Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
Randomized Controlled Trial
. 2023 Apr 1;9(4):511-518.
doi: 10.1001/jamaoncol.2022.7592.

Hyaluronic Acid Spacer for Hypofractionated Prostate Radiation Therapy: A Randomized Clinical Trial

Neil F Mariados  1 , Peter F Orio 3rd  2   3 , Zvi Schiffman  4 , Thanh John Van  4 , Alexander Engelman  5 , Rizwan Nurani  6   7 , Steven M Kurtzman  6 , Escarlata Lopez  8 , Michael Chao  9 , Thomas P Boike  10 , Alvaro A Martinez  10 , Glen Gejerman  11 , John Lederer  12 , John E Sylvester  13 , Gregory Bell  14 , Douglas Rivera  14 , Neal Shore  15 , Katie Miller  16 , Boris Sinayuk  17 , Michael L Steinberg  18 , Daniel A Low  18 , Amar U Kishan  18 , Martin T King  2   3
Affiliations
Randomized Controlled Trial

Hyaluronic Acid Spacer for Hypofractionated Prostate Radiation Therapy: A Randomized Clinical Trial

Neil F Mariados et al. JAMA Oncol. .

Abstract

Importance: Hypofractionated radiation therapy (RT) for prostate cancer has been associated with greater acute grade 2 gastrointestinal (GI) toxic effects compared with conventionally fractionated RT.

Objective: To evaluate whether a hyaluronic acid rectal spacer could (1) improve rectal dosimetry and (2) affect acute grade 2 or higher GI toxic effects for hypofractionated RT.

Design, setting, and participants: This randomized clinical trial was conducted from March 2020 to June 2021 among 12 centers within the US, Australia, and Spain, with a 6-month follow-up. Adult patients with biopsy-proven, T1 to T2 prostate cancer with a Gleason score 7 or less and prostate-specific antigen level of 20 ng/mL or less (to convert to μg/L, multiply by 1) were blinded to the treatment arms. Of the 260 consented patients, 201 patients (77.3%) were randomized (2:1) to the presence or absence of the spacer. Patients were stratified by intended 4-month androgen deprivation therapy use and erectile quality.

Main outcomes and measures: For the primary outcome, we hypothesized that more than 70% of patients in the spacer group would achieve a 25% or greater reduction in the rectal volume receiving 54 Gy (V54). For the secondary outcome, we hypothesized that the spacer group would have noninferior acute (within 3 months) grade 2 or higher GI toxic effects compared with the control group, with a margin of 10%.

Results: Of the 201 randomized patients, 8 (4.0%) were Asian, 26 (12.9%) Black, 42 (20.9%) Hispanic or Latino, and 153 (76.1%) White; the mean (SD) age for the spacer group was 68.6 (7.2) years and 68.4 (7.3) years for the control group. For the primary outcome, 131 of 133 (98.5%; 95% CI, 94.7%-99.8%) patients in the spacer group experienced a 25% or greater reduction in rectum V54, which was greater than the minimally acceptable 70% (P < .001). The mean (SD) reduction was 85.0% (20.9%). For the secondary outcome, 4 of 136 patients (2.9%) in the spacer group and 9 of 65 patients (13.8%) in the control group experienced acute grade 2 or higher GI toxic effects (difference, -10.9%; 95% 1-sided upper confidence limit, -3.5; P = .01).

Conclusions and relevance: The trial results suggest that rectal spacing with hyaluronic acid improved rectal dosimetry and reduced acute grade 2 or higher GI toxic effects. Rectal spacing should potentially be considered for minimizing the risk of acute grade 2 or higher toxic effects for hypofractionated RT.

Trial registration: ClinicalTrials.gov Identifier: NCT04189913.

PubMed Disclaimer

Conflict of interest statement

Conflict of Interest Disclosures: Dr Mariados reported personal fees from and being a limited partner/investor in a venture capital fund that own position in Palette Life Sciences outside the submitted work. Dr Orio reported personal fees from Palette Life Sciences and Theragenics outside the submitted work. Dr Engelman reported grants from Palette Life Sciences during the conduct of the study. Dr Nurani reported research support from Palette Life Sciences during the conduct of the study and research support from Boston Scientific and Bioprotect Ltd outside the submitted work. Dr Chao reported personal fees from Palette Life Sciences during the conduct of the study and grants from Palette Life Sciences outside the submitted work. Dr Martinez reported grants from Palette Life Sciences during the conduct of the study. Dr Gejerman reported grants from Palette Life Sciences during the conduct of the study and consulting for Palette Life Sciences outside the submitted work. Dr Lederer reported consulting fees from Palette Life Sciences outside the submitted work. Dr Sylvester reported grants from Palette Life Sciences during the conduct of the study as well as personal fees from Boston Scientific outside the submitted work. Dr Bell reported grants from Palette Life Sciences during the conduct of the study as well as personal fees from Palette Life Sciences outside the submitted work. Dr Sinayuk reported personal fees from Palette Life Sciences during the conduct of the study as well as personal fees from Palette Life Sciences outside the submitted work. Dr Steinberg reported personal fees from Viewray outside the submitted work. Dr Low reported being a principal investigator of a UCLA core lab contract contracted by Palette during the conduct of the study as well as personal fees from ViewRay outside the submitted work. Dr Kishan reported honoraria, research funding, and stock from ViewRay, Inc, honoraria and consulting fees from Varian Medical Systems, advisory board service for Boston Scientific and Janssen Biotechnologies, and research funding from Point Biopharma outside the submitted work. Dr King reported grants and personal fees from Palette Life Sciences during the conduct of the study and grants from Bayer Healthcare outside the submitted work. No other disclosures were reported.

Figures

Figure.
Figure.. Participant Flow Diagram
Consolidating Standards of Reporting Trials diagram. CT indicates computed tomography; MRI, magnetic resonance imaging.
See this image and copyright information in PMC

Comment in

  • Urologic Oncology: Prostate Cancer.
    Taneja SS. Taneja SS. J Urol. 2023 Aug;210(2):381-382. doi: 10.1097/JU.0000000000003541. Epub 2023 May 18. J Urol. 2023. PMID: 37199093 No abstract available.
  • Barrigel Spacer Injection Technique.
    Gejerman G, Goldstein MM, Chao M, Shore N, Lederer J, Crawford ED, Bukkapatnam R, Sylvester J, Orio PF 3rd. Gejerman G, et al. Pract Radiat Oncol. 2024 Jan-Feb;14(1):e57-e61. doi: 10.1016/j.prro.2023.08.009. Epub 2023 Aug 30. Pract Radiat Oncol. 2024. PMID: 37657504 No abstract available.

References

    1. Schad MD, Patel AK, Ling DC, Smith RP, Beriwal S. Hypofractionated prostate radiation therapy: adoption and dosimetric adherence through clinical pathways in an integrated oncology network. JCO Oncol Pract. 2021;17(4):e537-e547. doi:10.1200/OP.20.00508 - DOI - PubMed
    1. Pryor DI, Martin JM, Millar JL, et al. . Evaluation of hypofractionated radiation therapy use and patient-reported outcomes in men with nonmetastatic prostate cancer in Australia and New Zealand. JAMA Netw Open. 2021;4(11):e2129647. doi:10.1001/jamanetworkopen.2021.29647 - DOI - PMC - PubMed
    1. Nithiyananthan K, Creighton N, Currow D, Martin JM. Population-level uptake of moderately hypofractionated definitive radiation therapy in the treatment of prostate cancer. Int J Radiat Oncol Biol Phys. 2021;111(2):417-423. doi:10.1016/j.ijrobp.2021.04.033 - DOI - PubMed
    1. National Prostate Cancer Audit . NPCA annual report 2021. Accessed June 25, 202. https://www.npca.org/resources/3371-npca-2021-annual-report?gclid=CjwKCA...
    1. Zhou K, Renouf M, Perrocheau G, et al. . Cost-effectiveness of hypofractionated versus conventional radiotherapy in patients with intermediate-risk prostate cancer: an ancillary study of the Prostate Fractionated Irradiation Trial—PROFIT. Radiother Oncol. 2022;173:306-312. doi:10.1016/j.radonc.2022.06.014 - DOI - PubMed

Publication types

Associated data