Single-dose radiotherapy should be standard for metastatic spinal canal compression
CHICAGO — Patients with metastatic spinal canal compression who received a single radiation dose achieved ambulatory status and OS comparable to those who received a multifraction dose administered over 1 week, according to results of a prospective randomized phase 3 noninferiority trial presented at ASCO Annual Meeting.
“A single dose of radiotherapy, at least in our minds, is now recommended in this setting,” Peter Hoskin, MD, FCRP, FRCR, oncologist at Mount Vernon Cancer Centre in Middlesex, United Kingdom, said during a press conference. “This has enormous advantages for patients, many of whom have very short survival. Of course, it also is increasingly cost-effective.”
Up to 10% of all patients with cancer will develop metastatic spinal cord compression. The condition can put pressure on the spinal canal, causing back pain, tingling, numbness and difficulty walking.
Radiation therapy often is used to relieve pain, maintain or increase mobility, and improve neurological function. However, no standard radiation schedule exists. Treatment ranges from a single 8-Gy dose to 40 Gy administered in 20 fractions.
Hoskin and colleagues conducted the SCORAD III trial to determine whether single-dose radiotherapy demonstrated comparable efficacy to 20 Gy administered in five fractions without compromising outcomes.
The analysis included 688 patients (median age, 70 years; 73% men) treated at 47 centers in United Kingdom and Australia.
All patients had MRI– or CT scan–confirmed spinal cord or cauda eqina (C1-S2) compression treatable within a single radiation field. Patients had not undergone prior radiation therapy to the same area, and all had a life expectancy of at least 8 weeks.
Common tumors included prostate (44%), lung (18%), breast (11%) and gastrointestinal (11%).
Researchers randomly assigned patients to external beam spinal canal radiation therapy in a single 8-Gy dose (n = 345) or in a 20-Gy dose administered in five fractions over 5 days (n = 343). Baseline characteristics were comparable between groups.
Investigators stratified results by center, ambulatory status, primary tumor site, and presence or absence of nonskeletal metastases.
Ambulatory status at week 8 served as the primary endpoint. Researchers assessed patient status on a four-point scale: grade 1, full function; grade 2, ability to walk with a walking aid, such as a walker or cane; grade 3, difficulty walking, even with walking aids; grade 4, wheelchair dependent.
Most patients (66%) had ambulatory status 1 or 2 at study entry.
Researchers established a noninferiority margin of 11% for comparing the proportion of patients who had ambulatory status 1 or 2 at week 8.
A comparable percentage of evaluable patients assigned single-dose and multifraction radiation therapy either maintained or improved to ambulatory status 1 or 2 by week 8 (69.5% vs. 73.3%; risk difference, –3.78; 90% CI, –11.85 to 4.28).
Hoskin and colleagues reported no statistically significant differences between the single-fraction and multifraction groups with regard to rates of overall positive response (risk difference, –3.78; 95% CI, –11.85 to –4.28), overall negative response (risk difference, 3.78; 95% CI, –4.28 to 11.85), or percentage of patients whose ambulatory status changed from grade 1 or 2 before radiation therapy to grade 3 or grade 4 after radiation therapy (risk difference, 3.96%; 95% CI, –2.32 to 10.25).
Researchers reported median survival of 13 weeks in the entire cohort. Results revealed no significant difference in OS between the single-dose and multifraction groups (12.4 weeks vs. 13.7 weeks; HR = 1.02; 95% CI, 0.86-1.21).
Grade 3 and grade 4 adverse events occurred in similar percentages of patients in the single-dose and multifraction groups (20.6% vs. 20.4%); however, fewer patients assigned the single-dose schedule experienced grade 1 or grade 2 events (51% vs. 56.9%).
Underrepresentation of younger patients and patients with metastatic breast cancer may limit the findings, according to researchers. Surgery in addition to or instead of radiation therapy may be appropriate for certain patients, and there may be cases when short-course radiation is not ideal, investigators added.
“Our findings establish single-dose radiotherapy as the standard of care for metastatic spinal canal compression, at least for patients with a short life expectancy,” Hoskin said in a press release. “For patients, this means fewer hospital visits and more time with family. ...
“Longer radiation may be more effective for preventing regrowth of metastases in the spine than single-dose radiation,” he added. “Therefore, a longer course of radiation may still be better for patients with a longer life expectancy, but we need more research to confirm this.” – by Mark Leiser
Hoskin P, et al. Abstract LBA10004. Presented at: ASCO Annual Meeting; June 2-6, 2017; Chicago.
Disclosure: Cancer Research UK funded the study. The researchers report research funding to their institutions from AstraZeneca and Varian Medical Systems; honoraria from and consultant/advisory roles with Amtene and Eisai; and travel, accommodations or expenses from Eisai and Teva.