Publications by authors named "Martin J van den Bent"

205 Publications

Effect of antiepileptic drugs in glioma patients on self-reported depression, anxiety, and cognitive complaints.

J Neurooncol 2021 Apr 6. Epub 2021 Apr 6.

Department of Neurology, Leiden University Medical Center, PO BOX 9600, Leiden, 2300 RC, The Netherlands.

Introduction: AEDs have been associated with depression, anxiety, and cognitive impairment, all frequent complications of glioma and its subsequent treatment, with considerable morbidity and an adverse effect on health-related quality of life. This study aimed to determine the independent association between AED use and self-reported depression, anxiety, and subjective cognitive impairment in glioma patients.

Methods: In this multicenter cross-sectional study, depression and anxiety were assessed with the HADS and subjective cognitive impairment was assessed with the MOS-CFS. Univariable logistic regression analyses were performed on all potential confounding predictor variables. Potential confounders were included in the multivariable analyses if p-value < 0.1, to evaluate whether use of AEDs was independently related to depression, anxiety, and/or subjective cognitive impairment.

Results: A total of 272 patients were included. Prevalence of depression differed significantly between patients not using (10%) and using AEDs (21%, unadjusted Odds Ratio [uOR] = 2.29 [95%CI 1.05-4.97], p = 0.037), but after correction for confounders the statistical significant difference was no longer apparent (adjusted Odds Ratio [aOR] = 1.94 [95%CI 0.83-4.50], p = 0.125). Prevalences of anxiety (aOR = 1.17 [95%CI 0.59-2.29], p = 0.659) and subjective cognitive impairment (aOR = 0.83 [95%CI 0.34-2.04], p = 0.684) did not differ significantly before or after adjustment of confounders between patients not using (19% and 16%, respectively) and using AEDs (26% and 21%, respectively).

Conclusions: Our results indicate AED use was not independently associated with concurrent depression, anxiety, or subjective cognitive impairment in glioma patients. Alternative factors seem to have a greater contribution to the risk of developing neuropsychiatric symptoms in glioma patients.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1007/s11060-021-03747-1DOI Listing
April 2021

First-line antiepileptic drug treatment in glioma patients with epilepsy: Levetiracetam vs valproic acid.

Epilepsia 2021 Mar 18. Epub 2021 Mar 18.

Department of Neurology, Leiden University Medical Center, Leiden, The Netherlands.

Objective: This study aimed at estimating the cumulative incidence of antiepileptic drug (AED) treatment failure of first-line monotherapy levetiracetam vs valproic acid in glioma patients with epilepsy.

Methods: In this retrospective observational study, a competing risks model was used to estimate the cumulative incidence of treatment failure, from AED treatment initiation, for the two AEDs with death as a competing event. Patients were matched on baseline covariates potentially related to treatment assignment and outcomes of interest according to the nearest neighbor propensity score matching technique. Maximum duration of follow-up was 36 months.

Results: In total, 776 patients using levetiracetam and 659 using valproic acid were identified. Matching resulted in two equal groups of 429 patients, with similar covariate distribution. The cumulative incidence of treatment failure for any reason was significantly lower for levetiracetam compared to valproic acid (12 months: 33% [95% confidence interval (CI) 29%-38%] vs 50% [95% CI 45%-55%]; P < .001). When looking at specific reasons of treatment failure, treatment failure due to uncontrolled seizures was significantly lower for levetiracetam compared to valproic acid (12 months: 16% [95% CI 12%-19%] vs 28% [95% CI 23%-32%]; P < 0.001), but no differences were found for treatment failure due to adverse effects (12 months: 14% [95% CI 11%-18%] vs 15% [95% CI 11%-18%]; P = .636).

Significance: Our results suggest that levetiracetam may have favorable efficacy compared to valproic acid, whereas level of toxicity seems similar. Therefore, levetiracetam seems to be the preferred choice for first-line AED treatment in patients with glioma.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1111/epi.16880DOI Listing
March 2021

Adolescents and Young Adults Living With an Uncertain or Poor Cancer Prognosis: The "New" Lost Tribe.

J Natl Compr Canc Netw 2021 03 2;19(3):240-246. Epub 2021 Mar 2.

Department of Psychosocial Research and Epidemiology, Netherlands Cancer Institute.

Historically, adolescent and young adult (AYA) patients with cancer, diagnosed for the first time at age 15 through 39 years, have often been identified as a "lost tribe" without a medical "home"; neither pediatric nor adult oncology services were able to provide age-appropriate care to this specific group. Internationally, AYA care programs are being established to bridge the gap between the age-defined healthcare worlds and to address the specific needs of AYAs with cancer. However, AYA care programs mostly focus on improving cure rates and addressing survivorship issues, and direct less attention to the unique needs of those living with an uncertain and/or poor cancer prognosis. Additionally, palliative care services are typically poorly equipped to address the age-specific needs of this group. Given that increasingly more AYAs with an uncertain and/or poor cancer prognosis are gaining life years because of novel treatments, and sometimes even face the prospect of long-term disease control, AYA care programs should address the unique palliative care needs of this "new" lost tribe within AYA oncology. This report provides a definition and description of the AYA population living with an uncertain and/or poor cancer prognosis in terms of epidemiologic, clinical, and psychosocial characteristics and challenges, and provides perspectives for future research and care initiatives. It also highlights the need to comprehensively examine the experience of AYAs who are living with uncertain and/or poor cancer prognosis to adjust best care practices for this unique group.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.6004/jnccn.2020.7696DOI Listing
March 2021

Extent of radiological response does not reflect survival in primary central nervous system lymphoma.

Neurooncol Adv 2021 Jan-Dec;3(1):vdab007. Epub 2021 Feb 15.

Department of Neuro-Oncology, Erasmus MC Cancer Institute, Brain Tumor Center, University Medical Center Rotterdam, Rotterdam, The Netherlands.

Background: In primary central nervous system lymphoma (PCNSL), small enhancing lesions can persist after treatment. It is unknown whether a difference in response category (complete response [CR], complete response unconfirmed [CRu], or partial response [PR]) reflects survival. We aimed to determine the value of a central radiology review on response assessment and whether the extent of response influenced progression-free and/or overall survival.

Methods: All patients in the HOVON 105/ALLG NHL 24 study with at least a baseline MRI and one MRI made for response evaluation available for central review were included. Tumor measurements were done by 2 independent central reviewers, disagreements were adjudicated by a third reviewer. Crude agreement and interobserver agreement (Cohen's kappa) were calculated. Differences in progression-free and overall survival between different categories of response at the end-of-protocol-treatment were assessed by the log-rank test in a landmark survival-analysis.

Results: Agreement between the central reviewers was 61.7% and between local and central response assessment was 63.0%. Cohen's kappa's, which corrects for expected agreement, were 0.44 and 0.46 (moderate), respectively. Progression agreement or not was 93.3% (kappa 0.87) between local and central response assessment. There were no significant differences in progression-free and overall survival between patients with CR, CRu, or PR at the end-of-protocol-treatment, according to both local and central response assessment.

Conclusions: Reliability of response assessment (CR/CRu/PR) is moderate even by central radiology review and these response categories do not reliably predict survival. Therefore, primary outcome in PCNSL studies should be survival rather than CR or CR/CRu-rate.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1093/noajnl/vdab007DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7883767PMC
February 2021

MMSE is an independent prognostic factor for survival in primary central nervous system lymphoma.

J Neurooncol 2021 Apr 21;152(2):357-362. Epub 2021 Feb 21.

Department of Neuro-Oncology, Erasmus MC Cancer Institute, Brain Tumor Center, University Medical Center Rotterdam, Dr. Molewaterplein 40, 3015 GD, Rotterdam, Netherlands.

Introduction: To assess the value of the Mini-Mental State Examination (MMSE)-score at baseline in predicting survival in adult primary central nervous system lymphoma (PCNSL) patients.

Methods: In the HOVON 105/ ALLG NHL 24 phase III study patients with newly-diagnosed PCNSL were randomized between high-dose methotrexate-based chemotherapy with or without rituximab. Data on potential (MMSE-score), and known baseline prognostic factors (age, performance status, serum LDH, cerebrospinal fluid total protein, involvement of deep brain structures, multiple cerebral lesions, and the IELSG-score) were collected prospectively. Multivariable stepwise Cox regression analyses were used to assess the prognostic value of all factors on progression-free survival (PFS) and overall survival (OS) among patients with available MMSE score at baseline. Age was analyzed as continuous variable, the MMSE-score both as a continuous and as a categorical variable.

Results: In univariable analysis, age, MMSE-score and whether the patient received rituximab were statistically significantly prognostic factors for PFS. Age and MMSE-score were statistically significantly associated with OS. In a multivariable analysis of the univariately significant factors only MMSE-score was independently associated with the survival endpoints, as a continuous variable (HR for PFS 1.04, 95% CI 1.01-1.08; OS 1.06 (95% CI 1.02-1.10) and as categorical variable HR (< 27 versus ≥ 27 for PFS 1.55 (1.02-2.35); OS 1.68 (1.05-2.70). In our population, performance status, serum LDH, and CSF protein level were not of prognostic value.

Conclusion: Neurocognitive disturbances, measured with the MMSE at baseline, are an unfavorable prognostic factor for both PFS and OS in adult PCNSL patients up to 70 years-old.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1007/s11060-021-03708-8DOI Listing
April 2021

Impact of depatuxizumab mafodotin on health-related quality of life and neurological functioning in the phase II EORTC 1410/INTELLANCE 2 trial for EGFR-amplified recurrent glioblastoma.

Eur J Cancer 2021 Apr 15;147:1-12. Epub 2021 Feb 15.

Department of Neurology, Brain Tumor Center at Erasmus MC Cancer Institute, University Medical Center Rotterdam, Rotterdam, the Netherlands. Electronic address:

Background: In the EORTC 1410/INTELLANCE 2 randomised, phase II study (NCT02343406), with the antibody-drug conjugate depatuxizumab mafodotin (Depatux-M, ABT-414) in patients with recurrent EGFR-amplified glioblastoma, the primary end-point (overall survival) was not met, and the drug had ocular dose-limiting toxicity. This study reports results from the prespecified health-related quality of life (HRQoL) and neurological deterioration-free survival (NDFS) exploratory analysis.

Patients And Methods: Patients (n = 260) were randomised 1:1:1 to receive either Depatux-M 1.25 mg/kg or 1.0 mg/kg intravenously every 2 weeks with oral temozolomide (TMZ) 150 mg/m, Depatux-M alone, or TMZ or oral lomustine (CCNU) 110 mg/m (TMZ/CCNU). HRQoL outcomes were recorded using the EORTC core Quality of Life QLQ-C30, and brain cancer-specific QLQ-BN20 questionnaires. Questionnaires were completed at baseline, weeks 8 and 16, and month 6, and changes from baseline to each time point were calculated. NDFS was defined as time to first deterioration in World Health Organisation performance status.

Results: Compliance with HRQoL was 88.1% at baseline and decreased to 37.9% at month 6. Differences from baseline between Depatux-M arms and TMZ/CCNU in global health/QoL status throughout treatment did not reach clinical relevance (≥10 points). Self-reported visual disorders deteriorated to a clinically relevant extent with Depatux-M arms versus TMZ/CCNU at all timepoints (mean differences range: 24.6-35.1 points). Changes from baseline for other HRQoL scales and NDFS were generally similar between treatment arms.

Conclusions: Depatux-M had no impact on HRQoL and NDFS in patients with EGFR-amplified recurrent glioblastoma, except for more visual disorders, an expected side-effect of the study drug.

Clinical Trial Registration: NCT02343406.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.ejca.2021.01.010DOI Listing
April 2021

Establishing anchor-based minimally important differences for the EORTC QLQ-C30 in glioma patients.

Neuro Oncol 2021 Feb 18. Epub 2021 Feb 18.

European Organisation for Research and Treatment of Cancer (EORTC), Brussels, Belgium.

Background: Minimally important differences (MIDs) allow interpretation of the clinical relevance of health-related quality of life (HRQOL) results. This study aimed to estimate MIDs for all EORTC QLQ-C30 scales for interpreting group-level results in brain tumor patients.

Methods: Clinical and HRQOL data from three glioma trials were used. Clinical anchors were selected for each EORTC QLQ-C30 scale, based on correlation (>0.30) and clinical plausibility of association. Changes in both HRQOL and the anchors were calculated, and for each scale and time period, patients were categorized into one of three clinical change groups: deteriorated by one anchor category, no change, or improved by one anchor category. Mean change method and linear regression were applied to estimate MIDs for interpreting within-group change and between-group differences in change over time, respectively. Distribution-based methods were applied to generate supportive evidence.

Results: A total of 1687 patients were enrolled in the three trials. The retained anchors were performance status and eight Common Terminology Criteria for Adverse Events (CTCAE) scales. MIDs for interpreting within-group change ranged from 4 to 12 points for improvement and -4 to -14 points for deterioration. MIDs for between-group difference in change ranged from 4 to 9 for improvement and -4 to -16 for deterioration. Most anchor-based MIDs were closest to the 0.3SD distribution-based estimates (range: 3-10).

Conclusions: MIDs for the EORTC QLQ-C30 scales generally ranged between 4-11 points for both within-group mean change and between-group mean difference in change. These results can be used to interpret QLQ-C30 results from glioma trials.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1093/neuonc/noab037DOI Listing
February 2021

Neurocognitive functioning and radiologic changes in primary CNS lymphoma patients: results from the HOVON 105/ ALLG NHL 24 randomised controlled trial.

Neuro Oncol 2021 Feb 9. Epub 2021 Feb 9.

Erasmus MC Cancer Institute, Brain Tumor Center, University Medical Center Rotterdam, Department of Neuro-Oncology, the Netherlands.

Background: To analyze the effect of treatment on neurocognitive functioning and the association of neurocognition with radiological abnormalities in primary central nervous system lymphoma (PCNSL).

Methods: 199 patients from a phase III trial (HOVON 105/ALLG NHL 24), randomized to standard chemotherapy with or without rituximab, followed in patients ≤60 years-old by 30Gy WBRT, were asked to participate in a neuropsychological evaluation before and during treatment, and up to 2 years post-treatment. Scores were transformed into a standardized z-score; clinically relevant changes were defined as a change in z-score of ≥1 standard deviation. The effect of WBRT was analyzed in irradiated patients. All MRIs were centrally assessed for white matter abnormalities and cerebral atrophy, and their relation with neurocognitive scores over time in each domain was calculated.

Results: 125/199 patients consented to neurocognitive evaluation. Statistically significant improvements in neurocognition were seen in all domains. A clinically relevant improvement was seen only in the motor speed domain, without differences between the arms. In the follow-up of irradiated patients (n=43), no change was observed in any domain score, compared to after WBRT. Small but significant inverse correlations were found between neurocognitive scores over time and changes in white matter abnormalities (regression coefficients: -0.048 to -0.347) and cerebral atrophy (-0.212 to -1.774).

Conclusions: Addition of rituximab to standard treatment in PCNSL patients did not impact neurocognitive functioning up to two years post-treatment, nor did treatment with 30Gy WBRT in patients ≤60 years-old. Increased white matter abnormalities and brain atrophy showed weak associations with neurocognition.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1093/neuonc/noab021DOI Listing
February 2021

Detection of Aneuploidy in Cerebrospinal Fluid from Patients with Breast Cancer can Improve Diagnosis of Leptomeningeal Metastases.

Clin Cancer Res 2021 Jan 29. Epub 2021 Jan 29.

Department of Medical Oncology, Erasmus MC Cancer Institute, Erasmus University Medical Center, Rotterdam, the Netherlands.

Purpose: Detection of leptomeningeal metastasis is hampered by limited sensitivities of currently used techniques: MRI and cytology of cerebrospinal fluid (CSF). Detection of cell-free tumor DNA in CSF has been proposed as a tumor-specific candidate to detect leptomeningeal metastasis at an earlier stage. The aim of this study was to investigate mutation and aneuploidy status in CSF-derived cell-free DNA (cfDNA) of patients with breast cancer with a clinical suspicion of leptomeningeal metastasis.

Experimental Design: cfDNA was isolated from stored remnant CSF and analyzed by targeted next-generation sequencing (NGS; = 30) and the modified fast aneuploidy screening test-sequencing system (mFAST-SeqS; = 121). The latter method employs selective amplification of long interspaced nuclear elements sequences that are present throughout the genome and allow for fast and cheap detection of aneuploidy. We compared these results with the gold standard to diagnose leptomeningeal metastasis: cytology.

Results: Leptomeningeal metastasis was cytology proven in 13 of 121 patients. Low DNA yields resulted in insufficient molecular coverage of NGS for the majority of samples (success rate, 8/30). The mFAST-SeqS method, successful in 112 of 121 (93%) samples, detected genome-wide aneuploidy in 24 patients. Ten of these patients had cytology-proven leptomeningeal metastasis; 8 additional patients were either concurrently diagnosed with central nervous system metastases by radiological means or developed these soon after the lumbar puncture. The remaining six cases were suspected of leptomeningeal metastasis, but could not be confirmed by cytology or imaging. Aneuploidy was associated with development of leptomeningeal metastasis and significantly worse overall survival.

Conclusions: Aneuploidy in CSF-derived cfDNA may provide a promising biomarker to improve timely detection of leptomeningeal metastasis.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1158/1078-0432.CCR-20-3954DOI Listing
January 2021

Determining medical decision-making capacity in brain tumor patients: why and how?

Neurooncol Pract 2020 Dec 16;7(6):599-612. Epub 2020 Jul 16.

Department of Neurology, Leiden University Medical Center, Leiden, the Netherlands.

Background: Brain tumor patients are at high risk of impaired medical decision-making capacity (MDC), which can be ethically challenging because it limits their ability to give informed consent to medical treatments or participation in research. The European Association of Neuro-Oncology Palliative Care Multidisciplinary Task Force performed a systematic review to identify relevant evidence with respect to MDC that could be used to give recommendations on how to cope with reduced MDC in brain tumor patients.

Methods: A literature search in several electronic databases was conducted up to September 2019, including studies with brain tumor and other neurological patients. Information related to the following topics was extracted: tools to measure MDC, consent to treatment or research, predictive patient- and treatment-related factors, surrogate decision making, and interventions to improve MDC.

Results: A total of 138 articles were deemed eligible. Several structured capacity-assessment instruments are available to aid clinical decision making. These instruments revealed a high incidence of impaired MDC both in brain tumors and other neurological diseases for treatment- and research-related decisions. Incapacity appeared to be mostly determined by the level of cognitive impairment. Surrogate decision making should be considered in case a patient lacks capacity, ensuring that the patient's "best interests" and wishes are guaranteed. Several methods are available that may help to enhance patients' consent capacity.

Conclusions: Clinical recommendations on how to detect and manage reduced MDC in brain tumor patients were formulated, reflecting among others the timing of MDC assessments, methods to enhance patients' consent capacity, and alternative procedures, including surrogate consent.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1093/nop/npaa040DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7716185PMC
December 2020

A basic review on systemic treatment options in WHO grade II-III gliomas.

Cancer Treat Rev 2021 Jan 13;92:102124. Epub 2020 Nov 13.

Division of Oncology, Department of Medicine I, Medical University of Vienna, Waehringer Guertel 18-20, 1090 Vienna, Austria. Electronic address:

WHO grade II-III gliomas are rare primary brain tumors occurring at a median age of about 35-55 years. Median survival is longer in WHO grade II-III glioma compared with WHO grade IV glioblastoma as survival times of up to 10 years and longer can be observed. Maximal safe resection and adjuvant therapies including chemotherapy and radiotherapy are the mainstay of treatment. Clinical trials in WHO grade II-III tumors are challenging due to the rarity and the long follow up times. The 2016 WHO Classification of Central Nervous Tumours introduced a new diagnostic framework relying on molecular characteristics, providing the definition of prognostically more homogenous subgroups compared to the histopathological analysis. Most available evidence on the adjuvant treatment of WHO II-III gliomas was generated in the pre-molecular era, challenging the interpretation of study results. The present review therefore summarizes the available data from prospective trials on systemic treatment options in WHO grade II-III glioma, considering molecular markers, recently published results and future outlooks in the field.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.ctrv.2020.102124DOI Listing
January 2021

Memory in low-grade glioma patients treated with radiotherapy or Temozolomide. A correlative analysis of EORTC study 22033-26033.

Neuro Oncol 2020 Nov 1. Epub 2020 Nov 1.

Department of Radiation Oncology (MAASTRO), GROW - School for Oncology andDevelopmental Biology, Maastricht University Medical Centre, Maastricht, the Netherlands.

Background: EORTC study 22033-26033 showed no difference in progression-free survival between high-risk low-grade glioma receiving either radiotherapy (RT) or Temozolomide (TMZ) chemotherapy alone as primary treatment. Considering the potential long-term deleterious impact of radiotherapy on memory functioning, this study aims to determine whether TMZ is associated with less impaired memory functioning.

Methods: Using the Visual Verbal Learning Test (VVLT), memory functioning was evaluated at baseline and subsequently every 6 months. Minimal compliance for statistical analyses was set at 60%. Conventional indices of memory performance (VVLT Immediate Recall, Total Recall, Learning Capacity, and Delayed Recall) were used as outcome measures. Using a mixed linear model memory functioning was compared between treatment arms and over time.

Results: Neuropsychological assessment was performed in 98 patients ( 53 RT, 46 TMZ). At 12 months compliance had dropped to 66%, restricting analyses to baseline, 6 months, and 12 months. At baseline, patients in either treatment arm did not differ in memory functioning, gender, age, or educational level. Over time, patients in both arms showed improvement in Immediate Recall (p = 0.017) and total number of words recalled (Total Recall; p < 0.001, albeit with delayed improvement in radiotherapy patients (group by time; p = 0.011). Memory functioning was not associated with radiotherapy gross, clinical, or planned target volumes.

Conclusion: In patients with high-risk low-grade glioma there is no indication that in the first year after treatment radiotherapy has a deleterious effect on memory function when compared to TMZ chemotherapy.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1093/neuonc/noaa252DOI Listing
November 2020

Radiographic read paradigms and the roles of the central imaging laboratory in neuro-oncology clinical trials.

Neuro Oncol 2021 02;23(2):189-198

UCLA Brain Tumor Imaging Laboratory (BTIL), Center for Computer Vision and Imaging Biomarkers, University of California Los Angeles, Los Angeles, California, USA.

Determination of therapeutic benefit in intracranial tumors is intimately dependent on serial assessment of radiographic images. The Response Assessment in Neuro-Oncology (RANO) criteria were established in 2010 to provide an updated framework to better characterize tumor response to contemporary treatments. Since this initial update a number of RANO criteria have provided some basic principles for the interpretation of changes on MR images; however, the details of how to operationalize RANO and other criteria for use in clinical trials are ambiguous and not standardized. In this review article designed for the neuro-oncologist or treating clinician, we outline essential steps for performing radiographic assessments by highlighting primary features of the Imaging Charter (referred to as the Charter for the remainder of this article), a document that describes the clinical trial imaging methodology and methods to ensure operationalization of the Charter into the workings of a clinical trial. Lastly, we provide recommendations for specific changes to optimize this methodology for neuro-oncology, including image registration, requirement of growing tumor for eligibility in trials of recurrent tumor, standardized image acquisition guidelines, and hybrid reader paradigms that allow for both unbiased measurements and more comprehensive interpretation.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1093/neuonc/noaa253DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7906061PMC
February 2021

Pleural metastasis of anaplastic meningioma.

Radiol Case Rep 2020 Dec 19;15(12):2668-2671. Epub 2020 Oct 19.

Department of Medical Oncology, Erasmus MC Cancer Institute, Erasmus University Medical Centre, PO box 2040, 3000 CB, Rotterdam, The Netherlands.

A 52-year-old woman presented to the emergency department with several days of progressive dyspnoea and thoracic pain. Her medical history included a (recurrent) anaplastic meningioma, for which she was treated with surgery and radiotherapy. A chest X-ray showed occurrence of total opacification of the left lower lobe and a chest computed tomography demonstrated a pleural mass of 12 × 9 × 15 cm in the left lower lobe. Biopsy of the pleural mass revealed a metastasis of the patient's anaplastic meningioma. Extracranial metastases from meningioma are extremely uncommon (≤ 0.1%-0.2% of cases), but important for a patient's prognosis.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.radcr.2020.10.020DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7577895PMC
December 2020

Response to Letter to Editor.

Neuro Oncol 2020 11;22(11):1706-1707

UCLA Brain Tumor Imaging Laboratory, Center for Computer Vision and Imaging Biomarkers, David Geffen School of Medicine, University of California Los Angeles, Los Angeles, California, USA.

View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1093/neuonc/noaa202DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7690353PMC
November 2020

Noninvasive Characterization of Tumor Angiogenesis and Oxygenation in Bevacizumab-treated Recurrent Glioblastoma by Using Dynamic Susceptibility MRI: Secondary Analysis of the European Organization for Research and Treatment of Cancer 26101 Trial.

Radiology 2020 10 28;297(1):164-175. Epub 2020 Jul 28.

From the Department of Neuroradiology, Heidelberg University Hospital, Im Neuenheimer Feld 400, 69120 Heidelberg, Germany (P.K., G.B., I.P., M.S., M.F., U.N., S.H., M.B.); Center of Functionally Integrative Neuroscience and MINDLab, Aarhus University Hospital, Aarhus, Denmark (M.B.H., L.Ø.); Neurology Clinic, Heidelberg University Hospital, Heidelberg, Germany (M.N., T.K., A.W., W.W.); Department of Neurology, Medical University Innsbruck, Innsbruck, Austria (M.N.); Medical Image Computing, German Cancer Research Center (DKFZ), Heidelberg, Germany (F.I., K.H.M.H.); Clinical Cooperation Unit Neurooncology, German Cancer Research Center (DKFZ), Heidelberg, Germany (T.K., W.W.); Department of Neuropathology, Institute of Pathology, Heidelberg University Hospital, Heidelberg, Germany (F.S., A.v.D.); Clinical Cooperation Unit Neuropathology, German Cancer Research Center (DKFZ), Heidelberg, Germany (F.S., A.v.D.); Department of Neurology, University Hospital and University of Zurich, Zurich, Switzerland (M.W.); Department of Neurology, Medical Faculty Mannheim, MCTN, University of Heidelberg, Mannheim, Germany (M.P.); Pattern Analysis and Learning Group, Department of Radiation Oncology, Heidelberg University Hospital, Heidelberg, Germany (K.H.M.H.); Department of Neuroradiology, Aarhus University Hospital, Aarhus, Denmark (L.Ø.); Brain Tumor Center at Erasmus MC Cancer Institute, Rotterdam, the Netherlands (M.J.v.d.B.); and European Organization for Research and Treatment of Cancer (EORTC), Brussels, Belgium (T.G.).

Background Relevance of antiangiogenic treatment with bevacizumab in patients with glioblastoma is controversial because progression-free survival benefit did not translate into an overall survival (OS) benefit in randomized phase III trials. Purpose To perform longitudinal characterization of intratumoral angiogenesis and oxygenation by using dynamic susceptibility contrast agent-enhanced (DSC) MRI and evaluate its potential for predicting outcome from administration of bevacizumab. Materials and Methods In this secondary analysis of the prospective randomized phase II/III European Organization for Research and Treatment of Cancer 26101 trial conducted between October 2011 and December 2015 in 596 patients with first recurrence of glioblastoma, the subset of patients with availability of anatomic MRI and DSC MRI at baseline and first follow-up was analyzed. Patients were allocated into those administered bevacizumab (hereafter, the BEV group; either bevacizumab monotherapy or bevacizumab with lomustine) and those not administered bevacizumab (hereafter, the non-BEV group with lomustine monotherapy). Contrast-enhanced tumor volume, noncontrast-enhanced T2 fluid-attenuated inversion recovery (FLAIR) signal abnormality volume, Gaussian-normalized relative cerebral blood volume (nrCBV), Gaussian-normalized relative blood flow (nrCBF), and tumor metabolic rate of oxygen (nTMRO) was quantified. The predictive ability of these imaging parameters was assessed with multivariable Cox regression and formal interaction testing. Results A total of 254 of 596 patients were evaluated (mean age, 57 years ± 11; 155 men; 161 in the BEV group and 93 in non-BEV group). Progression-free survival was longer in the BEV group (3.7 months; 95% confidence interval [CI]: 3.0, 4.2) compared with the non-BEV group (2.5 months; 95% CI: 1.5, 2.9; = .01), whereas OS was not different ( = .15). The nrCBV decreased for the BEV group (-16.3%; interquartile range [IQR], -39.5% to 12.0%; = .01), but not for the non-BEV group (1.2%; IQR, -17.9% to 23.3%; = .19) between baseline and first follow-up. An identical pattern was observed for both nrCBF and nTMRO values. Contrast-enhanced tumor and noncontrast-enhanced T2 FLAIR signal abnormality volumes decreased for the BEV group (-66% [IQR, -83% to -35%] and -33% [IQR, -71% to -5%], respectively; < .001 for both), whereas they increased for the non-BEV group (30% [IQR, -17% to 98%], = .001; and 10% [IQR, -13% to 82%], = .02, respectively) between baseline and first follow-up. None of the assessed MRI parameters were predictive for OS in the BEV group. Conclusion Bevacizumab treatment decreased tumor volumes, angiogenesis, and oxygenation, thereby reflecting its effectiveness for extending progression-free survival; however, these parameters were not predictive of overall survival (OS), which highlighted the challenges of identifying patients that derive an OS benefit from bevacizumab. © RSNA, 2020 See also the editorial by Dillon in this issue.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1148/radiol.2020200978DOI Listing
October 2020

Consensus recommendations for a dynamic susceptibility contrast MRI protocol for use in high-grade gliomas.

Neuro Oncol 2020 09;22(9):1262-1275

Department of Biophysics, Medical College of Wisconsin, Milwaukee, Wisconsin, USA.

Despite the widespread clinical use of dynamic susceptibility contrast (DSC) MRI, DSC-MRI methodology has not been standardized, hindering its utilization for response assessment in multicenter trials. Recently, the DSC-MRI Standardization Subcommittee of the Jumpstarting Brain Tumor Drug Development Coalition issued an updated consensus DSC-MRI protocol compatible with the standardized brain tumor imaging protocol (BTIP) for high-grade gliomas that is increasingly used in the clinical setting and is the default MRI protocol for the National Clinical Trials Network. After reviewing the basis for controversy over DSC-MRI protocols, this paper provides evidence-based best practices for clinical DSC-MRI as determined by the Committee, including pulse sequence (gradient echo vs spin echo), BTIP-compliant contrast agent dosing (preload and bolus), flip angle (FA), echo time (TE), and post-processing leakage correction. In summary, full-dose preload, full-dose bolus dosing using intermediate (60°) FA and field strength-dependent TE (40-50 ms at 1.5 T, 20-35 ms at 3 T) provides overall best accuracy and precision for cerebral blood volume estimates. When single-dose contrast agent usage is desired, no-preload, full-dose bolus dosing using low FA (30°) and field strength-dependent TE provides excellent performance, with reduced contrast agent usage and elimination of potential systematic errors introduced by variations in preload dose and incubation time.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1093/neuonc/noaa141DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7523451PMC
September 2020

Validation of diffusion MRI phenotypes for predicting response to bevacizumab in recurrent glioblastoma: post-hoc analysis of the EORTC-26101 trial.

Neuro Oncol 2020 11;22(11):1667-1676

Department of Neuroradiology, Heidelberg University Hospital, Heidelberg, Germany.

Background: This study validated a previously described diffusion MRI phenotype as a potential predictive imaging biomarker in patients with recurrent glioblastoma receiving bevacizumab (BEV).

Methods: A total of 396/596 patients (66%) from the prospective randomized phase II/III EORTC-26101 trial (with n = 242 in the BEV and n = 154 in the non-BEV arm) met the inclusion criteria with availability of anatomical and diffusion MRI sequences at baseline prior treatment. Apparent diffusion coefficient (ADC) histograms from the contrast-enhancing tumor volume were fitted to a double Gaussian distribution and the mean of the lower curve (ADClow) was used for further analysis. The predictive ability of ADClow was assessed with biomarker threshold models and multivariable Cox regression for overall survival (OS) and progression-free survival (PFS).

Results: ADClow was associated with PFS (hazard ratio [HR] = 0.625, P = 0.007) and OS (HR = 0.656, P = 0.031). However, no (predictive) interaction between ADClow and the treatment arm was present (P = 0.865 for PFS, P = 0.722 for OS). Independent (prognostic) significance of ADClow was retained after adjusting for epidemiological, clinical, and molecular characteristics (P ≤ 0.02 for OS, P ≤ 0.01 PFS). The biomarker threshold model revealed an optimal ADClow cutoff of 1241*10-6 mm2/s for OS. Thereby, median OS for BEV-patients with ADClow ≥ 1241 was 10.39 months versus 8.09 months for those with ADClow < 1241 (P = 0.004). Similarly, median OS for non-BEV patients with ADClow ≥ 1241 was 9.80 months versus 7.79 months for those with ADClow < 1241 (P = 0.054).

Conclusions: ADClow is an independent prognostic parameter for stratifying OS and PFS in patients with recurrent glioblastoma. Consequently, the previously suggested role of ADClow as predictive imaging biomarker could not be confirmed within this phase II/III trial.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1093/neuonc/noaa120DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7690360PMC
November 2020

Glioblastoma in adults: a Society for Neuro-Oncology (SNO) and European Society of Neuro-Oncology (EANO) consensus review on current management and future directions.

Neuro Oncol 2020 08;22(8):1073-1113

Department of Neurology, Erasmus MC Cancer Institute, Rotterdam, the Netherlands.

Glioblastomas are the most common form of malignant primary brain tumor and an important cause of morbidity and mortality. In recent years there have been important advances in understanding the molecular pathogenesis and biology of these tumors, but this has not translated into significantly improved outcomes for patients. In this consensus review from the Society for Neuro-Oncology (SNO) and the European Association of Neuro-Oncology (EANO), the current management of isocitrate dehydrogenase wildtype (IDHwt) glioblastomas will be discussed. In addition, novel therapies such as targeted molecular therapies, agents targeting DNA damage response and metabolism, immunotherapies, and viral therapies will be reviewed, as well as the current challenges and future directions for research.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1093/neuonc/noaa106DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7594557PMC
August 2020

cIMPACT-NOW update 6: new entity and diagnostic principle recommendations of the cIMPACT-Utrecht meeting on future CNS tumor classification and grading.

Brain Pathol 2020 07 19;30(4):844-856. Epub 2020 Apr 19.

International Agency for Research on Cancer, World Health Organization, Lyon, France.

cIMPACT-NOW (the Consortium to Inform Molecular and Practical Approaches to CNS Tumor Taxonomy) was established to evaluate and make practical recommendations on recent advances in the field of CNS tumor classification, particularly in light of the rapid progress in molecular insights into these neoplasms. For Round 2 of its deliberations, cIMPACT-NOW Working Committee 3 was reconstituted and convened in Utrecht, The Netherlands, for a meeting designed to review putative new CNS tumor types in advance of any future World Health Organization meeting on CNS tumor classification. In preparatory activities for the meeting and at the actual meeting, a list of possible entities was assembled and each type and subtype debated. Working Committee 3 recommended that a substantial number of newly recognized types and subtypes should be considered for inclusion in future CNS tumor classifications. In addition, the group endorsed a number of principles-relating to classification categories, approaches to classification, nomenclature, and grading-that the group hopes will also inform the future classification of CNS neoplasms.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1111/bpa.12832DOI Listing
July 2020

Fast-growing oligodendrogliomas are aggressive tumors-the real life biomarker?

Neuro Oncol 2020 07;22(7):907-908

Brain Tumor Center at Erasmus Medical Center Cancer Institute, Rotterdam, the Netherlands.

View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1093/neuonc/noaa097DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7339876PMC
July 2020

Urgent Considerations for the Neuro-oncologic Treatment of Patients with Gliomas During the COVID-19 Pandemic.

Neuro Oncol 2020 Apr 11. Epub 2020 Apr 11.

Department of Neurosurgery, Inova Neuroscience and Spine Institute, Virginia Commonwealth University.

The COVID-19 outbreak is posing unprecedented risks and challenges for all communities and healthcare systems, worldwide. There are unique considerations for many adult patients with gliomas who are vulnerable to the novel coronavirus due to older age and immunosuppression. As patients with terminal illnesses, they present ethical challenges for centers that may need to ration access to ventilator care due to insufficient critical care capacity. It is urgent for the neuro-oncology community to develop a pro-active and coordinated approach to the care of adults with gliomas in order to provide them with the best possible oncologic care while also reducing their risk of viral infection during times of potential healthcare system failure. In this article, we present an approach developed by an international multi-disciplinary group to optimize the care of adults with gliomas during this pandemic. We recommend measures to promote strict social distancing and minimize exposures for patients, address risk and benefit of all therapeutic interventions, pro-actively develop end of life plans, educate patients and caregivers and ensure the health of the multi-disciplinary neuro-oncology workforce. This pandemic is already changing neuro-oncologic care delivery around the globe. It is important to highlight opportunities to maximize the benefit and minimize the risk of glioma management during this pandemic and potentially, in the future.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1093/neuonc/noaa090DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7184330PMC
April 2020

Gray Areas in the Gray Matter: Mutations in Glioma.

Am Soc Clin Oncol Educ Book 2020 Mar;40:1-8

Departments of Therapeutic Radiology and Pathology, Yale School of Medicine, New Haven, CT.

Since the first discovery of isocitrate dehydrogenase ( mutations in cancer, considerable progress has been made in our understanding of their contribution to cancer development. For glioma, this has helped to identify two diagnostic groups of tumors (oligodendroglioma and astrocytoma ) with distinct clinical characteristics and that are now diagnosed by the presence of the mutations. The metabolic changes occurring as the consequence of the altered substrate affinity of the mutant IDH protein results in a cascade of intracellular changes, also inducing a relative sensitivity to chemotherapy and radiotherapy compared with tumors. Pharmacologic blockade of the mutant enzyme with first-in-class inhibitors has been efficacious for the treatment of mutant acute myeloid leukemia (AML) and is currently being evaluated in phase III trials for mutant glioma (INDIGO) and cholangiocarcinoma (ClarIDHy). It seems likely that acquired resistance to mutant IDH inhibitors will eventually emerge, and combination therapies to augment the antitumor activity of mutant IDH inhibitors have already been initiated. Approaches to exploit, rather than inhibit, the unique metabolism of mutant cancer cells have emerged from laboratory studies and are now also being tested in the clinic. Results of these clinical trials are eagerly awaited and will likely provide new key insights and direction of the treatment of mutant human cancer.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1200/EDBK_280967DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7673204PMC
March 2020

Quantification of leptomeningeal metastases from solid tumors remains a challenging issue.

Neuro Oncol 2020 05;22(5):592-593

Brain Tumor Center at Erasmus Medical Center Cancer Institute, Rotterdam, The Netherlands.

View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1093/neuonc/noaa056DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7229239PMC
May 2020

"Real world" use of a highly reliable imaging sign: "T2-FLAIR mismatch" for identification of IDH mutant astrocytomas.

Neuro Oncol 2020 07;22(7):936-943

Department of Neurosurgery, Massachusetts General Hospital, Boston, Massachusetts, USA.

AbstractThe T2-FLAIR (fluid attenuated inversion recovery) mismatch sign is an easily detectable imaging sign on routine clinical MRI studies that suggests diagnosis of isocitrate dehydrogenase (IDH)-mutant 1p/19q non-codeleted gliomas. Multiple independent studies show that the T2-FLAIR mismatch sign has near-perfect specificity, but low sensitivity for diagnosing IDH-mutant astrocytomas. Thus, the T2-FLAIR mismatch sign represents a non-invasive radiogenomic diagnostic finding with potential clinical impact. Recently, false positive cases have been reported, many related to variable application of the sign's imaging criteria and differences in image acquisition, as well as to differences in the included patient populations. Here we summarize the imaging criteria for the T2-FLAIR mismatch sign, review similarities and differences between the multiple validation studies, outline strategies to optimize its clinical use, and discuss potential opportunities to refine imaging criteria in order to maximize its impact in glioma diagnostics.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1093/neuonc/noaa041DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7339896PMC
July 2020

Consensus recommendations for a standardized brain tumor imaging protocol for clinical trials in brain metastases.

Neuro Oncol 2020 06;22(6):757-772

UCLA Brain Tumor Imaging Laboratory, Center for Computer Vision and Imaging Biomarkers, David Geffen School of Medicine, University of California Los Angeles, Los Angeles, California, USA.

A recent meeting was held on March 22, 2019, among the FDA, clinical scientists, pharmaceutical and biotech companies, clinical trials cooperative groups, and patient advocacy groups to discuss challenges and potential solutions for increasing development of therapeutics for central nervous system metastases. A key issue identified at this meeting was the need for consistent tumor measurement for reliable tumor response assessment, including the first step of standardized image acquisition with an MRI protocol that could be implemented in multicenter studies aimed at testing new therapeutics. This document builds upon previous consensus recommendations for a standardized brain tumor imaging protocol (BTIP) in high-grade gliomas and defines a protocol for brain metastases (BTIP-BM) that addresses unique challenges associated with assessment of CNS metastases. The "minimum standard" recommended pulse sequences include: (i) parameter matched pre- and post-contrast inversion recovery (IR)-prepared, isotropic 3D T1-weighted gradient echo (IR-GRE); (ii) axial 2D T2-weighted turbo spin echo acquired after injection of gadolinium-based contrast agent and before post-contrast 3D T1-weighted images; (iii) axial 2D or 3D T2-weighted fluid attenuated inversion recovery; (iv) axial 2D, 3-directional diffusion-weighted images; and (v) post-contrast 2D T1-weighted spin echo images for increased lesion conspicuity. Recommended sequence parameters are provided for both 1.5T and 3T MR systems. An "ideal" protocol is also provided, which replaces IR-GRE with 3D TSE T1-weighted imaging pre- and post-gadolinium, and is best performed at 3T, for which dynamic susceptibility contrast perfusion is included. Recommended perfusion parameters are given.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1093/neuonc/noaa030DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7283031PMC
June 2020

Glioma patient-reported outcome assessment in clinical care and research: a Response Assessment in Neuro-Oncology collaborative report.

Lancet Oncol 2020 02;21(2):e97-e103

Department of Neurology, Leiden University Medical Center, Leiden, Netherlands; Department of Neurology, Haaglanden Medical Center, The Hague, Netherlands.

Clinical trials of treatments for high-grade gliomas have traditionally relied on measures of response or time-dependent metrics; however, these endpoints have limitations because they do not characterise the functional or symptomatic effect of the condition on the person. Including clinical outcome assessments, such as patient- reported outcomes (PROs), to determine net clinical benefit of a treatment strategy is needed because of the substantial burden of symptoms and impaired functioning in this patient population. The US National Cancer Institute convened a meeting to review previous recommendations and existing PRO measures of symptoms and function that can be applied to current trials and clinical practice for high-grade gliomas. Measures were assessed for relevance, relationship to disease and therapy, sensitivity to change, psychometric properties, response format, patient acceptability, and use of self-report. The group also relied on patient input including the results of an online survey, a literature review on available clinical outcomes, expert opinion, and alignment with work done by other organisations. A core set of priority constructs was proposed that allows more comprehensive evaluation of therapies and comparison of outcomes among studies, and enhances efforts to improve the measurement of these core clinical outcomes. The proposed set of constructs was then presented to the Society for Neuro-Oncology Response Assessment in Neuro-Oncology Working Group and feedback was solicited.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/S1470-2045(19)30796-XDOI Listing
February 2020

Molecular Evolution of Wild-Type Glioblastomas Treated With Standard of Care Affects Survival and Design of Precision Medicine Trials: A Report From the EORTC 1542 Study.

J Clin Oncol 2020 01 19;38(1):81-99. Epub 2019 Nov 19.

Erasmus University Medical Center, Rotterdam, the Netherlands.

Purpose: Precision medicine trials in glioblastoma (GBM) are often conducted at tumor recurrence. However, second surgeries for recurrent GBM are not routinely performed, and therefore, molecular data for trial inclusion are predominantly derived from the primary sample. This study aims to establish whether molecular targets change during tumor progression and, if so, whether this affects precision medicine trial design.

Materials And Methods: We collected 186 pairs of primary-recurrent GBM samples from patients receiving chemoradiotherapy with temozolomide and sequenced approximately 300 cancer genes. , , and status was individually determined.

Results: The molecular profile of our cohort was identical to that of other GBM cohorts ( wild-type [WT], 95%; amplified, approximately 50%), indicating that patients amenable to second surgery do not represent a specific molecular subtype. Molecular events in WT GBMs were stable in approximately 80% of events, but changes in mutation status were observed for all examined genes (range, approximately 90% and 60% for and mutations, respectively), and such changes strongly affected targeted trial size and design. A similar pattern of GBM driver instability was observed within promoter-methylated tumors. promoter methylation status remained prognostic at tumor recurrence. The observation that hypermutation at GBM recurrence was rare (8%) and not correlated with outcome was relevant for immunotherapy-based treatments.

Conclusion: This large cohort of matched primary and recurrent WT tumors establishes the frequency of GBM driver instability after chemoradiotherapy with temozolomide. This allows per gene or pathway calculation of trial size at tumor recurrence, using molecular data of the primary tumor only. We also identify genes for which repeat surgery is necessary because of low mutation retention rate.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1200/JCO.19.00367DOI Listing
January 2020

Survival of diffuse astrocytic glioma, IDH1/2 wildtype, with molecular features of glioblastoma, WHO grade IV: a confirmation of the cIMPACT-NOW criteria.

Neuro Oncol 2020 04;22(4):515-523

Department of Neurology, the Brain Tumor Center, Erasmus MC, University Medical Center, Rotterdam, the Netherlands.

Background: The Consortium to Inform Molecular and Practical Approaches to CNS Tumor Taxonomy (cIMPACT-NOW) has recommended that isocitrate dehydrogenase 1 and 2 wildtype (IDH1/2wt) diffuse lower-grade gliomas (LGGs) World Health Organization (WHO) grade II or III that present with (i) a telomerase reverse transcriptase promoter mutation (pTERTmt), and/or (ii) gain of chromosome 7 combined with loss of chromosome 10, and/or (iii) epidermal growth factor receptor (EGFR) amplification should be reclassified as diffuse astrocytic glioma, IDH1/2 wildtype, with molecular features of glioblastoma, WHO grade IV (IDH1/2wt astrocytomas WHO IV). This paper describes the overall survival (OS) of IDH1/2wt astrocytoma WHO IV patients, and more in detail patients with tumors with pTERTmt only.

Methods: In this retrospective multicenter study, we compared the OS of 71 IDH1/2wt astrocytomas WHO IV patients, with radiological characteristics of LGGs, with the OS of 197 IDH1/2wt glioblastoma patients. Moreover, we compared the OS of 22 pTERTmt only astrocytoma patients with the OS of the IDH1/2wt glioblastoma patients.

Results: Median OS was similar for IDH1/2wt astrocytoma WHO IV patients (23.8 mo) and IDH1/2wt glioblastoma patients (19.2 mo) (Cox proportional hazards model: hazard ratio [HR] 1.27, 95% CI: 0.85-1.88, P = 0.242). OS was also similar in patients with IDH1/2wt astrocytomas WHO IV, pTERTmt only, and IDH1/2wt glioblastomas (HR 1.15, 95% CI: 0.64-2.10, P = 0.641).

Conclusions: The presented data confirm the cIMPACT-NOW recommendation and we propose that IDH1/2wt astrocytomas WHO IV in the absence of other qualifying mutations should be classified as IDH1/2wt glioblastomas.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1093/neuonc/noz200DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7158657PMC
April 2020