Newcastle, Callaghan, NSW, AustraliaDepartment of Radiation Oncology, Sir Charles Gairdner Hospital, Nedlands, WA, AustraliaSchool of Physics, University of Sydney, Sydney, NSW, AustraliaProstate Cancer Trials Group, School of Medicine and Public Health, University of Newcastle, Callaghan, NSW, AustraliaSchool of Mathematical and Physical Sciences, University of Newcastle, Callaghan, NSW, AustraliaDepartment of Radiation Oncology, Calvary Mater Newcastle, Waratah, NSW, AustraliaDepartment of Medical Physics, Liverpool Cancer Centre, Liverpool, NSW, AustraliaSouth Western Sydney Clinical School, University of New South Wales, Kensington, NSW, Australia0Centre for Medical Radiation Physics, University of Wollongong, Wollongong, NSW, AustraliaSchool of Mathematical and Physical Sciences, University of Newcastle, Callaghan, NSW, Australia1CSIRO, St Lucia, QLD, AustraliaDepartment of Medical Physics, Liverpool Cancer Centre, Liverpool, NSW, AustraliaSouth Western Sydney Clinical School, University of New South Wales, Kensington, NSW, Australia0Centre for Medical Radiation Physics, University of Wollongong, Wollongong, NSW, Australia2Cancer Research Team, Ingham Institute for Applied Medical Research, Liverpool, NSW, AustraliaDepartment of Medical Physics, Liverpool Cancer Centre, Liverpool, NSW, AustraliaSouth Western Sydney Clinical School, University of New South Wales, Kensington, NSW, Australia2Cancer Research Team, Ingham Institute for Applied Medical Research, Liverpool, NSW, Australia3School of Surgery, University of Western Australia, Perth, WA, Australia45D Clinics, Claremont, WA, Australia5GenesisCare WA, Wembley, WA, Australia6Radiotherapy Department, University College London Hospitals NHS Foundation Trust, London, United Kingdom7Department of Medical Physics and Biomedical Engineering, University College London, London, United Kingdom8Academic UroOncology Unit, The Institute of Cancer Research and the Royal Marsden NHS Trust, London, United Kingdom9MRC Clinical Trials Unit, Medical Research Council, London, United Kingdom0Clinical Trials and Statistics Unit, The Institute of Cancer Research, London, United KingdomDepartment of Radiation Oncology, Sir Charles Gairdner Hospital, Nedlands, WA, AustraliaDepartment of Physics, University of Western Australia, Perth, WA, Australia45D Clinics, Claremont, WA, AustraliaPurpose: Dose information from organ sub-regions has been shown to be more predictive of genitourinary toxicity than whole organ dose volume histogram information. This study aimed to identify anatomically-localized regions where 3D dose is associated with genitourinary toxicities in healthy tissues throughout the pelvic anatomy.Methods and Materials: Dose distributions for up to 656 patients of the Trans-Tasman Radiation Oncology Group 03.04 RADAR trial were deformably registered onto a single exemplar CT dataset. Voxel- based multiple comparison permutation dose difference testing, Cox regression modeling and LASSO feature selection were used to identify regions where 3D dose-increase was associated with late grade ≥ 2 genitourinary dysuria, incontinence and frequency, and late grade ≥ 1 haematuria. This was externally validated by registering dose distributions from the RT01 (up to n = 388) and CHHiP (up to n = 247) trials onto the same exemplar and repeating the voxel-based tests on each of these data sets. All three datasets were then combined, and the tests repeated.Results: Voxel-based Cox regression and multiple comparison permutation dose difference testing revealed regions where increased dose was correlated with genitourinary toxicity. Increased dose in the vicinity of the membranous and spongy urethra was associated with dysuria for all datasets. Haematuria was similarly correlated with increased dose at the membranous and spongy urethra, for the RADAR, CHHiP, and combined datasets. Some evidence was found for the association between incontinence and increased dose at the internal and external urethral sphincter for RADAR and the internal sphincter alone for the combined dataset. Incontinence was also strongly correlated with dose from posterior oblique beams. Patients with fields extending inferiorly and posteriorly to the CTV, adjacent to the membranous and spongy urethra, were found to experience increased frequency.Conclusions: Anatomically-localized dose-toxicity relationships were determined for late genitourinary symptoms in the urethra and urinary sphincters. Low-intermediate doses to the extraprostatic urethra were associated with risk of late dysuria and haematuria, while dose to the urinary sphincters was associated with incontinence.https://www.frontiersin.org/article/10.3389/fonc.2020.01174/fullexternal beam radiotherapyprostate cancerurinary toxicityvoxel-based analysisdose-toxicity relationships |
| spellingShingle | Marco Marcello Marco Marcello James W. Denham Angel Kennedy Annette Haworth Allison Steigler Peter B. Greer Peter B. Greer Lois C. Holloway Lois C. Holloway Lois C. Holloway Jason A. Dowling Jason A. Dowling Michael G. Jameson Michael G. Jameson Michael G. Jameson Michael G. Jameson Dale Roach Dale Roach Dale Roach David J. Joseph David J. Joseph David J. Joseph Sarah L. Gulliford Sarah L. Gulliford David P. Dearnaley Matthew R. Sydes Emma Hall Martin A. Ebert Martin A. Ebert Martin A. Ebert Increased Dose to Organs in Urinary Tract Associates With Measures of Genitourinary Toxicity in Pooled Voxel-Based Analysis of 3 Randomized Phase III Trials Frontiers in Oncology external beam radiotherapy prostate cancer urinary toxicity voxel-based analysis dose-toxicity relationships |
| title | Increased Dose to Organs in Urinary Tract Associates With Measures of Genitourinary Toxicity in Pooled Voxel-Based Analysis of 3 Randomized Phase III Trials |
| title_full | Increased Dose to Organs in Urinary Tract Associates With Measures of Genitourinary Toxicity in Pooled Voxel-Based Analysis of 3 Randomized Phase III Trials |
| title_fullStr | Increased Dose to Organs in Urinary Tract Associates With Measures of Genitourinary Toxicity in Pooled Voxel-Based Analysis of 3 Randomized Phase III Trials |
| title_full_unstemmed | Increased Dose to Organs in Urinary Tract Associates With Measures of Genitourinary Toxicity in Pooled Voxel-Based Analysis of 3 Randomized Phase III Trials |
| title_short | Increased Dose to Organs in Urinary Tract Associates With Measures of Genitourinary Toxicity in Pooled Voxel-Based Analysis of 3 Randomized Phase III Trials |
| title_sort | increased dose to organs in urinary tract associates with measures of genitourinary toxicity in pooled voxel based analysis of 3 randomized phase iii trials |
| topic | external beam radiotherapy prostate cancer urinary toxicity voxel-based analysis dose-toxicity relationships |
| url | https://www.frontiersin.org/article/10.3389/fonc.2020.01174/full |
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