Hemangioblastoma of the posterior fossa. The role of multimodality treatment

The authors made a review of a series of patients with hemangioblastomas of the posterior fossa treated between 1973 and 1993. A total of 32 patients were analyzed with 24 patients receiving resection, 8 patients receiving radiosurgery and 2 patients receiving conventional radiotherapy. The mortality in the patients with a resection was considered acceptable with 2 deaths (8%) and with a morbidity of 3 patients (12.5%). A review of the literature suggests that conventional radiotherapy with high doses (45-60 Gy) may have a role in the post-operative control of hemangioblastomas and in some cases could be employed even before the resection in order to facilitate the surgery. The radiosurgical treatment is regarded like adjuvant. Poor results were obtained with radiosurgery in large tumors where low doses (less than 20 Gy) were used. Because of the rarity and complexity of these tumors, mainly when associated with von Hippel-Lindau disease, a multicenter study could be useful with the assessment of the optimal utilization and combination of these treatment modalities.     

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.     

Comparison of parental and health care professional preferences for the acellular or whole cell pertussis vaccine

PURPOSE: To evaluate the efficacy and toxicity of gamma knife radiosurgery in the treatment of melanoma metastases to the brain. PATIENTS AND METHODS: We retrospectively reviewed 55 patients with single or multiple intracranial melanoma metastases treated at the University of California, San Francisco, with gamma knife radiosurgery from 1991 through 1995. Sixteen patients were treated with gamma knife radiosurgery for recurrence following previous radiation therapy, 11 received radiosurgery as a boost to whole-brain radiation therapy, and 28 had radiosurgery alone for initial management of brain metastases. The median minimum radiosurgery tumor dose for 140 treated lesions was 19 Gy (range, 10-22 Gy) prescribed at the 35% to 90% isodose contour (median, 50%). The median total target volume per patient was 6.1 cc (range, 0.25-28.3 cc). RESULTS: With a median follow-up of 75 weeks in living patients, the median survival times were 35 weeks overall: 35 weeks for patients with solitary metastases versus 33 weeks for those with multiple metastases. A factor that was significant in univariate analysis of survival was total target volume treated. This parameter remained significant on multivariate analysis. The actuarial median freedom from progression analyzed by lesion for 113 lesions in 46 patients with imaging follow-up was 89 weeks with 6-month and 1-year actuarial freedom from progression rates of 89% (95% confidence interval, 80%-95%) and 77% (95% confidence interval, 62%-87%). In univariate analysis, improved freedom from progression was associated with smaller target volume treated, smaller maximum diameter, or higher prescribed dose. Four patients (7%) developed acute Radiation Therapy Oncology Group grade > or = 2 morbidity, and five patients (9%) developed late grade > or = 2 morbidity. DISCUSSION: Median survival and freedom from progression in patients treated with radiosurgery for melanoma metastatic to the brain are comparable to results in published radiosurgery series of grouped histologies. For melanoma patients, total intracranial tumor volume appears to be of greater prognostic significance than the absolute number of metastases treated. We conclude that gamma knife radiosurgery is effective and should be considered among various management strategies.     

Effects of gamma knife radiosurgery for brain tumors: clinical evaluation

BACKGROUND: Gamma knife radiosurgery is a safe and effective alternative to microsurgery in the management of selected intracranial lesions. In our initial three-year experience with gamma knife radiosurgery, 431 patients were treated using this method. This report presents the treatment results for three different types of brain tumors: benign meningiomas, malignant metastases and gliomas. METHODS: A retrospective study was performed to analyze a consecutive series of 71 meningiomas, 31 metastatic tumors and 21 gliomas treated by gamma knife radiosurgery between March 1993 and May 1996. The treatment results were investigated using regular magnetic resonance examinations and tumor volume measurement at six-month intervals to observe sequential changes of the tumors. Patients with meningiomas were further divided into three groups according to the peripheral radiation doses: high-dose (20-17 Gy, n = 18), medium-dose (16-15 Gy, n = 33) and low-dose (14-12 Gy, n = 20). The Generalized Estimation Equation was applied to compare treatment results in these three groups with different doses and tumor volumes. RESULTS: Volume measurements of the 71 meningiomas showed that 76% decreased in size, 16% stabilized and 8% increased in size. The volumes increased most frequently in the early stage (6-12 months) after treatment and subsequently regressed after the twelfth month. The tumor control rate for meningiomas in our three-year follow-up was over 90%. For meningiomas, the statistical analysis showed that both the radiation dose and tumor volume were significantly related to the development of adverse radiation effects (p < 0.05). In metastatic tumors, rapid tumor regression after radiosurgery was found in 87% of the patients. In gliomas, radiosurgery effectively inhibited tumor growth in selected patients with small, circumscribed, less infiltrative tumors. Ependymomas and low-grade astrocytomas had more favorable outcomes than other gliomas. CONCLUSIONS: Gamma knife radiosurgery is effective for controlling tumor growth in benign meningiomas for up to three years after surgery. In selected cases of malignant metastasis and gliomas, most patients appeared to benefit from the treatment with symptomatic improvement and prolonged survival. Treatment strategy and dose selection in radiosurgery should be adjusted to optimize tumor control and avoid adverse radiation effects.     

Pharmacokinetics of the PDGF-antagonist trapidil in patients with and without renal impairment

BACKGROUND: From July 1989 to February 1996, 130 patients underwent stereotactic radiosurgery. We report the results of the first 50 patients eligible for a minimum of three years of follow-up. METHODS: Twenty women and 30 men, (mean age: 37.5 years) were treated by dynamic rotation on a 6 MV linear accelerator. Prior treatment was embolization in seventeen, surgery in three and embolization and surgery in six. All had DSA and enhanced CT scanning, while some had MRI. Forty-seven treatments used a single isodose. Restricting eloquent normal tissue to 15 Gy, margin doses (at 50-90% isodose) were 12 Gy (one patient); 15 Gy (sixteen patients); 20 Gy (31 patients); 25 Gy (two patients). Maximum diameters were: < 1.5 cm (12 patients); < 2.0 cm (nine patients); < 2.5 cm (twelve patients); < 3.0 cm (thirteen patients; 3.0 cm (four patients). RESULTS: Forty-five patients were evaluable at three years, with thirty-nine having angiography. Twenty-five had angiographically confirmed obliterations; two had parenchymal AVMs obliterated but with residual dural components; four had MRI evidence of obliteration (refused angiography). One patient acutely had a seizure; one patient (with hemorrhages, resection, and embolizations preceding two applications of radiosurgery, separated by 3.5 years) had worsening of memory. CONCLUSIONS: Our uncorrected (five patients unevaluable at three years) and corrected angiographically confirmed obliteration rates are 54% and 60% respectively. Our follow-up (98% accounting of cohort; 78% angiographic rate) and explicit derivation of denominators help delineate the efficacy of radiosurgery at these doses.     

Interim report on the radiosurgical treatment of cerebral arteriovenous malformations. The influence of size, dose, time, and technical factors on obliteration rate

During the authors' initial 4-year experience with radiosurgery using the Leksell cobalt-60 gamma unit, they treated 121 patients with cerebral arteriovenous malformations (AVMs). The radiosurgical dose to the margin of the nidus was 20 Gy for lesions less than 2.0 cm in diameter (volume < or = 4.2 cm3); 18 Gy for malformations 2.1 to 3.0 cm in diameter (volume 4.2-14.1 cm3); and 16 Gy for malformations greater than 3.0 cm (volume > 14.1 cm3). Fifty-one patients underwent follow-up angiography between 1 and 3 years after treatment, and complete obliteration of the nidus was confirmed in 38 (74.5%) of these patients. Thirty-two (74.4%) of 43 AVMs with volumes of 10 cm3 or less and six (75%) of eight larger AVMs (volume 11-30 cm3) showed complete obliteration. Analysis of the time course of AVM nidus shrinkage and obliteration showed that most of the radiosurgically induced effect had occurred by 36 months after treatment. Retrospective analysis of the dose plans for 10 AVMs that were not obliterated by 36 months after gamma knife radiosurgery at the authors' institution (eight cases) or elsewhere (two cases) revealed that six AVMs had not been covered completely by the prescribed isodose. Six (5%) of the 121 patients developed neurological deficits as a direct result of radiosurgical treatment. The authors infer from these data that malformations up to 30 cm3 in volume (approximately 4.0 cm in average diameter) can be treated effectively with an acceptably low complication rate using a radiosurgical dose of 16 Gy to the margin of the nidus. The obliteration rate for the larger malformations that were treated with a dose of 16 to 18 Gy appears to be similar to that for smaller ones treated with 18 to 20 Gy. As more experience accrues using radiosurgery to treat AVMs, patient selection criteria and the variables associated with successful obliteration of the nidus should become more clearly defined.     

Prevalence, morphology and biology of renal cell carcinoma in von Hippel-Lindau disease compared to sporadic renal cell carcinoma

PURPOSE: Renal cell carcinoma occurs as a sporadic tumor but may be part of the autosomal dominant von Hippel-Lindau disease, characterized by retinal and central nervous system hemangioblastoma, pheochromocytoma, pancreatic cysts and renal cell carcinoma. We determine the prevalence of von Hippel-Lindau disease in a series of unselected renal cell carcinoma cases by molecular genetic analysis, and compare sporadic to von Hippel-Lindau renal cell carcinoma with respect to morphology and biology. MATERIALS AND METHODS: We established registers comprising 63 subjects with von Hippel-Lindau renal cell carcinoma, belonging to 30 distinct families (register A), and 460 unselected patients operated on for renal cell carcinoma in an 11-year period (register B). Molecular genetic analysis of the von Hippel-Lindau gene was performed for living patients of register A, representing 80% of von Hippel-Lindau families, and register B, 62% living patients, to identify von Hippel-Lindau germline mutations. In addition, register B was evaluated by a questionnaire (95% response) for familial occurrence of von Hippel-Lindau disease. RESULTS: The prevalence of von Hippel-Lindau renal cell carcinoma was 1.6% in 189 consenting unselected renal cell carcinoma patients. Risk factors for occult germline von Hippel-Lindau gene mutations in register B included familial renal cell carcinoma in 3 of 3 patients (100%), multifocal or bilateral renal cell carcinoma in 1 of 10 (10%) and age younger than 50 years at diagnosis in 1 of 33 (3%). Compared to sporadic von Hippel-Lindau renal cell carcinoma was characterized by an occurrence 25 years earlier, association with renal cysts, multifocal and bilateral tumors, cystic organization and low grade histology, and a better 10-year survival (p < 0.001 each). In von Hippel-Lindau disease metastases occurred only in tumors larger than 7 cm. CONCLUSIONS: von Hippel-Lindau differs from sporadic renal cell carcinoma in morphology and biology. Our data provide arguments for planning surgery for von Hippel-Lindau renal cell carcinoma and should stimulate future investigations.     

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)     

Trends in surgical management of astrocytomas and other brain gliomas

PURPOSE: Retrospective analysis of the influence of clinical and technical factors on local control and survival after radiosurgery for brain metastasis. PATIENTS AND METHODS: From January 1994 to December 1996, 42 patients presenting with 71 metastases underwent radiosurgery for brain metastasis. The median age was 56 years and the median Karnofsky index 80. Primary sites included: lung (20 patients), kidney (seven), breast (five), colon (two), melanoma (three), osteosarcoma (one) and it was unknown for three patients. Seventeen patients had extracranial metastasis. Twenty-four patients were treated at recurrence which occurred after whole brain irradiation (12 patients), surgical excision (four) or after both treatments (eight). Thirty-six sessions of radiosurgery have been realized for one metastasis and 13 for two, three or four lesions. The median metastasis diameter was 21 mm and the median volume 1.7 cm3. The median peripheral dose to the lesion was 14 Gy, and the median dose at the isocenter 20 Gy. RESULTS: Sixty-five metastases were evaluable for response analysis. The overall local control rate was 82% and the 1-year actuarial rate was 72%. In univariate analysis, theoretical radioresistance (P = 0.001), diameter less than 3 cm (P = 0.039) and initial treatment with radiosurgery (P = 0.041) were significantly associated with increased local control. Only the first two factors remained significant in multivariate analysis. No prognostic factor of overall survival was identified. The median survival was 12 months. Six patients had a symptomatic oedema (RTOG grade 2), only one of which requiring a surgical excision. CONCLUSION: In conclusion, 14 Gy delivered at the periphery of metastasis seems to be a sufficient dose to control most brain metastases, with a minimal toxicity. Better results were obtained for lesions initially treated with radiosurgery, theoretically radioresistant and with a diameter less than 3 cm.     

The role of stereotactic radiosurgery in the treatment of malignant skull base tumors

PURPOSE: To determine the efficacy and toxicity of stereotactic radiosurgery in the treatment of malignant skull base tumors. METHODS AND MATERIALS: Thirty-two patients with 35 newly diagnosed or recurrent malignant skull base tumors < or = 33.5 cm3 were treated using the Leksell Gamma unit. Tumor histologies included: adenoid cystic carcinoma [12], basal cell carcinoma [1], chondrosarcoma [1], chordoma [8], nasopharyngeal carcinoma [3], osteogenic sarcoma [2], and squamous cell carcinoma [8]. RESULTS: After a median follow-up of 2.3 years, 83% +/- 15% (+/-95% confidence interval) of patients experienced a symptomatic response to treatment. Local control at the skull base was 95 +/- 9% at 2 years and 78 +/- 23% at 3 years. Local-regional control above the clavicles was 75 +/- 15% at 1 year and 51 +/- 20% at 2 years. Overall and cause specific survival were identical, 82 +/- 13% at 1 year, 76 +/- 14% at 2 years, and 72 +/- 16% at 3 years. One patient developed a radiation-induced optic neuropathy 12 months after radiosurgery. CONCLUSION: Stereotactic radiosurgery using the Leksell Gamma Unit can provide durable tumor control and symptomatic relief with acceptable toxicity in the majority of patients with malignant tumors 4 cm or less in size involving the skull base. Further evaluation of more patients with longer follow-up is warranted.     

Assessment of neuropsychological changes in patients with arteriovenous malformation (AVM) after radiosurgery

PURPOSE: The purpose of this study was to investigate neuropsychological effects of radiosurgery in patients with cerebral arteriovenous malformation (AVM), with special focus on attention and memory. This report describes the study setup and presents the first results during a follow-up of up to 1 year. MATERIALS AND METHODS: Seventy-nine patients were studied before, acutely after radiosurgery, and during the regular follow-up (subacute phase: Weeks 6-12, chronic phase: Months 6-12). Radiosurgery was performed using a modified linear accelerator (minimum doses to the target volume: 15-22 Gy, median 20 Gy). Estimated whole brain dose was 0.5 to 2 Gy. Neuropsychological testing included assessment of general intelligence (Wechsler Adult Intelligence Scale), attention (modified Trail-Making Test A, Digit Symbol Test, D2 Test, Wiener Determination Machine) and memory (Rey Auditory Verbal Learning Test, Benton Visual Retention Test). During follow-up, alternate test versions were used. Neuropsychological deficits were defined as a test score of at least one standard deviation (SD) below the mean of the normal distribution. RESULTS: The pretherapeutic evaluation revealed marked deviations from the normal population; 24% had deficits in intelligence (range 23-31% in different subtests), attention (35%, 23-59%) and memory (48%, 31-61%). The overall percentage of aberrant results was reduced by 12% (memory) to 14% (attention) in the chronic phase up to 12 months after therapy. The improvement in test scores was significant (p < 0.05) in 3 of 4 subtests of attention functions. CONCLUSIONS: The acute tolerance of radiosurgery seems to be very good in these patients, showing no relevant increase in number of patients with neuropsychological deficits. Although the long-term follow-up needs to be further increased, our data indicate a tendency to slight improvement in the overall neuropsychological performance of AVM patients in the chronic phase after radiosurgery.     

Two-dimensional electrophoresis southern transfer method for detecting human genome variability using a LINE-1 sequence probe

BACKGROUND: Because of a tendency for diffuse, clinically undetectable local spread, cutaneous angiosarcoma is difficult to treat with surgery alone. Radiation is a rational treatment modality for this disease, because a wide region of dermis can be treated, whereas the underlying normal tissues are spared. METHODS: The authors retrospectively studied 14 patients with dermal angiosarcoma of the head and neck who were treated with electron-beam radiation from 1970 to 1989. Primary tumors were located in the scalp and forehead (11 patients) and in the upper face (3 patients). Eleven patients presented with multiple foci of disease. Three patients were treated with radiotherapy alone; the other 11 were treated with chemotherapy (10 patients) and/or surgery (7 patients). Surgical excisions were limited procedures for patients whose disease readily could be encompassed; total scalp resections were not performed. Patients were irradiated with a multiple-field electron-beam technique. Six patients presented postoperatively for radiotherapy with no macroscopic disease in the treatment field and were given a median dose of 60 Gy (range, 50-66 Gy) over a median of 40 days (range, 37-43 days). Eight patients were irradiated with clinically evident disease; doses ranged from 55 to 75 Gy over a median of 44 days (range, 33-66 days). RESULTS: Five of the six patients irradiated without clinically detectable disease were controlled in the treatment field, but only two are currently disease free. Of the eight patients irradiated with macroscopic tumor, initial disease recurrence occurred in the radiation field in two patients and at the radiation field margin in three patients. The actuarial 5-year control rates above the clavicles for patients irradiated with and without clinical disease were 24% and 40%, respectively (P = 0.03). The 5-year actuarial incidence of distant metastases for all patients was 63%. The 5-year actuarial survival rate for patients irradiated with and without clinical disease was 13% and 50%, respectively (P = .04). CONCLUSIONS: Radiation is an effective modality for treating local disease, especially when used after surgical resection of macroscopic tumor. Our current strategy is to resect clinically evident tumor in patients presenting with focal, limited disease, and to follow this resection with moderate dose, very wide-field radiation. The survival outcome for patients presenting with diffuse multifocal disease is bleak, but some patients can be controlled infield with radiation. There must be continued efforts to develop effective systemic therapy.     

High-dose-rate intracavitary brachytherapy in the management of cervical and vaginal intraepithelial neoplasia

PURPOSE: To assess the effectiveness of high-dose rate intracavitary brachytherapy (HDR-ICR) in patients with grade 3 cervical intraepithelial neoplasia (CIN-3) and grade 3 vaginal intraepithelial neoplasia (VAIN-3). METHODS AND MATERIALS: This was a retrospective analysis in 20 patients with CIN-3 (n = 14) or VAIN-3 (n = 6), average age 61.9 years, managed with HDR-ICR at Kanagawa Cancer Center. Two patients with CIN-3 with microinvasive foci and 11 other patients with CIN-3 were treated with HDR-ICR for cervical lesions. Six patients with CIN-3 after hysterectomy received HDR-ICR for recurrent or residual VAIN-3 lesions. One patient received radiation therapy for both CIN-3 and VAIN-3 lesions. All these patients but one were postmenopausal. RESULTS: Seventeen patients were treated with HDR-ICR alone, and three with combined external radiation therapy. The dose was calculated at Point A located 2 cm superior to the external os and 2 cm lateral to the axis of the intrauterine tube for intact uterus. For lesions of the vaginal stump, the dose was calculated at a point 1 cm superior to the vaginal apex or 1 cm beyond vaginal mucosa. In the 14 patients treated for CIN-3 lesions, the mean total dose of HDR-ICR was 26.1 Gy (range 20-30). Six patients received HDR-ICR for VAIN-3 lesions with mean dose of 23.3 Gy (range 15-30). At follow-up (mean 90.5 months; range 13-153), 14 patients were alive and 6 had died owing to nonmalignant intercurrent disease. No patient developed recurrent disease. Rectal bleeding occurred in three patients, but this symptom subsided spontaneously. Moderate and severe vaginal reactions were noted in two patients, in whom the treatment had included the entire vagina. CONCLUSIONS: HDR-ICR can be employed as the primary management strategy for postmenopausal women with CIN-3. In intraepithelial neoplasia involving the vaginal wall after hysterectomy, HDR-ICR should be considered as an alternative to total vaginectomy.     

Stereotactic radiosurgery for recurrent malignant gliomas

PURPOSE: To evaluate the role of stereotactic radiosurgery in the management of recurrent malignant gliomas. PATIENTS AND METHODS: We treated 35 patients with large (median treatment volume, 28 cm3) recurrent tumors that had failed to respond to conventional treatment. Twenty-six patients (74%) had glioblastomas multiforme (GBM) and nine (26%) had anaplastic astrocytomas (AA). RESULTS: The mean time from diagnosis to radiosurgery was 10 months (range, 1 to 36), from radiosurgery to death, 8.0 months (range, 1 to 23). Twenty-one GBM (81%) and six AA (67%) patients have died. The actuarial survival time for all patients was 21 months from diagnosis and 8 months from radiosurgery. Twenty-two of 26 patients (85%) died of local or marginal failure, three (12%) of noncontiguous failure, and one (4%) of CSF dissemination. Age (P = .0405) was associated with improved survival on multivariate analysis, and age (P = .0110) and Karnofsky performance status (KPS) (P = .0285) on univariate analysis. Histology, treatment volume, and treatment dose were not significant variables by univariate analysis. Seven patients required surgical resection for increasing mass effect a mean of 4.0 months after radiosurgery, for an actuarial reoperation rate of 31%. Surgery did not significantly influence survival. At surgery, four patients had recurrent tumor, two had radiation necrosis, and one had both tumor and necrosis. The actuarial necrosis rate was 14% and the pathologic findings could have been predicted by the integrated logistic formula for developing symptomatic brain injury. CONCLUSION: Stereotactic radiosurgery appears to prolong survival for recurrent malignant gliomas and has a lower reoperative rate for symptomatic necrosis than does brachytherapy. Patterns of failure are similar for both of these techniques.     

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.     

Putative control of angiogenesis in hemangioblastomas by the von Hippel-Lindau tumor suppressor gene

The hypoxia-inducible endothelial cell-specific mitogen vascular endothelial growth factor/vascular permeability factor (VEGF/VPF) is expressed in low amounts in adult human brain, but is highly upregulated in the perinecrotic palisading cells of glioblastomas. We observed high VEGF expression in cerebellar hemangioblastomas, which are highly vascular, nonnecrotic and presumably nonhypoxic tumors, and hypothesized that a mechanism other than hypoxia leads to VEGF upregulation. Because hemangioblastomas develop in patients with von Hippel-Lindau disease, and mutations of the von Hippel-Lindau tumor suppressor (VHL) gene have also been reported in sporadic hemangioblastomas, we investigated VHL expression in normal cerebellum and in hemangioblastomas and tested the hypothesis that mutations in the VHL gene lead to upregulation of VEGE We observed constitutive expression of VHL mRNA, but downregulation of VEGF mRNA in the postnatal cerebellum. In the adult cerebellum, VHL is predominantly expressed in neuronal cells. In hemangioblastomas, VHL expression appears to be restricted to stromal cells, suggesting that the neoplastic component is the stromal cell. VHL-deficient renal cell carcinoma cells (786-0) produced significantly higher levels of VEGF mRNA and protein compared with 786-0/ wt10 cells, which were stably transfected with the wild-type VHL gene. Our observations suggest that VHL mutations affect stromal cells in hemangioblastomas and that VEGF is upregulated in stromal cells as a consequence of mutations in the VHL gene.     

Clinical stage IE primary lymphoma of the nasal cavity: radiation therapy and chemotherapy

PURPOSE: To determine the appropriate radiation therapy and chemotherapy for primary lymphoma of the nasal cavity to improve the local control and survival rates. MATERIALS AND METHODS: Of the 25 adult patients with stage IE nasal lymphoma, nine underwent local radiation therapy alone and 16 underwent radiation therapy and chemotherapy (intravenous infusion). Radiation doses to the involved area were 22-54 Gy (median dose, 49 Gy). RESULTS: The 5- and 10-year cause-specific survival rates were 91% and 73%, respectively. The 5- and 10-year disease-free survival rates were 83% and 59%, respectively. Eight patients developed recurrent disease: six at the local site, one in the cervical nodes, and one in the small intestine. Five of the six patients with local recurrence received less than 50 Gy. Four of the six patients developed recurrent disease in the treated area; the other two patients developed marginal recurrences. Prognostic factors such as age, sex, maximum tumor size, and lactate dehydrogenase level were of limited value. CONCLUSION: The most common recurrence site was the local site. To improve the local control rate, the involved area should be treated with high-dose radiation therapy. The clinical results did not demonstrate the usefulness of combination chemotherapy for stage IE nasal lymphoma.     

Radiosurgery alone or in combination with whole-brain radiotherapy for brain metastases

PURPOSE: Evaluation of the treatment outcome after radiosurgery (RS) alone or in combination with whole-brain radiotherapy (WBRT) with special attention to prescribed dose and its influence on local control and survival. PATIENTS AND METHODS: Between September 1984 and January 1997, 236 patients with 311 brain metastases treated with radiosurgery met the following inclusion criteria: one to three brain metastases per patient; no previous WBRT; and Kamofsky performance status (KPS) > or = 50%. One hundred fifty-eight patients treated only with RS received a median dose of 20 Gy prescribed to the 80% isodose line; 78 patients received RS with a median dose of 15 Gy/80% and an additional course of WBRT. RESULTS: For the entire series, overall median survival was 5.5 months, with control of CNS disease achieved in 92% of the treated brain metastases; the results were not significantly different between patients treated by RS with or without WBRT. However, in patients without evidence of extracranial disease, median survival was increased for patients who received WBRT (15.4 vs 8.3 months; P=.08). Additionally, there was a suggestion that increased doses for patients treated with RS only resulted in improved outcome. Four lesions were suspicious for radiation necrosis by magnetic resonance imaging (MRI); in one of the four lesions, radiation necrosis was confirmed histologically. The incidence of transient low-grade toxicity was 18%; symptoms could be treated by the temporary administration of steroids. CONCLUSION: RS is an effective, noninvasive means of controlling brain metastases when used alone or in combination with WBRT. There is a trend for superior local control and especially in patients without extracranial disease for superior survival when RS is used in conjunction with WBRT. Randomized trials would seem to be warranted, comparing the benefit of RS with or without additional WBRT.     

A novel mutation of the GTP-cyclohydrolase I gene in a patient with hereditary progressive dystonia/dopa-responsive dystonia

PURPOSE: To evaluate re-treatment with an additional course of low-dose irradiation in patients with progressive or recurrent choroidal neovascular membranes (CNVMs). MATERIALS AND METHODS: Ten patients who had received 14 Gy of external-beam radiation therapy in seven fractions for subfoveal CNVMs were found to have recurrent or persistent neovascularization at follow-up. They received an additional 15 Gy of radiation therapy administered in five daily fractions with a standard lens-sparing technique. Before reirradiation, visual acuity ranged from 20/80 to counting fingers. The median time between radiation courses was 6.5 months (range, 2-16 months). After re-treatment, the patients were followed up with angiography and visual field testing. The median follow-up was 18.5 months (range, 12-21 months). RESULTS: Eight of 10 patients (80%) maintained their visual acuity at 1 year and three of seven (43%) at 18 months. Visual acuity was stabilized in five of the 10 patients at their last follow-up. No acute or late side effects of irradiation were noted. CONCLUSION: Additional radiation therapy in selected patients with CNVMs who have failed to benefit from previous irradiation is well tolerated and appears to stabilize the disease process in a substantial proportion of these patients.     

Radiation therapy in the management of desmoid tumors

PURPOSE: To evaluate the outcome of patients with extra-mesenteric desmoid tumors treated with radiation therapy, with or without surgery. METHODS AND MATERIALS: The outcome for 75 patients receiving radiation for desmoid tumor with or without complete gross resection between 1965 and 1994 was retrospectively reviewed utilizing univariate and multivariate statistical methods. RESULTS: With a median follow-up of 7.5 years, the overall freedom from relapse was 78% and 75% at 5 and 10 years, respectively. Of the total, 23 patients received radiation for gross disease because it was not resectable. Of these 23 patients, 7 sustained local recurrence, yielding a 31% actuarial relapse rate at 5 years. Radiation dose was the only significant determinant of disease control in this group. A dose of 50 Gy was associated with a 60% relapse rate, whereas higher doses yielded a 23% relapse rate (p < 0.05). The other 52 patients received radiation in conjunction with gross total resection of tumor. The 5- and 10-year relapse rates were 18% and 23%, respectively. No factor correlated significantly with disease outcome. There was no evidence that radiation doses exceeding 50 Gy improved outcome. Positive resection margins were not significantly deleterious in this group of irradiated patients. For all 75 patients, there was no evidence that radiation margins exceeding 5 cm beyond the tumor or surgical field improved local-regional control. Ultimately, 72 of the 75 patients were rendered disease-free, but 3 required extensive surgery (amputation, hemipelvectomy) to achieve this status. Significant radiation complications were seen in 13 patients. Radiation dose correlated with the incidence of complications. Doses of 56 Gy or less produced a 5% 15-year complication rate, compared to a 30% incidence with higher doses (p < 0.05). CONCLUSIONS: Radiation is an effective modality for desmoid tumors, either alone or as an adjuvant to resection. For patients with negative resection margins, postoperative radiation is not recommended. Patients with positive margins should almost always receive 50 Gy of postoperative radiation. Unresectable tumors should be irradiated to a dose of approximately 56 Gy, with a 75% expectation of local control.