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Bruce E. Pollock and John C. Flickinger

Object. Radiosurgery is an effective treatment strategy for properly selected patients harboring arteriovenous malformations (AVMs). Grading scales that are currently used to predict patient outcomes after AVM resection are unreliable tools for the prediction of the results of AVM radiosurgery.

Methods. A grading system was developed to predict outcomes following AVM radiosurgery, based on the multivariate analysis of data obtained in 220 patients treated between 1987 and 1991 (Group 1). The dependent variable in all analyses was excellent patient outcome (complete AVM obliteration without any new neurological deficit). The grading scale was tested on a separate set of 136 patients with AVMs treated between 1990 and 1996 at a different center (Group 2).

One hundred twenty-one (55%) of 220 Group 1 patients had excellent outcomes. Multivariate analysis identified five variables related to excellent patient outcomes: AVM volume (p = 0.001), patient age (p < 0.001), AVM location (p < 0.001), previous embolization (p = 0.02), and number of draining veins (p = 0.001). Regression analysis modeling permitted removal of two significant variables (previous embolization and number of draining veins) and resulted in the following equation to predict patient outcomes after AVM radiosurgery: AVM score = (0.1)(AVM volume in cm3) + (0.02)(patient age in years) + (0.3)(location of lesion: frontal or temporal) = 0; parietal, occipital, intraventricular, corpus callosum, cerebellar = 1; or basal ganglia, thalamic, or brainstem = 2). Seventy-nine (58%) of 136 Group 2 patients had excellent outcomes. All variables in the model remained significant for the Group 2 patients: AVM volume (p = 0.01), patient age (p = 0.01), and AVM location (p < 0.001). Testing of the entire model on the Group 2 patients demonstrated that the AVM score could be used to predict patient outcomes after radiosurgery (p < 0.0001). All patients with an AVM score of 1 or lower had an excellent outcome compared with only 39% of patients with an AVM score higher than 2. The Spetzler—Martin grade (p = 0.13), the K index (p = 0.26), and the obliteration prediction index (p = 0.21) did not correlate with excellent patient outcomes.

Conclusions. Despite significant differences in preoperative patient characteristics and dose prescription guidelines at the two centers, the proposed AVM grading system strongly correlated with patient outcomes after single-session radiosurgery for both patient groups. Although further testing of this model by independent centers using prospective methodology is still required, this system allows a more accurate prediction of outcomes from radiosurgery to guide choices between surgical and radiosurgical management for individual patients with AVMs.

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John C. Flickinger, Douglas Kondziolka, Ajay Niranjan and L. Dade Lunsford

Object. The goal of this study was to define tumor control and complications of radiosurgery encountered using current treatment methods for the initial management of patients with unilateral acoustic neuroma.

Methods. One hundred ninety patients with previously untreated unilateral acoustic neuromas (vestibular schwannomas) underwent gamma knife radiosurgery between 1992 and 1997. The median follow-up period in these patients was 30 months (maximum 85 months). The marginal radiation doses were 11 to 18 Gy (median 13 Gy), the maximum doses were 22 to 36 Gy (median 26 Gy), and the treatment volumes were 0.1 to 33 cm3 (median 2.7 cm3).

The actuarial 5-year clinical tumor-control rate (no requirement for surgical intervention) for the entire series was 97.1 ± 1.9%. Five-year actuarial rates for any new facial weakness, facial numbness, hearing-level preservation, and preservation of testable speech discrimination were 1.1 ± 0.8%, 2.6 ± 1.2%, 71 ± 4.7%, and 91 ± 2.6%, respectively. Facial weakness did not develop in any patient who received a marginal dose of less than 15 Gy (163 patients). Hearing levels improved in 10 (7%) of 141 patients who exhibited decreased hearing (Gardner-Robertson Classes II–V) before undergoing radiosurgery. According to multivariate analysis, increasing marginal dose correlated with increased development of facial weakness (p = 0.0342) and decreased preservation of testable speech discrimination (p = 0.0122).

Conclusions. Radiosurgery for acoustic neuroma performed using current procedures is associated with a continued high rate of tumor control and lower rates of posttreatment morbidity than those published in earlier reports.

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Satoshi Maesawa, John C. Flickinger, Douglas Kondziolka and L. Dade Lunsford

Object. The goal of this study was to define treatment results of repeated arteriovenous malformation (AVM) radiosurgery, namely AVM obliteration and complications.

Methods. The authors analyzed their experience with repeated AVM radiosurgery performed in 41 patients for whom follow-up review lasted at least 2 years. The median duration of follow up was 34 months (range 7–65 months) after repeated radiosurgery in this group. The residual nidus was located within the area of focus (in field) of the initial radiosurgery in 28 patients (68%). Initial doses to the margin varied from 12.5 to 20 Gy (median 18 Gy). During repeated treatment the dose to the margin varied from 12.5 to 20 Gy (median 17 Gy) and the retreated volumes ranged from 0.4 to 7 cm3 (median 2.1 cm3).

Follow-up angiography performed at least 2 years postradiosurgery revealed complete AVM obliteration in 21 (70%) of 30 patients. The estimated overall 2-year obliteration rate, based on findings on magnetic resonance imaging (eight of 11 obliterated) and angiography (29 of 41 obliterated) was 71%. Obliteration rates correlated with margin doses (p = 0.0045) with a trend toward higher rates in cases with in-field nidus persistence (p = 0.0637). The dose—response curve for AVM nidus obliteration was not significantly different from that of the initial radiosurgery. In two patients (5%) intracranial AVM hemorrhage developed within 125.9 risk years after repeated radiosurgery (1.6% per patient year). Persistent symptomatic adverse radiation effects developed in two (5%) of 41 patients following repeated radiosurgery. Postradiosurgical imaging changes were identified in 11 (27%) of 41 patients, which correlated with a 12-Gy volume from repeated surgery (p = 0.019).

Conclusions. When necessary, repeated AVM radiosurgery achieves obliteration with an acceptable risk. Despite the effects of previous irradiation, repeated radiosurgery required similar or slightly higher radiation doses to achieve the same in-field obliteration rates as those needed to obliterate an AVM that had not been treated by radiation previously.

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L. Dade Lunsford, Salvador Somaza, Douglas Kondziolka and John C. Flickinger

✓ The authors investigated the outcome of stereotactic biopsy and radiotherapy in 35 consecutive adult patients with nonanaplastic, nonpilocytic astrocytomas who were diagnosed between 1982 and 1992. The median patient age at presentation was 32 years. All received fractionated external-beam radiation therapy (median dose 56 Gy) as the initial management strategy. Additional treatment in two patients included intracavitary irradiation with colloidal phosphorus-32.

Six patients (17%) had documented tumor progression during the follow-up interval and died. Three others died of causes unrelated to their tumor. Median survival after stereotactic biopsy and irradiation was 118 months (9.8 years). Median survival from the time of onset of neurological symptoms was 148 months (12.3 years). Only three patients required delayed cytoreductive surgery.

The outcome of brain astrocytomas, although improved because of earlier diagnosis and therapy, does not substantiate this tumor as having benign behavior; early recognition with neuroimaging, immediate histological diagnosis via stereotactic biopsy, and initial fractionated radiation therapy may provide the potential for longer survival for patients with low-grade astrocytomas. The majority of such surviving patients have a satisfactory quality of life, which is manifested by prolonged normal functional and employment status. The survival data reported in this prospective Phase I–II clinical trial suggest that stereotactic biopsy and radiation therapy are appropriate initial management strategies for astrocytomas.

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Douglas Kondziolka, Atul Patel, L. Dade Lunsford and John C. Flickinger

Object

Multiple brain metastases are a common health problem, frequently found in patients with cancer. The prognosis, even after treatment with whole-brain radiation therapy (WBRT), is poor, with an average expected survival time of less than 6 months. Investigators at numerous centers have evaluated the role of stereotactic radiosurgery in retrospective case series of patients harboring solitary or multiple tumors. Tumor resection is used mainly for patients with large tumors that cause acute neurological syndromes. The authors conducted a randomized trial in which they compared radiosurgery combined with WBRT with WBRT alone.

Methods

Twenty-seven patients were randomized (14 to recieve WBRT alone and 13 to receive WBRT combined with radiosurgery). The rate of local failure at 1 year was 100% after WBRT alone but only 8% in patients in whom boost radiosurgery was performed. The median time to local failure was 6 months after WBRT alone (95% confidence interval (CI) 3.5–8.5) in comparison to 36 months (95% CI 15.6–57) after WBRT and radiosurgery (p = 0.0005). The median time to the development of any brain failure was improved in the combined modality group (p = 0.002). Survival was shown to be related to the extent of extracranial disease (p = 0.02).

Conclusions

Combined WBRT and radiosurgery for the treatment of patients with two to four brain metastases significantly improves control of brain disease. Whole-brain radiation therapy alone does not provide lasting and effective care when treating most patients. Surgical resection remains important for patients with large symptomatic tumors and in whom limited extracranial disease has been demonstrated.

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Douglas Kondziolka, L. Dade Lunsford and John C. Flickinger

Management options for patients with vestibular schwannomas (acoustic neuromas) include observation, tumor resection, stereotactic radiosurgery, and fractionated radiotherapy. In this report the authors review their 15-year experience with radiosurgery and discuss indications and expectations in relation to the different approaches. They conducted a survey of neurosurgeons to determine management preferences in two different cases of intra- and extra-canalicular tumor presentations. Patient decisions must be based on quality information derived from peer-reviewed literature.

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Douglas Kondziolka, John C. Flickinger and L. Dade Lunsford

✓ Stereotactic radiosurgery is commonly used for selected patients with benign cranial base tumors. The goal of radiosurgery is cessation of tumor growth and preservation of neurological function. Over the last 2 decades, the technique of radiosurgery has evolved due to improved imaging, better radiosurgical devices and software, and the continued analysis of results. In this report, the authors discuss technical concepts and dose selection in skull base radiosurgery.

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Patrick Breen, John C. Flickinger, Douglas Kondziolka and Augusto J. Martinez

Object. The authors studied outcomes in patients who had undergone radiotherapy for nonfunctional pituitary adenoma to assess long-term tumor control and to identify factors affecting tumor control such as higher radiation doses, improved imaging, and histological characteristics of the tumor.

Methods. In this retrospective study, the authors evaluated 120 patients who received radiotherapy for nonfunctional pituitary adenomas between 1960 and 1991. The median follow-up period was 9 years (range 1 month–32 years). Radiation doses varied between 37.6 and 65.6 Gy (median 46.7 Gy).

Tumors progressed in 15 of the 120 patients by 1 to 25 years after radiotherapy. Actuarial tumor control rates at 10, 20, and 30 years were 87.5 ± 3.6%, 77.6 ± 6.3%, and 64.7 ± 12.9%, respectively. Tumor progression after radiotherapy occurred significantly more often (p = 0.0397) in patients with oncocytoma than in patients with nononcocytic null cell adenoma. No other factors correlated significantly with tumor control. One case of optic and oculomotor neuropathy developed 4.5 years after a maximum dose of 50 Gy in 25 fractions. Radiation-induced neoplasms (meningioma and glioblastoma multiforme) developed at a rate of 2.7% at 10 and 30 years.

Conclusions. The oncocytic variant of null cell pituitary adenoma appears less sensitive to control by radiotherapy than nononcocytic undifferentiated cell adenoma. A follow-up period extending beyond 20 years is needed adequately to assess the efficacy of radiotherapy for tumor control. Doses of 40 or 45 Gy in 20 or 25 fractions, respectively, appear optimal.

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Peter C. Gerszten, John J. Moossy, John C. Flickinger and William C. Welch

Object. The authors of clinical studies have demonstrated a significant association between the presence of extensive post—lumbar discectomy peridural scar formation and the recurrence of low-back and radicular pain. Low-dose perioperative radiotherapy has been demonstrated to inhibit peridural fibrosis after laminectomy in animal models. The present study was designed to evaluate the clinical efficacy of preoperative irradiation in patients with failed—back surgery syndrome due to peridural fibrosis who underwent reexploration and nerve root decompression.

Methods. Ten patients with symptomatic post—discectomy peridural fibrosis were randomized. Half of the patients underwent 700-cGy external-beam irradiation to the operative site 24 hours prior to reexploration and decompressive treatment of their symptomatic nerve root(s) (treatment group) and the other half underwent reexploration and decompressive treatment without preoperative irradiation (control group). All patients underwent simulated irradiation so neither patient nor surgeon was aware of the patient's group. In all patients the antiadhesion product ADCON-L was placed over the affected nerve root at the time of surgery. Clinical outcome was assessed using the American Association of Neurological Surgeons/Congress of Neurological Surgeons Joint Section Lumbar Disc Herniation Study Questionnaire at baseline, 6 weeks, 3 months, and 1 year follow up.

Five men and five women (mean age 42 years) underwent randomization and surgery. Three patients underwent reexploration at L4–5, four at L5—S1, and three at both levels. No complication was associated with irradiation, and no new neurological deficits occurred. At 1-year follow-up examination, three irradiation-treated patients were pain free and two experienced improvement. In the control group, three patients experienced improved pain relief and two were unchanged. There was a trend toward better outcome at 1 year in the radiotherapy-treated group (p = 0.056).

Conclusions. Preoperative low-dose external-beam irradiation improved clinical outcomes after reexploration and decompression of nerve roots affected by postlaminectomy peridural fibrosis causing radicular pain. The addition of preoperative irradiation may improve outcome in patients who undergo reoperation for recurrent radicular pain associated with a significant amount of peridural fibrosis, particularly now that no antiadhesion product is available for clinical use.