A case series of osseous metastases in patients with glioblastoma.

BACKGROUND: Extracranial metastases occur in <2% of cases of glioblastoma (GBM). When metastases do occur, bone is the most common destination. Herein, we review clinical characteristics of GBM patients with osseous metastases and evaluate both potential risk factors and prognostic significance. METHODS: Using an institutional database, we identified and retrospectively analyzed 6 patients with both GBM and osseous metastases. We collected data on patient demographics, tumor genetics, clinical courses, and outcomes. Given the rarity of metastatic GBM, we conducted historical comparisons using previously published literature. RESULTS: Five patients with osseous metastases (83%) were male, with a median age of 46 years at GBM diagnosis (range: 20-84). All patients had IDH-wildtype, MGMT promoter unmethylated GBM and 5 (83%) had alterations in TP53. All patients underwent surgical resection for GBM followed by radiation with concurrent and adjuvant temozolomide. Four patients (67%) received bevacizumab prior to bone metastasis diagnosis. Bone metastases were discovered at a median of 12.2 months (range: 5.3-35.2) after GBM diagnosis and 4.8 months after starting bevacizumab (range: 3.5-13.2). Three patients (50%) received immunotherapy. After osseous metastasis diagnosis, the median survival was 25 days (range: 13-225). CONCLUSION: In our cohort, most patients were male and young at the time of GBM diagnosis. All patients had IDH-wildtype, MGMT promoter unmethylated GBM, and most had alterations in TP53, which may be important for osseous metastasis. Most patients received bevacizumab, which has been associated with earlier metastasis. Osseous metastases of GBM occur and portend a dismal prognosis in an already aggressive malignancy.

Telehealth Utilization in Neuro-Oncology: Commentary on a Single Institution Experience After the COVID-19 Pandemic.

PURPOSE: During the COVID-19 pandemic, regulatory and reimbursement policy changes provided patients improved access to neuro-oncology by telehealth. Here we discuss benefits and limitations of telehealth use in neuro-oncology. We review utilization of telemedicine services following the COVID-19 pandemic. RECENT FINDINGS: Utilization of telemedicine by neuro-oncology during the COVID-19 pandemic was 52%, compared to 27-29% for other solid tumors groups. Following the pandemic, between January 2021 and April 2024, telehealth utilization has remained high in neuro-oncology with approximately 30% of all visits completed by telemedicine, compared to 10-15% for other solid tumor groups. The striking difference between telehealth visit utilization in neuro-oncology and general medical oncology even after expiration of the COVID-19 Public Health Emergency expiration and end of pandemic-related restrictions, underscores the potential value of convenient access to care for patients with central nervous system tumors. Given widespread use of telehealth in neuro-oncology, prospective evaluation to determine the safety, usability, and acceptance of video-enabled, telehealth visits is critical. Such data may lead to broader adoption of telehealth, lead to regulatory and reimbursement reform for telehealth sustainability, and improve clinical trial access and accruals.

Proton versus photon craniospinal irradiation for adult medulloblastoma: A dosimetric, toxicity, and exploratory cost analysis.

Background: This study aimed to determine whether proton craniospinal irradiation (CSI) decreased the dose to normal tissue and resulted in less toxicity than photon CSI for adult patients. Methods: This single-institution retrospective analyzed differences in radiation doses, acute toxicity, and cost between proton and CSI for adult medulloblastoma patients. Results: Of 39 total patients, 20 were treated with photon CSI prior to 2015, and 19 were treated with proton CSI thereafter. Median age was 28 years (range 18-66). The molecular subtype was most commonly sonic hedgehog (68%). Patients most commonly received 36 Gy CSI in 20 fractions with a boost to 54-55.8 Gy (92%). Proton CSI delivered significantly lower mean doses to cochleae, lacrimal glands, lens, parotid glands, pharyngeal constrictors, esophagus, lungs, liver, and skin (all P < .001). Patients receiving proton CSI had significantly lower rates of acute dysphagia of any grade (5% versus 35%, P = .044) and decreased median weight loss during radiation (+1.0 versus -2.8 kg, P = .011). Weight loss was associated with acute hospitalization (P = .009). Median follow-up was 2.9 and 12.9 years for proton and photon patients, respectively, limiting late toxicity and outcome comparisons. At the last follow-up, 5 photon patients had died (2 of progressive disease, 3 without recurrence ages 41-63) and 21% had experienced major cardiovascular events. At 10 years, 89% were alive and 82% were recurrence free. Conclusions: This study demonstrates dosimetric improvements with proton CSI, potentially leading to decreased acute toxicity including dysphagia and weight loss during treatment.

Carcinoembryonic antigen-expressing oncolytic measles virus derivative in recurrent glioblastoma: a phase 1 trial.

Measles virus (MV) vaccine strains have shown significant preclinical antitumor activity against glioblastoma (GBM), the most lethal glioma histology. In this first in human trial (NCT00390299), a carcinoembryonic antigen-expressing oncolytic measles virus derivative (MV-CEA), was administered in recurrent GBM patients either at the resection cavity (Group A), or, intratumorally on day 1, followed by a second dose administered in the resection cavity after tumor resection on day 5 (Group B). A total of 22 patients received study treatment, 9 in Group A and 13 in Group B. Primary endpoint was safety and toxicity: treatment was well tolerated with no dose-limiting toxicity being observed up to the maximum feasible dose (2×107 TCID50). Median OS, a secondary endpoint, was 11.6 mo and one year survival was 45.5% comparing favorably with contemporary controls. Other secondary endpoints included assessment of viremia, MV replication and shedding, humoral and cellular immune response to the injected virus. A 22 interferon stimulated gene (ISG) diagonal linear discriminate analysis (DLDA) classification algorithm in a post-hoc analysis was found to be inversely (R = -0.6, p = 0.04) correlated with viral replication and tumor microenvironment remodeling including proinflammatory changes and CD8 + T cell infiltration in post treatment samples. This data supports that oncolytic MV derivatives warrant further clinical investigation and that an ISG-based DLDA algorithm can provide the basis for treatment personalization.

Recurrent Pleomorphic Xanthoastrocytoma Presenting With Diffuse Leptomeningeal Spread.

We report a case highlighting key clinical, CSF, and imaging findings of recurrent pleomorphic xanthoastrocytoma with leptomeningeal spread.

Withdrawal of bevacizumab is associated with rebound growth of vestibular schwannomas in neurofibromatosis type 2-related schwannomatosis patients.

Background: Neurofibromatosis type 2 (NF2)-related schwannomatosis is an autosomal dominant tumor-predisposition syndrome characterized by bilateral vestibular schwannomas (VS). In patients with VS associated with NF2, vascular endothelial growth factor A inhibitor, bevacizumab, is a systemic treatment option. The aim of this study is to retrospectively evaluate NF2 patient responses to bevacizumab on VS growth and symptom progression. Methods: This is a retrospective analysis of patients seen at the Mayo Clinic Rochester Multidisciplinary NF2 Clinic. Results: Out of 76 patients with NF2 evaluated between 2020 and 2022, we identified 19 that received treatment with bevacizumab. Thirteen of these patients discontinued bevacizumab after median treatment duration of 12.2 months. The remaining 6 patients are currently receiving bevacizumab treatment for a median duration of 9.4 months as of March, 2023. Fifteen patients had evaluable brain MRI data, which demonstrated partial responses in 5 patients, stable disease in 8, and progression in 2. Within 6 months of bevacizumab discontinuation, 5 patients had rebound growth of their VS greater than 20% from their previous tumor volume, while 3 did not. Three patients with rebound growth went on to have surgery or irradiation for VS management. Conclusions: Our single-institution experience confirms prior studies that bevacizumab can control progression of VS and symptoms associated with VS growth. However, we note that there is the potential for rapid VS growth following bevacizumab discontinuation, for which we propose heightened surveillance imaging and symptom monitoring for at least 6 months upon stopping anti-VEGF therapy.

Belzutifan in adults with VHL-associated central nervous system hemangioblastoma: a single-center experience.

PURPOSE: Belzutifan is a selective inhibitor of hypoxia-inducible factor 2 alpha (HIF-2a) that has emerged as a targeted therapy option for Von Hippel-Lindau (VHL) syndrome-associated tumors with recent FDA approval. There is limited real-world evidence regarding safety and efficacy in CNS hemangioblastoma. Our objective was to report on our clinical experience with belzutifan in adult patients with VHL-associated CNS hemangioblastoma. METHODS: We retrospectively reviewed our institutional experience of belzutifan in adult patients (> 18 years of age at time of therapy) with VHL and craniospinal CNS hemangioblastomas not amenable to surgical resection. The period for study review was October 2021 to March 2023. RESULTS: 4 patients (all female) with a median age of 36 years at time of belzutifan initiation were included. Median duration of therapy at last follow-up was 11 months (6-17 months). All patients had radiographic response to therapy after a median of 3 months (2-5 months), with maximal response to therapy after a median of 8 months (3-17 months). Therapy was well tolerated, with the most common adverse effect being anemia. No patients had treatment pauses or dose adjustments due to belzutifan-related toxicity. No patients experienced hypoxia. CONCLUSION: We showed that belzutifan is safe and well-tolerated with strong disease response for CNS hemangioblastoma in adults with VHL, supporting continued use of belzutifan in this patient population. Future studies should assess duration of treatment, effects of cessation after long-term use, and markers of therapeutic response.

Clinical, Neurophysiologic, and Pathologic Features in Patients With Early-Onset Postradiation Neuropathy.

OBJECTIVES: The objective of this study was to study early-onset radiation-induced neuropathy reviewing neurologic course, steroid response, and available nerve biopsies. METHODS: Patients coded with radiation-induced neuropathy within 6 months of radiation were reviewed from January 1,1999, to August 31, 2022. Patients had to have electrodiagnostically confirmed neuropathy localized within or distal to radiation fields. Neurologic course and nerve biopsies were reviewed. RESULTS: Twenty-eight patients (16 male and 12 female patients, mean age 63.8 years) were identified. The average radiation dose was 4,659 cGy (range 1,000-7,208). Tumor infiltration was not observed on MRI and PET. Postradiation onsets averaged 2 months (range 0-5). Localizations included brachial (n = 4) plexopathies, lumbosacral (n = 12) plexopathies, radiculopathies (n = 10), and mononeuropathies (n = 2). Neuropathic pain (n = 25) and weakness (n = 25) were typical. The clinical courses were subacute monophasic (n = 14), chronic progressive (n = 8), or static (n = 1), and 5 were without follow-up. Nerve biopsies (n = 8) showed an inflammatory ischemic process with perivascular inflammatory infiltrates (n = 7) or microvasculitis (n = 2). Nine patients, 7 with monophasic courses, received steroid burst therapy with symptom improvement in 8. No patients recovered entirely back to baseline. DISCUSSION: In contrast to chronic radiation-induced neuropathy, early-onset patients most commonly have painful monophasic courses with residual deficits, possibly steroid responsive. An ischemic inflammatory pathogenesis is suggested.

Management and Long-term Outcomes of Adults With Medulloblastoma: A Single-Center Experience.

BACKGROUND AND OBJECTIVES: Medulloblastomas are embryonal tumors predominantly affecting children. Recognition of molecularly defined subgroups has advanced management. Factors influencing the management and prognosis of adult patients with medulloblastoma remains poorly understood. METHODS: We examined the management, prognostic factors, and, when possible, molecular subgroup differences (subset) in adult patients (aged 18 years or older) with medulloblastoma from our center (specialty Neuro-Oncology clinic within a large academic practice) diagnosed between 1992 and 2020. Molecular subtyping corresponding to the 2021 WHO Classification was performed. Kaplan-Meier estimates (with log-rank test) were performed for univariate survival analysis with Cox regression used for multivariate analyses. RESULTS: We included 76 adult patients with medulloblastoma (62% male), with a median age of 32 years at diagnosis (range: 18-66) and median follow-up of 7.7 years (range: 0.6-27). A subset of 58 patients had molecular subgroup characterization-37 SHH-activated, 12 non-WNT/non-SHH, and 9 WNT-activated. Approximately 67% underwent gross total resection, 75% received chemotherapy at diagnosis, and 97% received craniospinal irradiation with boost. The median overall survival (OS) for the whole cohort was 14.8 years. The 2-, 5-, and 10-year OS rates were 93% (95% CI 88-99), 86% (78-94), and 64% (53-78), respectively. Survival was longer for younger patients (aged 30 years or older: 9.9 years; younger than 30 years: estimated >15.4 years; log-rank p < 0.001). There was no survival difference by molecular subgroup or extent of resection. Only age at diagnosis remained significant in multivariate survival analyses. DISCUSSION: We report one of the largest retrospective cohorts in adult patients with medulloblastoma with molecular subtyping. Survival and molecular subgroup frequencies were similar to prior reports. Survival was better for adult patients younger than 30 years at diagnosis and was not significantly different by molecular subgroup or management characteristics (extent of resection, RT characteristics, or chemotherapy timing or regimen).

Genomic markers of recurrence risk in atypical meningioma following gross total resection.

Background: Meningiomas are the most common primary central nervous system (CNS) tumor in adults and CNS World Health Organization grade 2 (atypical) meningiomas show an intermediate risk of recurrence/progression. Molecular parameters are needed to better inform management following gross total resection (GTR). Methods: We performed comprehensive genomic analysis of tumor tissue from 63 patients who underwent radiologically confirmed GTR of a primary grade 2 meningioma, including a CLIA-certified target next-generation sequencing panel (n = 61), chromosomal microarray (n = 63), genome-wide methylation profiling (n = 62), H3K27me3 immunohistochemistry (n = 62), and RNA-sequencing (n = 19). Genomic features were correlated with long-term clinical outcomes (median follow-up: 10 years) using Cox proportional hazards regression modeling and published molecular prognostic signatures were evaluated. Results: The presence of specific copy number variants (CNVs), including -1p, -10q, -7p, and -4p, was the strongest predictor of decreased recurrence-free survival (RFS) within our cohort (P < .05). NF2 mutations were frequent (51%) but did not show a significant association with RFS. DNA methylation-based classification assigned tumors to DKFZ Heidelberg benign (52%) or intermediate (47%) meningioma subclasses and was not associated with RFS. H3K27 trimethylation (H3K27me3) was unequivocally lost in 4 tumors, insufficient for RFS analysis. Application of published integrated histologic/molecular grading systems did not improve prediction of recurrence risk over the presence of -1p or -10q alone. Conclusions: CNVs are strong predictors of RFS in grade 2 meningiomas following GTR. Our study supports incorporation of CNV profiling into clinical evaluation to better guide postoperative patient management, which can be readily implemented using existing, clinically validated technologies.

Management and Long-Term Outcomes of Patients With Recurrent Stroke-Like Episodes After Cranial Radiotherapy.

BACKGROUND: Recurrent Stroke-Like Episodes of transient negative neurologic symptoms are a long-term consequence of cranial radiation therapy (RT) that may lead to significant functional impairment and worsen quality of life. We assessed management patterns and clinical course at our institution to assess optimal management strategy and understand long-term outcomes. METHODS: We conducted a retrospective review of all patients with recurrent negative neurologic symptoms after cranial RT who were treated at Mayo Clinic (Rochester), with follow-up extending through October 2021 with a goal of assessing for clinical change in the setting of medical management. Descriptive statistics and Fisher exact tests were performed for group comparisons. RESULTS: Twenty-five patients were included. Median age at diagnosis was 28.7 years (range: 3.0 to 65.8). Median time from RT to symptom onset was 14.6 years (range: 3.3 to 30.5). The most common presentations included hemiparesis (56%), visual field (33%) and hemisensory (22%) loss, and aphasia (22%). Therapeutics used specifically for management of recurrent episodes included antiseizure medications (92%), antiplatelets (68%), verapamil (52%), statins (48%), glucocorticoids (24%), antivirals (20%), and angiotensin converting enzyme inhibitor/ Angiotensin receptor blockers (16%). Antivirals were less commonly used in patients with cessation (Fisher exact, P =0.0235). Progressive encephalopathy was more commonly seen in those without cessation (Fisher exact, P =0.0072), and in all patients who died at last follow-up. CONCLUSIONS: Although retrospective experience from a single institution, our cohort represents one of the largest with management data reported for this complex clinical scenario. We hope that our findings may be used as a reference for clinicians in the management of this challenging clinical scenario.

Initial results of a phase II trial of 18F-DOPA PET-guided re-irradiation for recurrent high-grade glioma.

PURPOSE: In-field high-grade glioma (HGG) recurrence is a common challenge with limited treatment options, including re-irradiation. The radiotracer 3,4-dihydroxy-6-[18F]-fluoro-L-phenylalanine (18F-DOPA) crosses the blood brain barrier and demonstrates high uptake in tumor, but low uptake in normal tissue. This study investigated whether 18F-DOPA positron emission tomography (PET) and MRI guided re-irradiation for recurrent HGG may improve progression free survival (PFS). METHODS: Adults with recurrent or progressive HGG previously treated with radiation were eligible. The primary endpoint was a 20% improvement from the historical control PFS at 3 months (PFS3) of 20% with systemic therapy alone. Re-RT dose was 35 Gy in 10 fractions. The target volume was MRI T1 contrast-enhancement defined tumor plus 18F-DOPA PET defined tumor. RESULTS: Twenty patients completed treatment per protocol. Diagnosis was most commonly glioblastoma, IDH-wildtype (60%). MRI-defined volumes were expanded by a median 43% (0-436%) by utilizing 18F-DOPA PET. PFS3 was 85% (95% CI 63.2-95.8%), meeting the primary endpoint of PFS3 ≥ 40%. With 9.7 months median follow-up, 17 (85%) had progressed and 15 (75%) had died. Median OS from re-RT was 8.8 months. Failure following re-RT was within both the MRI and PET tumor volumes in 75%, MRI only in 13%, PET only in 0%, and neither in 13%. Four (20%) patients experienced grade 3 toxicity, including CNS necrosis (n = 2, both asymptomatic with bevacizumab initiation for radiographic findings), seizures (n = 1), fatigue (n = 1), and nausea (n = 1). No grade 4-5 toxicities were observed. CONCLUSION: 18F-DOPA PET-guided re-irradiation for progressive high-grade glioma appears safe and promising for further investigation.

Predicting access to postoperative treatment after glioblastoma resection: an analysis of neighborhood-level disadvantage using the Area Deprivation Index (ADI).

PURPOSE: Social determinants of health (SDoH)-socioeconomic and environmental factors-impact outcomes. The Area Deprivation Index (ADI), a composite of seventeen SDoH factors, has been correlated with poorer outcomes. We aimed to compare outcomes and treatment access for glioblastoma, a universally fatal malignant brain tumor, in patients more (ADI 34-100%) versus less disadvantaged (ADI 0-33%). METHODS: A 5-year retrospective study of Rhode Island Hospital and Mayo Clinic databases was conducted from 2012 to 2017 for patients ≥ 18 years with glioblastoma. Patient addresses were matched to ADI percentiles and grouped into more (top 66% ADI) and less disadvantaged. Adjusted multivariable regressions were used to compare outcomes between groups. RESULTS: A total of 434 patients met inclusion; 92.9% were insured, 56.2% were more disadvantaged (n = 244), and the more disadvantaged cohort was younger on average (62 years). After adjustment, the more disadvantaged group had decreased odds of receiving gross total resection (adjusted odds ratio (aOR) 0.43, 95% CI [0.27-0.68]; p < 0.001). This cohort also had decreased odds of undergoing chemotherapy (aOR 0.51[0.26-0.98]), radiation (aOR 0.39[0.20-0.77]), chemoradiation (aOR 0.42[0.23-0.77]), tumor-treating fields (aOR 0.39[0.16-0.93]), and clinical trial participation (aOR 0.47[0.25-0.91]). No differences in length of survival or postoperative Karnofsky Performance Status Scale were observed. CONCLUSION: More disadvantaged glioblastoma patients had decreased odds of receiving gross total resection. They also exhibited decreased odds of receiving standard of care like chemoradiation as well as participating in a clinical trial, compared to the less disadvantaged group. More research is needed to identify modifiable SDoH barriers to post-operative treatment in disadvantaged patients with glioblastoma.

Panobinostat in adults with H3 K27M-mutant diffuse midline glioma: a single-center experience.

INTRODUCTION: Diffuse midline gliomas (DMG) with the H3 K27M-mutation are a well-described entity with most DMG harboring this mutation, with notable heterogeneity in adults. No therapy has been proven to improve survival in this tumor type. Panobinostat is a histone deacetylase inhibitor that may have therapeutic benefit. METHODS: We report our retrospective experience with use of panobinostat in adults (> 18 years) with H3 K27M-mutant DMG treated at Mayo Clinic (Rochester) from January 2016 to August 2020, with follow-up until October 2021. Survival was calculated using the Kaplan-Meier method. RESULTS: 4 patients with H3 K27M-mutant glioma were treated with panobinostat as compassionate use. Patients had a median age of 40 years (range 22-62 years) and 2 were female. Tumor location was midline for all patients, spinal cord (n = 2), brainstem (n = 1), and thalamus (n = 1). All tumors were IDH1/IDH2 wildtype. 3 patients received radiotherapy followed by adjuvant panobinostat. All patients had no other pharmacologic therapy utilized prior to or during panobinostat therapy aside from concurrent dexamethasone utilized in 3 patients. No patient experienced a grade 2 or higher (per CTCAE grade) adverse effect. The median overall survival was 42 months, median progression free survival of 19 months, 2 patients were alive at last follow up (both with spinal cord tumors and received radiation). The best response was stable disease in 2 patients and a partial response in 1 patient. CONCLUSIONS: This is the first report of clinical outcomes of panobinostat in adults with H3 K27M-mutant DMG. We showed that it is well-tolerated at the dosage schedule that we describe, with no serious adverse effects throughout the study period.

IDH-wild-type glioblastoma cell density and infiltration distribution influence on supramarginal resection and its impact on overall survival: a mathematical model.

OBJECTIVE: Recent studies have proposed resection of the T2 FLAIR hyperintensity beyond the T1 contrast enhancement (supramarginal resection [SMR]) for IDH-wild-type glioblastoma (GBM) to further improve patients' overall survival (OS). GBMs have significant variability in tumor cell density, distribution, and infiltration. Advanced mathematical models based on patient-specific radiographic features have provided new insights into GBM growth kinetics on two important parameters of tumor aggressiveness: proliferation rate (ρ) and diffusion rate (D). The aim of this study was to investigate OS of patients with IDH-wild-type GBM who underwent SMR based on a mathematical model of cell distribution and infiltration profile (tumor invasiveness profile). METHODS: Volumetric measurements were obtained from the selected regions of interest from pre- and postoperative MRI studies of included patients. The tumor invasiveness profile (proliferation/diffusion [ρ/D] ratio) was calculated using the following formula: ρ/D ratio = (4π/3)2/3 × (6.106/[VT21/1 - VT11/1])2, where VT2 and VT1 are the preoperative FLAIR and contrast-enhancing volumes, respectively. Patients were split into subgroups based on their tumor invasiveness profiles. In this analysis, tumors were classified as nodular, moderately diffuse, or highly diffuse. RESULTS: A total of 101 patients were included. Tumors were classified as nodular (n = 34), moderately diffuse (n = 34), and highly diffuse (n = 33). On multivariate analysis, increasing SMR had a significant positive correlation with OS for moderately and highly diffuse tumors (HR 0.99, 95% CI 0.98-0.99; p = 0.02; and HR 0.98, 95% CI 0.96-0.99; p = 0.04, respectively). On threshold analysis, OS benefit was seen with SMR from 10% to 29%, 10% to 59%, and 30% to 90%, for nodular, moderately diffuse, and highly diffuse, respectively. CONCLUSIONS: The impact of SMR on OS for patients with IDH-wild-type GBM is influenced by the degree of tumor invasiveness. The authors' results show that increasing SMR is associated with increased OS in patients with moderate and highly diffuse IDH-wild-type GBMs. When grouping SMR into 10% intervals, this benefit was seen for all tumor subgroups, although for nodular tumors, the maximum beneficial SMR percentage was considerably lower than in moderate and highly diffuse tumors.

Initial Results of a Phase 2 Trial of 18F-DOPA PET-Guided Dose-Escalated Radiation Therapy for Glioblastoma.

PURPOSE: Our previous work demonstrated that 3,4-dihydroxy-6-[18F]-fluoro-L-phenylalanine (18F-DOPA) positron emission tomography (PET) is sensitive and specific for identifying regions of high density and biologically aggressive glioblastoma. The purpose of this prospective phase 2 study was to determine the safety and efficacy of biologic-guided, dose-escalated radiation therapy (DERT) using 18F-DOPA PET in patients with glioblastoma. METHODS AND MATERIALS: Patients with newly diagnosed, histologically confirmed glioblastoma aged ≥18 years without contraindications to 18F-DOPA were eligible. Target volumes included 51, 60, and 76 Gy in 30 fractions with a simultaneous integrated boost, and concurrent and adjuvant temozolomide for 6 months. 18F-DOPA PET imaging was used to guide DERT. The study was designed to detect a true progression-free survival (PFS) at 6 months (PFS6) rate ≥72.5% in O6-methylguanine methyltransferase (MGMT) unmethylated patients (DE-Un), with an overall significance level (alpha) of 0.20 and a power of 80%. Kaplan-Meier analysis was performed for PFS and overall survival (OS). Historical controls (HCs) included 139 patients (82 unmethylated) treated on prospective clinical trials or with standard RT at our institution. Toxicities were evaluated with Common Terminology Criteria for Adverse Events v4.0. RESULTS: Between January 2014 and December 2018, 75 evaluable patients were enrolled (39 DE-Un, 24 methylated [DE-Mth], and 12 indeterminate). PFS6 for DE-Un was 79.5% (95% confidence interval, 63.1%-90.1%). Median PFS was longer for DE-Un patients compared with historical controls (8.7 months vs 6.6 months; P = .017). OS was similarly longer, but the difference was not significant (16.0 vs 13.5 months; P = .13). OS was significantly improved for DE-Mth patients compared with HC-Mth (35.5 vs 23.3 months; P = .049) despite nonsignificant improvement in PFS (10.7 vs 9.0 months; P = .26). Grade 3 central nervous system necrosis occurred in 13% of patients, but treatment with bevacizumab improved symptoms in all cases. CONCLUSIONS: 18F-DOPA PET-guided DERT appears to be safe, and it significantly improves PFS in MGMT unmethylated glioblastoma. OS is significantly improved in MGMT methylated patients. Further investigation of 18F-DOPA PET biologic guided DERT for glioblastoma is warranted.

A Comprehensive Study of Spindle Cell Oncocytoma of the Pituitary Gland: Series of 6 Cases and Meta-Analysis of 85 Cases.

OBJECTIVE: To discuss optimal treatment strategy for spindle cell oncocytoma (SCO) of the pituitary gland. METHODS: Institutional cases were retrospectively reviewed. A systematic literature search and subsequent quantitative synthesis were performed for further analysis. The detailed features were summarized and the tumor control rate (TCR) was calculated. RESULTS: Eighty-five patients (6 institutional and 79 literature) were included. The annual incidence was approximately 0.01-0.03/100,000. The mean age was 56 years. Vision loss was present in 60%. Seventy-three percent showed hormonal abnormalities. On magnetic resonance imaging, tumor was avidly enhancing, and the normal gland was commonly displaced anterosuperiorly. Evidence of hypervascularity was seen in 77%. Gross total resection (GTR) was achieved in only 24% because of its hypervascular, fibrous, and adhesive nature. The mean postoperative follow-up was 3.3 years for institutional cases and 2.3 years for the integrated cohort. The TCR was significantly better after GTR (5-year TCR, 75%; P = 0.012) and marginally better after non-GTR + upfront radiotherapy (5-year TCR, 76%; P = 0.103) than after non-GTR alone (5-year TCR, 24%). The TCRs for those with low Ki-67 index (≤5%) were marginally better than those with higher Ki-67 index (5-year rate, 57% vs. 23%; P = 0.110). CONCLUSIONS: Frequent endocrine-related symptoms, hypervascular signs, and anterosuperior displacement of the gland support preoperative diagnosis of SCO. GTR seems to have better long-term tumor control, whereas the fibrous, hypervascular, and adhesive nature of SCO makes it difficult to achieve GTR. In patients with non-GTR, radiotherapy may help decrease tumor progression.

Temozolomide desensitization followed by metronomic dosing in patients with hypersensitivity.

PURPOSE: Temozolomide is the most effective chemotherapy for malignant glioma. Hypersensitivity requiring interruption of therapy may significantly impact patient survival. We have successfully employed temozolomide desensitization followed by metronomic dosing of temozolomide. Our purpose was to report patient characteristics and outcomes in patients with glioma (Grade 2-4) and temozolomide hypersensitivity managed by desensitization and metronomic dosing. METHODS: We performed an observational study of 15 patients at Mayo Clinic (Rochester) with a diagnosis of glioma who underwent temozolomide desensitization with subsequent metronomic dosing from May 2012 to January 2017. We calculated overall and progression-free survival using the Kaplan-Meier method, and log-rank analyses to assess for differences in survival by WHO Grade or treatment initiation. RESULTS: Median age at time of desensitization was 49.3 years (26.8-64.7 years). Median follow-up after desensitization was 35.5 months. One patient (6.7%) was unable to resume temozolomide due to recurrent allergy. The median time from first desensitization to discontinuation of metronomic temozolomide was 4.2 months (0-15.2 months). Median OS and PFS for the whole sample were 181.7 months and 44.9 months. For Grade 4, OS was 100% at 1 year, 40% at 3 years, 20% at 5 years; and PFS was 60% at 1 year, 40% at 3 years, and 20% at 5 years. CONCLUSION: Our results suggest that rapid-desensitization followed by metronomic temozolomide should be considered in patients with glioma who experience hypersensitivity. This strategy provides comparable outcomes to therapy with standard protocols, with the majority of patients able to tolerate temozolomide after desensitization with favorable disease control.