Image Fusion for Radiosurgery, Neurosurgery and Hypofractionated Radiotherapy.

Precise target detection is essential for radiosurgery, neurosurgery and hypofractionated radiotherapy because treatment results and complication rates are related to accuracy of the target definition. In skull base tumors and tumors around the optic pathways, exact anatomical evaluation of cranial nerves are important to avoid adverse effects on these structures close to lesions. Three-dimensional analyses of structures obtained with MR heavy T2-images and image fusion with CT thin-sliced sections are desirable to evaluate fine structures during radiosurgery and microsurgery. In vascular lesions, angiography is most important for evaluations of whole structures from feeder to drainer, shunt, blood flow and risk factors of bleeding. However, exact sites and surrounding structures in the brain are not shown on angiography. True image fusions of angiography, MR images and CT on axial planes are ideal for precise target definition. In malignant tumors, especially recurrent head and neck tumors, biologically active areas of recurrent tumors are main targets of radiosurgery. PET scan is useful for quantitative evaluation of recurrences. However, the examination is not always available at the time of radiosurgery. Image fusion of MR diffusion images with CT is always available during radiosurgery and useful for the detection of recurrent lesions. All images are fused and registered on thin sliced CT sections and exactly demarcated targets are planned for treatment. Follow-up images are also able to register on this CT. Exact target changes, including volume, are possible in this fusion system. The purpose of this review is to describe the usefulness of image fusion for 1) skull base, 2) vascular, 3) recurrent target detection, and 4) follow-up analyses in radiosurgery, neurosurgery and hypofractionated radiotherapy.

Optimal hypofractionated conformal radiotherapy for large brain metastases in patients with high risk factors: a single-institutional prospective study.

BACKGROUND: A single-institutional prospective study of optimal hypofractionated conformal radiotherapy for large brain metastases with high risk factors was performed based on the risk prediction of radiation-related complications. METHODS: Eighty-eight patients with large brain metastases ≥10 cm(3) in critical areas treated from January 2010 to February 2014 using the CyberKnife were evaluated. The optimal dose and number of fractions were determined based on the surrounding brain volume circumscribed with a single dose equivalent (SDE) of 14 Gy (V14) to be less than 7 cm(3) for individual lesions. Univariate and multivariate analyses were conducted. RESULTS: As a result of optimal treatment, 92 tumors ranging from 10 to 74.6 cm(3) (median, 16.2 cm(3)) in volume were treated with a median prescribed isodose of 57% and a median fraction number of five. In order to compare the results according to the tumor volume, the tumors were divided into the following three groups: 1) 10-19.9 cm(3), 2) 20-29.9 cm(3) and 3) ≥30 cm(3). The lesions were treated with a median prescribed isodose of 57%, 56% and 55%, respectively, and the median fraction number was five in all three groups. However, all tumors ≥20 cm(3) were treated with ≥ five fractions. The median SDE of the maximum dose in the three groups was 47.2 Gy, 48.5 Gy and 46.5 Gy, respectively. Local tumor control was obtained in 90.2% of the patients, and the median survival was nine months, with a median follow-up period of seven months (range, 3-41 months). There were no significant differences in the survival rates among the three groups. Six tumors exhibited marginal recurrence 7-36 months after treatment. Ten patients developed symptomatic brain edema or recurrence of pre-existing edema, seven of whom required osmo-steroid therapy. No patients developed radiation necrosis requiring surgical resection. CONCLUSION: Our findings demonstrate that the administration of optimal hypofractionated conformal radiotherapy based on the dose-volume prediction of complications (risk line for hypofractionation), as well as Kjellberg's necrosis risk line used in single-session radiosurgery, is effective and safe for large brain metastases or other lesions in critical areas.

Five-fraction CyberKnife radiotherapy for large brain metastases in critical areas: impact on the surrounding brain volumes circumscribed with a single dose equivalent of 14 Gy (V14) to avoid radiation necrosis.

The efficacy and toxicity of five-fraction CyberKnife radiotherapy were evaluated in patients with large brain metastases in critical areas. A total of 85 metastases in 78 patients, including tumors >30 cm(3) (4 cm in diameter) were treated with five-fraction CyberKnife radiotherapy with a median marginal dose of 31 Gy at a median prescribed isodose of 58%. Changes in the neurological manifestations, local tumor control, and adverse effects were investigated after treatment. The surrounding brain volumes circumscribed with 28.8 Gy (single dose equivalent to 14 Gy: V14) were measured to evaluate the risk of radiation necrosis. Neurological manifestations, such as motor weakness, visual disturbances and aphasia improved in 28 of 55 patients (50.9%). Local tumor control was obtained in 79 of 85 metastases (92.9%) during a median follow-up of eight months. Symptomatic edema occurred in 10 patients, and two of them (2.6%) required surgical resection because of radiation necrosis. The V14 of these patients was 3.0-19.7 cm(3). There were 16 lesions with a V14 of ≥7.0 cm(3), and two of these lesions developed extensive brain edema due to radiation necrosis. None of the patients with a V14 of <7.0 cm(3) exhibited edema requiring surgical intervention. We therefore conclude that a high rate of local tumor control and low rates of complications can be obtained after five-fraction CyberKnife radiotherapy for large metastases in critical areas. The V14 of the surrounding brain is therefore a useful indicator for the risk of radiation necrosis in patients with large metastases.

Spinal epidural arteriovenous fistulas with unusual manifestation of sudden onset of severe neurological deficits: case report.

Spinal epidural arteriovenous fistulas with perimedullary venous drainage cause venous hypertension, and usually manifest as slowly progressive myelopathy. We treated two patients presenting with sudden onset of severe neurological deficits. Moreover, in Case 1, the venous drainage was exclusively epidural and no perimedullary venous drainage was present. Angiographic findings of this patient were characterized by a slow-flow fistula with marked retention of the epidural venous drainage. Rapidly progressing thrombosis of the epidural venous plexus may have caused the sudden onset of the symptoms. In Case 2, hematomyelia may also be possibly associated with the sudden onset of the symptoms. Early diagnosis and treatment are essential to achieve favorable outcome in such cases because venous congestion results in irreversible venous infarction within a short period.

Three-fraction CyberKnife radiotherapy for brain metastases in critical areas: referring to the risk evaluating radiation necrosis and the surrounding brain volumes circumscribed with a single dose equivalence of 14 Gy (V14).

The efficacy and toxicity of three-fraction CyberKnife radiotherapy were evaluated in patients with brain metastases in critical areas. One hundred and fifty-nine metastases in 145 patients including tumors >10 cm(3) were treated with three-fraction CyberKnife radiotherapy with a median marginal dose of 27 Gy at a median prescribed isodose of 60%. Changes in the neurological manifestations, local tumor control and adverse effects were investigated after treatment. The surrounding brain volumes circumscribed with 23.1 Gy (single dose equivalence of 14 Gy: V14) were measured to evaluate the risk of adverse effects. Neurological manifestations, such as motor weakness, visual disturbances and aphasia improved in 26 of 97 patients (26.8%). Local tumor control was obtained in 137 of 143 metastases (95.8%) during a median follow-up of 7 months. Nine patients had symptomatic edema and three of them (2.1%) required surgical resection because of radiation necrosis. The V14 of these patients was 4.6-31.5 cm(3). There were 35 lesions with a V14 of 7 cm(3) or more and three of them developed extensive brain edema due to radiation necrosis. None of the patients with a V14 of <7 cm(3) exhibited edema requiring an operation. We therefore conclude that a high rate of local tumor control and low rates of complications are obtained after three-fraction CyberKnife radiotherapy for metastases in critical areas. The V14 of the surrounding brain therefore seems to be a useful indicator for the risk evaluation of radiation necrosis in patients with larger metastases.

Other skull-base tumors.

Therapeutic policy and radiosurgical results for nonvestibular schwannomas and chordomas are reported. Fourteen patients with nonvestibular schwannomas treated with marginal doses of 12-15 Gy were followed for 5-13 years. All patients except one were stable and did not require additional treatments. Seven patients with chordomas were treated with marginal doses of 14-20 Gy. Five of them showed unchanged or decreased size of tumors during the follow-up of 4.5-7 years. Two patients required a second treatment and 1 died due to tumor progression outside of the treatment volume. No adverse effects were experienced in any of these patients. Gamma knife radiosurgery is an effective treatment for nonvestibular schwannomas and chordomas. However, multisession radiosurgery may be required for aggressive chordomas.

Long-term results of Gamma Knife surgery for arteriovenous malformations: 10- to 15-year follow up in patients treated with lower doses.

OBJECT: Several adverse effects such as brain edema, necrosis, arterial stenosis, hemorrhage after obliteration, and delayed cyst formation have been reported as early and late complications of Gamma Knife surgery (GKS) for arteriovenous malformations (AVMs). These adverse effects seem to be decreased in a lower-dose treatment regimen compared with the classic higher margin doses of 25 Gy because the radiation insult to the surrounding tissue is minimized. Long-term results of lower-dose GKS for AVMs are presented. METHODS: One hundred fourteen patients with AVMs were treated with lower-dose GKS (< or = 20-Gy margin dose). There were 68 male and 46 female patients, aged 10 to 68 years (mean 35.4 years). The evaluation of AVM nidi and dose planning were performed using both angiography and MR imaging in all cases to exclude the surrounding brain tissue. The mean margin dose was 19.5 Gy. Total angiographically documented obliteration was achieved in 65 (85.5%) of 76 patients. Eleven patients underwent a second treatment, including staged treatment for large AVMs; total AVM obliteration has been achieved in six of them to date. Of 38 patients in whom no follow-up examination could be performed, 19 of them were healthy and 10 were lost from follow up. Nine patients experienced bleeding during the latency period, and four of them suffered lethal hemorrhage. Symptomatic early complications were extensive brain edema after repeated GKS in one patient and an adverse effect on the internal capsule in one. Delayed cyst formation was found in one patient as a late complication 10 years after treatment. No treatment-related death has been noted to date. CONCLUSIONS: Lower-dose GKS is an effective and safe treatment for patients with AVMs and may decrease long-term adverse effects to the surrounding brain.

Low-dose radiosurgery for large vestibular schwannomas: long-term results of functional preservation.

OBJECT: The author conducted a study to assess the long-term results obtained in patients who underwent GKS for large vestibular schwannomas (> 3 cm in diameter). Facial and cochlear nerve functions were evaluated. METHODS: Twenty consecutive large tumors in 18 patients (including two cases of neurofibromatosus Type 2 [NF2]) were followed for more than 6 years. There were eight tumors that were more than 4 cm in maximum diameter. Microsurgery had already been performed prior to GKS in 11 patients (nine recurrent and two residual tumors). Four patients (including one with NF2) died during the follow-up period of other diseases or by accident. Fourteen of 15 tumors were stable or decreased in size. Microsurgery was performed in one patient 2 years after radiosurgery. Facial nerve function was preserved in all patients and hearing preserved in four of five patients with cochlear nerve function prior to radiosurgery. No adverse effects of radiosurgery have been observed to date. CONCLUSIONS: Gamma knife surgery seems to have a place in the low-dose treatment of selected large vestibular schwannoma in patients with a reasonable chance of retaining facial function and pretreatment hearing level. Patients with severe brainstem compression should first be undergo microsurgery.

Hemorrhage risks and obliteration rates of arteriovenous malformations after gamma knife radiosurgery.

OBJECT: The purpose of this study was to analyze the risk of hemorrhage and the obliteration rate after treatment of patients with arteriovenous malformations (AVMs). METHODS: Between 1991 and 1995, 115 patients were treated using gamma knife radiosurgery (GKS). Surgical planning was based on angiograms and three-dimensional images. The angiographic features of the AVMs and the risk factors for hemorrhage were then evaluated. Hemorrhages occurred in eight patients (7%) 7 to 42 months after GKS. Based on AVM morphology, the rates of hemorrhage were five (7.6%) of 66 for AVMs with a single draining vein, seven (14%) of 66 for AVMs with deep drainage, four (26.7%) of 15 for AVMs with a varix, four (28.6%) of 14 for AVMs with venous obstruction, eight (17.0%) of 47 for high-flow (shunt- and mixed-type) AVMs, and five (35.7%) of 14 for large AVMs with a volume of more than 10 cm3. No hemorrhages were observed in association with low-flow (moyamoya-type) AVMs in this series. Total AVM obliteration was achieved in 81.3% of 80 patients who underwent angiography. The obliteration rate was 91.3% for moyamoyatype AVMs and 67.6% for shunt- and mixed-type AVMs. Early obliteration within 12 months was achieved in 63% of the moyamoya-type AVMs. CONCLUSIONS: Moyamoya-type AVMs seem to be at risk for post-GKS hemorrhage. Intravascular embolization should be considered prior to GKS for mixed- and shunt-type AVMs in an attempt to reduce the hemodynamic stress and thereby decrease the risk of hemorrhage.