Stereotactic body radiation therapy (SBRT) was superior to conventional radiation therapy in reducing pain from spinal metastases in a phase II/III study reported by Arjun Sahgal, MD, and colleagues at the 2020 American Society for Radiation Oncology (ASTRO) Annual Meeting (Abstract LBA 2). More than twice as many patients with spinal metastases experienced complete reduction in pain lasting at least 6 months when treated with SBRT vs conventional radiation therapy.
At 3 months, there was a 21% absolute increase in complete response to pain in patients randomly assigned to receive SBRT vs conventional radiation therapy. The complete responses remained durable at 6 months and were statistically significant in favoring the SBRT arm.
“This is the first phase III randomized trial that has shown that dose escalation with modern radiation therapy techniques improves pain outcomes for patients with spinal bone metastases,” said first study author Dr. Sahgal, Professor and Deputy Chief of Radiation Oncology at Sunnybrook Health Sciences Center of the University of Toronto, Canada. ““Pain deteriorates a patient’s quality of life and nobody with advanced cancer should have to endure this kind of pain. Patients with painful spinal metastases who meet the eligibility criteria should be offered this treatment.”
"Patients with painful spinal metastases who meet the eligibility criteria should be offered this treatment."— Arjun Sahgal, MD
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Two-thirds of patients with cancer will experience bone metastasis, most commonly to the spine. Seventy percent of patients with terminal cancer will develop spinal metastases prior to death. Spinal metastases are painful and cause bone instability and neurologic symptoms that can include difficulty walking as well as bowel and bladder problems. Once spinal metastases are present, cancer is rarely curable—the goal of treatment at such a stage is palliative care to alleviate pain.
Radiation to the spine reduces tumor volume and pain. Conventional radiation therapy is delivered via multiple fractions of lower-dose radiation, whereas SBRT utilizes very high doses of radiation in fewer fractions, allowing for more focal delivery of radiation and shorter treatment times.
“No definitive standard of care dose has yet been established for radiation therapy to treat painful spinal metastasis,” Dr. Sahgal told the virtual meeting audience.
“The goal of the study was to evaluate the role of spinal SBRT and determine if we could improve complete pain response for painful spinal metastases. We used an SBRT scheme developed at the University of Toronto [24 Gy in two SBRT fractions] and compared it with standard conventional radiation therapy [20 Gy in five fractions],” he explained.
Study Details
The Canadian Cancer Trials Group study enrolled 229 patients with metastases in up to three contiguous segments of the spine. They were randomly assigned 1:1 to receive treatment with SBRT (n = 114) or conventional radiation (n = 115). Patients reported baseline pain scores of > 2 on the Brief Pain Inventory (scale of 1–10), with a median score of 5.
The primary endpoint was complete pain response rate at 3 months. Secondary endpoints included complete response rate at 6 months, radiation site–specific progression-free survival at 3 and 6 months, quality of life, change in the total Spinal Instability Score (SINS) score at 3 and 6 months, and overall survival. SINS is used to assess tumor-related instability of the vertebral column.
Initially, the study was designed as a phase II randomized controlled trial; it was converted to a phase III randomized controlled trial without interruption of accrual between January 2016 and September 209.
An intent-to-treat analysis of pain response was performed on all 229 patients, and safety analysis was performed on 225.
Reduction in Pain
At 3 months, both groups reported reductions in pain due to spinal metastases. Complete response rates were 35% for the SBRT arm vs 14% for the conventional radiation therapy arm (P < .001); partial response rates were 18% and 25%, respectively.
Stable disease was observed in 24% and 30% of patients, respectively. Progressive disease was reported in 6% and 12%. Mean change in total SINS score was −0.94 for SBRT and −0.49 for conventional radiation therapy.
At 6 months, the difference between groups in complete pain response was maintained. Complete pain response was reported in 32% of the SBRT group vs 16% of the conventional radiation therapy group (P = .004).
In a multivariate analysis for complete pain response at 3 and 6 months adjusted for age, sex, primary cancer type, performance status, and pain score at baseline, only SBRT emerged as a significant factor. The odds ratio of being pain-free at 3 months with SBRT vs conventional radiation therapy was 3.47 and at 6 months, 2.45 (P = .007).
No difference was observed between treatment arms in site-specific progression-free survival or overall survival. After 3 months, 92% of those in the SBRT arm and 86% of those in the conventional radiation therapy arm were cancer-free at the treated site. At 6 months, the rates of site-specific progression-free survival were 75% and 69%, respectively.
Safety and Quality of Life
Both treatments were safe in terms of fracture rates, and no spinal cord damage was reported in either arm of the study. Both arms had similar and low rates of serious adverse events, and no deaths occurred due to treatment.
Patients treated with SBRT had higher satisfaction on quality-of-life measures related to financial considerations, but other quality of life measures were similar between the two treatment arms.
"Patients felt they were in a financially better position coming to the hospital and getting two treatments, rather than five,” Dr. Sahgal said. “Even though the complexity of the treatment was greater, it was better for the patient.”
Dr. Sahgal said that for many years, he was frustrated with inadequate pain control for patients with advanced-stage cancer. “We saw we were getting improvements in pain, but our patients were not pain-free. With the development of SBRT, and spinal SBRT in particular, we started to wonder if we could do better. With these new research results, we think we can.”
Disclosure: For full disclosures of the study authors, visit myastroapp2020.com.
