Genetic characterization and mutational profiling of foramen magnum meningiomas: a multi-institutional study.

OBJECTIVE: Foramen magnum (FM) meningiomas pose significant surgical challenges and have high morbidity and mortality rates. This study aimed to investigate the distribution of clinically actionable mutations in FM meningiomas and identify clinical characteristics associated with specific mutational profiles. METHODS: The authors conducted targeted next-generation sequencing of 62 FM meningiomas from three international institutions, covering all relevant meningioma genes (AKT1, KLF4, NF2, POLR2A, PIK3CA, SMO, TERT promoter, and TRAF7). Patients with a radiation-induced meningioma or neurofibromatosis type 2 (NF2) were excluded from the study. Additionally, patient and tumor characteristics, including age, sex, radiological features, and tumor location, were retrospectively collected and evaluated. RESULTS: The study cohort consisted of 46 female and 16 male patients. Clinically significant driver mutations were detected in 58 patients (93.5%). The most commonly observed alteration was TRAF7 mutations (26, 41.9%), followed by AKT1E17K mutations (19, 30.6%). Both mutations were significantly associated with an anterolateral tumor location relative to the brainstem (p = 0.0078). NF2 mutations were present in 11 cases (17.7%) and were associated with posterior tumor location, in contrast to tumors with TRAF7 and AKT1E17K mutations. Other common mutations in FM meningiomas included POLR2A mutations (8, 12.9%; 6 POLR2AQ403K and 2 POLR2AH439_L440del), KLF4K409Q mutations (7, 11.3%), and PIK3CA mutations (4, 6.5%; 2 PIK3CAH1047R and 2 PIK3CAE545K). POLR2A and KLF4 mutations exclusively occurred in female patients and showed no significant association with specific tumor locations. All tumors harboring AKT1E17K and POLR2A mutations displayed meningothelial histology. Ten tumors exhibited intratumoral calcification, which was significantly more frequent in NF2-mutant compared with AKT1-mutant FM meningiomas (p = 0.047). CONCLUSIONS: These findings provide important insights into the molecular genetics and clinicopathological characteristics of FM meningiomas. The identification of specific genetic alterations associated with tumor location, volume, calcification, histology, and sex at diagnosis may have implications for personalized treatment strategies in the future.

Rationale for the Development of a Novel Clinical Grading Scale for Postoperative Facial Nerve Function: Results of a Multidisciplinary International Working Group.

OBJECTIVE: The objective of the current study was to present the results of an international working group survey identifying perceived limitations of existing facial nerve grading scales to inform the development of a novel grading scale for assessing early postoperative facial paralysis that incorporates regional scoring and is anchored in recovery prognosis and risk of associated complications. STUDY DESIGN: Survey. SETTING: A working group of 48 multidisciplinary clinicians with expertise in skull base, cerebellopontine angle, temporal bone, or parotid gland surgery. RESULTS: House-Brackmann grade is the most widely used system to assess facial nerve function among working group members (81%), although more than half (54%) agreed that the system they currently use does not adequately estimate the risk of associated complications, such as corneal injury, and confidence in interrater and intrarater reliability is generally low. Simplicity was ranked as the most important attribute of a novel postoperative facial nerve grading system to increase the likelihood of adoption, followed by reliability and accuracy. There was widespread consensus (91%) that the eye is the most critical facial region to focus on in the early postoperative setting. CONCLUSIONS: Members were invited to submit proposed grading systems in alignment with the objectives of the working group for subsequent validation. From these data, we plan to develop a simple, clinically anchored, and reproducible staging system with regional scoring for assessing early postoperative facial nerve function after surgery of the skull base, cerebellopontine angle, temporal bone, or parotid gland.

Proton Radiotherapy for Vestibular Schwannomas in Patients with NF2-Related Schwannomatosis: A Case Series.

(1) Background: This study aimed to evaluate the efficacy and treatment-related toxicity of proton radiotherapy (PRT) for vestibular schwannoma (VS) in patients with neurofibromatosis type 2-related schwannomatosis (NF2). (2) Methods: Consecutive NF2 patients treated with PRT for VS between 2004 and 2016 were retrospectively evaluated, focusing on tumor volume, facial and trigeminal nerve function, hearing, tinnitus, vestibular symptoms, and the need for salvage therapy after PRT. (3) Results: Eight patients were included (median age 36 years, 50% female). Median follow-up was 71 months. Five (63%) patients received fractionated PRT and three (38%) received PRT radiosurgery for VS. Six patients (75%) received prior VS surgery; three also received bevacizumab. Six patients (75%) did not require salvage therapy after PRT. Two patients (25%) with residual hearing lost it after PRT, and six had already lost ipsilateral hearing prior to PRT. Tumor and treatment-related morbidity could be evaluated in six patients. Following PRT, conditions that occurred or worsened were: facial paresis in five (83%), trigeminal hypoesthesia in two (33%), tinnitus in two (33%), and vestibular symptoms in four patients (67%). (4) Conclusion: After PRT for VS, the majority of the NF2 patients in the cohort did not require additional therapy. Tumor and/or treatment-related cranial nerve deficits were common. This is at least partly explained by the use of PRT as a salvage treatment after surgery or bevacizumab, in the majority of cases. There remains the further opportunity to elucidate the efficacy and toxicity of proton radiotherapy as a primary treatment.

Alliance A071401: Phase II Trial of Focal Adhesion Kinase Inhibition in Meningiomas With Somatic NF2 Mutations.

PURPOSE: Patients with progressive or recurrent meningiomas have limited systemic therapy options. Focal adhesion kinase (FAK) inhibition has a synthetic lethal relationship with NF2 loss. Given the predominance of NF2 mutations in meningiomas, we evaluated the efficacy of GSK2256098, a FAK inhibitor, as part of the first genomically driven phase II study in recurrent or progressive grade 1-3 meningiomas. PATIENTS AND METHODS: Eligible patients whose tumors screened positively for NF2 mutations were treated with GSK2256098, 750 mg orally twice daily, until progressive disease. Efficacy was evaluated using two coprimary end points: progression-free survival at 6 months (PFS6) and response rate by Macdonald criteria, where PFS6 was evaluated separately within grade-based subgroups: grade 1 versus 2/3 meningiomas. Per study design, the FAK inhibitor would be considered promising in this patient population if either end point met the corresponding decision criteria for efficacy. RESULTS: Of 322 patients screened for all mutation cohorts of the study, 36 eligible and evaluable patients with NF2 mutations were enrolled and treated: 12 grade 1 and 24 grade 2/3 patients. Across all grades, one patient had a partial response and 24 had stable disease as their best response to treatment. In grade 1 patients, the observed PFS6 rate was 83% (10/12 patients; 95% CI, 52 to 98). In grade 2/3 patients, the observed PFS6 rate was 33% (8/24 patients; 95% CI, 16 to 55). The study met the PFS6 efficacy end point both for the grade 1 and the grade 2/3 cohorts. Treatment was well tolerated; seven patients had a maximum grade 3 adverse event that was at least possibly related to treatment with no grade 4 or 5 events. CONCLUSION: GSK2256098 was well tolerated and resulted in an improved PFS6 rate in patients with recurrent or progressive NF2-mutated meningiomas, compared with historical controls. The criteria for promising activity were met, and FAK inhibition warrants further evaluation for this patient population.

Three-dimensional (3D) Printed Vestibular Schwannoma for Facial Nerve Tractography Validation.

OBJECTIVES: Predicting the course of cranial nerve (CN) VII in the cerebellopontine angle (CPA) on preoperative imaging for vestibular schwannoma (VS) may help guide surgical resection and reduce complications. Diffusion MRI based tractography has been used to identify cranial nerve trajectory, but intraoperative validation of this novel approach is challenging. Currently, validation is based on operative report descriptions of the course of cranial nerves, but yields a simplified picture of the three-dimensional (3D) course of CN VII. In this study, we investigate the accuracy of tractography with detailed patient-specific 3D-printed VS tumors. DESIGN: Retrospective case review. SETTING: Tertiary referral center. PARTICIPANTS: Twenty adult VS surgical candidates. MAIN OUTCOME MEASURES: We compared tractography with intraoperative 3D course of CN VII. The surgeons were blinded to tractography and drew the intraoperative course of the CN VII on a patient specific 3D-printed tumor model for detailed comparison with tractography. RESULTS: Of 20 patients, one was excluded due to subtotal removal and inability to assess CN VII course. In the remaining 19 patients, 84% (16/19) tractography was successful. In 94% of tumors with tractography (15/16), the intraoperative description of CN VII course matched the tractography finding. The maximum distance, however, between tractography and intraoperative course of CN VII was 3.7 mm ±â€Š4.2 mm. CONCLUSION: This study presents a novel approach to CN VII tractography validation in VS. Although descriptions of CN VII intraoperatively match tractography, caution is warranted as quantitative measures suggest a clinically significant distance between tractography and CN VII course.

American Neurotology Society, American Otological Society, and American Academy of Otolaryngology - Head and Neck Foundation Guide to Enhance Otologic and Neurotologic Care During the COVID-19 Pandemic.

: This combined American Neurotology Society, American Otological Society, and American Academy of Otolaryngology - Head and Neck Surgery Foundation document aims to provide guidance during the coronavirus disease of 2019 (COVID-19) on 1) "priority" of care for otologic and neurotologic patients in the office and operating room, and 2) optimal utilization of personal protective equipment. Given the paucity of evidence to inform otologic and neurotologic best practices during COVID-19, the recommendations herein are based on relevant peer-reviewed articles, the Centers for Disease Control and Prevention COVID-19 guidelines, United States and international hospital policies, and expert opinion. The suggestions presented here are not meant to be definitive, and best practices will undoubtedly change with increasing knowledge and high-quality data related to COVID-19. Interpretation of this guidance document is dependent on local factors including prevalence of COVID-19 in the surgeons' local community. This is not intended to set a standard of care, and should not supersede the clinician's best judgement when managing specific clinical concerns and/or regional conditions.Access to otologic and neurotologic care during and after the COVID-19 pandemic is dependent upon adequate protection of physicians, audiologists, and ancillary support staff. Otolaryngologists and associated staff are at high risk for COVID-19 disease transmission based on close contact with mucosal surfaces of the upper aerodigestive tract during diagnostic evaluation and therapeutic procedures. While many otologic and neurotologic conditions are not imminently life threatening, they have a major impact on communication, daily functioning, and quality of life. In addition, progression of disease and delay in treatment can result in cranial nerve deficits, intracranial and life-threatening complications, and/or irreversible consequences. In this regard, many otologic and neurotologic conditions should rightfully be considered "urgent," and almost all require timely attention to permit optimal outcomes. It is reasonable to proceed with otologic and neurotologic clinic visits and operative cases based on input from expert opinion of otologic care providers, clinic/hospital administration, infection prevention and control specialists, and local and state public health leaders. Significant regional variations in COVID-19 prevalence exist; therefore, physicians working with local municipalities are best suited to make determinations on the appropriateness and timing of otologic and neurotologic care.

Working Toward Consensus on Sporadic Vestibular Schwannoma Care: A Modified Delphi Study.

OBJECTIVE: To address variance in clinical care surrounding sporadic vestibular schwannoma, a modified Delphi study was performed to establish a general framework to approach vestibular schwannoma care. A multidisciplinary panel of experts was established with deliberate representation from key stakeholder societies. External validity of the final statements was assessed through an online survey of registered attendees of the 8th Quadrennial International Conference on Vestibular Schwannoma. STUDY DESIGN: Modified Delphi method. METHODS: The panel consisted of 16 vestibular schwannoma experts (8 neurotology and 8 neurosurgery) and included delegates representing the AAOHNSF, AANS/CNS tumor section, ISRS, and NASBS. The modified Delphi method encompassed a four-step process, comprised of one prevoting round to establish a list of focus areas and three subsequent voting rounds to successively refine individual statements and establish levels of consensus. Thresholds for achieving moderate consensus, at ≥67% agreement, and strong consensus, at ≥80% agreement, were determined a priori. All voting was performed anonymously via the Qualtrics online survey tool and full participation from all panel members was required before procession to the next voting round. RESULTS: Through the Delphi process, 103 items were developed encompassing hearing preservation (N = 49), tumor control and imaging surveillance (N = 20), preferred treatment (N = 24), operative considerations (N = 4), and complications (N = 6). As a result of item refinement, moderate (4%) or strong (96%) consensus was achieved in all 103 final statements. Seventy-nine conference registrants participated in the online survey to assess external validity. Among these survey respondents, moderate (N = 21, 20%) or strong (N = 73, 71%) consensus was achieved in 94 of 103 (91%) statements, and no consensus was reached in 9 (9%). Of the four items with moderate consensus by the expert panel, one had moderate consensus by the conference participants and three had no consensus. CONCLUSION: This modified Delphi study on sporadic vestibular schwannoma codifies 100% consensus within a multidisciplinary expert panel and is further supported by 91% consensus among an external group of clinicians who regularly provide care for patients with vestibular schwannoma. These final 103 statements address clinically pragmatic items that have direct application to everyday patient care. This document is not intended to define standard of care or drive insurance reimbursement, but rather to provide a general framework to approach vestibular schwannoma care for providers and patients.

Super-resolution Diffusion Tensor Imaging for Delineating the Facial Nerve in Patients with Vestibular Schwannoma.

Objectives Predicting the course of cranial nerves (CNs) VII and VIII in the cerebellopontine angle on preoperative imaging for vestibular schwannoma (VS) may help guide surgical resection and reduce complications. Diffusion magnetic resonance imaging dMRI is commonly used for this purpose, but is limited by its resolution. We investigate the use of super-resolution reconstruction (SRR), where several different dMRIs are combined into one dataset. We hypothesize that SRR improves the visualization of the CN VII and VIII. Design Retrospective case review. Setting Tertiary referral center. SRR was performed on the basis of axial and parasagittal single-shot epiplanar diffusion tensor imaging on a 3.0-tesla MRI scanner. Participants Seventeen adult patients with suspected neoplasms of the lateral skull base. Main Outcome Measures We assessed separability of the two distinct nerves on fractional anisotropy (FA) maps, the tractography of the nerves through the cerebrospinal fluid (CSF), and FA in the CSF as a measure of noise. Results SRR increases separability of the CN VII and VIII (16/17 vs. 0/17, p = 0.008). Mean FA of CSF surrounding the nerves is significantly lower in SRRs (0.07 ± 0.02 vs. 0.13 ± 0.03 [axial images]/0.14 ± 0.05 [parasagittal images], p = 0.00003/ p = 0.00005). Combined scanning times (parasagittal and axial) used for SRR were shorter (8 minute 25 seconds) than a comparable high-resolution scan (15 minute 17 seconds). Conclusion SRR improves the resolution of CN VII and VIII. The technique can be readily applied in the clinical setting, improving surgical counseling and planning in patients with VS.

Genomic Analysis of Posterior Fossa Meningioma Demonstrates Frequent AKT1 E17K Mutations in Foramen Magnum Meningiomas.

Objective Posterior fossa meningiomas are surgically challenging tumors that are associated with high morbidity and mortality. We sought to investigate the anatomical distribution of clinically actionable mutations in posterior fossa meningioma to facilitate identifying patients amenable for systemic targeted therapy trials. Methods Targeted sequencing of clinically targetable AKT1 , SMO , and PIK3CA mutations was performed in 61 posterior fossa meningioma using Illumina NextSeq 500 to a target depth of >500 × . Samples were further interrogated for 53 cancer-relevant RNA fusions by the Archer FusionPlex panel to detect gene rearrangements. Results AKT 1 ( E17K ) mutations were detected in five cases (8.2%), four in the foramen magnum and one in the cerebellopontine angle. In contrast, none of the posterior fossa tumors harbored an SMO ( L412F ) or a PIK3CA ( E545K ) mutation. Notably, the majority of foramen magnum meningiomas (4/7, 57%) harbored an AKT1 mutation. In addition, common clinically targetable gene fusions were not detected in any of the cases. Conclusion A large subset of foramen magnum meningiomas harbor AKT1 E17K mutations and are therefore potentially amenable to targeted medical therapy. Genotyping of foramen magnum meningiomas may enable more therapeutic alternatives and guide their treatment decision process.

Brachytherapy as an Adjuvant for Recurrent Atypical and Malignant Meningiomas.

BACKGROUND: Recurrent atypical and malignant meningiomas have poor outcomes with surgical therapy alone. Neither adjuvant chemotherapy nor postoperative radiation therapy remedies this problem. OBJECTIVE: To evaluate our experience with the treatment of 15 patients treated with I-125 or Cs-131 brachytherapy radiation seeds as an adjuvant in these difficult cases. METHODS: Patients with high-grade recurrent meningioma who underwent resection and intraoperative placement of brachytherapy seeds at our institution from 2002 to 2014 were identified and studied by retrospective chart review. RESULTS: Fifteen patients with median age of 68.8 yr were treated with I-125 (n = 13) or Cs-131 (n = 2) brachytherapy seeds for cases of recurrent, grade II (n = 8), or grade III (n = 7) meningioma at our institution from 2002 to 2014. These lesions originated from a variety of locations including, convexity (3), falcine (3), frontal (2), occipital (1), parietal (2), 2 sphenoid wing (2), and temporal (2), based recurrent meningiomas. Patients had a median of 2 prior open surgical interventions and received local radiation therapy with a median dose of 55 Gy prior to brachytherapy. Survival at 2.5 yr was 56% for grade II and 17% for grade III lesions. Survival was significantly associated with patient age but not tumoral pathology. Forty percent of patients required reoperations for wound complications following brachytherapy. CONCLUSION: Brachytherapy with implantation of permanent radiation seeds provides a viable alternative treatment for recurrent meningioma while carrying a significant clinical risk of wound infection and need for reoperation.

Germline and somatic BAP1 mutations in high-grade rhabdoid meningiomas.

Background: Patients with meningiomas have widely divergent clinical courses. Some entirely recover following surgery alone, while others have relentless tumor recurrences. This clinical conundrum is exemplified by rhabdoid meningiomas, which are designated in the World Health Organization Classification of Tumours as high grade, despite only a subset following an aggressive clinical course. Patient management decisions are further exacerbated by high rates of interobserver variability, biased against missing possibly aggressive tumors. Objective molecular determinants are needed to guide classification and clinical decision making. Methods: To define genomic aberrations of rhabdoid meningiomas, we performed sequencing of cancer-related genes in 27 meningiomas from 18 patients with rhabdoid features and evaluated breast cancer [BRCA]1-associated protein 1 (BAP1) expression by immunohistochemistry in 336 meningiomas. We assessed outcomes, germline status, and family history in patients with BAP1-negative rhabdoid meningiomas. Results: The tumor suppressor gene BAP1, a ubiquitin carboxy-terminal hydrolase, is inactivated in a subset of high-grade rhabdoid meningiomas. Patients with BAP1-negative rhabdoid meningiomas had reduced time to recurrence compared with patients with BAP1-retained rhabdoid meningiomas (Kaplan-Meier analysis, 26 mo vs 116 mo, P < .001; hazard ratio 12.89). A subset of patients with BAP1-deficient rhabdoid meningiomas harbored germline BAP1 mutations, indicating that rhabdoid meningiomas can be a harbinger of the BAP1 cancer predisposition syndrome. Conclusion: We define a subset of aggressive rhabdoid meningiomas that can be recognized using routine laboratory tests. We implicate ubiquitin deregulation in the pathogenesis of these high-grade malignancies. In addition, we show that familial and sporadic BAP1-mutated rhabdoid meningiomas are clinically aggressive, requiring intensive clinical management.

Genomic Characterization of Brain Metastases Reveals Branched Evolution and Potential Therapeutic Targets.

UNLABELLED: Brain metastases are associated with a dismal prognosis. Whether brain metastases harbor distinct genetic alterations beyond those observed in primary tumors is unknown. We performed whole-exome sequencing of 86 matched brain metastases, primary tumors, and normal tissue. In all clonally related cancer samples, we observed branched evolution, where all metastatic and primary sites shared a common ancestor yet continued to evolve independently. In 53% of cases, we found potentially clinically informative alterations in the brain metastases not detected in the matched primary-tumor sample. In contrast, spatially and temporally separated brain metastasis sites were genetically homogenous. Distal extracranial and regional lymph node metastases were highly divergent from brain metastases. We detected alterations associated with sensitivity to PI3K/AKT/mTOR, CDK, and HER2/EGFR inhibitors in the brain metastases. Genomic analysis of brain metastases provides an opportunity to identify potentially clinically informative alterations not detected in clinically sampled primary tumors, regional lymph nodes, or extracranial metastases. SIGNIFICANCE: Decisions for individualized therapies in patients with brain metastasis are often made from primary-tumor biopsies. We demonstrate that clinically actionable alterations present in brain metastases are frequently not detected in primary biopsies, suggesting that sequencing of primary biopsies alone may miss a substantial number of opportunities for targeted therapy.

Racial/ethnic differences in survival among elderly patients with a primary glioblastoma.

BACKGROUND: Few studies have assessed racial/ethnic differences in survival after primary glioblastoma diagnosis. We investigate these differences, incorporating information on White, Hispanics and Asians, as well as White, non-Hispanics and Blacks, among elderly individuals with a primary glioblastoma utilizing the population-based Surveillance, Epidemiology and End Results (SEER) Program-Medicare linked database. METHODS: A total of 1,530 individuals diagnosed > = 66 years of age from 6/1/91 to 12/31/99 in the SEER data were linked with Medicare information from 1/1/91 to 12/31/01. All individuals had Medicare Parts A and B and were non-HMO for 6 months before and 12 months after diagnosis to gather pre-diagnosis co-morbidities and post-diagnosis first course of treatment. Survival differences by race/ethnicity and by race/ethnicity stratified by treatment type and/or median household income were examined using Kaplan-Meier and multivariable Cox proportional hazards models. RESULTS: Significant racial/ethnic differences existed between White, non-Hispanics and Blacks in marital status, income and SEER registry region for the entire US. In analysis limited to the West region, significant racial/ethnic differences existed for income only. Overall there were no differences in survival between White, non-Hispanics and Blacks, however, in analysis limited to the West region, Asians had a lower risk of death compared to White, non-Hispanics [HR = 0.67, 95% CI (0.43, 1.03)]. Asians who had multiple treatments also had a lower risk of death compared to White, non-Hispanics [HR = 0.65, 95% CI (0.41, 1.01)]. CONCLUSIONS: Racial/ethnic differences in survival after primary glioblastoma diagnosis exist and may be partially explained by racial/ethnic differences in treatment and income.

Virtual cisternoscopy: 3D MRI models of the cerebellopontine angle for lesions related to the cranial nerves.

This study was conducted to show that high-resolution magnetic resonance imaging (MRI) can aid in the neurosurgical approach to lesions affecting the cranial nerves (CNs) in the cerebellopontine angle (CPA). Three patients with symptomatology related to CNs VII and VIII underwent MRI examinations performed on a 1.5-Tesla Siemens MR scanner. As part of these routine examinations, the imaging technique of constructive interference in the steady state (CISS) was used to collect a volume of data through the brainstem and internal auditory canals. This high-resolution technique acquires a three-dimensional (3D) volume of data at 0.7-mm intervals. Parameters included TR 12.3/TE 5.9, number of acquisitions of 2, a matrix of 230 x 512, bandwidth of 130 Hz per pixel, and time of 8:40. Data were transferred to a commercially available GE workstation and reconstructed into a 3D surface-rendered model. This interactive method allows the model to be visualized from any angle, including that of a standard skull base approach of suboccipital craniotomy for access to the CPA cistern. The images shown include the CPA cistern as seen from the suboccipital surgical approach. CNs V, VII, and VIII can easily be seen in relation to the pons and petrous face. The relationship between the CNs and acoustic neuromas and skull base tumors can be evaluated. Vascular structures, which are often seen in relation to CNs VII and VIII, can be viewed in a 3D format to determine the need for microvascular decompression. Direct intraoperative photographs taken through the operating microscope confirmed the anatomic accuracy of the 3D models. Imaging used for interactive neurosurgical planning must demonstrate a high degree of anatomic detail. Virtual cisternoscopy using CISS MRI technique can achieve the required resolution. Reconstruction algorithms to create surface rendering can generate images with similar 3D anatomic detail to that seen during neurosurgical approaches to the CPA cistern.

In vivo 3-T MR spectroscopy in the distinction of recurrent glioma versus radiation effects: initial experience.

PURPOSE: To determine if 3-T magnetic resonance (MR) spectroscopy allows accurate distinction of recurrent tumor from radiation effects in patients with gliomas of grade II or higher. MATERIALS AND METHODS: This blinded prospective study included 14 patients who underwent in vivo 3-T MR spectroscopy prior to stereotactic biopsy. All patients received a previous diagnosis of glioma (grade II or higher) and high-dose radiation therapy (>54 Gy). Prior to MR spectroscopy, conventional MR imaging was performed at 1.5 T to identify a gadolinium-enhanced region within the irradiated volume. Diagnosis was assigned by means of histopathologic analysis of the biopsy samples. RESULTS: Sixteen of 17 biopsy locations could be classified as predominantly tumor or predominantly radiation effect on the basis of the ratio of choline at the biopsy site to normal creatine level by using a value greater than 1.3 as the criterion for tumor. The remaining case, classified as recurrent tumor on the basis of MR spectroscopy results, was diagnosed as predominantly radiation effect on the basis of histopathologic findings. Disease in this patient progressed to biopsy-proven recurrence within 3 months. Overall, the ratio of choline at the biopsy site to normal creatine level was significantly elevated (unpaired two-tailed Student t test, P <.002) in those biopsy samples composed predominantly of tumor (n = 9) compared with those containing predominantly radiation effects (n = 8). The ratio was not significantly different between the two histopathologic groups. CONCLUSION: In vivo 3-T MR spectroscopy has sufficient spatial resolution and chemical specificity to allow distinction of recurrent tumor from radiation effects in patients with treated gliomas.