Intraventricular Rituximab in Pediatric CD20-positive Refractory Primary Central Nervous System Lymphoma.

Primary central nervous system lymphoma (PCNSL) is a rare and aggressive type of extranodal non-Hodgkin lymphoma that carries an unsatisfactory prognosis. Treating refractory PCNSL is challenging because of resistance to conventional cytotoxic and intrathecal chemotherapies. Therefore, novel therapeutic approaches are needed. Here, we report a 12-year-old boy with CD20-positive PCNSL, which was refractory to combination chemotherapy and intravenous rituximab. However, the patient achieved complete remission after repeated intraventricular rituximab administration. The results of this case indicate that intraventricular rituximab is an effective option to treat refractory PCNSL in children.

Three-dimensional multimodality fusion imaging as an educational and planning tool for deep-seated meningiomas.

INTRODUCTION: The utility of surgical simulation with three-dimensional multimodality fusion imaging (3D-MFI) has been demonstrated. However, its potential in deep-seated brain lesions remains unknown. The aim of this study was to investigate the impact of 3D-MFI in deep-seated meningioma operations. MATERIAL AND METHODS: Fourteen patients with deeply located meningiomas were included in this study. We constructed 3D-MFIs by fusing high-resolution magnetic resonance (MR) and computed tomography (CT) images with a rotational digital subtraction angiogram (DSA) in all patients. The surgical procedure was simulated by 3D-MFI prior to operation. To assess the impact on neurosurgical education, the objective values of surgical simulation by 3D-MFIs/virtual reality (VR) video were evaluated. To validate the quality of 3D-MFIs, intraoperative findings were compared. The identification rate (IR) and positive predictive value (PPV) for the tumor feeding arteries and involved perforating arteries and veins were also assessed for quality assessment of 3D-MFI. RESULTS: After surgical simulation by 3D-MFIs, near-total resection was achieved in 13 of 14 (92.9%) patients without neurological complications. 3D-MFIs significantly contributed to the understanding of surgical anatomy and optimal surgical view (p < .0001) and learning how to preserve critical vessels (p < .0001) and resect tumors safety and extensively (p < .0001) by neurosurgical residents/fellows. The IR of 3D-MFI for tumor-feeding arteries and perforating arteries and veins was 100% and 92.9%, respectively. The PPV of 3D-MFI for tumor-feeding arteries and perforating arteries and veins was 98.8% and 76.5%, respectively. CONCLUSIONS: 3D-MFI contributed to learn skull base meningioma surgery. Also, 3D-MFI provided high quality to identify critical anatomical structures within or adjacent to deep-seated meningiomas. Thus, 3D-MFI is promising educational and surgical planning tool for meningiomas in deep-seated regions.

Genome-wide methylation profiles in primary intracranial germ cell tumors indicate a primordial germ cell origin for germinomas.

Intracranial germ cell tumors (iGCTs) are the second most common brain tumors among children under 14 in Japan. The World Health Organization classification recognizes several subtypes of iGCTs, which are conventionally subclassified into pure germinoma or non-germinomatous GCTs. Recent exhaustive genomic studies showed that mutations of the genes involved in the MAPK and/or PI3K pathways are common in iGCTs; however, the mechanisms of how different subtypes develop, often as a mixed-GCT, are unknown. To elucidate the pathogenesis of iGCTs, we investigated 61 GCTs of various subtypes by genome-wide DNA methylation profiling. We showed that pure germinomas are characterized by global low DNA methylation, a unique epigenetic feature making them distinct from all other iGCTs subtypes. The patterns of methylation strongly resemble that of primordial germ cells (PGC) at the migration phase, possibly indicating the cell of origin for these tumors. Unlike PGC, however, hypomethylation extends to long interspersed nuclear element retrotransposons. Histologically and epigenetically distinct microdissected components of mixed-GCTs shared identical somatic mutations in the MAPK or PI3K pathways, indicating that they developed from a common ancestral cell.

Characteristics and surgical strategies for posterior clinoid process meningioma: two case reports and review of the literature.

Clinical and radiological features or characteristics of posterior clinoid process (PCP) meningiomas have rarely been described because of their extreme scarcity and terminological confusion. Therefore, the strategies in the surgical intervention for PCP meningiomas have not been well established. Moreover, the presence of deep and critical neuroanatomical structures and relatively high morbidity, which can be difficult to predict preoperatively, make their surgical excision more challenging. We report two surgical cases of PCP meningioma and discuss the appropriate assessment of preoperative features and surgical strategies with review of the literature. Our study suggests that PCP meningioma may be characterized by the anterior displacement of internal carotid artery, and infero-laterally shifted posterior communicating arteries, and homonymous hemianopsia, a distinctive clinical feature. One of the key issues in PCP meningioma surgery is preservation of the optic nerve. Unlocking the optic nerve by anterior clinoidectomy and dissection, the falciform ligament is the important step to preserve vision for larger tumors. Complication with the perforators is also hazardous of these challenging surgeries than anterior clinoid meningiomas for their specific neuroanatomical structures and might not be feasible to avoid even with additional techniques and critical monitoring. A combination and multi-staged-surgical approach can be options of tailor-made surgical strategy in cases with tumor adhesion to the perforators.

Recurrent neomorphic mutations of MTOR in central nervous system and testicular germ cell tumors may be targeted for therapy.

Germ cell tumors constitute a heterogeneous group that displays a broad spectrum of morphology. They often arise in testes; however, extragonadal occurrence, in particular brain, is not uncommon, and whether they share a common pathogenesis is unknown. We performed whole exome sequencing in 41 pairs of central nervous system germ cell tumors (CNS GCTs) of various histology and their matched normal tissues. We then performed targeted sequencing of 41 selected genes in a total of 124 CNS GCTs, 65 testicular germ cell tumors (tGCTs) and 8 metastatic GCTs to the CNS. The results showed that mutually exclusive mutations of genes involved in the MAPK pathway were most common (48.4 %), typically in KIT (27.4 %), followed by those in the PI3K pathway (12.9 %), particularly in MTOR (6.5 %), among the 124 CNS GCTs. Pure germinomas and non-germinomatous germ cell tumors (NGGCTs), as well as CNS and testicular GCTs, showed similar mutational profiles, suggesting that GCTs share a common molecular pathogenesis. Mutated MTOR identified in CNS GCTs upregulated phosphorylation of the AKT pathway proteins including AKT and 4EBP1 in nutrient-deprived conditions and enhanced soft-agar colony formation; both events were suppressed in a dose-dependent manner by addition of the MTOR inhibitor pp242. Our findings indicate that the dominant genetic drivers of GCTs regardless of the site of origin are activation of the MAPK and/or PI3K pathways by somatic point mutations. Mutated MTOR represents a potential target for novel targeted therapies for refractory GCTs.

Multimodal approach to detect osseous involvement in meningioma: additional value of (18)F-fluoride PET/CT for conventional imaging.

PURPOSE: To compare the diagnostic performance of fluorine 18 ((18)F) fluoride positron emission tomography (PET)/computed tomography (CT) with that of conventional imaging (CT and magnetic resonance [MR] imaging) in evaluating the osseous involvement in meningioma. MATERIALS AND METHODS: The study was approved by the ethics committee and institutional review board and was conducted according to the Declarations of Helsinki and Tokyo. Written informed consent was obtained from all patients. A retrospective comparative study between (18)F-fluoride PET/CT and conventional imaging was conducted to detect osseous involvement in patients with a verified diagnosis of meningioma. Osseous involvement was verified by using definitive surgery (including drilling or careful sampling of the skull in all patients). The diagnostic performance, determined by calculating the sensitivity, specificity, positive predictive value ( PPV positive predictive value ), negative predictive value ( NPV negative predictive value ), and accuracy, was assessed. RESULTS: Data sets from a total of 78 patients with proven meningioma were compared. Osseous involvement was histopathologically confirmed in 25 patients (32%). The sensitivity, specificity, PPV positive predictive value , NPV negative predictive value , and accuracy were 92.0%, 86.8%, 76.7%, 95.8%, and 88.5% for (18)F-fluoride PET/CT and 64.0%, 83.0%, 64.0%, 83.0%, and 76.9% for conventional imaging, respectively. The receiver operating characteristic ( ROC receiver operating characteristic ) analysis revealed that the area under the ROC receiver operating characteristic curve ( Az area under the ROC curve ) value of (18)F-fluoride PET/CT was significantly greater than that of conventional imaging (0.965 ± 0.02 [standard error] vs 0.703 ± 0.066 [standard error], P < .0001). CONCLUSION: An approach using (18)F-fluoride PET/CT improves preoperative detection of osseous involvement. In those without abnormal (18)F-fluoride uptake within the skull, the patient may proceed directly to conventional surgery. However, a positive finding of osseous involvement at (18)F-fluoride PET/CT should prompt confirmation by drilling or sampling of bone.

Tumor hypoxia and microscopic diffusion capacity in brain tumors: a comparison of (62)Cu-Diacetyl-Bis (N4-Methylthiosemicarbazone) PET/CT and diffusion-weighted MR imaging.

OBJECTIVES: The aim of this study was to clarify the relationship between tumor hypoxia and microscopic diffusion capacity in primary brain tumors using (62)Cu-Diacetyl-Bis (N4-Methylthiosemicarbazone) ((62)Cu-ATSM) PET/CT and diffusion-weighted MR imaging (DWI). METHODS: This study was approved by the institutional human research committee and was HIPAA compliant, and informed consent was obtained from all patients. (62)Cu-ATSM PET/CT and DWI were performed in a total of 40 primary brain tumors of 34 patients with low grade glioma (LGG, n = 13), glioblastoma (GBM, n = 20), and primary central nervous system lymphoma (PCNSL, n = 7). (62)Cu-ATSM PET/CT parameters and apparent diffusion coefficient (ADC) obtained by DWI were compared. RESULTS: High intensity signals by (62)Cu-ATSM PET/CT and DWI in patients with GBM and PCNSL, and low intensity signals in LGG patients were observed. An inverse correlation was found between maximum SUV (SUVmax) and minimum ADC (ADCmin) (r = -0.583, p < 0.0001), and between tumor/brain ratio (T/Bratio) and ADCmin for all tumors (r = -0.532, p < 0.0001). Both SUVmax and T/Bratio in GBM were higher than LGG (p < 0.0001 and p < 0.0001), and those in PCNSL were also higher than GBM (p = 0.033 and p = 0.044). The ADCmin was lower in GBM (p = 0.011) and PCNSL (p = 0.01) than in LGG, while no significant difference was found between GBM and PCNSL (p = 0.90). CONCLUSION: Tumor hypoxia assessed by (62)Cu-ATSM PET/CT correlated with microscopic diffusion capacity obtained by DWI in brain tumors. Both (62)Cu-ATSM PET/CT and DWI were considered feasible imaging methods for grading glioma. However, (62)Cu-ATSM PET/CT provided additional diagnostic information to differentiate between GBM and PCNSL.

Occipitocervical fusion with relief of odontoid invagination: atlantoaxial distraction method using cylindrical titanium cage for basilar invagination--case report.

A 65-year-old woman presented with basilar invagination manifesting as neck pain, dysesthesia around the lips, and truncal ataxia. The radiological findings demonstrated invagination of the odontoid process into the medulla oblongata and vertical atlantoaxial subluxation with C1 assimilation. The clivo-axial angle was 88° and the cervicomedullary angle was 115°, indicating severe basilar invagination. We planned occipitocervical fusion with atlantoaxial distraction using a cylindrical titanium cage. C2 pedicle screws were inserted, and the atlantoaxial joint was opened to translocate the odontoid process downward. A cylindrical titanium cage packed with local bone graft was inserted into the opened facet joint space. Occipital-C2 fusion was completed by fastening the occipital bone plates with pedicle screws using titanium rods. Postoperatively, the apex of the odontoid process descended by 7 mm, and the clivo-axial and cervicomedullary angles opened to 112° and 125°, respectively. Invagination of the odontoid process into the medulla oblongata was relieved. The preoperative symptoms improved, and she remained symptom-free without requiring anterior decompression over 2 years. Bone fusion of the atlantoaxial joints was completed with sustained facet distraction 12 months after the surgery, and adequate relief of the basilar invagination was maintained. The atlantoaxial distraction method using a cylindrical titanium cage can be a useful option in posterior fusion surgery for basilar invagination.

Upregulating mutations in the TERT promoter commonly occur in adult malignant gliomas and are strongly associated with total 1p19q loss.

Telomere lengthening is one of the key events in most cancers, and depends largely on telomerase activation. Telomerase activation is a well-known phenomenon in gliomas; however, its mechanism remains obscure. In this study, we investigated the presence of mutations in the promoter of the telomerase reverse transcriptase (TERT) gene in a series of 546 gliomas. We found a high incidence of mutually exclusive mutations located at two hot spots, C228T and C250T, in all subtypes of gliomas (55 %). The frequency of mutation was particularly high among primary glioblastomas (70 %) and pure oligodendroglial tumors (74 %), while relatively low in diffuse astrocytomas and anaplastic astrocytomas (19 and 25 %, respectively). The expression level of TERT in tumors carrying those mutations was on average 6.1 times higher than that of wild-type tumors, indicating that the mutated promoter leads to upregulation of TERT. TERT promoter mutations were observed in almost all tumors harboring concurrent total 1p19q loss and IDH1/2 mutations (98 %). Otherwise TERT promoter mutations were mostly observed among IDH wild-type tumors. Most EGFR amplifications (92 %) were also associated with TERT promoter mutations. Our data indicate that mutation of the TERT promoter is one of the major mechanisms of telomerase activation in gliomas. The unique pattern of TERT promoter mutations in relation to other genetic alterations suggests that they play distinct roles in the pathogenesis of oligodendroglial and astrocytic tumors. Our results shed a new light on the role of telomerase activation in the development of adult gliomas.

Posterior transjugular and transcervical approach for glomus tumours within the head and neck.

Glomus tumours within the head and neck are highly vascular in nature and are surrounded by vital neurovascular structures. The aim of this study is to review the step-by-step surgical techniques for a posterior transjugular approach and transcervical approach and to clarify the advantages of these approaches in the treatment of glomus tumours within the head and neck. The advantage of these approaches is that a wide operative field from the jugular bulb to the cervical portion can be obtained. In addition, the bloodless operative field that is achieved by the preoperative embolisation appeared to contribute to reducing the risk of cranial nerve injury.

Trans-membrane peptide therapy for malignant glioma by use of a peptide derived from the MDM2 binding site of p53.

A new strategy is required against glioblastoma, a highly aggressive and fatal disease. In recent studies the protein transduction domains (PTDs) of some proteins, which are able to cross biological membranes, have been identified as critical domains for protein transduction. Here, we show that this protein-delivery system is a powerful tool for transduction of p53, a biologically active tumor-suppressor protein, into cancer cells, to suppress their proliferation. A 15-amino-acid sequence corresponding to the mouse double minutes clone2 (MDM2) binding site of p53 was shown by cell proliferation assay and MTT assay to have a proliferation-inhibiting effect on glioma cells. The polyarginine11R as a PTD, nuclear localization sequence (NLS), and laminin (Ln) fused to the p53 peptide corresponding to the MDM2 binding site (p53-NLS-Ln-11R) effectively penetrated the plasma membrane of the glioma cells and was translocated into the nucleus. At a 10 µM: concentration, this peptide inhibited the proliferation of human glioma cells, whether the p53 gene had mutated or not. These results suggest that this protein-transduction method using the p53-NSL-Ln-11R peptide may become a promising glioma therapy as an alternative gene therapy.

Axonal regeneration and functional recovery driven by endogenous Nogo receptor antagonist LOTUS in a rat model of unilateral pyramidotomy.

The adult mammalian central nervous system (CNS) rarely recovers from injury. Myelin fragments contain axonal growth inhibitors that limit axonal regeneration, thus playing a major role in determining neural recovery. Nogo receptor-1 (NgR1) and its ligands are among the inhibitors that limit axonal regeneration. It has been previously shown that the endogenous protein, lateral olfactory tract usher substance (LOTUS), antagonizes NgR1-mediated signaling and accelerates neuronal plasticity after spinal cord injury and cerebral ischemia in mice. However, it remained unclear whether LOTUS-mediated reorganization of descending motor pathways in the adult brain is physiologically functional and contributes to functional recovery. Here, we generated LOTUS-overexpressing transgenic (LOTUS-Tg) rats to investigate the role of LOTUS in neuronal function after damage. After unilateral pyramidotomy, motor function in LOTUS-Tg rats recovered significantly compared to that in wild-type animals. In a retrograde tracing study, labeled axons spanning from the impaired side of the cervical spinal cord to the unlesioned hemisphere of the red nucleus and sensorimotor cortex were increased in LOTUS-Tg rats. Anterograde tracing from the unlesioned cortex also revealed enhanced ipsilateral connectivity to the impaired side of the cervical spinal cord in LOTUS-Tg rats. Moreover, electrophysiological analysis showed that contralesional cortex stimulation significantly increased ipsilateral forelimb movement in LOTUS-Tg rats, which was consistent with the histological findings. According to these data, LOTUS overexpression accelerates ipsilateral projection from the unlesioned cortex and promotes functional recovery after unilateral pyramidotomy. LOTUS could be a future therapeutic option for CNS injury.

Oxidative stress-responsive apoptosis inducing protein (ORAIP) plays a critical role in cerebral ischemia/reperfusion injury.

Oxidative stress is known to play a critical role in the pathogenesis of various disorders, especially in ischemia/reperfusion (I/R) injury. We identified an apoptosis-inducing humoral factor and named this novel post translationally modified secreted form of eukaryotic translation initiation factor 5A (eIF5A) "oxidative stress-responsive apoptosis inducing protein" (ORAIP). The purpose of this study was to investigate the role of ORAIP in the mechanisms of cerebral I/R injury. Hypoxia/reoxygenation induced expression of ORAIP in cultured rat cerebral neurons, resulting in extensive apoptosis of these cells, which was largely suppressed by neutralizing anti-ORAIP monoclonal antibody (mAb) in vitro. Recombinant-ORAIP induced extensive apoptosis of cerebral neurons. Cerebral I/R induced expression of ORAIP in many neurons in a rat tandem occlusion model in vivo. In addition, we analyzed the effects of intracerebroventricular administration of neutralizing anti-ORAIP mAb on the development of cerebral infarction. Cerebral I/R significantly increased ORAIP levels in cerebrospinal fluid. Treatment with intracerebroventricular administration of neutralizing anti-ORAIP mAb reduced infarct volume by 72%, and by 55% even when started after reperfusion. These data strongly suggest that ORAIP plays a pivotal role and will offer a critical therapeutic target for cerebral I/R injury induced by thrombolysis and thrombectomy for acute ischemic stroke.

The risk of hemorrhage after radiosurgery for cerebral arteriovenous malformations.

BACKGROUND: Angiography shows that stereotactic radiosurgery obliterates most cerebral arteriovenous malformations after a latency period of a few years. However, the effect of this procedure on the risk of hemorrhage is poorly understood. METHODS: We performed a retrospective observational study of 500 patients with malformations who were treated with radiosurgery with use of a gamma knife. The rates of hemorrhage were assessed during three periods: before radiosurgery, between radiosurgery and the angiographic documentation of obliteration of the malformation (latency period), and after angiographic obliteration. RESULTS: Forty-two hemorrhages were documented before radiosurgery (median follow-up, 0.4 year), 23 during the latency period (median follow-up, 2.0 years), and 6 after obliteration (median follow-up, 5.4 years). As compared with the period between diagnosis and radiosurgery, the risk of hemorrhage decreased by 54 percent during the latency period (hazard ratio, 0.46; 95 percent confidence interval, 0.26 to 0.80; P=0.006) and by 88 percent after obliteration (hazard ratio, 0.12; 95 percent confidence interval, 0.05 to 0.29; P<0.001). The risk was significantly reduced during the period after obliteration, as compared with the latency period (hazard ratio, 0.26; 95 percent confidence interval, 0.10 to 0.68; P=0.006). The reduction was greater among patients who presented with hemorrhage than among those without hemorrhage at presentation and similar in analyses that took into account the delay in confirming obliteration by means of angiography and analyses that excluded data obtained during the first year after diagnosis. CONCLUSIONS: Radiosurgery significantly decreases the risk of hemorrhage in patients with cerebral arteriovenous malformations, even before there is angiographic evidence of obliteration. The risk of hemorrhage is further reduced, although not eliminated, after obliteration.

Region-specific proliferative response of neural progenitors to exogenous stimulation by growth factors following ischemia.

The most effective way to augment neural progenitor proliferation after ischemia is still unknown. We administered various agents into the rat cerebral ventricle after transient global ischemia and compared the neural progenitor response in the anterior subventricular zone (aSVZ), dentate gyrus subgranular zone, posterior periventricle, and hypothalamus. We demonstrated that cocktail administration of epidermal growth factor (EGF) and fibroblast growth factor-2 (FGF-2) remarkably increased the numbers of neural progenitors in all four regions examined. The addition of Notch ligand DLL4 to the cocktail elicited the largest progenitor response in the aSVZ and hypothalamus. Our results suggest that EGF and FGF-2, combined with DLL4, represent the universally applicable regimen for the expansion of the neural progenitor pool following ischemia.

Long-term outcome following radical temporal bone resection for lateral skull base malignancies: a neurosurgical perspective.

OBJECT: Primary temporal bone malignancy is a rare form of tumor for which the therapeutic strategy remains controversial. In this study, the authors reviewed their experience with radical temporal bone resection (TBR) of such lesions and analyzed the long-term results to provide treatment recommendations. METHODS: Between 1994 and 2006, 17 patients (10 men and 7 women) underwent total or subtotal TBR for primary temporal bone malignancies. Tumors were graded according to the University of Pittsburgh system. The effects of surgical margins and tumor extensions on patient survival were analyzed using the Kaplan-Meier method. RESULTS: All tumors, except 1, were graded T4 (most advanced). Subtotal TBR was performed in 14 patients, and total TBR was performed in 3. The surgical margin was tumor negative in 10 patients and tumor positive in 7. For large tumors extending into the infratemporal fossa or encroaching on the jugular foramen, orbitozygomatic (3 patients) and posterior transjugular (4 patients) approaches were combined with the standard approach, and en bloc resection with a negative margin was achieved in all cases but 1. The follow-up time ranged from 0.3-11.6 years (mean 3.3 years). The 5-year recurrence-free and disease-specific survival rates were 67.5 and 60.1%, respectively. When a negative surgical margin was achieved, the survival rates improved to 100 and 89%, respectively. CONCLUSIONS: The neurosurgical skull base technique could improve the probability of en bloc resection with a tumor-free margin for extensive temporal bone malignancies, which would cure a subset of patients. The active participation of neurosurgeons would improve patient care in this field.

Cyst formation after stereotactic radiosurgery for intracranial meningioma.

The authors report 2 cases of delayed cyst formation after gamma knife radiosurgery for 3 meningioma lesions. All 3 lesions reported here had a distinctive feature before gamma knife treatment of small and spotty intratumoral cysts. One patient experienced an intriguing clinical course of spontaneous regression of the enlarged cyst, and 2 of the 3 lesions became symptomatic requiring surgical interventions. Cyst formation as a postradiosurgical complication is relatively rare in meningioma patients in the literature, and its pathogenesis is unclear. We describe herein the clinical courses of these 2 patients and review the relevant literature in this report. From our experience of these 2 cases, we suggest that we should be aware of the possible development of spotty intratumoral cysts into larger cysts after stereotactic radiosurgery and that we should carefully observe such patients after the treatment.

Prognostic implications of 62Cu-diacetyl-bis (N4-methylthiosemicarbazone) PET/CT in patients with glioma.

OBJECTIVE: The potential of positron emission tomography/computed tomography using 62Cu-diacetyl-bis (N4-methylthiosemicarbazone) (62Cu-ATSM PET/CT), which was originally developed as a hypoxic tracer, to predict therapeutic resistance and prognosis has been reported in various cancers. Our purpose was to investigate prognostic value of 62Cu-ATSM PET/CT in patients with glioma, compared to PET/CT using 2-deoxy-2-[18F]fluoro-D-glucose (18F-FDG). METHOD: 56 patients with glioma of World Health Organization grade 2-4 were enrolled. All participants had undergone both 62Cu-ATSM PET/CT and 18F-FDG PET/CT within mean 33.5 days prior to treatment. Maximum standardized uptake value and tumor/background ratio were calculated within areas of increased radiotracer uptake. The prognostic significance for progression-free survival and overall survival were assessed by log-rank test and Cox's proportional hazards model. RESULTS: Disease progression and death were confirmed in 37 and 27 patients in follow-up periods, respectively. In univariate analysis, there was significant difference of both progression-free survival and overall survival in age, tumor grade, history of chemoradiotherapy, maximum standardized uptake value and tumor/background ratio calculated using 62Cu-ATSM PET/CT. Multivariate analysis revealed that maximum standardized uptake value calculated using 62Cu-ATSM PET/CT was an independent predictor of both progression-free survival and overall survival (p < 0.05). In a subgroup analysis including patients of grade 4 glioma, only the maximum standardized uptake values calculated using 62Cu-ATSM PET/CT showed significant difference of progression-free survival (p < 0.05). CONCLUSIONS: 62Cu-ATSM PET/CT is a more promising imaging method to predict prognosis of patients with glioma compared to 18F-FDG PET/CT.