Treatment of spinal epidural metastases. Randomized prospective comparison of laminectomy and radiotherapy. Direct decompressive surgical resection in the treatment of spinal cord compression caused by metastatic cancer: a randomised trial. A pilot randomised comparison of dexamethasone 96 mg vs 16 mg per day for malignant spinal-cord compression treated by radiotherapy: TROG 01.05 Superdex study. Effect of high-dose dexamethasone in carcinomatous metastatic spinal cord compression treated with radiotherapy: a randomised trial. Initial bolus of conventional versus high-dose dexamethasone in metastatic spinal cord compression. Short-course versus split-course radiotherapy in metastatic spinal cord compression: results of a phase III, randomized, multicenter trial.
Metastases to the spinal epidural space with compression of the spinal cord or cauda equina are commonly encountered by physicians in a variety of clinical field. In the recent past, decompressive laminectomy followed by radiotheray was thought to be the best available treatment. More recently, radiotherapy alone has been advocated as an alternative treatment mode with a similar rate of effectiveness. This study compares laminectomy followed by radiotherapy to radiotherapy alone in the treatment of spinal epidural metastases in a randomized, prospective clinical trial. No significant difference was found in the effectiveness of the two treatment methods in regard to pain relief, improved ambulation, or improved sphincter function. Patients with an incomplete myelographic block fared well regardless of treatment, and those with a complete block fared poorly. Because of the limited size of this study and because of certain unforeseen design defects, the results are suggestive but not conclusive. Suggestions are made for a future randomized, prospective multicenter study that would conclusively answer the perplexing question as to the most efficacious method for treating spinal epidural metastases. The standard treatment for spinal cord compression caused by metastatic cancer is corticosteroids and radiotherapy. The role of surgery has not been established. We assessed the efficacy of direct decompressive surgery.
                In this randomised, multi-institutional, non-blinded trial, we randomly assigned patients with spinal cord compression caused by metastatic cancer to either surgery followed by radiotherapy (n=50) or radiotherapy alone (n=51). Radiotherapy for both treatment groups was given in ten 3 Gy fractions. The primary endpoint was the ability to walk. Secondary endpoints were urinary continence, muscle strength and functional status, the need for corticosteroids and opioid analgesics, and survival time. All analyses were by intention to treat.
                After an interim analysis the study was stopped because the criterion of a predetermined early stopping rule was met. Thus, 123 patients were assessed for eligibility before the study closed and 101 were randomised. Significantly more patients in the surgery group (42/50, 84%) than in the radiotherapy group (29/51, 57%) were able to walk after treatment (odds ratio 6.2 [95% CI 2.0-19.8] p=0.001). Patients treated with surgery also retained the ability to walk significantly longer than did those with radiotherapy alone (median 122 days vs 13 days, p=0.003). 32 patients entered the study unable to walk; significantly more patients in the surgery group regained the ability to walk than patients in the radiation group (10/16 [62%] vs 3/16 [19%], p=0.01). The need for corticosteroids and opioid analgesics was significantly reduced in the surgical group.
                Direct decompressive surgery plus postoperative radiotherapy is superior to treatment with radiotherapy alone for patients with spinal cord compression caused by metastatic cancer. To test the viability of a full-scale randomised comparison of two steroid doses given with radiotherapy for malignant spinal-cord compression (MSCC), to test Internet randomisation and to compare different functional outcome measures.
                A log of screened patients at eight recruiting centres was maintained. Patients were randomised via the Superdex website to either 96 mg or 16 mg daily of dexamethasone. Radiotherapy treatment was 30 Gy in 10 fractions. Outcomes assessed used ambulation, Barthel Index ambulation, Functional Independence Measure (FIM) ambulation and Functional Improvement Score (FIS) at 1 month.
                One hundred and thirty-one patients were screened. Ninety-three (71%) were ineligible, 65% of these were because duration of prior steroid use was greater than 12 h, failure to meet strict definition of magnetic resonance imaging, defined MSCC, multi-level disease or previous spinal-cord compression treatment. Twenty of the 38 eligible patients were randomised, including seven outside standard office hours. There was a high rate of serious adverse events (n = 9), but only one was considered likely to be related to study medication. At baseline, 75% were ambulant, 70% had FIM ambulation scores greater than 5 and 50% had Barthel Index ambulation scores greater than 2. At day 28, including all randomised patients (by scoring four dead patients as non-ambulant), ambulation scores by the various definitions were 60%, 45% and 40%, respectively. For the 16 patients evaluable at day 28, the mean FIS was -1.4. Median survival was 69 days and 1-year survival 13%.
                Web randomisation was successful; however, the high ineligibility rate precludes a full-scale dexamethasone dose trial in Australia. Choice of measure of ambulation has potentially significant effects on outcomes and implications for the design of any future MSCC trials. Referral delays are of concern. We performed a randomised single blind trial of high-dose dexamethasone as an adjunct to radiotherapy in patients with metastatic spinal cord compression from solid tumours. After stratification for primary tumour and gait function, 57 patients were allocated randomly to treatment with either high-dose dexamethasone or no steroidal treatment. Dexamethasone was administered as a bolus of 96 mg intravenously, followed by 96 mg orally for 3 days and then tapered in 10 days. A successful treatment result defined as gait function after treatment was obtained in 81% of the patients treated with dexamethasone compared to 63% of the patients receiving no dexamethasone therapy. Six months after treatment, 59% of the patients in the dexamethasone group were still ambulatory compared to 33% in the no dexamethasone group. Life table analysis of patients surviving with gait function showed a significantly better course in patients treated with dexamethasone (P < 0.05). Median survival was identical in the two treatment groups. Similar results were found in subgroup analysis of 34 patients with breast cancer as the primary malignancy. Significant side-effects were reported in 3 (11%) of the patients receiving glucocorticoids, 2 of whom discontinued the treatment. We conclude that high-dose glucocorticoid therapy should be given as adjunct treatment in patients with metastatic epidural spinal cord compression. We randomly assigned dexamethasone in an initial bolus of 10 mg IV or 100 mg IV followed by 16 mg daily orally to 37 patients with metastatic spinal cord compression. The average pain score before the start of treatment was 5.2 (SD = 2.8) and decreased significantly (p less than 0.001) to 3.8 at 3 hrs, 2.8 at 24 hrs, and 1.4 after 1 week. There were no differences between the conventional and high-dose group on pain, ambulation, or bladder function. Hypofractionated radiotherapy (RT) is often used in the treatment of metastatic spinal cord compression (MSCC). This randomized trial was planned to assess the clinical outcome and toxicity of two different hypofractionated RT regimens in MSCC.
                Three hundred patients with MSCC were randomly assigned to a short-course RT (8 Gy x 2 days) or to a split-course RT (5 Gy x 3; 3 Gy x 5). Only patients with a short life expectancy entered the protocol. Median follow-up was 33 months (range, 4 to 61 months).
                A total of 276 (92%) patients were assessable; 142 (51%) treated with the short-course and 134 (49%) treated with the split-course RT regimen. There was no significant difference in response, duration of response, survival, or toxicity found between the two arms. When short- versus split-course regimens were compared, after RT 56% and 59% patients had back pain relief, 68% and 71% were able to walk, and 90% and 89% had good bladder function, respectively. Median survival was 4 months and median duration of improvement was 3.5 months for both arms. Toxicity was equally distributed between the two arms: grade 3 esophagitis or pharyngitis was registered in four patients (1.5%), grade 3 diarrhea occurred in four patients (1.5%), and grade 3 vomiting or nausea occurred in 10 patients (6%). Late toxicity was never recorded.
                Both hypofractionated RT schedules adopted were effective and had acceptable toxicity. However, considering the advantages of the short-course regimen in terms of patient convenience and machine time, it could become the RT regimen of choice in the clinical practice for MSCC patients.
Patients with stable spines retaining the ability to walk may be treated with radiotherapy. One trial indicates that short course radiotherapy suffices in patients with unfavourable histologies or predicted survival of less than six months. There is some evidence of benefit from decompressive surgery in ambulant patients with poor prognostic factors for radiotherapy; and in non-ambulant patients with a single area of compression, paraplegia < 48 hours, non-radiosensitive tumours and a predicted survival of more than three months. High dose corticosteroids carry a significant risk of serious adverse effects.