Trigeminal neuralgia pain relief after gamma knife stereotactic radiosurgery.

OBJECTIVES: To report outcomes of patients with medical and/or surgical refractory trigeminal neuralgia (TN) treated with gamma knife stereotactic radiosurgery (GK SRS). METHODS: One hundred and forty-nine patients with 152 cases of TN treated with GK SRS were analyzed. All patients, except one, received a dose of 40Gy to the 50% isodose volume. The Barrow Neurological Institute (BNI) pain intensity score was used to grade pain. Actuarial rates of pain relief were calculated. Multiple factors were analyzed for association with pain relief. RESULTS: The median follow up was 27 months (4-71 months). Overall 92% of cases achieved a BNI score I-III after GK SRS. Of those who had pain relief after GK SRS, 32% developed pain recurrence defined as a BNI score of IV or V. The actuarial rate of freedom from pain recurrence (BNI scores I-III) of all treated cases at 1, 2 and 3-years was 76%, 69% and 60%, respectively. On univariate analysis age ≥70 was predictive of better pain relief (p=0.046). Type of pain, prior surgery, multiple sclerosis, number of isocenters, treated nerve length, volume and thickness and distance from the root entry zone to the isocenter were not significant for maintaining a BNI score of I-III. Those who achieved a BNI score of I or II were more likely to maintain pain relief compared to those who only achieved a BNI score of III (93% vs 38% at three years, p<0.01). The rate of pain relief of twenty-seven patients who underwent repeat GK SRS was 70% and 62% at 1 and 2 years, respectively. Toxicity after first GK SRS was minimal with 25% of cases experiencing only new or worsening post-treatment numbness. CONCLUSION: GK SRS provides acceptable pain relief with limited morbidity in patients with medical and/or surgical refractory TN.

Tumor volume as a predictor of survival and local control in patients with brain metastases treated with Gamma Knife surgery.

OBJECT: The aim of this study was to examine tumor volume as a prognostic factor for patients with brain metastases treated with Gamma Knife surgery (GKS). METHODS: Two hundred fifty patients with 1-14 brain metastases who had initially undergone GKS alone at a single institution were retrospectively reviewed. Patients who received upfront whole brain radiation therapy were excluded. Survival times were estimated using the Kaplan-Meier method. Univariate and multivariate analyses using Cox proportional hazard regression models were used to determine if various prognostic factors could predict overall survival, distant brain failure, and local control. RESULTS: Median overall survival was 7.1 months and the 1-year local control rate was 91.5%. Median time to distant brain failure was 8.0 months. On univariate analysis an increasing total tumor volume was significantly associated with worse survival (p = 0.031) whereas the number of brain metastases, analyzed as a continuous variable, was not (p = 0.082). After adjusting for age, Karnofsky Performance Scale score, and extracranial disease on multivariate analysis, total tumor volume was found to be a better predictor of overall survival (p = 0.046) than number of brain metastases analyzed as a continuous variable (p = 0.098). A total tumor volume cutoff value of ≥ 2 cm(3) (p = 0.008) was a stronger predictor of overall survival than the number of brain metastases (p = 0.098). Larger tumor volume and extracranial disease, but not the number of brain metastases, were predictive of distant brain failure on multivariate analysis. Local tumor control at 1 year was 97% for lesions < 2 cm(3) compared with 75% for lesions ≥ 2 cm(3) (p < 0.001). CONCLUSIONS: After adjusting for other factors, a total brain metastasis volume was a strong and independent predictor for overall survival, distant brain failure, and local control, even when considering the number of metastases.

Differentiation between intra-axial metastatic tumor progression and radiation injury following fractionated radiation therapy or stereotactic radiosurgery using MR spectroscopy, perfusion MR imaging or volume progression modeling.

OBJECTIVE: To determine the accuracy of magnetic resonance spectroscopy (MRS), perfusion MR imaging (MRP), or volume modeling in distinguishing tumor progression from radiation injury following radiotherapy for brain metastasis. METHODS: Twenty-six patients with 33 intra-axial metastatic lesions who underwent MRS (n=41) with or without MRP (n=32) after cranial irradiation were retrospectively studied. The final diagnosis was based on histopathology (n=4) or magnetic resonance imaging (MRI) follow-up with clinical correlation (n=29). Cho/Cr (choline/creatinine), Cho/NAA (choline/N-acetylaspartate), Cho/nCho (choline/contralateral normal brain choline) ratios were retrospectively calculated for the multi-voxel MRS. Relative cerebral blood volume (rCBV), relative peak height (rPH) and percentage of signal-intensity recovery (PSR) were also retrospectively derived for the MRPs. Tumor volumes were determined using manual segmentation method and analyzed using different volume progression modeling. Different ratios or models were tested and plotted on the receiver operating characteristic curve (ROC), with their performances quantified as area under the ROC curve (AUC). MRI follow-up time was calculated from the date of initial radiotherapy until the last MRI or the last MRI before surgical diagnosis. RESULTS: Median MRI follow-up was 16 months (range: 2-33). Thirty percent of lesions (n=10) were determined to be radiation injury; 70% (n=23) were determined to be tumor progression. For the MRS, Cho/nCho had the best performance (AUC of 0.612), and Cho/nCho >1.2 had 33% sensitivity and 100% specificity in predicting tumor progression. For the MRP, rCBV had the best performance (AUC of 0.802), and rCBV >2 had 56% sensitivity and 100% specificity. The best volume model was percent increase (AUC of 0.891); 65% tumor volume increase had 100% sensitivity and 80% specificity. CONCLUSION: Cho/nCho of MRS, rCBV of MRP, and percent increase of MRI volume modeling provide the best discrimination of intra-axial metastatic tumor progression from radiation injury for their respective modalities. Cho/nCho and rCBV appear to have high specificities but low sensitivities. In contrast, percent volume increase of 65% can be a highly sensitive and moderately specific predictor for tumor progression after radiotherapy. Future incorporation of 65% volume increase as a pretest selection criterion may compensate for the low sensitivities of MRS and MRP.

Prospective staged volume radiosurgery for large arteriovenous malformations: indications and outcomes in otherwise untreatable patients.

OBJECTIVE: The obliteration response of an arteriovenous malformation (AVM) to radiosurgery is strongly dependent on dose and volume. For larger volumes, the dose must be reduced for safety, but this compromises obliteration. In 1992, we prospectively began to stage anatomic components in order to deliver higher single doses to symptomatic AVMs > 15 ml in volume. METHODS: During a 17-year interval at the University of Pittsburgh, 1040 patients underwent radiosurgery for a brain AVM. Out of 135 patients who had multiple procedures, 37 patients underwent prospectively staged volume radiosurgery for symptomatic otherwise unmanageable larger malformations. Twenty-eight patients who were managed before 2002 were included in this study to achieve sufficient follow-up in assessing the outcomes. The median age was 37 years (range, 13-57 yr). Thirteen patients had previous hemorrhages and 13 patients had attempted embolization. Separate anatomic volumes were irradiated at 3 to 8 months (median, 5 mo) intervals. The median initial AVM volume was 24.9 ml (range, 10.2-57.7 ml). Twenty-six patients had two stages and two had three-stage radiosurgery. Seven patients had repeat radiosurgery after a median interval of 63 months. The median target volume was 12.3 ml. (range, 4.2-20.8 ml.) at Stage I and 11.5 ml. (range, 2.8-22 ml.) at Stage II. The median margin dose was 16 Gy at both stages. Median follow-up after the last stage of radiosurgery was 50 months (range, 3-159 mo). RESULTS: Four patients (14%) sustained a hemorrhage after radiosurgery; two died and two patients recovered with mild permanent neurological deficits. Worsened neurological deficits developed in one patient. Seizure control was improved in three patients, was stable in eight patients and worsened in two. Magnetic resonance imaging showed T2 prolongation in four patients (14%). Out of 28 patients, 21 had follow-up more than 36 months. Out of 21 patients, seven underwent repeat radiosurgery and none of them had enough follow- up. Of 14 patients followed for more than 36 months, seven (50%) had total, four (29%) near total, and three (21%) had moderate AVM obliteration. CONCLUSIONS: Prospective staged volume radiosurgery provided imaging defined volumetric reduction or closure in a series of large AVMs unsuitable for any other therapy. After 5 years, this early experience suggests that AVM related symptoms can be stabilized and anticipated bleed rates can be reduced.

Prospective staged volume radiosurgery for large arteriovenous malformations: indications and outcomes in otherwise untreatable patients.

OBJECTIVE: The obliteration response of an arteriovenous malformation (AVM) to radiosurgery is strongly dependent on dose and volume. For larger volumes, the dose must be reduced for safety, but this compromises obliteration. In 1992, we prospectively began to stage anatomic components in order to deliver higher single doses to symptomatic AVMs >15 ml in volume. METHODS: During a 17-year interval at the University of Pittsburgh, 1040 patients underwent radiosurgery for a brain AVM. Out of 135 patients who had multiple procedures, 37 patients underwent prospectively staged volume radiosurgery for symptomatic otherwise unmanageable larger malformations. Twenty-eight patients who were managed before 2002 were included in this study to achieve sufficient follow-up in assessing the outcomes. The median age was 37 years (range, 13-57 yr). Thirteen patients had previous hemorrhages and 13 patients had attempted embolization. Separate anatomic volumes were irradiated at 3 to 8 months (median, 5 mo) intervals. The median initial AVM volume was 24.9 ml (range, 10.2-57.7 ml). Twenty-six patients had two stages and two had three-stage radiosurgery. Seven patients had repeat radiosurgery after a median interval of 63 months. The median target volume was 12.3 ml. (range, 4.2-20.8 ml.) at Stage I and 11.5 ml. (range, 2.8-22 ml.) at Stage II. The median margin dose was 16 Gy at both stages. Median follow-up after the last stage of radiosurgery was 50 months (range, 3-159 mo). RESULTS: Four patients (14%) sustained a hemorrhage after radiosurgery; two died and two patients recovered with mild permanent neurological deficits. Worsened neurological deficits developed in one patient. Seizure control was improved in three patients, was stable in eight patients and worsened in two. Magnetic resonance imaging showed T2 prolongation in four patients (14%). Out of 28 patients, 21 had follow-up more than 36 months. Out of 21 patients, seven underwent repeat radiosurgery and none of them had enough follow- up. Of 14 patients followed for more than 36 months, seven (50%) had total, four (29%) near total, and three (21%) had moderate AVM obliteration. CONCLUSIONS: Prospective staged volume radiosurgery provided imaging defined volumetric reduction or closure in a series of large AVMs unsuitable for any other therapy. After 5 years, this early experience suggests that AVM related symptoms can be stabilized and anticipated bleed rates can be reduced.

Long-term results after radiosurgery for benign intracranial tumors.

BACKGROUND: Stereotactic radiosurgery is the principal therapeutic alternative to resecting benign intracranial tumors. The goals of radiosurgery are the long-term prevention of tumor growth, the maintenance of patient function, and the prevention of new neurological deficits or adverse radiation effects. Evaluation of long-term outcomes more than 10 years after radiosurgery is needed. METHODS: We evaluated 285 consecutive patients who underwent radiosurgery for benign intracranial tumors between 1987 and 1992. Serial imaging studies were obtained, and clinical evaluations were performed. Our series included 157 patients with vestibular schwannomas, 85 patients with meningiomas, 28 patients with pituitary adenomas, 10 patients with other cranial nerve schwannomas, and 5 patients with craniopharyngiomas. Prior surgical resection had been performed in 44% of these patients, and prior radiotherapy had been administered in 5%. The median follow-up period was 10 years. RESULTS: Overall, 95% of the 285 patients in this series had imaging-defined local tumor control (63% had tumor regression, and 32% had no further tumor growth). The actuarial tumor control rate at 15 years was 93.7%. In 5% of the patients, delayed tumor growth was identified. Resection was performed after radiosurgery in 13 patients (5%). No patient developed a radiation-induced tumor. Eighty-one percent of the patients were still alive at the time of this analysis. Normal facial nerve function was maintained in 95% of patients who had normal function before undergoing treatment for acoustic neuromas. CONCLUSION: Stereotactic radiosurgery provided high rates of tumor growth control, often with tumor regression, and low morbidity rates in patients with benign intracranial tumors when evaluated over the long term. This study supports radiosurgery as a reliable alternative to surgical resection for selected patients with benign intracranial tumors.

Gamma knife radiosurgery of imaging-diagnosed intracranial meningioma.

PURPOSE: To evaluate tumor control and outcome from radiosurgery of meningiomas diagnosed by imaging without pathologic verification. METHODS AND MATERIALS: A total of 219 meningiomas diagnosed by imaging criteria underwent gamma knife radiosurgery to a median marginal tumor dose of 14 Gy (range 8.9-20), a median treatment volume of 5.0 cm(3) (range 0.47-56.5), and a median maximal dose of 28 Gy (range 22-50). The median follow-up was 29 months (range 2-164). RESULTS: Tumor progression developed in 7 cases, 2 of which turned out to be different tumors (metastatic nasopharyngeal adenoid cystic carcinoma and chondrosarcoma). One tumor was controlled, but the development of other brain metastases suggested a different diagnosis. The actuarial tumor control rate was 93.2% +/- 2.7% at 5 and 10 years. The actuarial rate of identifying a diagnosis other than meningioma was 2.3% +/- 1.4% at 5 and 10 years. The actuarial rate of developing any postradiosurgical injury reaction was 8.8% +/- 3.0% at 5 and 10 years. No pretreatment variables correlated with tumor control in univariate or multivariate analysis. The risk of postradiosurgery sequelae was lower (5.3% +/- 2.3%) in patients treated after 1991 (with stereotactic MRI and lower doses; p = 0.0104) and tended to increase with treatment volume (p = 0.0537). CONCLUSION: Radiosurgery of meningioma diagnosed by imaging without tissue confirmation is associated with a high rate of tumor control and acceptable morbidity but carries a small risk (2.3%) of an incorrect diagnosis.

An analysis of the dose-response for arteriovenous malformation radiosurgery and other factors affecting obliteration.

PURPOSE: The aim of this study was to better understand arteriovenous malformation (AVM) obliteration rates after radiosurgery. METHODS AND MATERIALS: We studied obliteration after Gamma knife radiosurgery in 351 AVM patients with 3-11 years of follow-up imaging. The median marginal dose was 20 Gy (range: 12-30) and median treatment volume was 5.7 cm(3) (range: 0.26-24). Stereotactic targeting was with angiography alone in 250 AVMs, and additional magnetic resonance (MR) imaging in 101 AVMs. RESULTS: We documented obliteration by angiography in 193/264 (73%) AVM, and by MR alone in 75/87 (86%) AVM for a 75% corrected obliteration rate. We identified persistent out-of-field nidus in 18% of embolized vs. 5% of non-embolized patients, (P = 0.006). Multivariate analysis correlated in-field obliteration with marginal dose (P < 0.0001) and sex (P < or = 0.026, but not for overall obliteration P = 0.19). A mathematical dose-response model for overall obliteration was constructed to generate a dose-response curve for AVM obliteration with a maximum overall obliteration rate of 88% and minimal improvement above 25 Gy. We could not define the value of alpha/beta for AVM obliteration to a level of statistical significance. CONCLUSION: The rate of AVM obliteration from radiosurgery depends on the marginal dose administered with a dose-response curve that reaches a maximum of approximately 88%. The dose-response plateau reflects problems with target definition which is made more difficult by prior embolization.