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  • 1
    Online Resource
    Online Resource
    Perfusion imaging with arterial spin labeling (ASL)–MRI predicts malignant progression in low‑grade (WHO grade II) gliomas
    Springer Science and Business Media LLC ; 2021
    In:  Neuroradiology Vol. 63, No. 12 ( 2021-12), p. 2023-2033
    Details
    In: Neuroradiology, Springer Science and Business Media LLC, Vol. 63, No. 12 ( 2021-12), p. 2023-2033
    Abstract: Predicting malignant progression of grade II gliomas would allow for earlier initiation of treatment. The hypothesis for this single-centre, case–control study was that the perfusion signal on ASL-MRI predicts such malignant progression in the following 12 months. Methods Consecutive patients with the following criteria were included: ≥ 18 years, grade II glioma (biopsied or resected) and an ASL-MRI 6–12 months prior to malignant progression (cases) or stable disease (controls). Malignant progression was defined either radiologically (new T1w-contrast enhancement) or histologically (neurosurgical tissue sampling). Three controls were matched with each case. Some patients served as their own control by using earlier imaging. The ASL-MRIs were reviewed by two neuroradiologists and classified as positive (hyper-intense or iso-intense compared to cortical grey matter) or negative (hypo-intense). In patients with epilepsy, a neurologist reviewed clinicoradiological data to exclude peri-ictal pseudoprogression. The statistical analysis included diagnostic test properties, a Cohen’s Kappa interrater reliability coefficient and stratification for previous radiotherapy. Results Eleven cases (median age = 48, IQR = 43–50 years) and 33 controls (43, 27–50 years) were included. Malignant progression appeared at 37 months (median, IQR = 17–44) after first surgery. Thirty ASL-MRIs were assessed as negative and 14 as positive. None of the MRIs showed signs of peri-ictal pseudoprogression. ASL significantly predicted subsequent malignant progression (sensitivity = 73%; specificity = 82%; OR = 12; 95%-CI = 2.4–59.1; p = 0.002). The interrater reliability coefficient was 0.65. In stratified analysis, ASL-MRI predicted malignant progression both in patients with previous radiotherapy and in those without (Mantel–Haenszel test, p = 0.003). Conclusion Perfusion imaging with ASL-MRI can predict malignant progression within 12 months in patients with grade II glioma.
    Type of Medium: Online Resource
    ISSN: 0028-3940 , 1432-1920
    URL: Article
    DOI: 10.1007/s00234-021-02737-4
    RVK:
    XA 10000
    Language: English
    Publisher: Springer Science and Business Media LLC
    Publication Date: 2021
    detail.hit.zdb_id: 1462953-7
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  • 2
    Online Resource
    Online Resource
    Assessing the efficacy and safety of mycophenolate mofetil versus azathioprine in patients with autoimmune hepatitis (CAMARO trial): study protocol for a randomised controlled trial
    Springer Science and Business Media LLC ; 2022
    In:  Trials Vol. 23, No. 1 ( 2022-12-13)
    Details
    In: Trials, Springer Science and Business Media LLC, Vol. 23, No. 1 ( 2022-12-13)
    Abstract: Currently, the standard therapy for autoimmune hepatitis (AIH) consists of a combination of prednisolone and azathioprine. However, 15% of patients are intolerant to azathioprine which necessitates cessation of azathioprine or changes in therapy. In addition, not all patients achieve complete biochemical response (CR). Uncontrolled data indicate that mycophenolate mofetil (MMF) can induce CR in a majority of patients. Better understanding of first-line treatment and robust evidence from randomised clinical trials are needed. The aim of this study was to explore the potential benefits of MMF as compared to azathioprine, both combined with prednisolone, as induction therapy in a randomised controlled trial in patients with treatment-naive AIH. Methods CAMARO is a randomised (1:1), open-label, parallel-group, multicentre superiority trial. All patients with AIH are screened for eligibility. Seventy adult patients with AIH from fourteen centres in the Netherlands and Belgium will be randomised to receive MMF or azathioprine. Both treatment arms will start with prednisolone as induction therapy. The primary outcome is biochemical remission, defined as serum levels of alanine aminotransferase and immunoglobulin G below the upper limit of normal. Secondary outcomes include safety and tolerability of MMF and azathioprine, time to remission, changes in Model For End-Stage Liver Disease (MELD)-score, adverse events, and aspects of quality of life. The study period will last for 24 weeks. Discussion The CAMARO trial investigates whether treatment with MMF and prednisolone increases the proportion of patients in remission compared with azathioprine and prednisolone as the current standard treatment strategy. In addition, we reflect on the challenges of conducting a randomized trial in rare diseases. Trial registration EudraCT 2016-001038-91 . Prospectively registered on 18 April 2016. Graphical Abstract
    Type of Medium: Online Resource
    ISSN: 1745-6215
    URL: Article
    DOI: 10.1186/s13063-022-06890-w
    Language: English
    Publisher: Springer Science and Business Media LLC
    Publication Date: 2022
    detail.hit.zdb_id: 2040523-6
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  • 3
    Online Resource
    Online Resource
    Long-term wellbeing and neurocognitive functioning of diffuse low-grade glioma patients and their caregivers: A longitudinal study spanning two decades
    Oxford University Press (OUP) ; 2023
    In:  Neuro-Oncology Vol. 25, No. 2 ( 2023-02-14), p. 351-364
    Details
    In: Neuro-Oncology, Oxford University Press (OUP), Vol. 25, No. 2 ( 2023-02-14), p. 351-364
    Abstract: While patients with diffuse low-grade glioma (LGG) often survive for years, there is a risk of tumor progression which may impact patients’ long-term health-related quality of life (HRQOL) and neurocognitive functioning (NCF). We present a follow-up of LGG patients and their informal caregivers (T3) who took part in our previous HRQOL investigations (T1, M = 7 and T2 M = 13 years after diagnosis). Methods Participants completed HRQOL (short form-36 health survey [SF-36]; EORTC-BN20), fatigue (Checklist Individual Strength [CIS] ), and depression (Center for Epidemiological Studies-Depression [CES-D]) questionnaires and underwent NCF assessments. T3 scores were compared with matched controls. Changes over time (T1–T2–T3) on group and participant level were assessed. Where available, histology of the initial tumor was revised and immunohistochemical staining for IDH1 R132H mutant protein was performed. Results Thirty patients and nineteen caregivers participated. Of N = 11 with tissue available, 3 patients had confirmed diffuse LGG. At T3, patients (M = 26 years after diagnosis) had HRQOL and NCF similar to, or better than controls, yet 23.3% and 53.3% scored above the cut-off for depression (≥16 CES-D) and fatigue (≥35 CIS), respectively. Caregivers’ HRQOL was similar to controls but reported high rates of fatigue (63.2%). Over time, patients’ mental health improved (P & lt; .05). Minimal detectable change in HRQOL over time was observed in individual patients (30% improvement; 23.3% decline; 20% both improvement and decline) with 23.3% remaining stable. NCF remained stable or improved in 82.8% of patients. Conclusions While HRQOL and NCF do not appear greatly impacted during long-term survivorship in LGG, depressive symptoms and fatigue are persistent.
    Type of Medium: Online Resource
    ISSN: 1522-8517 , 1523-5866
    URL: Article
    DOI: 10.1093/neuonc/noac185
    Language: English
    Publisher: Oxford University Press (OUP)
    Publication Date: 2023
    detail.hit.zdb_id: 2094060-9
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  • 4
    Online Resource
    Online Resource
    Table_3.DOCX
    Frontiers Media SA ; 2021
    In:  Frontiers in Neurology Vol. 12 ( 2021-11-18)
    Details
    In: Frontiers in Neurology, Frontiers Media SA, Vol. 12 ( 2021-11-18)
    Abstract: Background: Diffuse gliomas, which are at WHO grade II-IV, are progressive primary brain tumors with great variability in prognosis. Our aim was to investigate whether pre-operative cognitive functioning is of added value in survival prediction in these patients. Methods: In a retrospective cohort study of patients undergoing awake craniotomy between 2010 and 2019 we performed pre-operative neuropsychological assessments in five cognitive domains. Their added prognostic value on top of known prognostic factors was assessed in two patient groups [low- (LGG) and high-grade gliomas (HGG]). We compared Cox proportional hazards regression models with and without the cognitive domain by means of loglikelihood ratios tests (LRT), discriminative performance measures (by AUC), and risk classificatio n [by Integrated Discrimination Index (IDI)]. Results: We included 109 LGG and 145 HGG patients with a median survival time of 1,490 and 511 days, respectively. The domain memory had a significant added prognostic value in HGG as indicated by an LRT ( p -value = 0.018). The cumulative AUC for HGG with memory included was.78 ( SD = 0.017) and without cognition 0.77 ( SD = 0.018), IDI was 0.043 (0.000–0.102). In LGG none of the cognitive domains added prognostic value. Conclusions: Our findings indicated that memory deficits, which were revealed with the neuropsychological examination, were of additional prognostic value in HGG to other well-known predictors of survival.
    Type of Medium: Online Resource
    ISSN: 1664-2295
    URL: Article
    URL: Article
    URL: Article
    URL: Article
    DOI: 10.3389/fneur.2021.773908
    DOI: 10.3389/fneur.2021.773908.s001
    DOI: 10.3389/fneur.2021.773908.s002
    DOI: 10.3389/fneur.2021.773908.s003
    Language: Unknown
    Publisher: Frontiers Media SA
    Publication Date: 2021
    detail.hit.zdb_id: 2564214-5
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  • 5
    Online Resource
    Online Resource
    Table_1.DOCX
    Frontiers Media SA ; 2021
    In:  Frontiers in Neurology Vol. 12 ( 2021-9-7)
    Details
    In: Frontiers in Neurology, Frontiers Media SA, Vol. 12 ( 2021-9-7)
    Abstract: The onco-metabolite 2-hydroxyglutarate (2HG), a biomarker of IDH-mutant gliomas, can be detected with 1 H MR spectroscopy ( 1 H-MRS). Recent studies showed measurements of 2HG at 7T with substantial gain in signal to noise ratio (SNR) and spectral resolution, offering higher specificity and sensitivity for 2HG detection. In this study, we assessed the sensitivity of semi-localized by adiabatic selective refocusing (sLASER) and J-difference MEsher-GArwood-semi-LASER (MEGA-sLASER) for 2HG detection at 7T. We performed spectral editing at long TE using a TE-optimized sLASER sequence (110 ms) and J-difference spectroscopy using MEGA-sLASER ( TE = 74ms) in phantoms with different 2HG concentrations to assess the sensitivity of 2HG detection. The robustness of the methods against B 0 inhomogeneity was investigated. Moreover, the performance of these two techniques was evaluated in four patients with IDH1-mutated glioma. In contrary to MEGA-sLASER, sLASER was able to detect 2HG concentration as low as 0.5 mM. In case of a composite phantom containing 2HG with overlapping metabolites, MEGA-sLASER provided a clean 2HG signal with higher fitting reliability (lower %CRLB). The results demonstrate that sLASER is more robust against field inhomogeneities and experimental or motion-related artifacts which promotes to adopt sLASER in clinical implementations.
    Type of Medium: Online Resource
    ISSN: 1664-2295
    URL: Article
    URL: Article
    DOI: 10.3389/fneur.2021.718423
    DOI: 10.3389/fneur.2021.718423.s001
    Language: Unknown
    Publisher: Frontiers Media SA
    Publication Date: 2021
    detail.hit.zdb_id: 2564214-5
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  • 6
    Online Resource
    Online Resource
    Effect of radiation therapy on cerebral cortical thickness in glioma patients: Treatment-induced thinning of the healthy cortex
    Oxford University Press (OUP) ; 2020
    In:  Neuro-Oncology Advances Vol. 2, No. 1 ( 2020-01-01)
    Details
    In: Neuro-Oncology Advances, Oxford University Press (OUP), Vol. 2, No. 1 ( 2020-01-01)
    Abstract: With overall survival of brain tumors improving, radiation induced brain injury is becoming an increasing issue. One of the effects of radiation therapy (RT) is thinning of the cerebral cortex, which could be one of the factors contributing to cognitive impairments after treatment. In healthy brain, cortex thickness varies between 1 and 4.5 mm. In this study, we assess the effect of RT on the thickness of the cerebral cortex and relate the changes to the local dose. Methods We identified 28 glioma patients with optimal scan quality. Clinical CTs and MRIs at baseline and 1 year post-RT were collected and coregistered. The scans were processed via an automated image processing pipeline, which enabled measuring changes of the cortical thickness, which were related to local dose. Results Three areas were identified where significant dose-dependent thinning occurred, with thinning rates of 5, 6, and 26 μm/Gy after 1 year, which corresponds to losses of 5.4%, 7.2%, and 21.6% per 30 Gy per year. The first area was largely located in the right inferior parietal, supramarginal, and superior parietal regions, the second in the right posterior cingulate and paracentral regions, and the third almost completely in the right lateral orbital frontal region. Conclusions We have identified three areas susceptible to dose-dependent cortical thinning after radiation therapy. Should future prospective studies conclude that irradiation of these areas lead to cognitive decline, they need to be spared in order to prevent this debilitating consequence of treatment.
    Type of Medium: Online Resource
    ISSN: 2632-2498
    URL: Article
    DOI: 10.1093/noajnl/vdaa060
    Language: English
    Publisher: Oxford University Press (OUP)
    Publication Date: 2020
    detail.hit.zdb_id: 3009682-0
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  • 7
    Online Resource
    Online Resource
    Practice variation in re-resection for recurrent glioblastoma: A nationwide survey among Dutch neuro-oncology specialists
    Oxford University Press (OUP) ; 2023
    In:  Neuro-Oncology Practice Vol. 10, No. 4 ( 2023-04-14), p. 360-369
    Details
    In: Neuro-Oncology Practice, Oxford University Press (OUP), Vol. 10, No. 4 ( 2023-04-14), p. 360-369
    Abstract: Despite current best treatment options, a glioblastoma almost inevitably recurs after primary treatment. However, in the absence of clear evidence, current guidelines on recurrent glioblastoma are not well-defined. Re-resection is one of the possible treatment modalities, though it can be challenging to identify those patients who will benefit. Therefore, treatment decisions are made based on multidisciplinary discussions. This study aimed to investigate the current practice variation between neuro-oncology specialists. Methods In this nationwide study among Dutch neuro-oncology specialists, we surveyed possible practice variation. Via an online survey, 4 anonymized recurrent glioblastoma cases were presented to neurosurgeons, neuro-oncologists, medical oncologists, and radiation oncologists in The Netherlands using a standardized questionnaire on whether and why they would recommend a re-resection or not. The results were used to provide a qualitative analysis of the current practice in The Netherlands. Results The survey was filled out by 56 respondents, of which 15 (27%) were neurosurgeons, 26 (46%) neuro-oncologists, 2 (4%) medical oncologists, and 13 (23%) radiation oncologists. In 2 of the 4 cases, there appeared to be clinical equipoise. Overall, neurosurgeons tended to recommend re-resection more frequently compared to the other specialists. Neurosurgeons and radiation oncologists showed opposite recommendations in 2 cases. Conclusions This study showed that re-resection of recurrent glioblastoma is subject to practice variation both between and within neuro-oncology specialties. In the absence of unambiguous guidelines, we observed a relationship between preferred practice and specialty. Reduction of this practice variation is important; to achieve this, adequate prospective studies are essential.
    Type of Medium: Online Resource
    ISSN: 2054-2577 , 2054-2585
    URL: Article
    DOI: 10.1093/nop/npad016
    Language: English
    Publisher: Oxford University Press (OUP)
    Publication Date: 2023
    detail.hit.zdb_id: 2768945-1
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  • 8
    Online Resource
    Online Resource
    Complications, compliance, and undertreatment do not explain the relationship between cognition and survival in diffuse glioma patients
    Oxford University Press (OUP) ; 2022
    In:  Neuro-Oncology Practice Vol. 9, No. 4 ( 2022-07-15), p. 284-298
    Details
    In: Neuro-Oncology Practice, Oxford University Press (OUP), Vol. 9, No. 4 ( 2022-07-15), p. 284-298
    Abstract: Cognitive deficits occur in all different grades of glioma. In a recent study, we found these deficits to be independently, and possibly causally, related to survival in diffuse gliomas. In this study, we investigated whether the relationship between cognition and survival was mediated by three different factors: undertreatment, complications of treatment, and compliance. We hypothesized that patients with cognitive impairment may undergo less intensive treatment, be less compliant, and suffer more from complications, resulting in shortened survival for cognitively impaired patients. Methods In a retrospective cohort study of patients undergoing awake craniotomy between operative neuropsychological assessments in five cognitive domains. We used Structural Equation Modeling to perform mediation analyses. Mediation analyses are analyses to evaluate whether a variable is a factor in the causal chain, referred to as an intermediate factor. Results In total 254 patients were included, of whom 111 patients were LGG patients and 143 were HGG patients. The most frequently impaired domain was memory (37.8% ≤–2 SD) in HGG and attention and executive functioning in LGG (33.3≤–1.5 SD). We confirmed the significant association between different cognitive domains and survival. These associations could not be explained by one of the aforementioned intermediate factors. Conclusions This suggests that other mechanisms should be involved in the relation between cognition and survival. Hypothetically, cognitive functioning can act as a marker for diffuse infiltration of the tumor or cognitive functioning and survival could be determined by overlapping germline and somatic tumoral molecular-genetic factors.
    Type of Medium: Online Resource
    ISSN: 2054-2577 , 2054-2585
    URL: Article
    DOI: 10.1093/nop/npac027
    Language: English
    Publisher: Oxford University Press (OUP)
    Publication Date: 2022
    detail.hit.zdb_id: 2768945-1
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  • 9
    Online Resource
    Online Resource
    Discontinuation rate of azathioprine
    Wiley ; 2020
    In:  Liver International Vol. 40, No. 11 ( 2020-11), p. 2878-2878
    Details
    In: Liver International, Wiley, Vol. 40, No. 11 ( 2020-11), p. 2878-2878
    Type of Medium: Online Resource
    ISSN: 1478-3223 , 1478-3231
    URL: Issue
    URL: Article
    DOI: 10.1111/liv.v40.11
    DOI: 10.1111/liv.14615
    Language: English
    Publisher: Wiley
    Publication Date: 2020
    detail.hit.zdb_id: 2124684-1
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  • 10
    Online Resource
    Online Resource
    Tumor-related neurocognitive dysfunction in patients with diffuse glioma: a retrospective cohort study prior to antitumor treatment
    Oxford University Press (OUP) ; 2019
    In:  Neuro-Oncology Practice Vol. 6, No. 6 ( 2019-12-07), p. 463-472
    Details
    In: Neuro-Oncology Practice, Oxford University Press (OUP), Vol. 6, No. 6 ( 2019-12-07), p. 463-472
    Abstract: Impairments in neurocognitive functioning (NCF) frequently occur in glioma patients. Both the tumor and its treatment contribute to these impairments. We aimed to quantify NCF in glioma patients before treatment and to investigate which factors influence NCF. Methods We performed a retrospective cohort study in diffuse glioma patients according to STROBE (Strengthening the Reporting of Observational Studies in Epidemiology) criteria. All patients had undergone neuropsychological assessment as part of routine clinical care, before awake surgery. We studied “overall NCF” and NCF in 5 neurocognitive domains separately. For “overall NCF” and per domain, we performed analyses at 2 different levels of outcome measures: (1) group level: mean cognitive functioning of the study sample, and (2) individual level: the percentage of impaired patients. We performed multivariable logistic regression analyses to investigate which factors were associated with the occurrence of cognitive impairments. Results From our cohort of glioma patients (2010-2016), 168 patients met all the inclusion criteria. All cognitive domains were significantly affected at the group level. The percentages of neurocognitive impairments (–2SD) were highest for Executive Functioning, Psychomotor Speed, and Memory (26.5%, 23.2%, and 19.3%, respectively). Patients with high-grade glioma were affected more severely than patients with low-grade glioma. Tumor volume, isocitrate dehydrogenase status, WHO grade, and histology were associated with the occurrence of domain-specific impairments. Conclusions Cognitive impairment occurs in the majority of treatment-naive glioma patients. The domains Executive Functioning, Speed, and Memory are involved most frequently. These impairments in NCF are explained not only by tumor location and volume, but also by other (biological) mechanisms.
    Type of Medium: Online Resource
    ISSN: 2054-2577 , 2054-2585
    URL: Article
    DOI: 10.1093/nop/npz008
    Language: English
    Publisher: Oxford University Press (OUP)
    Publication Date: 2019
    detail.hit.zdb_id: 2768945-1
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