Treating asymptomatic, high-risk bone metastases with radiation can reduce painful complications and hospitalizations and possibly prolong overall survival in people whose cancer has spread to multiple sites, a phase II clinical trial shows. The results of the multicenter randomized trial (NCT03523351) will be presented today at the American Society for Radiation Oncology (ASTRO) Annual Meeting.

The results of clinical trials show radiation oncologists may play an important role in the treatment of widespread bone metastases even in the absence of symptoms. Palliative radiation has historically focused on reducing existing pain and other symptoms when a patient’s cancer is no longer considered curable. The researchers hoped to show that painful complications could be prevented by treating asymptomatic bone metastases with radiation, and were surprised to find that the benefits could extend beyond comfort.

“That radiation to prevent pain could potentially extend life is mind-boggling,” said Erin F. Gillespie, MD, lead study author and radiation oncologist at Memorial Sloan Kettering Cancer Center in New York. “This suggests that cancer treatment is not the only thing that can help people live longer.”

The study follows the observation that many patients hospitalized for painful bone metastases have evidence of these lesions on imaging scans months earlier, Dr. Gillespie said. Although external beam radiation therapy is the standard of care for painful lesions, it has not been used for asymptomatic lesions except for oligometastatics; generally, patients remain on systemic therapy until the lesions become symptomatic. Dr. Gillespie and her colleagues wanted to determine “if and when we can intervene earlier these symptoms occur to prevent hospitalization and debilitation from cancer.”

For the study, researchers identified 78 adults with metastatic solid malignancy and more than five metastatic lesions, including at least one asymptomatic high-risk bone lesion. Whether the lesion was high-risk was determined by its size (if it was 2 centimeters or more in diameter); its location at the junction of the spine; whether it affects the hip joint or the sacroiliac joint; or if it was in one of the long bones of the body, such as those in the arms and legs. Between all enrolled patients, there were a cumulative 122 bone metastases.

Among the participants of the study, the most common types of first cancer were lung (27%), breast (24%) and prostate (22%). Participants were randomly assigned to standard treatment, which could include systemic treatment (such as chemotherapy or targeted drugs) or observation, with or without radiation therapy for all high-risk bone metastases. Radiation doses varied but were generally low (ie, not ablative). All patients were followed for at least 12 months or until they succumbed to their disease.

The primary endpoint was to determine whether treatment of asymptomatic lesions could prevent skeletal-related events (SREs), a common and often painful and debilitating complication a bone metastases. SREs include pain, fractures, and compression of the spinal cord, requiring surgery or radiation. They can contribute to increased risk of death and higher health care costs.

The researchers found that treating asymptomatic lesions with radiation reduced the number of SREs and SRE-related hospitalizations and increased overall survival compared to people who did not receive radiation. At the end of one year, SREs occurred in 1 of 62 lesions (1.6%) in patients receiving radiation compared with 14 of 49 lesions (29%) in those receiving standard care (p

After a median follow-up of 2.4 years, overall survival was significantly greater for patients treated with radiation therapy, compared to those who did not (hazard ratio 0.50, 95% confidence interval 0.28-0.91, p=0.02). Median overall survival was 1.1 years for the 11 patients who experienced an SRE, compared with 1.5 years for the 67 patients who did not have an SRE.

After the first three months, patients in the radiation group reported less pain than those in the standard treatment group (with

Although it wasn’t in the original plan of the study, Dr. Gillespie said the team did an unplanned analysis of what injuries were most likely to cause SREs. While they expected metastases in long bones to cause more fractures and pain, they found that metastases in the spine were more likely to cause subsequent pain, spinal cord compression, or fracture. However, the numbers are small and further evaluation will be needed to confirm them.

Treating these lesions “even with low doses of radiation seemed to be sufficient to prevent the lesions from progressing and causing problems,” Dr. Gillespie said.

Dr. Gillespie emphasized that due to the small size of the study, his findings, although hypothesis-generating, were not definitive, and a larger study was needed to replicate and extend this analysis. “Our trial results contribute to a growing field of research exploring the potential of early adjuvant therapy, but they still need to be confirmed in a larger phase III trial,” she explained.

She also said that future studies should seek to answer questions such as: “Does this apply to someone with early metastatic disease who may not have any symptomatic lesions? At what point would they benefit from radiation intervention? There are many patients with multiple sites of metastases, but how do you identify the lesions that are most likely to become problematic?”

“And once we confirm that this is correct,” she said, “how do we ensure that patients who can benefit get access to this treatment?”