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Clinical Trial
. 2024 Jan 1;42(1):38-46.
doi: 10.1200/JCO.23.00753. Epub 2023 Sep 25.

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

Erin F Gillespie  1   2 , Joanna C Yang  1   3 , Noah J Mathis  1 , Catherine B Marine  1 , Charlie White  4 , Zhigang Zhang  4 , Christopher A Barker  1 , Rupesh Kotecha  5 , Alyson McIntosh  6 , Max Vaynrub  7 , Meredith K Bartelstein  7 , Aaron Mitchell  4   8 , David M Guttmann  1 , Divya Yerramilli  1 , Daniel S Higginson  1 , Yoshida J Yamada  1 , Zachary A Kohutek  1   9 , Simon N Powell  1 , Jillian Tsai  1   10 , Jonathan T Yang  1   2
Affiliations
Clinical Trial

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

Erin F Gillespie et al. J Clin Oncol. .

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.

Trial registration: ClinicalTrials.gov NCT03523351.

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Conflict of interest statement

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).

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.

Figures

FIG 1.
FIG 1.
CONSORT diagram.
FIG 2.
FIG 2.
Time-to-SRE on the basis of randomization arm among patients evaluable for the primary end point (n = 111 bone metastases among 71 total patients). RT, radiation therapy; SRE, skeletal-related event.
FIG 3.
FIG 3.
OS in the intention-to-treat population (n = 78 patients) by randomization arm. OS, overall survival; RT, radiation therapy.
FIG A1.
FIG A1.
Time-to-SRE on the basis of high-risk definition among all patients evaluable for the primary end point. This was specified by the treating physician for each bone metastasis lesion at the time of enrollment. SRE, skeletal-related event.
FIG A2.
FIG A2.
Opioid-free probability among patients not on opioids at baseline (n = 52) by randomization arm. RT, radiation therapy.
FIG A3.
FIG A3.
Patient-reported outcomes for pain and quality of life at baseline, 3, 6 and 12 months. (A) BPI is reported as average scores. (B) EQ-5D-5L is a validated questionnaire with a five-component scale including mobility, self-care, usual activities, pain/discomfort, and anxiety/depression; composite scores are reported. BPI, Brief Pain Inventory; EQ-5D-5L, EuroQol 5-dimension 5-level; RT, radiation therapy.
See this image and copyright information in PMC

Comment in

  • Metastasis-Directed Therapy: A Moving Target Advancing Progress Forward.
    Deek MP, Tran PT, Jabbour SK. Deek MP, et al. J Clin Oncol. 2024 Jan 1;42(1):4-7. doi: 10.1200/JCO.23.01274. Epub 2023 Sep 25. J Clin Oncol. 2024. PMID: 37748118 Free PMC article. No abstract available.
  • Reply to A.W. Chan et al.
    Gillespie EF, Vaynrub M, Yang JT. Gillespie EF, et al. J Clin Oncol. 2024 Apr 10;42(11):1328-1329. doi: 10.1200/JCO.23.02566. Epub 2024 Feb 6. J Clin Oncol. 2024. PMID: 38320232 Free PMC article. No abstract available.

References

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