Continued Benefit to Rectal Separation for Prostate Radiation Therapy: Final Results of a Phase III Trial

Daniel A. Hamstra, Neil Mariados, John Sylvester, Dhiren Shah, Lawrence Karsh, Richard Hudes, David Beyer, Steven Kurtzman, Jeffrey Bogart, R. Alex Hsi, Michael Kos, Rodney Ellis, Mark Logsdon, Shawn Zimberg, Kevin Forsythe, Hong Zhang, Edward Soffen, Patrick Francke, Constantine Mantz, Peter RossiTheodore DeWeese, Stephanie Daignault-Newton, Benjamin W. Fischer-Valuck, Anupama Chundury, Hiram Gay, Walter Bosch, Jeff Michalski

Research output: Contribution to journalArticle

Abstract

Purpose SpaceOAR, a Food and Drug Administration–approved hydrogel intended to create a rectal–prostate space, was evaluated in a single-blind phase III trial of image guided intensity modulated radiation therapy. A total of 222 men were randomized 2:1 to the spacer or control group and received 79.2 Gy in 1.8-Gy fractions to the prostate with or without the seminal vesicles. The present study reports the final results with a median follow-up period of 3 years. Methods and Materials Cumulative (Common Terminology Criteria for Adverse Events, version 4.0) toxicity was evaluated using the log-rank test. Quality of life (QOL) was examined using the Expanded Prostate Cancer Index Composite (EPIC), and the mean changes from baseline in the EPIC domains were tested using repeated measures models. The proportions of men with minimally important differences (MIDs) in each domain were tested using repeated measures logistic models with prespecified thresholds. Results The 3-year incidence of grade ≥1 (9.2% vs 2.0%; P=.028) and grade ≥2 (5.7% vs 0%; P=.012) rectal toxicity favored the spacer arm. Grade ≥1 urinary incontinence was also lower in the spacer arm (15% vs 4%; P=.046), with no difference in grade ≥2 urinary toxicity (7% vs 7%; P=0.7). From 6 months onward, bowel QOL consistently favored the spacer group (P=.002), with the difference at 3 years (5.8 points; P<.05) meeting the threshold for a MID. The control group had a 3.9-point greater decline in urinary QOL compared with the spacer group at 3 years (P<.05), but the difference did not meet the MID threshold. At 3 years, more men in the control group than in the spacer group had experienced a MID decline in bowel QOL (41% vs 14%; P=.002) and urinary QOL (30% vs 17%; P=.04). Furthermore, the control group were also more likely to have experienced large declines (twice the MID) in bowel QOL (21% vs 5%; P=.02) and urinary QOL (23% vs 8%; P=.02). Conclusions The benefit of a hydrogel spacer in reducing the rectal dose, toxicity, and QOL declines after image guided intensity modulated radiation therapy for prostate cancer was maintained or increased with a longer follow-up period, providing stronger evidence for the benefit of hydrogel spacer use in prostate radiation therapy.

Original languageEnglish (US)
Pages (from-to)976-985
Number of pages10
JournalInternational Journal of Radiation Oncology Biology Physics
Volume97
Issue number5
DOIs
StatePublished - Apr 1 2017

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spacers
Prostate
radiation therapy
Radiotherapy
Quality of Life
toxicity
Hydrogel
grade
Prostatic Neoplasms
Control Groups
cancer
thresholds
rank tests
terminology
composite materials
Seminal Vesicles
logistics
Urinary Incontinence
food
Terminology

ASJC Scopus subject areas

  • Radiation
  • Oncology
  • Radiology Nuclear Medicine and imaging
  • Cancer Research

Cite this

Continued Benefit to Rectal Separation for Prostate Radiation Therapy : Final Results of a Phase III Trial. / Hamstra, Daniel A.; Mariados, Neil; Sylvester, John; Shah, Dhiren; Karsh, Lawrence; Hudes, Richard; Beyer, David; Kurtzman, Steven; Bogart, Jeffrey; Hsi, R. Alex; Kos, Michael; Ellis, Rodney; Logsdon, Mark; Zimberg, Shawn; Forsythe, Kevin; Zhang, Hong; Soffen, Edward; Francke, Patrick; Mantz, Constantine; Rossi, Peter; DeWeese, Theodore; Daignault-Newton, Stephanie; Fischer-Valuck, Benjamin W.; Chundury, Anupama; Gay, Hiram; Bosch, Walter; Michalski, Jeff.

In: International Journal of Radiation Oncology Biology Physics, Vol. 97, No. 5, 01.04.2017, p. 976-985.

Research output: Contribution to journalArticle

Hamstra, DA, Mariados, N, Sylvester, J, Shah, D, Karsh, L, Hudes, R, Beyer, D, Kurtzman, S, Bogart, J, Hsi, RA, Kos, M, Ellis, R, Logsdon, M, Zimberg, S, Forsythe, K, Zhang, H, Soffen, E, Francke, P, Mantz, C, Rossi, P, DeWeese, T, Daignault-Newton, S, Fischer-Valuck, BW, Chundury, A, Gay, H, Bosch, W & Michalski, J 2017, 'Continued Benefit to Rectal Separation for Prostate Radiation Therapy: Final Results of a Phase III Trial', International Journal of Radiation Oncology Biology Physics, vol. 97, no. 5, pp. 976-985. https://doi.org/10.1016/j.ijrobp.2016.12.024
Hamstra, Daniel A. ; Mariados, Neil ; Sylvester, John ; Shah, Dhiren ; Karsh, Lawrence ; Hudes, Richard ; Beyer, David ; Kurtzman, Steven ; Bogart, Jeffrey ; Hsi, R. Alex ; Kos, Michael ; Ellis, Rodney ; Logsdon, Mark ; Zimberg, Shawn ; Forsythe, Kevin ; Zhang, Hong ; Soffen, Edward ; Francke, Patrick ; Mantz, Constantine ; Rossi, Peter ; DeWeese, Theodore ; Daignault-Newton, Stephanie ; Fischer-Valuck, Benjamin W. ; Chundury, Anupama ; Gay, Hiram ; Bosch, Walter ; Michalski, Jeff. / Continued Benefit to Rectal Separation for Prostate Radiation Therapy : Final Results of a Phase III Trial. In: International Journal of Radiation Oncology Biology Physics. 2017 ; Vol. 97, No. 5. pp. 976-985.
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abstract = "Purpose SpaceOAR, a Food and Drug Administration–approved hydrogel intended to create a rectal–prostate space, was evaluated in a single-blind phase III trial of image guided intensity modulated radiation therapy. A total of 222 men were randomized 2:1 to the spacer or control group and received 79.2 Gy in 1.8-Gy fractions to the prostate with or without the seminal vesicles. The present study reports the final results with a median follow-up period of 3 years. Methods and Materials Cumulative (Common Terminology Criteria for Adverse Events, version 4.0) toxicity was evaluated using the log-rank test. Quality of life (QOL) was examined using the Expanded Prostate Cancer Index Composite (EPIC), and the mean changes from baseline in the EPIC domains were tested using repeated measures models. The proportions of men with minimally important differences (MIDs) in each domain were tested using repeated measures logistic models with prespecified thresholds. Results The 3-year incidence of grade ≥1 (9.2{\%} vs 2.0{\%}; P=.028) and grade ≥2 (5.7{\%} vs 0{\%}; P=.012) rectal toxicity favored the spacer arm. Grade ≥1 urinary incontinence was also lower in the spacer arm (15{\%} vs 4{\%}; P=.046), with no difference in grade ≥2 urinary toxicity (7{\%} vs 7{\%}; P=0.7). From 6 months onward, bowel QOL consistently favored the spacer group (P=.002), with the difference at 3 years (5.8 points; P<.05) meeting the threshold for a MID. The control group had a 3.9-point greater decline in urinary QOL compared with the spacer group at 3 years (P<.05), but the difference did not meet the MID threshold. At 3 years, more men in the control group than in the spacer group had experienced a MID decline in bowel QOL (41{\%} vs 14{\%}; P=.002) and urinary QOL (30{\%} vs 17{\%}; P=.04). Furthermore, the control group were also more likely to have experienced large declines (twice the MID) in bowel QOL (21{\%} vs 5{\%}; P=.02) and urinary QOL (23{\%} vs 8{\%}; P=.02). Conclusions The benefit of a hydrogel spacer in reducing the rectal dose, toxicity, and QOL declines after image guided intensity modulated radiation therapy for prostate cancer was maintained or increased with a longer follow-up period, providing stronger evidence for the benefit of hydrogel spacer use in prostate radiation therapy.",
author = "Hamstra, {Daniel A.} and Neil Mariados and John Sylvester and Dhiren Shah and Lawrence Karsh and Richard Hudes and David Beyer and Steven Kurtzman and Jeffrey Bogart and Hsi, {R. Alex} and Michael Kos and Rodney Ellis and Mark Logsdon and Shawn Zimberg and Kevin Forsythe and Hong Zhang and Edward Soffen and Patrick Francke and Constantine Mantz and Peter Rossi and Theodore DeWeese and Stephanie Daignault-Newton and Fischer-Valuck, {Benjamin W.} and Anupama Chundury and Hiram Gay and Walter Bosch and Jeff Michalski",
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TY - JOUR

T1 - Continued Benefit to Rectal Separation for Prostate Radiation Therapy

T2 - Final Results of a Phase III Trial

AU - Hamstra, Daniel A.

AU - Mariados, Neil

AU - Sylvester, John

AU - Shah, Dhiren

AU - Karsh, Lawrence

AU - Hudes, Richard

AU - Beyer, David

AU - Kurtzman, Steven

AU - Bogart, Jeffrey

AU - Hsi, R. Alex

AU - Kos, Michael

AU - Ellis, Rodney

AU - Logsdon, Mark

AU - Zimberg, Shawn

AU - Forsythe, Kevin

AU - Zhang, Hong

AU - Soffen, Edward

AU - Francke, Patrick

AU - Mantz, Constantine

AU - Rossi, Peter

AU - DeWeese, Theodore

AU - Daignault-Newton, Stephanie

AU - Fischer-Valuck, Benjamin W.

AU - Chundury, Anupama

AU - Gay, Hiram

AU - Bosch, Walter

AU - Michalski, Jeff

PY - 2017/4/1

Y1 - 2017/4/1

N2 - Purpose SpaceOAR, a Food and Drug Administration–approved hydrogel intended to create a rectal–prostate space, was evaluated in a single-blind phase III trial of image guided intensity modulated radiation therapy. A total of 222 men were randomized 2:1 to the spacer or control group and received 79.2 Gy in 1.8-Gy fractions to the prostate with or without the seminal vesicles. The present study reports the final results with a median follow-up period of 3 years. Methods and Materials Cumulative (Common Terminology Criteria for Adverse Events, version 4.0) toxicity was evaluated using the log-rank test. Quality of life (QOL) was examined using the Expanded Prostate Cancer Index Composite (EPIC), and the mean changes from baseline in the EPIC domains were tested using repeated measures models. The proportions of men with minimally important differences (MIDs) in each domain were tested using repeated measures logistic models with prespecified thresholds. Results The 3-year incidence of grade ≥1 (9.2% vs 2.0%; P=.028) and grade ≥2 (5.7% vs 0%; P=.012) rectal toxicity favored the spacer arm. Grade ≥1 urinary incontinence was also lower in the spacer arm (15% vs 4%; P=.046), with no difference in grade ≥2 urinary toxicity (7% vs 7%; P=0.7). From 6 months onward, bowel QOL consistently favored the spacer group (P=.002), with the difference at 3 years (5.8 points; P<.05) meeting the threshold for a MID. The control group had a 3.9-point greater decline in urinary QOL compared with the spacer group at 3 years (P<.05), but the difference did not meet the MID threshold. At 3 years, more men in the control group than in the spacer group had experienced a MID decline in bowel QOL (41% vs 14%; P=.002) and urinary QOL (30% vs 17%; P=.04). Furthermore, the control group were also more likely to have experienced large declines (twice the MID) in bowel QOL (21% vs 5%; P=.02) and urinary QOL (23% vs 8%; P=.02). Conclusions The benefit of a hydrogel spacer in reducing the rectal dose, toxicity, and QOL declines after image guided intensity modulated radiation therapy for prostate cancer was maintained or increased with a longer follow-up period, providing stronger evidence for the benefit of hydrogel spacer use in prostate radiation therapy.

AB - Purpose SpaceOAR, a Food and Drug Administration–approved hydrogel intended to create a rectal–prostate space, was evaluated in a single-blind phase III trial of image guided intensity modulated radiation therapy. A total of 222 men were randomized 2:1 to the spacer or control group and received 79.2 Gy in 1.8-Gy fractions to the prostate with or without the seminal vesicles. The present study reports the final results with a median follow-up period of 3 years. Methods and Materials Cumulative (Common Terminology Criteria for Adverse Events, version 4.0) toxicity was evaluated using the log-rank test. Quality of life (QOL) was examined using the Expanded Prostate Cancer Index Composite (EPIC), and the mean changes from baseline in the EPIC domains were tested using repeated measures models. The proportions of men with minimally important differences (MIDs) in each domain were tested using repeated measures logistic models with prespecified thresholds. Results The 3-year incidence of grade ≥1 (9.2% vs 2.0%; P=.028) and grade ≥2 (5.7% vs 0%; P=.012) rectal toxicity favored the spacer arm. Grade ≥1 urinary incontinence was also lower in the spacer arm (15% vs 4%; P=.046), with no difference in grade ≥2 urinary toxicity (7% vs 7%; P=0.7). From 6 months onward, bowel QOL consistently favored the spacer group (P=.002), with the difference at 3 years (5.8 points; P<.05) meeting the threshold for a MID. The control group had a 3.9-point greater decline in urinary QOL compared with the spacer group at 3 years (P<.05), but the difference did not meet the MID threshold. At 3 years, more men in the control group than in the spacer group had experienced a MID decline in bowel QOL (41% vs 14%; P=.002) and urinary QOL (30% vs 17%; P=.04). Furthermore, the control group were also more likely to have experienced large declines (twice the MID) in bowel QOL (21% vs 5%; P=.02) and urinary QOL (23% vs 8%; P=.02). Conclusions The benefit of a hydrogel spacer in reducing the rectal dose, toxicity, and QOL declines after image guided intensity modulated radiation therapy for prostate cancer was maintained or increased with a longer follow-up period, providing stronger evidence for the benefit of hydrogel spacer use in prostate radiation therapy.

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