SAN FRANCISCO — In patients with malignant spinal cord compression (MSCC), a single high dose of external-beam radiation therapy (EBRT) preserves mobility just as well as the standard approach of several lower doses of EBRT delivered over 5 days.
These results from a phase 3 trial were presented here at the American Society for Radiation Oncology 56th Annual Meeting.
"Our study objective was not to determine if 10 Gy in 1 fraction is superior to 20 [total] Gy given in 5 doses, but to ensure that the single treatment was not inferior to the standard of care," said lead author Pierre Thirion, MD, consultant radiation oncologist at St. Luke's Radiation Oncology Network in Dublin.
"We demonstrated equivalence between the 2 schedules regarding efficacy and toxicity, so we can say that a single high dose of EBRT is a cheaper and more convenient treatment that delivers equivalent efficacy without increasing toxicity," he toldMedscape Medical News.
Asked to comment on the study, Tracy Balboni, MD, MPH, associate professor of radiation oncology, Harvard Medical School, Boston, told Medscape Medical News that this study adds support to the use of a single higher dose of radiation therapy in managing patients with what she calls a "devastating condition."
"MSCC can result in loss of function of the limbs below the compression and also loss of ability to control bowel and bladder functions," Dr. Balboni said. "It's an important condition to control given its implications for patient mobility and quality of life."
Details of Clinical Trial Results
The study conducted by Dr. Thirion and colleagues, as part of the All Ireland Co-operative Oncology Research Group (ICORG), involved 116 patients with MSCC who had not undergone surgery. The current standard of care for MSCC is decompressive surgery followed by radiotherapy, but in reality, many patients are unable to undergo surgery because of poor general health, Dr. Thirion explained.
The median age of the patients was 69 years, and the median Karnofsky performance status score was 60 of a possible 100. The 3 main primary tumor sites were the prostate, breast, and lung.
The MSCC sites were 67.0% thoracic, 24.0% lumbar, 4.3% cervical, and 2.6% sacral. A few patients had MSCC in more than 1 area of the spine.
Patients were randomized to receive radiation in a single 10 Gy dose or to receive the standard of care — 5 fractions of 4 Gy (total dose, 20 Gy) delivered over 5 days.
The primary end point was change in mobility at 5 weeks, assessed using a modified Tomita scoring system.
At 5-week follow-up, there was no significant difference in the reduction in mean mobility scores between the 38 evaluable patients in the single-dose group and the 38 in the standard-of-care group (0.08 vs 0.29).
Table. Treatment Response at 5-Week Follow-up
| Treatment Group | Condition Improved, % | Condition Stabilized, % |
| Standard of care | 10.5 | 57.9 |
| Single high dose | 10.5 | 68.4 |
Secondary end points included changes in bladder function (measured using an in-house scoring scale), acute and long-term adverse effects, and overall survival.
There was no significant difference in bladder function scores between the single-dose group and the standard-of-care group at 5 weeks (overall response rate, 86.8% vs 75.7%). Bladder function remained stable in the majority of patients in both groups.
Median neurologic deterioration-free survival was about 1.4 months in both groups, and overall survival was about 4 months in both groups.
Overall toxicity in both groups was low.
Patients Remain Independent
"Despite the poor overall outcomes for MSCC patients, preserving mobility is important for several reasons," Dr. Thirion explained.
First, preserving mobility allows patients to remain independent for longer and to maintain the ability to carry out the activities of daily living, he said. In addition, it allows patients to stay at home, decreasing their care needs and related costs.
It is also associated with longer survival; preserved mobility was a key independent prognostic factor at week 5 in this particular study.
"This study provides a clear picture of what EBRT provides regarding efficacy and toxicity when using a short course of radiotherapy, and it establishes a single-fraction schedule (either 8 Gy or 10 Gy, depending on the study) as a clinical standard to which future trials can be compared," Dr. Thirion explained.
"It also helps reduce the burden of treatment and frequency of hospital visits for this patient population," he said. "For patients who are similar to those in this trial, I think a single-fraction schedule should be considered."
A Few Caveats
This study demonstrates comparable rates of preserved and improved neurologic function with the 2 radiation schedules, so results suggest that the single-dose regimen is just as effective as the 5-dose regimen, reducing the time and inconvenience of treatment, Dr. Balboni noted.
However, there are a few caveats to consider in this study, she pointed out.
It is important to note that the single dose used in this study — 10 Gy — is considered to be potentially unsafe for larger volumes of the spinal cord, particularly if there are "hot spots" in the radiation delivered, causing some areas of the spinal cord to receive doses higher than the prescribed 10 Gy," she said.
The toxic effects of radiation related to the spinal cord typically result in paralysis below the level of injury — exactly what radiation is attempting to correct, Dr. Balboni added.
Notably, these effects weren't seen in this particular study, probably because patients had such short lifespans and radiation myelopathy is generally not seen until patients have received a minimum of a few months of radiation therapy.
A more commonly used single-dose treatment for cord compression is 8 Gy, which is within the safety tolerance of the spinal cord, she said.
Dr. Balboni noted that there are studies showing that 20 Gy (delivered in 5 fractions) is inferior to longer, more intense regimens in MSCC management. This suggests that the 2 regimens used in this study might not be sufficiently durable for patients with longer life expectancies.
Nevertheless, "this study provides data to support the use of a more convenient, less burdensome single dose of radiation treatment for spinal cord compression among patients who can't undergo surgery," Dr. Balboni observed. In light of concerns about issues of durability and toxicity to the spinal cord relevant to patients living longer than approximately 3 to 4 months, "this is a tool that is most applicable to patients with life expectancies of a few months or less," she added.
Dr. Thirion and Dr. Balboni have disclosed no relevant financial relationships.
American Society for Radiation Oncology (ASTRO) 56th Annual Meeting: Abstract LBA2. Presented September 15, 2014.
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