At ASCO 2017

CHICAGO (FRONTLINE MEDICAL NEWS) – A single dose of radiation therapy appears to work as well as multiple doses given over a week for treating spinal cord compression due to metastatic cancer, according to findings of the SCORAD III trial reported at the annual meeting of the American Society of Clinical Oncology.

“There is no standard radiotherapy schedule,” first author Peter Hoskin, MD, FCRP, FRCR, an oncologist at the Mount Vernon Cancer Centre in Middlesex, England, noted in a press briefing. “A range of radiation doses are used internationally, from single doses of 8 to 10 Gy ranging up to 4 weeks of treatment delivering 40 Gy.”

The noninferiority phase III trial enrolled nearly 700 patients in the United Kingdom and Australia with spinal cord compression due to metastases, the majority of whom were able to walk at baseline. They were randomized evenly to receive either 8 Gy of radiation in a single fraction or 20 Gy split into five fractions given over consecutive days.

Results showed that at 8 weeks, more than two-thirds of patients in each group were able to walk, the trial’s primary endpoint. The lower bound of the confidence interval for the difference between groups fell just outside the trial’s margin for noninferiority.

Additionally, the two groups were statistically indistinguishable with respect to median overall survival, bowel and bladder function, and the rate of grade 3 or 4 toxicity.

“A single dose of 8 Gy is as effective as 20 Gy in five fractions for a range of clinically relevant endpoints, particularly ambulatory status, both at 8 weeks and indeed at all time points between 1 week and 12 weeks,” Dr. Hoskin summarized. The trial also underscores the importance of early diagnosis, as the majority of patients who were ambulatory initially remained so with radiation therapy, regardless of dosing schedule.

“A single dose of radiotherapy in our minds is now recommended in this setting. It has major advantages for these patients,” he maintained. “An important thing to realize is that these patients had a very short survival; median survival in this study was only 13 weeks. A single dose has enormous advantages in those patients with short survival times, and of course, it is increasingly cost effective.”

Findings in context

The trial population was not fully representative of all patients with spinal cord compression due to metastases, with underrepresentation of some cancers, such as breast cancer, and the modest survival, Dr. Hoskin acknowledged.

Some patients on the trial have survived for many months and even years, he noted. “We have looked at patients at longer times, although it was not in the protocol, and there was no obvious difference [in outcomes]. But there is some evidence to suggest that for the longer-surviving patients, a more prolonged fractionation may be appropriate, although clearly that needs to be investigated properly in a formal randomized trial.”

“This is the first study that really shows equal outcomes in terms of meaningful benefits for patients with a single dose of radiotherapy versus a much longer course, allowing patients to spend more time with their families, more time doing the things they want to do,” commented ASCO Expert Joshua A. Jones, MD, MA, of the Hospital of the University of Pennsylvania in Philadelphia.

“We still have work to do to figure out for patients who have longer than this average survival of 3 months what is the most appropriate regimen,” he agreed. “But for many patients, this is going to provide tremendous benefit with the idea that sometimes, less really is more.”

Study details

SCORAD III, which was funded by Cancer Research UK, enrolled 688 patients with metastatic prostate (44%), lung (18%), breast (11%), and gastrointestinal (11%) cancers.

At baseline, 66% were able to walk without or with an aid (ambulatory status 1 or 2), whereas the rest were unable to walk but still had some limb power (ambulatory status 3) or had flaccid paraplegia (ambulatory status 4).

At 8 weeks, the proportion of patients with ambulatory status 1 or 2 was 69.5% in the group who received the 8-Gy single-dose radiation therapy and 73.3% in the group who received the 20-Gy multidose radiation therapy, for a risk difference of –3.78%, reported Dr. Hoskin.

The 90% confidence interval for the difference between groups of –11.85% to 4.28% slightly exceeded the trial’s predefined 11% margin for noninferiority.

Among patients having ambulatory status 1 or 2 at baseline, the proportion maintaining that status at 8 weeks was 62.20% with the single dose and 63.07% with multiple doses. Median overall survival was 12.4 weeks and 13.7 weeks, respectively, a nonsignificant difference.

Patients in the single-dose and multidose groups had similar rates of grade 3 or 4 toxicity (20.6% vs. 20.4%), but the former had a lower rate of grade 1 or 2 toxicity (51.0% vs. 56.9%).