Stereotactic radiosurgery for pilocytic astrocytomas when multimodal therapy is necessary

OBJECT: The goal of this study was to examine the role of stereotactic radiosurgery in the treatment of patients with recurrent or unresectable pilocytic astrocytomas. METHODS: During a 13-year interval, 37 patients (median age 14 years) required multimodal treatment of recurrent or unresectable pilocytic astrocytomas. Tumors involved the brainstem in 18 patients, cerebellum in three, thalamus in five, temporal lobe in four, and parietal lobe in two, as well as the hypothalamus, optic tract, corpus callosum, insular cortex, and third ventricle in one patient each. Diagnosis was confirmed with the aid of stereotactic biopsy in 12 patients, open biopsy in five, partial resection in eight, and near-total resection in 12. Multimodal treatment included fractionated radiation therapy in 10 patients, stereotactic intracavitary irradiation of tumor in four, chemotherapy in two, cyst drainage in six, ventriculoperitoneal shunt placement in three, and additional cytoreductive surgery in four. Tumor volumes varied from 0.42 to 25 cm3. The median radiosurgical dose to the tumor margin was 15 Gy (range 9.6-22.5 Gy). After radiosurgery, serial imaging demonstrated complete tumor resolution in 10 patients, reduced tumor volume in eight, stable tumor volume in seven, and delayed tumor progression in 12. No procedure-related death was encountered. Thirty-three (89%) of 37 patients are alive at a median follow-up period of 28 months after radiosurgery and 59 months after diagnosis. Eight patients participated in follow-up review for more than 60 months. Three patients died of local tumor progression. CONCLUSIONS: Stereotactic radiosurgery is a valuable adjunctive strategy in the management of recurrent or unresectable pilocytic astrocytomas. Despite the favorable histological characteristics and prognosis usually associated with this neoplasm, an adverse location, recurrence, or progression of this disease requires alternative therapeutic approaches such as radiosurgery.     

Radiosurgery for treatment of recurrent intracranial hemangiopericytomas

OBJECTIVE: Hemangiopericytomas are highly aggressive meningeal tumors with tendencies for recurrence and metastasis. The purpose of this retrospective, single-institution review was to evaluate the efficacy and role of stereotactic radiosurgery in the management of recurrent hemangiopericytomas. METHODS: We reviewed data for patients who underwent stereotactic radiosurgery at the University of Pittsburgh between 1987 and 2001. Fourteen patients underwent radiosurgery for 15 discrete tumors. Prior treatments included transsphenoidal resection (n = 1), craniotomy and resection (n = 27), embolization (n = 1), and conventional radiotherapy (n = 7). Clinical and radiological responses were evaluated. Follow-up periods varied from 5 to 76 months (mean, 31.3 mo; median, 21 mo). The mean radiation dose to the tumor margin was 15 Gy. RESULTS: Seventy-nine percent of patients (11 of 14 patients) with recurrent hemangiopericytomas demonstrated local tumor control after radiosurgery. Twelve of 15 tumors (i.e., 80%) dramatically decreased in size on follow-up imaging scans. Regional intracranial recurrences were retreated with radiosurgery for two patients (i.e., 15%); neither of those two patients experienced long-term tumor control. Local recurrences occurred 12 to 75 months (median, 21 mo) after radiosurgery. Local tumor control and survival rates at 5 years after radiosurgery were 76 and 100%, respectively (Kaplan-Meier method). We could not correlate prior irradiation or tumor size with tumor control. Twenty-nine percent of the patients (4 of 14 patients) developed remote metastases. Radiosurgery did not seem to offer protection against the development of intra- or extracranial metastases. CONCLUSION: Gamma knife radiosurgery provided local tumor control for 80% of recurrent hemangiopericytomas. When residual tumor is identified after resection or radiotherapy, early radiosurgery should be considered as a feasible treatment modality. Despite local tumor control, patients are still at risk for distant metastasis. Diligent clinical and radiological follow-up monitoring is necessary.     

Stereotactic biopsy and resection of thalamic astrocytomas

In this study of 72 patients who had histologically verified thalamic astrocytomas, 44 patients underwent stereotactic serial biopsy, 22 underwent stereotactic resection of the neoplasm, and an additional 6 patients underwent stereotactic biopsy followed by stereotactic resection of the tumor at a later date. Of the 50 patients who underwent stereotactic biopsy, 3 were neurologically worse after the procedure (morbidity, 6%), and 3 additional patients with Grade 4 astrocytomas who preoperatively were rapidly deteriorating neurologically, died within 30 days of the procedure. Of the 28 patients who underwent stereotactic resection, 14 were neurologically improved after the procedure, 10 were unchanged, and 4 were worse. One additional patient died 10 days postoperatively. Thirty-four patients had Grade 4 astrocytomas: 27 underwent stereotactic biopsies. The mean survival after biopsy and irradiation for patients with Grade 4 astrocytomas was 21.4 weeks. The mean survival was 62 weeks in 7 patients with Grade 4 astrocytomas who underwent stereotactic resection and radiation therapy. The mean survival time after biopsy and radiation therapy for patients who had Grade 3 and Grade 2 lesions was 54.4 weeks and 91 weeks, respectively. Twenty-three patients had pilocytic astrocytomas; 8 underwent stereotactic biopsies, and 19 underwent stereotactic resection of the tumor (4 of these underwent biopsy prior to resection). There was no neurological morbidity, but one patient died after resection. Many of those who underwent resection were deteriorating due to an enlarging tumor mass or recurring cyst, and had undergone more conservative therapies such as biopsy and radiation. Even though stereotactic biopsy is appropriate in many patients harboring thalamic astrocytomas, selected patients with significant mass effect from solid tumor or recurring cyst can benefit from stereotactic resection.     

Stereotactic radiosurgery for anterior foramen magnum meningiomas

BACKGROUND: Total microsurgical resection is the procedure of choice for growing and symptomatic foramen magnum meningiomas. We hypothesized that for patients with advanced age, complicating medical conditions, or residual or recurrent meningiomas at the foramen magnum, stereotactic radiosurgery would be a useful adjunctive (n = 2) or alternative (n = 3) treatment. METHODS: We report our experience in five elderly patients (73-84 years) who underwent gamma knife radiosurgery. The median tumor volume was 10.5 ml and the tumor margin dose varied from 10 to 16 Gy. Because of the irregular tumor volumes along the inferior clivus, multiple isocenters of irradiation were required (range, 2-8; mean 4.4). RESULTS: During the follow-up interval of 1-5 years (median, 3 years), one patient died of an intercurrent illness, and all remaining patients were stable without any further deterioration in their clinical condition. Follow-up imaging studies revealed a reduction in tumor volume in one patient and no further growth in the remaining four. CONCLUSION: We believe that stereotactic radiosurgery provides safe and effective management for patients who are poor candidates for resection of their foramen magnum meningiomas.     

Stereotactic management of craniopharyngiomas

Eleven patients with craniopharyngiomas underwent 13 stereotactic procedures (intracavitary irradiation, n = 7; radiosurgery, n = 6). Nine patients (82%) had recurrent tumors after prior surgery (median, 2 operations). The median patient age was 50 years (range, 6-63 years). At a median follow-up of 38 months (range, 24-102 months), no patient had progression of the treated tumor component. Two patients developed new cysts, so the actuarial 2- and 4-year progression-free survival rates were 91 and 73%, respectively. Visual function improved in 3 patients, remained stable in 6 patients, and worsened in 1 patient. Two patients (both without prior surgery) not having diabetes insipidus pre-operatively continued to have normal posterior pituitary function. Stereotactic techniques should be considered for patients with craniopharyngiomas, especially those who have failed prior surgical resection.     

Stereotactic radiosurgery as a salvage treatment for locally persistent and recurrent nasopharyngeal carcinoma.

BACKGROUND: The purpose of this work was to study the efficacy of stereotactic radiosurgery as a salvage treatment in patients with locally persistent and recurrent nasopharyngeal carcinoma (NPC). METHODS: Between March 1996 and August 1997, 10 patients with locally persistent or recurrent NPC were treated by linac-based stereotactic radiosurgery. Four patients had radiosurgery for persistent disease after a first course of radiotherapy, 3 had radiosurgery as a boost after reirradiation for local recurrence, and 3 had radiosurgery for disease that recurred after reirradiation. The tumor volume ranged from 1.3 to 23.7 cc (median: 5.2). Treatment was prescribed at 80% isodose line and ranged from 12 to 18 Gy (median: 13.4), with a mean tumor surface dose ranged from 10-21 Gy (median: 14). The median clinical follow-up was 10.5 months (range 8-27), and the median imaging follow-up was 9.5 months (range 6-26). RESULTS: One patient had complete regression of tumor after radiosurgery, five had reduction in tumor size, three had no change, and one had progression of tumor. The overall response rate to radiosurgery was 60% (6/10), with 10% (1/10) developing in-field progression. Excluding patients receiving radiosurgery as a boost treatment after reirradiation, the response rate was 57% (4/7) and none developed in-field progression. Only one patient developed a new cranial neuropathy in the absence of disease progression. CONCLUSION: In selected patients with locally persistent or recurrent NPC, stereotactic radiosurgery can be considered as a salvage treatment with good short-term local control. The complications appear to be minimal except for treating recurrence in the cavernous sinus. Early results are encouraging although more experience and longer follow-up are still needed to better define the role of radiosurgery in the management of persistent and recurrent NPC.     

Stereotactic radiosurgery for brainstem metastases.

OBJECT: Brainstem metastases portend a dismal prognosis. Surgical resection is not part of routine management and radiation therapy has offered little clinical benefit. Radiosurgery provides a safe and effective treatment for many patients with brain metastasis, but its role in the brainstem has not been evaluated. In this study the authors examine the role of radiosurgery in the treatment of brainstem metastases. METHODS: The authors reviewed the outcomes after stereotactic radiosurgery in 26 patients with 27 brainstem metastases. Tumor locations included the pons (21 tumors) and midbrain (six tumors): 14 patients had additional tumors in other locations. Twenty patients presented with brainstem signs. The median dose to the tumor margin was 16 Gy (range 12-20 Gy). Twenty-four patients received fractionated whole-brain radiation therapy (WBRT) and 12 underwent additional chemotherapy or immunotherapy. The median follow-up time in these patients was 9.5 months (range 1-43 months). After radiosurgery, the local control rate in brainstem tumors was 95%. In one patient in whom the tumor initially decreased in size, tumor enlargement was seen 7 months later. The median survival time was 11 months after diagnosis and 9 months after radiosurgery. Thirteen patients improved, 10 were stable, and three deteriorated. Eventually, 22 patients died, 18 of progression of their extracranial disease, three of new tumor growth (including one hemorrhage into a new brain metastasis), and one of extracranial disease plus new brain tumor growth. CONCLUSIONS: Although they have slightly lower than the expected survival rates of patients with nonbrainstem tumors, patients with brainstem metastases may achieve effective palliation after stereotactic radiosurgery and WBRT.     

Permanent Iodine-125 Implants in the Treatment of Low-Grade Gliomas

We report a retrospective study on the use of the permanent iodine-125 (¹²⁵I) implants in the management of low-grade gliomas. From July 1988 to July 1997, 16 patients with low-grade gliomas underwent permanent ¹²⁵I implants in the management of their lesions. There were 7 males and 9 females ranging in age from 4 to 48 years (mean 19). The location was in the cerebral hemisphere in 7 patients, brainstem in 5 patients and thalamus/basal ganglia in 4 patients. Prior to brachytherapy, 9 patients underwent surgical resection and 7 patients underwent stereotactic biopsy procedures. Fourteen patients were treated as part of the initial management and 2 were recurrent. The histological diagnosis was: 9 WHO grade II astrocytomas, 3 oligodendrogliomas, 2 gemistocytic astrocytomas, 1 pilocytic astrocytoma, and 1 ependymoma. The tumor volume ranged from 0.7 to 33.4 cc (mean 8.4). Stereotactic treatment planning was used to encompass the contrast-enhancing rim of the tumor visualized by computerized tomography with an initial dose rate of 0.05 Gy/hour with ¹²⁵I. The total activity ranged from 0.8 to 20.5 mCi. With a median follow-up period of 35 months (range, 4–105 months), the 2- and 5-year survival rates were 93.7% and 87.5%, respectively. Three patients underwent reoperation after implants, two of three had recurrent disease, and one had radiation necrosis. Permanent ¹²⁵I implants appear to be safe and effective as a part of the multimodality management of low-grade gliomas.     

Analysis of treatment outcome after stereotactic radiosurgery for cavernous sinus meningiomas

OBJECT: The long-term outcome of stereotactic radiosurgery for cavernous sinus (CS) meningiomas is not fully understood. The authors retrospectively reviewed their experience with 40 CS meningiomas treated with gamma knife radiosurgery. METHODS: Follow-up periods for the 40 patients ranged from 12 to 123 months (median 42 months), and the overall tumor control rates were 86.4% at 3 years and 82.3% at 10 years. Factors associated with tumor recurrence in univariate analysis were histological malignancy (p < 0.0001), partial treatment (p < 0.0001), suprasellar tumor extension (p = 0.0201), or extension in more than three directions outside the CS (p = 0.0345). When the tumor was completely covered with a dose to the margin that was higher than 14 Gy (Group A, 22 patients), no patient showed recurrence within the median follow-up period of 37 months. On the other hand, when a part of the tumor was treated with 10 to 12 Gy (Group B, 15 patients) or did not receive radiation therapy (Group C, three patients), the recurrence rates were 20% and 100%, respectively. Neurological deterioration was seen in nine patients, but all symptoms were transient or very mild. CONCLUSIONS: The data indicate that stereotactic radiosurgery can control tumor growth if the whole mass can be irradiated by dosages of more than 14 Gy. When optimal radiosurgical planning is not feasible because of a tumor's large size, irregular shape, or proximity to visual pathways, use of limited surgical resection before radiosurgery is the best option and should provide sufficient long-term tumor control with minimal complications.     

Primary retroperitoneal tumors. Treatment modality and prognostic factors

BACKGROUND: Primary Retroperitoneal Tumors (PRT) form a heterogeneous group of malignant mesenchymal and neuroectodermal neoplasms making up only 1% of all solid neoplasms. METHODS: From 1965 to 1997, 27 patients (16 females and 9 males, age range 19-79 years) underwent operations at the General and Cardiovascular Institute of University of Milan for primary retroperitoneal tumors (22 malignant and 5 benign, sarcomas represented 68% of all malignant tumors). A retrospective analysis of these patients was performed to determine the prognostic parameters associated with a favourable prognosis. All patients were admitted with severe abdominal pain or a palpable mass, other symptoms included fewer and weight loss. The median duration of symptoms before presentation was 16 months (range 15 days-5 years). Before surgical treatment abdominal and pulmonary CT scanning and MRN were undertaken on all patients with PRT to define the size of the tumor and the involvement of other retroperitoneal structures. RESULTS: Complete resection was possible in 54% of malignant tumors (n = 12), incomplete resection was performed in 14% (n = 3) and in 31% (n = 7) only biopsy was possible. Recurrent tumor developed in 25% of patients with total resection (n = 3), (median time to recurrence 5 years). Independent treatment variables (size, signs and symptoms, histopathologic findings and grade) and treatment-dependent variables (type of surgical treatment and adjuvant chemotherapy) were analyzed. Patients with complete resection had a 12 month survival of 100% (n = 12) compared to 50% (n = 1) for those undergoing partial resection and 14.2% (n = 1) for those with simple biopsy. A 24-month survival of the patients undergoing complete resection was 25% (n = 3). Median survival for type of surgical treatment was 28 months for complete resection compared to 14 months for partial resection and only 8 months for biopsy. Twelve-months survival for tumor grade was 100% (n = 7) for low grade tumor (G1), compared to 66.6% (n = 4) for median differentiated tumors (G2), and 37.5% (n = 3) for high grade tumors (G3). Twenty-four-months survival was 28.5% (n = 2) for low grade tumors compared to 16.6% (n = 1) of median differentiated tumors. High grade tumors were associated with a 35-month median survival time compared to 17 months for median differentiated tumors and 10 months for low grade tumors. Other variables (histopathologic findings, size, symptoms) had not significant impact on survival. Operative mortality rate was 3.7% (n = 1). The overall 2 years survival rate in patients with totally resected tumors was 25% (n = 3), (2G1, 1G2), while the 5 year survival rate was 16.6% (n = 2), (2G1). CONCLUSIONS: Complete surgical excision and low grade of the tumor are the most important parameters of survival. Recurrent disease is a vexing problem; a careful and prolonged follow-up based on the use of CT and MRN is recommended.     

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.     

Radiosurgery as primary management for meningiomas extending into the internal auditory canal

Stereotactic radiosurgery is increasingly utilized as primary management for patients with skull base meningiomas. This study reviews the results of stereotactic radiosurgery for patients with meningiomas extending into the internal auditory canal (IAC) to determine the risk of facial weakness or hearing loss. From 1990 to 2002, 16 patients had radiosurgery for meningiomas extending into the IAC. The median patient age was 63 years. Ten patients had symptoms of vestibulocochlear nerve dysfunction before radiosurgery. The median tumor volume was 5.1 cm3; the median tumor extension into the IAC was 7 mm (range, 3-12). The median tumor margin dose was 15 Gy. The median follow-up was 36 months. Ten meningiomas (63%) decreased in size, and 6 tumors were unchanged. No patient developed facial weakness. One patient (6%) had worsened facial sensation. Three of 14 patients (21%) with either normal hearing clinically (n = 5) or documented Gardner-Robertson class 1-2 before radiosurgery (n = 9) had decreased hearing after radiosurgery. The 1-, 2- and 5-year actuarial incidences of hearing preservation were 93, 84 and 42%, respectively. Three patients (19%) had improved hearing after radiosurgery. One patient with class 2 hearing improved to class 1; 2 patients with no speech discrimination before radiosurgery (class 5) improved to a class 3 status following the procedure. The risk of facial weakness or hearing loss is low after radiosurgery for patients with meningiomas extending into the IAC. Radiosurgery is an excellent alternative to surgical excision for meningiomas in this location, especially if a subtotal resection is likely or a hearing-sacrificing operation such as a translabyrinthine approach is contemplated.     

Radiosurgery and stereotactic radiation therapy of skull base meningiomas: proposal of a grading system

OBJECTIVE: The development of a grading system to guide treatment selection, and predict treatment difficulty and outcome of skull base meningiomas infiltrating the cavernous sinus which are managed by stereotactic radiosurgery (SRS) and stereotactic radiotherapy (SRT), based on an 8-year experience with stereotactic radiation of skull base meningiomas. METHODS: T1 gadoliniun-enhanced magnetic resonance imaging (MRI) of 40 patients with skull base meningiomas, with or without prior surgery, who underwent radiosurgery or stereotactic radiation therapy from 1991 to 1998 at the UCLA Medical Center were reviewed, and the result of treatment was related to the tumor grade. Grade was based on tumor infiltration of the cavernous sinus and extension into adjacent structures. Treatment was performed with a linac-based system. The dose prescribed to the periphery of the tumor for SRS patients (n = 34) ranged from 12 to 22 Gy, and the maximum dose delivered to the tumor ranged from 24 to 46 Gy. SRT (n = 6). Treatment was planned using a single isocenter, usually prescribed to the 90% isodose volume, bringing the fractionation scheme to the maximal tolerance of the optic apparatus. The periphery dose ranged from 24 to 46 Gy with a maximum dose of 45 to 51 Gy. Clinical and MRI follow-up was performed every six months for the first 3 years and every year thereafter. RESULTS: Grade I meningiomas were restricted to the cavernous sinus (n = 12). Grade II cavernous sinus meningiomas extended to the clivus and/or the petrous bone, without compression of the brainstem (n = 9). Grade III meningiomas had superior and/or anterior extension with compression of the optic nerve or tract (n = 9). Grade IV tumors compressed the brain stem (n = 8), and Grade V were bilateral lesions (n = 2). Tumor control rates were 90% for Grade I, 86% for Grade II, 86% for Grade III, 42% for Grade IV and no control for tumors Grade V. Complications were not related to tumor grade. CONCLUSION: This grading system correlated with outcome and difficulty in planning radiosurgery. Failure of treatment was more likely to occur in patients with higher Grade tumors.     

Low-grade glioma on stereotactic biopsy: how often is the diagnosis accurate?

The objective of the present study was an evaluation of the incidence and risk factors for erroneous histopathological diagnosis of low-grade glioma after stereotactic biopsy. Twenty-eight tumors diagnosed as low-grade glioma after stereotactic biopsy and surgically resected thereafter were analyzed. There were 13 astrocytomas, 7 oligodendrogliomas, and 8 mixed gliomas. All neoplasms had a lobar location. Seven tumors had contrast enhancement on MRI. The number of tissue samples obtained during stereotactic biopsy was one in 19 cases, two in 4, and three or more in 5. Complete diagnostic agreement in tumor typing and grading after stereotactic biopsy and surgical resection was attained in 10 cases (36%). Agreement in tumor typing was marked in 16 cases (57%). Erroneous typing was more frequent in tumors with an MIB-1 index of less than 3% (P = 0.0629) and mixed gliomas (P = 0.0801). Overgrading of WHO grade I tumors was marked in 3 cases (11%) and undergrading of WHO grade III gliomas in 8 cases (28%). Tumor undergrading was more frequent in cases with an MIB-1 index of more than 3% (P = 0.0045). The MIB-1 index detected after stereotactic biopsy was nearly always lower compared with those established after surgical resection (P < 0.0001). In conclusion, the histopathological diagnosis of low-grade glioma established after stereotactic biopsy is associated with a substantial risk of inaccuracy. Tumors with low proliferative activity and mixed gliomas are especially susceptible for erroneous tumor typing. Undergrading of high-grade gliomas may be suspected if the MIB-1 index in the tumor specimen constitutes more, than 3%.     

Radiosurgery in patients with renal cell carcinoma metastasis to the brain: long-term outcomes and prognostic factors influencing survival and local tumor control

OBJECT: Renal cell carcinoma is a leading cause of death from cancer and its incidence is increasing. In many patients with renal cell cancer, metastasis to the brain develops at some time during the course of the disease. Corticosteroid therapy, radiotherapy, and resection have been the mainstays of treatment. Nonetheless, the median survival in patients with renal cell carcinoma metastasis is approximately 3 to 6 months. In this study the authors examined the efficacy of gamma knife surgery in treating renal cell carcinoma metastases to the brain and evaluated factors affecting long-term survival. METHODS: The authors conducted a retrospective review of 69 patients undergoing stereotactic radiosurgery for a total of 146 renal cell cancer metastases. Clinical and radiographic data encompassing a 14-year treatment interval were collected. Multivariate analyses were used to determine significant prognostic factors influencing survival. The overall median length of survival was 15 months (range 1-65 months) from the diagnosis of brain metastasis. After radiosurgery, the median survival was 13 months in patients without and 5 months in those with active extracranial disease. In a multivariate analysis, factors significantly affecting the rate of survival included the following: 1) younger patient age (p = 0.0076); 2) preoperative Karnofsky Performance Scale score (p = 0.0012); 3) time from initial cancer diagnosis to brain metastasis diagnosis (p = 0.0017); 4) treatment dose to the tumor margin (p = 0.0252); 5) maximal treatment dose (p = 0.0127); and 6) treatment isodose (p = 0.0354). Prior tumor resection, chemotherapy, immunotherapy, or whole-brain radiation therapy did not correlate with extended survival. Postradiosurgical imaging of the brain demonstrated that 63% of the metastases had decreased, 33% remained stable, and 4% eventually increased in size. Two patients (2.9%) later underwent a craniotomy and resection for a tumor refractory to radiosurgery or a new symptomatic metastasis. Eighty-three percent of patients died of progression of extracranial disease. CONCLUSIONS: Stereotactic radiosurgery for treatment of renal cell carcinoma metastases to the brain provides effective local tumor control in approximately 96% of patients and a median length of survival of 15 months. Early detection of brain metastases, aggressive treatment of systemic disease, and a therapeutic strategy including radiosurgery can offer patients an extended survival.     

Proton beam radiosurgery for vestibular schwannoma: tumor control and cranial nerve toxicity

OBJECTIVE: We sought to determine the tumor control rate and cranial nerve function outcomes in patients with vestibular schwannomas who were treated with proton beam stereotactic radiosurgery. METHODS: Between November 1992 and August 2000, 88 patients with vestibular schwannomas were treated at the Harvard Cyclotron Laboratory with proton beam stereotactic radiosurgery in which two to four convergent fixed beams of 160-MeV protons were applied. The median transverse diameter was 16 mm (range, 2.5-35 mm), and the median tumor volume was 1.4 cm(3) (range, 0.1-15.9 cm(3)). Surgical resection had been performed previously in 15 patients (17%). Facial nerve function (House-Brackmann Grade 1) and trigeminal nerve function were normal in 79 patients (89.8%). Eight patients (9%) had good or excellent hearing (Gardner-Robertson [GR] Grade 1), and 13 patients (15%) had serviceable hearing (GR Grade 2). A median dose of 12 cobalt Gray equivalents (range, 10-18 cobalt Gray equivalents) was prescribed to the 70 to 108% isodose lines (median, 70%). The median follow-up period was 38.7 months (range, 12-102.6 mo). RESULTS: The actuarial 2- and 5-year tumor control rates were 95.3% (95% confidence interval [CI], 90.9-99.9%) and 93.6% (95% CI, 88.3-99.3%). Salvage radiosurgery was performed in one patient 32.5 months after treatment, and a craniotomy was required 19.1 months after treatment in another patient with hemorrhage in the vicinity of a stable tumor. Three patients (3.4%) underwent shunting for hydrocephalus, and a subsequent partial resection was performed in one of these patients. The actuarial 5-year cumulative radiological reduction rate was 94.7% (95% CI, 81.2-98.3%). Of the 21 patients (24%) with functional hearing (GR Grade 1 or 2), 7 (33.3%) retained serviceable hearing ability (GR Grade 2). Actuarial 5-year normal facial and trigeminal nerve function preservation rates were 91.1% (95% CI, 85-97.6%) and 89.4% (95% CI, 82-96.7%). Univariate analysis revealed that prescribed dose (P = 0.005), maximum dose (P = 0.006), and the inhomogeneity coefficient (P = 0.03) were associated with a significant risk of long-term facial neuropathy. No other cranial nerve deficits or cancer relapses were observed. CONCLUSION: Proton beam stereotactic radiosurgery has been shown to be an effective means of tumor control. A high radiological response rate was observed. Excellent facial and trigeminal nerve function preservation rates were achieved. A reduced prescribed dose is associated with a significant decrease in facial neuropathy.     

Clinical Outcome of Supratentorial Astrocytoma WHO Grade II

Summary  Objective. There are divergent opinions about the prognostic value of the extent of surgery and of different histological subtypes in supratentorial astrocytomas WHO grade II.  Methods. We reviewed 75 consecutive patients (36 females, 39 males) with supratentorial astrocytomas WHO grade II (59 primary and 16 recurrent tumours) operated on between 1991 and 1995.  Results. Gross total resection could be achieved in 40 astrocytomas, subtotal resection (including biopsy) was performed in 35 cases. Histological assessment confirmed 60 fibrillary, 6 gemistocytic, 9 oligo-astrocytic and no protoplasmic astrocytomas. There were no postoperative deaths. Early outcome 6 to 12 weeks after surgery according to the Glasgow Outcome Scale was good in 46 patients, 24 patients had moderate, and 5 had severe neurological deficits. Survival rates 1, 2, 3, and 4 years following surgery were 100%, 96%, 96%, 96% for patients who underwent gross total tumour resection and 86%, 77%, 77%, 64% for patients with subtotal tumour resection. The cumulative recurrence or progression rates after 4 years were 26% after gross total resection and 80% after subtotal resection, and this result is statistically significant. Recurrences after gross total resection or progressions after subtotal resection occurred more often in gemistocytic astrocytomas (40% and 100%, respectively) than in other subtypes. Dedifferentiation to a more malignant tumour seems to be more prominent in the gemistocytic subtype.  Conclusion. Gross total resection should be the leading therapeutic option for patients with astrocytomas WHO grade II. For the gemistocytic subtype further studies will have to prove whether additional radiotherapy is of any benefit.     

Stereotactic radiation treatment for recurrent nonbenign meningiomas

OBJECT: The authors analyzed the results of stereotactic radiosurgery (SRS) and stereotactic radiotherapy (SRT) for the treatment of recurrent meningiomas that were described at initial resection as showing aggressive, atypical, or malignant features (nonbenign). METHODS: Twenty-five patients who underwent SRS and/or SRT for nonbenign meningiomas between December 1992 and August 2004 were included. Thirteen of these patients underwent treatment for multiple primary or recurrent lesions. In all, 52 tumors were treated. All histological sections were reviewed and reclassified according to World Health Organization (WHO) 2000 guidelines as benign (Grade I), atypical (Grade II), or anaplastic (Grade III) meningiomas. The median follow-up period was 42 months. Seventeen (68%) of the cases were reclassified as follows: WHO Grade I (five cases), Grade II (11 cases), and Grade III (one case). Malignant progression occurred in eight cases (32%) during the follow-up period; these cases were considered as a separate group. The 3-year progression-free survival (PFS) rates for the Grades I, II, and III, and malignant progression groups were 100, 83, 0, and 11%, respectively (p < 0.001). In the Grade II group, the 3-year PFS rates for patients treated with SRS and SRT were 100 and 33%, respectively (p = 0.1). After initial treatment, 22 new tumors required treatment using SRS or SRT; 17 (77%) of them occurred inside the original resection cavity. Symptomatic edema developed in one patient (4%). CONCLUSIONS: Stereotactic radiation treatment provided effective local control of "aggressive" Grade I and Grade II meningiomas, whereas Grade III lesions were associated with poor outcome. The outcome of cases in the malignant progression group was intermediate between that of the Grade II and Grade III groups, with the lesions showing a tendency toward malignancy.     

Independent association of extent of resection with survival in patients with malignant brain astrocytoma

OBJECT: With recent advances in the adjuvant treatment of malignant brain astrocytomas, it is increasingly debated whether extent of resection affects survival. In this study, the authors investigate this issue after primary and revision resection of these lesions. METHODS: The authors retrospectively reviewed the cases of 1215 patients who underwent surgery for malignant brain astrocytomas (World Health Organization [WHO] Grade III or IV) at a single institution from 1996 to 2006. Patients with deep-seated or unresectable lesions were excluded. Based on MR imaging results obtained < 48 hours after surgery, gross-total resection (GTR) was defined as no residual enhancement, near-total resection (NTR) as having thin rim enhancement of the resection cavity only, and subtotal resection (STR) as having residual nodular enhancement. The independent association of extent of resection and subsequent survival was assessed via a multivariate proportional hazards regression analysis. RESULTS: Magnetic resonance imaging studies were available for review in 949 cases. The mean age and mean Karnofsky Performance Scale (KPS) score at time of surgery were 51 +/- 16 years and 80 +/- 10, respectively. Surgery consisted of primary resection in 549 patients (58%) and revision resection for tumor recurrence in 400 patients (42%). The lesion was WHO Grade IV in 700 patients (74%) and Grade III in 249 (26%); there were 167 astrocytomas and 82 mixed oligoastrocytoma. Among patients who underwent resection, GTR, NTR, and STR were achieved in 330 (35%), 388 (41%), and 231 cases (24%), respectively. Adjusting for factors associated with survival (for example, age, KPS score, Gliadel and/or temozolomide use, and subsequent resection), GTR versus NTR (p < 0.05) and NTR versus STR (p < 0.05) were independently associated with improved survival after both primary and revision resection of glioblastoma multiforme (GBM). For primary GBM resection, the median survival after GTR, NTR, and STR was 13, 11, and 8 months, respectively. After revision resection, the median survival after GTR, NTR, and STR was 11, 9, and 5 months, respectively. Adjusting for factors associated with survival for WHO Grade III astrocytoma (age, KPS score, and revision resection), GTR versus STR (p < 0.05) was associated with improved survival. Gross-total resection versus NTR was not associated with an independent survival benefit in patients with WHO Grade III astrocytomas. The median survival after primary resection of WHO Grade III (mixed oligoastrocytomas excluded) for GTR, NTR, and STR was 58, 46, and 34 months, respectively. CONCLUSIONS: In the authors' experience with both primary and secondary resection of malignant brain astrocytomas, increasing extent of resection was associated with improved survival independent of age, degree of disability, WHO grade, or subsequent treatment modalities used. The maximum extent of resection should be safely attempted while minimizing the risk of surgically induced neurological injury.