Modular organization is fundamental to cortical processing, but its presence is human association cortex is unknown. We characterized phoneme processing with 128-1024 channel micro-arrays at 50-200µm pitch on superior temporal gyrus of 7 patients. High gamma responses were highly correlated within ~1.7mm diameter modules, sharply delineated from adjacent modules with distinct time-courses and phoneme-selectivity. We suggest that receptive language cortex may be organized in discrete processing modules.

OBJECTIVE Whether obesity is associated with meningioma and the impact of obesity by gender has been debated. The primary objective of this study was to investigate differences in BMI between male and female patients undergoing craniotomy for meningioma and compare those with patients undergoing craniotomy for other intracranial tumors. The secondary objective was to compare meningioma location and progression-free survival (PFS) between obese and nonobese patients in a multi-institutional cohort. METHODS National data were obtained from the National Surgical Quality Improvement Program (NSQIP) database. Male and female patients were analyzed separately. Patients undergoing craniotomies for meningioma were compared with patients of the same sex undergoing craniotomies for other intracranial tumors. Institutional data from two academic centers were collected for all male and an equivalent number of female meningioma patients undergoing meningioma resection. Multivariate regression controlling for age was used to determine differences in meningioma location. Kaplan-Meier curves and log-rank tests were computed to investigate differences in PFS. RESULTS From NSQIP, 4163 male meningioma patients were compared with 24,266 controls, and 9372 female meningioma patients were compared with 21,538 controls. Male and female patients undergoing meningioma resection were more likely to be overweight or obese compared with patients undergoing craniotomy for other tumors, with the odds ratio increasing with increasing weight class (all p < 0.0001). In the multi-institutional cohort, meningiomas were more common along the skull base in male patients (p = 0.0123), but not in female patients (p = 0.1246). There was no difference in PFS between obese and nonobese male (p = 0.4104) or female (p = 0.5504) patients. Obesity was associated with increased risk of pulmonary embolism in both male and female patients undergoing meningioma resection (p = 0.0043). CONCLUSIONS Male and female patients undergoing meningioma resection are more likely to be obese than patients undergoing craniotomy for other intracranial tumors. Obese males are more likely to have meningiomas in the skull base compared with other locations, but this association was not found in females. There was no significant difference in PFS among obese patients. The mechanism by which obesity increases meningioma incidence remains to be determined.

Purpose To inquire into clinical practices perceived to mitigate patients' intraoperative distress during awake craniotomies. Methods This mixed-methods study involved administration of Amsterdam Preoperative Anxiety and Information Scale and PTSD Checklist prior to the awake craniotomy to evaluate anxiety and information-seeking related to the procedure and symptoms of PTSD. Generalized Anxiety Disorder Scale and Depression Module of the Patient Health Questionnaire were administered before and after the procedure to evaluate generalized anxiety and depression. Patient interviews were conducted 2-weeks postprocedure and included a novel set of patient experience scales to assess patients' recollection of intraoperative pain, overall distress, anxiety, distress due to noise, perception of empowerment, perception of being well-prepared, overall satisfaction with anaesthesia management, and overall satisfaction with the procedure. Qualitative data were analysed using conventional content analysis. Results Participants (n = 14) had undergone an awake craniotomy for tissue resection due to primary brain tumours or medically-refractory focal epilepsy. Validated self-report questionnaires demonstrated reduced levels of generalized anxiety (pre mean = 8.66; SD = 6.41; post mean= 4.36; SD = 4.24) following the awake craniotomy. Postprocedure interviews revealed very high satisfaction with the awake craniotomy and anaesthesia management and minimal levels of intraoperative pain, anxiety, and distress. The most stressful aspects of the procedure included global recognition of medical diagnosis, anxiety provoked by unfamiliar sights, sounds, and sensations, a perception of a lack of information or misinformation, and long periods of immobility. Important factors in alleviating intraoperative distress included the medical team's ability to promote patient perceptions of control, establish compassionate relationships, address unfamiliar intraoperative sensations, and deliver effective anaesthesia management. Conclusion Compassion, communication, and patient perception of control were critical in mitigating intraoperative distress. Clinical practice recommendations with implications for all clinicians involved in patient care during awake craniotomies are provided. Use of these interventions and strategies to reduce distress are important to holistic patient care and patient experiences of care and may improve the likelihood of optimal brain mapping procedures to improve clinical outcomes during awake craniotomies.

- OBJECTIVE: We examined the utility of passive high gamma mapping (HGM) as an adjunct to conventional awake brain mapping during glioma resection. We compared functional and survival outcomes before and after implementing intraoperative HGM. - METHODS: This was a retrospective cohort study of 75 patients who underwent a first-time, awake craniotomy for glioma resection. Patients were stratified by whether their operation occurred before or after the implementation of a U.S. Food and Drug AdministrationLapproved high-gamma mapping tool in July 2017. - RESULTS: The preimplementation and postimplementation cohorts included 28 and 47 patients, respectively. Median intraoperative time (261 vs. 261 minutes, P = 0.250) and extent of resection (97.14% vs. 98.19%, P = 0.481) were comparable between cohorts. Median Karnofsky performance status at initial follow-up was similar between cohorts (P = 0.650). Multivariable Cox regression models demonstrated an adjusted hazard ratio for overall survival of 0.10 (95% confidence interval: 0.02e0.43, P = 0.002) for the postimplementation cohort relative to the preimplementation cohort. Progression-free survival adjusted for insular involvement showed an adjusted hazard ratio of 1.00 (95% confidence interval: 0.49e2.06, P = 0.999) following HGM implementation. Falling short of statistical significance, prevalence of intraoperative seizures and/or afterdischarges decreased after HGM implementation as well (12.7% vs. 25%, P = 0.150). - CONCLUSIONS: Our results tentatively indicate that passive HGM is a safe and potentially useful adjunct to electrical stimulation mapping for awake cortical mapping, conferring at least comparable functional and survival outcomes with a nonsignificant lower rate of intraoperative epileptiform events. Considering the limitations of our study design and patient cohort, further investigation is needed to better identify optimal use cases for HGM.

2079 Background: Bizaxofusp (MDNA55) is designed to selectively deliver a potent toxin payload to tumor cells by targeting the IL-4 receptor (IL-4R) overexpressed by GBM, but not normal brain. Localized delivery of bizaxofusp minimizes risk of off-target toxicities and systemic exposure while eliciting effective tumor cell killing. Bizaxofusp was evaluated using convection-enhanced delivery in MDNA55-05 (NCT02858895), a single-arm, open-label, multi-center Ph2 study in nonresectable recurrent GBM (rGBM). Methods: The study population comprised of de novo IDH wild-type GBM patients with 1st or 2nd relapse that were non-resectable. Forty-four patients were administered a single treatment of bizaxofusp (range: 18-240 μg). The primary endpoint was OS; secondary endpoints were safety and tumor response. IL-4R expression in tumor biopsies was determined using a validated assay. OS was compared to an eligibility matched external control arm (emECA) of 81 contemporaneous rGBM subjects receiving standard of care. The emECA was further refined by propensity-score balancing (pbECA) to the bizaxofusp arm based on known prognostic factors, resulting in a weighted sample size of 40.8. OS was defined as time from relapse (to unify index date in both arms) or treatment start (for analysis of tumor response) to death/censor. Tumor response was assessed following RANO and mRANO criteria. Results: Bizaxofusp showed an acceptable safety profile at doses up to 240 μg. TRAEs were primarily neurological or aggravation of pre-existing neurological deficits associated with GBM and were manageable with standard measures. Results showed that IL-4R expression did not impact mOS except in patients receiving low doses of bizaxofusp. The bizaxofusp arm had significantly longer median OS (mOS) than contemporaneous emECA (12.4 vs 7.7 months; HR: 0.64, 95% CI 0.46-0.93; p = 0.02). Survival benefit was also evident when compared to the pbECA: (12.4 vs 7.2 months; HR: 0.72, 95% CI 0.46-1.1; p = 0.27). Patients with tumor control (SD or PR/CR, n=21) had significantly longer mOS than patients with tumor progression (n=23) (16.7 vs 8.5 months; HR = 0.5, 95% CI 0.27-0.9; p = 0.01). Among patients with tumor control who had pseudoprogression (PsP) per mRANO, mOS (22.8 months) was significantly longer than patients with tumor progression (HR: 0.49, 95% CI 0.25-0.98; p = 0.049). Conclusions: Bizaxofusp achieved significant OS benefit in patients with nonresectable rGBM compared to contemporaneous emECA. Patients who experienced tumor control, including those with PsP, showed significantly longer survival than patients with tumor progression. Phase 3 ready registrational trial will comprise a high dose bizaxofusp arm and a hybrid control arm with 1/3 randomized subjects and 2/3 pmECA. Clinical trial information: NCT02858895 .

BACKGROUND:Papillary tumor of the pineal region (PTPR) is a rare neuroepithelial tumor with Central Nervous System (CNS) World Health Organization (WHO) grade II or III classification. Due to its rarity, there is no clear census on treatment. The purpose of this study is to identify the optimal treatment plan focused on extending overall survival (OS). METHODS:This is an institutional case series with review of the literature. Fifty-three publications were analyzed. Only cases with histological diagnosis of PTPR were included. Data collected included demographics, treatment modalities, disease progression, and OS. RESULTS:The analysis included 105 patients from the literature and 3 new cases (54 female, 50%) with an average age of 33.1 years (range 1-73 years). The average lesion size was 26.4 mm (range 5-50 mm) in longest axis. All patients underwent an initial resection. There were 46 cases of surgery alone. The remaining cases received adjuvant therapy including radiation (RT), stereotactic radiosurgery (SRS), chemotherapy (CT), or RT and CT. The average follow-up was 61.4 months (range 1-240 months). OS at 1 year was 96.9%, at 5 years was 87.5%, and at 10 years was 80.2%. Overall progression-free survival (PFS) was 57.4%. Statistical significance was observed in PFS in the surgery plus SRS group and surgery plus CT and RT group. Surgery with SRS had the best PFS (75%), and OS at 1 year (100%) and 5 years (88.9%). Surgery with CT and RT had the best OS at 10 years (85.7%). CONCLUSION:We describe a case series and literature review of PTPR to help guide the most effective treatment strategies for this rare disease entity. We recommend surgery followed by SRS as the treatment of choice because of its best PFS and 5-year survival rates. We would also recommend adding chemotherapy in the event of disease progression or recurrence as adjuvant radiation and chemotherapy provided the best 10-year survival.

Modular organization at approximately 1 mm scale could be fundamental to cortical processing, but its presence in human association cortex is unknown. Using custom-built, high-density electrode arrays placed on the cortical surface of 7 patients undergoing awake craniotomy for tumor excision, we investigated receptive speech processing in the left (dominant) human posterior superior temporal gyrus. Responses to consonant-vowel syllables and noise-vocoded controls recorded with 1,024 channel micro-grids at 200 μm pitch demonstrated roughly circular domains approximately 1.7 mm in diameter, with sharp boundaries observed in 128 channel linear arrays at 50 μm pitch, possibly consistent with a columnar organization. Peak latencies to syllables in different modules were bimodally distributed centered at 252 and 386 ms. Adjacent modules were sharply delineated from each other by their distinct time courses and stimulus selectivity. We suggest that receptive language cortex may be organized in discrete processing modules.

Patients with high-grade glioma (HGG) have an extremely poor prognosis compounded by a lack of advancement in clinical care over the past few decades. Regardless of classification, most newly diagnosed patients receive the same treatment, radiation and temozolomide (RT/TMZ). We developed a functional precision oncology test that prospectively identifies individual patient’s response to this treatment regimen. Tumor tissues isolated from patients with newly diagnosed HGG enrolled in 3D PREDICT REGISTRY were evaluated for response to chemotherapeutic agents using the 3D Predict™ Glioma test. Patients receiving RT/TMZ were followed for 2 years. Clinical outcomes including imaging, assessments, and biomarker measurements were compared to patient matched test-predicted therapy response. Median survival between test-predicted temozolomide responders and test-predicted temozolomide non-responders revealed a statistically significant increase in progression-free survival when using the test to predict response across multiple subgroups including HGG (5.8 months), glioblastoma (4.7 months), and MGMT unmethylated glioblastoma (4.7 months). Overall survival was also positively separated across the subgroups at 7.6, 5.1, and 6.3 months respectively. The strong correlation of 3D Predict Glioma test results with clinical outcomes demonstrates that this functional test is prognostic in patients treated with RT/TMZ and supports aligning clinical treatment to test-predicted response across varying HGG subgroups.

Additional example of patient experiencing immune-related pseudoprogression (PsP)

Correlation between duration of clinical benefit (DOCB) and overall survival (OS) for the standard RANO, iRANO, and mRANO criteria. (A) Correlation between radiographic DOCB using the standard RANO criteria applied to local measurements and OS for patients who died. (B) Correlation between radiographic DOCB using the iRANO criteria applied to local measurements and OS for patients who died. (C) Correlation between radiographic DOCB using the mRANO criteria applied to local measurements and OS for patients who died. (D) Correlation between radiographic DOCB using the standard RANO criteria applied to IRF-determined measurements and OS for patients who died. (E) Correlation between radiographic DOCB using the iRANO criteria applied to IRF-determined measurements and OS for patients who died. (F) Correlation between radiographic DOCB using the mRANO criteria applied to IRF-determined measurements and OS for patients who died. Solid circles = patients who progressed. Open circles = patients who were censored (not used in correlation analysis, only for visualization purposes).

Medicenna Imaging Charter for Independent Radiologic Review of MDNA55-05.

BACKGROUND:Steroids are used ubiquitously in the preoperative management of patients with brain tumor. The rate of improvement in focal deficits with steroids and the prognostic value of such a response are not known. OBJECTIVE:To determine the rate at which focal neurological deficits respond to preoperative corticosteroids in patients with brain metastases and whether such an improvement could predict long-term recovery of neurological function after surgery. METHODS:Patients with brain metastases and related deficits in language, visual field, or motor domains who received corticosteroids before surgery were identified. Characteristics between steroid responders and nonresponders were compared. RESULTS:Ninety six patients demonstrated a visual field (13 patients), language (19), or motor (64) deficit and received dexamethasone in the week before surgery (average cumulative dose 43 mg; average duration 2.7 days). 38.5% of patients' deficits improved with steroids before surgery, while 82.3% of patients improved by follow-up. Motor deficits were more likely to improve both preoperatively ( P = .014) and postoperatively ( P = .010). All 37 responders remained improved at follow-up whereas 42 of 59 (71%) of nonresponders ultimately improved ( P < .001). All other clinical characteristics, including dose and duration, were similar between groups. CONCLUSION:A response to steroids before surgery is highly predictive of long-term improvement postoperatively in brain metastasis patients with focal neurological deficits. Lack of a response portends a somewhat less favorable prognosis. Duration and intensity of therapy do not seem to affect the likelihood of response.

BACKGROUND:MDNA55 is an interleukin 4 receptor (IL4R)-targeting toxin in development for recurrent GBM, a universally fatal disease. IL4R is overexpressed in GBM as well as cells of the tumor microenvironment. High expression of IL4R is associated with poor clinical outcomes. METHODS:MDNA55-05 is an open-label, single-arm phase IIb study of MDNA55 in recurrent GBM (rGBM) patients with an aggressive form of GBM (de novo GBM, IDH wild-type, and nonresectable at recurrence) on their 1st or 2nd recurrence. MDNA55 was administered intratumorally as a single dose treatment (dose range of 18 to 240 ug) using convection-enhanced delivery (CED) with up to 4 stereo-tactically placed catheters. It was co-infused with a contrast agent (Gd-DTPA, Magnevist®) to assess distribution in and around the tumor margins. The flow rate of each catheter did not exceed 10μL/min to ensure that the infusion duration did not exceed 48 h. The primary endpoint was mOS, with secondary endpoints determining the effects of IL4R status on mOS and PFS. RESULTS:MDNA55 showed an acceptable safety profile at doses up to 240 μg. In all evaluable patients (n = 44) mOS was 11.64 months (80% one-sided CI 8.62, 15.02) and OS-12 was 46%. A subgroup (n = 32) consisting of IL4R High and IL4R Low patients treated with high-dose MDNA55 (>180 ug) showed the best benefit with mOS of 15 months, OS-12 of 55%. Based on mRANO criteria, tumor control was observed in 81% (26/32), including those patients who exhibited pseudo-progression (15/26). CONCLUSIONS:MDNA55 demonstrated tumor control and promising survival and may benefit rGBM patients when treated at high-dose irrespective of IL4R expression level.Trial Registration: Clinicaltrials.gov NCT02858895.

This study tests the generalisability of three Brain Tumor Segmentation (BraTS) challenge models using a multi-center dataset of varying image quality and incomplete MRI datasets. In this retrospective study, DeepMedic, no-new-Unet (nn-Unet), and NVIDIA-net (nv-Net) were trained and tested using manual segmentations from preoperative MRI of glioblastoma (GBM) and low-grade gliomas (LGG) from the BraTS 2021 dataset (1251 in total), in addition to 275 GBM and 205 LGG acquired clinically across 12 hospitals worldwide. Data was split into 80% training, 5% validation, and 15% internal test data. An additional external test-set of 158 GBM and 69 LGG was used to assess generalisability to other hospitals’ data. All models’ median Dice similarity coefficient (DSC) for both test sets were within, or higher than, previously reported human inter-rater agreement (range of 0.74–0.85). For both test sets, nn-Unet achieved the highest DSC (internal = 0.86, external = 0.93) and the lowest Hausdorff distances (10.07, 13.87 mm, respectively) for all tumor classes ( p < 0.001). By applying Sparsified training, missing MRI sequences did not statistically affect the performance. nn-Unet achieves accurate segmentations in clinical settings even in the presence of incomplete MRI datasets. This facilitates future clinical adoption of automated glioma segmentation, which could help inform treatment planning and glioma monitoring.

Abstract BACKGROUND Bizaxofusp (MDNA55) is an IL4R-targeting toxin in development for recurrent (r)GBM, a universally fatal disease with mOS of 6-9 months. IL-4R is overexpressed in GBM and surrounding tumor microenvironment, with high expression associated with poor clinical outcome. Method: Efficacy and safety were evaluated in a single-arm, open-label, multi-center Ph2 study using convection-enhanced delivery of Bizaxofusp. The primary endpoint of mOS was compared to results from a blinded eligibility-matched external control arm (ECA). OS was defined as time from relapse to death/censor. IL-4R expression was determined by immunohistochemistry of available archival tumor tissues from both arms. RESULTS Bizaxofusp showed an acceptable safety profile at doses of up to 240 μg. Forty-four subjects were treated with Bizaxofusp per protocol; 81 ECA subjects met the eligibility criteria of the study. The Bizaxofusp group had a significantly longer mOS (12.85 months compared to 7.7 months for ECA; HR, 0.62; 95% CI, 0.42-0.89). Amongst the unmethylated MGMT and high IL-4R sub-groups, subjects treated with Bizaxofusp had significantly longer mOS when compared to the ECA. Eleven patients (25%) treated with Bizaxofusp survived >24 months; 3 patients were still alive (29.9, 32.8 and 40.1 months) at last follow-up. High IL-4R expression was associated with improved survival (mOS, 15.8 versus 9.8 months; HR, 0.7; 95% CI, 0.39-1.46) at all doses. However at high doses (180 μg) subjects with low IL-4R expression had significantly longer survival versus low dose Bizaxofusp (mOS, 15.4 versus 9.1 months; HR, 0.28; 95% CI, 0.09-0.91). CONCLUSION In patients with rGBM, a single treatment of Bizaxofusp resulted in significantly improved OS compared to eligibility-matched ECA. High-dose Bizaxofusp was equally effective irrespective of IL4R expression. A Phase 3 registration trial will use a novel hybrid design with a propensity-matched ECA comprising two-thirds of the control arm, setting a new precedent for GBM clinical trials.

OBJECTIVE The study objective was to evaluate intraoperative experience with newly developed high-spatial-resolution microelectrode grids composed of poly(3,4-ethylenedioxythiophene) with polystyrene sulfonate (PEDOT:PSS), and those composed of platinum nanorods (PtNRs). METHODS A cohort of patients who underwent craniotomy for pathological tissue resection and who had high-spatial-resolution microelectrode grids placed intraoperatively were evaluated. Patient demographic and baseline clinical variables as well as relevant microelectrode grid characteristic data were collected. The primary and secondary outcome measures of interest were successful microelectrode grid utilization with usable resting-state or task-related data, and grid-related adverse intraoperative events and/or grid dysfunction. RESULTS Included in the analysis were 89 cases of patients who underwent a craniotomy for resection of neoplasms (n = 58) or epileptogenic tissue (n = 31). These cases accounted for 94 grids: 58 PEDOT:PSS and 36 PtNR grids. Of these 94 grids, 86 were functional and used successfully to obtain cortical recordings from 82 patients. The mean cortical grid recording duration was 15.3 ± 1.15 minutes. Most recordings in patients were obtained during experimental tasks (n = 52, 58.4%), involving language and sensorimotor testing paradigms, or were obtained passively during resting state (n = 32, 36.0%). There were no intraoperative adverse events related to grid placement. However, there were instances of PtNR grid dysfunction (n = 8) related to damage incurred by suboptimal preoperative sterilization (n = 7) and improper handling (n = 1); intraoperative recordings were not performed. Vaporized peroxide sterilization was the most optimal sterilization method for PtNR grids, providing a significantly greater number of usable channels poststerilization than did steam-based sterilization techniques (median 905.0 [IQR 650.8-935.5] vs 356.0 [IQR 18.0-597.8], p = 0.0031). CONCLUSIONS High-spatial-resolution microelectrode grids can be readily incorporated into appropriately selected craniotomy cases for clinical and research purposes. Grids are reliable when preoperative handling and sterilization considerations are accounted for. Future investigations should compare the diagnostic utility of these high-resolution grids to commercially available counterparts and assess whether diagnostic discrepancies relate to clinical outcomes.

Abstract Background The prospects of a patient with suspected glioblastoma may rely heavily on the indication for surgical resection versus biopsy only. Biopsy percentages vary considerably across hospitals and guidelines for treatment of glioblastoma lack criteria for surgical decision-making. To identify patient and tumor characteristics associated with the decision to resect or biopsy a glioblastoma and to develop and validate a prediction model for decision support. Material and Methods Clinical data and pre-operative MRI scans were collected for adults who underwent first-time surgery for supratentorial glioblastoma from a registry-based cohort study of 12 hospitals from the Netherlands, Germany, France, Italy, and the United States between 1st of January 2007 and 31st of December 2011. The main outcome was the type of surgical procedure: surgical resection or biopsy only. Predictors were patient- and tumor-related characteristics. Radiological factors were extracted from MRI using an automated tumor segmentation method. A prediction model was constructed using multivariable logistic regression analysis. The model was cross-validated and externally validated with a leave-one-hospital-out approach. Results Out of 1053 patients treated for glioblastoma, 28% underwent biopsy only. Biopsy rates varied from 15-40% across hospitals. The prediction model showed excellent discrimination with an average area under the curve of 0.86. Of the patient-related characteristics, younger age was associated more with resection and Karnofsky Performance Score of 60 or less with biopsy. Of the tumor-related characteristics, a location in the right hemisphere, unifocality, no tumor midline crossing, and no involvement of the cortical spinal tract, were associated with resection, as well as a high expected resectability index, a location in the right occipital lobe, and a higher percentage of tumor in Schaefer’s dorsal or ventral attention, limbic, and default networks. External validation proved acceptable to outstanding discrimination with areas under the curve ranging between 0.79 and 0.92 for hospitals. Conclusion A prediction model is presented and validated to support the decision to resect or to biopsy a patient with a suspected supratentorial glioblastoma. In this prediction model, tumor-related characteristics were more informative than patient-related factors. This may support surgical decision-making for individual patients, or facilitate comparisons of patient cohorts between surgeons or institutions.

Abstract Standard of care (SOC) therapy for newly diagnosed (ND) glioblastoma (GBM) patients consist of temozolomide (TMZ) concurrent with radiation therapy. It is well known that patients with an unmethylated MGMT promoter are less likely to respond to TMZ, however, this trend is not universal. We have previously shown that 3D Predict™ glioma can identify patient response to TMZ, often differentially than the methylation status would predict. Here we present expanded clinical data relating to functional ex vivo testing capable of identifying patients responsive to alkylating therapies such as TMZ, regardless of methylation status. METHODS Fresh tissue specimens taken from ND GBM patients enrolled into the 3D PREDICT clinical study were examined by 3D Predict glioma to evaluate ex vivo therapeutic response to TMZ. Overall Survival (OS) and Progression Free Survival (PFS) in patients having ≥ 6 months follow-up post-surgery or < 6 months follow up but experiencing progression/death as of September 1, 2022 will be presented. Prospective correlation of clinical response and test-predicted response will be demonstrated in this expanded cohort of ND GBM patients. IMPACT This data has the potential to change treatment for ND GBM patients by stratifying according to functional therapeutic response rather than epigenetic factors that are not completely predictive of clinical response. It is feasible that 3D Predict glioma could dramatically impact patient care by determining which unmethylated patients should be treated with TMZ, and methylated patients who would potentially derive greater benefit from clinical trials or other treatment regimens.