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Constantinos G. Hadjipanayis, Douglas Kondziolka, Paul Gardner, Ajay Niranjan, Shekhar Dagam, John C. Flickinger, and L. Dade Lunsford

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.

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John Y. K. Lee, Ajay Niranjan, James McInerney, Douglas Kondziolka, John C. Flickinger, and L. Dade Lunsford

Object. To evaluate long-term outcomes of patients who have undergone stereotactic radiosurgery for cavernous sinus meningiomas, the authors retrospectively reviewed their 14-year experience with these cases.

Methods. One hundred seventy-six patients harbored meningiomas centered within the cavernous sinus. Seventeen patients were lost to follow-up review, leaving 159 analyzable patients, in whom 164 procedures were performed. Seventy-six patients (48%) underwent adjuvant radiosurgery after one or more attempts at surgical resection. Eighty-three patients (52%) underwent primary radiosurgery. Two patients (1%) had previously received fractionated external-beam radiation therapy. Four patients (2%) harbored histologically verified atypical or malignant meningiomas. Conformal multiple isocenter gamma knife surgery was performed. The median dose applied to the tumor margin was 13 Gy.

Neurological status improved in 46 patients (29%), remained stable in 99 (62%), and eventually worsened in 14 (9%). Adverse effects of radiation occurred after 11 procedures (6.7%). Tumor volumes decreased in 54 patients (34%), remained stable in 96 (60%), and increased in nine (6%). The actuarial tumor control rate for patients with typical meningiomas was 93.1 ± 3.3% at both 5 and 10 years. For the 83 patients who underwent radiosurgery as their sole treatment, the actuarial tumor control rate at 5 years was 96.9 ± 3%.

Conclusions. Stereotactic radiosurgery provided safe and effective management of cavernous sinus meningiomas. We believe it is the preferred management strategy for tumors of suitable volume (average tumor diameter ≤ 3 cm or volume ≤ 15 cm3).

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Douglas Kondziolka, Lawrence Wechsler, Elizabeth Tyler-Kabara, and Cristian Achim

Cellular therapy has been evaluated in small animals, subhuman primates, and now humans for the potential repair of brain injury due to stroke. Experimental striate stroke models have proven useful for the purpose of evaluating different treatment paradigms. Early clinical trials involving neuronal transplantation in patients suffering motor-related stroke in the basal ganglia region have begun.

This research will be described in this report.

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Jason P. Sheehan, Ming-Hsi Sun, Douglas Kondziolka, John Flickinger, and L. Dade Lunsford

Object. Lung carcinoma is the leading cause of death from cancer. More than 25% of those patients with lung cancer develop a brain metastasis at some time during the course of their disease. Corticosteroid therapy, radiotherapy, and resection have been the mainstays of treatment. Nonetheless, the median survival for patients with lung carcinoma metastasis is approximately 3 to 6 months. The authors examine the efficacy of gamma knife radiosurgery (GKS) for treating non—small cell lung carcinoma (NSCLC) metastases to the brain and evaluate factors affecting long-term patient survival.

Methods. A retrospective review of 273 patients who had undergone GKS to treat a total of 627 NSCLC metastases was performed. Clinical and neuroimaging data encompassing a 14-year treatment interval were collected. Univariate and multivariate analyses were performed to determine significant prognostic factors influencing patient survival.

The overall median patient survival time was 15 months (range 1–116 months) from the diagnosis of brain metastases. The median survival was 10 months from GKS treatment in those patients with adenocarcinoma and 7 months for those with other histological tumor types. In patients with no active extracranial disease at the time of GKS, the median survival time was 16 months. In multivariate analyses, factors significantly affecting survival included: 1) female sex (p = 0.014); 2) preoperative Karnofsky Performance Scale score (p < 0.0001); 3) adenocarcinoma histological subtype (p = 0.0028); 4) active systemic disease (p = 0.0001); and 5) time from lung cancer diagnosis to the development of brain metastasis (p = 0.0074). Prior tumor resection or whole-brain radiation therapy did not correlate with extended patient survival time.

Postradiosurgical imaging of brain metastases revealed that 60% decreased, 24% remained stable, and 16% eventually increased in size. Factors affecting local tumor control included tumor volume (p = 0.042) and treatment isodose (p = 0.015). Fourteen patients (5.1%) later underwent craniotomy and tumor resection for tumor refractory to GKS or a new symptomatic metastasis.

Conclusions. Gamma knife surgery for NSCLC metastases affords effective local tumor control in approximately 84% of patients. Early detection of brain metastases, aggressive treatment of systemic disease, and a therapeutic strategy including GKS can afford patients an extended survival time.

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Jason P. Sheehan, Douglas Kondziolka, John Flickinger, and L. Dade Lunsford

Object. Nonfunctioning pituitary adenomas comprise approximately 30% of all pituitary tumors. The purpose of this retrospective study is to evaluate the efficacy and role of gamma knife radiosurgery (GKS) in the management of residual or recurrent nonfunctioning pituitary adenomas.

Methods. A review was conducted of the data obtained in 42 patients who underwent adjuvant GKS at the University of Pittsburgh between 1987 and 2001. Prior treatments included transsphenoidal resection, craniotomy and resection, or conventional radiotherapy. Endocrinological, ophthalmological, and radiological responses were evaluated. The duration of follow-up review varied from 6 to 102 months (mean 31.2 months). Fifteen patients were observed for more than 40 months. The mean radiation dose to the tumor margin was 16 Gy. Conformal radiosurgery planning was used to restrict the dose to the optic nerve and chiasm.

Tumor control after GKS was achieved in 100% of patients with microadenomas and 97% of patients with macroadenomas. Gamma knife radiosurgery was equally effective in controlling adenomas with cavernous sinus invasion and suprasellar extension. No patient developed a new endocrinological deficiency following GKS. One patient's tumor enlarged with an associated decline in visual function. Another patient experienced a deterioration of visual fields despite a decrease in tumor size.

Conclusions. Gamma knife radiosurgery can achieve tumor control in virtually all residual or recurrent nonfunctioning pituitary adenomas. Dose sparing facilitates tumor management even when the adenoma is close to the optic apparatus or invades the cavernous sinus.

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Constantinos G. Hadjipanayis, Ghassan Bejjani, Clayton Wiley, Toshinori Hasegawa, Melissa Maddock, and Douglas Kondziolka

✓ Sinus histiocytosis or Rosai—Dorfman disease (RDD) is a rare idiopathic histioproliferative disorder typically characterized by painless cervical lymphadenopathy, fever, and weight loss. Extranodal, intracranial disease is uncommon. In this report the authors describe the first case of intracranial RDD treated with stereotactic radiosurgery after resection.

This 52-year-old man with known RDD presented with a 7-day course of fever, headache, diplopia, left facial paresthesias, and difficulty swallowing. No cranial nerve deficits were evident on examination, but right submandibular and inguinal node enlargements were noted. On neuroimaging, the patient was found to have a homogeneously contrast-enhancing petroclival lesion with extension into the left cavernous sinus.

The patient underwent a combined left petrosal craniotomy and partial labyrinthectomy with duraplasty for biopsy sampling and partial microsurgical resection of the lesion. Microscopic examination of the biopsy specimen revealed the presence of a mixed cellular population with predominant mature histiocytes consistent with RDD. The residual tumor was treated with stereotactic radiosurgery 2 months after resection. On follow-up imaging the lesion had regressed significantly, with only slight dural enhancement remaining.

Microsurgical resection for histological diagnosis, followed by stereotactic radiosurgery for residual tumor represents one treatment alternative in the management of intracranial RDD in which a complete resection carries the potential for excess morbidity.

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Jason P. Sheehan, Ming-Hsi Sun, Douglas Kondziolka, John Flickinger, and L. Dade Lunsford

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.

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

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

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Jason P. Sheehan, Douglas Kondziolka, John Flickinger, and L. Dade Lunsford

Object

Nonfunctioning pituitary adenomas comprise approximately 30% of all pituitary tumors. The purpose of this retrospective study was to evaluate the efficacy and role of gamma knife surgery (GKS) in the treatment of these lesions.

Methods

The authors conducted a review of cases in which GKS was performed at the University of Pittsburgh between 1987 and 2001. Forty-six patients with nonfunctioning pituitary adenomas and with at least 6 months of follow-up data were identified. In 41 of these patients some form of prior treatment such as transsphenoidal resection, craniotomy and resection, or conventional radiation therapy had been conducted. Five patients were deemed ineligible for microsurgery, and GKS served as the primary treatment modality. Endocrinological, ophthalmological, and radiological responses were evaluated. The mean radiation dose to the margin was 16 Gy.

In all patients with microadenomas and 91% of those with macroadenomas tumor control was demonstrated after radiosurgery. Gamma knife surgery had essentially equal efficacy in terms of achieving tumor control in cases of adenomas with cavernous sinus invasion and suprasellar extension. No new endocrinopathies were noted following radiosurgery. In two patients, however, tumor growth and decline in visual function occurred.

Conclusions

Gamma knife surgery is safe and effective in treating nonfunctioning pituitary adenomas. Radiosurgery may serve as a primary treatment modality in some or as a salvage treatment in others. Treatment must be tailored to meet the patient's symptoms, overall health, and tumor morphometry.

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Costas G. Hadjipanayis, Douglas Kondziolka, John C. Flickinger, and L. Dade Lunsford

Object

This study was conducted to examine the role of radiosurgery in the management of patients with recurrent or unresectable low-grade astrocytomas.

Methods

During a 13-year interval, 49 patients underwent stereotactic radiosurgery as part of multimodal treatment of their recurrent or unresectable low-grade astrocytomas. Thirty-seven of these patients (median age 14 years) harbored pilocytic astrocytomas and 12 patients harbored World Health Organization (WHO) Grade II fibrillary astrocytomas (median age 25 years). Tumors involved the brainstem in 22 cases, cerebellum in four, thalamus in six, temporal lobe in five, frontal lobe in four, and parietal lobe in three, as well as the hypothalamus, corpus callosum, insular cortex, optic tract, and third ventricle in one patient each. Each diagnosis was confirmed with the aid of stereotactic biopsy sampling in 17 patients, open biopsy sampling in five, partial resection in 13, and near-total resection in 14. Multimodal treatment included fractionated radiotherapy in 14 patients, stereotactic intracavitary irradiation in five, chemotherapy in two, cyst drainage in eight, ventriculoperitoneal shunt placement in five, and additional cytoreductive surgery in five. Tumor volumes ranged from 0.42 to 45.1 cm3. The median radiosurgical dose to the tumor margin was 15 Gy (range 9.6–22.5 Gy).

After radiosurgery, serial neuroimaging demonstrated complete tumor resolution in 11 patients, reduced tumor volume in 12, stable tumor volume in 10, and delayed tumor progression in 16. No procedure-related death was encountered. Forty-five of 49 patients are alive at a median follow-up period of 32 months after radiosurgery and 63 months after diagnosis. Sixteen patients participated in follow-up review for more than 60 months. Three patients died of local tumor progression.

Conclusions

Stereotactic radiosurgery is a potential alternative or adjunctive intervention in the management of selected patients with pilocytic or WHO Grade II fibrillary astrocytomas, usually performed for small-volume tumors in an attempt to avoid larger-field fractionated radiotherapy.