11C-methionine- and 18F-FDG-PET double-negative metastatic brain tumor from lung adenocarcinoma with paradoxical high 18F-FDG uptake: A case report.

Background: Imaging with 18F-fluorodeoxyglucose (FDG)-positron emission tomography (PET) and 11C-methionine (MET)-PET can delineate primary and metastatic brain tumors. Lesion size affects the sensitivity of both scans and histopathological features can also influence FDG-PET, but the effects on MET-PET have not been elucidated. Case Description: We report an unusual case of metastatic brain tumors without accumulation of FDG or MET, contrasting with high FDG uptake in the primary lung lesion. The brain lesions were identified as adenocarcinoma with a more mucus-rich background, contributing to the indistinct accumulation of both FDG and MET. Conclusion: Histopathological characteristics can affect both MET and FDG accumulation, leading to findings contradicting those of the primary lesion.

Efficacy of cancer-specific anti-podoplanin CAR-T cells and oncolytic herpes virus G47Δ combination therapy against glioblastoma.

Glioblastoma is a devastating malignant brain tumor with a poor prognosis despite standard therapy. Podoplanin (PDPN), a type I transmembrane mucin-like glycoprotein that is overexpressed in various cancers, is a potential therapeutic target for the treatment of glioblastoma. We previously reported the efficacy of chimeric antigen receptor (CAR)-T cells using an anti-pan-PDPN monoclonal antibody (mAb; NZ-1)-based third-generation CAR in a xenograft mouse model. However, NZ-1 also reacted with PDPN-expressing normal cells, such as lymphatic endothelial cells, pulmonary alveolar type I cells, and podocytes. To overcome possible on-target-off-tumor effects, we produced a cancer-specific mAb (CasMab, LpMab-2)-based CAR. LpMab-2 (Lp2) reacted with PDPN-expressing cancer cells but not with normal cells. In this study, Lp2-CAR-transduced T cells (Lp2-CAR-T) specifically targeted PDPN-expressing glioma cells while sparing the PDPN-expressing normal cells. Lp2-CAR-T also killed patient-derived glioma stem cells, demonstrating its clinical potential against glioblastoma. Systemic injection of Lp2-CAR-T cells inhibited the growth of a subcutaneous glioma xenograft model in immunodeficient mice. Combination therapy with Lp2-CAR-T and oncolytic virus G47Δ, a third-generation recombinant herpes simplex virus (HSV)-1, further inhibited the tumor growth and improved survival. These findings indicate that the combination therapy of Lp2-CAR-T cells and G47Δ may be a promising approach to treat glioblastoma.

Impact of the extent of resection on the survival of patients with grade II and III gliomas using awake brain mapping.

PURPOSE: The aim of this study was to assess the effect of the extent of resection (EOR) of tumors on survival in a series of patients with grade II and III gliomas (GII/III-gliomas) who underwent awake brain mapping. METHODS: We retrospectively analyzed 126 patients with GII/III-gliomas in the dominant and non-dominant hemisphere who underwent awake brain surgery at the same institution between December 2012 and May 2020. RESULTS: EOR cut-off values for improved progression-free survival (PFS) were determined by a receiver operator characteristic (ROC) analysis of 5-year PFS. The ROC for EOR showed a cut-off value of ≥ 85.3%. The median PFS rate of patients with GII/III-gliomas in the group with an EOR ≥ 100%, including supratotal resection (n = 47; median survival [MS], not reached), was significantly higher than that in the group with an EOR < 90% (n = 52; MS, 43.1 months; 95% CI 37.7-48.5 months; p = 0.03). In patients with diffuse astrocytomas and anaplastic astrocytomas, the group with EOR ≥ 100%, including supratotal resection (n = 25; MS, not reached), demonstrated a significantly better PFS rate than did the group with an EOR < 100% (n = 45; MS, 35.8 months; 95% CI 19.9-51.6 months; p = 0.03). Supratotal or gross total resection was correlated with better PFS in IDH-mutant type of diffuse astrocytomas and anaplastic astrocytomas (n = 19; MS, not reached vs. n = 35; MS, 40.6 months; 95% CI 22.3-59.0 months; p = 0.02). By contrast, supratotal or gross total resection was not associated with longer PFS rates in patients with IDH-wild type of diffuse astrocytomas and anaplastic astrocytomas. CONCLUSIONS: The present study demonstrates a significant association between tumor EOR and survival in patients with GII/III gliomas. The EOR cut-off value for 5-year PFS was ≥ 85.3%. It is noteworthy that supratotal or gross total resection significantly correlated with better PFS in IDH-mutant type of WHO grade II and III astrocytic tumors. In light of our finding that EOR did not correlate with PFS in patients with aggressive IDH-wild type of diffuse astrocytomas and anaplastic astrocytomas, we suggest treatments that are more intensive will be needed for the control of these tumors.

Effects of insular resection on interactions between cardiac interoception and emotion recognition.

The insular cortex is considered an important region for feeling emotions through interoception. Most studies that report the role of the insula in integrating interoception and emotion have used neuroimaging techniques such as functional magnetic resonance imaging (fMRI); however, there are limited neuropsychological studies. The effects of insular lesions on emotion and interoception have not been suitably investigated. In this study, we examined the role of the insular cortex in cardiac interoception and recognizing emotions from facial expressions by comparing them pre- and post-operatively in patients with glial tumors or brain metastases associated with the insular lobe. Although no significant difference in interoceptive accuracy was observed between the two phases, there were significant associations between the changes in interoceptive accuracy and sensitivity to expressions of anger and happiness. An increased error rate in the heartbeat counting task in the post-operation phase was associated with a decreased accuracy in recognizing anger and happiness. Since most patients had left insula lesions, generalizability of the findings to patients with right lesions is a future subject. To the best of our knowledge, this is the first study to examine the change in interoception and emotion after insular resection in humans. The study results indicate that removal of the insula affects the recognition of emotions such as anger and happiness through interoceptive processing.

Intraoperative seizure outcome of levetiracetam combined with perampanel therapy in patients with glioma undergoing awake brain surgery.

OBJECTIVE: This study aimed to evaluate the efficacy of levetiracetam (LEV) combined with perampanel (PER) therapy for intraoperative seizure treatment to determine whether a combination of LEV and PER can aid in the prevention of intraoperative intractable seizures during awake surgery. METHODS: The authors performed a retrospective cohort study in 78 consecutive patients with glioma who underwent awake surgery using intraoperative direct electrical stimulation mapping. To prevent intraoperative seizures, 50 patients were treated with the antiepileptic drug LEV only (LEV group) from January 2017 to January 2019, while the remaining 28 patients were treated with LEV plus PER (LEV + PER group) between March 2019 and January 2020. LEV (1000-3000 mg) and/or PER (2-4 mg) were administered before the surgery. RESULTS: Preoperative seizures with International League Against Epilepsy (ILAE) class II-VI occurred in 44% of the patients in the LEV group and in 35.7% of patients in the LEV + PER group, with no significant difference between groups (p = 0.319). Total intraoperative seizures occurred in 18 patients (36.0%) in the LEV therapy group and in 2 patients (7.1%) in the LEV + PER group (p = 0.009). Of these, there were no patients (0%) with intractable seizures in the LEV + PER group. Regarding factors that influence intraoperative seizures in glioma patients during awake brain surgery, multivariate logistic regression models revealed that the occurrence of intraoperative seizures was significantly related to the involvement of motor-related regions (positive vs negative, HR 6.98, 95% CI 1.71-28.56, p = 0.007), preoperative seizure (ILAE class II-VI vs ILAE class I, HR 4.44, 95% CI 1.22-16.11, p = 0.024), and LEV + PER group (positive vs negative, HR 0.07, 95% CI 0.01-0.44, p = 0.005). Treatment-related adverse effects were rare and mild, including sleepiness, tiredness, and dizziness in both treatment groups. CONCLUSIONS: This study demonstrates that LEV + PER therapy is significantly associated with a lower risk of intraoperative seizures compared with LEV therapy alone in patients with glioma during awake brain mapping. These findings will help neurosurgeons conduct safe and reliable awake surgeries and reduce the rate of intraoperative intractable seizures during such procedures.

Survival Benefit of Supratotal Resection in a Long-term Survivor of IDH-wildtype Glioblastoma: A Case Report and Literature Review.

Glioblastoma multiforme (GBM) is an aggressive cancer type, with fewer than 3-5% of patients surviving for more than 3 years. We describe a 48-year-old right-handed man who presented with generalized seizure attacks. Magnetic resonance imaging (MRI) revealed a heterogeneous gadolinium-enhancing lesion in the left inferior parietal lobule. The patient underwent awake surgery, and tumor resection included abnormalities on T2-weighted MRI, with subcortical mapping used to identify the deep functional boundaries. After supratotal resection, the tumor was diagnosed as GBM without isocitrate dehydrogenase (IDH) 1 and 2 mutations. At a follow-up evaluation, 9 years and 2 months after the surgery, the patient appeared healthy, and no relapse or recurrence was observed. We present the case of a long-term survivor of IDH-wildtype GBM. This case suggests that supratotal resection with intraoperative awake brain mapping can improve survival without impairing the patient's neurological functions.

Long-term survival in patients with primary intracranial germ cell tumors treated with surgery, platinum-based chemotherapy, and radiotherapy: a single-institution study.

OBJECTIVE: The current study aimed to evaluate the treatment outcomes and toxicities of patients with intracranial germ cell tumors (GCTs). METHODS: This study retrospectively included 110 consecutive patients (70 patients in the germinomatous group and 40 patients in the nongerminomatous GCT [NGGCT] groups) receiving surgery, platinum-based chemotherapy, and radiotherapy for newly diagnosed primary intracranial GCTs. In the authors' protocol, patients with GCTs were further divided into the following four groups: the germinomatous group and the NGGCT groups (mature teratoma, intermediate prognosis, or poor prognosis). RESULTS: The median overall survival (OS) and progression-free survival (PFS) rates of the patients in the germinomatous group were significantly higher than those in the NGGCT group (p < 0.001). The 5-, 10-, and 20-year OS rates in the germinomatous group were 97.1%, 95.7%, and 93.2%, respectively, with a median follow-up of 11.0 years. On the contrary, the 5-, 10-, and 20-year OS rates in the NGGCT group were 67.3%, 63.4%, and 55.4%, respectively. The 5-, 10-, and 20-year PFS rates were 91.4%, 86.6%, and 86.6%, respectively, in the germinomatous group, whereas those of the NGGCT group were approximately 67.4%, 60.2%, and 53.5%, respectively. Based on the four types of classification in our study, the 5-, 10-, and 20-year OS rates in the NGGCT intermediate prognosis group were 78.9%, 71.8%, and 53.8%, respectively. On the contrary, the 3- and 5-year OS rates in the NGGCT poor prognosis group were 42.9% and 34.3%, respectively. Moreover, toxicities with the treatment of intracranial GCTs were found to be tolerable in the present study population. The multivariate survival models for OS in the NGGCT intermediate prognosis and poor prognosis groups demonstrated that only the alpha-fetoprotein status was significantly associated with worsened OS (HR 3.88, 95% CI 1.29-11.66; p = 0.02). CONCLUSIONS: The authors found that platinum-based chemotherapy and radiotherapy result in favorable survival outcomes in patients with germinomatous GCTs. Clinical outcomes were still unfavorable in the NGGCT intermediate prognosis and poor prognosis groups; therefore, a new protocol that increases the survival rate of patients belonging in both groups should be considered.

Navigated repetitive transcranial magnetic stimulation as preoperative assessment in patients with brain tumors.

We aimed to investigate clinical parameters that affected the results of navigated repetitive transcranial magnetic stimulation (nrTMS) language mapping by comparing the results of preoperative nrTMS language mapping with those of direct cortical stimulation (DCS) mapping. In the prospective, non-randomized study, patients had to meet all of the following inclusion criteria: the presence of left- or right-side brain tumors in the vicinity of or inside the areas anatomically associated with language functions; awake brain surgery scheduled; and age >18 years. Sixty one patients were enrolled, and this study included 42 low-grade gliomas and 19 high-grade gliomas (39 men, 22 women; mean age, 41.1 years, range 18-72 years). The tumor was located in the left and right hemisphere in 50 (82.0%) and 11 (18.0%) patients, respectively. In the 50 patients with left-side gliomas, nrTMS language mapping showed 81.6% sensitivity, 59.6% specificity, 78.5% positive predictive value, and 64.1% negative predictive value when compared with the respective DCS values for detecting language sites in all regions. We then investigated how some parameters, including age, tumor type, tumor volume, and the involvement of anatomical language-related regions, affected different subpopulations. Based on the receiver operating curve statistics, subgroup analysis showed that the non-involvement of language-related regions afforded significantly better the area under the curve (AUC) values (AUC = 0.81, 95% confidence interval (CI): 0.74-0.88) than the involvement of language-related regions (AUC = 0.58, 95% CI: 0.50-0.67; p < 0.0001). Our findings suggest that nrTMS language mapping could be a reliable method, particularly in obtaining responses for cases without tumor-involvement of classical perisylvian language areas.

Trautmann-focused mastoidectomy for a simple, safe presigmoid approach: technical note.

The presigmoid approach (PSA) is selected to obtain more lateral access to cerebellopontine angle tumors, brainstem cavernous malformations, or vertebrobasilar artery aneurysms than the standard retrosigmoid approach. However, mastoidectomy for the PSA can be considered time-consuming and to carry a higher risk of complications due to the anatomical complexity of the region. The authors established a method of minimized mastoidectomy focused on exposing Trautmann's triangle as the corridor for the PSA while maximizing procedural simplicity and safety and maintaining a sufficient operative view. The authors present their method of minimized mastoidectomy in a cadaver dissection and operative cases, showing potential as a useful option for the PSA.

Preoperative predictive factors affecting return to work in patients with gliomas undergoing awake brain mapping.

PURPOSE: This study aimed to investigate the preoperative predictive factors affecting return to work in patients with gliomas in the left cerebral hemisphere undergoing awake surgery. METHODS: We retrospectively reviewed 50 consecutive glioma patients who underwent awake surgery from January 2012 to July 2017. Adult patients older than 18 years, who reported working prior to surgery, were recruited for this study. RESULTS: Comparing sociodemographic, disease-related and preoperative neurocognitive variables of glioma patients who returned to work and those who did not, binomial logistic regression models for preoperative predictors affecting return to work revealed significant differences in age and sole breadwinner status as sociodemographic variables, tumour volume as a disease-related variable, and Verbal IQ, Performance IQ, general memory, attention/concentration, and working memory as neurocognitive variables. Multivariate logistic regression models demonstrated that the independent factors associated with propriety of returning to work 1 year after surgery was the sociodemographic variable sole breadwinner status (yes vs no; OR = 15.00, 95% CI 2.22-101.35, p = 0.01), the disease-related variable tumour volume (per 1 cm3; OR = 0.98, 95% CI 0.96-0.99, p = 0.04), and the preoperative neurocognitive variable general memory (≥ 100 vs < 100; OR = 21.70, 95% CI 2.60-183.94, p = 0.01). CONCLUSIONS: Our results suggest that three predictive factors including sole breadwinner status, tumour volume and general memory that can be assessed in the preoperative stage substantially contribute to returning to work in patients with gliomas in the left cerebral hemisphere, 1 year after awake surgery.

Anterior insular cortex stimulation and its effects on emotion recognition.

With the objective to investigate the role of the insula in recognizing emotion, we performed direct electrical stimulation over the anterior insular cortex during awake surgery while simultaneously delivering an emotional sensitivity task. We registered 18 consecutive patients with brain tumors associated with the insular lobe, who were undergoing tumor resection. An emotional sensitivity task was employed to measure the patients' ability to recognize emotions from facial expressions before, during, and after awake surgery. Furthermore, we performed voxel-based lesion symptom mapping (VLSM) to identify the association between relevant brain lesions and emotion recognition. When we performed direct electrical stimulation over the anterior insular cortex during awake surgery, the results showed that the ability to recognize anger was significantly enhanced with the presence of anterior insular stimulation (p < 0.05). Comparing the performance in the emotional sensitivity task before and after surgery, the performance in the anger condition became worse (p < 0.01), but became better in the sadness condition after surgery (p < 0.01). In the case of anger recognition, lower scores in the correct response index were associated with lesions involving the left insula in the VLSM study. Direct electrical stimulation over the anterior insular cortex enhanced anger recognition in patients with insular tumors. In contrast, accuracy of anger recognition was significantly reduced, and sadness was improved, when the performance of emotional sensitivity was compared pre- and post-surgery. Our findings suggest that the insular cortex is involved in changes in emotion recognition, including anger and sadness recognition by modulating arousal level that is closely connected with interoception.

Neurocognitive and functional outcomes in patients with diffuse frontal lower-grade gliomas undergoing intraoperative awake brain mapping.

OBJECTIVE: Lower-grade gliomas (LGGs) are often observed within eloquent regions, which indicates that tumor resection in these areas carries a potential risk for neurological disturbances, such as motor deficit, language disorder, and/or neurocognitive impairments. Some patients with frontal tumors exhibit severe impairments of neurocognitive function, including working memory and spatial awareness, after tumor removal. The aim of this study was to investigate neurocognitive and functional outcomes of frontal LGGs in both the dominant and nondominant hemispheres after awake brain mapping. METHODS: Data from 50 consecutive patients with diffuse frontal LGGs in the dominant and nondominant hemispheres who underwent awake brain surgery between December 2012 and September 2018 were retrospectively analyzed. The goal was to map neurocognitive functions such as working memory by using working memory tasks, including digit span testing and N-back tasks. RESULTS: Due to awake language mapping, the frontal aslant tract was frequently identified as a functional boundary in patients with left superior frontal gyrus tumors (76.5%). Furthermore, functional boundaries were identified while evaluating verbal and spatial working memory function by stimulating the dorsolateral prefrontal cortex using the digit span and visual N-back tasks in patients with right superior frontal gyrus tumors (7.1%). Comparing the preoperative and postoperative neuropsychological assessments from the Wechsler Adult Intelligence Scale-Third Edition (WAIS-III) and Wechsler Memory Scale-Revised (WMS-R), significant improvement following awake surgery was observed in mean Perceptual Organization (Z = -2.09, p = 0.04) in WAIS-III scores. Postoperative mean WMS-R scores for Visual Memory (Z = -2.12, p = 0.03) and Delayed Recall (Z = -1.98, p = 0.04) were significantly improved compared with preoperative values for every test after awake surgery. No significant deterioration was noted with regard to neurocognitive functions in a comprehensive neuropsychological test battery. In the postoperative course, early transient speech and motor disturbances were observed in 30.0% and 28.0% of patients, respectively. In contrast, late permanent speech and motor disturbances were observed in 0% and 4.0%, respectively. CONCLUSIONS: It is noteworthy that no significant postoperative deterioration was identified compared with preoperative status in a comprehensive neuropsychological assessment. The results demonstrated that awake functional mapping enabled favorable neurocognitive and functional outcomes after surgery in patients with diffuse frontal LGGs.

Characterization of Intraoperative Motor Evoked Potential Monitoring for Surgery of the Pediatric Population with Brain Tumors.

OBJECTIVE: We investigated the relationship between the reliability of the transcranial or transcortical motor evoked potential (MEP) response and age in pediatric patients aged ≤15 years with brain tumor. METHODS: We retrospectively analyzed the data from 60 consecutive patients aged ≤15 years who had undergone brain tumor surgery that involved intraoperative MEP monitoring from October 2009 to May 2016. RESULTS: A total of 41 patients with reliable signals (MEP response group) and 19 patients without reliable signals (MEP nonresponse group) were included in the present study. The mean age at surgery, body height, and body weight were significantly greater in the MEP response group than in the MEP nonresponse group. When the MEP success rates during surgery of the pediatric population with brain tumors were analyzed in relation to patient age, the transcortical MEP success rate in the 0-5-year age group (10.0%) was significantly lower than that in the 6-10-year age group (71.4%; P = 0.009) and that in the 11-15-year age group (75.0%; P = 0.015). CONCLUSIONS: The transcortical MEP response was monitored less successfully during brain tumor surgery in patients aged ≤5 years than in patients aged 6-15 years. Although MEP monitoring techniques can be applied during surgery of pediatric populations with brain tumors similar to that used for adult patients, the limitations of the low transcortical MEP response rate in young patients should be considered.

Supratotal Resection of Diffuse Frontal Lower Grade Gliomas with Awake Brain Mapping, Preserving Motor, Language, and Neurocognitive Functions.

OBJECTIVE: Extended margin tumor resection beyond the abnormal area detected by magnetic resonance imaging, defined as supratotal resection, could improve the outcomes of patients with lower grade gliomas (LGGs). The aim of the present study was to assess the surgical outcomes of awake brain mapping to achieve supratotal resection with determination of the normal brain tissue boundaries beyond the tumor of frontal LGGs, in both dominant and nondominant hemispheres. METHODS: We analyzed the data from 9 patients with diffuse frontal LGGs who had undergone supratotal resection with awake surgery from January 2016 to November 2017. RESULTS: The frontal aslant tract was identified as the functional boundary in 4 of 5 left frontal tumor cases (80%). Working memory impairments during dorsolateral prefrontal cortex stimulation with digit span and/or visual N-back tasks were detected in all 4 patients (100%) with right-frontal tumor. The neurocognitive outcomes were significantly improved after surgery, as shown by the mean Wechsler adult intelligence scale III scores for verbal intelligence quotient (P = 0.04) and verbal comprehension (P = 0.03) and the mean Wechsler memory scale-revised scores for generalized memory (P = 0.04) and delayed recall (P = 0.04). CONCLUSIONS: The results of the present study have provided evidence that awake mapping can enable the preservation of higher neurocognitive function, including working memory and spatial cognition in patients with nondominant right frontal tumors. Despite the small number of cases, our findings suggest the surgical benefit of awake surgery for supratotal resection of diffuse frontal LGGs.

Podoplanin: An emerging cancer biomarker and therapeutic target.

Podoplanin (PDPN) is a transmembrane receptor glycoprotein that is upregulated on transformed cells, cancer associated fibroblasts and inflammatory macrophages that contribute to cancer progression. In particular, PDPN increases tumor cell clonal capacity, epithelial mesenchymal transition, migration, invasion, metastasis and inflammation. Antibodies, CAR-T cells, biologics and synthetic compounds that target PDPN can inhibit cancer progression and septic inflammation in preclinical models. This review describes recent advances in how PDPN may be used as a biomarker and therapeutic target for many types of cancer, including glioma, squamous cell carcinoma, mesothelioma and melanoma.

Immunohistochemical ATRX expression is not a surrogate for 1p19q codeletion.

The IDH-mutant and 1p/19q co-deletion (1p19q codel) provides significant diagnostic and prognostic value in lower-grade gliomas. As ATRX mutation and 1p19q codel are mutually exclusive, ATRX immunohistochemistry (IHC) may substitute for 1p19q codel, but this has not been comprehensively examined. In the current study, we performed ATRX-IHC in 78 gliomas whose ATRX statuses were comprehensively determined by whole exome sequencing. Among the 60 IHC-positive and 18 IHC-negative cases, 86.7 and 77.8% were ATRX-wildtype and ATRX-mutant, respectively. ATRX mutational patterns were not consistent with ATRX-IHC. If our cohort had only used IDH status and IHC-based ATRX expression for diagnosis, 78 tumors would have been subtyped as 48 oligodendroglial tumors, 16 IDH-mutant astrocytic tumors, and 14 IDH-wildtype astrocytic tumors. However, when the 1p19q codel test was performed following ATRX-IHC, 8 of 48 ATRX-IHC-positive tumors were classified as "1p19q non-codel" and 3 of 16 ATRX-IHC-negative tumors were classified as "1p19q codel"; a total of 11 tumors (14%) were incorrectly classified. In summary, we observed dissociation between ATRX-IHC and actual 1p19q codel in 11 of 64 IDH-mutant LGGs. In describing the complex IHC expression of ATRX somatic mutations, our results indicate the need for caution when using ATRX-IHC as a surrogate of 1p19q status.

A novel high-sensitivity assay to detect a small fraction of mutant IDH1 using droplet digital PCR.

Detection of mutations in the isocitrate dehydrogenase 1 (IDH1) gene is useful for accurate diagnosis of lower grade gliomas, as described in the 2016 World Health Organization classification of tumors of the central nervous system. Conventional analysis tools, including Sanger DNA sequencing and immunohistochemistry, might fail to detect a small fraction of mutant IDH1 owing to their limited sensitivity. Considering that lower grade gliomas are infiltrative in nature, a highly sensitive detection assay for IDH1 mutation is required for their accurate diagnosis. In this study, we successfully established a droplet digital PCR (ddPCR) system to detect a small fraction of IDH1 mutation. We could detect 0.05% of mutant IDH1 allele in 30 ng DNA. Using this assay, we could detect a small fraction of mutant IDH1 in a glioma case, identified as a wildtype tumor according to the conventional assays. Additionally, in a small amount of DNA derived from the cerebrospinal fluid, we could detect an IDH1 mutation. In conclusion, the ddPCR system is useful to identify a small fraction of IDH1 mutation in diffuse infiltrative gliomas. This might be useful for precision medicine of these gliomas in the near future and also for the non-invasive diagnosis of these gliomas.

Comparing the Efficacy of DeVIC Therapy and High-dose Methotrexate Monotherapy with Whole-brain Radiation Therapy for Newly-diagnosed Primary Central Nervous System Lymphoma: A Single Institution Study.

BACKGROUND/AIM: In the current study, we aimed to compare DeVIC (dexamethasone, etoposide, ifosfamide and carboplatin) chemotherapy with high-dose methotrexate (HD-MTX) monotherapy plus whole-brain radiation therapy (WBRT) for newly-diagnosed primary central nervous system lymphoma (PCNSL), in terms of their efficacies and tolerability. PATIENTS AND METHODS: A total of 21 consecutive patients with PCNSL were treated with DeVIC therapy and WBRT, between 2002 and 2010. From 2010 to 2014, 14 consecutive patients with PCNSL were treated with HD-MTX followed by WBRT. RESULTS: Overall response rates of complete and partial response for initial chemotherapy were significantly better with DeVIC therapy (95.2%) than with HD-MTX monotherapy (50%). Furthermore, one-year and two-year progression-free survival (PFS) rates were better in the DeVIC cohort than in the HD-MTX cohort. DeVIC therapy yielded higher early response rates, longer PFS, and manageable adverse events, and may be potentially better for the treatment of cases that are refractory to MTX-based therapy. CONCLUSION: Our retrospective clinical study revealed that DeVIC therapy is comparable with that of HD-MTX monotherapy plus WBRT, for newly diagnosed PCNSL.

A novel all-in-one intraoperative genotyping system for IDH1-mutant glioma.

IDH1 gene mutation has been demonstrated to be an oncogenic driver in a majority of lower-grade gliomas (LGGs). In contrast to other central nervous neoplasms and normal brain tissue without IDH1 mutation, almost 80% of LGGs exhibit IDH1 mutation. Therefore, expeditious detection of IDH1 mutation is useful, not only for intraoperative diagnosis of these gliomas but also for determination of the border between the tumor and normal brain tissue. In this study, we established a rapid genotyping assay with a simple DNA extraction method, involving only incubation of the tumor specimen with Tris-EDTA buffer, which can be easily performed in an operating room. In all 11 tested cases, we could identify the IDH1 status within 90-100 min intraoperatively. In a case of anaplastic astrocytoma, IDH-mutant, we could detect the tumor border by IDH1 profiling. In addition, with this assay, we could detect IDH1 mutation using cell-free tumor DNA derived from cerebrospinal fluid in a case of glioblastoma, IDH-mutant. Considering that clinical trials of mutated IDH1 inhibitors are ongoing, less-invasive intraoperative IDH1 gene profiling might be useful for decision making of the overall treatment strategy of LGGs. Our assay might be a useful tool for precision medicine and surgery of IDH1-mutant gliomas.