A Phase II study of anti-epidermal growth factor receptor radioimmunotherapy in the treatment of glioblastoma multiforme.

OBJECT: This single-institution Phase II study tests the efficacy of adjuvant radioimmunotherapy with (125)I-labeled anti-epidermal growth factor receptor 425 murine monoclonal antibody ((125)I-mAb 425) in patients with newly diagnosed glioblastoma multiforme (GBM). METHODS: A total of 192 patients with GBM were treated with (125)I-mAb 425 over a course of 3 weekly intravenous injections of 1.8 GBq following surgery and radiation therapy. The primary end point was overall survival, and the secondary end point was toxicity. Additional subgroup analyses were performed comparing treatment with (125)I-mAb 425 (RIT, 132 patients), (125)I-mAb 425 and temozolomide (TMZ+RIT, 60 patients), and a historical control group (CTL, 81 patients). RESULTS: The median age was 53 years (range 19-78 years), and the median Karnofsky Performance Scale score was 80 (range 60-100). The percentage of patients who underwent debulking surgery was 77.6% and that of those receiving temozolomide was 31.3%. The overall median survival was 15.7 months (95% CI 13.6-17.8 months). The 1- and 2-year survivals were 62.5 and 25.5%, respectively. For subgroups RIT and TMZ+RIT, the median survivals were 14.5 and 20.2 months, respectively. No Grade 3 or 4 toxicity was seen with the administration of (125)I-mAb 425. The CTL patients lacked Karnofsky Performance Scale scores, had poorer survival, were older, and were less likely to receive radiation therapy. On multivariate analysis, the hazard ratios for RIT versus CTL, TMZ+RIT versus CTL, and TMZ+RIT versus RIT were 0.49 (p < 0.001), 0.30 (p < 0.001), and 0.62 (p = 0.008), respectively. CONCLUSIONS: In this large Phase II study of 192 patients with GBM treated with anti-epidermal growth factor receptor (125)I-mAb 425 radioimmunotherapy, survival was 15.7 months, and treatment was safe and well tolerated.

Spinal vascular malformations: an historical perspective.

In this historical perspective, the author identifies three epochs in the development of the concepts and treatment of spinal vascular lesions: 1) early observations (1860s-1912), with the lesions during this time period recognized only at autopsy; 2) the "middle ages" (1912-1960), with surgical intervention sporadic and yielding dismal results; and 3) the modern era (beginning in the 1960s), coincident with parallel dramatic advances in radiology, microsurgical instrumentation, and anesthesiology. These advances resulted in a better understanding of the pathophysiological aspects and angioarchitecture of the lesions. Whereas the nomenclature of the lesions in the past was confusing, a new understanding of these diseases that has emerged during the modern era has permitted refinement of the classification of the lesions as distinct biological entities. Modern diagnostic imaging has enabled identification of patients who may benefit from surgical or embolic occlusion, and treatment has become rationally based. Future progress in the management of spinal vascular lesions may be anticipated, with improvement in noninvasive imaging for early detection of suspected abnormalities. Furthermore, advances in spinal cord neuroprotection may expand the range of future options for surgical or embolic intervention.

Radioiodinated (I-125) monoclonal antibody 425 in the treatment of high grade glioma patients: ten-year synopsis of a novel treatment.

The present report is the follow-up of patients enrolled in a phase II clinical trial using I-MAb 425 as an adjuvant treatment for high grade gliomas. Patient median survivals support published data from an earlier preliminary report. From January 29, 1987 to January 25, 1997, 180 patients diagnosed with astrocytoma with anaplastic foci (AAF) and glioblastoma multiforme (GBM) were treated as outpatients with an average of three weekly intravenous or intraarterial injections of radiolabeled MAb 425. The mean dose was 140 mCi (5.2 GBq). Only one patient who received a single dose of more than 60 mCi (2.2 GBq) experienced acute toxicity. Patients received prior surgery and radiation therapy, with and without chemotherapy. Overall median survival for patients with GBM and AAF was 13.4 and 50.9 months, respectively, with Karnofsky Performance Status (KPS) ranging from 40 to 100 and age ranging from 11 to 75 years. Prognostic factors (KPS and age) correlated positively with increased survival, with KPS the most important determinant of median survival. Data analysis was performed on patients followed 5 years or longer. We conclude that the administration of I-MAb 425 with intensive medical management demonstrates a significant increase in median survival and should be considered a therapeutic regimen for the management of patients with high grade gliomas.

Cerebrospinal fluid leaks following spinal surgery: use of fat grafts for prevention and repair. Technical note.

Cerebrospinal fluid (CSF) leaks are relatively common following spinal surgery. A midline dural tear in the spine is readily repaired by direct application of sutures; however, far-lateral or ventral dural tears are problematic. Fat is an ideal sealant because it is impermeable to water. In this paper the author reports his experience with using fat grafts for the prevention or repair of CSF leaks and proposes a technique in which a large sheet of fat, harvested from the patient's subcutaneous layer, is used to cover not only the dural tear(s) but all of the exposed dura and is tucked into the lateral recess. This procedure prevents CSF from seeping around the fat, which may be tacked to the dura with a few sutures. Fibrin glue is spread on the surface of the fat and is further covered with Surgicel or Gelfoam. For ventral dural tears (associated with procedures in which disc material is excised), fat is packed into the disc space to seal off the ventral dural leak. Dural suture lines following spinal intradural exploration are prophylatically protected from CSF leakage in the same manner. With one exception, 27 dural tears noted during 1650 spinal procedures were successfully repaired using this technique. There was one case of postoperative CSF leakage in 140 cases in which intradural exploration for tumor or other lesions was undertaken. Both postoperative CSF leaks were controlled by applying additional skin sutures. The use of a fat graft is recommended as a rapid, effective means of prevention and repair of CSF leaks following spinal surgery.

Lumbar disk pseudotumor: an unusual presentation of lumbar spinal fracture and stenosis.

We present an unusual case of a primary lumbar disk-space mass that presumably developed secondary to a chronic hyperextension spinal fracture associated with spinal stenosis. This injury resulted in the appearance of a lumbar intervertebral disk-space mass or pseudotumor. The pseudotumor most likely resulted from a prior spinal fracture, leading to a fused hyperextension deformity in a patient with underlying chronic degenerative spinal disease.