Comparison of stereotactic radiosurgery and brachytherapy in the treatment of recurrent glioblastoma multiforme

The purpose of this study was to compare the efficacy of stereotactic radiosurgery (SRS) and brachytherapy in the treatment of recurrent glioblastoma multiforme (GBM). The patients had either progressive GBM or pathologically proven GBM at recurrence after previous treatment for a lower grade astrocytoma. Thirty-two patients were treated with interstitial brachytherapy, and 86 received treatment with stereotactic radiosurgery (SRS). The patient characteristics were similar in the two groups. Those patients treated with SRS had a median tumor volume of 10.1 cm3 and received a median peripheral tumor dose of 13 Gy. Patients treated with brachytherapy had a median tumor volume of 29 cm3. Median dose to the periphery of the tumor volume was 50 Gy delivered at a median dose rate of 43 cGy/hour. Twenty-one patients (24%) treated with SRS were alive, with a median follow-up of 17.5 months. Median actuarial survival, measured from the time of treatment for recurrence, for all patients treated with SRS was 10.2 months, with survivals of 12 and 24 months being 45 and 19%, respectively. A younger age and a smaller tumor volume were predictive of better outcome. The tumor dose, the interval from initial diagnosis, and the need for reoperation were not predictive of outcome after SRS. Five patients (16%) treated with brachytherapy were alive, with a median follow-up of 43.3 months. The median actuarial survival for all patients treated with brachytherapy was 11.5 months. Survivals of 12 and 24 months were 44 and 17%, respectively.(ABSTRACT TRUNCATED AT 250 WORDS)     

Magnetic resonance imaging changes after stereotactic radiation therapy for childhood low grade astrocytoma

BACKGROUND: Stereotactic radiotherapy (SRT) is fractionated radiotherapy delivered under stereotactic guidance to produce highly focal and precise therapy. We studied the incidence of imaging changes that can mimic tumor progression after completion of SRT for childhood low grade astrocytoma. METHODS: Between June 1992 and September 1994, we prospectively treated 28 children with low grade astrocytomas with SRT. The patients ranged in age from 2 to 22 years (median: 10 yrs) and none had received prior radiation therapy or radiosurgery. Routine fractionation was employed (180-200 centigray[cGy]) to a total dose of 5220-6000 cGy over 5 to 6 weeks. All of the patients underwent initial and follow-up magnetic resonance imaging (MRI) according to protocol. RESULTS: Median clinical follow-up for the 28 patients was 24 months (range, 5-32 mos) with a median radiographic follow-up of 15 months (range, 3-26 mos). Fifteen patients had reduction in tumor size, one patient had stable disease. Twelve patients (43%) developed increased size of the lesion, increased signal intensity or enhancement, cysts or cavitations, and an increase in edema or mass effect on follow-up MRI. Most of these changes occurred between 9 and 12 months after the start of SRT and resolved or decreased by 15 to 21 months. All but one patient had normal or stable neurologic examinations. CONCLUSIONS: Treatment-related MRI changes are common after conventionally fractionated schedules using stereotactic radiation techniques for patients with low grade astrocytomas. These changes can be distinguished from tumor progression by their transient nature as well as the general absence of clinical symptoms.     

Adaptation and verification of the relocatable Gill-Thomas-Cosman frame in stereotactic radiotherapy

PURPOSE: Stereotactic radiotherapy (SRT) combines techniques of stereotactic radiosurgery (SRS) with radiation therapy fractionation schemes. Fractionation in SRT necessitates a relocatable immobilization system to precisely reproduce the patient's position at each treatment. The Gill-Thomas-Cosman (GTC) head frame is such an immobilization device compatible with the Brown-Roberts-Wells (BRW) stereotactic system. We describe this device, our modifications to the original design, the repeat position accuracy, and the daily verification procedure. METHODS AND MATERIALS: The original GTC frame was tested on volunteers. This testing led to an improved strapping system, the decision to construct the oral fixation appliance at our dental clinic, and the construction of a depth confirmation helmet to rapidly confirm the position of the frame on a daily basis. The GTC frame, at our institution, is not acceptable for children requiring anesthesia, and a new frame, the "Boston Childrens' Hospital" frame, was designed. This device uses the base ring of the GTC frame. Airway access is maintained through fixation on the nasal-glabellar region and the ear canal rather than the hard palate and upper gingiva. RESULTS: The modifications of the GTC frame and the verification protocol result in repeat positioning of the frame with respect to the patient anatomy, with a standard deviation of 0.4 mm for both the modified GTC frame and the Boston Childrens' Hospital frame. The relocatibility of the frames has been established in over 2,000 patient setups in over 60 patients to date. DISCUSSION: The GTC frame is a noninvasive and versatile fixation system that provides patient comfort, as well as accurate relocatibility for SRT. The frame is not appropriate for single fraction radiosurgery, as a large setup error (> 2 mm) for a single treatment cannot be excluded. The GTC frame is compatible with the BRW system, and treatment planning for SRT and SRS patients is identical. We currently treat 10-13 SRT patients per day with intracranial neoplasms on a dedicated stereotactic therapy unit. In addition, the Boston Childrens' Hospital frame allows the use of stereotactic therapy in the treatment of children under 6 years of age. This population will benefit especially from precise and highly focal cranial irradiation.     

Arnold-Chiari malformation in a captive African lion cub

PURPOSE: Surgery and systemic chemotherapy offer modest benefit to patients with recurrent glioblastoma multiforme. These tumors are associated with rapid growth and progressive neurological deterioration. Radiosurgery offers a rational alternative treatment, delivering intensive local therapy. A pilot protocol to treat recurrent glioblastoma was developed using fractionated stereotactic radiosurgery with concurrent intravenous (i.v.) Taxol as a radiation sensitizer. METHODS AND MATERIALS: The treatment outcome was analyzed in 14 patients with recurrent glioblastoma treated with fractionated stereotactic radiosurgery and concurrent Taxol. Median tumor volume was 15.7 cc and patients received a mean radiation dose of 6.2 Gy at 90% isodose line, 4 times weekly. The median dose of Taxol was 120 mg/m2. RESULTS: The median survival was 14.2 months, 1-year survival was 50%. CONCLUSIONS: Survival for this small group of patients was similar to or better than historical controls or patients treated with single-fraction radiosurgery alone. This data should stimulate the investigation of both fractionated radiosurgery and the development of radiation sensitizers to further enhance treatment.     

Psychosocial consequences of weight cycling

PURPOSE: To perform stereotactic radiation therapy (SRT) without cranially fixated stereotactic frames, we developed a dual computed tomography (CT) linear accelerator (linac) treatment unit. METHODS AND MATERIALS: This unit is composed of a linac, CT, and motorized table. The linac and CT are set up at opposite ends of the table, which is suitable for both machines. The gantry axis of the linac is coaxial with that of the CT scanner. Thus, the center of the target detected with the CT can be matched easily with the gantry axis of the linac by rotating the table. Positioning is confirmed with the CT for each treatment session. Positioning and treatment errors with this unit were examined by phantom studies. Between August and December 1994, 8 patients with 11 lesions of primary or metastatic brain tumors received SRT with this unit. All lesions were treated with 24 Gy in three fractions to 30 Gy in 10 fractions to the 80% isodose line, with or without conventional external beam radiation therapy. RESULTS: Phantom studies revealed that treatment errors with this unit were within 1 mm after careful positioning. The position was easily maintained using two tiny metallic balls as vertical and horizontal marks. Motion of patients was negligible using a conventional heat-flexible head mold and dental impression. The overall time for a multiple noncoplanar arcs treatment for a single isocenter was less than 1 h on the initial treatment day and usually less than 20 min on subsequent days. Treatment was outpatient-based and well tolerated with no acute toxicities. Satisfactory responses have been documented. CONCLUSION: Using this treatment unit, multiple fractionated SRT is performed easily and precisely without cranially fixated stereotactic frames.     

Transnasal stereotactic surgery of pituitary adenomas concomitant with acromegaly

Since 1960 we have performed stereotactic transsphenoidal cryohypophysectomy in 70 patients with pituitary adenomas, 42 women and 28 men, aged 11-59 years. The dominant clinical syndrome was acromegaly in 50 patients, galactorrhea in 9, amenorrhea in 5, adiposogenital dystrophy in 4 and gigantism with mild endocrine symptomatology in 2 patients. In 67 patients the histological structure of the tumor was established by biopsy (50 patients with eosinophil adenoma, 10 with mixed-type adenoma, 4 with chromophobe adenoma and 3 with basophil adenoma). Somatotropic hormone, human growth hormone, prolactin, ACTH and 17-ketosteroid levels indicated active/inactive adenomas. In 42 cases the adenoma was only intrasellar, which was confirmed by contrast X-ray investigations, CT scanning, angiography and ophthalmological investigation. Transnasal stereotactic cryohypophysectomy was performed in all 70 cases using a stereotactic apparatus especially designed for operations on the pituitary. All patients (except 2) tolerated the operation well. No complications occurred. Vision deteriorated after operation in 1 patient. Thrombosis of the left middle cerebral artery developed in another patient. All the other patients noted improvement directly after operation - rapid diminution of signs of acromegaly and rapid restoration of normal values in hormonal tests. Six patients with continuing growth of the tumor underwent a second operation 1.5-6 years after the first operation. We conclude from our own clinical experience and information from the literature that transnasal stereotactic cryodestruction is highly effective and relatively safe in the management of pituitary adenoma.     

The lazaroid U74389G protects normal brain from stereotactic radiosurgery-induced radiation injury

PURPOSE: To test an established model of stereotactic radiosurgery-induced radiation injury with pretreatments of either methylprednisolone or the lazaroid U74389G. METHODS AND MATERIALS: Nine cats received stereotactic radiosurgery with a linear accelerator using and animal radiosurgery device. Each received a dose of 125.0 Gy prescribed to the 84% isodose shell to the anterior limb of the right internal capsule. One animal received no pretreatment, two received citrate vehicle, three received 30 mg/kg of methylprednisolone, and three received 5 mg/kg of U74389G. After irradiation, the animals had frequent neurologic examinations, and neurologic deficits developed in all of them. Six months after the radiation treatment, the animals were anesthetized, and had gadolinium-enhanced magnetic resonance (MR) scans, followed by Evans blue dye perfusion, euthanasia, and brain fixation. RESULTS: Magnetic resonance scans revealed a decrease in the size of the lesions from a mean volume of 0.45 +/- 0.06 cm(3) in the control, vehicle-treated, and methylpredniosolone-treated animals to 0.22 +/- 0.14 cm(3) in the U74389G-treated group. The scans also suggested the absence of necrosis and ventricular dilatation in the lazaroid-treated group. Gross pathology revealed that lesions produced in the untreated, vehicle-treated, and methylprednisolone-treated cats were similar and were characterized by a peripheral zone of Evans blue dye staining with a central zone of a mature coagulative necrosis and focal hemorrhage. However, in the U74389G-treated animals, the lesions were found to have an area of Evans blue dye staining, but lacked discrete areas of necrosis and hemorrhage. CONCLUSION: These results suggest that the lazaroid U74389G protects the normal brain from radiation injury produced by stereotactic radiosurgery.     

Permanent I-125 brain stem implants in children

Between 1988 and 1997, 28 children have had iodine-125 implants for CNS tumors performed in our institution. Ten had stereotactic implantation in the brain stem region, and nine had the diagnosis of brain stem glioma (8 diffuse pontine, 1 midbrain tumor). Their ages ranged from 1.8 to 12 years. All patients had histological confirmation of malignancy (7 high-grade glioma, 2 low-grade glioma, 1 PNET). Diffuse pontine glioma patients received external beam radiation (50 Gy) followed by a fractionated stereotactic boost of 3 Gyx4 fractions. After 4-6 weeks, patients were reevaluated for stereotactic interstitial I-125 therapy. The planned implant dose was 82.9 Gy to the enhancing tumor (4 cGy per h). Preliminary results indicated that no surgical complications were associated with the catheter placement. Four patients have died (7-9 months from diagnosis) and four patients remain alive (5-38 months from diagnosis, median 10 months). Two autopsies confirmed the presence of progressive glioblastoma multiforme and intralesional necrosis. In one patient who received an implant alone for midbrain LGA, necrosis without tumor was found on biopsy after 36 months. He was successfully treated with hyperbaric oxygen therapy. The implementation of permanent I-125 implants appears to have a role in the management of pediatric CNS malignancy. This study confirms the results of previous reports regarding the safety of stereotactic interstitial brachytherapy in the brain stem. Tumor control for patients with high-grade brain stem glioma remains poor even with high focal radiation doses.     

Preservation of cranial nerve function after treatment of acoustic neurinomas with fractionated stereotactic radiotherapy. Preliminary observations in 26 patients

Twenty-seven acoustic tumors in 26 patients were treated with multiple fractionated linear-accelerator-based stereotactic radiotherapy (SRT). All patients with intact pretreatment facial nerve function with either small or large tumor volumes have thus far experienced no treatment-related facial neuropathy, including 9 patients with a mean follow-up of 22.4 +/- 1.6 months. The incidence of evaluable trigeminal neuropathy was 13%, and in 5 of 7 patients with serviceable pretreatment hearing, audiometry was unchanged in the immediate posttreatment period. Longer follow-up will be necessary to evaluate hearing preservation after SRT. Tumor response with central necrosis was seen in all assessable patients. SRT can be performed for cerebellopontine angle tumors with accuracy and reproducibility. It achieves a biological response similar to single fraction radiosurgery and may lower the incidence of facial and trigeminal neuropathies.     

Preoperative cortical localization with functional MRI for use in stereotactic radiosurgery

Accurate localization of the lesion with respect to functionally significant brain is essential to safe stereotactic radiosurgical dose planning. We report the use of functional MR imaging in 3 patients to identify critical areas of surrounding brain and to provide assistance with dose planning, especially with regard to shaping the peripheral isodose around the lesion. We used a functional MRI system employing a conventional 1.5-tesla MRI unit that can detect decreases in deoxyhemoglobin concentration occurring with performance of specific tasks. Two of the patients had supratentorial arteriovenous malformations and 1 patient had a recurrent parasagittal meningioma. Functional MRI provided information on the location of speech, motor, and sensory cortex in these patients. Radiosurgical dose plans were constructed that kept these cortical areas outside of the 30% isodose curves. We believe that the safety of supratentorial parenchymal radiosurgery will be enhanced by the localization of critical brain regions around the target.     

Monte Carlo dosimetry study of a 6 MV stereotactic radiosurgery unit

Small-field and stereotactic radiosurgery (SRS) dosimetry with radiation detectors, used for clinical practice, have often been questioned due to the lack of lateral electron equilibrium and uncertainty in beam energy. A dosimetry study was performed for a dedicated 6 MV SRS unit, capable of generating circular radiation fields with diameters of 1.25-5 cm at isocentre using the BEAM/EGS4 Monte Carlo code. With this code the accelerator was modelled for radiation fields with a diameter as small as 0.5 cm. The radiation fields and dosimetric characteristics (photon spectra, depth doses, lateral dose profiles and cone factors) in a water phantom were evaluated. The cone factor (St) for a specific cone c at depth d is defined as St(d, c) = D(d, c)/D(d, c(ref)), where c(ref) is the reference cone. To verify the Monte Carlo calculations, measurements were performed with detectors commonly used in SRS such as small-volume ion chambers, a diamond detector, TLDs and films. Results show that beam energies vary with cone diameter. For a 6 MV beam, the mean energies in water at the point of maximum dose for a 0.5 cm cone and a 5 cm cone are 2.05 MeV and 1.65 MeV respectively. The values of St obtained by the simulations are in good agreement with the results of the measurements for most detectors. When the lateral resolution of the detectors is taken into account, the results agree within a few per cent for most fields and detectors. The calculations showed a variation of St with depth in the water. Based on calculated electron spectra in water, the validity of the assumption that measured dose ratios are equal to measured detector readings was verified.     

Flow cytometric analysis of peripheral blood and bone marrow for tumor cells in patients with neuroblastoma

PURPOSE: To report initial clinical experience with a novel high-precision stereotactic radiotherapy system. METHODS AND MATERIALS: Sixty patients ranging in age from 2 to 82 years received a total of 1426 treatments with the University of Florida frameless stereotactic radiotherapy system. Of the total, 39 (65%) were treated with stereotactic radiotherapy (SRT) alone, and 21 (35%) received SRT as a component of radiotherapy. Pathologic diagnoses included meningiomas (15 patients), low-grade astrocytomas (11 patients), germinomas (9 patients), and craniopharyngiomas (5 patients). The technique was used as means of dose escalation in 11 patients (18%) with aggressive tumors. Treatment reproducibility was measured by comparing bite plate positioning registered by infrared light-emitting diodes (IRLEDs) with the stereotactic radiosurgery reference system, and with measurements from each treatment arc for the 1426 daily treatments (5808 positions). We chose 0.3 mm vector translation error and 0.3 degrees rotation about each axis as the maximum tolerated misalignment before treating each arc. RESULTS: With a mean follow-up of 11 months, 3 patients had recurrence of malignant disease. Acute side effects were minimal. Of 11 patients with low grade astrocytomas, 4 (36%) had cerebral edema and increased enhancement on MR scans in the first year, and 2 required steroids. All had resolution and marked tumor involution on follow-up imaging. Bite plate reproducibility was as follows. Translational errors: anterior-posterior, 0.01 +/- 0.10; lateral, 0.02 +/- 0.07; axial, 0.01 +/- 0.10. Rotational errors (degrees): anterior-posterior, 0.00 +/- 0.03; lateral, 0.00 +/- 0.06; axial, 0.01 +/- 0.04. No patient treatment was delivered beyond the maximum tolerated misalignment. Daily treatment was delivered in approximately 15 min per patient. CONCLUSION: Our initial experience with stereotactic radiotherapy using the infrared camera guidance system was good. Patient selection and treatment strategies are evolving rapidly. Treatment accuracy was the best reported, and the treatment approach was practical.     

Computer-assisted CT-guided stereotactic biopsy and brachytherapy of brain tumors

From March 1991 to September 1993, 26 patients (aged 4-78 years) with brain tumors (4 glioblastoma multiforme, 10 nonglioblastoma multiforme, 1 mixed oligoastrocytoma, 2 carniopharyngiomas, 2 meningiomas and 7 metastases) were treated with stereotactic techniques at the Centro Internacional de Restauración Neurológica, La Habana, Cuba. A total of 28 stereotactic surgical procedures were performed with no operative mortality; they included biopsies in all cases, 1 stereotactic microsurgical resection and 12 permanent implants of 192Ir, followed by external beam fractionated radiation therapy (40-60 Gy). The present paper shows that the combined use of a stereotactic approach, a comprehensive and reliable stereotactic dosimetric planning system, stereotactic brachytherapy with 192Ir and complementary percutaneous radiation treatment constitutes a promising strategy for brain tumor management.     

Pathological changes in surgically resected angiographically occult vascular malformations after radiation

OBJECTIVE: The goal of this study was to evaluate the pathological changes associated with radiation treatment (stereotactic radiosurgery or conventional irradiation) of angiographically occult vascular malformations (AOVMs). METHODS: Eleven patients underwent surgical resection of an AOVM in the mesial temporal lobe, brain stem, thalamus, or basal ganglia after previous radiation treatment. The indications for surgery were recurrent symptomatic bleeding from the lesion in 10 patients and recurrent intractable seizures in 1 patient. Radiation was used as the initial therapy because the risk of surgical resection was deemed too high. Three patients received conventional radiation therapy of 3000 to 5400 rads at an outside institution. One patient received radiosurgery with the gamma knife at another institution using a dose of 15 Gy to the margin. The remaining 7 patients received stereotactic radiosurgery with a helium-ion particle beam. The dose range was from 18 to 26 Gy equivalents. The interval from radiation to surgical resection ranged from 1 to 10 years, with a mean of 3.5 years. These lesions were compared with 10 nonirradiated cavernous malformations. RESULTS: One irradiated lesion was identified pathologically as a true arteriovenous malformation despite being angiographically occult. This lesion did not demonstrate significant changes in the vasculature but did have radiation necrosis of the surrounding brain 5 years after 25 Gy equivalents of helium-ion radiosurgery. Two other specimens were too small to identify the type of vascular malformation adequately. Of the remaining eight malformations identified as cavernous malformations, six showed a combination of marked fibrosis of the vascular channels, fibrinoid necrosis, and ferrugination. However, the fibrinoid necrosis was the only finding unique to the irradiated lesions compared with nonirradiated controls. All the irradiated lesions still had patent vascular channels; none were completely thrombosed. CONCLUSION: Radiosurgery or conventional radiation therapy did not cause histologic vascular obliteration in intracranial AOVMs evaluated 1 to 10 years (mean 3.5 yr) after radiation delivery. It should be recognized that these patients are irradiation failures who may not be representative of all irradiated patients. However, recurrent bleeding from AOVMs may relate to poor radiation response in some patients.     

Dosimetry studies with TLDs for stereotactic radiation techniques for intraocular tumours

Between March 1993 and January 1997, stereotactic radiation techniques were used to irradiate 66 intraocular tumour patients with the Gamma Knife (Leksell Gamma Knife, model B unit) at the University of Vienna, Austria. This study investigates the dosimetry for stereotactic irradiation of ocular structures. For the dosimetry program KULA 4.4, Gamma Knife stereotactic irradiation of the eye represents an extreme frontal skull position. In addition, irradiation of the eye may be performed in the usual supine position in exceptional cases only. With the patient in the prone position, the dose planning program has to calculate with a significantly large number of single-beam extrapolations. In our first experiment we measured the isocentre dose for eight different gamma-angle positions, both in prone and supine positions, using TLD measurements in an Alderson head phantom. We found a maximum deviation of +/- 1.6% using these individually calibrated TLDs. In the second experiment we examined the dose cross profiles for the two most frequently used treatment positions (supine position, gamma = 65 degrees, and prone position, gamma = 140 degrees). For this purpose we implanted a specially designed TLD array into the orbit of a human cadaver head. We found excellent agreement of the dose values measured for the isocentre as well as the posterior part of the eye with orbit with deviations of less than -2.7%. However, for the anterior part of the eye, deviations between computer-generated calculations and the TLD measurements were found to range up to -30%. These differences were noticed both for supine and prone positions. For the Gamma Knife stereotactic irradiation of ocular tumours or pathologies, precautions should be taken to avoid significant underdosage in the anterior part of the radiation field.     

Can advanced hemostatic parameters detect disseminated intravascular coagulation more accurately in patients with cirrhosis of the liver?

BACKGROUND: A regimen of multi-drug chemotherapy alternating with split course hyperfractionated radiation therapy (HFRT) was adopted for the treatment of patients with rhabdomyosarcoma (RMS). The purpose of this treatment regimen was to allow for the timely delivery of radiation and chemotherapy, reduce treatment-related toxicity, and improve compliance. PROCEDURE: Forty-four patients with stages II-IV RMS were treated with HFRT and received 5,400 cGy. The treatment was administered in two courses (3,000 and 2,400 cGy) and separated by a 4-week interval. HFRT consisted of 150 cGy delivered twice a day, 5 days a week with an interfraction interval of 4-6 hours. A limited comparison was made between the HFRT patients and 42 historical patients with comparable clinical characteristics who were treated with similar chemotherapy and conventionally fractionated radiation therapy (CFRT) (median 4,800 cGy, range 4,000-5,680 cGy). RESULTS: HFRT patients completed radiation therapy in 59.1 +/- 9.4 days (mean +/- SD) and CFRT patients completed treatment in 56.6 +/- 10.5 days compared to an expected 52 and 40 days, respectively. With a median follow-up of 55 months for the HFRT patients and 104 months for the CFRT patients, no differences in local control or survival were noted. Nine of 44 (21%) HFRT and 8/42 (19%) CFRT patients experienced local failure. The median time to local failure was 15 months for patients in the HFRT group and 11 months for patients in the CFRT group. CONCLUSIONS: The results of the HFRT regimen were acceptable in terms of toxicity and compliance. No improvement in local control was obtained by alternating radiation and chemotherapy. The lack of difference between patients treated with HFRT and CFRT may be related to the lengthened treatment time of the split course regimen, the small difference in total dose, and tumor repopulation.     

Risk analysis of linear accelerator radiosurgery

PURPOSE: To evaluate the toxicity of stereotactic single-dose irradiation and to compare the own results with already existing risk prediction models. METHODS AND MATERIALS: Computed tomography (CT) or magnetic-resonance (MR) images, and clinical data of 133 consecutive patients treated with linear accelerator radiosurgery were analyzed retrospectively. Using the Cox proportional hazards model the relevance of treatment parameters and dose-volume relationships on the occurrence of radiation-induced tissue changes (edema, localized blood-brain barrier breakdown) were assessed. RESULTS: Sixty-two intraparenchymal lesions (arteriovenous malformation (AVM): 56 patients, meningioma: 6 patients) and 73 skull base tumors were selected for analysis. The median follow-up was 28.1 months (range: 9.0-58.9 months). Radiation-induced tissue changes (32 out of 135, 23.7%) were documented on CT or MR images 3.6-58.7 months after radiosurgery (median time: 17.8 months). The actuarial risk at 2 years for the development of neuroradiological changes was 25.8% for all evaluated patients, 38.4% for intraparenchymal lesions, and 14.6% for skull base tumors. The coefficient: total volume recieving a minimum dose of 10 Gy (VTREAT10) reached statistical significance in a Cox proportional hazards model calculated for all patients, intraparenchymal lesions, and AVMs. In skull base tumors, the volume of normal brain tissue covered by the 10 Gy isodose line (VBRAIN10) was the only significant variable. CONCLUSIONS: These results demonstrate the particular vulnerability of normal brain tissue to single dose irradiation. Optimal conformation of the therapeutic isodose line to the 3D configuration of the target volume may help to reduce side effects.     

Preventive effects of an antiallergic drug, pemirolast potassium, on restenosis after percutaneous transluminal coronary angioplasty

PURPOSE: Radiosurgery is an effective treatment for cerebral arteriovenous malformations. We conducted the present study to investigate the feasibility and efficacy of gamma knife radiosurgery for dural arteriovenous fistulas (DAVFs) of the cavernous sinus. METHODS: Eighteen patients (12 women and six men; 29-75 years old [mean age, 55 years]) with DAVFs of the cavernous sinus (Barrow's type B:1, C:7, and D:10) treated by gamma knife radiosurgery were enrolled in the study. DAVFs were bilateral in six patients and unilateral in 12. Stereotactic X-ray angiography and MR imaging were performed for targeting the radiosurgery. Areas of arteriovenous communication targeted for irradiation were first outlined on the X-ray angiograms. The target regions were then transferred to and displayed on the MR images. Dose planning was based on findings on the integrated images. Prescribed maximum target doses were 22 to 38 Gy (mean, 28 Gy). The targets were covered by 50% to 90% isodose levels. Radiation doses to the surrounding optic apparatus were kept to less than 8 Gy. The patients were followed up with color Doppler sonography and MR imaging. When noninvasive imaging suggested obliteration, X-ray angiography was performed to verify the results. RESULTS: The DAVFs were totally obliterated in 12 (80%) of the 15 patients. In the other three, one was almost completely obliterated at 14 months and two were partially obliterated at 19 and 27 months, respectively, after radiosurgery. No complications or symptom worsening occurred during the follow-up period. CONCLUSION: Gamma knife radiosurgery is a feasible, effective, and safe treatment for DAVFs of the cavernous sinus. Integration of stereotactic X-ray angiography and MR imaging not only aids treatment efficacy but also protects the relevant vital structures, especially the optic apparatus, from the hazards of radiation.     

125I plaque therapy for uveal melanoma. Analysis of the impact of time and dose factors on local control

BACKGROUND: 125I episcleral plaque therapy has gained wide acceptance for the treatment of uveal melanoma because of its potential to preserve vision, salvage the globe, and provide good local control. A rigorous analysis of the optimum radiation dose, dose rate, and overall treatment time has not been reported with this technique. METHODS: One hundred fifty patients with uveal melanoma treated with 125I plaques between 1982 and 1990 and included in the uveal melanoma study (UMS) database of the Wills Eye Hospital were analyzed. Mean patient age was 60.7 years (range: 17.7-84.6 years). Initial mean tumor size was 9.7 x 8.5 x 3.7 mm with a range of 4.5 to 21.5 mm in basal dimension and 1.2 to 11.8 mm in height. Mean dose to the tumor apex was 94.77 gray (Gy) (29.5-141 Gy). Mean dose rate to the tumor apex was 92.9 cGy/hr (10-292 cGy/hr); the mean dose to the base was 359 Gy (181-692 Gy); the mean dose rate to the base was 348 cGy/hr (112-893 cGy/hr); and mean duration of treatment was 124.7 hours (range: 28-333 hours) RESULTS: With a median follow-up of 68 months, there have been 33 local failures. Mean time to local failure was 19 months (range: 6-78 months). Actuarial local control is 81% at 5 years. Multivariate analysis demonstrates significant correlation of local failure with larger tumor dimension (P = 0.0046), close proximity to the optic disc (P = 0.0029), lower radiation dose to the tumor apex (P = 0.03), lower radiation dose rate to the tumor apex and base (P = 0.01 and 0.03), and longer overall treatment time (P = < 0.0001). CONCLUSIONS: This retrospective analysis reinforces the importance of dose rate, minimum tumor dose, overall treatment time, maximum tumor basal dimension, and proximity to the optic nerve in the treatment of uveal melanoma.