A randomised assessment of image guided radiotherapy within a phase 3 trial of conventional or hypofractionated high dose intensity modulated radiotherapy for prostate cancer.


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:
01 2020
Historique:
received: 17 04 2019
revised: 24 10 2019
accepted: 25 10 2019
pubmed: 27 11 2019
medline: 26 6 2020
entrez: 27 11 2019
Statut: ppublish

Résumé

Image-guided radiotherapy (IGRT) improves treatment set-up accuracy and provides the opportunity to reduce target volume margins. We introduced IGRT methods using standard (IGRT-S) or reduced (IGRT-R) margins in a randomised phase 2 substudy within CHHiP trial. We present a pre-planned analysis of the impact of IGRT on dosimetry and acute/late pelvic side effects using gastrointestinal and genitourinary clinician and patient-reported outcomes (PRO) and evaluate efficacy. CHHiP is a randomised phase 3, non-inferiority trial for men with localised prostate cancer. 3216 patients were randomly assigned to conventional (74 Gy in 2 Gy/fraction (f) daily) or moderate hypofractionation (60 or 57 Gy in 3 Gy/f daily) between October 2002 and June 2011. The IGRT substudy included a second randomisation assigning to no-IGRT, IGRT-S (standard CTV-PTV margins), or IGRT-R (reduced CTV-PTV margins). Primary substudy endpoint was late RTOG bowel and urinary toxicity at 2 years post-radiotherapy. Between June 2010 to July 2011, 293 men were recruited from 16 centres. Median follow-up is 56.9(IQR 54.3-60.9) months. Rectal and bladder dose-volume and surface percentages were significantly lower in IGRT-R compared to IGRT-S group; (p < 0.0001). Cumulative proportion with RTOG grade ≥ 2 toxicity reported to 2 years for bowel was 8.3(95% CI 3.2-20.7)%, 8.3(4.7-14.6)% and 5.8(2.6-12.4)% and for urinary 8.4(3.2-20.8)%, 4.6(2.1-9.9)% and 3.9(1.5-9.9)% in no IGRT, IGRT-S and IGRT-R groups respectively. In an exploratory analysis, treatment efficacy appeared similar in all three groups. Introduction of IGRT was feasible in a national randomised trial and IGRT-R produced dosimetric benefits. Overall side effect profiles were acceptable in all groups but lowest with IGRT and reduced margins. 97182923.

Sections du résumé

BACKGROUND AND PURPOSE
Image-guided radiotherapy (IGRT) improves treatment set-up accuracy and provides the opportunity to reduce target volume margins. We introduced IGRT methods using standard (IGRT-S) or reduced (IGRT-R) margins in a randomised phase 2 substudy within CHHiP trial. We present a pre-planned analysis of the impact of IGRT on dosimetry and acute/late pelvic side effects using gastrointestinal and genitourinary clinician and patient-reported outcomes (PRO) and evaluate efficacy.
MATERIALS AND METHODS
CHHiP is a randomised phase 3, non-inferiority trial for men with localised prostate cancer. 3216 patients were randomly assigned to conventional (74 Gy in 2 Gy/fraction (f) daily) or moderate hypofractionation (60 or 57 Gy in 3 Gy/f daily) between October 2002 and June 2011. The IGRT substudy included a second randomisation assigning to no-IGRT, IGRT-S (standard CTV-PTV margins), or IGRT-R (reduced CTV-PTV margins). Primary substudy endpoint was late RTOG bowel and urinary toxicity at 2 years post-radiotherapy.
RESULTS
Between June 2010 to July 2011, 293 men were recruited from 16 centres. Median follow-up is 56.9(IQR 54.3-60.9) months. Rectal and bladder dose-volume and surface percentages were significantly lower in IGRT-R compared to IGRT-S group; (p < 0.0001). Cumulative proportion with RTOG grade ≥ 2 toxicity reported to 2 years for bowel was 8.3(95% CI 3.2-20.7)%, 8.3(4.7-14.6)% and 5.8(2.6-12.4)% and for urinary 8.4(3.2-20.8)%, 4.6(2.1-9.9)% and 3.9(1.5-9.9)% in no IGRT, IGRT-S and IGRT-R groups respectively. In an exploratory analysis, treatment efficacy appeared similar in all three groups.
CONCLUSION
Introduction of IGRT was feasible in a national randomised trial and IGRT-R produced dosimetric benefits. Overall side effect profiles were acceptable in all groups but lowest with IGRT and reduced margins.
ISRCTN
97182923.

Identifiants

pubmed: 31767473
pii: S0167-8140(19)33453-X
doi: 10.1016/j.radonc.2019.10.017
pmc: PMC7005673
pii:
doi:

Banques de données

ISRCTN
['ISRCTN97182923']

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

62-71

Subventions

Organisme : Cancer Research UK
ID : C1491/A15955
Pays : United Kingdom
Organisme : Cancer Research UK
ID : SP2312/021
Pays : United Kingdom
Organisme : Department of Health
Pays : United Kingdom
Organisme : Cancer Research UK
ID : 10588
Pays : United Kingdom
Organisme : Cancer Research UK
ID : C8262/A7253
Pays : United Kingdom
Organisme : Cancer Research UK
ID : 12518
Pays : United Kingdom
Organisme : Cancer Research UK
ID : C1491/A9895
Pays : United Kingdom
Organisme : Cancer Research UK
ID : 7253
Pays : United Kingdom

Informations de copyright

Copyright © 2019 The Authors. Published by Elsevier B.V. All rights reserved.

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Auteurs

Julia Murray (J)

The Institute of Cancer Research, London, UK; Royal Marsden NHS Foundation Trust, London, UK.

Clare Griffin (C)

The Institute of Cancer Research, London, UK.

Sarah Gulliford (S)

The Institute of Cancer Research, London, UK; Department of Radiotherapy, University College London Hospitals NHS Foundation Trust, UK.

Isabel Syndikus (I)

Clatterbridge Cancer Centre, Wirral, UK.

John Staffurth (J)

Cardiff University/Velindre Cancer Centre, UK.

Miguel Panades (M)

Lincoln County Hospital, UK.

Christopher Scrase (C)

Ipswich Hospital, UK.

Chris Parker (C)

The Institute of Cancer Research, London, UK; Royal Marsden NHS Foundation Trust, London, UK.

Vincent Khoo (V)

The Institute of Cancer Research, London, UK; Royal Marsden NHS Foundation Trust, London, UK.

Jamie Dean (J)

The Institute of Cancer Research, London, UK.

Helen Mayles (H)

Clatterbridge Cancer Centre, Wirral, UK.

Philip Mayles (P)

Clatterbridge Cancer Centre, Wirral, UK.

Simon Thomas (S)

Addenbrooke's Hospital, Cambridge, UK.

Olivia Naismith (O)

Royal Marsden NHS Foundation Trust, London, UK.

Angela Baker (A)

Royal Berkshire Hospital, Reading, UK.

Helen Mossop (H)

The Institute of Cancer Research, London, UK.

Clare Cruickshank (C)

The Institute of Cancer Research, London, UK.

Emma Hall (E)

The Institute of Cancer Research, London, UK.

David Dearnaley (D)

The Institute of Cancer Research, London, UK; Royal Marsden NHS Foundation Trust, London, UK. Electronic address: david.dearnaley@icr.ac.uk.

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Classifications MeSH