Intralesional immunotherapy of brain tumors with combined Corynebacterium parvum and recombinant interleukin-2 in mice.

Clinical observations and experimental work suggested that inflammatory cells attracted to the brain exert a nonspecific antineoplastic effect. Intralesional treatment of implanted malignant murine brain tumors (KHT sarcomas) with killed Corynebacterium parvum produced an inflammatory cell infiltrate and increased survival in C3H mice relative to that in untreated control C3H mice. This antitumor effect was enhanced when recombinant interleukin-2 was sequentially added as a second intralesional immunomodifier. A high percentage of mice so treated were cured. Inflammatory cells in the brains of treated mice divided for 1-2 weeks, and metabolic activity of astrocytes increased. These findings form the basis for a recently initiated immunotherapy protocol in patients with recurrent glioblastoma multiforme.

Linear accelerator-based stereotaxic radiosurgery for brain metastases:the influence of number of lesions on survival.

PURPOSE: To evaluate the influence of the number of brain metastases on survival after stereotaxic radiosurgery and factors that affect the risk of delayed radiation necrosis after treatment. MATERIALS AND METHODS: Between March 1989 and December 1993, 120 consecutive patients underwent linear accelerator-based stereotaxic radiosurgery for brain metastases identified by computed tomography (CT) or magnetic resonance imaging (MRI) scans. The influence of various clinical factors on outcome was assessed using Kaplan-Meier plots of survival from the date of radiosurgery, and univariate and multivariate analyses. RESULTS: The median survival time was 32 weeks. Progressive brain metastases, both local and regional, caused 25 of 104 deaths. Patients with two metastases (n = 30) or a solitary metastasis (n = 70) had equivalent actuarial survival times (P = .07; median, 37 weeks; maximum, 211+ weeks). Patients treated to three or more metastases (n = 20) had significantly shorter survival times (P < .002; median, 14 weeks; maximum, 63 weeks). Prognostic factors associated with prolonged survival included a pretreatment Karnofsky performance status > or = 70% and fewer than three metastases. Delayed radiation necrosis at the treated site developed in 20 patients and correlated with prior or concurrent delivery of whole-brain irradiation and the logarithm of the tumor volume. CONCLUSION: Survival duration is equivalent for patients with one or two brain metastases and is similar to that reported for patients with a solitary metastasis managed by surgical resection and whole-brain irradiation. Survival after radiosurgery for three or more metastases was similar to that reported for whole-brain irradiation.

Self-audible venous bruits and high jugular bulb.

The association between self-audible bruits and ipsilateral high jugular bulbs was demonstrated in five patients, emphasizing the benign nature of the condition. Symptoms included a unilateral pulsatile "whooshing" that was eliminated by gentle pressure on the neck or extreme head rotation to the symptomatic side and was enhanced by conditions that increased cardiac output. The bruits were not audible to examiners. On the basis of one patient with an intracranial tumor, it is proposed that raised intracranial pressure alone, in the absence of a jugular bulb abnormality, is an insufficient explanation for a venous self-audible bruit.

Radiosurgery for skull base malignancies and nasopharyngeal carcinoma.

PURPOSE: Patients with skull base lesions present a challenging management problem because of intractable symptoms and limited therapeutic options. In 1989 we began treating selected patients with skull base lesions using linac stereotactic radiosurgery. In this study the efficacy and toxicity of this therapeutic modality is investigated. METHODS AND MATERIALS: Forty-seven patients with 59 malignant skull base lesions were treated with linac radiosurgery between 1989 and 1995. Eleven patients were treated for primary nasopharyngeal carcinoma using radiosurgery as a boost (7 Gy-16 Gy, median: 12 Gy) to the nasopharynx after a course of fractionated radiotherapy (64.8-70 Gy) without chemotherapy. Another 37 patients were treated for 48 skull base metastases or local recurrences from primary head and neck cancers. Eight of these patients had 12 locally recurrent nasopharyngeal carcinoma lesions occuring 6-96 months after standard radiotherapy, including one patient with nasopharyngeal carcinoma who developed a regional relapse after radiotherapy with a stereotactic boost. Lesion volumes by CT or MRI ranged from 0 to 51 cc (median: 8 cc). Radiation doses of 7.0 Gy-35.0 Gy (median: 20.0 Gy) were delivered to recurrent lesions, usually as a single fraction. RESULTS: All 11 patients who received radiosurgery as a nasopharyngeal boost after standard fractionated radiotherapy remain locally controlled (follow-up: 2-34 months, median: 18). However, one patient required a second radiosurgical treatment for regional relapse outside the initial radiosurgery volume. Thirty-three of 48 (69%) recurrent/metastatic lesions have been locally controlled, including 7 of 12 locally recurrent nasopharyngeal lesions. Follow-up for all patients with recurrent lesions ranged from 1 to 60 months (median: 9 months). Local control did not correlate with lesion size (p = 0.80), histology (p = 0.78), or radiosurgical dose (p = 0.44). Major complications developed after 5 of 59 treatments (8.4%), including three cranial nerve palsies, one CSF leak, and one trismus. Complications were not correlated with radiosurgical volume (p = 0.20), prior skull base irradiation (p = 0.90), or radiosurgery dose > 20 Gy (p = 0.49). CONCLUSION: Stereotactic radiosurgery is a reasonable treatment modality for patients with skull base malignancies, including patients with primary and recurrent nasopharyngeal carcinoma. The dose distribution obtained with stereotactic radiosurgery provides better homogeneity than an intracavitary implant when used as a boost for nasopharyngeal lesions, especially lesions which involve areas distant to the nasopharyngeal mucosa.

Stereotactic radiosurgical boost following radiotherapy in primary nasopharyngeal carcinoma: impact on local control.

PURPOSE: Treatment of patients with nasopharyngeal carcinoma using external beam radiation therapy (EBRT) alone results in significant local recurrence. Although intracavitary brachytherapy can be used as a component of management, it may be inadequate if there is extension of disease to the skull base. To improve local control, stereotactic radiosurgery was used to boost the primary tumor site following fractionated radiotherapy in patients with nasopharyngeal carcinoma. METHODS AND MATERIALS: Twenty-three consecutive patients were treated with radiosurgery following radiotherapy for nasopharyngeal carcinoma from 10/92 to 5/98. All patients had biopsy confirmation of disease prior to radiation therapy; Stage III disease (1 patient), Stage IV disease (22 patients). Fifteen patients received cisplatinum-based chemotherapy in addition to radiotherapy. Radiosurgery was delivered using a frame-based LINAC as a boost (range 7 to 15 Gy, median 12 Gy) following fractionated radiation therapy (range 64.8 to 70 Gy, median 66 Gy). RESULTS: All 23 patients (100%) receiving radiosurgery as a boost following fractionated radiation therapy are locally controlled at a mean follow-up of 21 months (range 2 to 64 months). There have been no complications of treatment caused by radiosurgery. However, eight patients (35%) have subsequently developed regional or distant metastases. CONCLUSIONS: Stereotactic radiosurgical boost following fractionated EBRT provides excellent local control in advanced stage nasopharynx cancer and should be considered for all patients with this disease. The treatment is safe and effective and may be combined with cisplatinum-based chemotherapy.

Registration error quantification of a surface-based multimodality image fusion system.

This paper presents a new reference data set and associated quantification methodology to assess the accuracy of registration of computerized tomography (CT) and magnetic-resonance (MR) images. Also described is a new semiautomatic surface-based system for registering and visualizing CT and MR images. The registration error of the system was determined using a reference data set that was obtained from a cadaver in which rigid fiducial tubes were inserted prior to imaging. Registration error was measured as the distance between an analytic expression for each fiducial tube in one image set and transformed samples of the corresponding tube obtained from the other. Registration was accomplished by first identifying surfaces of similar anatomic structures in each image set. A transformation that best registered these structures was determined using a nonlinear optimization procedure. Even though the root-mean-square (rms) distance at the registered surfaces was similar to that reported by other groups, it was found that rms distances for the tubes were significantly larger than the final rms distances between the registered surfaces. It was also found that minimizing rms distance at the surface did not minimize rms distance for the tubes.

Treatment of cranial base meningiomas with linear accelerator radiosurgery.

OBJECTIVE: Radiosurgery is increasingly being used to treat cranial base tumors. Since 1989, 55 patients with cranial base meningiomas were treated at Stanford University Medical Center with linear accelerator radiosurgery. An analysis of the clinical and radiographic results of this patient population was the focus of this study. METHODS: The mean patient age was 55.1 years (range, 28-82 yr). The mean tumor volume was 7.33 cm3 (range, 0.45-27.65 cm3). The radiation dose averaged 18.3 Gy (range, 12-25 Gy), delivered with an average of 2.2 isocenters (range, 1-5). Patients were evaluated retrospectively through clinic notes from follow-up examinations, and residual tumor volume was measured during follow-up imaging studies. The length of follow-up averaged 48.4 months (range, 17-81 mo). RESULTS: Tumor stabilization after radiosurgery was noted in 38 patients (69%), shrinkage in 16 patients (29%), and enlargement in only 1 patient (2%). The results of follow-up magnetic resonance imaging demonstrated decreased central contrast uptake in 11 meningiomas (20%), possibly indicating evidence of central tumor necrosis or tumor vessel obliteration. Neurological status was improved in 15 patients in the series (27%) and unchanged in 34 patients (62%). Three patients (5%) died during the follow-up period, all as a result of causes other than tumor progression. Three patients (5%) developed new permanent symptoms (one patient with seizures, one patient with mild right hemiparesis, and one patient with both vagal and hypoglossal nerve palsy). All other complications were transient, including partial trigeminal nerve palsy in seven patients and diplopia in three patients. The 2-year actuarial tumor control rate was 98%. CONCLUSIONS: Although our follow-up period is short, this experience corroborates previous reports that radiosurgery can be used to ablate selected small cranial base meningiomas, with good clinical results and modest morbidity.

Characterization of spatial distortion in magnetic resonance imaging and its implications for stereotactic surgery.

The different sources of spatial distortion in magnetic resonance images are reviewed from the point of view of stereotactic target localization. The extents of the two most complex sources of spatial distortion, gradient field nonlinearities and magnetic field inhomogeneities, are discussed both qualitatively and quantitatively. Several ways by which the spatial distortion resulting from these sources can be minimized are discussed. The clinical relevance of the spatial distortion along with some strategies to minimize the localization errors in magnetic resonance-guided stereotaxy are presented.

Pachymeningitis associated with a pulmonary nodule.

The authors report a case of hypertrophic pachymeningitis, a rare cause of spinal cord compression. In this patient, dural inflammation was associated with a histologically identical pulmonary lesion. Such an association has not been described previously and supports the hypothesis that this disease is related to other connective tissue disorders.

Failure of intracisternal tissue plasminogen activator to prevent vasospasm in certain patients with aneurysmal subarachnoid hemorrhage.

Recent experimental and clinical reports suggest that the intracisternal administration of recombinant tissue plasminogen activator (tPA) within 72 hours of subarachnoid hemorrhage decreases the incidence of severe angiographic and clinical vasospasm. In this report, we present four of eight patients with aneurysmal subarachnoid hemorrhage who developed angiographic and clinical vasospasm with delayed neurological deterioration, despite the use of intracisternal tPA after early aneurysm clipping. One patient did not clear her massive subarachnoid hemorrhage with tPA; one patient had extremely poor collateral flow with occlusion of one cervical internal carotid artery and 80% stenosis of the other cervical internal carotid artery; the other two patients had a subarachnoid hemorrhage 7 to 12 days after their sentinel hemorrhage. Three patients ultimately made excellent or good recoveries, and one was left with hemiparesis. The four other patients treated by this protocol did not develop vasospasm. We conclude that intracisternal tPA may not prevent vasospasm in certain patients. This may relate to inadequate clearing of the subarachnoid clot, pre-existing poor collateral supply, or the occurrence of prior subarachnoid hemorrhage.

Hydrocephalus and intraspinal tumor.

Hydrocephalus with spinal subarachnoid obstruction is rare, and its cause is obscure. Two such patients are presented. The pathophysiology is reviewed. Spinal absorptive pathways for cerebrospinal fluid are postulated to play a critical role in such cases.

Stereotactic, angiography-guided clipping of a distal, mycotic intracranial aneurysm using the Cosman-Roberts-Wells system: technical note.

We describe the use of stereotactic, angiographic guidance for localization and clipping of a small, distal intracranial bacterial aneurysm. The technique uses the commercially available Suetens-Gybels-Vandermeulen angiographic localizer with the widely used Cosman-Roberts-Wells stereotactic system. This method is simple and easy to use and significantly decreased the operative time. It may be quite useful for surgically treating mycotic and other peripheral aneurysms.

Stereotactic radiosurgery of angiographically occult vascular malformations: 14-year experience.

OBJECTIVE: Radiosurgery is generally effective in obliterating true arteriovenous malformations, but less is known about its effects on angiographically occult vascular malformations (AOVMs). Since July 1983, 57 patients with surgically inaccessible AOVMs of the brain were treated using helium ion (47 patients) or linear accelerator (10 patients) radiosurgery. This study retrospectively evaluates the response of these AOVMs to treatment. METHODS: All patients presented with previous hemorrhage. The mean patient age was 35.6 years (range, 13-71 yr). The mean AOVM volume was 2.25 cm3 (range, 0.080-15.2 cm3), treated with a mean of 18.0 Gy equivalent (physical dose x relative biological effectiveness, which is 1.3 for helium ion Bragg peak) (range, 7.0-40 Gy equivalent). The Drake scale scores before treatment were as follows: excellent (25 patients), good (26 patients), and poor (6 patients). The mean follow-up period was 7.5 years (range, 9 mo-13.8 yr). RESULTS: Eighteen patients (32%) bled symptomatically (20 hemorrhages) after radiosurgery. Sixteen hemorrhages occurred within 36 months after radiosurgery (9.4% annual bleed rate; 16 hemorrhages/171 patient yr); 4 hemorrhages occurred more than 36 months after treatment (1.6% annual bleed rate; 4 hemorrhages/257 patient yr) (P < 0.001). Complications included symptomatic radiation edema (four patients, 7%), necrosis (one patient, 2%), and increased seizure frequency (one patient, 2%). Eight patients underwent surgical resection of their AOVMs 8 to 59 months after radiosurgery because of subsequent hemorrhage. The Drake scale scores after treatment were as follows: excellent (25 patients), good (24 patients), poor (3 patients), and dead (5 patients, 3 of whom died as a result of causes unrelated to the AOVMs or radiosurgery). CONCLUSION: Radiosurgery may be useful for AOVMs located in surgically inaccessible regions of the brain. A significant decrease in bleed rate exists more than 3 years after treatment compared with the bleed rate within 3 years of treatment. Because current neuroradiological techniques are not able to image obliterative response in these slow-flow vascular lesions, longer term clinical follow-up is required.

Image-guided hypo-fractionated stereotactic radiosurgery to spinal lesions.

OBJECTIVE: This article demonstrates the technical feasibility of noninvasive treatment of unresectable spinal vascular malformations and primary and metastatic spinal tumors by use of image-guided frameless stereotactic radiosurgery. METHODS: Stereotactic radiosurgery delivers a high dose of radiation to a tumor volume or vascular malformation in a limited number of fractions and minimizes the dose to adjacent normal structures. Frameless image-guided radiosurgery was developed by coupling an orthogonal pair of x-ray cameras to a dynamically manipulated robot-mounted linear accelerator that guides the therapy beam to treatment sites within the spine or spinal cord, in an outpatient setting, and without the use of frame-based fixation. The system relies on skeletal landmarks or implanted fiducial markers to locate treatment targets. Sixteen patients with spinal lesions (hemangioblastomas, vascular malformations, metastatic carcinomas, schwannomas, a meningioma, and a chordoma) were treated with total treatment doses of 1100 to 2500 cGy in one to five fractions by use of image-guided frameless radiosurgery with the CyberKnife system (Accuray, Inc., Sunnyvale, CA). Thirteen radiosurgery plans were analyzed for compliance with conventional radiation therapy. RESULTS: Tests demonstrated alignment of the treatment dose with the target volume within +/-1 mm by use of spine fiducials and the CyberKnife treatment planning system. Tumor patients with at least 6 months of follow-up have demonstrated no progression of disease. Radiographic follow-up is pending for the remaining patients. To date, no patients have experienced complications as a result of the procedure. CONCLUSION: This experience demonstrates the feasibility of image-guided robotic radiosurgery for previously untreatable spinal lesions.

Treatment of hemangioblastomas in von Hippel-Lindau disease with linear accelerator-based radiosurgery.

OBJECTIVE: Stereotactic radiosurgery is increasingly being used to treat hemangioblastomas, particularly those that are in surgically inaccessible locations or that are multiple, as is common in von Hippel-Lindau disease. The purpose of this study was to retrospectively evaluate the effectiveness of radiosurgery in the treatment of hemangioblastomas. METHODS: From 1989 to 1996, 29 hemangioblastomas in 13 patients with von Hippel-Lindau disease were treated with linear accelerator-based radiosurgery. The mean patient age was 40 years (range, 31-57 yr). The radiation dose to the tumor periphery averaged 23.2 Gy (range, 18-40 Gy). The mean tumor volume was 1.6 cm3 (range, 0.07-65.4 cm3). Tumor response was evaluated in serial, contrast-enhanced, computed tomographic and magnetic resonance imaging scans. The mean follow-up period was 43 months (range, 11-84 mo). RESULTS: Only one (3%) of the treated hemangioblastomas progressed. Five tumors (17%) disappeared, 16 (55%) regressed, and 7 (24%) remained unchanged in size. Five of nine patients with symptoms referable to treated hemangioblastomas experienced symptomatic improvement. During the follow-up period, one patient died as a result of progression of untreated hemangioblastomas in the cervical spine. Three patients developed radiation necrosis, two of whom were symptomatic. CONCLUSION: Although follow-up monitoring is limited, stereotactic radiosurgery provides a high likelihood of local control of hemangioblastomas and is an attractive alternative to multiple surgical procedures for patients with von Hippel-Lindau disease.

Fractionated stereotactic radiosurgery and preservation of hearing in patients with vestibular schwannoma: a preliminary report.

OBJECTIVE: Microsurgery and stereotactic radiosurgery (SRS) for vestibular schwannomas are associated with a relatively high incidence of sensorineural hearing loss. A prospective trial of fractionated SRS was undertaken in an attempt to preserve hearing and minimize incidental cranial nerve injury. METHODS: Thirty-three patients with vestibular schwannomas were treated with 2100 cGy in three fractions during a 24-hour period using conventional frame-based linear accelerator radiosurgery. The median tumor diameter was 20 mm (range, 7-42 mm). Baseline and follow-up evaluations included audiometry and contrast-enhanced magnetic resonance imaging. End points were tumor progression, preservation of serviceable hearing, and treatment-related complications. RESULTS: Thirty-one patients (32 tumors) were assessable for tumor progression and treatment-related complications and 21 patients for preservation of serviceable hearing, with a median follow-up interval of 2 years (range, 0.5-4.0 yr). Tumor regression or stabilization was documented in 30 patients (97%) and tumor progression in 1 (3%). The patient with tumor progression remains asymptomatic and has not required surgical intervention. Five patients (16%) developed trigeminal nerve injury at a median of 6 months (range, 4-12 mo) after SRS; two of these patients had preexisting trigeminal neuropathy. One patient (3%) developed facial nerve injury (House-Brackmann Class 3) 7 months after SRS. Preservation of useful hearing (Gardner-Robertson Class 1-2) was 77% at 2 years. All patients with pretreatment Gardner-Robertson Class 1 to 2 hearing maintained serviceable (Class 1-3) hearing as of their last follow-up examination. CONCLUSION: Three-fraction SRS with a conventional stereotactic frame is feasible and well tolerated in the treatment of acoustic neuroma. This study demonstrates a high rate of hearing preservation and few treatment-related complications among a relatively high-risk patient cohort (tumors >15 mm or neurofibromatosis Type 2). Longer follow-up will be required to assess the durability of tumor control.

Analysis of the proliferative potential of residual tumor after radiosurgery for intraparenchymal brain metastases.

A retrospective immunohistochemical study of radiosurgically treated brain metastases was performed to determine whether residual tumor has reduced proliferative potential. The monoclonal antibodies MIB-10 and PC-10 were used as markers for proliferation. The experimental group consisted of pathological specimens obtained from five patients in whom brain metastasis previously had been treated with radiosurgery. Pathological specimens obtained from 10 patients with brain metastases, matched in histology to diseases in the experimental group but untreated by radiosurgery, served as controls. A significant decrease in proliferative indices was observed in metastatic brain cancers after radiosurgery (p < 0.001). These results indicate that the persistent tumor that is present at the site of a metastasis previously treated with radiosurgery is less viable and may not in itself be a significant finding.

Chorea as a manifestation of epidural hematoma. Case report.

A child with epidural hematoma presented with choreiform movements which promptly resolved following the evacuation of the hematoma.

Cerebral hemicorticectomy for epilepsy.

Hemicorticectomy resulted in total or near-total control of seizures in 10 of 11 children with chronic epilepsy. During a median follow-up period of 5.5 years, there have been no deaths or delayed complications. The surgical outcome after hemicorticectomy compares favorably with that of more extensive surgical procedures, yet is associated with significantly less risk. The technique for hemicorticectomy is described and illustrated.

Posterior fossa stereotaxic biopsy using the Brown-Roberts-Wells stereotaxic system. Technical note.

Stereotaxic biopsy has been shown to be a reliable means of diagnosing posterior fossa lesions. The authors describe a technique for infratentorial transcerebellar stereotaxic access to posterior fossa parenchymal lesions using the Brown-Roberts-Wells apparatus in its standard commercial configuration. The necessity for tissue diagnosis of these lesions is briefly discussed.