Durable Pain Control After Single Radiotherapy to Bone Metastases

Pam Harrison

September 23, 2019

CHICAGO — New data show that a single fraction of high-dose radiation leads to better and more durable pain control than standard multifraction (SMF) radiation therapy in patients with bone metastases predominantly limited to areas outside the spine.

 "Our intent-to-treat analysis revealed that single-fraction stereotactic body radiotherapy (SBRT) with either 12 Gy or 16 Gy was not inferior to SMF radiotherapy with regard to pain control and time to local progression," the investigators report.

"What was very nice for us to learn is that by giving a higher dose in a single fraction, we were able to achieve the best of both words," lead investigator Quynh-Nhu Nguyen, MD, from the University of Texas MD Anderson Cancer Center in Houston, told Medscape Medical News.

"We delivered treatment in a single fraction that is convenient for patients, and we gave a higher dose that was safe and, in this instance, more effective in terms of pain response and also duration of response, so it's a win-win scenario," she said.

"There are at least 16 randomized controlled trials comparing single-fraction vs multifraction radiotherapy in patients with painful bone metastases, so there is level-one evidence to support giving a single fraction in this setting," she explained.

"Yet in both Europe and in the United States, most clinicians still use multifraction radiotherapy," she noted.

"This is probably because there were questions about the durability of response with a single-fraction [approach] given at the lower dose, which meant that patients had to undergo retreatment at a rate that was twice as high as patients who received multifraction radiotherapy," she added.

The new study was presented here at the annual meeting of The American Society for Radiation Oncologists (ASTRO) and was published earlier this year in JAMA Oncology.

The team is now in the process of accruing patients for a phase 3 trial to compare the two  approaches with the goal of changing paradigms and practice, Nguyen commented.

Better Pain Outcomes

The trial was conducted in 160 patients with radiologically confirmed painful bone metastases (mostly nonspine), of whom 81 received sterotactic body radiotherapy (SBRT) at a dose of 12 Gy if lesions were 4 cm or larger or 16 Gy if lesions were under 4 cm in size; the other 79 received SMT radiation therapy delivered at a dose of 30 Gy given in 10 fractions. 

"The primary endpoint evaluated was progression of pain defined as worsening pain score (by at least 2 categories on MD Anderson Symptom Inventory (MDASI), as well as ≥50% increase in dose of opioid medication, reirradiation rate, and pathologic fracture," the investigators note.

At 1 month, 44% of patients in the SBRT arm achieved either a complete response (CR) or a partial response (PR) compared with 30% in the SMF radiation therapy group (P =.18). At 3 months, 38% of SBRT patients maintained either CR or PR vs 21% in the SMF group (p=.05).

Among evaluable patients who received treatment per protocol, there were more pain responders at 2 weeks in the SBRT group, at 62%, than in the SMF radiation group, at 36% (P =.01), and this held true at both 3 and 9 months.

Table. Complete and Partial Responders by Per Protocol Analysis

 

SBRT

SMF RT

P value

3 months

72%

49%

P =.03

9 months

77%

46%

P =.04

SBRT = stereotactic body radiotherapy
SMF RT = standard multifraction radiation therapy

Local progression-free survival (PFS) rates were also higher in the sterotactic group than in the multifraction radiation group at both 1 and 2 years, the investigators point out.

Among patients who were still alive at 1 year and especially at 2 years — and most were not — 100% of patients in the SBRT group were still free of progression at 1 year compared with 90.5% of those in the standard radiation group.

At 2 years (and in very few patients), 100% of patients in the SBRT group were still free of progression vs 75.6% in the standard radiotherapy group (P =.01).

In contrast, no differences in toxic effects were observed between the two treatment groups. For example, 21% of patients in the SBRT group experienced grade 2 nausea compared with 25.3% for those in the standard radiation therapy group.

Rates of grade 3 nausea and rates of grade 2 and 3 vomiting were low in both groups.

Palliation at the Heart of Radiation Oncology 

Asked by Medscape Medical News to comment on the findings, Kenneth Merrell, MD, Mayo Clinic School of Medicine, Rochester, Minnesota, said that it was interesting to see that the use of SBRT in this study led to better pain responses at multiple time points — even within 2 weeks of treatment — and it also appeared to offer more durable control of the irradiated lesion.

However, despite these investigators using a higher radiation dose in the SBRT group than had been used in earlier studies, "the dose spectrum in this study was at the lower end than what is typical for SBRT," noted Merrell, who was not involved with the study. This raises some questions, he said, about what the best dose might really be if SBRT is used for pain relief in patients with metastatic disease.

The characteristic of the tumors was also unknown in this study; this might make a difference, he said, when selecting which patients may be better served by this approach vs the standard approach.

However, as Merrell also stressed, "palliation is at the heart of what we do with radiation oncology and it's always a search to find an optimal palliative treatment that helps relieve pain and suffering while minimizing side effects."

For now, the single-fraction SBRT approach is definitely one option for such patients, Merrell said, but he suggested further questions need to be answered before single-fraction SBRT can be considered standard-of-care in this setting.

Nguyen has disclosed no relevant financial relationships. Merrell declares he has received travel honoraria from AstraZeneca.

American Society for Radiation Oncology (ASTRO) 2019 Annual Meeting: Abstract 100. Presented September 16, 2019.

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