James M. Strottmann

Risk of symptomatic brain tumor recurrence and neurologic deficit after radiosurgery alone in patients with newly diagonised brain metastases: results and implications

PURPOSE A single-institution experience using primary stereotactic radiosurgery (SRS) alone in the management of newly diagnosed brain metastases was analyzed to identify the risk of symptomatic brain tumor recurrence (BTR) and neurologic deficit associated with such a treatment strategy. METHODS AND MATERIALS Thirty-six patients were treated for newly diagnosed single/multiple brain metastases using SRS alone followed by planned observation. SRS minimum tumor dose ranged from 8 to 25 Gy (median: 20 Gy). Factors evaluated in analysis of treatment outcome included number of metastases, site of metastasis, primary tumor site, histology, extent of intracranial and extracranial disease, and interval to diagnosis of brain metastasis. RESULTS Median and 1-year survival for the entire group was 9 months and 36%, respectively. BTR anywhere in the brain occurred in 47% (17/36) of patients. Forty-seven percent of BTR (8/17) recurred at the site of original metastasis; 35% (6/17) recurred at both original [corrected] and distant sites in the brain, and 18% (3/17) recurred at distant only [corrected] brain sites. Seventy-one percent (12/17) of the patients were symptomatic at the time of recurrence, and 59% (10/17) had an associated neurologic deficit. Multivariate analysis found that only the extent of disease was a predictor of BTR. Patients who had disease limited to the brain only had a BTR rate of 80% (8/10) vs. 35% (9/26) who had disease involving the brain, primary site, and/or other extracranial metastatic sites (p = 0.03). CONCLUSIONS Use of primary SRS alone in this setting is associated with an increasingly significant risk of BTR with increasing survival time. In addition, the majority of such recurrences are symptomatic and associated with a neurologic deficit, a finding not analyzed in recently reported experiences withholding whole brain radiation therapy as part of the primary treatment of brain metastasis.

High-Dose Intra-Arterial Cisplatin Boost With Hyperfractionated Radiation Therapy for Advanced Squamous Cell Carcinoma of the Head and Neck

PURPOSE To evaluate the tolerance and efficacy of intra-arterial (IA) cisplatin boost with hyperfractionated radiation therapy (HFX-RT) in patients with advanced squamous cell carcinoma of the head and neck (SCCHN). PATIENTS AND METHODS Forty-two patients with locally advanced primary SCCHN were treated on consecutive phase I/II studies of HFX-RT (receiving a total of 76.8 to 81.6 Gy, given at 1.2 Gy bid) and IA cisplatin (150 mg/m(2) received at the start of and during RT boost treatment). RESULTS Acute grade 3 to 4 toxicities were as follows: grade 4 and grade 3 mucosal toxicity occurred in three (7%) and 31 patients (69%), respectively, and grade 3 hematologic, infectious, and skin events occurred in one patient each. Eight of 24 patients (33%) were unable to receive a second planned dose of IA cisplatin because of general anxiety (n = 5), nausea and/or emesis (n = 2), or asymptomatic occlusion of an external carotid artery (n = 1). Thirty-seven patients (88%) experienced complete response (CR) at primary site. Twenty-nine (85%) of 34 patients presenting with nodal disease experienced CR. The actuarial 2-year rates of locoregional control and disease-specific and overall survival are 73%, 63%, and 57%, respectively, with a median active follow-up of 30 months. CONCLUSION In this highly unfavorable subset of patients, these results seem superior to previously reported chemoradiation regimens in more favorable patients. Use of a second dose of IA cisplatin boost was associated with increased toxicity without obvious therapeutic gain. This novel strategy allows for an incremental increase in the treatment intensity of the HFX-RT regimen recently established as superior to once-a-day RT.

Advantages of preelectrophoretic conjugation of polypeptides with fluorescent dyes

A rapid simple procedure is described for the conjugation of proteins, glycoproteins, and peptides with the fluorescent dye fluorescein isothiocyanate during the time required to polymerize a polyacrylamide gel. Such conjugation does not perturb the electrophoretic mobility of the polypeptides in detergent containing gels. The location of polypeptide . dye conjugate is evident by inspection immediately upon removal of a gel from an electrophoresis cabinet avoiding the time required for postelectrophoretic staining and destaining procedures. The sensitivity of detection of polypeptide . fluorescein conjugates is at least equivalent to that obtained using Coomassie blue.

Imaging of the optic nerve and visual pathways

The visual pathway extends from the globes anteriorly to the occipital cortex posteriorly. A wide variety of disease processes may produce visual dysfunction. Because the optic nerve is a fiber tract of the brain covered by meninges, it can be affected by many of the same pathologic processes that occur in the brain and meninges. Physical examination and diagnostic tests of visual function performed by the clinician can frequently identify the anatomic location of the causative lesion in the patient with vision loss. This enables the radiologist to optimize the imaging evaluation of the patient. This article reviews the normal anatomy of the optic nerve and visual pathways, presents computed tomography (CT) and magnetic resonance (MR) imaging techniques for evaluation of these structures, and discusses the pathologic processes intrinsic to the optic nerve and visual pathways.

The prognostic significance of midline shift at presentation on survival in patients with glioblastoma multiforme

PURPOSE While patients with glioblastoma multiforme (GBM) who present with midline shift have a presumably worse prognosis, there is little literature evaluating the prognostic significance of this presentation in multivariate analysis in the context of other known prognostic factors. METHODS AND MATERIALS From March 1981 to September 1993, 219 patients underwent irradiation for intracranial glioma at our institution. One hundred fourteen patients with a diagnosis of a primary GBM were analyzed for the influence of the presence of midline shift at diagnosis on survival with respect to other known prognostic factors, including age, Karnofsky performance status (KPS), and extent of surgery. Eighty-five patients (74%) presented with midline shift. Surgical treatment consisted of subtotal/total resection in 86 patients (75%). Among patients presenting with midline shift, 68 (80%) underwent subtotal/total resection before irradiation. RESULTS Multivariate analysis of the entire cohort of patients found none of the potential prognostic factors analyzed to significantly influence survival. The overall median survival was 6 months. However, when multivariate analysis was limited to patients with a KPS of > or = 70, only the presence of midline shift and age were found to significantly influence survival. Patients with a KPS > or = 70 and with midline shift present at diagnosis had a median survival of 8 months, as compared to 14 months for those not having midline shift at presentation (p = 0.04). Patients with a KPS > or = 70 and age > 50 years had a median survival of 5 months as compared to 11 months for those < or = 50 (p = 0.02). CONCLUSION In this series, where 80% of patients who presented with a midline shift underwent decompressive resection of GBM before irradiation, the presence of midline shift at diagnosis remained an independent prognostic factor influencing survival among good performance status patients. While the role of decompressive surgery in this setting is likely of some benefit, the extent of this benefit remains to be defined.

Combined stereotactic split-course fractionated gamma knife radiosurgery and conventional radiation therapy for unfavorable gliomas: a phase I study

The purpose of this paper was to note a potential source of error in magnetic resonance (MR) imaging. Magnetic resonance images were acquired for stereotactic planning for GKS of a vestibular schwannoma in a female patient. The images were acquired using three-dimensional sequence, which has been shown to produce minimal distortion effects. The images were transferred to the planning workstation, but the coronal images were rejected. By examination of the raw data and reconstruction of sagittal images through the localizer side plate, it was clearly seen that the image of the square localizer system was grossly distorted. The patient was returned to the MR imager for further studies and a metal clasp on her brassiere was identified as the cause of the distortion.A-60-year-old man with medically intractable left-sided maxillary division trigeminal neuralgia had severe cardiac disease, was dependent on an internal defibrillator and could not undergo magnetic resonance imaging. The patient was successfully treated using computerized tomography (CT) cisternography and gamma knife radiosurgery. The patient was pain free 2 months after GKS. Contrast cisternography with CT scanning is an excellent alternative imaging modality for the treatment of patients with intractable trigeminal neuralgia who are unable to undergo MR imaging.The authors describe acute deterioration in facial and acoustic neuropathies following radiosurgery for acoustic neuromas. In May 1995, a 26-year-old man, who had no evidence of neurofibromatosis Type 2, was treated with gamma knife radiosurgery (GKS; maximum dose 20 Gy and margin dose 14 Gy) for a right-sided intracanalicular acoustic tumor. Two days after the treatment, he developed headache, vomiting, right-sided facial weakness, tinnitus, and right hearing loss. There was a deterioration of facial nerve function and hearing function from pretreatment values. The facial function worsened from House-Brackmann Grade 1 to 3. Hearing deteriorated from Grade 1 to 5. Magnetic resonance (MR) images, obtained at the same time revealed an obvious decrease in contrast enhancement of the tumor without any change in tumor size or peritumoral edema. Facial nerve function improved gradually and increased to House-Brackmann Grade 2 by 8 months post-GKS. The tumor has been unchanged in size for 5 years, and facial nerve function has also been maintained at Grade 2 with unchanged deafness. This is the first detailed report of immediate facial neuropathy after GKS for acoustic neuroma and MR imaging revealing early possibly toxic changes. Potential explanations for this phenomenon are presented.In clinical follow-up studies after radiosurgery, imaging modalities such as computerized tomography (CT) and magnetic resonance (MR) imaging are used. Accurate determination of the residual lesion volume is necessary for realistic assessment of the effects of treatment. Usually, the diameters rather than the volume of the lesion are measured. To determine the lesion volume without using stereotactically defined images, the software program VOLUMESERIES has been developed. VOLUMESERIES is a personal computer-based image analysis tool. Acquired DICOM CT scans and MR image series can be visualized. The region of interest is contoured with the help of the mouse, and then the system calculates the volume of the contoured region and the total volume is given in cubic centimeters. The defined volume is also displayed in reconstructed sagittal and coronal slices. In addition, distance measurements can be performed to measure tumor extent. The accuracy of VOLUMESERIES was checked against stereotactically defined images in the Leksell GammaPlan treatment planning program. A discrepancy in target volumes of approximately 8% was observed between the two methods. This discrepancy is of lesser interest because the method is used to determine the course of the target volume over time, rather than the absolute volume. Moreover, it could be shown that the method was more sensitive than the tumor diameter measurements currently in use. VOLUMESERIES appears to be a valuable tool for assessing residual lesion volume on follow-up images after gamma knife radiosurgery while avoiding the need for stereotactic definition.This study was conducted to evaluate the geometric distortion of angiographic images created from a commonly used digital x-ray imaging system and the performance of a commercially available distortion-correction computer program. A 12 x 12 x 12-cm wood phantom was constructed. Lead shots, 2 mm in diameter, were attached to the surfaces of the phantom. The phantom was then placed inside the angiographic localizer. Cut films (frontal and lateral analog films) of the phantom were obtained. The films were analyzed using GammaPlan target series 4.12. The same procedure was repeated with a digital x-ray imaging system equipped with a computer program to correct the geometric distortion. The distortion of the two sets of digital images was evaluated using the coordinates of the lead shots from the cut films as references. The coordinates of all lead shots obtained from digital images and corrected by the computer program coincided within 0.5 mm of those obtained from cut films. The average difference is 0.28 mm with a standard deviation of 0.01 mm. On the other hand, the coordinates obtained from digital images with and without correction can differ by as much as 3.4 mm. The average difference is 1.53 mm, with a standard deviation of 0.67 mm. The investigated computer program can reduce the geometric distortion of digital images from a commonly used x-ray imaging system to less than 0.5 mm. Therefore, they are suitable for the localization of arteriovenous malformations and other vascular targets in gamma knife radiosurgery.

Preliminary report of a phase I study of combined fractionated stereotactic radiosurgery and conventional external beam radiation therapy for unfavorable gliomas

PURPOSE To determine the tolerance and toxicities of fractionated stereotactic radiosurgery (FSRS) given in combination with conventional external beam radiation therapy (CEBRT). METHODS AND MATERIALS From March 1995 to September 1998, 14 patients with previously unirradiated and unfavorable glioma (malignant glioma, n = 8; unfavorable low-grade glioma, n = 5; and recurrent glioma, n = 1) were stratified into 3 groups according to tumor volume (TV) to determine the initial FSRS dose schedule: Group A (n = 3): TV </= 5 cc (7 Gy x 2 pre- and post-CEBRT]; Group B (n = 6): 5 cc < TV </= 15 cc [7 Gy x 2 pre- and 7 Gy x 1 post-CEBRT]; and Group C (n = 5): 15 cc < TV </= 30 cc (7 Gy x 1 pre- and post-CEBRT). All patients received CEBRT to 59.4 Gy at 1.8 Gy/fraction. Dose escalation was planned, if toxicity was acceptable. RESULTS All patients were able to complete CEBRT without interruption or experiencing disease progression. Unacceptable toxicity has been limited to patients in groups B (grade 4, n = 2/6) and C (grade 4, n = 2/5). Eight patients required reoperation, with 3 (38%) having necrosis without evidence of tumor. Eleven patients (79%) have had objective partial (>/=50% reduction, n = 2) or minor (>20% reduction, n = 9) imaging response. Follow-up ranged from 9 to 51 months (median 15 months), with 7 patients alive at 22-51 months. CONCLUSIONS Imaging response and the ability of these patients with unfavorable intracranial gliomas to complete therapy without interruption or experiencing disease progression is very encouraging. Excessive toxicity of combined FSRS and CEBRT as evaluated thus far in this study was seen for patients with group B/C lesions. Evaluation of this novel treatment strategy with dose modification is ongoing.

Bilateral intraorbital abscesses and cavernous sinus thromboses secondary to Streptococcus milleri with a favorable outcome.

A 51-year-old woman with left proptosis, diplopia, headache, and nausea was found to have bilateral intraorbital abscesses, left superior ophthalmic vein thrombosis, bilateral cavernous sinus thromboses, and a left temporal lobe intracerebral abscess. Because the paranasal sinuses were unaffected, a dental origin was suspected and confirmed. The causative organism was Streptococcus milleri. Aggressive surgical intervention included bilateral orbital abscess drainage and dental extraction, and medical therapy included intravenous metronidazole, ceftriaxone, heparin, and methylprednisolone. A left sixth cranial nerve paresis was the only long-term sequela.

Langerhans cell histiocytosis involving the corpus callosum and cerebellum: gadolinium-enhanced MRI

Langerhans cell histiocytosis is a systemic disorder consisting of abnormal histiocyte proliferation, in the form of focal deposits. Central nervous system involvement is most common in the hypothalamus, although other sites have been described, such as the cerebellum and the meninges. We present a case with presumed involvement of the corpus callosum and cerebellum, demonstrating gadolinium enhancement on MRI.

CERVICOTHORACIC CHORDOMA PRESENTING AS PROGRESSIVE DYSPNEA AND DYSPHAGIA

Chordomas are generally considered rare primary osseous neoplasms of the basiocciput and axial skeleton that account for approximately 1% to 4% of the malignant neoplasms of bone. 1 These neoplasms grow slowly but have a strong tendency toward local invasion, and although they were once thought to have a low incidence of metastatic spread, recent reviews are demonstrating a more significant metastatic potential. 2-5Approximately 50% of chordomas arise from the sacrococcygeal area of the axial skeleton, 35% are found in the basiocciput area in the region of the clivus, and the remaining 15% arise from the true vertebrae cephalad to the sacrum. 6 Of those arising in the vertebrae, a predilection for the cervical spine has been reported. 7