October 23, 2022 – Treating asymptomatic high-risk bone metastases with radiation can reduce painful complications and hospitalizations, and potentially extend overall survival in people whose cancer has spread to multiple sites, according to a Phase II clinical trial. Results from the multicenter, randomized study (NCT03523351) will be presented today at the American Society for Radiation Oncology (ASTRO) Annual Meeting.
The results of the clinical study suggest that radiation oncologists can play a valuable role in treating widespread bone metastases even in the absence of symptoms. Palliative radiation has historically focused 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 treating asymptomatic bone metastases with radiation, and were surprised that the benefits can go beyond convenience.
“It raises concern that radiation to prevent pain could potentially prolong life,” said Erin F. Gillespie, MD, lead author of the study and a radiation oncologist at Memorial Sloan Kettering Cancer Center in New York. “It suggests that treatment to cure the cancer isn’t the only thing that can help people live longer.”
The study arose from the observation that many patients hospitalized for painful bone metastases had evidence of these lesions on imaging scans a few months earlier, said Dr. Gillespie. Although external beam radiation therapy is standard treatment for painful lesions, it has not been used for asymptomatic lesions outside the oligometastatic setting; Generally, patients remain on systemic therapy until the lesions become symptomatic. dr Gillespie and her colleagues wanted to determine “if and when we could intervene before these symptoms appear to prevent hospitalization and debilitation from cancer.”
For the study, researchers identified 78 adults with a metastatic solid tumor malignancy and more than five metastatic lesions, including at least one asymptomatic high-risk bone lesion. Whether a lesion posed a high risk was determined by its size (if it was 2 centimeters in diameter or larger); its location in the junctional spine; whether it was the hip or the sacroiliac joint; or if it was in one of the body’s long bones, such as those found in the arms and legs. There were a total of 122 bone metastases among 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 of care, which could include systemic treatment (such as chemotherapy or targeted drugs) or observation, with or without radiotherapy, to treat all 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 they succumbed to their 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 spinal cord pain, fractures, and compression that require surgery or radiation. They can contribute to a higher risk of death and health care 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, patients in the radiation arm had SREs in 1 of 62 lesions (1.6%) compared to 14 of 49 lesions (29%) in patients receiving standard of 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 receive radiotherapy (hazard ratio 0.50, 95% confidence interval 0.28-0.91, p= 0.02). The median overall survival was 1.1 years for the 11 patients who developed an SRE compared to 1.5 years for the 67 patients who did not develop an SRE.
After the first three months, patients in the radiation arm reported less pain than those in the standard treatment 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 point in the study.
Although it wasn’t in the original study design, Dr. Gillespie, the team conducted an unscheduled analysis of which lesions are most likely to cause SREs. While they expected that metastases in the long bones might cause more fractures and pain, they found that it was metastases in the spine that were most likely to cause subsequent pain, cord compression, or fractures. However, the numbers are small and need further analysis for confirmation.
Treating these lesions with “even low doses of radiation seemed appropriate to prevent the lesion from progressing and causing problems,” said Dr. Gillespie.
dr Gillespie stressed that due to the small size of the study, their results, while hypothesized, were not definitive and a larger study was needed to replicate and expand on these analyses. “Our study results add to a growing area of study examining the potential of early supportive care, but they have yet to be confirmed in a larger Phase III study,” she explained.
She also said that future research should try to answer questions like, “Does this apply to someone in the early course of their metastatic disease who may not have symptomatic lesions? At what point would they benefit from an intervention involving radiation? There are many patients with multiple metastatic sites, but how do we identify the lesions that are most likely to become problematic?”
“And once we’ve confirmed that this is the right thing to do,” she said, “how do we make sure that patients who could benefit get access to this treatment?”
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