Direct decompressive surgical resection in the treatment of spinal cord compression caused by metastatic cancer: a randomised trial.

BACKGROUND: 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. METHODS: 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. FINDINGS: 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. INTERPRETATION: Direct decompressive surgery plus postoperative radiotherapy is superior to treatment with radiotherapy alone for patients with spinal cord compression caused by metastatic cancer.

Clinical approach to metastatic epidural spinal cord compression.

Metastatic epidural spinal cord compression (MESCC) is a devastating complication of cancer that occurs when cancer metastasizes to the spine and then secondarily compresses the spinal cord. It is a relatively common complication of cancer and. in the United States, more than 20,000 cases of MESCC are diagnosed annually. If left untreated, virtually 100% of these patients would become paraplegic; therefore, it is considered a true medical emergency and immediate intervention is required. Even with aggressive therapy, results can often be unsatisfactory. Although most patients with MESCC have limited survival, up to one third will survive beyond one year. Thus. it is essential to consider aggressive therapy to preserve or improve the quality of life and prevent paraplegia.

Selecting treatment for patients with malignant epidural spinal cord compression-does age matter?: results from a randomized clinical trial.

STUDY DESIGN: Randomized clinical trial. OBJECTIVE.: To determine if age affects outcomes from differing treatments in patients with spinal metastases. SUMMARY OF BACKGROUND DATA: Recently, class I data were published supporting surgery with radiation over radiation alone for patients with malignant epidural spinal cord compression (MESCC). However, the criteria to properly select candidates for surgery remains controversial and few independent variables which predict success after treatment have been identified. METHODS: Data for this study was obtained in a randomized clinical trial comparing surgery versus radiation for MESCC. Hazard ratios were determined for the effect of age and the interaction between age and treatment. Age estimates at which prespecified relative risks could be expected were calculated with greater than 95% confidence to suggest possible age cut points for further stratification. Multivariate models and Kaplan-Meier curves were tested using stratified cohorts for both treatment groups in the randomized trial each divided into 2 age groups. RESULTS: Secondary data analysis with age stratification demonstrated a strong interaction between age and treatment (hazard ratio = 1.61, P = 0.01), such that as age increases, the chances of surgery being equal to radiation alone increases. The best estimate for the age at which surgery is no longer superior to radiation alone was calculated to be between 60 and 70 years of age (95% CI), using sequential prespecified relative risk ratios. Multivariate modeling and Kaplan-Meier curves for stratified treatment groups showed that there was no difference in outcome between treatments for patients >or=65 years of age. Ambulation preservation was significantly prolonged in patients <65 years of age undergoing surgery compared to radiation alone (P = 0.002). CONCLUSION: Age is an important variable in predicting preservation of ambulation and survival for patients being treated for spinal metastases. Our results provide compelling evidence for the first time that particular age cut points may help in selecting patients for surgical or nonsurgical intervention based on outcome.

Percutaneous sacroplasty for the treatment of sacral insufficiency fractures.

OBJECTIVE: The purpose of this article is to illustrate the effectiveness and utility of percutaneous sacroplasty in the treatment of sacral insufficiency fractures. We also outline the technical considerations in performing the procedure. CONCLUSION: Percutaneous sacroplasty is an effective treatment for sacral insufficiency fractures. Most patients experience significant relief within the first 48 hr.

Recursive partitioning analysis classifications I and II: applicability evaluated in a randomized trial for resected single brain metastases.

PURPOSE: Radiation Therapy Oncology Group (RTOG) recursive partitioning analysis (RPA) prognostic classes I and II for patients with brain metastases is derived from a database made up primarily of patients with unresected and multiple metastases. An analysis of a previously published randomized trial was performed to determine the applicability of these RPA prognostic classes in the setting of resection of single metastases to the brain. PATIENTS AND METHODS: Ninety-five patients with single metastases to the brain that were treated with complete surgical resection entered this study. Patients were randomly assigned to treatment with postoperative whole brain radiotherapy (WBRT) (n = 49 patients) or no further brain treatment (n = 46 patients). All patients entered on this study had a Karnofsky performance status of > or =70. Therefore, although the RTOG RPA has 3 classes, only patients with RPA classes I (n = 26) or II (n = 69) were eligible for this study analysis. RESULTS: For RPA class I, the median survival was 10.9 months versus 9.8 months for class II patients (P = 0.45). Multivariate analysis showed that only postoperative WBRT, independent of RPA class I or II, lessened the risk of brain tumor recurrence (P < 0.0001). CONCLUSION: This analysis of a randomized trial evaluating postoperative WBRT in the treatment of single metastases to the brain showed no difference in survival between RPA class I or II patients. In addition, the use of postoperative WBRT after complete surgical resection of single brain metastases results in substantially better control of disease in the brain independent of RPA classes I or II.

A phase I trial of continuously infused intratumoral bleomycin for the treatment of recurrent glioblastoma multiforme.

Intratumoral (IT) chemotherapy has theoretical advantages in the treatment of brain tumors. The blood-brain barrier is not a factor in drug delivery, and large concentrations of drug can be instilled in the tumor with little systemic toxicity. Bleomycin has activity against gliomas and is a cell cycle selective agent whose efficacy should be enhanced by continuous infusion. We performed a phase I trial to test the feasibility of IT chemotherapy using a refillable, sustained release device, and to determine the maximum tolerable dose of IT bleomycin. The study was an open-ended dose escalation study. A modified Ommaya reservoir (containing a semipermeable membrane) was implanted with the delivery tube in the center of the tumor. Groups of three patients with recurrent glioblastoma multiforme were entered at progressively higher dose levels of bleomycin. The study closed when all patients at a given starting dose level developed toxicity. Nine patients received doses ranging from 5 to 34 U/wk; the median total cumulative dose was 195 U. No dose limiting systemic toxicity was detected. Neurologic toxicity occurred only at doses above 16 U/wk. We conclude that continuously infused IT bleomycin is well tolerated; the MTD (and recommended dose for a phase II efficacy trial) of IT bleomycin is 16 U/wk.