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September 25, 2023

Prophylactic Radiation Therapy Versus Standard of Care for Patients With High-Risk Asymptomatic Bone Metastases: A Multicenter, Randomized Phase II Clinical Trial

Authors: Erin F. Gillespie, MD, MPH https://orcid.org/0000-0002-1386-1542 [email protected], Joanna C. Yang, MD, MPH, Noah J. Mathis, BA https://orcid.org/0000-0003-1125-6282, Catherine B. Marine, BA https://orcid.org/0009-0009-1736-2255, Charlie White, MS https://orcid.org/0000-0003-1671-3155, Zhigang Zhang, PhD, Christopher A. Barker, MD, … Show All … , Rupesh Kotecha, MD https://orcid.org/0000-0001-6927-0402, Alyson McIntosh, MD https://orcid.org/0000-0002-9551-2644, Max Vaynrub, MD https://orcid.org/0000-0001-7364-3259, Meredith K. Bartelstein, MD https://orcid.org/0000-0001-6506-7765, Aaron Mitchell, MD, MPH https://orcid.org/0000-0003-3639-3515, David M. Guttmann, MD, Divya Yerramilli, MD, MBE https://orcid.org/0000-0003-3565-5018, Daniel S. Higginson, MD https://orcid.org/0000-0002-6686-7454, Yoshida J. Yamada, MD, Zachary A. Kohutek, MD, Simon N. Powell, MD, PhD https://orcid.org/0000-0002-8183-4765, Jillian Tsai, MD, PhD https://orcid.org/0000-0003-0400-2655, and Jonathan T. Yang, MD, PhDAuthors Info & Affiliations
J Clin Oncol 42, 38-46(2024)
Volume 42, Number 1
DOI: 10.1200/JCO.23.00753

 

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Abstract

Purpose

External-beam radiation therapy (RT) is standard of care (SOC) for pain relief of symptomatic bone metastases. We aimed to evaluate the efficacy of radiation to asymptomatic bone metastases in preventing skeletal-related events (SRE).

Methods

In a multicenter randomized controlled trial, adult patients with widely metastatic solid tumor malignancies were stratified by histology and planned SOC (systemic therapy or observation) and randomly assigned in a 1:1 ratio to receive RT to asymptomatic high-risk bone metastases or SOC alone. The primary outcome of the trial was SRE. Secondary outcomes included hospitalizations for SRE and overall survival (OS).

Results

A total of 78 patients with 122 high-risk bone metastases were enrolled between May 8, 2018, and August 9, 2021, at three institutions across an affiliated cancer network in the United States. Seventy-three patients were evaluable for the primary end point. The most common primary cancer types were lung (27%), breast (24%), and prostate (22%). At 1 year, SRE occurred in one of 62 bone metastases (1.6%) in the RT arm and 14 of 49 bone metastases (29%) in the SOC arm (P < .001). There were significantly fewer patients hospitalized for SRE in the RT arm compared with the SOC arm (0 v 4, P = .045). At a median follow-up of 2.5 years, OS was significantly longer in the RT arm (hazard ratio [HR], 0.49; 95% CI, 0.27 to 0.89; P = .018), which persisted on multivariable Cox regression analysis (HR, 0.46; 95% CI, 0.23 to 0.85; P = .01).

Conclusion

Radiation delivered prophylactically to asymptomatic, high-risk bone metastases reduced SRE and hospitalizations. We also observed an improvement in OS with prophylactic radiation, although a confirmatory phase III trial is warranted.

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Metastasis-Directed Therapy: A Moving Target Advancing Progress Forward

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Study Protocol

The following protocol information is provided solely to describe how the authors conducted the research underlying this article. The information provided may not reflect the complete protocol or any previous amendments or modifications. As described in the Information for Contributors, JCO requests only specific elements of the most recent version of the protocol. The protocol information is not intended to replace good clinical judgment in selecting appropriate therapy and in determining drug doses, schedules, and dose modifications. The treating physician or other health care provider is responsible for determining the best treatment for the patient. ASCO and JCO assume no responsibility for any injury or damage to persons or property arising out of the use of this protocol material or due to any errors or omissions. Readers seeking additional information about the protocol are encouraged to consult the corresponding author directly.

Please click the protocol link below to access the information.

Prior Presentation

Presented in part at the American Society of Radiation Oncology Annual Meeting, San Antonio, TX, October 23, 2022.

Support

Supported in part by the National Institutes of Health/National Cancer Institute (NIH/NCI) through Cancer Center Support Grant No. P30 CA008748 (Memorial Sloan Kettering) and NCI Career Development Award No. K08 CA252640 (E.F.G.).

Clinical Trial Information

Authors' Disclosures of Potential Conflicts of Interest

Prophylactic Radiation Therapy Versus Standard of Care for Patients With High-Risk Asymptomatic Bone Metastases: A Multicenter, Randomized Phase II Clinical Trial

The following represents disclosure information provided by authors of this manuscript. All relationships are considered compensated unless otherwise noted. Relationships are self-held unless noted. I = Immediate Family Member, Inst = My Institution. Relationships may not relate to the subject matter of this manuscript. For more information about ASCO's conflict of interest policy, please refer to www.asco.org/rwc or ascopubs.org/jco/authors/author-center.
Open Payments is a public database containing information reported by companies about payments made to US-licensed physicians (Open Payments).

Erin F. Gillespie

Other Relationship: eContour

Christopher A. Barker

Research Funding: Elekta (Inst), Amgen (Inst), Merck (Inst), Regeneron (Inst), EMD Serono/Merck (Inst), PSI (Inst), Alpha TAU Medical (Inst)
Uncompensated Relationships: Castle Biosciences

Rupesh Kotecha

Honoraria: Accuray, Elekta, BrainLAB, Elsevier, Peerview, Kazia Therapeutics, Castle Biosciences
Consulting or Advisory Role: ViewRay, Novocure
Speakers' Bureau: Novocure, GT Medical Technologies
Research Funding: Medtronic (Inst), Blue Earth Diagnostics (Inst), Novocure (Inst), GT Medical Technologies (Inst), AstraZeneca (Inst), Exelixis (Inst), ViewRay (Inst), BrainLAB (Inst), Cantex Pharmaceuticals, Inc (Inst)
Travel, Accommodations, Expenses: Peerview, Elekta, ViewRay, Novocure

Max Vaynrub

Honoraria: Leiden University Medical Center (Inst)

Aaron Mitchell

Daniel S. Higginson

Employment: Memorial Sloan-Kettering Cancer Center
Research Funding: AstraZeneca (Inst), Natera (Inst), SQZ Biotech (Inst)
Patents, Royalties, Other Intellectual Property: Daniel Higginson and Rama Damerla are inventors on a provisional patent application filed by their institution, Memorial Sloan Kettering Cancer Center (Inst), Daniel Higginson and Jonathan Leeman are inventors on a provisional patent application field by their institution, Memorial Sloan Kettering Cancer Center (Inst), Daniel Higginson and Suleman Hussain are inventors on a provisional patent application field by their institution, Memorial Sloan Kettering Cancer Center (Inst), Daniel Higginson and Grace Moore are inventors on a provisional patent application field by their institution, Memorial Sloan Kettering Cancer Center (Inst)

Yoshida J. Yamada

Employment: Memorial Sloan-Kettering Cancer Center
Leadership: Chordoma Foundation, Chordoma Foundation
Honoraria: Varian Medical Systems, brainLab, vision RT
Consulting or Advisory Role: University of Wollongong
Speakers' Bureau: BrainLAB, Vision RT, Varian Medical Systems
Research Funding: Varian Medical Systems
Other Relationship: University of Wollongong

Simon N. Powell

Consulting or Advisory Role: Varian Medical Systems, Philips Healthcare, Rain Therapeutics, AstraZeneca
Research Funding: Philips Healthcare, Varian Medical Systems
Travel, Accommodations, Expenses: AstraZeneca

Jillian Tsai

Employment: Princess Margaret Cancer Center.
Honoraria: Varian Medical Systems, Varian Medical Systems, Varian Medical Systems
Consulting or Advisory Role: Varian Medical Systems

Jonathan T. Yang

Employment: University of Washington, Fred Hutchinson Cancer Research Center
Stock and Other Ownership Interests: Nanocan Therapeutics
Consulting or Advisory Role: Galera Therapeutics, Nanocan Therapeutics, Kazia Therapeutics, AstraZeneca, Plus Therapeutics
Research Funding: AstraZeneca, Kazia Therapeutics, X-RAD Therapeutics, Debiopharm Group, Biocept
No other potential conflicts of interest were reported.