Showing papers by "Roger Stupp published in 2014"

Cilengitide combined with standard treatment for patients with newly diagnosed glioblastoma with methylated MGMT promoter (CENTRIC EORTC 26071-22072 study): a multicentre, randomised, open-label, phase 3 trial

Abstract: Summary Background Cilengitide is a selective αvβ3 and αvβ5 integrin inhibitor. Data from phase 2 trials suggest that it has antitumour activity as a single agent in recurrent glioblastoma and in combination with standard temozolomide chemoradiotherapy in newly diagnosed glioblastoma (particularly in tumours with methylated MGMT promoter). We aimed to assess cilengitide combined with temozolomide chemoradiotherapy in patients with newly diagnosed glioblastoma with methylated MGMT promoter. Methods In this multicentre, open-label, phase 3 study, we investigated the efficacy of cilengitide in patients from 146 study sites in 25 countries. Eligible patients (newly diagnosed, histologically proven supratentorial glioblastoma, methylated MGMT promoter, and age ≥18 years) were stratified for prognostic Radiation Therapy Oncology Group recursive partitioning analysis class and geographic region and centrally randomised in a 1:1 ratio with interactive voice response system to receive temozolomide chemoradiotherapy with cilengitide 2000 mg intravenously twice weekly (cilengitide group) or temozolomide chemoradiotherapy alone (control group). Patients and investigators were unmasked to treatment allocation. Maintenance temozolomide was given for up to six cycles, and cilengitide was given for up to 18 months or until disease progression or unacceptable toxic effects. The primary endpoint was overall survival. We analysed survival outcomes by intention to treat. This study is registered with ClinicalTrials.gov, number NCT00689221. Findings Overall, 3471 patients were screened. Of these patients, 3060 had tumour MGMT status tested; 926 patients had a methylated MGMT promoter, and 545 were randomly assigned to the cilengitide (n=272) or control groups (n=273) between Oct 31, 2008, and May 12, 2011. Median overall survival was 26·3 months (95% CI 23·8–28·8) in the cilengitide group and 26·3 months (23·9–34·7) in the control group (hazard ratio 1·02, 95% CI 0·81–1·29, p=0·86). None of the predefined clinical subgroups showed a benefit from cilengitide. We noted no overall additional toxic effects with cilengitide treatment. The most commonly reported adverse events of grade 3 or worse in the safety population were lymphopenia (31 [12%] in the cilengitide group vs 26 [10%] in the control group), thrombocytopenia (28 [11%] vs 46 [18%]), neutropenia (19 [7%] vs 24 [9%]), leucopenia (18 [7%] vs 20 [8%]), and convulsion (14 [5%] vs 15 [6%]). Interpretation The addition of cilengitide to temozolomide chemoradiotherapy did not improve outcomes; cilengitide will not be further developed as an anticancer drug. Nevertheless, integrins remain a potential treatment target for glioblastoma. Funding Merck KGaA, Darmstadt, Germany.

EANO guideline for the diagnosis and treatment of anaplastic gliomas and glioblastoma

Abstract: This guideline provides recommendations for diagnostic and therapeutic procedures for patients with malignant gliomas. We differentiate evidence-based standards from reasonable options or non-evidence-based measures that should no longer be considered. The recommendations herein should provide a framework and assurance for the choice of diagnostic procedures and therapeutic measures and aim to reduce complications from unnecessary treatment and cost. The guideline contributes to a critical appreciation of concurrent drugs with a focus on the controlled use of anticonvulsants and steroids. It should serve as a guideline for all professionals involved in the diagnostics and care of glioma patients and also as a source of knowledge for insurance companies and other institutions involved in the cost regulation of cancer care in Europe. Implementation of the recommendations summarised here will need interdisciplinary structures of care for patients with brain tumours and structured processes of diagnostic and therapeutic procedures.

The Neurologic Assessment in Neuro-Oncology (NANO) scale: a tool to assess neurologic function for integration into the Response Assessment in Neuro-Oncology (RANO) criteria.

Abstract: BACKGROUND: The Macdonald criteria and RANO criteria define radiologic parameters to classify therapeutic outcome among malignant glioma patients. While both scales specify that clinical status must be incorporated for overall assessment, neither provides specific parameters to do so. Furthermore, both scales prioritize clinical status over radiology in that response requires at least stable clinical status, while clinical deterioration is sufficient to declare progression. We hypothesized that a standardized metric to measure neurologic function will permit better overall response assessment in neuro-oncology. METHODS: An international group of neuro-oncologists convened bi- weekly for the past year to draft the Neurologic Assessment in Neuro-Oncology (NANO) criteria as an objective and quantifiable metric of neurologic function evaluable during a routine office examination. RESULTS: The NANO scale is a quick, clinician-friendly, and quantifiable evaluation of eight relevant neurologic domains based on direct observation/testing conducted during routine office visits. The score defines criteria for domain-specific and overall scores of response, progression, stable disease and not assessed. A given domain will be scored non-evaluable if it cannot be accurately assessed due to pre-existing conditions, co-morbid events, and/or concurrent medications. CONCLUSION: The NANO criteria aims to provide a more detailed and objective measure of neurologic function than currently exists. These criteria are designed to enable a consistent evaluation of neurologic function which will facilitate comparisons across clinical trials and therapeutic interventions. Implementation and validation of these criteria are planned, and future modifications are anticipated for further optimization.

Standards of care and novel approaches in the management of glioblastoma multiforme

Abstract: Glioblastoma multiforme (GBM) is the most common malignant primary brain tumor in adults. Standard therapeutic approaches provide modest improvement in the progression-free and overall survival, necessitating the investigation of novel therapies. We review the standard treatment options for GBM and evaluate the results obtained in clinical trials for promising novel approaches, including the inhibition of angiogenesis, targeted approaches against molecular pathways, immunotherapies, and local treatment with low voltage electric fields.

The accuracy of predicting survival in individual patients with cancer

Abstract: Object Estimating survival time in cancer patients is crucial for clinicians, patients, families, and payers. To provide appropriate and cost-effective care, various data sources are used to provide rational, reliable, and reproducible estimates. The accuracy of such estimates is unknown. Methods The authors prospectively estimated survival in 150 consecutive cancer patients (median age 62 years) with brain metastases undergoing radiosurgery. They recorded cancer type, number of brain metastases, neurological presentation, extracranial disease status, Karnofsky Performance Scale score, Recursive Partitioning Analysis class, prior whole-brain radiotherapy, and synchronous or metachronous presentation. Finally, the authors asked 18 medical, radiation, or surgical oncologists to predict survival from the time of treatment. Results The actual median patient survival was 10.3 months (95% CI 6.4–14). The median physician-predicted survival was 9.7 months (neurosurgeons = 11.8 months, radiation oncologists = 11....

Levetiracetam and pregabalin for antiepileptic monotherapy in patients with primary brain tumors. A phase II randomized study

Abstract: Seizures in patients with primary brain tumors represent a frequent problem, as at least one third of patients develop epilepsy in the course of disease.1,2 Subjects experiencing a first seizure should benefit from an antiepileptic drug (AED) prescription aimed at reducing further generalized convulsive events and improving quality of life.3 There is a wide consensus favoring the use of non-enzyme-inducing AEDs to avoid hepatic interactions potentially interfering with chemotherapy and other medications, such as steroids,4–8 but the level of evidence is still very limited, as recently pointed out.9 Furthermore, although all the newer AEDs were initially registered as add-on drugs in combination, recent experience suggests efficacy as single agents. Among the newer AEDs, levetiracetam (LEV) and pregabalin (PGB) are considered among the most favorable compounds in terms of potential pharmacokinetic drug-drug interactions. LEV binds to a synaptic vesicle protein,10 lacks hepatic catabolism (it is excreted partly unchanged in the urine and partly undergoes extrahepatic hydrolysis),11 and is available in oral and intravenous formulations. It can be quickly titrated, displaying therapeutic efficacy within hours,12 and its bioavailability in the CSF seems longer than the plasmatic half-life.13 PGB modulates Q-type voltage-sensitive calcium channels,14 does not undergo any metabolic transformation (it has a complete renal excretion), and therefore does not have any impact on the hepatic cytochromic system.15,16 Despite being limited to oral formulations, it may also be titrated rapidly, exerting therapeutic efficacy within 48 h,17 and as opposed to gabapentin, which has an identical mechanism of action, PGB does not depend on a saturable intestinal resorption.18 This study was conducted to determine the safety and efficacy of AED monotherapy with LEV or PGB in patients with primary brain tumors and epilepsy and to collect prospective data on seizure control in brain tumor patients.

Cilengitide treatment of newly diagnosed glioblastoma patients does not alter patterns of progression

Abstract: The integrin antagonist cilengitide has been explored as an adjunct with anti-angiogenic properties to standard of care temozolomide chemoradiotherapy (TMZ/RT → TMZ) in newly diagnosed glioblastoma. Preclinical data as well as anecdotal clinical observations indicate that anti-angiogenic treatment may result in altered patterns of tumor progression. Using a standardized approach, we analyzed patterns of progression on MRI in 21 patients enrolled onto a phase 2 trial of cilengitide added to TMZ/RT → TMZ in newly diagnosed glioblastoma. Thirty patients from the experimental treatment arm of the EORTC/NCIC pivotal TMZ trial served as a reference. MRIcro software was used to map location and extent of initial preoperative and recurrent tumors on MRI of both groups into the same stereotaxic space which were then analyzed using an automated tool of image analysis. Clinical and outcome data of the cilengitide-treated patients were similar to those of the EORTC/NCIC trial except for a higher proportion of patients with a methylated O(6)-methylguanyl-DNA-methyltransferase gene promoter. Analysis of recurrence pattern revealed neither a difference in the size of the recurrent tumor nor in the distance of the recurrences from the preoperative tumor location between groups. Overall frequencies of distant recurrences were 20 % in the reference group and 19 % (4/21 patients) in the cilengitide group. Compared with TMZ/RT → TMZ alone, the addition of cilengitide does not alter patterns of progression. This analysis does not support concerns that integrin antagonism by cilengitide may induce a more aggressive phenotype at progression, but also provides no evidence for an anti-invasive activity of cilengitide in patients with newly diagnosed glioblastoma.

NT-40Interim Analysis of the EF-14 Trial: A Prospective, Multi-center Trial of NovoTTF-100A Together With Temozolomide Compared to Temozolomide Alone in Patients with Newly Diagnosed GBM

Abstract: METHODS: We conducted an international, multicenter, prospective, randomized phase III trial in newly diagnosed GBM patients. After completion of radiotherapy (RT) with concomitant temozolomide (TMZ), patients were randomized (2:1) to adjuvant TMZ with NovoTTF or adjuvant TMZ alone. The primary endpoint was progression-free survival (PFS), with overall survival (OS) an important secondary endpoint. Here we report on a pre-specified interim analysis of the first 315 patients randomized, after a minimum follow-up of 18 months (range 18-60 months).

European perspective for effective cancer drug development

Abstract: Health systems and the clinical research landscape evolve continuously owing to increased risk aversion, scrutiny by funding bodies, and costs of clinical trials. In this context, however, current drug development procedures are far from optimal, as exemplified by the late-stage failure of several drugs. The identification of new drugs urgently requires approaches based on a solid understanding of cancer biology, and that will support the design of robust confirmatory trials. The complexity and the costs of drug development are now beyond the knowledge and operational capacity of single organisations, therefore, a drastic deviation from the traditional path of drug discovery and new forms of multidisciplinary partnerships are needed to succeed in this sector. The European Organisation for Research and Treatment of Cancer (EORTC) proposes the use of collaborative molecular screening platforms (CMSPs) as a new approach to tackle this issue. These CMSPs have the advantage of optimizing the expertise of several partners and combining efforts alongside with cost-sharing models for efficient patient selection. This article describes some of the challenges to advancing drug development and improving medical treatments and how these hurdles can be overcome.

Health-related quality of life in small-cell lung cancer: a systematic review on reporting of methods and clinical issues in randomised controlled trials.

Abstract: Small-cell lung cancer represents about 15% of all lung cancers; increasingly, randomised controlled trials of this disease measure the health-related quality of life of patients. In this Systematic Review we assess the adequacy of reporting of health-related quality-of-life methods in randomised controlled trials of small-cell lung cancer, and the potential effect of this reporting on clinical decision making. Although overall reporting of health-related quality of life was acceptable, improvements are needed to optimise the use of health-related quality of life in randomised controlled trials.

Combination of MRI and dynamic FET PET for initial glioma grading.

Abstract: Aim: MRI and PET with 18F-fluoro-ethyl-tyrosine (FET) have been increasingly used to evaluate patients with gliomas. Our purpose was to assess the additive value of MR spectroscopy (MRS), diffusion imaging and dynamic FET-PET for glioma grading. Patients, methods: 38 patients (42 ± 15 aged, F/M: 0.46) with untreated histologically proven brain gliomas were included. All underwent conventional MRI, MRS, diffusion sequences, and FET-PET within 3±4 weeks. Performances of tumour FET time-activity-curve, early-to-middle SUVmax ratio, choline / creatine ratio and ADC histogram distribution pattern for gliomas grading were assessed, as compared to histology. Combination of these parameters and respective odds were also evaluated. Results: Tumour time-activity-curve reached the best accuracy (67%) when taken alone to distinguish between low and high-grade gliomas, followed by ADC histogram analysis (65%). Combination of time-activity-curve and ADC histogram analysis improved the sensitivity from 67% to 86% and the specificity from 63-67% to 100% (p < 0.008). On multivariate logistic regression analysis, negative slope of the tumour FET time-activity-curve however remains the best predictor of high-grade glioma (odds 7.6, SE 6.8, p = 0.022). Conclusion: Combination of dynamic FET-PET and diffusion MRI reached good performance for gliomas grading. The use of FET-PET/MR may be highly relevant in the initial assessment of primary brain tumours.

Treatment of primary CNS lymphoma.

Abstract: Primary central nervous system lymphoma is a particular challenge in clinical neuro-oncology. In contrast to most other malignant brain tumors, it may be considered a curable disease at least in younger patients who can tolerate intensive treatment regimens. Yet, therapeutic progress has been limited with little measurable improvement in outcome over the last two decades, mainly due to the low incidence of this tumor, which impedes the execution of large randomized clinical trials, and the failure of most large cooperative groups to conduct such trials. Whenever possible, high-dose methotrexate (HD-MTX) is the backbone of the therapeutic regimen. Response rates can be increased by the addition of second agents like ifosfamide or cytarabine, however, their impact on overall survival is less clear. Similarly, the use of the anti-CD20 antibody rituximab, commonly used in the treatment of B cell lymphomas outside the CNS, remains controversial and has not been examined in adequate clinical trials. The prognosis of patients, who do not qualify for HD-MTX-based chemotherapy, is considerably poorer. Radiation therapy is an active treatment with high response rates but does typically not result in long-lasting remissions. It remains an important therapeutic option as a salvage therapy in patients progressing on or no longer responding to HD-MTX-based treatment. The combination of HD-MTX and radiation therapy does not prolong overall survival. It is associated with significant neurotoxicity, and it should be avoided. Another matter of debate is whether consolidation therapy by other means, such as high-dose chemotherapy followed by stem cell support, is the most promising regimen. Given these numerous uncertainties, neuro-oncologists should strive for a treatment of PCNSL patients within clinical trials to allow for the development of improved therapeutic regimens.

Clinical management and outcome of histologically verified adult brainstem gliomas in Switzerland: a retrospective analysis of 21 patients

Abstract: Because of low incidence, mixed study populations and paucity of clinical and histological data, the management of adult brainstem gliomas (BSGs) remains non-standardized. We here describe characteristics, treatment and outcome of patients with exclusively histologically confirmed adult BSGs. A retrospective chart review of adults (age >18 years) was conducted. BSG was defined as a glial tumor located in the midbrain, pons or medulla. Characteristics, management and outcome were analyzed. Twenty one patients (17 males; median age 41 years) were diagnosed between 2004 and 2012 by biopsy (n = 15), partial (n = 4) or complete resection (n = 2). Diagnoses were glioblastoma (WHO grade IV, n = 6), anaplastic astrocytoma (WHO grade III, n = 7), diffuse astrocytoma (WHO grade II, n = 6) and pilocytic astrocytoma (WHO grade I, n = 2). Diffuse gliomas were mainly located in the pons and frequently showed MRI contrast enhancement. Endophytic growth was common (16 vs. 5). Postoperative therapy in low-grade (WHO grade I/II) and high-grade gliomas (WHO grade III/IV) consisted of radiotherapy alone (three in each group), radiochemotherapy (2 vs. 6), chemotherapy alone (0 vs. 2) or no postoperative therapy (3 vs. 1). Median PFS (24.1 vs. 5.8 months; log-rank, p = 0.009) and mOS (30.5 vs. 11.5 months; log-rank, p = 0.028) was significantly better in WHO grade II than in WHO grade III/IV tumors. Second-line therapy considerably varied. Histologically verification of adult BSGs is feasible and has an impact on postoperative treatment. Low-grade gliomas can simple be followed or treated with radiotherapy alone. Radiochemotherapy with temozolomide can safely be prescribed for high-grade gliomas without additional CNS toxicities.

Questions regarding the optimal use of bevacizumab in glioblastoma: a moving target

Abstract: The saga of bevacizumab in brain tumors has been ongoing for many years. Despite encouraging initial reports targeting the vascular endothelial growth factor (VEGF) pathway by a neutralizing monoclonal antibody (bevacizumab) or a receptor tyrosine kinase inhibitor (cediranib), the few subsequent controlled studies were largely disappointing. Opportunities for adequate clinical investigation with bevacizumab were missed or delayed for many years. Nevertheless, these agents undoubtedly have a clinically meaningful benefit in selected patients. However, we lackclinical or biomarkers allowing identification of specific patients that benefit from these therapies. The highly variable clinical practice reflects the contradictory reports and the paucity of prospective and controlled trials. The absence of adequate data also prevented regulatory approval in many countries, especially in the European Union, thus preventing access to bevacizumab for patients. Numerous basic questions remain unresolved years after the drug has entered routine clinical use. 1 Two reports analyzing retrospectively large institutional databases on management of recurrent glioblastoma appear in this issue of Neuro-Oncology, 2,3 and two pivotal prospective randomized trials on the use of bevacizumab in newly diagnosed patients were recently reported. 4,5 Thus, it is timely to briefly review some of the available data and discuss their limitations.

The Neurologic Assessment in Neuro-Oncology (NANO) Scale: A Tool to Assess Neurologic Function for Integration in the Radiologic Assessment in Neuro-Oncology (RANO) Criteria (S22.005)

Abstract: OBJECTIVE: To develop a standardized metric to measure neurologic function that will permit better overall response assessment in neuro-oncology. BACKGROUND: The Macdonald criteria and RANO (response assessment in neuro-oncology) criteria define radiologic parameters to classify therapeutic outcome among malignant glioma patients. While both scales specify that clinical status must be incorporated for overall assessment, neither provides specific parameters to do so. Furthermore, both scales prioritize clinical status over radiology in that response requires at least stable clinical status, while clinical status is sufficient to declare progression. DESIGN/METHODS: An international group of neuro-oncologists convened bi-weekly for the past year to draft the Neurologic Assessment in Neuro-Oncology (NANO) criteria as an objective and quantifiable metric of neurologic function evaluable during a routine office examination. RESULTS: The NANO scale is a quick, oncology-friendly, quantifiable evaluation of eight relevant neurologic domains based on direct observation/testing conducted during routine office visits. The score defines criteria for domain-specific and overall scores of response, progression, stable disease and not assessed. A given domain will be scored non-evaluable if it cannot be accurately assessed due to pre-existing conditions, co-morbid events, and/or concurrent medications. CONCLUSIONS: The NANO criteria provide a more detailed and objective measure of neurologic function than currently exists for brain tumor patients. These criteria enable a consistent evaluation of neurologic function that can be assessed across clinical trials and therapeutic interventions. Implementation and validation of these criteria are planned and will likely be regularly refined for further optimization. Disclosure: Dr. Nayak has nothing to disclose. Dr. DeAngelis has received personal compensation for activities with the NFL Players Association as a consultant. Dr. Wen has received personal compensation for activities with Roche, Novartis, Merck, and NeOnc. Dr. Wen has received personal compensation in an editorial capacity for Up to Date and Journal of Neuro-Oncology. Dr. Wen has received research support from Amgen, Astra Zeneca, Eisai, Exelixis, Genentech, Inc., Merck, Novartis, Sanofi-Aventis, and Vascular Biogenics. Dr. Brandes has nothing to disclose. Dr. Soffietti has nothing to disclose. Dr. Lin has nothing to disclose. Dr. Peereboom has nothing to disclose. Dr. Chamberlain has received personal compensation for activities with Genentech/Roche as a speaker. Dr. Chamberlain has received compensation for serving on the advisory boards of Genentech/Roche. Dr. Chamberlain has received research support from Exelixis, MedImmune, Myriad, NCCN and Northwestern University/Genentech. Dr. Macdonald has received personal compensation for activities with Schering AG as a consultant. Dr. Galanis has nothing to disclose. Dr. Perry has nothing to disclose. Dr. Jaeckle has nothing to disclose. Dr. Mehta has nothing to disclose. Dr. Stupp has nothing to disclose. Dr. Van Den Bent has received personal compensation for activities with Schering-Plough Corp. as a member of scientific advisory boards and the speaker9s bureau. Dr. Van Den Bent has received research support from Schering-Plough Corp. Dr. Reardon has received personal compensation for activities with Merck Schering, Roche Diagnostics Inc., EMD Serono, Abbott and Abogenix.

Addition of lomustine for bevacizumab-refractory recurrent glioblastoma.

Abstract: analogues for the targeted treatment of cancer . J Med Chem 2006 ; 49 : 4392 – 408 . Burris HA 3rd , Rugo HS , Vukelja SJ , Vogel CL , Borson RA , [5] Limentani S , et al . Phase II study of the antibody drug conjugate trastuzumab-DM1 for the treatment of human epidermal growth factor receptor 2 (HER2)-positive breast cancer after prior HER2-directed therapy . J Clin Oncol 2011 ; 29 : 398 – 405 . Carlson JA , Nooruddin Z , Rusthoven C , Elias A , Borges VF , [6] Diamond JR , et al . Trastuzumab emtansine and stereotactic radiosurgery: An unexpected increase in clinically signifi cant brain edema . Neuro Oncol Epub 2014 Feb 3 . DeAngelis L , Posner J . Neurologic complications of cancer [7] (Contemporary Neurology Series) . Vol. 73. 2nd ed. New York: Oxford University Press; 2009 . Gabos Z , Sinha R , Hanson J , Chauhan N , Hugh J , Mackey [8] JR , et al . Prognostic signifi cance of human epidermal growth factor receptor positivity for the development of brain metastasis after newly diagnosed breast cancer . J Clin Oncol 2006 ; 24 : 5658 – 63 . Pestalozzi BC , Zahrieh D , Price KN , Holmberg SB , Lindtner [9] J , Collins J , et al . Identifying breast cancer patients at risk for central nervous system (CNS) metastases in trials of the International Breast Cancer Study Group (IBCSG) . Ann Oncol 2006 ; 17 : 935 – 44 . Chang J , Clark GM , Allred DC , Mohsin S , Chamness G , [10] Elledge RM . Survival of patients with metastatic breast carcinoma: Importance of prognostic markers of the primary tumor . Cancer 2003 ; 97 : 545 – 53 . Kallioniemi OP , Holli K , Visakorpi T , Koivula T , Helin HH , [11] Isola JJ . Association of c-erbB-2 protein over-expression with high rate of cell proliferation, increased risk of visceral metastasis and poor long-term survival in breast cancer . Int J Cancer 1991 ; 49 : 650 – 5 . Genentech . (2013) Direct healthcare professional communi[12] cation of cases of severe hemorrhage reported with Kadcyla ®

The changing world of drug development: an academic research organization’s perspective on the “Seven Wonders” of the future world of anticancer drug development

Abstract: Cancer poses a considerable economic burden to healthcare systems worldwide, so healthcare payers will only pay for "performance" in the future. It is likely that new "wonders" have emerged and as a scientific community we need to learn how we can make future cancer research more efficient. Biobanking and imaging platforms will allow full use of this wealth of data for defining and testing hypotheses before the launch of fewer, but ambitious, pivotal clinical studies targeting large therapeutic benefit. Clinical trials must be based on optimized trial designs with sound methodologies and high qualities. These multidisciplinary therapeutic strategies need to be in the new generation of patient treatment planning. In order to accelerate patient access to new treatments and techniques, better harmonized regulatory procedures and new forms of multi-stakeholder collaboration are needed in future drug development.

At-26clinical management and outcome of histologically verified adult brainstem gliomas in switzerland: a retrospective analysis of 21 patients

Abstract: BACKGROUND: Because of low incidence, mixed study populations and paucity of clinical and histological data, the management of adult brainstem gliomas remains non-standardized. We here describe characteristics, treatment and outcome of patients with exclusively histologically confirmed adult brainstem gliomas. METHODS: A retrospective chart review of adults (> age 18 years) was conducted. Brainstem glioma was defined as a glial tumor located in the midbrain, pons or medulla. Characteristics, management and outcome were analyzed. RESULTS: 21 patients (17 males; median age 41 years) were diagnosed between 2004 and 2012 by biopsy (n = 15), partial (n = 4) or complete resection (n = 2). Diagnoses were glioblastoma (WHO grade IV, n = 6), anaplastic astrocytoma (WHO grade III, n = 7), diffuse astrocytoma (WHO grade II, n = 6) and pilocytic astrocytoma (WHO grade I, n = 2). Diffuse gliomas were mainly located in the pons and frequently showed MRI contrast enhancement. Endophytic growth was common (16 versus 5). Postoperative therapy in low-grade (WHO grade I/II) and high-grade gliomas (WHO grade III/IV) consisted of radiotherapy alone (3 in each group), radiochemotherapy (2 versus 6), chemotherapy alone (0 versus 2) or no postoperative therapy (3 versus 1). Median PFS (24.1 versus 5.8 months; log-rank, p = 0.009) and mOS (30.5 versus 11.5 months; log-rank, p = 0.028) was significantly better in WHO grade II than in WHO grade III/IV tumors. Second-line therapy considerably varied. CONCLUSIONS: Histologically verification of adult brainstem glioma is feasible and has an impact on postoperative treatment. Low-grade gliomas can simple be followed or treated with radiotherapy alone. Radiochemotherapy with temozolomide can safely be prescribed for high-grade gliomas without additional CNS toxicities.