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W A Friedman

Publications and source records attributed to W A Friedman.

At least 19 recordsLinked to original sources
PubMed1996

A multiinstitutional outcome and prognostic factor analysis of radiosurgery for resectable single brain metastasis.

PURPOSE: Recent randomized trials of selected patients with single brain metastasis comparing resection followed by whole-brain radiotherapy (WBRT) to WBRT alone have shown a statistically significant survival advantage for surgery and WBRT. A multiinstitutional retrospective study was performed, which identified comparable patients who were treated with stereotactic radiosurgery (RS) and WBRT. METHODS AND MATERIALS: The RS databases of four institutions were reviewed to identify patients who met the following criteria: single-brain metastasis; no prior cranial surgery or WBRT; age > 18 years; surgically resectable lesion; Karnofsky Performance Status (KPS) > or = 70 at time of RS; nonradiosensitive histology. One hundred twenty-two patients were identified who met these criteria. Patients were categorized by: (a) status of the primary, (b) status of non-CNS metastasis, (c) age, (d) baseline KPS (from 70-100), (e) histology, (f) time from diagnosis of primary to the detection of the brain metastasis, (g) gender, and (h) tumor volume. RS was performed with a linear accelerator based technique (peripheral dose range was 10-27 Gy, median was 17 Gy). WBRT was performed in all but five patients who refused WBRT (dose range was 25-40 Gy, median was 37.5 Gy). RESULTS: The median follow-up for all patients was 123 weeks. The overall local control rate (defined as lack of progression in the RS volume) was 86%. Intracranial recurrence outside of the RS volume was seen in 27 patients (22%). The actuarial median survival from date of RS is 56 weeks, and the 1-year and 2-year actuarial survival rates are 53% and 30%. The median duration of functional independence (sustained KPS > or = 70) is 44 weeks. Nineteen of 77 deaths were attributed to CNS progression (25% of all deaths). Multivariate analysis revealed the following factors to be statistically significant predictors of survival: baseline KPS (p < .0001) and absence of other sites of metastasis (p = 0.008). CONCLUSION: The RS in conjunction with WBRT for single brain metastasis can produce substantial functional survival, especially in patients with good performance status and without extracranial metastasis. These results are comparable to recent randomized trials of resection and WBRT. The advantages of RS over surgery in terms of cost, hospitalization, morbidity, and wider applicability strongly suggest that a randomized trial to compare RS with surgery is warranted.

Adult↗
PubMed1996

Accelerated hyperfractionated radiotherapy for malignant gliomas.

PURPOSE: To evaluate accelerated hyperfractionated radiotherapy for the treatment of malignant gliomas. METHODS AND MATERIALS: Between April 1985 and June 1994, 70 adult patients with pathologically confirmed malignant glioma (75% glioblastoma multiforme, 25% anaplastic astrocytoma) suitable for high-dose therapy were selected for treatment with accelerated hyperfractionated radiotherapy, 1.5 Gy twice daily to a total target dose of 60 Gy. Two patients were excluded from analysis (one patient had a fatal pulmonary embolism after 18 Gy; one patient discontinued therapy after 28.5 Gy against medical advice and without sequelae or progression). The 68 patients in the study group had a median age of 52 years and a median Karnofsky performance status of 90. Stereotactic implant (125I) or stereotactic radiosurgery boosts were delivered to 16 patients (24%) in the study group. Minimum follow-up was 6 months. RESULTS: Median survival was 13.8 months and median progression-free survival was 7.4 months. The absolute Kaplan-Meier survival rate was 16% at 2 years and 4% at 5 years. Multivariate analysis for the prognostic impact of age, gender, histology, Karnofsky performance status, symptomatology, surgical resection vs. biopsy, and boost vs. nonboost therapy revealed that Karnofsky performance status > or = 90, boost therapy, and surgical excision predicted significantly improved outcome. No severe toxicity occurred in patients treated with accelerated hyperfractionated radiotherapy alone, although 5% required steroids temporarily for edema. Progression occurred during treatment in one patient (1.5%). CONCLUSION: This regimen of accelerated hyperfractionated radiotherapy is well tolerated and leads to results comparable with those of standard therapy. The rate of disease progression during treatment is significantly better (p = 0.001) than is reported for patients treated with standard fractionation, with or without chemotherapy. This regimen is a reasonable starting point for future trials and may have some advantages over standard fractionation.

Adolescent↗
PubMed1996

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.

Animals↗
PubMed1995

Treatment selection factors for stereotactic radiosurgery of intracranial metastases.

PURPOSE: To define treatment selection criteria for patients with intracranial metastases treated with stereotactic radiosurgery. METHODS AND MATERIALS: Between August 1989 and July 1993, 25 patients with intracranial metastases (28 lesions) were treated with stereotactic radiosurgery at the University of Florida. Thirteen patients were treated for progressive intracranial disease after external-beam radiotherapy, and 12 were treated with radiosurgery as an adjunct to initial treatment. Minimum eligibility criteria included histologic verification of primary disease, Karnofsky performance status 50% or greater, three or fewer intracranial metastases, radiographically distinct lesion(s) 4 cm or less in diameter, and reasonably well-controlled primary disease. Univariate and multivariate analyses tested the prognostic significance of Karnofsky performance status, lesion volume, number of lesions, treatment dose (both external beam and stereotactic), histology, site of primary disease, and time interval (less than or greater than 1 year) from primary diagnosis to development of intracranial metastasis or from treatment of intracranial disease to recurrence. RESULTS: Local control was achieved in 84% of 28 lesions treated. The only significant prognostic indicator among the tested variables was the interval to development or recurrence of intracranial metastasis. CONCLUSION: Although stereotactic radiosurgery improves local control rates and is likely to offer improved palliation for a select cohort of patients, the selection criteria for such patients remain poorly defined. Our data suggest that an interval of greater than 1 year from primary disease diagnosis to development of intracranial metastasis, or from treatment of intracranial metastasis to its recurrence, defines a patient cohort that is more likely to benefit from this treatment technique.

Adenocarcinoma↗
PubMed1995

Radiosurgery in the initial management of malignant gliomas: survival comparison with the RTOG recursive partitioning analysis. Radiation Therapy Oncology Group.

PURPOSE: To evaluate the impact of stereotactic radiosurgery on the survival of patients treated with malignant gliomas. METHODS AND MATERIALS: A total of 115 patients from three institutions (75 from the Joint Center for Radiation Therapy, 30 from the University of Wisconsin, and 10 from the University of Florida) were treated with a combination of surgery, external beam radiation therapy, and linac-based radiosurgery as part of similar institutional protocols from March 1988 through July 1993. Patients were stratified into six prognostic classes (classes 1-6) based on the recursive partitioning analysis of multiple prognostic factors previously reported by the Radiation Therapy Oncology Group. RESULTS: The actuarial 2-year and median survival for all patients analyzed was 45% and 96 weeks, respectively. In comparison to the results from a previously published analysis of 1578 patients entered on three Radiation Therapy Oncology Group external beam radiotherapy protocols from 1974 to 1989, those patients treated with radiosurgery had a significantly improved 2-year and median survival (p = 0.01) corresponding with a standardized mortality risk ratio of 0.51 [95% confidence interval (CI): 0.31, 0.85]. This improvement in survival was seen predominantly for the worse prognostic classes (classes 3-6). The 2-year survival for the radiosurgical patients compared with the previously reported patients was 81% vs. 76% for classes 1/2, 75% vs. 35% for class 3, 34% vs. 15% for class 4, and 21% vs. 6% for classes 5/6, respectively. Although Karnofsky performance status and prognostic class were significant on univariate analysis, only the Karnofsky score was a significant predictor of outcome on multivariate analysis. Median and 2-year survival for patients with a Karnofsky score > or = 70 was 106 weeks and 51%, respectively, as compared to 38 weeks and 0% for patients with a Karnofsky score < 70% (p = 0.001). CONCLUSIONS: The addition of radiosurgery to conventional treatment (surgery and external beam radiotherapy) of malignant gliomas appears to improve survival when compared to historical reports. These results should be interpreted with caution because the recursive partitioning model does not completely predict the prognosis of the patients treated in the present study. Although this study suggests that radiosurgery may prolong survival in patients with malignant gliomas, the role of radiosurgery in the management of these patients remains to be defined by a prospective randomized trial.

Brain Neoplasms↗
PubMed1995

Linac radiosurgery for high-grade gliomas: the University of Florida experience.

PURPOSE: Stereotactic radiosurgery has been reported as a promising boost technique for the treatment of selected patients with high-grade glioma. The first 11 patients given this treatment at the University of Florida are reported. METHODS AND MATERIALS: Six patients with glioblastoma multiforme and five with anaplastic astrocytoma were carefully selected for treatment with linac radiosurgery. All patients had a Karnofsky performance status > or = 90%. Median age of patients was 42.1 years. External-beam radiotherapy delivered a median dose of 60 Gy. Stereotactic radiosurgery was delivered to the enhancing tumor volume without margin. Median treatment volume was 14 cm3 (equivalent sphere diameter, 3 cm). The maximum volume of any tumor treated was 22.5 cm3 (equivalent sphere diameter, 3.5 cm). Median stereotactic radiosurgery boost dose was 12.5 Gy, and median prescription sphere was the 80% isodose shell. RESULTS: Despite rigorous selection and aggressive stereotactic boost irradiation, this patient cohort had a median actuarial survival of 17 months. All patients have had progression of intracranial disease within 1 year of radiosurgery, and only 3 of 11 remain alive with a median follow-up of 13 months. CONCLUSION: These results differ significantly from others reported. Comparative analysis suggests tumor volume may be an important prognostic factor in patients treated with stereotactic radiosurgery. Future studies need to define appropriate patient cohorts for the boost technique.

Adolescent↗
PubMed1995

Stereotactic biopsy of brainstem mass lesions.

BACKGROUND: Appropriate therapy of brainstem lesions is guided by accurate diagnosis. Because the majority of brainstem lesions are not amenable to surgical resection, stereotactic biopsy is an attractive method of obtaining pathological tissue. METHODS: We reviewed the medical records of all patients who underwent stereotactic biopsy of brainstem mass lesions at our institution by the senior author (WAF) over a 10-year period ending in December 1993. RESULTS: Twenty-four patients ranging in age from 3 to 68 years underwent stereotactic biopsy of brainstem mass lesions at our institution by the senior author (WAF) over a 10-year period ending in December 1993. RESULTS: Twenty-four patients ranging in age from 3 to 68 years underwent stereotactic biopsy of mass lesions of the brainstem. Sixteen lesions were located primarily in the pons, 7 in the midbrain, and 1 in the medulla. Twenty-two of the biopsies were approached transfrontally and two were approached via the suboccipital transcerebellar route. Pathological diagnosis was made in 23 of the 24 patients. The histologic diagnosis was astrocytoma in 16 patients, metastasis in 3, lymphoma in 1, germinoma in 1, chordoma in 1, progressive multifocal leukencephalopathy in 1, and was nondiagnostic in 1. Complications included 1 case of increased hemiparesis, 1 case of obstructive hydrocephalus, and 1 death. Six patients were less than 20 years of age and in each of these patients the preoperative diagnosis was astrocytoma. In all of these patients the pathology revealed astrocytoma. In the adult patients the pathology was more varied, with 7 of the 18 patients having tumors or pathology other than astrocytoma. CONCLUSIONS: The data suggest that, in adult patients, brainstem lesions are of varied pathology and stereotactic biopsy can provide adequate tissue for diagnosis. The data also suggest that the diagnosis of brainstem glioma in children can often be made without submitting the patient to the risk of surgery.

Adolescent↗
PubMed1995

Intracranial arteriovenous malformations: quantitative analysis of magnitude contrast MR angiography versus gradient-echo MR imaging versus conventional angiography.

PURPOSE: To quantitatively analyze magnitude contrast (MC) magnetic resonance (MR) angiography and gradient-echo (GRE) MR imaging for evaluation of persistent transnidal blood flow in intracranial arteriovenous malformations (AVMs) of various sizes before or after stereotaxic radiosurgery. MATERIALS AND METHODS: Thirty-three patients with AVMs underwent 42 MC MR angiographic (maximum intensity projection [MIP] and source imaging), GRE imaging with and without flow compensation, and conventional angiographic studies within 90 days of each other. RESULTS: For MIP, source, and GRE images, the sensitivities for detection of large AVMs (> 1 cm) were 95%, 100%, and 100%, respectively, and for small AVMs (< or = 1 cm) were 27%, 50%, and 67%, respectively. MC MR angiography and GRE imaging depicted all eight nidi that were completely thrombosed on conventional angiograms. CONCLUSION: GRE imaging and MC MR angiography reliably depict AVMs larger than 1 cm. GRE is more sensitive for detection of small residual nidi (< 1 cm). Source images must be evaluated to accurately assess low-flow lesions. Neither GRE nor MR angiography is reliable for detection of mean nidus diameters less than 0.36 cm.

Cerebral Angiography↗
PubMed1995

Linear accelerator radiosurgery for arteriovenous malformations: the relationship of size to outcome.

Between May, 1988 and August, 1993, 158 patients with arteriovenous malformations (AVMs) were treated radiosurgically at the University of Florida. A mean dose of 1560 cGy was directed to the periphery of the lesions, which had a mean volume of 9 cc (0.5 to 45.3 cc). One hundred thirty-nine of these individuals were treated with one isocenter. The mean follow-up interval was 33 months with clinical information available on 153 of these patients. Patients were followed until magnetic resonance (MR) studies suggested complete AVM thrombosis. An arteriogram was then performed, if possible, to verify occlusion status. If arteriography revealed any persistent nidus at 36 months posttreatment, the residual nidus was re-treated. Outcome categories of AVMs analyzed included the following possibilities: 1) angiographic cure; 2) angiographic failure; 3) re-treatment; 4) MR image suggested cure; 5) MR image suggested failure; 6) patient refused follow-up evaluation; 7) patient lost to follow-up study; or 8) patient deceased. The endpoints for success or failure of radiosurgery were as follows: angiographic occlusion (success), re-treatment (failure), and death due to AVM hemorrhage (failure). Fifty-six patients in this series reached one of the endpoints. Successful endpoints were seen in 91% of AVMs between 1 and 4 cc in volume, 100% of AVMs 4 to 10 cc in volume, and 79% of AVMs greater than 10 cc in volume. The more traditional measure of radiosurgical success, percentage of angiograms showing complete obliteration, was obtained in 81% of AVMs between 1 and 4 cc in volume, 89% of AVMs between 4 and 10 cc in volume, and 69% of AVMs greater than 10 cc in volume. A detailed analysis of the relationship of all outcome categories to size is presented.

Adolescent↗
PubMed1994

Linear accelerator-based stereotactic radiosurgery for acoustic schwannomas.

PURPOSE: Stereotactic radiosurgery (SRS) is currently being investigated for treatment of acoustic schwannomas in patients who are not good surgical candidates. The vast majority of the available data is based on gamma knife-treated patients. We present the largest series of patients treated with linear accelerator-based SRS. METHODS AND MATERIALS: Thirty-two patients with acoustic schwannomas were treated with SRS between July 1988 and February 1993; follow-up ranged from 4-59 months. Age ranged from 34-88 years (mean, 62 years). The primary presenting symptom was hearing loss in 30 patients and dementia in two patients. Indications for SRS were age > 65 years (17 patients); recurrence after surgery (13 patients); and medical infirmity (two patients). Dose to the periphery of the lesion ranged from 10-22.5 Gy (mean, 15.5 Gy) specified at the 68-90% isodose line (mean, 80%). Collimator size ranged from 12-35 mm (mean, 23 mm), indicating that the sizes of the tumors were significantly larger than those reported in most gamma knife series. RESULTS: Follow-up magnetic resonance imaging (MRI) and/or computed tomography (CT) scans revealed the following at 1 year: tumor regression, 12 patients (63%); and no change, seven patients (37%). At 2 years, 11 tumors (73%) were smaller and four tumors (27%) were unchanged. At 3 years, seven patients (78%) had experienced tumor regression and two (22%) had no change. No patient experienced tumor progression after SRS. Seven patients (22%) suffered one or more treatment complications: new onset of 5th and/or 7th cranial nerve deficit (six patients), ataxia (two patients), and/or hydrocephalus necessitating VP shunt (two patients). CONCLUSION: Linear accelerator-based SRS provides excellent short-term local control and a relatively low incidence of complications for acoustic schwannomas. Our data compare favorably with results obtained with gamma knife-based SRS. Additional follow-up will be necessary to evaluate the long-term results of treatment.

Adult↗
PubMed1994

Radiosurgical treatment of a hemangioblastoma: case report.

A hemangioblastoma of the fourth ventricle was treated with radiosurgery after attempts at surgical resection failed. No change in the size of the lesion has been seen in 2 years of follow-up, and the patient's neurological status remains normal. A brief review of the rationale for conventional radiation therapy and radiosurgery in the management of persistent/recurrent hemangioblastomas is presented.

Adult↗
PubMed1994

Temporal characteristics of radiosurgical lesions in an animal model.

To characterize the temporal course of radiosurgical lesions, 19 cats were irradiated in an animal linear accelerator radiosurgical device. The animals were followed clinically and, at 3.5, 6, 12, 18, 23, 29, and 63 weeks, were studied with gadolinium-enhanced magnetic resonance (MR) imaging. They were then sacrificed after Evans blue dye perfusion, and gross pathological and histopathological studies were performed. Mild neurological deficits developed between 3.5 and 4.5 weeks, correlating with the onset of mass effect both grossly and radiographically and with the maximum amount of white matter edema on T2-weighted MR imaging and microscopic examination. Clinical improvement occurred within several weeks as these resolved. The lesions were of similar size at all time intervals. Gadolinium-enhanced MR imaging demonstrated lesions with peripheral areas of enhancement and central nonenhancing regions which correlated histologically with areas of vascular proliferation and radiation necrosis, respectively. In the early lesions at 3.5 and 6 weeks, necrosis and edema were predominant. From 12 to 29 weeks, an intermediate stage was observed, with resorption of the necrotic debris as evidenced by progressive cavitation and microglial response and by increased perilesional vascularity. At 63 weeks, resorption was still taking place, but gliosis and diminution of the vascular response were seen.

Animals↗
PubMed1993

Delayed computed tomography contrast enhancement patterns in biopsy proven cases.

After a stereotactic brain biopsy of intracranial lesions, many neurosurgeons routinely obtain a noncontrast computed tomographic scan to rule out hemorrhage. We have observed there is often a significant delayed contrast enhancement on this postoperative scan, and the pattern of this enhancement frequently differs from the preoperative pattern. To assess these changes and to determine if they are related to lesion pathology or other clinical factors, the pre- and postoperative scans of 89 patients who underwent stereotactic biopsies were reviewed. Despite an average time delay of 153 minutes between scans, 81% of the lesions enhanced similarly or better on the postbiopsy image. One lesion enhanced only on the postoperative image, and in two cases, new lesions were seen postoperatively. Ring and other enhancing lesions tended to fill in with time, becoming homogeneous. The area of contrast enhancement increased in 83%. The borders of the lesions tended to become less sharp with time. No patterns of delayed enhancement, which give histologically definitive diagnostic information, were found. The tendency toward an increased area of contrast enhancement with time suggests that computed tomographic scans taken at the time of contrast injection may not show the true extent of the lesion. For patients undergoing computed tomography-guided stereotactic biopsies or radiosurgery of poorly enhancing lesions, the localization scan might be delayed after the administration of contrast medium to improve resolution and target selection.

Adult↗
PubMed1993

Modifications based on computed tomographic imaging in planning the radiosurgical treatment of arteriovenous malformations.

Early in the course of treating arteriovenous malformations with radiosurgery, it was noted that the nidus isocenter and diameter, as identified by stereotactic angiography, often differed from that identified by stereotactic enhanced computed tomography (CT). To assess the sources of discrepancy between the arteriographic and CT representations of the nidus, dosimetry (from treatment records stored on an optical disk) was reviewed in 81 consecutive cases. In 44 cases, the isocenters differed by an average of 3.6 mm and the collimator size differed. Fourteen nidi were larger on CT (average, 2.6 mm), and 30 were smaller on CT (average, 4.0 mm). Overall, the angiographic and the CT nidus differed in 75% of the cases reviewed. Sources of error in the angiographic nidus determination included overlapping vessels, bony structures, fine filamentous arterioles, and irregular shapes.

Angiography, Digital Subtraction↗
PubMed1993

LINAC radiosurgery: an animal model.

Fifteen cats were irradiated with an animal LINAC (linear accelerator) radiosurgery device. After 6 months, they were studied with gadolinium-enhanced magnetic resonance (MR) imaging, gross pathology after Evans blue perfusion, and histopathology. The lesion size was relatively constant in the cats receiving a dose of 7500, 10,000, 12,500, or 15,000 cGy to the 84% isodose line of a 1-cm collimator. The composition of the lesion correlated with dose: the lower-dose lesions were found histologically to contain areas of edema, demyelination, reactive gliosis, and vascular proliferation; the higher-dose lesions contained increasing amounts of hemorrhage and coagulative necrosis. The borders of the lesions were sharply demarcated from surrounding normal brain. Gadolinium-enhanced MR studies correlated well with areas of blood-brain barrier breakdown, as confirmed by areas of Evans blue staining. This model could serve as the basis for further studies of the biological effects of LINAC radiosurgery.

Animals↗
PubMed1993

Radiosurgery for arteriovenous malformations.

Radiosurgery has been shown, in multiple reports using various radiosurgical methodologies, to be a safe and effective means of treating AVMs. The major drawback of this treatment method is that it does not provide, as does open surgery, immediate protection against re-hemorrhage. For those lesions in the appropriate size range (< 3.5 cm in diameter) which are not amenable to treatment with surgical and/or endovascular techniques, radiosurgery has become an accepted and valuable part of the neurosurgical treatment armamentarium.

Adolescent↗
PubMed1992

Individual variation in locomotor behavior and maximal oxygen consumption in mice.

Individual differences in open-field activity and emotionality (number of defecations and urinations), voluntary wheel running, voluntary and forced maximal sprint running speed on a photocell-timed racetrack, swimming endurance, and maximal oxygen consumption (VO2max) were studied in 35 random bred male ICR mice. With the exception of latency in the open field and voluntary speed on a racetrack, all measurements were significantly repeatable on two successive trial days. Maximal oxygen consumption (corrected for body size) was positively correlated with amount of wheel running during each day of a 7-day test, and the correlation became stronger throughout the testing period; however, none of the daily correlations reached statistical significance. The first factor from a principal components (PC) analysis showed positive loadings (component correlations) for all measures of speed in the open field, for both voluntary and forced maximal speeds on the racetrack, and for VO2max, but a negative loading for emotionality. Wheel running and VO2max loaded positively on PC 2. Only swimming endurance loaded strongly on PC 3; this trait was uncorrelated with any other measure of physiology or behavior. These results suggest that measures of both voluntary and forced locomotor speed, as well as amount of voluntary wheel running, may be related to aerobic physiological capacities in untrained mice.

Animals↗