Treating high-risk asymptomatic bone metastases with radiation can relieve pain and prolong survival

Treating high-risk asymptomatic bone metastases with radiation can relieve pain and prolong survival

A phase II clinical trial suggests that treating high-risk asymptomatic bone metastases with radiation may reduce painful complications and hospital stays and potentially extend overall survival in people whose cancer has spread to multiple sites. Results from the multicenter, randomized trial (NCT03523351) will be presented today at the American Society for Radiation Oncology (ASTRO) Annual Meeting.

Clinical trial results suggest that radiation oncologists can play a valuable role in the management of extensive bone metastases, even in the absence of symptoms. The focus of palliative radiation has historically been on relieving existing pain and other symptoms when a patient's cancer is no longer considered curable. Researchers hoped to show that painful complications could be prevented by irradiating asymptomatic bone metastases and were surprised that the benefits might extend beyond comfort.

It's thought-provoking that radiation to prevent pain could potentially prolong life. It suggests that treatment to cure cancer is not the only way to help people live longer.”

Erin F. Gillespie, MD, lead study author and radiation oncologist, Memorial Sloan Kettering Cancer Center in New York

The study arose from the observation that many patients hospitalized for painful bone metastases had evidence of these lesions on imaging scans several months earlier, said Dr. Gillespie. Although external beam radiation therapy is included in the treatment of painful lesions, it has not been used in asymptomatic lesions outside of the oligometastatic setting; In general, patients continue to receive systemic therapy until lesions become symptomatic. Dr. Gillespie and her colleagues wanted to find out “if and when we can intervene before these symptoms appear to prevent hospitalization and cancer-related debility.”

For the study, researchers identified 78 adults with a metastatic malignant solid tumor and more than five metastatic lesions, including at least one asymptomatic high-risk bone lesion. Whether a lesion was high risk was determined by its size (if it was 2 centimeters or larger in diameter); its location in the connecting spine; whether it was the hip or the sacroiliac joint; or if it was in one of the long bones of the body, such as those found in the arms and legs. A total of 122 bone metastases occurred in all included patients.

Among study participants, the most common primary cancers 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 agents) or observation with or without radiation therapy to treat any of their high-risk bone metastases. Radiation doses varied but were typically low (i.e., non-ablative). All patients were followed for at least 12 months or until death from disease.

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

The researchers found that treating the 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 in the radiation arm, compared with 14 of 49 lesions (29%) in patients receiving standard care (p < 0.001). Significantly fewer patients in the radiation arm were hospitalized for SREs (0 vs. 4, p = 0.045).

After a median follow-up of 2.4 years, overall survival was significantly longer in patients who received radiotherapy than in 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 experience an SRE.

After the first three months, patients in the radiation arm reported less pain than those in the standard care arm (p<0.05), a trend that continued but was no longer statistically significant for the remainder of the study. There were no significant differences in quality of life between the two arms at any time during the study.

Although this was not in the original study design, Dr. Gillespie said the team conducted an unplanned analysis of which lesions were most likely to cause SREs. While they expected that these might cause more fractures and pain in the long bones, they found that it was metastases in the spine that were most likely to cause subsequent pain, spinal cord compression or fractures. However, the numbers are small and require further evaluation to confirm.

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

Dr. Gillespie emphasized that due to the small size of the study, the results are hypothesis-generating but not definitive and a larger study is needed to repeat and expand these analyses. “Our study results add to a growing field of study examining the potential of early supportive care, but they still need to be confirmed in a larger Phase III trial,” she said.

She also said future research should aim to answer questions such as: "Is this true for someone early in their metastatic disease who may not have symptomatic lesions? At what point would they benefit from radiation intervention? There are many patients." with multiple metastatic sites, but how do we identify the lesions that are most likely to become problematic?”

“And if we confirm that this is the right thing to do,” she said, “how do we ensure that patients who could benefit from this have access to this treatment?”

Source:

American Society for Radiation Oncology

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