Relationships between rectal and perirectal doses and rectal bleeding or tenesmus in pooled voxel-based analysis of 3 randomised phase III trials.


Journal

Radiotherapy and oncology : journal of the European Society for Therapeutic Radiology and Oncology
ISSN: 1879-0887
Titre abrégé: Radiother Oncol
Pays: Ireland
ID NLM: 8407192

Informations de publication

Date de publication:
09 2020
Historique:
received: 13 02 2020
revised: 25 07 2020
accepted: 28 07 2020
pubmed: 4 8 2020
medline: 15 4 2021
entrez: 4 8 2020
Statut: ppublish

Résumé

This study aimed to identify anatomically-localised regions where planned radiotherapy dose is associated with gastrointestinal toxicities in healthy tissues throughout the pelvic anatomy. Planned dose distributions for up to 657 patients of the Trans Tasman Radiation Oncology Group 03.04 RADAR trial were deformably registered onto a single exemplar computed tomography dataset. Voxel-based multiple comparison permutation dose difference testing, Cox regression modelling and LASSO feature selection were used to identify regions where dose-increase was associated with grade ≥2 rectal bleeding (RB) or tenesmus, according to the LENT/SOMA scale. This was externally validated by registering dose distributions from the RT01 (n = 388) and CHHiP (n = 241) trials onto the same exemplar and repeating the tests on each of these data sets, and on all three datasets combined. Voxel-based Cox regression and permutation dose difference testing revealed regions where increased dose was correlated with gastrointestinal toxicity. Grade ≥2 RB was associated with posteriorly extended lateral beams that manifested high doses (>55 Gy) in a small rectal volume adjacent to the clinical target volume. A correlation was found between grade ≥2 tenesmus and increased low-intermediate dose (∼25 Gy) at the posterior beam region, including the posterior rectum and perirectal fat space (PRFS). The serial response of the rectum with respect to RB has been demonstrated in patients with posteriorly extended lateral beams. Similarly, the parallel response of the PRFS with respect to tenesmus has been demonstrated in patients treated with the posterior beam.

Sections du résumé

BACKGROUND AND PURPOSE
This study aimed to identify anatomically-localised regions where planned radiotherapy dose is associated with gastrointestinal toxicities in healthy tissues throughout the pelvic anatomy.
MATERIALS AND METHODS
Planned dose distributions for up to 657 patients of the Trans Tasman Radiation Oncology Group 03.04 RADAR trial were deformably registered onto a single exemplar computed tomography dataset. Voxel-based multiple comparison permutation dose difference testing, Cox regression modelling and LASSO feature selection were used to identify regions where dose-increase was associated with grade ≥2 rectal bleeding (RB) or tenesmus, according to the LENT/SOMA scale. This was externally validated by registering dose distributions from the RT01 (n = 388) and CHHiP (n = 241) trials onto the same exemplar and repeating the tests on each of these data sets, and on all three datasets combined.
RESULTS
Voxel-based Cox regression and permutation dose difference testing revealed regions where increased dose was correlated with gastrointestinal toxicity. Grade ≥2 RB was associated with posteriorly extended lateral beams that manifested high doses (>55 Gy) in a small rectal volume adjacent to the clinical target volume. A correlation was found between grade ≥2 tenesmus and increased low-intermediate dose (∼25 Gy) at the posterior beam region, including the posterior rectum and perirectal fat space (PRFS).
CONCLUSIONS
The serial response of the rectum with respect to RB has been demonstrated in patients with posteriorly extended lateral beams. Similarly, the parallel response of the PRFS with respect to tenesmus has been demonstrated in patients treated with the posterior beam.

Identifiants

pubmed: 32745667
pii: S0167-8140(20)30696-4
doi: 10.1016/j.radonc.2020.07.048
pii:
doi:

Types de publication

Clinical Trial, Phase III Journal Article Randomized Controlled Trial Research Support, Non-U.S. Gov't

Langues

eng

Sous-ensembles de citation

IM

Pagination

281-292

Subventions

Organisme : Cancer Research UK
ID : 10588
Pays : United Kingdom
Organisme : Cancer Research UK
ID : 12518
Pays : United Kingdom
Organisme : Cancer Research UK
ID : 7253
Pays : United Kingdom
Organisme : Medical Research Council
ID : MC_UU_12023/28
Pays : United Kingdom

Informations de copyright

Crown Copyright © 2020. Published by Elsevier B.V. All rights reserved.

Auteurs

Marco Marcello (M)

Department of Physics, University of Western Australia, Crawley, Australia; Department of Radiation Oncology, Sir Charles Gairdner Hospital, Nedlands, Australia. Electronic address: 20739859@student.uwa.edu.au.

James W Denham (JW)

School of Medicine and Public Health, University of Newcastle, Callaghan, Australia.

Angel Kennedy (A)

Department of Radiation Oncology, Sir Charles Gairdner Hospital, Nedlands, Australia.

Annette Haworth (A)

School of Physics, University of Sydney, Camperdown, Australia.

Allison Steigler (A)

Prostate Cancer Trials Group, School of Medicine and Public Health, University of Newcastle, Callaghan, Australia.

Peter B Greer (PB)

School of Mathematical and Physical Sciences, University of Newcastle, Callaghan, Australia; Department of Radiation Oncology, Calvary Mater Newcastle, Waratah, Australia.

Lois C Holloway (LC)

Department of Medical Physics, Liverpool Cancer Centre, Australia; South Western Sydney Clinical School, University of New South Wales, Liverpool, Australia; Centre for Medical Radiation Physics, University of Wollongong, Australia.

Jason A Dowling (JA)

School of Mathematical and Physical Sciences, University of Newcastle, Callaghan, Australia; CSIRO, Herston, Australia.

Michael G Jameson (MG)

Department of Medical Physics, Liverpool Cancer Centre, Australia; South Western Sydney Clinical School, University of New South Wales, Liverpool, Australia; Centre for Medical Radiation Physics, University of Wollongong, Australia; Cancer Research Team, Ingham Institute for Applied Medical Research, Liverpool, Australia.

Dale Roach (D)

Department of Medical Physics, Liverpool Cancer Centre, Australia; South Western Sydney Clinical School, University of New South Wales, Liverpool, Australia; Cancer Research Team, Ingham Institute for Applied Medical Research, Liverpool, Australia.

David J Joseph (DJ)

School of Surgery, University of Western Australia, Crawley, Australia; 5D Clinics, Claremont, Australia; GenesisCare WA, Wembley, Australia.

Sarah L Gulliford (SL)

Radiotherapy Department, University College London Hospitals NHS Foundation Trust, United Kingdom; Department of Medical Physics and Biomedical Engineering, University College London, United Kingdom.

David P Dearnaley (DP)

Academic UroOncology Unit, The Institute of Cancer Research and the Royal Marsden NHS Trust, London, Australia.

Mathew R Sydes (MR)

MRC Clinical Trials Unit, Institute of Clinical Trials and Methodology, University College, London, United Kingdom.

Emma Hall (E)

Clinical Trials and Statistics Unit, The Institute of Cancer Research, Sutton, United Kingdom.

Martin A Ebert (MA)

Department of Physics, University of Western Australia, Crawley, Australia; Department of Radiation Oncology, Sir Charles Gairdner Hospital, Nedlands, Australia; 5D Clinics, Claremont, Australia.

Articles similaires

[Redispensing of expensive oral anticancer medicines: a practical application].

Lisanne N van Merendonk, Kübra Akgöl, Bastiaan Nuijen
1.00
Humans Antineoplastic Agents Administration, Oral Drug Costs Counterfeit Drugs

Smoking Cessation and Incident Cardiovascular Disease.

Jun Hwan Cho, Seung Yong Shin, Hoseob Kim et al.
1.00
Humans Male Smoking Cessation Cardiovascular Diseases Female
Humans United States Aged Cross-Sectional Studies Medicare Part C
1.00
Humans Yoga Low Back Pain Female Male

Classifications MeSH