The evidence supporting this protocol comes from the George et al. 2015r Cochrane review of 7 randomised trials (including 723 patients) and the systematic review by Loblaw et al.r
Radiation therapy (RT) is the most widely used treatment in the management of malignant spinal cord compression.
The Cochrane review by George et al. included 7 randomised trials (n = 723).r The Patchell et al. study was the only trial to compare surgery plus RT vs RT alone and reported the following outcomes:r
- Overall ability to walk after treatment was 84% with surgery plus RT (RR = 0.67, CI:0.53-0.86) vs 57% with RT alone.
- Ability to walk was maintained by 94% with surgery plus RT vs 74% with RT alone.
- Regaining ability to walk after treatment was achieved by 63% with surgery plus RT vs 19% with RT alone.
- Median length of time able to walk was 122 days with surgery plus RT vs 13 days with RT alone (p = 0.003).
- Median survival was 126 days with surgery plus RT vs 100 days with RT alone.
- Serious adverse effects (perforated gastric ulcer, psychoses and death due to infection) were reported by 17% of patients receiving high dose corticosteroid (96-100 mg dexamethasone) vs 0% in moderate to low dose (10-16 mg dexamethasone) patients.r
The study reported by Patchell et al. 2005 excluded patients with multiple levels of spinal cord compression and some radiosensitive tumours (lymphomas, leukaemia, multiple myeloma, and germ-cell tumours).r It is important to note that patients with pathological fractures and spinal instability were included in the randomisation, a situation which radiation therapy alone would not be expected to reverse and may have contributed to the poorer ambulatory outcomes in the radiation therapy alone arm. The Patchell study was a small trial in a highly selected population. A requirement of the trial was neurosurgical anterior decompression within 24 hours of diagnosis, which may not be achievable in many settings. The generalisability of the results has been questioned by subsequent non-randomised analyses which showed no benefit.r Palliative spinal cord radiation therapy for cord compromise may not reverse neurological deficits, but may still be appropriate to improve pain control.
Dose fractionation schedules
A range of doses are considered reasonable and should be based on individual prognostic assessment. Dose prescriptions ranging from 8 Gy in a single fraction to 30 Gy in 10 fractions are commonly used. The majority of current data is for a dose fractionation of 20 Gy in 5 fractions. The existing literature doesn’t support doses above 20 Gy in 5 fractions for endpoints such as ambulatory status, motor function, local progression free survival and overall survival.
Poor prognosis patients
Hoskin et al. 2019 reported the outcome of the SCORAD study, a multicentre UK and Australian randomised control trial.r The trial compared a single 8 Gy in 1 fraction to 20 Gy in 5 fractions in patients with limited life expectancy that were unsuitable for surgical decompression and had no prior irradiation to the same area. This study aimed to demonstrate non-inferiority of the shorter regimen with a primary endpoint of ambulatory status at 8 weeks. The patient group included poor prognosis patients with 255 out of 686 randomised patients dying before the 8 week assessment. The criterion for non-inferiority was not met for the primary endpoint but was met for 11 secondary endpoints. For grade 1-2 ambulatory status at 8 weeks, 115 of 166 (69.3%) patients were ambulatory in the single fraction arm vs 128 of 176 patients (72.7%) of the multi-fraction arm. The lower boundary of the confidence interval (-11.5%) overlapped the non-inferiority (-11%) at this time point (p = 0.06) but was met for all other time points. The clinical significance of this remains uncertain. Single fraction radiation therapy remains a reasonable fractionation schedule in this patient group.
Maranzano et al. 2011 reported on 2 randomised controlled trials of poor prognosis patients comparing dose schedules.r The first study compared short course versus split-course dose schedulesr and the second study compared single versus short course dose schedules.r They reported no significant differences in symptomatic response, duration of response, overall survival, toxicity between single and short course radiation therapy, or between short course and split-course radiation therapy. There was a higher rate of in-field failures with single course compared to short course, and short course compared to split-course, however these differences did not reach statistical significance.
Poor-intermediate prognosis patients
Rades et al 2016r reported on the SCORE-2 trial which randomised 203 patients with poor to intermediate prognosis to 20 Gy in 5 fractions over one week vs 30 Gy in 10 fractions over two weeks. The authors reported 20 Gy was not inferior to 30 Gy on motor function at 1 month (primary endpoint) and was not inferior to 30 Gy for secondary endpoints of motor function at 3 and 6 months, post radiation therapy ambulatory status at 1, 3 and 6 months, local progression free survival and overall survival.
Rades et al 2011r reported on the SCORE-1 prospective non-randomised trial of 265 patients that compared short course (8 Gy in 1 fraction or 20 Gy in 5 fractions) to long course (30 Gy in 10 fractions, 37.5 Gy in 15 fractions or 40 Gy in 20 fractions). The study had a median follow-up of 13 months. The primary endpoint of local control at 1 year was improved with long course (81%) compared to short course (61%). The secondary endpoints of motor function improvement and overall survival was no different between short course and long course. Favourable prognosis patients can be considered for long course radiation therapy.