Stereotactic body radiation therapy (SBRT) was superior to conventional radiation therapy in reducing pain from spinal metastases in a phase II/III study reported at the virtual edition of the 2020 American Society for Radiation Oncology (ASTRO) Annual Meeting.¹ More than twice as many patients with painful 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 SBRT vs conventional radiation therapy. The complete responses remained durable at 6 months and were statistically significant favoring the SBRT arm.

“This is the first phase III randomized trial showing that dose escalation with modern radiation therapy techniques improves pain outcomes for patients with spinal bone metastases,” stated lead author Arjun Sahgal, MD, Professor and Deputy Chief of Radiation Oncology at Sunnybrook Health Sciences Centre of the University of Toronto, Canada. “Pain has a detrimental effect on 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 for this trial should be offered SBRT.”

“This is the first phase III randomized trial showing that dose escalation with modern radiation therapy techniques improves pain outcomes for patients with spinal bone metastases.”

— Arjun Sahgal, MD

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Two-thirds of patients with cancer will experience bone metastases, most commonly in the spine. A total of 70% 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, the cancer is rarely curable, and the goal of treatment becomes 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 whether 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 said.

Study Details

The Canadian Cancer Trials Group (CCTG) study enrolled 229 patients with painful metastases in up to three contiguous segments of the spine and randomly assigned them 1:1 to treatment with SBRT (n = 114) or conventional radiation therapy (n = 115). Patients reported baseline pain scores of at least 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 Neoplastic Score (SINS) at 3 and 6 months, and overall survival. The 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 2019.

Key Results

An intent-to-treat analysis of pain response was performed on all 229 patients, and safety analysis was performed on 225 of them.

At 3 months, both groups reported reductions in pain due to spinal metastases. Complete response rates were 35% with SBRT vs 14% with conventional radiation therapy (P < .001); partial response rates were 18% and 25%, respectively. Stable disease was observed in 24% and 30%, respectively. Progressive disease was reported in 6% and 12%, respectively. The mean change in total SINS was –0.94 for SBRT and –0.49 for conventional radiation therapy.

At 6 months, the difference between the groups in complete pain response held up. Complete pain response was reported in 32% of the SBRT group vs 16% of the conventional-radiotherapy 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 free of pain at 3 months with SBRT vs conventional radiation therapy was 3.47, and at 6 months, it was 2.45 (P = .007).

No difference was observed between the 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-radiotherapy arm were cancer-free at the treated site. At 6 months, the rates of site-specific progression-free survival were 75% and 69%, respectively.

Both treatments were considered to be 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.

Quality-of-Life Outcomes

Patients treated with SBRT had higher satisfaction on quality-of-life measures related to financial considerations. However, 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 to get two treatments rather than five. Even though the treatment complexity was greater [with SBRT], it was better for the patient,” Dr. Sahgal said.

Dr. Sahgal said that for many years, he was frustrated with inadequate pain control for patients with advanced-stage cancer. “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,” he noted.

Additional Commentary

Press conference moderator Sue S. Yom, MD, PhD, of the University of California San Francisco, said this was one of five practice-changing studies to be featured at the first ASTRO press conference.

According to Dr. Yom, the advantages of stereotactic radiation techniques such as SBRT include delivery of higher doses of radiation with shorter treatment times, “which may be a special advantage during the COVID-19 pandemic.” However, SBRT is more expensive, more technically complex, requires additional resources, and takes more time to plan than conventional radiation techniques.

“Evidence to justify SBRT was presented in the Sahgal trial. This is a practice-changing study.”

— Sue S. Yom, MD, PhD

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“Evidence to justify SBRT was presented in the SC.24 trial. This is a practice-changing study. Increased doses of radiation to metastatic sites over only two fractions of SBRT allowed significantly more patients to experience complete pain relief. The actual resolution of spinal metastases was also superior [in the SBRT arm],” she said.

“Quality of life assessed by patients showed that SBRT was superior in terms of financial perception. Even a difference between two vs five treatments led to a difference in quality of life based on financial considerations. So, this is significant to patients and is an additional reason in support of SBRT in these metastatic patients,” Dr. Yom said.

DISCLOSURE: Dr. Sahgal has served in a leadership role for Elekta AB; has received honoraria from AbbVie, BrainLAB, ElektaAB, and Varian Medical Systems; has served as a consultant or advisor to AbbVie, BrainLAB, Elekta, Merck, Roche, Varian, and VieCure; has received institutional research funding from Elekta and Varian Medical Systems; holds patents or other intellectual property in clustering software for Gamma Knife treatment planning; has been reimbursed for travel, accommodations, or other expenses by BrainLAB, Elekta, and Varian Medical Systems; and has held other relationships with Accuray, BrainLAB, Elekta, Elekta AB, Elekta MR Linac Research Consortium, Elekta Spine, International Stereotactic Radiosurgery Society, Medtronic Kyphon, Oligometastases and Linac Based SRS Consortia, and Varian Medical Systems. Dr. Yom has received institutional research funding from BioMimetix, Bristol Myers Squibb, Genentech, and Merck and holds patents or other intellectual property in Springer and UpToDate.

REFERENCE

1. Sahgal A, Myrehaug SD, Siva S, et al: CCTG SC.24/TROG 17.06: A randomized phase II/III study comparing 24 Gy in 2 stereotactic body radiotherapy fractions vs 20 Gy in 5 conventional palliative radiotherapy fractions for patients with painful spinal metastases. 2020 ASTRO Annual Meeting. Abstract LBA 2. Presented October 26, 2020.