Tomoyuki Koga

Extended field stereotactic radiosurgery for recurrent glioblastoma.

Stereotactic radiosurgery (SRS) is among the few therapeutic options for glioblastoma that recurs after standard radiation and chemotherapy, but its efficacy has been limited.

Long-term control of disseminated pleomorphic xanthoastrocytoma with anaplastic features by means of stereotactic irradiation

Pleomorphic xanthoastrocytoma (PXA) is a rare astrocytic neoplasm of the brain. Some PXAs are accompanied by anaplastic features and are difficult to manage because of frequent recurrences that lead to early death. No previous reports have demonstrated consistent efficacy of adjuvant radiotherapy or chemotherapy for this disease. We report a case of PXA with anaplastic features treated with stereotactic irradiation (STI) that resulted in long-term control of repeatedly recurring nodules throughout the neuraxis. A 47-year-old woman presented with an epileptic seizure due to a large tumor in the right frontal lobe. The tumor was resected and diagnosed as PXA with anaplastic features. Sixteen months later, a relapse at the primary site was noted and treated with stereotactic radiosurgery using Gamma Knife. Two years later, the patient developed a tumor nodule in the cervical spinal cord that histologically corresponded to a small-cell glioma with high cellularity and prominent MIB-1 (mindbomb homolog 1) labeling. In the following months, multiple nodular lesions appeared throughout the CNS, and STI was performed six times for eight intracranial lesions using Gamma Knife and twice using a linear accelerator, for three spinal cord lesions in total. All lesions treated with STI were well controlled, and the patient was free from symptomatic progression for 50 months. However, diffuse dissemination along the craniospinal axis eventually progressed, and she died 66 months after initial diagnosis. Autopsy showed that the nodules remained well demarcated from the surrounding nervous system tissue. STI may be an effective therapeutic tool for controlling nodular dissemination of PXA with anaplastic features.

Outcomes of Diffusion Tensor Tractography–Integrated Stereotactic Radiosurgery

PURPOSE To analyze the effect of use of tractography of the critical brain white matter fibers created from diffusion tensor magnetic resonance imaging on reduction of morbidity associated with radiosurgery. METHODS AND MATERIALS Tractography of the pyramidal tract has been integrated since February 2004 if lesions are adjacent to it, the optic radiation since May 2006, and the arcuate fasciculus since October 2007. By visually confirming the precise location of these fibers, the dose to these fiber tracts was optimized. One hundred forty-four consecutive patients with cerebral arteriovenous malformations who underwent radiosurgery with this technique between February 2004 and December 2009 were analyzed. RESULTS Tractography was prospectively integrated in 71 of 155 treatments for 144 patients. The pyramidal tract was visualized in 45, the optic radiation in 22, and the arcuate fasciculus in 13 (two tracts in 9). During the follow-up period of 3 to 72 months (median, 23 months) after the procedure, 1 patient showed permanent worsening of pre-existing dysesthesia, and another patient exhibited mild transient hemiparesis 12 months later but fully recovered after oral administration of corticosteroid agents. Two patients had transient speech disturbance before starting integration of the arcuate fasciculus tractography, but no patient thereafter. CONCLUSION Integrating tractography helped prevent morbidity of radiosurgery in patients with brain arteriovenous malformations.

The value of image coregistration during stereotactic radiosurgery

BackgroundCoregistration of any neuroimaging studies into treatment planning for stereotactic radiosurgery became easily applicable using the Leksell Gamma Knife 4C, a new model of gamma knife. The authors investigated the advantage of this image processing.MethodSince installation of the Leksell Gamma Knife 4C at the authors’ institute, 180 sessions of radiosurgery were performed. Before completion of planning, coregistration of frameless images of other modalities or previous images was considered to refine planning. Treatment parameters were compared for planning before and after refinement by use of coregistered images.FindingsCoregistered computed tomography clarified the anatomical structures indistinct on magnetic resonance imaging. Positron emission tomography visualized lesions disclosing metabolically high activity. Coregistration of prior imaging distinguished progressing lesions from stable ones. Diffusion-tensor tractography was integrated for lesions adjacent to the corticospinal tract or the optic radiation. After refinement of planning in 36 sessions, excess treated volume decreased (p = 0.0062) and Paddick conformity index improved (p < 0.001). Maximal dose to the white matter tracts was decreased (p < 0.001).ConclusionImage coregistration provided direct information on anatomy, metabolic activity, chronological changes, and adjacent critical structures. This gathered information was sufficiently informative during treatment planning to supplement ambiguous information on stereotactic images, and was useful especially in reducing irradiation to surrounding normal structures.

The long-term outcomes of radiosurgery for arteriovenous malformations in pediatric and adolescent populations

OBJECT Although stereotactic radiosurgery (SRS) has been accepted as a therapeutic option for arteriovenous malformations (AVMs) in children and adolescents, substantial data are still lacking regarding the outcomes of SRS for AVMs in this age group, especially long-term complications. This study aimed to clarify the long-term outcomes of SRS for the treatment of AVM in pediatric patients aged ≤ 18 years. METHODS Outcomes of 116 patients who were aged 4-18 years when they underwent SRS between 1990 and 2009 at the study institute were analyzed retrospectively. RESULTS The median follow-up period after SRS was 100 months, with 6 patients followed up for more than 20 years. Actuarial obliteration rates at 3 and 5 years after SRS were 68% and 88%, respectively. Five hemorrhages occurred in 851 patient-years of follow-up. The annual bleeding rate after SRS before obliteration was calculated as 1.3%, which decreased to 0.2% after obliteration. Shorter maximum nidus diameter (p = 0.02) and higher margin dose (p = 0.03) were associated with a higher obliteration rate. Ten patients experienced adverse events after SRS. Of them, 4 patients presented with delayed complications years after SRS (range 9-20 years after SRS). CONCLUSIONS SRS can reduce the risk of hemorrhage in pediatric and adolescent AVMs, with an acceptable risk of complications in the long term. However, adverse events such as expanding hematoma and radiation necrosis that can occur after substantial follow-up should be taken into account at the time that treatment decisions are made and informed consent is obtained.

The long-term outcomes of radiosurgery for intracranial hemangioblastomas

BACKGROUND Optimal timing in the treatment of intracranial hemangioblastoma (HB) remains controversial, particularly for patients of von Hippel-Lindau disease (VHL) with multiple small lesions. We evaluated efficacy of stereotactic radiosurgery (SRS) for intracranial HB based on the longer follow-up data with a larger number of patients and lesions. METHODS Twenty-one patients (11 men, 10 women) initially underwent SRS for 57 intracranial HBs. Seven patients had sporadic lesions and 14 had VHL-related lesions. During the follow-up, 40 lesions were additionally treated in VHL patients in 10 SRS treatments. Thus, a total of 97 lesions were included in this study. Median tumor volume was 0.13 cm(3) (range, 0.004-9.5 cm(3)), and median margin dose was 18 Gy (range, 14-20 Gy). RESULTS Median duration of follow-up was 96 months (range, 3-235 mo) after initial SRS treatment. Ten tumors in 7 patients showed progression after SRS. Actuarial tumor control rates after SRS at 5 and 10 years were 94% and 80%, respectively. Factors associated with longer control were solid lesion (P = .03), smaller volume (P = .01), and lesions associated with VHL (P = .0005) in univariate analysis. Five- and 10-year tumor control rates were 67% and 44% for sporadic patients and 97% and 83% for VHL patients. CONCLUSION SRS could be offered as an effective treatment for small, solid, and VHL-associated HBs. If the tumors show apparent enlargement in size or can possibly become symptomatic along with a slight increase in size, SRS should be recommended before they present with the clinical symptoms.

Delayed complication after Gamma Knife surgery for mesial temporal lobe epilepsy

OBJECT Despite the controversy over the clinical significance of Gamma Knife surgery (GKS) for refractory mesial temporal lobe epilepsy (MTLE), the modality has attracted attention because it is less invasive than resection. The authors report long-term outcomes for 7 patients, focusing in particular on the long-term complications. METHODS Between 1996 and 1999, 7 patients with MTLE underwent GKS. The 50% marginal dose covering the medial temporal structures was 18 Gy in 2 patients and 25 Gy in the remaining 5 patients. RESULTS High-dose treatment abolished the seizures in 2 patients and significantly reduced them in 2 others. One patient in this group was lost to follow-up. However, 2 patients presented with symptomatic radiation necrosis (SRN) necessitating resection after 5 and 10 years. One patient who did not need necrotomy continued to show radiation necrosis on MRI after 10 years. One patient died of drowning while swimming in the sea 1 year after GKS, before seizures had disappeared completely. CONCLUSIONS High-dose treatment resulted in sufficient seizure control but carried a significant risk of SRN after several years. Excessive target volume was considered as a reason for delayed necrosis. Drawbacks such as a delay in seizure control and the risk of SRN should be considered when the clinical significance of this treatment is evaluated.

Long-term outcomes of stereotactic radiosurgery for arteriovenous malformations in the thalamus.

BACKGROUNDArteriovenous malformations (AVMs) in the thalamus carry a high risk of hemorrhage. Although stereotactic radiosurgery (SRS) is widely accepted because of the high surgical morbidity and mortality of these lesions, precise long-term outcomes are largely unknown. OBJECTIVETo review our experience with SRS for thalamic AVMs based on the latest follow-up data. METHODSForty-eight patients with thalamic AVMs were treated by SRS using the Leksell Gamma Knife and were followed. Long-term outcomes including the obliteration rate, hemorrhage after treatment, and adverse effects were retrospectively analyzed. RESULTSThe annual hemorrhage rate before SRS was 14%. The mean follow-up period after SRS was 66 months (range 6–198 months). The actuarial obliteration rate confirmed by angiography was 82% at 5 years after treatment, and the annual hemorrhage rate after SRS was 0.36%. Factors associated with higher obliteration rates were previous hemorrhage (P = .004) and treatment using new planning software (P = .001). Persistent worsening of neurological symptoms was observed in 17% and more frequently seen in patients who were treated using older planning software (P = .04) and a higher margin dose (P = .02). The morbidity rate for patients who received treatment planned using new software with a margin dose not more than 20 Gy was 12%. CONCLUSIONSRS for thalamic AVMs achieved a high obliteration rate and effectively decreased the risk of hemorrhage, with less morbidity compared with other modalities. Longer follow-up to evaluate the risk of delayed complications and the effort to minimize the morbidity is necessary.

Role of Gamma Knife surgery in the treatment of intracranial dural arteriovenous fistulas

OBJECT The goal of this study was to assess the efficacy of Gamma Knife surgery (GKS) in the management of dural arteriovenous fistulas (dAVFs). METHODS The authors performed a retrospective analysis of a group of 22 patients who underwent GKS for dAVFs at the University of Tokyo Hospital between 1991 and 2009. The patients underwent CT or MR imaging with contrast enhancement every 6 months after GKS; when obliteration of a dAVF was indicated by these images, patients also underwent angiography. Follow-up in these patients ranged from 12 months to 100 months (median 33 months) after GKS. RESULTS Obliteration of the dAVF was confirmed by neuroimaging in 12 patients (55%). According to a Kaplan-Meier analysis, obliteration rates for the dAVFs were 51% at 3 years and 80% at 5 years. The obliteration rate for lesions without cortical venous drainage (CVD) was 86%, which was significantly higher than the rate for dAVFs with CVD (47%) (p = 0.007). Hemorrhage at presentation (p = 0.03), a target volume less than 1.5 cm(3) (p = 0.009), and Cognard Type III or IV dAVF (p = 0.005) were factors associated with a higher obliteration rate. Among 10 patients whose dAVFs were not obliterated by the initial GKS, 5 patients underwent additional treatment and complete obliteration was achieved in all. Relief of tinnitus was obtained in 5 (83%) of 6 patients with transverse-sigmoid sinus dAVFs, and ophthalmic symptoms improved in 2 (67%) of 3 patients with cavernous sinus dAVFs. No patient experienced interval hemorrhage or radiation-induced complications after treatment. CONCLUSIONS Gamma Knife surgery is a safe and effective treatment for dAVF. It can be a first line of therapy in the multidisciplinary treatment strategy for dAVFs, especially when significant morbidity is anticipated with other therapeutic options. One should be very careful about recommending GKS for patients harboring dAVFs with CVD because of the expected natural history of such a lesion and the possibility of other therapeutic options.

Outcomes of radiosurgery for brainstem arteriovenous malformations.

BACKGROUND:Arteriovenous malformations (AVMs) in the brainstem yield a high risk of hemorrhage. Although stereotactic radiosurgery (SRS) is accepted, because of high surgical morbidity and mortality, outcomes are still unclear. OBJECTIVE:We previously reported the early results of SRS for brainstem AVMs. Here, we obtained data from a longer follow-up for a larger number of patients and present precise outcomes based on the latest follow-up data. METHODS:Forty-four patients with brainstem AVMs were treated by SRS. Outcomes such as the rates of obliteration, hemorrhage after treatment, and adverse effects were retrospectively analyzed. RESULTS:The annual hemorrhage rate before SRS was 17.5%. The mean follow-up period after SRS was 71 months (range, 2-168 months). The actuarial obliteration rate confirmed by angiography was 52% at 5 years. Factors associated with higher obliteration rate were previous hemorrhage (P = .048) and higher margin dose (P = .048). For patients treated with a margin dose of ≥ 18 Gy, the obliteration rate was 71% at 5 years. Persistent worsening of neurological symptoms was observed in 5%. The annual hemorrhage rate after SRS was 2.4%. Four patients died of rebleeding, and disease-specific survival rate was 86% at 10 years after treatment. CONCLUSION:Nidus obliteration must be achieved for brainstem AVMs because they possibly cause lethal hemorrhage even after SRS. Treatment with a high margin dose is desirable to obtain favorable outcomes for these lesions. Additional treatment should be considered for an incompletely obliterated nidus.