Radiation therapy for high-risk, asymptomatic bone metastases can prevent pain and prolong life

A phase II clinical trial showed that treating high-risk, asymptomatic bone metastases with radiation therapy may reduce painful complications and hospitalizations, and may prolong overall survival in patients whose cancer has spread to multiple sites
.
The results of the multicenter randomized trial (NCT03523351) will be presented
today at the annual meeting of the American Society of Radiation Oncology (ASTRO).

Clinical trial results suggest that radiation oncologists may play a valuable role in treating widespread bone metastases, even in the absence of symptoms
.
Palliative radiation therapy has historically focused on relieving pre-existing pain and other symptoms
when a patient's cancer is no longer considered curable.
The researchers hoped that treating asymptomatic bone metastases with radiation therapy could prevent painful complications and were surprised to learn that the benefits might be more than just comfort
.

The study's lead author, Irene F.
Gillespie, MD
, a radiation oncologist at Memorial Sloan Kettering Cancer Center in New York, said, "It is thought-provoking that preventing pain through radiation may prolong life.
" "This shows that treating cancer is not the only way to
help people live longer.
"

Dr.
Gillespie said the study stemmed from the observation that many patients hospitalized for painful bone metastases had evidence
of these lesions on imaging scans months earlier.
Although external beam radiation therapy is the standard treatment for painful lesions, it has not been used for asymptomatic lesions other than less metastatic lesions; In general, patients continue systemic therapy until symptoms
develop.
Dr.
Gillespie and her colleagues wanted to determine "if and when we can intervene before these symptoms appear to prevent hospitalization and frailty
caused by cancer.
" ”

In this study, researchers identified 78 adults with metastatic solid tumor malignancies and more than 5 metastatic lesions, including at least one asymptomatic high-risk bone lesion
.
The size of the lesion (if the diameter is greater than or equal to 2 cm) determines whether it is at high risk; Its location is at the junction; whether it involves the hip or sacroiliac joint; Or it is in a long bone of the body, such as bones found in arms and legs
.
Of all enrolled patients, there were a cumulative total of 122 bone metastases
.

Among study participants, the most common types of primary cancers were lung cancer (27%), breast cancer (24%), and prostate cancer (22%)
.
Participants were randomly assigned to receive standard treatment, including systemic therapy (such as chemotherapy or targeted drugs) or observation, with or without radiation therapy for all high-risk bone metastases
.
The radiation dose varies, but is usually lower (i.
e.
does not ablate).

All patients were followed for at least 12 months until they died of the disease
.

The primary endpoint was to determine whether treating asymptomatic lesions prevented bone-related events (SREs) – a common, often painful and debilitating complication
of bone metastasis.
SREs include pain, fractures, and spinal cord compression, requiring surgery or radiation therapy
.
They can lead to a higher risk of death and higher health care costs
.

The researchers found that treating asymptomatic lesions with radiotherapy reduced the number of SREs and SRE-related hospitalizations and prolonged overall survival compared to patients who did not receive radiotherapy
.
One year later, SREs (p<0.
001) developed in 1 of 62 lesions in patients receiving radiation therapy
, compared with 14 (29%) of 49 lesions in patients receiving standard care.
There was a significant decrease in hospitalization for SREs in the radiotherapy group (0 vs.
4, p=0.
045).

With a median follow-up of 2.
4 years, overall survival was significantly longer in patients who received radiotherapy (hazard ratio 0.
50, 95% confidence interval 0.
28 to 0.
91, p=0.
02) compared with those who did not receive radiotherapy.

The median overall survival of 11 patients with SRE was 1.
1 years, compared with 1.
5 years
for 67 patients without SREs.

After the first three months, patients in the radiotherapy group reported less pain than those in the standard care group (p<0.
05), a trend that continued, but was no longer statistically significant
in the rest of the study.
At any time in the study, there was no significant difference
in quality of life between the two groups.

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 metastases in long bones to cause more fractures and pain, they found that metastases in the spine were most likely to cause subsequent pain, spinal cord compression, or fractures
.
However, the number is small and requires further evaluation to confirm
.

Dr.
Gillespie said treating these lesions with "even low doses of radiation seems to be sufficient to prevent the lesions from worsening and causing problems.
"

Dr.
Gillespie stressed that due to the study's small size, its findings, while generating hypotheses, are not conclusive, and larger studies are needed to replicate and expand these analyses
.
"Our trial results add to a growing area of research into the potential of early supportive care, but they still need to be confirmed
in larger phase III trials," she explains.

She also said future research should seek to answer questions such as: "Does this apply to people who may not have any symptomatic lesions in the early course of metastatic disease?" Under what circumstances would they benefit from radiation intervention? Many patients have multiple metastases, but how do we identify those lesions that are most likely to have problems?"

"And, once we confirm that it's the right thing to do," she says, "how do we make sure that patients who might benefit have access to this treatment?"