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Randomized Phase II Trial Shows Benefits of Prophylactic Radiation Therapy for Asymptomatic Bone Metastases


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The use of prophylactic radiation therapy for patients with metastatic cancer who had asymptomatic, high-risk bone metastases reduced the incidence of skeletal-related events, reduced pain and the number of hospitalizations, and was associated with significantly longer overall survival compared with patients who did not receive radiotherapy. These findings are from a multicenter, randomized phase II study, which was presented at the 2022 American Society for Radiation Oncology (ASTRO) Annual Meeting.1


“This is the first randomized study of prophylactic radiation therapy for asymptomatic bone metastasis. Results indicate a promising new use of radiation therapy.”
— ERIN F. GILLESPIE, MD

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“The literature supports radiation for symptomatic bone metastases, but we all face clinical questions that arise frequently about whether to treat asymptomatic lesions, particularly those lesions in critical locations,” said lead author Erin F. Gillespie, MD, a radiation oncologist at Memorial Sloan Kettering Cancer Center, New York. “There is no prospective evidence to support the use of radiation therapy in this [prophylactic] setting. Once bone metastases become painful, they can lead to hospitalization. However, these asymptomatic lesions are often present on bone imaging before they become painful.”

Study Details

Dr. Gillespie and colleagues conducted a randomized phase II trial to compare radiation therapy vs no radiation therapy for high-risk, symptomatic bone metastasis in patients with several types of metastatic cancer. Between May 2018 and August 2021, the investigators enrolled 78 patients with 122 bone metastases from multiple institutions. Patients had a metastatic solid tumor with more than five metastatic lesions on imaging, including at least one but up to five asymptomatic, high-risk bone metastases. This metastatic disease population is distinct from patients with oligometastatic disease (often defined as one to five lesions).

The most common sites of primary cancers were the lungs (27%), breasts (24%), and prostate (22%). Participants were randomly assigned 1:1 to receive radiation to all high-risk bone metastases vs standard care alone. High-risk bone lesions were defined according to size; location in the spine, hip, or sacroiliac joint; or location in the long bones of the extremities. The primary endpoint of reduced skeletal-related events was evaluated in 71 patients. Secondary endpoints included the rates of hospitalization and overall survival. Physicians could choose the dose and fractionation of radiation.

At baseline, patient characteristics were well balanced in each arm. Median patient age was early 60s, and about half were women. Most had an Eastern Cooperative Oncology Group performance status of 0 or 1. About half of each arm used bone-modifying agents.

“About one-third had a more ablative dose of radiation, whereas the others were treated with standard doses,” Dr. Gillespie said.

Key Results

After 1 year, radiation therapy significantly reduced the incidence of skeletal-related events; 1.6% of patients assigned to radiation had a skeletal-related event compared with 29% of patients assigned to standard care (P < .001). Fewer patients assigned to radiation therapy were hospitalized for a skeletal-related event compared with standard care (0 vs 4; P = .045).

At a median of 2.4 years of follow-up, overall survival was significantly longer among patients assigned to radiation therapy, for a relative risk reduction of 51% (P = .016). Additionally, median overall survival among patients with a skeletal-related event was 1 year compared with 1.7 years for those who did not experience a skeletal-related event. In a multivariate analysis, radiation remained significantly associated with overall survival (P = .01). Additionally, a significant association between skeletal-related events and overall survival was found (P = .01), supporting this as the potential pathway to improved overall survival with radiation treatment.

KEY POINTS

  • In a phase II trial, the use of prophylactic radiation therapy for patients with metastatic cancer who had asymptomatic, high-risk bone metastases reduced the incidence of skeletal-related events as well as reduced pain and the number of hospitalizations.
  • This study also showed an overall survival benefit with radiation therapy, although this needs to be confirmed in a phase III trial.

Other benefits of radiation therapy included a reduction in pain at 1 year on the Brief Pain Inventory compared with standard care (P < .05).

Adverse events were fairly uncommon, and no grade 3 events were reported in the radiation arm. For grade 2 or higher adverse events, about a 10% increase was observed in patients treated with radiation vs no radiation.

“This is the first randomized study of prophylactic radiation therapy for asymptomatic bone metastasis. Results indicate a promising new use of radiation therapy. However, we need to identify patients who may benefit to avoid overuse of this modality. In this phase II study, radiation therapy had a significant overall survival benefit, but this needs to be confirmed in a phase III trial,” stated Dr. Gillespie. 

DISCLOSURE: Dr. Gillespie is cofounder of eContour and has received research grants from the Agency for Healthcare Research and Quality and the National Institutes of Health.

REFERENCE

1. Gillespie EF, Mathis NJ, Marine C, et al: Prophylactic radiation therapy vs. standard-of-care for patients with high-risk, asymptomatic bone metastases: A multicenter, randomized phase II trial. 2022 ASTRO Annual Meeting. Abstract LBA 04. Presented October 23, 2022.

The content in this post has not been reviewed by the American Society of Clinical Oncology, Inc. (ASCO®) and does not necessarily reflect the ideas and opinions of ASCO®.

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Benjamin Movsas, MD, who was not involved in the phase II trial of prophylactic radiation for bone metastases, commented: “I thought this was a very important study. We will need to see the details in the final paper, but this approach could make a meaningfuldifference in...

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