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Treating spinal lesions with fewer, higher doses of radiation reduces pain more effectively

Randomized phase II/III trial first to show SBRT superior to conventional radiation treatments in alleviating pain from spinal metastases
Monday, October 26, 2020

ARLINGTON, Va. October 26, 2020 — A new study shows using fewer and higher doses of high-precision radiation therapy is a more effective approach for treating painful spinal tumors than conventional radiation therapy. More than twice as many patients treated with stereotactic body radiation therapy (SBRT) reported an enduring, complete reduction in pain, compared to those treated with conventional radiation. Findings from the CCTG SC24 Canadian phase II/III trial (NCT02512965) will be presented today at the American Society for Radiation Oncology (ASTRO) Annual Meeting.

“This is the first phase III randomized trial that has shown an improvement with dose escalation for painful spinal lesions,” said lead author Arjun Sahgal, MD, a professor and deputy chief of radiation oncology at the Sunnybrook Health Sciences Centre of the University of Toronto. “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.”

Spinal metastases are lesions on the spine that have spread from cancer that first occurred elsewhere in the body. While cancer can spread to any part of the body, two-thirds of patients with cancer will experience bone metastases, most commonly in the spine; in fact, research has shown that 70% of patients with terminal cancer develop spinal metastases before they die. Tumors that grow in the spine can cause pain, bone instability and neurologic symptoms, such as weakness, difficulty walking and bowel and bladder problems. Once cancer has spread to the spine, it is rarely considered curable, though there are treatment options to help patients live longer with less pain.

Radiation therapy is commonly used to relieve the pain of spinal metastases, by shrinking the tumors and reducing inflammatory cells. It is delivered through multiple fractions of lower-dose, conventional radiation (CRT), or though SBRT, which allows radiation oncologists to target tumors precisely with very high doses of radiation in fewer fractions. No definitive standard-of-care dose has yet been established for radiation therapy to treat painful spinal metastases.

In this phase II/III study from the Canadian Cancer Trials Group, researchers randomized patients whose primary tumors (mainly in the breast, urinary tract or lung) had metastasized to painful spinal lesions. Patients were treated with either two SBRT fractions for a total dose of 24Gy (n=114), or five CRT fractions for a total dose 20Gy (n=115). Eligible patients reported initial pain scores of greater than two on a scale of 1-10 (with a median score of five) using the Brief Pain Inventory. Pain scores were measured again at three and six months.

Patients in both treatment groups experienced reductions in pain from spinal metastases. After three months, 35% of patients in the SBRT arm of the trial, compared to 14% of those in the CRT arm, reported a complete response rate, or no remaining pain from their lesions (p<0.001). Patients continued pain free for up to six months, when the study concluded, with 32% of those in the SBRT arm reporting no pain compared to 16% of those in the CRT arm (p=0.004).

“This was not just, ‘Oh, I feel a little bit better,’” said Dr. Sahgal, adding that patients experienced the reduction in pain without increasing the use of pain medications. Multivariable analyses confirmed that the type of radiation was the independent factor driving pain response, not characteristics such as the patient's age, performance status or type of primary cancer. “We applied a very stringent trial design to focus on the impact of radiation,” said Dr. Sahgal. “It was the radiation treatment that led to the improvement.”

There was no difference between the study arms in radiation site-specific progression-free survival or overall survival. After three months, 92% of patients in the SBRT arm and 86% of those in the CRT arm were cancer-free at the treated site (p=0.4); the rates at six months were 75% and 69% (p=0.4).

In terms of adverse events, both treatments were safe with respect to fractures and there was no radiation damage to the spinal cord observed in either cohort. Overall, both arms had low rates of serious adverse events and there were no fatal events.

The study also found higher satisfaction from patients in the SBRT arm with quality-of-life measures related to financial considerations, although other quality of life measures did not differ between the two groups. “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.”

A different study reported at ASTRO’s 2019 Annual Meeting (RTOG 0631) found no difference in pain reduction between patients treated for spinal metastases with SBRT and those treated with conventional radiation. In Dr. Sahgal's study, however, patients were given a higher dose of radiation, an SBRT dose of 24Gy in two fractions, compared to the earlier trial's dose of 16/18Gy in a single fraction.

Dr. Sahgal said he was motivated to conduct this research out of frustration over the years with being unable to adequately relieve the suffering of 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.”

CCTG SC24/TROG 17.06: A randomized phase II/III study comparing 24Gy in 2 stereotactic body radiotherapy (SBRT) fractions versus 20Gy in 5 conventional palliative radiotherapy (CRT) fractions for patients with painful spinal metastases (Abstract LBA-2)

Abstract LBA-2, American Society for Radiation Oncology (ASTRO) 2020 Annual Meeting

A. Sahgal1, S. D. Myrehaug2, S. Siva3, L. Masucci4, M. C. Foote5, M. Brundage6, J. Butler7, E. Chow2, M. G. Fehlings8, Z. Gabos9, J. Greenspoon10, M. Kerba11, Y. Lee12, M. C. Liu13, P. Maralani14, I. Thibault15, R. Wong16, M. Hum17, K. Ding18, and W. Parulekar17; 1Department of Radiation Oncology, Sunnybrook Odette Cancer Centre, University of Toronto, Toronto, ON, Canada, 2Department of Radiation Oncology, Odette Cancer Centre, Sunnybrook Health

Purpose/Objective(s): To compare complete response rates (CR) for pain between high dose SBRT and conventional low dose CRT to a painful site of spinal metastases.

Materials/Methods: In this randomized Phase 2/3 trial (NCT02512965), patients with a de novo site of painful spinal metastases were randomized (1:1) to 24Gy in 2 SBRT fractions or 20Gy in 5 CRT fractions. Inclusion criteria consisted of a target site spinal metastases (≤3 consecutive metastatically involved spinal segments) arising from a solid primary tumor causing a pain score of ≥2 using the Brief Pain Inventory (BPI), an ECOG of 0-2 and not mechanically unstable per the Spinal Instability Neoplasia Score classification system. Stratification factors were extra-osseous extension (yes/no) and radioresistant vs. radiosensitive type. The primary endpoint was the CR rate for pain in the treatment area at 3 months post-radiation using International Consensus Pain Response Endpoints. Secondary endpoints included the 6-month pain CR rate, radiation site progression-free-survival (RSS PFS: defined as the time from randomization to local progression or death), and quality of life (QoL). The study had an 80% power to show a 17% improvement in the 3-month CR rate in favor of the SBRT arm. Efficacy analyses were intent-to-treat and safety analyses were as treated. Adverse events (AE) were evaluated per the Common Terminology Criteria for Adverse Events version 4.0 (CTCAE v 4.0). The trial sponsor was the Canadian Cancer Trials Group (CCTG) in collaboration with the Trans Tasman Radiation Oncology Group (TROG).

Results: Of the 229 enrolled patients between Jan 2016 to Sept 2019, 115 were randomized to CRT and 114 to SBRT of which 4 patients in the SBRT arm were either ineligible or withdrew prior to radiation. 38 patients (22 in the CRT and 16 in the SBRT arm) were not evaluable for the primary endpoint. The median baseline worst pain score was 5 (range, 2-10) and SINS was 7 (range, 3-12) in both arms, and median follow-up was 6.7 months. At 3 months, 16/115 (14%) in the CRT arm vs. 40/114 (36%) in the SBRT arm (p<0.001) achieved a CR to pain. Significance was retained in multivariable analyses (MVA, p<0.001) and the risk ratio (RR) was 1.33 (95% C.I=1.14–1.55) favoring SBRT. At 6 months, 18/115 (16%) in the CRT arm vs. 37/114 patients (33%) in the SBRT arm achieved a CR (p=0.004), significance retained on MVA (p<0.001), and the RR was 1.24 (95% C.I. 1.07 – 1.44) favoring SBRT. The 3-month RSS PFS for CRT vs. SBRT was 86% vs. 92% (p=0.4), and at 6 months was 69% vs. 75% (p=0.42), respectively. For QoL outcomes, only financial perception at 1 month significantly differed (p=0.03) favoring SBRT. There were 20 (17%) vs. 12 (11%) post-radiation vertebral compression fractures, and 2 (2%) vs no (0%) patient progressed to malignant epidural spinal cord compression, in the CRT vs. SBRT arm, respectively. Grade 2+ AE were observed in 12% and 11% in the CRT and SBRT arms, respectively, and no Grade 5 events.

Conclusion: SBRT is superior to CRT in improving the CR rate for pain at 3 and 6 months post-radiation.

About the Canadian Cancer Trials Group

The Canadian Cancer Trials Group (CCTG) is a cancer clinical trials research cooperative that runs phase I-III trials to test anti-cancer and supportive therapies at over 85 institutions across Canada and more internationally. CCTG is one of the national programs of the Canadian Cancer Society (CCS) and from its operational centre at Queen’s University, the group has supported over 500 trials in over 40 countries, aimed at improving survival rates and quality of life for all people with cancer.

Media contact: Lisa Callahan, Communications Leader, Canadian Cancer Trials Group