Radiosurgery Group Research Articles

Comparison of the surgical and follow-up costs associated with microsurgical resection and stereotactic radiosurgery for vestibular schwannoma

The best approach to the management of vestibular schwannoma (VS) remains controversial. The aim of this study is to analyze the initial and follow-up costs of resection and stereotactic radiosurgery for patients with VS. Initial and follow-up costs in 53 cases in which patients with unilateral, previously unoperated VSs > 3 cm underwent resection (21 cases) or radiosurgery (32 cases) at the Mayo Clinic from June 2000 until July 2002 were analyzed for 36 months. Follow-up treatment-specific utilization records were gathered prospectively for patients not returning to the Mayo Clinic after treatment. Six-month moving averages of incremental follow-up costs were calculated for the 2 patient groups. The mean cost of surgery in the microsurgery group was $23,788 (95% confidence interval $22,280-$24,842) compared with $16,143 (95% confidence interval $15,277-$17,545) for the radiosurgical group. Mean incremental follow-up costs per month for patients in the microsurgery group started just > $1,000 per month, decreased steadily, and remained < $70 per month by the 10th month of follow-up. Mean incremental follow-up costs per month for patients in the radiosurgery group were <$10 per month for the first few months and thereafter increased to as much as $200 per month. Although the total cost of microsurgery is higher due to the costs of hospitalization, follow-up costs for radiosurgery are greater in general. From a societal perspective, radiosurgery is less expensive than microsurgical resection provided that the rate of tumor progression after radiosurgery remains low with long-term follow-up.

Complications of Skin-Sparing Mastectomy Followed by Immediate Breast Reconstruction

Skin-sparing mastectomy (SSM) followed by immediate breast reconstruction delivers superior cosmetic and functional outcome. However, SSM is vulnerable to complications of the native skin envelope. This study aims to compare the effects of radiofrequency coagulation and conventional diathermy on complications of SSM. Sixty consecutive patients suitable for SSM were randomized into conventional diathermy and radiosurgery groups. These groups were compared and the risk factors for SSM flap complications were evaluated. The SSM flap complication rate was 23.4%. There was no difference between the study groups regarding the SSM flap complications. Increased SSM flap complication rate was associated with smoking and the type of skin incision used. This study shows that high-frequency radiosurgery is comparable to conventional diathermy in terms of complication rates of SSM. Furthermore, this study reports an association between the tennis-racquet-type incision and an increased SSM flap complication rate compared with the round periareolar type incision.

Microsurgery plus whole brain irradiation versus Gamma Knife surgery alone for treatment of single metastases to the brain: a randomized controlled multicentre phase III trial

Is Gamma Knife surgery alone as effective as surgery plus whole brain irradiation (WBRT) for patients with a single, small-sized brain metastasis? Patients aged between 18 and 80 years harboring a single, resectable metastasis < or =3 cm in diameter, a Karnofsky performance score (KPS) > or =70, and a stable systemic disease were randomly assigned to microsurgery plus WBRT or Gamma Knife surgery alone. The primary end point was length of survival, secondary end points were recurrence of tumor in the brain, health related quality of life, and treatment related toxicity. Due to poor patient accrual, the study was stopped prematurely. The final analysis was based on 33 patients in the surgery and 31 patients in the radiosurgery group. Treatment results did not differ in terms of survival (P = 0.8), neurological death rates (P = 0.3), and freedom from local recurrence (P = 0.06). Patients of the radiosurgery group experienced more often distant recurrences (P = 0.04); after adjustment for the effects of salvage radiosurgery this difference was lost (P = 0.4). Radiosurgery was associated with a shorter hospital stay, less frequent and shorter timed steroid application (P < or = 0.001), and lower frequency of grade 1/2 toxicities (according to the RTOG/EORTC CNS toxicity criteria, P < or = 0.01). Improved scores for role functioning and quality of life were seen 6 weeks after radiosurgery (P < 0.05); this difference was lost 6 months after treatment. In patients harboring a single, small-sized metastasis, Gamma Knife surgery alone is less invasive; local tumor control seems to be as high as after surgery plus WBRT. Distant tumor control, however, is significantly less frequently achieved (after radiosurgery alone). The role of radiosurgical salvage therapy (alternatively to WBRT) for distant tumor control deserves further prospective evaluation.

MICROSURGERY OR RADIOSURGERY FOR CEREBRAL ARTERIOVENOUS MALFORMATIONS? A STUDY OF TWO PAIRED SERIES

To detect parameters that may augment the therapeutic strategy in patients with a cerebral arteriovenous malformation (AVM) that is considered equally suitable for treatment by neurosurgery or radiosurgery, we compared the efficacy and risks of these two methods in a paired series with similar patient and AVM characteristics. Two series of patients with AVM were studied, including a series of 39 patients treated using microsurgery (MS) and another series of 39 patients treated via radiosurgery (RS). These series were paired for age and sex, initial symptoms, size, location and Spetzler-Martin grade, and presence of embolization preceding treatment. We compared the posttreatment outcome in the two groups with respect to obliteration rate, neurological status, mortality rate, and recurrent bleeding. Statistical analysis was performed using paired Student's t test. The Glasgow Outcome Scale values and Modified Rankin Scores measured at discharge and 12 to 24 months were significantly better in the RS series than in the MS series. The obliteration rate tended to be higher in the MS series (91% versus 81%; P = 0.10, not significant), whereas the rate of neurological deficit was higher in the MS series than in the RS series (P < 0.001). The mortality rate was not significantly different in the two series, but the rate of recurrent bleeding was higher in the RS group (10% versus 0%; P = 0.04). Although the rate of cure was similar for patients treated with MS and RS, neurological morbidity was higher after MS and recurrent bleeding was more frequent after RS.

Treatment of Epileptogenic Cavernomas: Surgery versus Radiosurgery

Background: Epilepsy is the most common symptom of cavernoma. Although microsurgery is the mainstay treatment for epileptogenic cavernoma, this procedure may cause severe complications for some lesions. This report aimed to study if linear accelerator (LINAC) radiosurgery was an alternative treatment modality for epileptogenic cavernoma. Methods: In this retrospective study, 29 patients were diagnosed with epileptogenic cavernomas from September 1995 to March 2005. Fifteen patients were treated with surgical excision and 14 with LINAC radiosurgery. The evaluation of epilepsy control was according to Engel’s classification. Results: In the surgical group, 13 (86.7%) of 15 patients had a class I seizure-free outcome. In the radiosurgery group, class I control was achieved in 9 (64.3%) of 14 patients. However, there was no significant difference in the results of treatment between the two groups. Conclusions: LINAC radiosurgery is an alternative treatment for epileptogenic cavernomas, especially when the lesions are located in the central regions or eloquent areas of the brain.

The selection of the optimal therapeutic strategy for petroclival meningiomas

Background Broad experience with the management of petroclival meningiomas was analyzed to optimize therapeutic strategy. Methods The records of 75 patients with petroclival meningioma were reviewed. The population was divided into a microsurgery group (n = 49), a radiosurgery group (n = 12), a radiation therapy group (n = 5), and an observation group (n = 9) according to the modality of primary treatment. In the microsurgery group, the tumor was completely resected in 10 patients. Eleven of the 39 patients with incomplete resections sequentially underwent adjuvant radiation therapy or radiosurgery. The median follow-up period was 86 months (range, 48-210 months). The median follow-up period of the radiosurgery, the radiation therapy, and the observation group was 52 months (range, 48-71 months), 56 months (range, 51-72 months), and 63 months (range, 53-68 months), respectively. Management outcomes were evaluated with respect to tumor control rate, neurological deficit, and functional status assessed by the Karnofsky Performance Score. Results In the microsurgery group, 11 (22.4%) patients eventually showed tumor progression. However, there was only one recurrence if adjuvant therapy was used after incomplete removal. The incidence of favorable outcomes for cranial neuropathies was better in the incomplete resection group (69.2%) than for patients in the complete resection group (20%, P = .032). Moreover, a favorable functional outcome predominated in the incomplete resection group (76.9%) compared with the complete resection group (30%, P = .049). The disease was stable in both the radiation therapy and the radiosurgery groups during the follow-up period, with functional status and cranial nerve function perfectly preserved in these patients. No predictive factor other than short symptom duration was found to be significant. Conclusions Because the growth rate of petroclival meningioma is low and good functional status can be guaranteed, intended incomplete resection should be considered as an acceptable treatment option. Adjuvant treatment after surgery is useful in the control of residual tumors. Radiosurgery may be appropriate as the primary treatment in asymptomatic patients with small tumor; however, more aggressive treatment is needed in young patients or patients with short symptom durations.

Randomized comparison of stereotactic radiosurgery followed by conventional radiotherapy with carmustine to conventional radiotherapy with carmustine for patients with glioblastoma multiforme: Report of Radiation Therapy Oncology Group 93-05 protocol

Purpose Conventional treatment of glioblastoma multiforme (GBM) cures less than 5% of patients. We investigated the effect of stereotactic radiosurgery (SRS) added to conventional external beam radiation therapy (EBRT) with carmustine (BCNU) on the survival of patients with GBM. Methods and materials A total of 203 patients with supratentorial GBM (tumor ≤40 mm) were randomly assigned either to postoperative SRS followed by EBRT (60 Gy) plus BCNU (80 mg/m 2 Days 1–3 every 8 weeks for six cycles) or to EBRT with BCNU alone. The dose of radiosurgery was tumor size–dependent and ranged from 15 Gy for largest to 24 Gy for smallest tumors. RT and BCNU were identical in both arms. Results At a median follow-up time of 61 months, the median survival in the radiosurgery group was 13.5 months (95% confidence interval, 11.0–14.8) as compared with 13.6 months (95% confidence interval, 11.2–15.2, p = 0.5711) for the standard treatment group. There were also no significant differences in 2- and 3-year survival rates and in patterns of failure between the two arms. Quality of life deterioration and cognitive decline at the end of therapy, compared with baseline, were comparable and there was no difference in quality-adjusted survival between the arms. Conclusions Stereotactic radiosurgery followed by EBRT and BCNU does not improve the outcome in patients with GBM nor does it change the general quality of life or cognitive functioning.

Whole brain radiation therapy with or without stereotactic radiosurgery boost for patients with one to three brain metastases: phase III results of the RTOG 9508 randomised trial

Brain metastases occur in up to 40% of all patients with systemic cancer. We aimed to assess whether stereotactic radiosurgery provided any therapeutic benefit in a randomised multi-institutional trial directed by the Radiation Therapy Oncology Group (RTOG). Patients with one to three newly diagnosed brain metastases were randomly allocated either whole brain radiation therapy (WBRT) or WBRT followed by stereotactic radiosurgery boost. Patients were stratified by number of metastases and status of extracranial disease. Primary outcome was survival; secondary outcomes were tumour response and local rates, overall intracranial recurrence rates, cause of death, and performance measurements. From January, 1996, to June, 2001, we enrolled 333 patients from 55 participating RTOG institutions--167 were assigned WBRT and stereotactic radiosurgery and 164 were allocated WBRT alone. Univariate analysis showed that there was a survival advantage in the WBRT and stereotactic radiosurgery group for patients with a single brain metastasis (median survival time 6.5 vs 4.9 months, p=0.0393). Patients in the stereotactic surgery group were more likely to have a stable or improved Karnofsky Performance Status (KPS) score at 6 months' follow-up than were patients allocated WBRT alone (43% vs 27%, respectively; p=0.03). By multivariate analysis, survival improved in patients with an RPA class 1 (p<0.0001) or a favourable histological status (p=0.0121). WBRT and stereotactic boost treatment improved functional autonomy (KPS) for all patients and survival for patients with a single unresectable brain metastasis. WBRT and stereotactic radiosurgery should, therefore, be standard treatment for patients with a single unresectable brain metastasis and considered for patients with two or three brain metastases.

A comparison of surgical resection and stereotactic radiosurgery in the treatment of solitary brain metastases

Purpose To determine whether neurosurgery (NS) or stereotactic radiosurgery (RS) provided better local tumor control and enhanced patient survival. Methods and materials Retrospective review of all solitary brain metastases (SBM) patients newly diagnosed at Mayo Clinic Rochester between 1991 and 1999. Eligible patients satisfied tumor size and SBM site criteria to qualify for both NS and RS. Results There were no significant differences between 74 NS and 23 RS patients in terms of baseline characteristics (age, gender, systemic disease type, systemic disease status, signs/symptoms at SBM presentation) or percent of patients who received whole brain radiotherapy. Median follow-up for alive patients was 20 months (range 0–106 months). There was no significant difference in patient survival ( p = 0.15); the 1-year survival rate was 56% for the RS patients and 62% for the NS patients. Multivariate Cox regression analysis found that a significant prognostic factor for survival was a performance score of 0 or 1. There was a significant ( p = 0.020) difference in local tumor control between NS and RS for solitary brain metastasis; none of the RS group had local recurrence compared to 19 (58%) of the NS group. Conclusion The need for a Phase III study comparing these two techniques appears to be supported by the data from this study.

Treatment of acoustic neuroma: stereotactic radiosurgery vs. microsurgery

Purpose: Two major treatment options are available for patients with acoustic neuroma, microsurgery and radiosurgery. Our objective was to compare these two treatment modalities with respect to tumor growth control, hearing preservation, development of cranial neuropathies, complications, functional outcome, and patient satisfaction.Methods and Materials: To compare radiosurgery with microsurgery, we analyzed 96 patients with unilateral acoustic neuromas treated with Leksell Gamma Knife or microsurgery at Memorial Hermann Hospital, Houston, Texas, between 1993 and 2000. Radiosurgery technique involved multiple isocenter (1–30 single fraction fixed-frame magnetic resonance imaging) image-based treatment with a mean dose prescription of 14.5 Gy. Microsurgery included translabyrinthine, suboccipital, and middle fossa approaches with intraoperative neurophysiologic monitoring. Preoperative patient characteristics were similar except for tumor size and age. Patients undergoing microsurgery were younger with larger tumors compared to the radiosurgical group. The tumors were divided into small <2.0 cm, medium 2.0–3.9 cm, or large >4.0 cm. Median follow-up of the radiosurgical group was longer than the microsurgical group, 48 months (3–84 months) vs. 24 months (3–72 months).Results: There was no statistical significance in tumor growth control between the two groups, 100% in the microsurgery group vs. 91% in the radiosurgery group (p > 0.05). Radiosurgery was more effective than microsurgery in measurable hearing preservation, 57.5% vs. 14.4% (p = 0.01). There was no difference in serviceable hearing preservation between the two groups. Microsurgery was associated with a greater rate of facial and trigeminal neuropathy in the immediate postoperative period and at long-term follow-up. The rate of development of facial neuropathy was significantly higher in the microsurgical group than in the radiosurgical group (35% vs. 0%, p < 0.01 in the immediate postsurgical period and 35.3% vs. 6.1%, p = 0.008, at long-term follow-up). Similarly, the rate of trigeminal neuropathy was significantly higher in the microsurgical group than in the radiosurgical group (17% vs. 0% in the immediate postoperative period, p < 001, and 22% vs. 12.2%, p = 0.009, at long-term follow-up). There was no significant difference in exacerbation of preoperative tinnitus, imbalance, dysarthria, dysphagia, and headache. Patients treated with microsurgery had a longer hospital stay (2–16 days vs. 1–2 days, p < 0.01) and more perioperative complications (47.8% vs. 4.6%, p < 0.01) than did patients treated with radiosurgery. There was no correlation between the microsurgical approach used and postoperative symptoms. There was no difference in the postoperative functioning level, employment, and overall patient satisfaction. There was no correlation between the radiation dose, tumor size, number of isocenters used, and postoperative symptoms in the radiosurgical group.Conclusion: Radiosurgical treatment for acoustic neuroma is an alternative to microsurgery. It is associated with a lower rate of immediate and long-term development of facial and trigeminal neuropathy, postoperative complications, and hospital stay. Radiosurgery yields better measurable hearing preservation than microsurgery and equivalent serviceable hearing preservation rate and tumor growth control.

Radiosurgical boost for primary high-grade gliomas.

The purpose of this study was to retrospectively evaluate the survival of patients with high-grade gliomas treated with external beam radiotherapy with or without radiosurgical boost. From July 1993 to April 1998, 32 patients were selected, 15 of which received radiosurgery. Inclusion criteria were age > 18 years, histological confirmation of high-grade glioma, primary tumor treatment with curative intent, unifocal tumor and supratentorial location. All patients were found to be in classes III-VI, according to the recursive partitioning analysis proposed by the Radiation Therapy Oncology Group. The median interval between radiotherapy and radiosurgery was 5 weeks (range 1-13). Treatment volumes ranged from 2.9 to 70.3 cc (median 15.0 cc). Prescribed radiosurgery doses varied from 8.0 to 12.5 Gy (median 10.0 Gy). Radiosurgery and control groups were well balanced with respect to prognostic factor distributions. Median actuarial survival time in radiosurgery and control groups was 21.4 months and 11.6 months, respectively (p = 0.0254). Among patients with KPS > 80, median survival time was 11.0 months and 53.9 months in the control and radiosurgery groups, respectively (p = 0.0103). Radiosurgery was the single factor correlated with survival on Cox model analysis (p = 0.0362) and was associated with a 2.76 relative reduction in the risk of cancer death (95% confidence interval (CI) 1.07-7.13). Our results suggest that radiosurgery may confer a survival advantage for patients in RPA classes III-VI, especially for those with Karnofsky performance status >80. The definitive role of radiosurgical boost for patients with high-grade gliomas awaits the results of randomized trials.

Effects of Stereotactic Radiosurgery on an Animal Model of Hippocampal Epilepsy

Stereotactic radiosurgery has been shown in small clinical series to reduce or abolish seizures in patients with lesion-related or idiopathic epilepsy. The radiation dose necessary to eliminate epileptogenesis is unknown, and the histological and metabolic effects of radiosurgery remain undefined. We hypothesized that in a rat model of kainic acid-induced hippocampal epilepsy, radiosurgery could provide a significant reduction in seizure frequency while limiting biochemical and structural histological damage to the brain. Kainic acid (8 g) was injected into the rat hippocampus using stereotactic targeting. Focal seizures so generated were identified with scalp and depth electroencephalography (EEG). Epileptic rats were randomized to a control group (n = 20) and to radiosurgery groups in which maximum doses of 20, 40, 60, or 100 Gy (8-9 animals per group) were administered. Over a 42-day period, seizure frequency was determined by direct observation for 8 hours per week. Scalp EEG was performed weekly in all animals. Magnetic resonance imaging (MRI) studies (T1- and T2-weighted water-proton and quantitative sodium images) were obtained on Days 7, 21, and 42. As compared with the control group, treated animals showed significant reductions in the number of seizures during each successive week after 20-Gy radiosurgery (P = 0.01-0.002). When we combined the number of seizures observed in the latter half of the study (Weeks 4-6), we found a significant reduction in seizures after 20-Gy (P = 0.007), 40-Gy (P = 0.03), 60-Gy (P = 0.03), and 100-Gy (P = 0.03) radiosurgery as compared with control animals. Increasing doses of radiosurgery correlated with higher percentages of rats that became seizure-free by EEG criteria. MRI-determined total sodium concentration in the injected hippocampus was 49.8+/-3 mmol/L, compared with 42.8 mmol/L on the contralateral side (within normal limits). This significant increase in sodium concentration was present in control rats (because of the kainic acid) and did not change with increasing radiosurgery dose. No parenchymal effects from radiosurgery were identified after 20, 40, and 60 Gy, and only two rats had necrosis at 100 Gy. All animals showed hippocampal injury from kainic acid by proton MRI and histological examination. In this rat hippocampal epilepsy model, stereotactic radiosurgery was followed by a significant dose-dependent reduction in the frequency of observed and EEG-defined seizures. These effects were not accompanied by increased radiation-induced structural or metabolic brain injury as assessed by proton and sodium MRI or histological examination. The role of radiosurgery as a new, nondestructive surgical therapy for idiopathic epilepsy warrants further investigation.

Stereotactic radiosurgery plus whole brain radiotherapy versus radiotherapy alone for patients with multiple brain metastases

Purpose: Multiple brain metastases are a common health problem, frequently diagnosed in patients with cancer. The prognosis, even after treatment with whole brain radiation therapy (WBRT), is poor with average expected survivals less than 6 months. Retrospective series of stereotactic radiosurgery have shown local control and survival benefits in case series of patients with solitary brain metastases. We hypothesized that radiosurgery plus WBRT would provide improved local brain tumor control over WBRT alone in patients with two to four brain metastases.Methods: Patients with two to four brain metastases (all ≤25 mm diameter and known primary tumor type) were randomized to initial brain tumor management with WBRT alone (30 Gy in 12 fractions) or WBRT plus radiosurgery. Extent of extracranial cancer, tumor diameters on MRI scan, and functional status were recorded before and after initial care.Results: The study was stopped at an interim evaluation at 60% accrual. Twenty-seven patients were randomized (14 to WBRT alone and 13 to WBRT plus radiosurgery). The groups were well matched to age, sex, tumor type, number of tumors, and extent of extracranial disease. The rate of local failure at 1 year was 100% after WBRT alone but only 8% in patients who had boost radiosurgery. 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 plus radiosurgery (p = 0.0005). The median time to any brain failure was improved in the radiosurgery group (p = 0.002). Tumor control did not depend on histology (p = 0.85), number of initial brain metastases (p = 0.25), or extent of extracranial disease (p = 0.26). Patients who received WBRT alone lived a median of 7.5 months, while those who received WBRT plus radiosurgery lived 11 months (p = 0.22). Survival did not depend on histology or number of tumors, but was related to extent of extracranial disease (p = 0.02). There was no neurologic or systemic morbidity related to stereotactic radiosurgery.Conclusions: Combined WBRT and radiosurgery for patients with two to four brain metastases significantly improves control of brain disease. WBRT alone does not provide lasting and effective care for most patients.

Stereotactic Radiosurgery Versus Microsurgical Resection for the Initial Treatment of Metastatic Cancer to the Brain

The use of Stereotactic radiosurgery for the treatment of intracranial metastases from systemic cancer has grown considerably in the last few years. Review of the literature, however, reveals a paucity of well-controlled studies to substantiate this expansion. We conducted this study to address the issue of survival after treatment with either stereotactic radiosurgery or surgical resection. Whole brain radiation was instituted in both treatment arms. This was a retrospective, case-controlled study comparing patients whose only treatment for intracranial disease was either stereotactic radio-surgery or a single surgical resection. Controlling for age, histology, whole brain radiation, tumor size, number of intracranial lesions, and pre-procedural Karnofsky performance scores, we believe this study to be the most rigorous analysis to date. Patients in the radiosurgery group survived longer (median survival = 12.5 months) than those in the surgically resected group (median survival = 8 months). Statistical analysis of these curves did not show a significant difference. Considering only length of patient survival, there is no statistical difference between stereotactic radiosurgery and microsurgical resection for the treatment of new brain metastases from systemic cancer. This conclusion is based on strict criteria as outlined in the text. A larger, prospective, randomized investigation is needed to more definitively address the issue.

Reduction of hippocampal-kindled seizure activity in rats by stereotactic radiosurgery.

Radiosurgery may provide an alternative therapy for intractable epilepsy by eliminating or modifying abnormally active pacemaker neurons in epileptic foci. In the present study, the effect of radiosurgery on rat hippocampal kindling was examined. Rats received daily hippocampal stimulus trains until they were fully kindled. They then underwent radiosurgery of the kindled focus, receiving a single-dose of 0-, 10-, or 40-Gy. The 40-Gy group demonstrated an acute decrease in seizure threshold (3-5 days). Three months after radiosurgery, the threshold for seizures increased and the duration of afterdischarges decreased in the 40-Gy radiosurgery group compared to controls. The changes to both seizure threshold and afterdischarge duration were not significant in the 10-Gy group. These data suggest that radiosurgery is an effective means of reducing the epileptogenic activity of seizure foci.

Treatment selection for cerebral arteriovenous malformations: radiosurgery or microsurgery

The clinical results and patient characteristics of 318 cases of cerebral arteriovenous malformations (AVMs) were analyzed: 138 patients were treated by surgery including 98 cases of total removal and 17 cases of subtotal removal; 37 patients were treated conservatively; 139 patients were treated by gamma-knife and 6 patients were treated by linac-knife radiosurgery using stereotactic multi-converging arcs systems. Clinical data analysis was performed using the same protocol in both of the surgery and the radiosurgery groups. Operative mortality for total removal was one out of 98 cases (1%). There was one death by hemorrhage, one case of symptomatic rebleeding and two cases of asymptomatic bleeding in patients treated by radiosurgery. Thus, mortality was 1 out of 145 (0.7%). Patients with total resection of AVMs had the best clinical results in comparison with subtotal resection or with conservative treatment. Morbidity was the lowest in the patients treated by radiosurgery. However, the total obliteration rate was lower than the surgical cure rate. The decision for treatment should be based on an estimation of mortality, morbidity and cure rate for each treatment.

Surgery versus radiosurgery in the treatment of brain metastasis.

Surgery and radiosurgery are effective treatment modalities for brain metastasis. To compare the results of these treatment modalities, the authors followed 13 patients treated by radiosurgery and 62 patients treated by surgery who were retrospectively matched. Patients were matched according to the following criteria: histological characteristics of the primary tumor, extent of systemic disease, preoperative Karnofsky Performance Scale score, time to brain metastasis, number of brain metastases, and patient age and sex. For patients treated by radiosurgery, the median size of the treated lesion was 1.96 cm3 (range 0.41-8.25 cm3) and the median dose was 20 Gy (range 12-22 Gy). The median survival was 7.5 months for patients treated by radiosurgery and 16.4 months for those treated by surgery; this difference was found to be statistically significant using both univariate (p = 0.0018) and multivariate (p = 0.0009) analyses. The difference in survival was due to a higher rate of mortality from brain metastasis in the radiosurgery group than in the surgery group (p < 0.0001) and not due to a difference in the rate of death from systemic disease (p = 0.28). Log-rank analysis showed that the higher mortality rate found in the radiosurgery group was due to a greater progression rate of the radiosurgically treated lesions (p = 0.0001) and not due to the development of new brain metastasis (p = 0.75). On the basis of their data, the authors conclude that surgery is superior to radiosurgery in the treatment of brain metastasis. Patients who undergo surgical treatment survive longer and have a better local control. The data lead the authors to suggest that the indications for radiosurgery should be limited to surgically inaccessible metastatic tumors or patients in poor medical condition. Surgery should remain the treatment of choice whenever possible.

The radiobiology of human acoustic schwannoma xenografts after stereotactic radiosurgery evaluated in the subrenal capsule of athymic mice

An experimental model with xenograft transplantation into the subrenal capsule of athymic (nude) mice was used to evaluate the early response of human acoustic schwannomas to stereotactic radiosurgery. After xenograft placement, 45 mice underwent radiosurgery with single doses of 10, 20, or 40 Gy using a 201-source 60Co gamma unit (4-mm collimator, single isocenter, 80% isodose line). The 45 radiosurgery-treated xenografts were compared with 15 untreated xenografts and 15 xenografts in mice that underwent "sham radiosurgery." All five study groups were matched for the following pretreatment variables: patient of origin, animal weight, average xenograft diameter, and percentage of xenograft surface vascularity. Immediately prior to sacrifice of the mice all xenografts were evaluated in situ to determine the average tumor diameter, tumor volume, and percentage of surface vascularity. Mice were sacrificed 2 weeks, 1 month, or 3 months after radiosurgery. Blinded histological review was performed by an independent neuropathologist. Tumor volume was reduced 33.6% after 2 weeks (p = 0.023) and 45% after 3 months (p = 0.018) in the 40-Gy radiosurgery group. Tumor volume was reduced by 46.2% after 1 month (p = 0.0002) and 35.2% after 3 months (p = 0.032) in the 20-Gy radiosurgery group. An average volume reduction of 16.4% was observed after 3 months (p = 0.17) in the 10-Gy radiosurgery group. At 3 months after surgery, tumor surface vascularity was reduced by an average of 19.7% (p = 0.043) in the 40-Gy radiosurgery group and 5.8% (p = 0.12) in the 20-Gy radiosurgery group and was unchanged in the 10-Gy radiosurgery group and both control groups. Histological examination demonstrated a higher incidence of hemosiderin deposits (p = 0.026) and vascular mural hyalinization (p = 0.032) in radiosurgery xenografts versus control. The subrenal capsule xenograft in nude mice was an excellent model for studying the in vivo radiobiology of acoustic schwannomas after radiosurgery. Both cellular and vascular effects could be assessed serially in situ and the model was stable even 4 months after transplantation. Additional studies investigating radiobiology over periods better approximating the time course of clinical neuroimaging changes (6 to 12 months) are warranted.

Radiobiology of radiosurgery: Part II. The rat C6 glioma model.

We developed an experimental animal model to evaluate the potential role of stereotactic radiosurgery for glial neoplasms. Rats were randomized to control or treatment groups after implantation of C6 glioma cells into the right frontal region; 14 days later, 19 rats underwent stereotactic radiosurgical treatment of the induced tumor, using the 4-mm collimator of the gamma unit. Both groups were observed for up to 65 days after implantation. Treated animals had a mean survival of 39.2 days; the 22 control animals lived a mean of 29.4 days before death from tumor growth (P = 0.07). Six treated animals (32%), but only one control animal, survived the full observation period (P = 0.07). The mean tumor diameter in the control group was 9.64 mm; in the radiosurgery group, it was 6.47 mm (P = 0.001). Compared with tumors in control animals, treated tumors had a hypocellular appearance (P less than 0.001) and demonstrated cellular edema (P less than 0.005) under light microscopy, indicating a direct cytotoxic response to treatment. No difference was identified in the amount of tumor necrosis, intratumor hemorrhage, or degree of brain invasion between the two groups. Variations in the maximum treatment dose (30, 40, 50, 70, or 100 Gy) did not result in observed differences in tumor response. This in vivo rat malignant glioma model is a valuable tool to evaluate the tumoricidal effects of single-fraction, focused irradiation. Additional studies are warranted to evaluate dose-response relationships, radiation sensitizers, and use of radiosurgery with other adjuvant treatments.