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

Author(s): Erin F. Gillespie, MD, MPH^1,2; Joanna C. Yang, MD, MPH^1,3; Noah J. Mathis, BA¹; Catherine B. Marine, BA¹; Charlie White, MS⁴; Zhigang Zhang, PhD⁴; Christopher A. Barker, MD¹; Rupesh Kotecha, MD⁵; Alyson McIntosh, MD⁶; Max Vaynrub, MD⁷; Meredith K. Bartelstein, MD⁷; Aaron Mitchell, MD, MPH^4,8; David M. Guttmann, MD¹; Divya Yerramilli, MD, MBE¹; Daniel S. Higginson, MD¹; Yoshida J. Yamada, MD¹; Zachary A. Kohutek, MD^1,9; Simon N. Powell, MD, PhD¹; Jillian Tsai, MD, PhD^1,10; and Jonathan T. Yang, MD, PhD^1,2

Source: DOI: 10.1200/JCO.23.00753 Journal of Clinical Oncology

Dr. Maen Hussein's Thoughts

This article was recommended by Dr. Carrascosa. The study is promising, but the number of patients is small. Another thing to consider is the use of a bone enhancing agent (only 50% of patients had it on both arms). The authors recommended larger trials, which may help add a sub-analysis to assess the role of bone enhancing agents.

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.

Author Affiliations

¹Department of Radiation Oncology, Memorial Sloan Kettering Cancer Center, New York, NY; ²Department of Radiation Oncology, University of Washington, Seattle, WA; ³Department of Radiation Oncology, Washington University in St Louis, St Louis, MO; ⁴Department of Epidemiology and Biostatistics, Memorial Sloan Kettering Cancer Center, New York, NY; ⁵Department of Radiation Oncology, Miami Cancer Institute, Baptist Health South Florida, Miami, FL; ⁶Department of Radiation Oncology, Lehigh Valley Cancer Institute, Allentown, PAa; ⁷Department of Surgery, Orthopaedic Service, Memorial Sloan Kettering Cancer Center, New York, NY; ⁸Department of Medicine, Memorial Sloan Kettering Cancer Center, New York, NY; ⁹Department of Radiation Oncology, Vanderbilt University, Nashville, TN; ¹⁰Department of Radiation Oncology, Princess Margaret Hospital Cancer Centre, Toronto, Ontario, CA

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

From our radiation oncology colleagues, this is a study showing that for high-risk bone metastases, those treated prophylactically with radiation were associated with lower rates of skeletal related events. High risk was defined as a bulky (>2cm) lesion in the hip, long bone lesions occupying one-third (1/3) to two-thirds (2/3) of the cortical thickness, or disease of the vertebral body of the junctional spine or posterior element involvement.

Phase II Randomized Study of Salvage Radiation Therapy Plus Enzalutamide or Placebo for High-Risk Prostate-Specific Antigen Recurrent Prostate Cancer After Radical Prostatectomy: The SALV-ENZA Trial

Although not a practice changing study, this study makes a few points that may be seen in future studies. In the setting of biochem-recurrent prostate cancer after RP, novel anti-androgen agents may replace ADT in combination with salvage XRT as they appear to be active and less toxic than traditional ADT. Low/Intermediate risk patients are likely of benefit with median PSA at accrual of 0.3 in this study, not unlike other similar studies. The role of combination anti-hormone therapy + salvage radiation seems to be solidifying.

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

Dr. Maen Hussein's Thoughts

PURPOSE

METHODS

RESULTS

CONCLUSION

Author Affiliations

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

Phase II Randomized Study of Salvage Radiation Therapy Plus Enzalutamide or Placebo for High-Risk Prostate-Specific Antigen Recurrent Prostate Cancer After Radical Prostatectomy: The SALV-ENZA Trial

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