Anorectal dose–effect relations for late gastrointestinal toxicity following external beam radiotherapy for prostate cancer in the FLAME trial

Veerle H. Groen; Nicolaas P.A. Zuithoff; Marcel van Schie; Evelyn M. Monninkhof; Martina Kunze-Busch; Hans C.J. de Boer; Jochem van der Voort van Zyp; Floris J. Pos; Robert Jan Smeenk; Karin Haustermans; Sofie Isebaert; Cédric Draulans; Tom Depuydt; Helena M. Verkooijen; Uulke A. van der Heide; Linda G.W. Kerkmeijer

doi:10.1016/j.radonc.2021.06.033

Anorectal dose–effect relations for late gastrointestinal toxicity following external beam radiotherapy for prostate cancer in the FLAME trial

Veerle H. Groen, Nicolaas P.A. Zuithoff, Marcel van Schie, Evelyn M. Monninkhof, Martina Kunze-Busch, Hans C.J. de Boer, Jochem van der Voort van Zyp, Floris J. Pos, Robert Jan Smeenk, Karin Haustermans, Sofie Isebaert, Cédric Draulans, Tom Depuydt, Helena M. Verkooijen, Uulke A. van der Heide, Linda G.W. Kerkmeijer^*

^*Corresponding author for this work

Research output: Contribution to journal › Article › Academic › peer-review

17 Downloads (Pure)

Abstract

BACKGROUND AND PURPOSE: The phase III FLAME trial (NCT01168479) showed an increase in five-year biochemical disease-free survival, with no significant increase in toxicity when adding a focal boost to external beam radiotherapy (EBRT) for localized prostate cancer [Kerkmeijer et al. JCO 2021]. The aim of this study was to investigate the association between delivered radiation dose to the anorectum and gastrointestinal (GI) toxicity (grade ≥2).

MATERIAL AND METHODS: All patients in the FLAME trial were analyzed, irrespective of treatment arm. The dose-effect relation of the anorectal dose parameters (D2cm 3 and D50%) and GI toxicity grade ≥2 in four years of follow-up was assessed using a mixed model analysis for repeated measurements, adjusted for age, cardiovascular disease, diabetes mellitus, T-stage, baseline toxicity grade ≥1, hormonal therapy and institute.

RESULTS: A dose-effect relation for D2cm 3 and D50% was observed with adjusted odds ratios of 1.17 (95% CI 1.13-1.21, p < 0.0001) and 1.20 (95% CI 1.14-1.25, p < 0.0001) for GI toxicity, respectively.

CONCLUSION: Although there was no difference in toxicity between study arms, a higher radiation dose to the anorectum was associated with a statistically significant increase in GI toxicity following EBRT for prostate cancer. This dose-effect relation was present for both large and small anorectal volumes. Therefore, further increase in dose to the anorectum should be weighed against the benefit of focal dose escalation for prostate cancer.

Original language	English
Pages (from-to)	98-104
Number of pages	7
Journal	Radiotherapy and Oncology
Volume	162
Early online date	29 Jun 2021
DOIs	https://doi.org/10.1016/j.radonc.2021.06.033
Publication status	Published - Sept 2021

Keywords

Anorectal dose parameters
Dose-effect relations
External beam radiotherapy
Focal boosting
Gastrointestinal toxicity
Prostate cancer
Radiotherapy Dosage
Prostatic Neoplasms/radiotherapy
Humans
Clinical Protocols
Male
Gastrointestinal Diseases/etiology
Disease-Free Survival
Brachytherapy

Access to Document

10.1016/j.radonc.2021.06.033

1-s2.0-S0167814021066202-mainFinal published version, 812 KB

Cite this

Groen, V. H., Zuithoff, N. P. A., van Schie, M., Monninkhof, E. M., Kunze-Busch, M., de Boer, H. C. J., van der Voort van Zyp, J., Pos, F. J., Smeenk, R. J., Haustermans, K., Isebaert, S., Draulans, C., Depuydt, T., Verkooijen, H. M., van der Heide, U. A., & Kerkmeijer, L. G. W. (2021). Anorectal dose–effect relations for late gastrointestinal toxicity following external beam radiotherapy for prostate cancer in the FLAME trial. Radiotherapy and Oncology, 162, 98-104. https://doi.org/10.1016/j.radonc.2021.06.033

@article{b7be7ef6816a481a8e61164e96272c57,

title = "Anorectal dose–effect relations for late gastrointestinal toxicity following external beam radiotherapy for prostate cancer in the FLAME trial",

abstract = "BACKGROUND AND PURPOSE: The phase III FLAME trial (NCT01168479) showed an increase in five-year biochemical disease-free survival, with no significant increase in toxicity when adding a focal boost to external beam radiotherapy (EBRT) for localized prostate cancer [Kerkmeijer et al. JCO 2021]. The aim of this study was to investigate the association between delivered radiation dose to the anorectum and gastrointestinal (GI) toxicity (grade ≥2).MATERIAL AND METHODS: All patients in the FLAME trial were analyzed, irrespective of treatment arm. The dose-effect relation of the anorectal dose parameters (D2cm 3 and D50%) and GI toxicity grade ≥2 in four years of follow-up was assessed using a mixed model analysis for repeated measurements, adjusted for age, cardiovascular disease, diabetes mellitus, T-stage, baseline toxicity grade ≥1, hormonal therapy and institute. RESULTS: A dose-effect relation for D2cm 3 and D50% was observed with adjusted odds ratios of 1.17 (95% CI 1.13-1.21, p < 0.0001) and 1.20 (95% CI 1.14-1.25, p < 0.0001) for GI toxicity, respectively. CONCLUSION: Although there was no difference in toxicity between study arms, a higher radiation dose to the anorectum was associated with a statistically significant increase in GI toxicity following EBRT for prostate cancer. This dose-effect relation was present for both large and small anorectal volumes. Therefore, further increase in dose to the anorectum should be weighed against the benefit of focal dose escalation for prostate cancer.",

keywords = "Anorectal dose parameters, Dose-effect relations, External beam radiotherapy, Focal boosting, Gastrointestinal toxicity, Prostate cancer, Radiotherapy Dosage, Prostatic Neoplasms/radiotherapy, Humans, Clinical Protocols, Male, Gastrointestinal Diseases/etiology, Disease-Free Survival, Brachytherapy",

author = "Groen, {Veerle H.} and Zuithoff, {Nicolaas P.A.} and {van Schie}, Marcel and Monninkhof, {Evelyn M.} and Martina Kunze-Busch and {de Boer}, {Hans C.J.} and {van der Voort van Zyp}, Jochem and Pos, {Floris J.} and Smeenk, {Robert Jan} and Karin Haustermans and Sofie Isebaert and C{\'e}dric Draulans and Tom Depuydt and Verkooijen, {Helena M.} and {van der Heide}, {Uulke A.} and Kerkmeijer, {Linda G.W.}",

note = "Funding Information: This study is supported by the Dutch Cancer Society (KWF, project 10088). Publisher Copyright: {\textcopyright} 2021 The Authors",

year = "2021",

month = sep,

doi = "10.1016/j.radonc.2021.06.033",

language = "English",

volume = "162",

pages = "98--104",

journal = "Radiotherapy and Oncology",

issn = "0167-8140",

publisher = "Elsevier Ireland Ltd",

}

Groen, VH, Zuithoff, NPA, van Schie, M, Monninkhof, EM, Kunze-Busch, M, de Boer, HCJ, van der Voort van Zyp, J, Pos, FJ, Smeenk, RJ, Haustermans, K, Isebaert, S, Draulans, C, Depuydt, T, Verkooijen, HM, van der Heide, UA & Kerkmeijer, LGW 2021, 'Anorectal dose–effect relations for late gastrointestinal toxicity following external beam radiotherapy for prostate cancer in the FLAME trial', Radiotherapy and Oncology, vol. 162, pp. 98-104. https://doi.org/10.1016/j.radonc.2021.06.033

TY - JOUR

T1 - Anorectal dose–effect relations for late gastrointestinal toxicity following external beam radiotherapy for prostate cancer in the FLAME trial

AU - Groen, Veerle H.

AU - Zuithoff, Nicolaas P.A.

AU - van Schie, Marcel

AU - Monninkhof, Evelyn M.

AU - Kunze-Busch, Martina

AU - de Boer, Hans C.J.

AU - van der Voort van Zyp, Jochem

AU - Pos, Floris J.

AU - Smeenk, Robert Jan

AU - Haustermans, Karin

AU - Isebaert, Sofie

AU - Draulans, Cédric

AU - Depuydt, Tom

AU - Verkooijen, Helena M.

AU - van der Heide, Uulke A.

AU - Kerkmeijer, Linda G.W.

PY - 2021/9

Y1 - 2021/9

N2 - BACKGROUND AND PURPOSE: The phase III FLAME trial (NCT01168479) showed an increase in five-year biochemical disease-free survival, with no significant increase in toxicity when adding a focal boost to external beam radiotherapy (EBRT) for localized prostate cancer [Kerkmeijer et al. JCO 2021]. The aim of this study was to investigate the association between delivered radiation dose to the anorectum and gastrointestinal (GI) toxicity (grade ≥2).MATERIAL AND METHODS: All patients in the FLAME trial were analyzed, irrespective of treatment arm. The dose-effect relation of the anorectal dose parameters (D2cm 3 and D50%) and GI toxicity grade ≥2 in four years of follow-up was assessed using a mixed model analysis for repeated measurements, adjusted for age, cardiovascular disease, diabetes mellitus, T-stage, baseline toxicity grade ≥1, hormonal therapy and institute. RESULTS: A dose-effect relation for D2cm 3 and D50% was observed with adjusted odds ratios of 1.17 (95% CI 1.13-1.21, p < 0.0001) and 1.20 (95% CI 1.14-1.25, p < 0.0001) for GI toxicity, respectively. CONCLUSION: Although there was no difference in toxicity between study arms, a higher radiation dose to the anorectum was associated with a statistically significant increase in GI toxicity following EBRT for prostate cancer. This dose-effect relation was present for both large and small anorectal volumes. Therefore, further increase in dose to the anorectum should be weighed against the benefit of focal dose escalation for prostate cancer.

AB - BACKGROUND AND PURPOSE: The phase III FLAME trial (NCT01168479) showed an increase in five-year biochemical disease-free survival, with no significant increase in toxicity when adding a focal boost to external beam radiotherapy (EBRT) for localized prostate cancer [Kerkmeijer et al. JCO 2021]. The aim of this study was to investigate the association between delivered radiation dose to the anorectum and gastrointestinal (GI) toxicity (grade ≥2).MATERIAL AND METHODS: All patients in the FLAME trial were analyzed, irrespective of treatment arm. The dose-effect relation of the anorectal dose parameters (D2cm 3 and D50%) and GI toxicity grade ≥2 in four years of follow-up was assessed using a mixed model analysis for repeated measurements, adjusted for age, cardiovascular disease, diabetes mellitus, T-stage, baseline toxicity grade ≥1, hormonal therapy and institute. RESULTS: A dose-effect relation for D2cm 3 and D50% was observed with adjusted odds ratios of 1.17 (95% CI 1.13-1.21, p < 0.0001) and 1.20 (95% CI 1.14-1.25, p < 0.0001) for GI toxicity, respectively. CONCLUSION: Although there was no difference in toxicity between study arms, a higher radiation dose to the anorectum was associated with a statistically significant increase in GI toxicity following EBRT for prostate cancer. This dose-effect relation was present for both large and small anorectal volumes. Therefore, further increase in dose to the anorectum should be weighed against the benefit of focal dose escalation for prostate cancer.

KW - Anorectal dose parameters

KW - Dose-effect relations

KW - External beam radiotherapy

KW - Focal boosting

KW - Gastrointestinal toxicity

KW - Prostate cancer

KW - Radiotherapy Dosage

KW - Prostatic Neoplasms/radiotherapy

KW - Humans

KW - Clinical Protocols

KW - Male

KW - Gastrointestinal Diseases/etiology

KW - Disease-Free Survival

KW - Brachytherapy

UR - http://www.scopus.com/inward/record.url?scp=85110574479&partnerID=8YFLogxK

U2 - 10.1016/j.radonc.2021.06.033

DO - 10.1016/j.radonc.2021.06.033

M3 - Article

C2 - 34214614

AN - SCOPUS:85110574479

SN - 0167-8140

VL - 162

SP - 98

EP - 104

JO - Radiotherapy and Oncology

JF - Radiotherapy and Oncology

ER -

Anorectal dose–effect relations for late gastrointestinal toxicity following external beam radiotherapy for prostate cancer in the FLAME trial

Abstract

Keywords

Access to Document

Other files and links

Fingerprint

Cite this