Using radiation to treat high-risk, asymptomatic bone metastases could reduce painful complications and hospitalizations, and could potentially extend overall survival in patients whose cancer has spread to multiple sites, according to new research. Presented at the American Society for Radiation Oncology (ASTRO) Annual Meeting, the results of the multicenter, randomized trial also suggest that radiation oncologists may play a valuable role in treating widespread bone metastases even in the absence of symptoms (Abstract LBA 04).
Noting that palliative radiation has typically focused on reducing patients' existing pain and other symptoms when a patient's cancer is no longer considered curable, researchers from Memorial Sloan Kettering Cancer Center "hoped to show that painful complications could be prevented by treating asymptomatic bone metastases with radiation and were surprised to find the benefits may extend beyond comfort."
Study Details
For this study, investigators identified 78 adults with a metastatic solid tumor malignancy and more than five metastatic lesions, including at least one asymptomatic high-risk bone lesion. These lesions were deemed to be high risk based on their size (at least 2 cm or more in diameter), location in the junctional spine, whether the lesion involved the hip or sacroiliac joint, or if the lesion was located in one of the long bones of the body, such as those found in arms and legs. There were a cumulative 122 bone metastases among all enrolled patients.
Among study participants, the most common types of primary cancer were lung (27%), breast (24%), and prostate (22%). Participants were randomly assigned to receive standard treatment, which could include systemic treatment (such as chemotherapy or targeted agents) or observation, with or without radiation therapy to treat all of their high-risk bone metastases. Radiation doses varied but were typically low.
All patients were followed for at least 12 months or until they succumbed to their disease, the authors noted, adding that the study's primary endpoint was to determine whether treating asymptomatic lesions could prevent skeletal-related events (SREs), which typically include pain, fractures, and compression of the spinal cord that requires surgery or radiation. SREs can contribute to a higher risk of death and higher health care costs.
Overall, the researchers found that treating the asymptomatic lesions with radiation reduced the number of SREs and SRE-related hospitalizations, as well as extending overall survival, compared to people who received no radiation.
At the end of one year, for patients on the radiation arm, SREs occurred in 1 of 62 lesions (1.6%), compared to 14 of 49 lesions (29%) for those receiving standard care (p<0.001). Significantly fewer patients in the radiation arm were hospitalized for SREs. And, after a median 2.4 years of follow-up, overall survival was significantly longer for patients who received radiation therapy, compared to those who did not. Median overall survival was 1.1 years for the 11 patients who experienced an SRE, compared to 1.5 years for the 67 patients who had no SREs.
After the first 3 months, patients in the radiation arm reported less pain than those in the standard care arm, "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," according to the authors.
Fewer Side Effects
"Radiation is the standard of care to relieve pain from symptomatic bone metastases," stated Erin Gillespie, MD, Assistant Attending Radiation Oncologist at Memorial Sloan Kettering Cancer Center, and lead author of the study. "To date, no randomized data supports radiation for the prevention of symptoms in metastatic disease. We aimed to learn if treatment with radiation could prevent future complications related to high-risk bone metastases, even in the absence of pain or other symptoms."
Gillespie noted that the trial provides evidence that the side effects of radiation for high-risk bone metastases are typically minimal-no Grade 3 toxicities and only 10 percent Grade 2 toxicities compared to no radiation-and "can in fact improve overall pain-related quality of life," she said, adding that patients treated with radiation experienced fewer skeletal-related events and subsequent hospitalization.
This study is the first to support the use of radiation as a preventive treatment in the metastatic setting, Gillespie continued. She stressed the importance of understanding the types of high-risk lesions that were included in the study-junctional spine lesions or lesions 2 cm or greater in size, for example-and the fact that the majority of patients were already referred to radiation oncology for other indications.
"We don't yet know how broadly the findings can be applied to all metastatic patients and ideally should wait for a confirmatory trial before making broad practice change," Gillespie emphasized. "Bone-modifying agents like bisphosphonates that promote bone health and reduce skeletal events tend to be underused in routine practice (50% in this study), which is in part due to concerns of toxicity, especially with long-term use, raising the potential for low-toxicity targeted radiation as an alternative option for helping patients with bone metastases maintain quality of life."
Mark McGraw is a contributing writer.