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

Object. Glomus jugulare tumors are rare tumors that commonly involve the middle ear, temporal bone, and lower cranial nerves. Resection, embolization, and radiation therapy have been the mainstays of treatment. Despite these therapies, tumor control can be difficult to achieve particularly without undo risk of patient morbidity or mortality. The authors examine the safety and efficacy of gamma knife surgery (GKS) for glomus jugulare tumors.

Methods. A retrospective review was undertaken of the results obtained in eight patients who underwent GKS for recurrent, residual, or unresectable glomus jugulare tumors. The median radiosurgical dose to the tumor margin was 15 Gy (range 12–18 Gy). The median clinical follow-up period was 28 months, and the median period for radiological follow up was 32 months.

All eight patients demonstrated neurological stability or improvement. No cranial nerve palsies arose or deteriorated after GKS. In the seven patients in whom radiographic follow up was obtained, the tumor size decreased in four and remained stable in three.

Conclusions. Gamma knife surgery would seem to afford effective local tumor control and preserves neurological function in patients with glomus jugulare tumors. If long-term results with GKS are equally efficacious, the role of stereotactic radiosurgery will expand.

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

Object. Lung carcinoma is the leading cause of death from cancer. More than 50% of those with small cell lung cancer develop a brain metastasis. Corticosteroid agents, radiotherapy, and resection have been the mainstays of treatment. Nonetheless, median survival for patients with small cell lung carcinoma metastasis is approximately 4 to 5 months after cranial irradiation. In this study the authors examine the efficacy of gamma knife surgery for treating recurrent small cell lung carcinoma metastases to the brain following tumor growth in patients who have previously undergone radiation therapy, and they evaluate factors affecting survival.

Methods. A retrospective review of 27 patients (47 recurrent small cell lung cancer brain metastases) undergoing radiosurgery was performed. Clinical and radiographic data obtained during a 14-year treatment period were collected. Multivariate analysis was utilized to determine significant prognostic factors influencing survival.

The overall median survival was 18 months after the diagnosis of brain metastases. In multivariate analysis, factors significantly affecting survival included: 1) tumor volume (p = 0.0042); 2) preoperative Karnofsky Performance Scale score (p = 0.0035); and 3) time between initial lung cancer diagnosis and development of brain metastasis (p = 0.0127). Postradiosurgical imaging of the brain metastases revealed that 62% decreased, 19% remained stable, and 19% eventually increased in size. One patient later underwent a craniotomy and tumor resection for a tumor refractory to radiosurgery and radiation therapy. In three patients new brain metastases were demonstrating on follow-up imaging.

Conclusions. Stereotactic radiosurgery for recurrent small cell lung carcinoma metastases provided effective local tumor control in the majority of patients. Early detection of brain metastases, aggressive treatment of systemic disease, and a therapeutic strategy including radiosurgery can extend survival.

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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, 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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Gregory Neil Bowden, Jong Oh Kim, Andrew Faramand, Kevin Fallon, John Flickinger and L. Dade Lunsford

OBJECTIVE

The use of Gamma Knife stereotactic radiosurgery (GKSRS) for the treatment of extensive intracranial metastases has been expanding due to its superior dosimetry and efficacy. However, there remains a dearth of data regarding the dose parameters in actual clinical scenarios. The authors endeavored to calculate the radiation dose to the brain when treating ≥ 15 brain metastases with GKSRS.

METHODS

This retrospective analysis reviewed dosage characteristics for patients requiring single-session GKSRS for the treatment of ≥ 15 brain metastases. Forty-two patients met the inclusion criteria between 2008 and 2017. The median number of tumors at the initial GKSRS procedure was 20 (range 15–39 tumors), accounting for 865 tumors in this study. The median aggregate tumor volume was 3.1 cm3 (range 0.13–13.26 cm3), and the median marginal dose was 16 Gy (range 14–19 Gy).

RESULTS

The median of the mean brain dose was 2.58 Gy (range 0.95–3.67 Gy), and 79% of patients had a dose < 3 Gy. The 12-Gy dose volume was a median of 12.45 cm3, which was equivalent to 0.9% of the brain volume. The median percentages of brain receiving 5 Gy and 3 Gy were 6.7% and 20.4%, respectively. There was no correlation between the number of metastases and the mean dose to the brain (p = 0.8). A greater tumor volume was significantly associated with an increased mean brain dose (p < 0.001). The median of the mean dose to the bilateral hippocampi was 2.3 Gy. Sixteen patients had supplementary GKSRS, resulting in an additional mean dose of 1.4 Gy (range 0.2–3.8 Gy) to the brain.

CONCLUSIONS

GKSRS is a viable means of managing extensive brain metastases. This procedure provides a relatively low dose of radiation to the brain, especially when compared with traditional whole-brain radiation protocols.

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Greg Bowden, Hideyuki Kano, Ellen Caparosa, Seong-Hyun Park, Ajay Niranjan, John Flickinger and L. Dade Lunsford

OBJECT

Non–small cell lung cancer (NSCLC) is the most frequent cancer that metastasizes to brain. Stereotactic radiosurgery (SRS) has become the management of choice for most patients with such metastatic tumors. Therefore, the authors endeavored to elucidate the survival and SRS outcomes for patients with NSCLC metastasis at their center.

METHODS

In this single-institution retrospective analysis, the authors reviewed their experience with NSCLC metastasis during a 10-year period from 2001 to 2010. Seven hundred twenty patients underwent Gamma Knife radiosurgery. A total of 1004 SRS procedures were performed, and 3143 tumors were treated. The NSCLC subtype was adenocarcinoma in 386 patients, squamous cell carcinoma in 111 patients, and large cell carcinoma in 34 patients. The median aggregate tumor volume was 4.5 cm3 (range 0.1–88 cm3).

RESULTS

The median survival time after diagnosis of brain metastasis from NSCLC was 12.6 months, and the median survival after SRS was 8.5 months. The 1-, 2-, and 5-year survival rates after SRS were 39%, 21%, and 10%, respectively. Postradiosurgery survival was decreased in patients treated with prior whole-brain radiation therapy compared with SRS alone (p = 0.003). Aggregate tumor volume was inversely related to survival after SRS (p < 0.001), and the histological subgroups demonstrated significant survival differences (p = 0.023). The overall local tumor control rate in the entire group was 92.8%. One hundred seventy-four patients (24%) underwent repeat SRS for new or resistant metastatic deposits.

CONCLUSIONS

Stereotactic radiosurgery is an effective means of providing local control for NSCLC metastases. Neurological function and survival benefit from serial patient monitoring and repeat SRS for new tumors.

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Greg Bowden, Hideyuki Kano, Huai-che Yang, Ajay Niranjan, John Flickinger and L. Dade Lunsford

Object

The outcomes of stereotactic radiosurgery for arteriovenous malformations (AVMs) within or adjacent to the ventricular system are largely unknown. This study assessed the long-term outcomes and hemorrhage risks for patients with AVMs within this region who underwent Gamma Knife surgery (GKS) at the University of Pittsburgh.

Methods

The authors retrospectively identified 188 patients with ventricular-region AVMs who underwent a single-stage GKS procedure during a 22-year interval. The median patient age was 32 years (range 3–80 years), the median target volume was 4.6 cm3 (range 0.1–22 cm3), and the median marginal dose was 20 Gy (range 13–27 Gy).

Results

Arteriovenous malformation obliteration was confirmed by MRI or angiography in 89 patients during a median follow-up of 65 months (range 2–265 months). The actuarial rates of total obliteration were 32% at 3 years, 55% at 4 years, 60% at 5 years, and 64% at 10 years. Higher rates of AVM obliteration were obtained in the 26 patients with intraventricular AVMs. Twenty-five patients (13%) sustained a hemorrhage during the initial latency interval after GKS, indicating an annual hemorrhage rate of 3.4% prior to AVM obliteration. No patient experienced a hemorrhage after AVM obliteration was confirmed by imaging. Permanent neurological deficits due to adverse radiation effects developed in 7 patients (4%).

Conclusions

Although patients in this study demonstrated an elevated hemorrhage risk that remained until complete obliteration, GKS still proved to be a generally safe and effective treatment for patients with these high-risk intraventricular and periventriclar AVMs.