Faculty Profiles - Tanaka Shota

PDGFRBのgermline変異を認めたinfantile myofibromatosisの1例 Reviewed

高柳俊作, 田中将太, 井上瑞穂, 武笠晃丈, 中冨浩文, 斉藤延人

家族性腫瘍 14 ( 2 ) A44 - A44 2014.5

Effect of dural detachment on long-term tumor control for meningiomas treated using Simpson grade IV resection. Reviewed International journal

Yuta Fukushima, Soichi Oya, Hirofumi Nakatomi, Junji Shibahara, Shunya Hanakita, Shota Tanaka, Masahiro Shin, Kensuke Kawai, Masashi Fukayama, Nobuhito Saito

Journal of neurosurgery 119 ( 6 ) 1373 - 9 2013.12

Language：English Publishing type：Research paper (scientific journal) Publisher：AMER ASSOC NEUROLOGICAL SURGEONS

OBJECT: Meningiomas treated by subtotal or partial resection are associated with significantly shorter recurrence-free survival than those treated by gross-total resection. The Simpson grading system classifies incomplete resections into a single category, namely Simpson Grade IV, with wide variations in the volume and location of residual tumors, making it complicated to evaluate the achievement of surgical goals and predict the prognosis of these tumors. Authors of the present study investigated the factors related to necessity of retreatment and tried to identify any surgical nuances achievable with the aid of modern neurosurgical techniques for meningiomas treated using Simpson Grade IV resection. METHODS: This retrospective analysis included patients with WHO Grade I meningiomas treated using Simpson Grade IV resection as the initial therapy at the University of Tokyo Hospital between January 1995 and April 2010. Retreatment was defined as reresection or stereotactic radiosurgery due to postoperative tumor growth. RESULTS: A total of 38 patients were included in this study. Regrowth of residual tumor was observed in 22 patients with a mean follow-up period of 6.1 years. Retreatment was performed for 20 of these 22 tumors with regrowth. Risk factors related to significantly shorter retreatment-free survival were age younger than 50 years (p = 0.006), postresection tumor volume of 4 cm(3) or more (p = 0.016), no dural detachment (p = 0.001), and skull base location (p = 0.016). Multivariate analysis revealed that no dural detachment (hazard ratio [HR] 6.42, 95% CI 1.41-45.0; p = 0.02) and skull base location (HR 11.6, 95% CI 2.18-218; p = 0.002) were independent risk factors for the necessity of early retreatment, whereas postresection tumor volume of 4 cm(3) or more was not a statistically significant risk factor. CONCLUSIONS: Compared with Simpson Grade I, II, and III resections, Simpson Grade IV resection includes highly heterogeneous tumors in terms of resection rate and location of the residual mass. Despite the difficulty in analyzing such diverse data, these results draw attention to the favorable effect of dural detachment (instead of maximizing the resection rate) on long-term tumor control. Surgical strategy with an emphasis on detaching the tumor from the affected dura might be another important option in resection of high-risk meningiomas not amenable to gross-total resection.

DOI： 10.3171/2013.8.JNS13832

IDENTIFICATION OF DISTINCT SUBGROUP OF GLIOMA AND NOVEL GENES RELATED TO MALIGNANT PROGRESSION BY GENOME-WIDE METHYLATION ANALYSIS Reviewed

Saito Kuniaki, Mukasa Akitake, Nagae Genta, Nagane Motoo, Aihara Koki, Takayanagi Shunsaku, Tanaka Shota, Aburatani Hiroyuki, Saito Nobuhito

NEURO-ONCOLOGY 15 150 - 151 2013.11

網羅的メチル化解析により同定された神経膠腫悪性転化に伴うメチル化プロファイルの変化(Identification of distinct subgroup of glioma related to malignant progression by genome-wide methylation analysis)

齊藤邦昭, 武笠晃丈, 永江玄太, 永根基雄, 相原功輝, 高柳俊作, 田中將太, 油谷浩幸, 斉藤延人

日本癌学会総会記事 72回 125 - 125 2013.10

Stereotactic radiosurgery for intracranial gliomas. Reviewed International journal

Shota Tanaka, Masahiro Shin, Akitake Mukasa, Shunya Hanakita, Kuniaki Saito, Tomoyuki Koga, Nobuhito Saito

Neurosurgery clinics of North America 24 ( 4 ) 605 - 12 2013.10

Language：English Publishing type：Research paper (scientific journal) Publisher：W B SAUNDERS CO-ELSEVIER INC

This article presents an overview of stereotactic radiosurgery for intracranial glioma. It assists readers in reviewing up-to-date literature on this topic and determining indications of radiosurgery in the treatment of glioma. Discussion also includes its recent advances and future perspectives.

DOI： 10.1016/j.nec.2013.05.010

Stereotactic Radiosurgery for Trigeminal Pain Secondary to Benign Skull Base Tumors Reviewed

Shota Tanaka, Bruce E. Pollock, Scott L. Stafford, Michael J. Link

WORLD NEUROSURGERY 80 ( 3-4 ) 371 - 377 2013.9

Language：English Publishing type：Research paper (scientific journal) Publisher：ELSEVIER SCIENCE INC

OBJECTIVE: To assess the outcome of stereotactic radiosurgery (SRS) for patients with benign skull base tumors and trigeminal-related facial pain.
METHODS: We undertook a retrospective review of 31 consecutive patients (25 women, 6 men) with benign skull base tumors and trigeminal pain who underwent SRS between 1991 and 2008. The tumors included 17 posterior fossa meningiomas, 9 cavernous sinus meningiomas, and 5 trigeminal schwannomas. The median patient age was 62 years (range, 17-81 years). In all cases the tumor was the primary target for SRS. The median follow-up after SRS was 50 months (range, 12-184 months).
RESULTS: The actuarial tumor control rate after SRS was 95% at both 3 years and 5 years. Eighteen patients (58%) initially achieved complete resolution of trigeminal pain. Higher maximum dose was associated with initial complete pain resolution on a multivariate analysis. However, 7 patients had recurrent pain during follow-up. At last follow-up, only 7 patients (23%) remained pain-free off medications. Further treatment in addition to medical therapy was required for 6 patients (19%).
CONCLUSION: Although SRS offers excellent radiographic tumor control for benign skull base tumors, durable relief of tumor-related trigeminal pain without medication was noted in only one-fourth of patients at last follow-up.

DOI： 10.1016/j.wneu.2012.01.057

Update on glioma treatments in the United States Reviewed

Shota Tanaka, Andrew S. Chi, Patrick Y. Wen, David N. Louis, A. John Iafrate, Tracy T. Batchelor

Japanese Journal of Neurosurgery 22 ( 8 ) 590 - 596 2013.8

Language：English Publishing type：Research paper (scientific journal) Publisher：Japanese Congress of Neurological Surgeons

Despite the use of maximal standard treatments, the prognosis of patients with glioblastoma remains poor
hence novel therapies are desperately needed. Molecular targeted therapies have shown some promise in other malignancies, while they have not demonstrated remarkable tumor response or improved patient survival in glio-blastoma to date, due, in part, to the redundancy and crosstalk of multiple overactive molecular pathways and the lack of validated predictive biomarkers. At present, a comprehensive cancer genotyping platform that can reveal potentially targetable genes is being implemented into clinical practice at some cancer institutions in the United States. This may allow us to rationally tailor therapies to specific tumor genotypes that we predict may be susceptible. In this paper, an overview of current glioblastoma treatment strategies in the United States is presented.

DOI： 10.7887/jcns.22.590

Scopus

Gliomatosis cerebri: clinical characteristics, management, and outcomes. Reviewed International journal

Selby Chen, Shota Tanaka, Caterina Giannini, Jonathan Morris, Elizabeth S Yan, Jan Buckner, Daniel H Lachance, Ian F Parney

Journal of neuro-oncology 112 ( 2 ) 267 - 75 2013.4

Language：English Publishing type：Research paper (scientific journal) Publisher：SPRINGER

Gliomatosis cerebri is a rare diffusely infiltrating primary neoplastic glial process of the brain. Our objective is to review clinical presentation, management, and outcome in a large single institution series of gliomatosis cerebri patients. 54 consecutive gliomatosis cerebri cases presenting to Mayo Clinic Rochester between 1991 and 2008 were retrospectively reviewed. Inclusion criteria included involvement of at least three cerebral lobes, lack of a single discrete mass and pathological confirmation of diffuse glioma. Median overall survival (OS) was 18.5 months. Age, gender, presenting symptoms, and contrast enhancement did not correlate significantly with survival, though there was a trend toward decreased overall survival in patients above the median age of 46 years. Karnofsky performance score <70 was associated with poor OS (median 9.5 vs. 20.5 months, p = 0.02). Higher histologic grade was associated with poor progression-free survival (PFS; median for WHO grades II, III, and IV: 21.5, 6.5, and 4 months; p = 0.03) and OS (median 34, 15.5, and 8.5 months; p < 0.05). Radiation therapy was strongly associated with better prognosis (PFS 16.5 vs. 4.5 months, p < 0.01; OS 27.5 vs. 6.5, p < 0.01), but chemotherapy was not. Gliomatosis cerebri patients have a poor prognosis. Lower KPS upon presentation and higher histologic grade predict decreased survival. Surgery's role is limited beyond biopsy for diagnostic purposes. Radiotherapy appears beneficial, although selection bias could be present in this retrospective study. Chemotherapy's value is not as clear but this must be interpreted with caution given variable treatment regimens in this series.

DOI： 10.1007/s11060-013-1058-x

Presentation, management, and outcome of newly diagnosed glioblastoma in elderly patients. Reviewed International journal

Shota Tanaka, Fredric B Meyer, Jan C Buckner, Joon H Uhm, Elizabeth S Yan, Ian F Parney

Journal of neurosurgery 118 ( 4 ) 786 - 98 2013.4

Language：English Publishing type：Research paper (scientific journal)

OBJECT: Optimum management for elderly patients with newly diagnosed glioblastoma (GBM) in the temozolomide (TMZ) era is not well defined. The object of this study was to clarify outcomes in this population. METHODS: The authors retrospectively reviewed 105 consecutive cases involving elderly patients (age ≥ 65 years) with newly diagnosed GBM who were treated at the Mayo Clinic between 2003 and 2008. RESULTS: The patients' median age was 74 years (range 66-87 years), and the median Karnofsky Performance Status (KPS) score was 80 (range 40-90). Half of the patients underwent biopsy and half underwent resection. Patients with deep-seated lesions (19 patients [18%]) or multifocal lesions (34 patients [32%]) were more likely to have biopsy than resection (p = 0.0001 and 0.0009, respectively). New persistent neurological deficits developed in 7 patients (6.7%). Postoperative hemorrhage occurred in 6 patients (5.7%), all of whom underwent biopsy. Complete follow-up data regarding adjuvant treatment was available in 84 patients. Forty-one (49%) were treated with chemotherapy (mostly TMZ) and radiation therapy (RT), and 23 (27%) with RT alone. Nineteen (23%) received only palliative care after surgery (more common with biopsy, p = 0.03). Chemotherapy complications occurred in 28.6% (Grade 3 or 4 hematological complications in 11.9%). The median values for progression-free survival (PFS) and overall survival (OS) were 3.5 and 5.5 months. In a multivariate analysis, younger age (p = 0.03, risk ratio [RR] 0.34, 95% CI 0.13-0.89), single lesion (p = 0.02, RR 0.51, 95% CI 0.30-0.89), resection (p = 0.04, RR 0.54, 95% CI 0.31-0.94), and adjuvant treatment (p = 0.0001, RR 0.24, 95% CI 0.11-0.49) were associated with better OS. Only adjuvant treatment was significantly associated with prolonged PFS (p = 0.0007, RR 0.27, 95% CI 0.13-0.57). With combined therapy with resection, RT, and chemotherapy, the median PFS and OS were 8 and 12.5 months, respectively. CONCLUSIONS: The prognosis for GBM worsens with increasing age in elderly patients. With important risks, resection and adjuvant treatment are associated with prolonged survival. Although selection bias cannot be excluded in this retrospective study, advanced age alone should not necessarily preclude optimal resection followed by adjuvant radiochemotherapy.

DOI： 10.3171/2012.10.JNS112268

Diagnostic and therapeutic avenues for glioblastoma: no longer a dead end? Reviewed International journal

Shota Tanaka, David N Louis, William T Curry, Tracy T Batchelor, Jorg Dietrich

Nature reviews. Clinical oncology 10 ( 1 ) 14 - 26 2013.1

Language：English Publishing type：Research paper (scientific journal) Publisher：NATURE PUBLISHING GROUP

Glioblastomas are heterogeneous neoplasms that are driven by complex signalling pathways, and are among the most aggressive and challenging cancers to treat. Despite standard treatment with resection, radiation and chemotherapy, the prognosis of patients with glioblastomas remains poor. An increasing understanding of the molecular pathogenesis of glioblastomas has stimulated the development of novel therapies, including the use of molecular-targeted agents. Identification and validation of diagnostic, prognostic and predictive biomarkers has led to the advancement of clinical trial design, and identification of glioblastoma subgroups with a more-favourable prognosis and response to therapy. In this Review, we discuss common molecular alterations relevant to the biology of glioblastomas, targeted, antiangiogenic and immunotherapies that have impacted on the treatment of this disease, and the challenges and pitfalls associated with these therapies. In addition, we emphasize current biomarkers relevant to the management of patients with glioblastoma.

DOI： 10.1038/nrclinonc.2012.204

Increased Frameless Stereotactic Accuracy With High-Field Intraoperative Magnetic Resonance Imaging Reviewed

Shota Tanaka, Ross C. Puffer, Jason M. Hoover, Stephan J. Goerss, Laura M. Haugen, Kiaran McGee, Ian F. Parney

Operative Neurosurgery 71 ons321 - ons328 2012.12

Language：English Publishing type：Research paper (scientific journal) Publisher：Oxford University Press (OUP)

BACKGROUND: Frameless stereotaxy commonly registers preoperative magnetic resonance imaging (MRI) to patients by using surface scalp anatomy or adhesive fiducial scalp markers. Patients' scalps may shift slightly between preoperative imaging and final surgical positioning with pinion placement, introducing error. This might be reduced when frameless stereotaxy is performed in a high-field intraoperative MRI (iMRI), as patients are positioned before imaging. This could potentially improve accuracy.
OBJECTIVE: To compare frameless stereotactic accuracy using a high-field iMRI with that using standard preoperative MRI.
METHODS: Data were obtained in 32 adult patients undergoing frameless stereotactic-guided brain tumor surgery. Stereotactic images were obtained with 1.5T MRI scanner either preoperatively (14 patients) or intraoperative (18 patients). System-generated accuracy measurements and distances from the actual center of each fiducial marker to that represented by neuronavigation were recorded. Finally, accuracy at multiple deep targets was assessed by using a life-sized human head stereotactic phantom in which fiducials were placed on deformable foam to mimic scalp.
RESULTS: System-generated accuracy measurements were significantly better for the iMRI group (mean +/- SEM = 1.04 +/- 0.05 mm) than for the standard group (1.82 +/- 0.09 mm; P < .001). Measured distances from the actual center of scalp fiducial markers to that represented by neuronavigation were also significantly smaller for iMRI (1.72 +/- 0.10 mm) in comparison with the standard group (3.17 +/- 0.22 mm; P < .001). Deep accuracy in the phantom model was significantly better with iMRI (1.67 +/- 0.12 mm) than standard imaging (2.28 +/- 0.14 mm; P = .003).
CONCLUSION: Frameless stereotactic accuracy is increased by using high-field iMRI compared with standard preoperative imaging.

DOI： 10.1227/neu.0b013e31826a88a9

Increased frameless stereotactic accuracy with high-field intraoperative magnetic resonance imaging. Reviewed International journal

Shota Tanaka, Ross C Puffer, Jason M Hoover, Stephan J Goerss, Laura M Haugen, Kiaran McGee, Ian F Parney

Neurosurgery 71 ( 2 Suppl Operative ) ons321-7; discussion ons327-8 - 328 2012.12

Language：English Publishing type：Research paper (scientific journal) Publisher：LIPPINCOTT WILLIAMS & WILKINS

BACKGROUND: Frameless stereotaxy commonly registers preoperative magnetic resonance imaging (MRI) to patients by using surface scalp anatomy or adhesive fiducial scalp markers. Patients' scalps may shift slightly between preoperative imaging and final surgical positioning with pinion placement, introducing error. This might be reduced when frameless stereotaxy is performed in a high-field intraoperative MRI (iMRI), as patients are positioned before imaging. This could potentially improve accuracy. OBJECTIVE: To compare frameless stereotactic accuracy using a high-field iMRI with that using standard preoperative MRI. METHODS: Data were obtained in 32 adult patients undergoing frameless stereotactic-guided brain tumor surgery. Stereotactic images were obtained with 1.5T MRI scanner either preoperatively (14 patients) or intraoperative (18 patients). System-generated accuracy measurements and distances from the actual center of each fiducial marker to that represented by neuronavigation were recorded. Finally, accuracy at multiple deep targets was assessed by using a life-sized human head stereotactic phantom in which fiducials were placed on deformable foam to mimic scalp. RESULTS: : System-generated accuracy measurements were significantly better for the iMRI group (mean ± SEM = 1.04 ± 0.05 mm) than for the standard group (1.82 ± 0.09 mm; P < .001). Measured distances from the actual center of scalp fiducial markers to that represented by neuronavigation were also significantly smaller for iMRI (1.72 ± 0.10 mm) in comparison with the standard group (3.17 ± 0.22 mm; P < .001). Deep accuracy in the phantom model was significantly better with iMRI (1.67 ± 0.12 mm) than standard imaging (2.28 ± 0.14 mm; P = .003). CONCLUSION: Frameless stereotactic accuracy is increased by using high-field iMRI compared with standard preoperative imaging.

DOI： 10.1227/NEU.0b013e31826a88a9

Presentation, management, and outcome of elderly patients with newly-diagnosed anaplastic astrocytoma. Reviewed International journal

Shota Tanaka, Fredric B Meyer, Jan C Buckner, Joon H Uhm, Elizabeth S Yan, Ian F Parney

Journal of neuro-oncology 110 ( 2 ) 227 - 35 2012.11

Language：English Publishing type：Research paper (scientific journal) Publisher：SPRINGER

Few studies have assessed the presentation, management, and outcome of anaplastic astrocytoma (AA) in elderly patients in the temozolomide era. We retrospectively reviewed 42 consecutive patients aged >65 years with newly-diagnosed AA who underwent surgical resection or biopsy between 2003 and 2008. Median age and KPS score were 73 years (range, 66-88) and 80 (range, 50-90), respectively. Thirty-two patients (76 %) presented with focal deficits. Twenty patients (48 %) experienced seizures before surgery. Tumor enhanced diffusely in 24 patients (57 %) and sparsely in 18 patients (43 %). Biopsy (79 %) was more common than resection. Post-operatively, new persistent neurological deficits and hemorrhage were seen in two (4.8 %) and three (7.1 %) patients, respectively. Complete follow-up data regarding adjuvant treatment was available in 31 patients. Sixteen patients (52 %) received temozolomide and radiation therapy (RT), while nine patients (29 %) received RT alone. Chemotherapy-related grade 3/4 hematologic complication rate was 17.6 %. Median overall survival (OS) was 6.5 months (12 months with resection; 3.5 months with biopsy). Resection (P = 0.007, risk ratio = 0.21) and sparse enhancement (P = 0.007, risk ratio = 0.13) were associated with longer OS in multivariate analysis. Similarly, chemoradiation was associated with longer survival compared to RT alone (OS: P = 0.01, progression-free survival (PFS): P = 0.02) after adjusting for age, KPS, enhancement, and surgery. Resection was associated with longer survival among elderly patients with AA, although this could reflect selection bias. Similarly, adding chemotherapy to RT was associated with prolonged survival but carried important complication risks. In appropriately selected AA patients, aggressive treatments with radical resection and chemoradiation may be appropriate even in this age group.

DOI： 10.1007/s11060-012-0956-7

Gamma Knife surgery for the management of glomus tumors: a multicenter study. Reviewed International journal

Jason P Sheehan, Shota Tanaka, Michael J Link, Bruce E Pollock, Douglas Kondziolka, David Mathieu, Christopher Duma, A Byron Young, Anthony M Kaufmann, Heyoung McBride, Peter A Weisskopf, Zhiyuan Xu, Hideyuki Kano, Huai-che Yang, L Dade Lunsford

Journal of neurosurgery 117 ( 2 ) 246 - 54 2012.8

Language：English Publishing type：Research paper (scientific journal) Publisher：AMER ASSOC NEUROLOGICAL SURGEONS

OBJECT: Glomus tumors are rare skull base neoplasms that frequently involve critical cerebrovascular structures and lower cranial nerves. Complete resection is often difficult and may increase cranial nerve deficits. Stereotactic radiosurgery has gained an increasing role in the management of glomus tumors. The authors of this study examine the outcomes after radiosurgery in a large, multicenter patient population. METHODS: Under the auspices of the North American Gamma Knife Consortium, 8 Gamma Knife surgery centers that treat glomus tumors combined their outcome data retrospectively. One hundred thirty-four patient procedures were included in the study (134 procedures in 132 patients, with each procedure being analyzed separately). Prior resection was performed in 51 patients, and prior fractionated external beam radiotherapy was performed in 6 patients. The patients' median age at the time of radiosurgery was 59 years. Forty percent had pulsatile tinnitus at the time of radiosurgery. The median dose to the tumor margin was 15 Gy. The median duration of follow-up was 50.5 months (range 5-220 months). RESULTS: Overall tumor control was achieved in 93% of patients at last follow-up; actuarial tumor control was 88% at 5 years postradiosurgery. Absence of trigeminal nerve dysfunction at the time of radiosurgery (p = 0.001) and higher number of isocenters (p = 0.005) were statistically associated with tumor progression-free tumor survival. Patients demonstrating new or progressive cranial nerve deficits were also likely to demonstrate tumor progression (p = 0.002). Pulsatile tinnitus improved in 49% of patients who reported it at presentation. New or progressive cranial nerve deficits were noted in 15% of patients; improvement in preexisting cranial nerve deficits was observed in 11% of patients. No patient died as a result of tumor progression. CONCLUSIONS: Gamma Knife surgery was a well-tolerated management strategy that provided a high rate of long-term glomus tumor control. Symptomatic tinnitus improved in almost one-half of the patients. Overall neurological status and cranial nerve function were preserved or improved in the vast majority of patients after radiosurgery.

DOI： 10.3171/2012.4.JNS11214

Acute epidural spinal hemorrhage from vasculitis: resolution with immunosuppression. Reviewed International journal

Jeffrey T Jacob, Shota Tanaka, Christopher P Wood, Eelco F Wijdicks, Giuseppe Lanzino

Neurocritical care 16 ( 2 ) 311 - 5 2012.4

Language：English Publishing type：Research paper (scientific journal) Publisher：HUMANA PRESS INC

BACKGROUND: Angiographic vasculitis affecting the spine has been rarely described. The use of immunosuppression as a primary treatment and a review of the literature is presented. METHODS: Case report. RESULTS: A 61-year-old female presented with sudden onset back pain and headache. The patient was found to have acute spinal epidural hemorrhage and subsequent work-up demonstrated angiographic spinal vasculitis. Immunosuppression with cyclophosphamide resulted in clinical and radiographic improvement. CONCLUSIONS: Immunomodulating therapy should be considered in the management of select patients with spinal vasculitis which may lead to improved clinical outcome and potentially disease resolution.

DOI： 10.1007/s12028-011-9667-8

Safety of concurrent bevacizumab therapy and anticoagulation in glioma patients. Reviewed International journal

Andrew D Norden, Julia Bartolomeo, Shota Tanaka, Jan Drappatz, Abigail S Ciampa, Lisa M Doherty, Debra C Lafrankie, Sandra Ruland, Eudocia C Quant, Rameen Beroukhim, Patrick Y Wen

Journal of neuro-oncology 106 ( 1 ) 121 - 5 2012.1

Language：English Publishing type：Research paper (scientific journal) Publisher：SPRINGER

Venous thromboembolic events (VTE) are common in glioma patients and are typically treated with anticoagulant medications. The anti-angiogenic agent bevacizumab (BVZ) increases the risks of both VTE and hemorrhagic complications. Little is known about the hemorrhagic risk of anticoagulation in glioma patients receiving BVZ. We reviewed medical records from 282 BVZ-treated patients at our center and identified 64 who received concurrent anticoagulant therapy. The risk and severity of hemorrhagic complications were assessed. Fisher's exact test was used to compare the risk of hemorrhage between subjects who received and did not receive anticoagulants. Forty-seven patients (73%) had glioblastoma, 15 (23%) anaplastic glioma, and 2 (3%) other tumors. Thirteen (20%) and 51 (80%) patients received warfarin and low-molecular-weight heparin, respectively. The indication for anticoagulation was deep venous thrombosis in 37 patients (58%), pulmonary embolism in 22 (34%), and both in 5 (8%). Thirteen patients (20%) experienced hemorrhage, of which four hemorrhages (6%) were serious (grade ≥ 3): one patient had grade 5 intracerebral hemorrhage (ICH), one grade 4 ICH, one grade 3 epistaxis, and one grade 3 gastrointestinal hemorrhage. ICH was seen in seven patients (11%), of which five (8%) were grade 1. Among 218 patients who did not receive anticoagulants, there were two (1%) serious hemorrhages (both grade 4 ICH). Both the serious hemorrhage rate and overall ICH rate were higher in patients who received anticoagulants (P = 0.03 and 0.02, respectively). Anticoagulant use during BVZ therapy may increase the risk of hemorrhage in glioma patients, although it is generally well tolerated.

DOI： 10.1007/s11060-011-0642-1