Reducing the risk of rebleeding before early aneurysm surgery: a possible role for antifibrinolytic therapy

1997 ◽  
Vol 86 (2) ◽  
pp. 220-225 ◽  
Author(s):  
Thomas J. Leipzig ◽  
Kathleen Redelman ◽  
Terry G. Horner
Keyword(s):  
Surgical Intervention ◽  
High Dose ◽  
Aneurysm Surgery ◽  
Recurrent Hemorrhage ◽  
Content Type ◽  
Early Aneurysm Surgery ◽  
Antifibrinolytic Therapy ◽  
Symptomatic Vasospasm ◽  
Early Surgical Intervention ◽  
Fine Print

✓ Previous studies on the initial nonoperative management of aneurysmal subarachnoid hemorrhage (SAH) demonstrated that antifibrinolytic therapy reduced the risk of rebleeding by approximately 50%; however, prolonged antifibrinolytic treatment was associated with an increase in the incidence of hydrocephalus and delayed ischemic deficit. When early surgical intervention became routine for ruptured aneurysms, the use of antifibrinolytic therapy diminished. However, early surgery is generally performed in the first several days after SAH and the risk of rebleeding remains until the aneurysm is obliterated. Based on a review of the literature, the authors formed two hypotheses: 1) the high-dose intravenous administration of epsilon-aminocaproic acid (EACA), an antifibrinolytic agent, might reduce the risk of recurrent hemorrhage in the interval between SAH and early surgical intervention, and 2) a short course of EACA might not produce the increase in complications previously associated with its prolonged administration. The use of preoperative high-dose EACA therapy was evaluated in 307 patients to determine its safety and efficacy in reducing the incidence of rebleeding before early aneurysm surgery. All patients were admitted within 3 days of their SAH and were classified as Hunt and Hess Grades I to III. Only four patients (1.3%) suffered a recurrent hemorrhage. This compares favorably to the rebleeding rate of 5.7% reported for the early surgery group in the International Cooperative Study on the Timing of Aneurysm Surgery. The incidence of hydrocephalus or symptomatic vasospasm was not unduly elevated in patients receiving preoperative EACA. Thirty-five patients (11.4%) needed temporary cerebrospinal fluid drainage during their hospitalization and, overall, 8.8% required a ventriculoperitoneal shunt. The mean age of the patients who required a shunt was nearly 10 years older than the general study population. Seventy-one patients (23%) developed symptomatic vasospasm and 8.1% suffered a stroke. This study indicates that a brief course of high-dose EACA is safe and may be beneficial in diminishing the risk of rebleeding in good-grade patients prior to early surgical intervention. Further investigation is planned based on these promising results.

Antifibrinolytic therapy in the acute period following aneurysmal subarachnoid hemorrhage

1984 ◽  
Vol 61 (2) ◽  
pp. 225-230 ◽  
Author(s):  
Neal F. Kassell ◽  
James C. Torner ◽  
Harold P. Adams
Keyword(s):  
Subarachnoid Hemorrhage ◽  
Aneurysmal Subarachnoid Hemorrhage ◽  
Aneurysm Surgery ◽  
Cooperative Study ◽  
Content Type ◽  
Antifibrinolytic Therapy ◽  
Rebleeding Rate ◽  
Relationship Of ◽  
The Relationship ◽  
Fine Print

✓ Antifibrinolytic therapy remains a controversial issue in the management of subarachnoid hemorrhage (SAH). The relationship of antifibrinolytic therapy with mortality, rebleeding, ischemia, hydrocephalus, and clotting abnormalities was studied in 672 patients in the International Cooperative Study on the Timing of Aneurysm Surgery. The patients with antifibrinolytic therapy had a significantly lower rebleeding rate, but higher rates of ischemic deficits and hydrocephalus. The net result was no difference in mortality in the 1st month following the initial SAH. Further clinical trials are needed to determine the overall effects of antifibrinolytic therapy.

A randomized controlled trial of high-dose intravenous nicardipine in aneurysmal subarachnoid hemorrhage

1993 ◽  
Vol 78 (4) ◽  
pp. 537-547 ◽  
Author(s):  
E. Clarke Haley ◽  
Neal F. Kassell ◽  
James C. Torner ◽  
_ _
Keyword(s):  
Subarachnoid Hemorrhage ◽  
Aneurysmal Subarachnoid Hemorrhage ◽  
Controlled Trial ◽  
Treated Group ◽  
High Dose ◽  
Similar Frequency ◽  
Content Type ◽  
Symptomatic Vasospasm ◽  
Delayed Cerebral Vasospasm ◽  
Fine Print

✓ Because of their action as cerebral vasodilators, dihydropyridine calcium antagonists have received intense scrutiny for their potential benefit in ameliorating the devastating consequences of delayed cerebral vasospasm following aneurysmal subarachnoid hemorrhage (SAH). From October, 1987, to September, 1989, 41 North American neurosurgical centers in the Cooperative Aneurysm Study accrued 906 patients with recent (Days 0 to 7) aneurysmal SAH into a prospective randomized double-blind placebo-controlled trial of high-dose intravenous nicardipine to test whether treatment with this agent improved overall outcome. Eligible patients received 0.15 mg/kg/hr of either nicardipine or placebo by continuous infusion for up to 14 days following hemorrhage. The 449 patients randomly assigned to the nicardipine-treated group and the 457 patients assigned to the placebo-treated group were balanced with regard to prognostic factors for ischemic deficits from vasospasm and for overall outcome. Other medical and surgical interventions were used with similar frequency in both groups, except that antihypertensive agents were used less frequently in the nicardipine-treated patients (26% of the nicardipine-treated group vs. 43% of the placebo-treated group, p < 0.001), and more patients in the placebo-treated group had intentional hypervolemia, induced hypertension, and/or hemodilution administered therapeutically for symptomatic vasospasm (38% of the placebo-treated group vs. 25% of the nicardipine-treated group, p < 0.001). The incidence of symptomatic vasospasm during the treatment period was higher in the placebo-treated group (46%) than in the nicardipine-treated group (32%) (p < 0.001). Despite the reduction in symptomatic vasospasm in the nicardipine-treated group, overall outcome at 3 months was similar between the two groups. Fifty-five percent of nicardipine-treated patients were rated as having a good recovery according to the Glasgow Outcome Scale at follow-up review and 17% were dead, compared to 56% and 18%, respectively, in the placebo-treated group (not statistically significant). These data suggest that high-dose intravenous nicardipine treatment is associated with a reduced incidence of symptomatic vasospasm in patients with recent aneurysmal SAH, but not with an improvement in overall outcome at 3 months when compared to standard management in North America. It is postulated that, while nicardipine prevents vasospasm, hypertensive/hypervolemic therapy may be effective in reversing ischemic deficits from vasospasm once they occur.

Magnesium sulfate therapy after aneurysmal subarachnoid hemorrhage

2002 ◽  
Vol 96 (3) ◽  
pp. 510-514 ◽  
Author(s):  
Richard S. Veyna ◽  
Donald Seyfried ◽  
Don G. Burke ◽  
Chris Zimmerman ◽  
Mark Mlynarek ◽  
...  
Keyword(s):  
Subarachnoid Hemorrhage ◽  
Magnesium Sulfate ◽  
Aneurysmal Subarachnoid Hemorrhage ◽  
Control Group ◽  
High Dose ◽  
Content Type ◽  
Symptomatic Vasospasm ◽  
Male Patients ◽  
The Mean ◽  
Fine Print

Object. Vasospasm remains a significant source of neurological morbidity and mortality following aneurysmal subarachnoid hemorrhage (SAH), despite advances in current medical, surgical, and endovascular therapies. Magnesium sulfate therapy has been demonstrated to be both safe and effective in preventing neurological complications in obstetrical patients with eclampsia. Evidence obtained using experimental models of brain injury, cerebral ischemia, and SAH indicate that Mg may also have a role as a neuroprotective agent. The authors hypothesize that MgSO4 therapy is safe, feasible, and has a beneficial effect on vasospasm and, ultimately, on neurological outcome following aneurysmal SAH. Methods. A prospective randomized single-blind clinical trial of high-dose MgSO4 therapy following aneurysmal SAH (Hunt and Hess Grades II–IV) was performed in 40 patients, who were enrolled within 72 hours following SAH and given intravenous MgSO4 or control solution for 10 days. Serum Mg++ levels were maintained in the 4 to 5.5 mg/dl range throughout the treatment period. Clinical management principles were the same between groups (including early use of surgery or endovascular treatment, followed by aggressive vasospasm prophylaxis and treatment). Daily transcranial Doppler (TCD) ultrasonographic recordings were obtained, and clinical outcomes were measured using the Glasgow Outcome Scale (GOS). The patients' GOS scores and the TCD recordings were analyzed using the independent t-test. Forty patients were enrolled in the study: 20 (15 female and five male patients) received treatment and 20 (11 female and nine male patients) comprised a control group. The mean ages of the patients in these groups were 46 and 51, respectively, and the mean clinical Hunt and Hess grades were 2.6 ± 0.68 in the MgSO4 treatment group and 2.3 ± 0.73 in the control group (mean ± standard deviation [SD], p = 0.87). Fisher grades were similar in both groups. Mean middle cerebral artery velocities were 93 ± 27 cm/second in MgSO4-treated patients and 102 ± 34 cm/second in the control group (mean ± SD, p = 0.41). Symptomatic vasospasm, confirmed by angiography, occurred in six of 20 patients receiving MgSO4 and in five of 16 patients receiving placebo. Mean GOS scores were 3.8 ± 1.6 and 3.6 ± 1.5 (mean ± SD, p = 0.74) in the treatment and control groups, respectively. Significant adverse effects from treatment with MgSO4 did not occur. Conclusions. Administration of high-dose MgSO4 following aneurysmal SAH is safe, and steady Mg++ levels in the range of 4 to 5.5 mg/dl are easily maintained. This treatment does not interfere with neurological assessment, administration of anesthesia during surgery, or other aspects of clinical care. We observed a trend in which a higher percentage of patients obtained GOS scores of 4 or 5 in the group treated with MgSO4, but the trend did not reach a statistically significant level. A larger study is needed to evaluate this trend further.

Significance of vasospasm in the treatment of ruptured intracranial aneurysms

1977 ◽  
Vol 47 (3) ◽  
pp. 412-429 ◽  
Author(s):  
Isamu Saito ◽  
Yasuichi Ueda ◽  
Keiji Sano
Keyword(s):  
Intracranial Aneurysms ◽  
Surgical Intervention ◽  
Blood Clot ◽  
Timing Of Surgery ◽  
Neurological Deficits ◽  
Aneurysm Surgery ◽  
Content Type ◽  
Ruptured Intracranial Aneurysm ◽  
Ruptured Intracranial Aneurysms ◽  
Fine Print

✓ The authors have analyzed a total of 96 consecutive cases in which vasospasm followed subarachnoid hemorrhage (SAH). The SAH was caused by ruptured intracranial aneurysm or developed after aneurysm surgery. Usually at least 4 days elapsed between SAH and the onset of vasospasm. Vasospasm subsided an average of 2 weeks after onset. Of 68 patients with preoperative vasospasm, eight died due to cerebral edema resulting from ischemia, and 49% of the survivors had neurological deficits. Preoperative vasospasm was not aggravated by surgical intervention when operations were carried out more than 7 days after the onset of vasospasm. Postoperative vasospasm was found in 25 of 52 patients who underwent operation within 1 week after SAH (excluding cases in Grade V). Five of these patients died, all of whom underwent surgery between the fourth and seventh day after SAH (the day of SAH was counted as the first day). There were no deaths among 20 patients operated on within the first 3 days after SAH. Postoperative vasospasm was always mild in these cases, when it occurred, probably because blood clot or blood-stained cerebrospinal fluid was removed by operative procedures. In all cases, 4 to 11 days elapsed between the last SAH and the onset of postoperative vasospasm regardless of the timing of surgery.

A randomized trial of two doses of nicardipine in aneurysmal subarachnoid hemorrhage

1994 ◽  
Vol 80 (5) ◽  
pp. 788-796 ◽  
Author(s):  
E. Clarke Haley ◽  
Neal F. Kassell ◽  
James C. Torner ◽  
Laura L. Truskowski ◽  
Teresa P. Germanson ◽  
...  
Keyword(s):  
Subarachnoid Hemorrhage ◽  
Side Effects ◽  
Dose Group ◽  
Low Dose ◽  
Aneurysmal Subarachnoid Hemorrhage ◽  
High Dose ◽  
Content Type ◽  
Symptomatic Vasospasm ◽  
To Receive ◽  
Fine Print

✓ High-dose intravenous nicardipine has been shown to reduce the incidence of angiographic and symptomatic vasospasm in patients with aneurysmal subarachnoid hemorrhage (SAH), but treatment may be complicated by side effects, including hypotension or pulmonary edema/azotemia. From August, 1989, to January, 1991, 365 patients at 21 neurosurgical centers were entered into a randomized double-blind trial comparing high-dose (0.15 mg/kg/hr) nicardipine with a 50% lower dose (0.075 mg/kg/hr) administered by continuous intravenous infusion for up to 14 days following SAH. Patients in all neurological grades were eligible for the study. During the study period, 184 patients were randomly assigned to receive high-dose nicardipine and 181 to receive the low dose. There were no significant differences in patient age, admission neurological condition, or amount and distribution of blood clot on initial computerized tomography scan. Patients in the high-dose group received a significantly smaller proportion of the planned dose than those in the low-dose group (80% ± 0.2% vs. 86% ± 0.2%, p < 0.05), largely because of premature treatment termination after adverse medical events. The incidence of symptomatic vasospasm was 31% in both groups, and the overall 3-month outcomes were nearly identical. These data suggest that, from a clinical standpoint, the results of high-dose and low-dose nicardipine treatment are virtually equivalent, but administration of low-dose nicardipine is attended by fewer side effects.

Double-blind, randomized, vehicle-controlled study of high-dose tirilazad mesylate in women with aneurysmal subarachnoid hemorrhage. Part II. A cooperative study in North America

1999 ◽  
Vol 90 (6) ◽  
pp. 1018-1024 ◽  
Author(s):  
Giuseppe Lanzino ◽  
Neal F. Kassell ◽  
_ _
Keyword(s):  
Sequential Analysis ◽  
Aneurysmal Subarachnoid Hemorrhage ◽  
Study Drug ◽  
Treated Group ◽  
High Dose ◽  
Double Blind ◽  
Content Type ◽  
Symptomatic Vasospasm ◽  
Tirilazad Mesylate ◽  
Fine Print

Object. To test the safety and efficacy of high-dose (15 mg/kg/day) tirilazad mesylate in women suffering from aneurysmal subarachnoid hemorrhage (SAH), a prospective randomized, double-blind, vehicle-controlled trial (parallel to the one conducted in Europe, Australia, New Zealand, and South Africa) was performed at 65 North American neurosurgical centers.Methods. Of the 832 patients who were randomized, 823 received at least one dose of tirilazad (410 patients) or placebo vehicle containing citrate (413 patients). The two groups were similar with respect to their prognostic factors for overall outcome and delayed cerebral ischemia. There were no differences in medical and surgical interventions including hyperdynamic therapy (intentional hypervolemia, induced hypertension, and/or hemodilution) between the two treatment groups.In contrast to the accompanying study, the protocol for the North American study was formally amended, in that a sequential analysis of the primary efficacy end point, mortality rate at 91 days postdosing, was performed. This analysis revealed a statistically significant difference in mortality rates, favoring the study drug, among patients who were neurological Grade IV or V at admission (24.6% compared with 43.4% in the placebo-treated group, p = 0.016). No significant differences, however, were found when the entire patient population was considered (15.6% in the placebo-treated group and 13% in the tirilazad-treated group). Other major and secondary end points, which included rate of favorable outcome (74% in the placebo-treated group and 71% in the tirilazad-treated group); symptomatic vasospasm (38% in the placebo-treated group and 35% in the tirilazad-treated group); and vasospasm severity (severe symptomatic vasospasm in 14% of patients in both groups), were also not significantly different between the two groups. In patients with neurological Grades I through III, rates of favorable outcome advantageous to the vehicle-treated group were observed (83.3% compared with 76.7%, p = 0.04).Conclusions. High-dose tirilazad mesylate is well tolerated in women with aneurysmal SAH. Sequential analysis revealed a significant reduction in mortality rates among patients with neurological Grades IV and V, favoring the study drug and confirming the same effect observed in male patients in previous large studies. No beneficial effect was observed in patients who were in a good neurological grade at admission.

Early versus late intracranial aneurysm surgery in subarachnoid hemorrhage

1988 ◽  
Vol 69 (3) ◽  
pp. 326-331 ◽  
Author(s):  
Douglas Chyatte ◽  
Nicolee C. Fode ◽  
Thoralf M. Sundt
Keyword(s):  
Subarachnoid Hemorrhage ◽  
Intracranial Aneurysm ◽  
Surgical Intervention ◽  
Aneurysmal Subarachnoid Hemorrhage ◽  
Direct Result ◽  
Aneurysm Surgery ◽  
Content Type ◽  
Surgical Group ◽  
Fine Print

✓ The management results in 244 patients admitted to one institution within 3 days of aneurysmal subarachnoid hemorrhage (SAH) from January, 1979, to December, 1985, were analyzed with respect to the timing of surgical intervention. Twenty-six patients died prior to surgery. Patients surviving to surgery were divided into three groups according to the interval between preadmission SAH and surgery: 0 to 3 days (85 cases), 4 to 9 days (83 cases), and 10 or more days (50 cases). Of the patients who were categorized neurologically into Botterell Grades 1 and 2 (Hunt and Hess Grades I to III) on admission, 87% had an excellent or good result on follow-up evaluation. Patients undergoing surgery 0 to 3 days after SAH had a statistically significant increase in the incidence of postoperative ischemic symptoms (p < 0.005), which was balanced by similar complications preoperatively in the 10-day post-SAH surgical group. Most rebleeds occurred before admission but delaying surgery did increase the risk of rebleeding in the hospital (p < 0.0005). Management morbidity and mortality occurred primarily as a direct result of a severe initial hemorrhage; thus, the measured benefits of early surgery were less than might have been predicted.

Double-blind, randomized, vehicle-controlled study of high-dose tirilazad mesylate in women with aneurysmal subarachnoid hemorrhage. Part I. A cooperative study in Europe, Australia, New Zealand, and South Africa

1999 ◽  
Vol 90 (6) ◽  
pp. 1011-1017 ◽  
Author(s):  
Giuseppe Lanzino ◽  
Neal F. Kassell ◽  
Nicholas W. C. Dorsch ◽  
Alberto Pasqualin ◽  
Lennart Brandt ◽  
...  
Keyword(s):  
Cerebral Ischemia ◽  
Delayed Cerebral Ischemia ◽  
Study Drug ◽  
Treated Group ◽  
High Dose ◽  
Content Type ◽  
Symptomatic Vasospasm ◽  
Tirilazad Mesylate ◽  
Induced Hypertension ◽  
Fine Print

Object. Findings from previous multicenter clinical trials have suggested that tirilazad mesylate, a synthetic nonhormonal 21-aminosteroid, might be effective in preventing delayed cerebral ischemia following subarachnoid hemorrhage (SAH). This beneficial effect, however, was greater in males than females, possibly because of gender-related pharmacokinetic differences. The authors sought to assess the effects of administering a larger dose of tirilazad in women with SAH.Methods. To test the efficacy of a higher tirilazad mesylate dose in female patients, a prospective randomized, doubleblind, vehicle-controlled trial was conducted at 56 neurosurgical centers in Europe, Australia, New Zealand, and South Africa. Eight hundred nineteen patients were randomly assigned to receive either 15 mg/kg/day of tirilazad mesylate or a placebo containing the citrate vehicle. The two groups were similar in prognostic factors for delayed cerebral ischemia and overall outcome. High-dose tirilazad appeared to be well tolerated because no differences in the incidence of untoward medical events were noted between the two groups. Medical and surgical interventions were no different in the two treatment groups except for hyperdynamic therapy (intentional hypervolemia, induced hypertension, and/or hemodilution), which was more often used in the placebo-treated group to counteract symptomatic vasospasm (24% of patients given placebo compared with 18% of patients given tirilazad, p = 0.02).Mortality rates and overall outcome, assessed using the Glasgow Outcome Scale at 3 months post-SAH, were not different between the two groups, despite a significantly lower incidence of delayed cerebral ischemia in patients given tirilazad. Post hoc subgroup analysis by neurological grade also did not reveal significant differences in outcome, although a trend toward a lower mortality rate favoring the study drug was present in patients with neurological Grade IV and V at admission (32% compared with 37%). Symptomatic vasospasm occurred in 33.7% of the placebo-treated patients as opposed to 24.8% of the patients who were given tirilazad (p = 0.005). The severity of symptomatic vasospasm was also attenuated by administration of the study drug (severe symptomatic vasospasm was reported in 11% of the placebo-treated patients compared with 6% of patients in the tirilazad-treated group (p = 0.008). Clinical cerebral infarction from vasospasm was also reduced from 13% in the vehicle-treated group to 8% in the tirilazad-treated group (p < 0.04).Conclusions. The authors conclude that high-dose tirilazad mesylate is well tolerated in women with aneurysmal SAH. Although a significant reduction in the incidence of symptomatic vasospasm was observed in the treatment group, the primary end point (mortality rate at 3 months post-SAH) was not affected by the study drug. The use of other potentially effective rescue therapies (that is, hypervolemia, hemodilution, and induced hypertension) to counteract vasospasm may have been responsible for these contrasting observations between the two groups.

Dual-isotope single-photon emission computerized tomography scanning in patients with glioblastoma multiforme: association with patient survival and histopathological characteristics of tumor after high-dose radiotherapy

1998 ◽  
Vol 89 (1) ◽  
pp. 60-68 ◽  
Author(s):  
Richard B. Schwartz ◽  
B. Leonard Holman ◽  
Joseph F. Polak ◽  
Basem M. Garada ◽  
Marc S. Schwartz ◽  
...  
Keyword(s):  
Survival Rate ◽  
Glioblastoma Multiforme ◽  
Single Photon ◽  
Photon Emission ◽  
High Dose ◽  
Term Survival ◽  
Content Type ◽  
Dual Isotope ◽  
Fine Print

Object. The study was conducted to determine the association between dual-isotope single-photon emission computerized tomography (SPECT) scanning and histopathological findings of tumor recurrence and survival in patients treated with high-dose radiotherapy for glioblastoma multiforme. Methods. Studies in which SPECT with 201Tl and 99mTc-hexamethypropyleneamine oxime (HMPAO) were used were performed 1 day before reoperation in 47 patients with glioblastoma multiforme who had previously been treated by surgery and high-dose radiotherapy. Maximum uptake of 201Tl in the lesion was expressed as a ratio to that in the contralateral scalp, and uptake of 99mTc-HMPAO was expressed as a ratio to that in the cerebellar cortex. Patients were stratified into groups based on the maximum radioisotope uptake values in their tumor beds. The significance of differences in patient gender, histological characteristics of tissue at reoperation, and SPECT uptake group with respect to 1-year survival was elucidated by using the chi-square statistic. Comparisons of patient ages and time to tumor recurrence as functions of 1-year survival were made using the t-test. Survival data at 1 year were presented according to the Kaplan—Meier method, and the significance of potential differences was evaluated using the log-rank method. The effects of different variables (tumor type, time to recurrence, and SPECT grouping) on long-term survival were evaluated using Cox proportional models that controlled for age and gender. All patients in Group I (201Tl ratio < 2 and 99mTc-HMPAO ratio < 0.5) showed radiation changes in their biopsy specimens: they had an 83.3% 1-year survival rate. Group II patients (201T1 ratio < 2 and 99mTc-HMPAO ratio of ≥ 0.5 or 201Tl ratio between 2 and 3.5 regardless of 99mTc-HMPAO ratio) had predominantly infiltrating tumor (66.6%); they had a 29.2% 1-year survival rate. Almost all of the patients in Group III (201Tl ratio > 3.5 and 99mTc-HMPAO ratio ≥ 0.5) had solid tumor (88.2%) and they had a 6.7% 1-year survival rate. Histological data were associated with 1-year survival (p < 0.01); however, SPECT grouping was more closely associated with 1-year survival (p < 0.001) and was the only variable significantly associated with long-term survival (p < 0.005). Conclusions. Dual-isotope SPECT data correlate with histopathological findings made at reoperation and with survival in patients with malignant gliomas after surgical and high-dose radiation therapy.

Gamma knife radiosurgery in patients with advanced breast cancer undergoing bone marrow transplant

2002 ◽  
Vol 97 ◽  
pp. 663-665 ◽  
Author(s):  
Kenneth J. Levin ◽  
Emad F. Youssef ◽  
Andrew E. Sloan ◽  
Rajiv Patel ◽  
Rana K. Zabad ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Advanced Breast Cancer ◽  
Gamma Knife ◽  
Gamma Knife Radiosurgery ◽  
High Dose Chemotherapy ◽  
Advanced Breast ◽  
High Dose ◽  
Initial Management ◽  
Content Type ◽  
Fine Print

Object. Recent studies have suggested a high incidence of cognitive deficits in patients undergoing high-dose chemotherapy, which appears to be dose related. Whole-brain radiotherapy (WBRT) has previously been associated with cognitive impairment. The authors attempted to use gamma knife radiosurgery (GKS) to delay or avoid WBRT in patients with advanced breast cancer treated with high-dose chemotherapy and autologous bone marrow transplantation (HDC/ABMT) in whom brain metastases were diagnosed. Methods. A retrospective review of our experience from 1996 to 2001 was performed to identify patients who underwent HDC/ABMT for advanced breast cancer and brain metastasis. They were able to conduct GKS as initial management to avoid or delay WBRT in 12 patients following HDC/ABMT. All patients were women. The median age was 48 years (range 30–58 years). The Karnofsky Performance Scale score was 70 (range 60–90). All lesions were treated with a median prescription dose of 17 Gy (range 15–18 Gy) prescribed to the 50% isodose. Median survival was 11.5 months. Five patients (42%) had no evidence of central nervous system disease progression and no further treatment was given. Four patients were retreated with GKS and three of them eventually received WBRT as well. Two patients were treated with WBRT as the primary salvage therapy. The median time to retreatment with WBRT was 8 months after the initial GKS. Conclusions. Gamma knife radiosurgery can be effectively used for the initial management of brain metastases to avoid or delay WBRT in patients treated previously with HDC, with acceptable survival and preserved cognitive function.

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