Dose-escalated radiotherapy to 82 Gy for prostate cancer following insertion of a peri-rectal hydrogel spacer: 3-year outcomes from a phase II trial.


Journal

Radiation oncology (London, England)
ISSN: 1748-717X
Titre abrégé: Radiat Oncol
Pays: England
ID NLM: 101265111

Informations de publication

Date de publication:
25 Jul 2022
Historique:
received: 17 05 2022
accepted: 11 07 2022
entrez: 25 7 2022
pubmed: 26 7 2022
medline: 28 7 2022
Statut: epublish

Résumé

Dose-escalation to above 80 Gy during external beam radiotherapy for localised prostate cancer leads to improved oncological outcomes but also substantially increased rectal toxicity. The aim of this study was to demonstrate the safety and efficacy of escalating the dose to 82 Gy following insertion of a peri-rectal hydrogel spacer (HS) prior to radiotherapy. This was a single arm, open-label, prospective study of men with localised prostate cancer who were prescribed a course of intensity modulated radiotherapy escalated to 82 Gy in 2 Gy fractions following insertion of the SpaceOAR™ HS (Boston Scientific, Marlborough, MA). Patients were prescribed a standard course of 78 Gy in 2 Gy fractions where rectal dose constraints could not be met for the 82 Gy plan. The co-primary endpoints were the rate of grade 3 gastrointestinal (GI) and genitourinary (GU) adverse events (CTCAE, v4), and patient-reported quality of life (QoL) (EORTC QLQ-C30 and PR25 modules), up to 37.5 months post-treatment. Seventy patients received treatment on the study, with 64 (91.4%) receiving an 82 Gy treatment course. The median follow-up time post-treatment was 37.4 months. The rate of radiotherapy-related grade 3 GI and GU adverse events was 0% and 2.9%, respectively. There were 2 (2.9%) grade 3 adverse events related to insertion of the HS. Only small and transient declines in QoL were observed; there was no clinically or statistically significant decline in QoL beyond 13.5 months and up to 37.5 months post-treatment, compared to baseline. No late RTOG-defined grade ≥ 2 GI toxicity was observed, with no GI toxicity observed in any patient at 37.5 months post-treatment. Nine (12.9%) patients met criteria for biochemical failure within the follow-up period. Dose-escalation to 82 Gy, facilitated by use of a hydrogel spacer, is safe and feasible, with minimal toxicity up to 37.5 months post-treatment when compared to rates of rectal toxicity in previous dose-escalation trials up to 80 Gy. Trials with longer follow-up of oncological and functional outcomes are required to robustly demonstrate a sustained widening of the therapeutic window. Trial registration Australian New Zealand Clinical Trials Registry, ACTRN12621000056897 , 22/01/2021. Retrospectively registered.

Sections du résumé

BACKGROUND BACKGROUND
Dose-escalation to above 80 Gy during external beam radiotherapy for localised prostate cancer leads to improved oncological outcomes but also substantially increased rectal toxicity. The aim of this study was to demonstrate the safety and efficacy of escalating the dose to 82 Gy following insertion of a peri-rectal hydrogel spacer (HS) prior to radiotherapy.
METHODS METHODS
This was a single arm, open-label, prospective study of men with localised prostate cancer who were prescribed a course of intensity modulated radiotherapy escalated to 82 Gy in 2 Gy fractions following insertion of the SpaceOAR™ HS (Boston Scientific, Marlborough, MA). Patients were prescribed a standard course of 78 Gy in 2 Gy fractions where rectal dose constraints could not be met for the 82 Gy plan. The co-primary endpoints were the rate of grade 3 gastrointestinal (GI) and genitourinary (GU) adverse events (CTCAE, v4), and patient-reported quality of life (QoL) (EORTC QLQ-C30 and PR25 modules), up to 37.5 months post-treatment.
RESULTS RESULTS
Seventy patients received treatment on the study, with 64 (91.4%) receiving an 82 Gy treatment course. The median follow-up time post-treatment was 37.4 months. The rate of radiotherapy-related grade 3 GI and GU adverse events was 0% and 2.9%, respectively. There were 2 (2.9%) grade 3 adverse events related to insertion of the HS. Only small and transient declines in QoL were observed; there was no clinically or statistically significant decline in QoL beyond 13.5 months and up to 37.5 months post-treatment, compared to baseline. No late RTOG-defined grade ≥ 2 GI toxicity was observed, with no GI toxicity observed in any patient at 37.5 months post-treatment. Nine (12.9%) patients met criteria for biochemical failure within the follow-up period.
CONCLUSIONS CONCLUSIONS
Dose-escalation to 82 Gy, facilitated by use of a hydrogel spacer, is safe and feasible, with minimal toxicity up to 37.5 months post-treatment when compared to rates of rectal toxicity in previous dose-escalation trials up to 80 Gy. Trials with longer follow-up of oncological and functional outcomes are required to robustly demonstrate a sustained widening of the therapeutic window. Trial registration Australian New Zealand Clinical Trials Registry, ACTRN12621000056897 , 22/01/2021. Retrospectively registered.

Identifiants

pubmed: 35879722
doi: 10.1186/s13014-022-02103-5
pii: 10.1186/s13014-022-02103-5
pmc: PMC9316359
doi:

Substances chimiques

Hydrogels 0

Types de publication

Clinical Trial, Phase II Journal Article

Langues

eng

Sous-ensembles de citation

IM

Pagination

131

Commentaires et corrections

Type : CommentIn

Informations de copyright

© 2022. The Author(s).

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Auteurs

Andrew W See (AW)

Icon Cancer Centre, Richmond, Australia. Andrew.See@icon.team.

Patrick Bowden (P)

Icon Cancer Centre, Richmond, Australia.

Geoffrey Wells (G)

Urology Department, Eastern Health, Box Hill Hospital, Box Hill, Australia.

Sree Appu (S)

Department of Surgery, Monash University, Melbourne, Australia.
Cabrini Health, Malvern, Australia.
Department of Urology, Austin Health, Heidelberg, Australia.

Nathan Lawrentschuk (N)

Division of Cancer Surgery, Peter MacCallum Cancer Centre, Melbourne, Australia.
Department of Urology, Royal Melbourne Hospital, Melbourne, Australia.
Department of Surgery, University of Melbourne, Melbourne, Australia.
EJ Whitten Centre for Prostate Cancer Research, Epworth Healthcare, Melbourne, Australia.

Peter Liodakis (P)

Department of Urology, Austin Health, Heidelberg, Australia.
North Eastern Urology, Heidelberg, Australia.

Chloe Pandeli (C)

Icon Cancer Centre, Richmond, Australia.

Yolanda Aarons (Y)

Icon Cancer Centre, Richmond, Australia.

Lloyd M L Smyth (LML)

Icon Institute of Innovation and Research, South Brisbane, Australia.

Dean P McKenzie (DP)

Research Development and Governance Unit, Epworth HealthCare, Richmond, Australia.
Department of Health Sciences and Biostatistics, Swinburne University of Technology, Hawthorn, Australia.

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