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  • Perioperative fatigue in patients with diffuse glioma
    J Neurooncol. (IF 3.129) Pub Date : 2020-01-23
    Stine Schei, Ole Solheim, Asgeir Store Jakola, Lisa Millgård Sagberg

    Abstract Purpose Few studies have assessed fatigue in relation to glioma surgery. The purpose of this study was to explore the prevalence of pre- and postoperative high fatigue, perioperative changes, and factors associated with pre- and postoperative high fatigue in patients undergoing primary surgery for diffuse glioma. Methods A total of 112 adult patients were prospectively included. Patient-reported fatigue was assessed before and one month after surgery using the cancer-specific European Organization for Research and Treatment of Cancer questionnaire fatigue subscale. The scores were dichotomized as high fatigue (≥ 39) or low fatigue (< 39). A change in score of ≥ 10 was considered as a clinically significant change. Factors associated with pre- and postoperative high fatigue were explored in multivariable regression analyses. Results High fatigue was reported by 45% of the patients preoperatively and by 42% of the patients postoperatively. Female gender and low Karnofsky Performance Status (KPS) were associated with preoperative high fatigue, while postoperative complications, low KPS and low-grade histopathology were associated with postoperative high fatigue. In total 35/92 (38%) patients reported a clinically significant improvement of fatigue scores after surgery, 36/92 (39%) patients reported a clinically significant worsening of fatigue scores after surgery, and 21/92 (23%) patients reported no clinically significant change in fatigue scores after surgery. Patients with low-grade gliomas more often reported low fatigue before surgery and high fatigue after surgery, while patients with high-grade gliomas more often reported high fatigue before surgery and low fatigue after surgery. Conclusions Our findings indicate that fatigue is a common symptom in patients with diffuse glioma, both pre- and postoperatively. Perioperative changes were frequently seen. This is important knowledge when informing patients before and after surgery.

    更新日期:2020-01-23
  • Implantation of carmustine wafers (Gliadel ® ) for high-grade glioma treatment. A 9-year nationwide retrospective study
    J Neurooncol. (IF 3.129) Pub Date : 2020-01-23
    Charles Champeaux, Joconde Weller

    Abstract Background Carmustine wafers (CW) are approved to treat newly or recurrent high-grade gliomas (HGG). Widespread use has been limited regarding some doubtful uncertainties about their efficacy, related increased risk of infection and expensive cost. Objective To describe the epidemiology of CW implantation, search for related complications, long-term survival and associated prognostic factors. Methods We processed the French medico-administrative national database to retrieve appropriate cases operated between 2010 and 2018. A survival analysis was conducted. Results We identified 1659 patients treated in 39 institutions. Median age at CW implantation was 61 years and there was an over-representation of male (63.5%). 491 patients (29.6%) had previous diagnosis of glioma. Time between the first surgery and CW implantation was 0.9 years, IQR[0.6, 1.6]. The frontal lobe was the most frequently involved 29%. 131 patients (7.9%) had to be re operated on for a complication of which 121 for surgical site infection. At one year, 514 patients (31%) had died. Median overall survival (OS) was 1.4 years, 95% CI [1.3, 1.5]. OS at 1 and 2 year was 66%, 95%CI [63.7, 68.5], 32.3%, 95%CI [29.9, 35]. In the adjusted Cox regression, male gender & age at CW implantation were established as independent factors of OS in all three groups. Patients with recurrent HGG have a significant worse prognosis (HR = 0.71, 95% CI [0.62, 0.80] p < 0.001). A post-operative diagnosis of infection or intracranial bleeding eventually leading to a redo surgery was not associated with a decrease OS. Conclusion Over the past 9 years, there is a significant decrease utilisation of CW in France. OS after CW implantation is significantly variable as influenced by many factors such as age, gender or recurrent disease but not by post-operative complications. Compare to previous results, CW may increase the OS and this effect seems more pronounced when adjuvant RT/TMZ is given.

    更新日期:2020-01-23
  • Hypertension and proteinuria as clinical biomarkers of response to bevacizumab in glioblastoma patients
    J Neurooncol. (IF 3.129) Pub Date : 2020-01-23
    Bruno Carvalho, Rafaela Gonçalves Lopes, Paulo Linhares, Andreia Costa, Cláudia Caeiro, Ana Catarina Fernandes, Nuno Tavares, Lígia Osório, Rui Vaz

    Abstract Introduction Arterial hypertension and proteinuria are common side effects of antiangiogenic treatment and might represent a biomarker of response in patients with glioblastoma. The aim of this study was to assess the impact of these side effects in predicting therapeutic response to second line chemotherapy with bevacizumab. Methods We evaluated clinical and survival data of glioblastoma patients who underwent treatment with bevacizumab after progression under temozolomide, at CHUSJ between 2010 and 2017. We analysed treatment-related arterial hypertension, proteinuria grade, thrombotic and haemorrhagic events during treatment. Overall survival (OS) and progression free survival (PFS) under bevacizumab were calculated according to the Kaplan–Meier method. Multivariate analysis was performed using Cox proportional hazards method. Results We evaluated 140 patients. Arterial hypertension and proteinuria occurred in 23 (16.3%) and 17 (12.1%) patients, respectively. PFS during treatment with bevacizumab was 12 months (95% CI 7.9–16.1) in the hypertensive group and 4 months (95% CI 3.2–4.8) in the normotensive group (p = 0.005). Patients with proteinuria had a PFS of 10 months (95% CI 4.9–15.0) versus 4 months (95% CI 3.4–4.8) in patients without proteinuria (p = 0.002). Multivariate analysis revealed hypertension and proteinuria as independent prognostic factors of PFS and OS. Conclusion Our data suggest that hypertension and proteinuria can be effective predictors of response to antiangiogenic therapy in recurrent glioblastoma and are associated with longer disease control.

    更新日期:2020-01-23
  • Perioperative neurocognitive functions in patients with neuroepithelial intracranial tumors
    J Neurooncol. (IF 3.129) Pub Date : 2020-01-22
    Stefanie Bette, Corinna V. Gradtke, Jasmin Hernandez Cammardella, Jennifer Albertshauser, Benedikt Wiestler, Melanie Barz, Bernhard Meyer, Claus Zimmer, Yu-Mi Ryang, Florian Ringel, Jens Gempt

    Abstract Purpose This study aimed to assess perioperative neurocognitive functions in patients with surgery for intracranial neuroepithelial tumors. Methods Seventy-one patients [38 male, 33 female, mean age 47.2 years (range 18 to 81)] with surgery for an intracranial neuroepithelial tumor were included in this prospective single-center study. Mini-mental status examination (MMSE) and extensive neurocognitive testing (divided into the categories attention, memory, and executive functions and adjusted for age, sex, and education) were performed pre-(t0) and early postoperatively (t1). Part of the patient cohort (n = 32) also underwent neurocognitive testing during follow-up (t2). The Karnofsky Performance Status Scale (KPS) was used to assess patients’ functional independence. Patients’ quality of life was recorded by the Short Form 36 (SF 36) pre- and postoperatively in a part of the patient cohort. Pre- and postoperative comparisons were performed using the Wilcoxon-test for paired samples. Post hoc Bonferroni correction was performed to adjust for multiple testing. To assess the influence of risk factors on neurocognitive functions, Spearman correlations and the chi-squared test were performed. Subgroup analyses for patients with low-grade and high-grade tumors were performed. Results Postoperative deterioration was observed in 5 of 39 subtests of extensive neurocognitive testing in all 3 categories, whereas no improvement was shown. Patients with WHO Grade I tumors showed no deterioration of cognitive functions. Patients with WHO Grade II and III tumors showed significantly worse results in the executive functions category patients with WHO Grade IV tumors showed deterioration in the attention category. Significantly worse functional independence was recorded postoperatively and during follow-up (P < 0.001). Patients reported poorer physical health (SF 36, P = 0.001) at t1, whereas mental health did not differ significantly (P = 0.480). Risk factors for postoperative deterioration of cognition are low KPS scores, postoperative radiotherapy and tumor location in the temporal lobe. Conclusions After surgery on an intracranial neuroepithelial tumor, early postoperative deterioration of neurocognitive functions, functional independence and physical health occur. Similar results were also shown during follow-up suggesting that these effects are not only due to postoperative systemic factors or fatigue. This knowledge might improve perioperative surveillance of neurocognitive functions.

    更新日期:2020-01-22
  • Outcomes of whole-brain radiation with simultaneous in-field boost (SIB) for the treatment of brain metastases
    J Neurooncol. (IF 3.129) Pub Date : 2020-01-22
    Jim Zhong, Alex D. Waldman, Shravan Kandula, Bree R. Eaton, Roshan S. Prabhu, Stephen B. Huff, Hui-Kuo G. Shu

    Abstract Purpose Prospective studies have demonstrated increased local control with the addition of a radiosurgery (SRS) boost to whole-brain irradiation (WBRT) in patients with brain metastases. However, the clinical application of SRS boost can be limited by several factors, including tumor size, numbers of lesions, and high cost of care. Here, we investigate the use of WBRT with a simultaneous integrated boost (SIB) to visible lesions in patients with brain metastases. Materials From 2011 to 2016, patients were prospectively enrolled and prescribed a dose of 25 or 37.5 Gray (Gy) WBRT with a SIB dose of 45 or 52.5 Gy to the gross lesions in 10 or 15 fractions, respectively. All plans were optimized for dose coverage of the whole brain and lesions using volumetric arc therapy (VMAT). Comprehensive neurocognitive and quality of life assessments were conducted at baseline and at follow-up. Results Thirteen patients were treated on this protocol. The 1-year local control rates were 92% at the patient level, and 98.6% at the lesion level. The overall 1-year intracranial control was 46%. Patients had no significant declines in Mini-Mental State Examination (MMSE), Hopkins Verbal Learning Test-Revised (HVLT-R), and Medical Outcomes Study (MOS) Cognitive Functional status scores pre- and post-treatment. Conclusion WBRT with SIB to gross lesions using VMAT planning appears to be safe and effective in the treatment of brain metastases without significant cognitive decline. This treatment strategy should be considered in those patients with a high number of metastases or ones not amenable for radiosurgery. Clinical Trial Registration Code NCT01218542

    更新日期:2020-01-22
  • Alternative lengthening of telomeres is the major telomere maintenance mechanism in astrocytoma with isocitrate dehydrogenase 1 mutation
    J Neurooncol. (IF 3.129) Pub Date : 2020-01-20
    Monica Sofia Ventura Ferreira, Mia Dahl Sørensen, Stefan Pusch, Dagmar Beier, Anne-Sophie Bouillon, Bjarne Winther Kristensen, Tim Henrik Brümmendorf, Christoph Patrick Beier, Fabian Beier

    Abstract Purpose Isocitrate dehydrogenase 1 (IDH1) mutations are associated with improved survival in gliomas. Depending on the IDH1 status, TERT promoter mutations affect prognosis. IDH1 mutations are associated with alpha-thalassemia/mental retardation syndrome X-linked (ATRX) mutations and alternative lengthening of telomeres (ALT), suggesting an interaction between IDH1 and telomeres. However, little is known how IDH1 mutations affect telomere maintenance. Methods We analyzed cell-specific telomere length (CS-TL) on a single cell level in 46 astrocytoma samples (WHO II-IV) by modified immune-quantitative fluorescence in situ hybridization, using endothelial cells as internal reference. In the same samples, we determined IDH1/TERT promoter mutation status and ATRX expression. The interaction of IDH1R132H mutation and CS-TL was studied in vitro using an IDH1R132H doxycycline-inducible glioma cell line system. Results Virtually all ALTpositive astrocytomas had normal TERT promoter and lacked ATRX expression. Further, all ALTpositive samples had IDH1R132H mutations, resulting in a significantly longer CS-TL of IDH1R132H gliomas, when compared to their wildtype counterparts. Conversely, TERT promotor mutations were associated with IDHwildtype, ATRX expression, lack of ALT and short CS-TL. ALT, TERT promoter mutations, and CS-TL remained without prognostic significance, when correcting for IDH1 status. In vitro, overexpression of IDHR132H in the glioma cell line LN319 resulted in downregulation of ATRX and rapid TERT-independent telomere lengthening consistent with ALT. Conclusion ALT is the major telomere maintenance mechanism in IDHR132H mutated astrocytomas, while TERT promoter mutations were associated with IDHwildtype glioma. IDH1R132H downregulates ATRX expression in vitro resulting in ALT, which may contribute to the strong association of IDH1R132H mutations, ATRX loss, and ALT.

    更新日期:2020-01-21
  • Efficacy of sequential radiation and chemotherapy in treating glioblastoma with poor performance status
    J Neurooncol. (IF 3.129) Pub Date : 2020-01-20
    Elsa Parr, Richard L. Sleightholm, Michael J. Baine, Nicole A. Shonka, Tony J. Wang, Chi Zhang

    Abstract Introduction While the current standard of care after maximal safe resection for glioblastoma (GBM) is concomitant radiation and chemotherapy, the ideal therapy for patients with poor performance status remains in question due to concerns about treatment tolerance. We sought to evaluate an alternative regimen, sequential radiation and chemotherapy, to assess its efficacy as a treatment option for poorly performing patients. Methods We performed a retrospective analysis using the 2015 National Cancer Database in which the survival of patients with a KPS ≤ 70 who received sequential radiation and chemotherapy were compared to those who received radiation therapy alone. Survival outcomes were compared using Kaplan–Meier curves with log rank testing and Cox proportional hazard regression. Results There were 84 patients analyzed in this study, all of whom had a KPS between 10 and 70. Of those analyzed, 73.8% received radiation therapy alone, and 26.2% received sequential radiation and chemotherapy. There was no difference in survival between the two treatment groups (p = 0.84). Patient age of 70 years or older (n = 31) was associated with decreased survival (HR 1.06 per year, p < 0.0001), regardless of KPS and a KPS of < 70 correlated with a near-significant trend toward worse survival (HR 1.63, p = 0.06). Conclusions Treatment with sequential radiation and chemotherapy in poorly performing patients is not associated with an advantage in survival outcome when compared to radiation alone in GBM patients with poor performance status.

    更新日期:2020-01-21
  • Postoperative oscillatory brain activity as an add-on prognostic marker in diffuse glioma
    J Neurooncol. (IF 3.129) Pub Date : 2020-01-17
    Vera Belgers, Tianne Numan, Shanna D. Kulik, Arjan Hillebrand, Philip C. de Witt Hamer, Jeroen J. G. Geurts, Jaap C. Reijneveld, Pieter Wesseling, Martin Klein, Jolanda Derks, Linda Douw

    Progression-free survival (PFS) in glioma patients varies widely, even when stratifying for known predictors (i.e. age, molecular tumor subtype, presence of epilepsy, tumor grade and Karnofsky performance status). Neuronal activity has been shown to accelerate tumor growth in an animal model, suggesting that brain activity may be valuable as a PFS predictor. We investigated whether postoperative oscillatory brain activity, assessed by resting-state magnetoencephalography is of additional value when predicting PFS in glioma patients.

    更新日期:2020-01-17
  • Hospital teaching status associated with reduced inpatient mortality and perioperative complications in surgical neuro-oncology
    J Neurooncol. (IF 3.129) Pub Date : 2020-01-14
    Evan M. Luther, David McCarthy, Katherine M. Berry, Nikhil Rajulapati, Ashish H. Shah, Daniel G. Eichberg, Ricardo J. Komotar, Michael Ivan

    Studies have demonstrated that higher surgical volumes correlate with improved neurosurgical outcomes yet none exist evaluating the effects of hospital teaching status on the surgical neuro-oncology patient. We present the first analysis comparing brain tumor surgery perioperative outcomes at academic and non-teaching centers.

    更新日期:2020-01-14
  • Resection of recurrent glioblastoma multiforme in elderly patients: a pseudo-randomized analysis revealed clinical benefit
    J Neurooncol. (IF 3.129) Pub Date : 2020-01-13
    Mateo Tomas Fariña Nuñez, Pamela Franco, Debora Cipriani, Nicolas Neidert, Simon P. Behringer, Irina Mader, Daniel Delev, Christian Fung, Jürgen Beck, Roman Sankowski, Nils Henrik Nicolay, Dieter Henrik Heiland, Oliver Schnell

    Elderly patients constitute an expanding part of our society. Due to a continuously increasing life expectancy, an optimal quality of life is expected even into advanced age. Glioblastoma (GBM) is more common in older patients, but they are still often withheld from efficient treatment due to worry of worse tolerance and have a significantly worse prognosis compared to younger patients. Our retrospective observational study aimed to investigate the therapeutic benefit from a second resection in recurrent glioblastoma of elderly patients.

    更新日期:2020-01-14
  • Current status and treatment modalities in metastases to the pituitary: a systematic review
    J Neurooncol. (IF 3.129) Pub Date : 2020-01-13
    Sam Ng, Franklin Fomekong, Violaine Delabar, Timothée Jacquesson, Ciprian Enachescu, Gerald Raverot, Romain Manet, Emmanuel Jouanneau

    Abstract Background Metastases to the pituitary (MP) are uncommon, accounting for 0.4% of intracranial metastases. Through advances in neuroimaging and oncological therapies, patients with metastatic cancers are living longer and MP may be more frequent. This review aimed to investigate clinical and oncological features, treatment modalities and their effect on survival. Methods A systematic review was performed according to PRISMA recommendations. All cases of MP were included, excepted primary pituitary neoplasms and autopsy reports. Descriptive and survival analyses were then conducted. Results The search identified 2143 records, of which 157 were included. A total of 657 cases of MP were reported, including 334 females (50.8%). The mean ± standard deviation age was 59.1 ± 11.9 years. Lung cancer was the most frequent primary site (31.0%), followed by breast (26.2%) and kidney cancers (8.1%). Median survival from MP diagnosis was 14 months. Overall survival was significantly different between lung, breast and kidney cancers (P < .0001). Survival was impacted by radiotherapy (hazard ratio (HR) 0.49; 95% confidence interval (CI) 0.35–0.67; P < .0001) and chemotherapy (HR 0.58; 95% CI 0.36–0.92; P = .013) but not by surgery. Stereotactic radiotherapy tended to improve survival over conventional radiotherapy (HR 0.66; 95% CI 0.39–1.12; P = .065). Patients from recent studies (≥ 2010) had longer survival than others (HR 1.36; 95% CI 1.05–1.76; P = .0019). Conclusion This systematic review based on 657 cases helped to better identify clinical features, oncological characteristics and the effect of current therapies in patients with MP. Survival patterns were conditioned upon primary cancer histologies, the use of local radiotherapy and systemic chemotherapy, but not by surgery.

    更新日期:2020-01-13
  • Salvage gamma knife radiosurgery for active brain metastases from small-cell lung cancer after whole-brain radiation therapy: a retrospective multi-institutional study (JLGK1701)
    J Neurooncol. (IF 3.129) Pub Date : 2020-01-13
    Kiyoshi Nakazaki, Shoji Yomo, Takeshi Kondoh, Toru Serizawa, Hiroyuki Kenai, Jun Kawagishi, Sonomi Sato, Osamu Nagano, Hitoshi Aiyama, Hideya Kawai, Toshinori Hasegawa, Yoshiyasu Iwai, Yasushi Nagatomo, Yoshihisa Kida, Masakazu Nishigaki

    Abstract Purpose To evaluate the efficacy of gamma knife radiosurgery (GKS) for brain metastases (BMs) from small-cell lung cancer after whole-brain radiotherapy (WBRT). Methods We retrospectively analyzed the usefulness and safety of GKS in 163 patients from 15 institutions with 1–10 active BMs after WBRT. The usefulness and safety of GKS were evaluated using statistical methods. Results The median age was 66 years, and 79.1% of patients were men. The median number and largest diameter of BM were 2.0 and 1.4 cm, respectively. WBRT was administered prophylactically in 46.6% of patients. The median overall survival (OS) was 9.3 months, and the neurologic mortality was 20.0%. Crude incidences of local control failure and new lesion appearance were 36.6% and 64.9%, respectively. A BM diameter ≥ 1.0 cm was a significant risk factor for local progression (hazard ratio [HR] 2.556, P = 0.039) and neurologic death (HR 4.940, P = 0.031). Leukoencephalopathy at the final follow-up was more prevalent in the therapeutic WBRT group than in the prophylactic group (P = 0.019). The symptom improvement rate was 61.3%, and neurological function was preserved for a median of 7.6 months. Therapeutic WBRT was not a significant risk factor for OS, neurological death, local control, or functional deterioration (P = 0.273, 0.490, 0.779, and 0.560, respectively). Symptomatic radiation-related adverse effects occurred in 7.4% of patients. Conclusions GKS can safely preserve neurological function and prevent neurologic death in patients with 1–10 small, active BMs after prophylactic and therapeutic WBRT.

    更新日期:2020-01-13
  • Spatial distribution of malignant transformation in patients with low-grade glioma
    J Neurooncol. (IF 3.129) Pub Date : 2020-01-09
    Asgeir S. Jakola, David Bouget, Ingerid Reinertsen, Anne J. Skjulsvik, Lisa Millgård Sagberg, Hans Kristian Bø, Sasha Gulati, Kristin Sjåvik, Ole Solheim

    Abstract Background Malignant transformation represents the natural evolution of diffuse low-grade gliomas (LGG). This is a catastrophic event, causing neurocognitive symptoms, intensified treatment and premature death. However, little is known concerning the spatial distribution of malignant transformation in patients with LGG. Materials and methods Patients histopathological diagnosed with LGG and subsequent radiological malignant transformation were identified from two different institutions. We evaluated the spatial distribution of malignant transformation with (1) visual inspection and (2) segmentations of longitudinal tumor volumes. In (1) a radiological transformation site < 2 cm from the tumor on preceding MRI was defined local transformation. In (2) overlap with pretreatment volume after importation into a common space was defined as local transformation. With a centroid model we explored if there were particular patterns of transformations within relevant subgroups. Results We included 43 patients in the clinical evaluation, and 36 patients had MRIs scans available for longitudinal segmentations. Prior to malignant transformation, residual radiological tumor volumes were > 10 ml in 93% of patients. The transformation site was considered local in 91% of patients by clinical assessment. Patients treated with radiotherapy prior to transformation had somewhat lower rate of local transformations (83%). Based upon the segmentations, the transformation was local in 92%. We did not observe any particular pattern of transformations in examined molecular subgroups. Conclusion Malignant transformation occurs locally and within the T2w hyperintensities in most patients. Although LGG is an infiltrating disease, this data conceptually strengthens the role of loco-regional treatments in patients with LGG.

    更新日期:2020-01-09
  • Short non-coding RNA sequencing of glioblastoma extracellular vesicles
    J Neurooncol. (IF 3.129) Pub Date : 2020-01-07
    Tristan de Mooij, Timothy E. Peterson, Jared Evans, Brandon McCutcheon, Ian F. Parney

    Like all nucleated cells, glioblastoma (GBM) cells shed small membrane-encapsulated particles called extracellular vesicles (EVs). EVs can transfer oncogenic components and promote tumor growth by transferring short non-coding RNAs, altering target cell gene expression. Furthermore, GBM-derived EVs can be detected in blood and have potential to serve as liquid biopsies.

    更新日期:2020-01-07
  • Evidence of dose-response following hypofractionated stereotactic radiotherapy to the cavity after surgery for brain metastases
    J Neurooncol. (IF 3.129) Pub Date : 2020-01-06
    Sidyarth Garimall, Mihir Shanker, Erin Johns, Trevor Watkins, Sarah Olson, Michael Huo, Matthew C. Foote, Mark B. Pinkham

    A retrospective review of consecutive patients between January 2012 and December 2018 receiving hypofractionated stereotactic radiotherapy (HSRT) to the cavity after resection for brain metastases was performed.

    更新日期:2020-01-06
  • Adding DSC PWI and DWI to BT-RADS can help identify postoperative recurrence in patients with high-grade gliomas
    J Neurooncol. (IF 3.129) Pub Date : 2020-01-04
    Yuelong Yang, Yunjun Yang, Xiaoling Wu, Yi Pan, Dong Zhou, Hongdan Zhang, Yonglu Chen, Jiayun Zhao, Zihua Mo, Biao Huang

    Abstract Background The Brain Tumor Reporting and Data System (BT-RADS) category 3 is suitable for identifying cases with intermediate probability of tumor recurrence that do not meet the Response Assessment in Neuro-Oncology (RANO) criteria for progression. The aim of this study was to evaluate the added value of dynamic susceptibility contrast-enhanced perfusion-weighted imaging (DSC PWI) and diffusion-weighted imaging (DWI) to BT-RADS for differentiating tumor recurrence from non-recurrence in postoperative high-grade glioma (HGG) patients with category 3 lesions. Methods Patients with BT-RADS category 3 lesions were included. The maximal relative cerebral blood volume (rCBVmax) and the mean apparent diffusion coefficient (ADCmean) values were measured. The added value of DSC PWI and DWI to BT-RADS was evaluated by receiver operating characteristic (ROC) curve analysis. Results Fifty-one of 91 patients had tumor recurrence, and 40 patients did not. There were significant differences in rCBVmax and ADCmean between the tumor recurrence group and non-recurrence group. Compared to BT-RADS alone, the addition of DSC PWI to BT-RADS increased the area under curve (AUC) from 0.76 (95% confidence interval [CI] 0.66–0.84) to 0.90 (95% CI 0.81–0.95) for differentiating tumor recurrence from non-recurrence. The addition of DWI to BT-RADS increased the AUC from 0.76 (95% CI 0.66–0.84) to 0.88 (95% CI 0.80–0.94). The combination of BT-RADS, DSC PWI, and DWI exhibited the best diagnostic performance (AUC = 0.95; 95% CI 0.88–0.98) for differentiating tumor recurrence from non-recurrence. Conclusion Adding DSC PWI and DWI to BT-RADS can significantly improve the diagnostic performance for differentiating tumor recurrence from non-recurrence in BT-RADS category 3 lesions.

    更新日期:2020-01-04
  • Impact of postoperative radiotherapy on recurrence of primary intracranial atypical meningiomas
    J Neurooncol. (IF 3.129) Pub Date : 2020-01-03
    Naureen Keric, Darius Kalasauskas, Christian F. Freyschlag, Jens Gempt, Martin Misch, Alicia Poplawski, Nicole Lange, Ali Ayyad, Claudius Thomé, Peter Vajkoczy, Bernhard Meyer, Florian Ringel

    Atypical meningiomas (WHO grade II) have high recurrence rate. However, data on the effect of radiotherapy (RT) is still conflicting. The aim of this study was to evaluate the influence of postoperative RT on the recurrence of primary atypical intracranial meningiomas.

    更新日期:2020-01-04
  • Management of sinonasal adenocarcinomas with anterior skull base extension
    J Neurooncol. (IF 3.129) Pub Date : 2020-01-03
    Marco Ferrari, Paolo Bossi, Davide Mattavelli, Laura Ardighieri, Piero Nicolai

    Sinonasal adenocarcinomas (SNAC) are rare and heterogeneous. Management of SNAC follows a rather standardized and internationally accepted paradigm. Several refinements have been introduced during the last decade.

    更新日期:2020-01-04
  • Difference in the hypoxic immunosuppressive microenvironment of patients with neurofibromatosis type 2 schwannomas and sporadic schwannomas
    J Neurooncol. (IF 3.129) Pub Date : 2020-01-03
    Ryota Tamura, Yukina Morimoto, Mizuto Sato, Yuki Kuranari, Yumiko Oishi, Kenzo Kosugi, Kazunari Yoshida, Masahiro Toda

    Abstract Background Neurofibromatosis type 2 (NF2) patients uniformly develop multiple schwannomas. The tumor-microenvironment (TME) is associated with hypoxia and consists of immunosuppressive cells, including regulatory T cells (Tregs) and tumor-associated macrophages (TAMs). The hypoxic TME of NF2 schwannomas remains unclear. In addition, no comparative study has investigated immunosuppressive cells in NF2 and sporadic schwannomas. Methods In 22 NF2 and 21 sporadic schwannomas, we analyzed the immunohistochemistry for Ki-67, hypoxia-inducible factor-1α (HIF-1α), vascular endothelial growth factor receptor 1 (VEGFR1) and VEGFR2, platelet derived growth factor receptor-beta (PDGFR-β), programmed cell death-1 (PD-1)/ programmed cell death ligand-1 (PD-L1), Foxp3, CD163, CD3, and CD8 to assess the immunosuppressive TME. Results Most vessels in sporadic schwannomas exhibited slight or negative VEGFR1 and 2 expressions with pericytes coverage. In contrast, large vessels in NF2 schwannomas exhibited strong VEGFR1 and 2 expressions without pericytes. The number of CD3+, CD8+, and CD163+ cells was significantly higher in NF2 schwannomas than in sporadic ones. The expression of PD-L1 and nestin positive cell ratio was higher in NF2 schwannomas than that in sporadic ones. The number of CD163+ cells, nestin positive cell ratio, and HIF-1α expression were significantly associated with shorter progression-free survival in NF2 schwannomas. Conclusions This study presents the clinicopathological features of the differences in immunosuppressive cells and the expression of immune checkpoint molecules between NF2 and sporadic schwannomas. Hypoxic TME was first detected in NF2-schwannomas, which was associated with the tumor progression.

    更新日期:2020-01-04
  • Quality of life considerations for patients with anterior and central skull base malignancies
    J Neurooncol. (IF 3.129) Pub Date : 2020-01-03
    Christopher W. Noel, John R. de Almeida

    The extirpation of skull base malignancies may be associated with significant morbidity and can profoundly impact health related quality of life (HRQOL). In this review, we sought to provide an overview of HRQOL and the factors that influence it for patients with skull base malignancies.

    更新日期:2020-01-04
  • Management of advanced adenoid cystic carcinoma infiltrating the skull base: a contemporary review
    J Neurooncol. (IF 3.129) Pub Date : 2020-01-02
    E. Guazzo, B. Panizza

    This article provides an overview of the natural history and management of adenoid cystic carcinoma infiltrating the skull base (SB ACC).

    更新日期:2020-01-02
  • Optimal adjuvant therapy in elderly glioblastoma: results from a systematic review and network meta-analysis
    J Neurooncol. (IF 3.129) Pub Date : 2020-01-01
    Babusha Kalra, Sadhana Kannan, Tejpal Gupta

    Abstract Background There exists lack of consensus worldwide regarding the most optimal adjuvant therapy regimen in elderly patients with newly-diagnosed glioblastoma (GBM). Purpose To identify the most optimal adjuvant therapy regimen in elderly GBM patients through systematic review and network meta-analysis. Methods Prospective trials randomly assigning elderly GBM patients post-operatively to any adjuvant therapy regimen were included. The primary outcome measure was overall survival. Numbers of events, patients at-risk, and censored patients for survival were estimated from Kaplan–Meier survival curves in the interval of 0–12 months. The total person-time at risk and the mortality × 100 person-months was also estimated. The relative ranking probability of each treatment and rankograms were used to estimate the hierarchy of each intervention in terms of overall survival. The mean rank values and the surface under the cumulative ranking (SUCRA) curves were also calculated. Results A systematic literature search identified 1278 abstracts, that were screened to retrieve full-text manuscripts of potentially eligible articles. After detailed assessment, data from 1569 patients in 7 randomized controlled trials (RCTs) treated with one of following regimens was extracted and analyzed: normofractionated radiotherapy (RT) delivered over 5.5–6 weeks; moderately hypofractionated RT (2–3 weeks) either alone or in combination with temozolomide or bevacizumab; extremely hypofractionated RT (1-week); temozolomide monotherapy; and best supportive care alone. In terms of overall survival, moderately hypofractionated RT (3-weeks) with concurrent and adjuvant temozolomide emerged as the best and second-best adjuvant therapy option with 81% probability and 99.1% probability respectively. Using SUCRA, the surface area for moderately hypofractionated RT (3-weeks) with concurrent and adjuvant temozolomide reached almost 100%, confirming it as the best intervention. As expected, best supportive care alone was ranked as the worst treatment strategy. Conclusion Moderately hypofractionated RT (3-weeks) with concurrent and adjuvant temozolomide is the most optimal and preferred adjuvant therapeutic regimen in elderly GBM.

    更新日期:2020-01-01
  • Impact of brain metastasis velocity on neurologic death for brain metastasis patients experiencing distant brain failure after initial stereotactic radiosurgery
    J Neurooncol. (IF 3.129) Pub Date : 2020-01-01
    Michael C. LeCompte, Ryan T. Hughes, Michael Farris, Adrianna Masters, Michael H. Soike, Claire Lanier, Chase Glenn, Christina K. Cramer, Kounosuke Watabe, Jing Su, Jimmy Ruiz, Christopher T. Whitlow, Ge Wang, Adrian W. Laxton, Stephen B. Tatter, Michael D. Chan

    Patients with high rates of developing new brain metastases have an increased likelihood of dying of neurologic death. It is unclear, however, whether this risk is affected by treatment choice following failure of primary stereotactic radiosurgery (SRS).

    更新日期:2020-01-01
  • Prediagnostic symptoms and signs of adult glioma: the patients’ view
    J Neurooncol. (IF 3.129) Pub Date : 2020-01-01
    Marthe C. M. Peeters, Linda Dirven, Johan A. F. Koekkoek, Ellen G. Gortmaker, Lara Fritz, Maaike J. Vos, Martin J. B. Taphoorn

    Little is known about the symptoms glioma patients experience in the year before diagnosis, either or not resulting in health care usage. This study aimed to determine the incidence of symptoms glioma patients experienced in the year prior to diagnosis, and subsequent visits to a general practitioner (GP).

    更新日期:2020-01-01
  • A Phase Ib/II, open-label, multicenter study of INC280 (capmatinib) alone and in combination with buparlisib (BKM120) in adult patients with recurrent glioblastoma
    J Neurooncol. (IF 3.129) Pub Date : 2019-11-27
    Martin van den Bent, Analia Azaro, Filip De Vos, Juan Sepulveda, W. K. Alfred Yung, Patrick Y. Wen, Andrew B. Lassman, Markus Joerger, Ghazaleh Tabatabai, Jordi Rodon, Ralph Tiedt, Sylvia Zhao, Tiina Kirsilae, Yi Cheng, Sergio Vicente, O. Alejandro Balbin, Hefei Zhang, Wolfgang Wick

    Abstract Purpose To estimate the maximum tolerated dose (MTD) and/or identify the recommended Phase II dose (RP2D) for combined INC280 and buparlisib in patients with recurrent glioblastoma with homozygous phosphatase and tensin homolog (PTEN) deletion, mutation or protein loss. Methods This multicenter, open-label, Phase Ib/II study included adult patients with glioblastoma with mesenchymal-epithelial transcription factor (c-Met) amplification. In Phase Ib, patients received INC280 as capsules or tablets in combination with buparlisib. In Phase II, patients received INC280 only. Response was assessed centrally using Response Assessment in Neuro-Oncology response criteria for high-grade gliomas. All adverse events (AEs) were recorded and graded. Results 33 patients entered Phase Ib, 32 with altered PTEN. RP2D was not declared due to potential drug–drug interactions, which may have resulted in lack of efficacy; thus, Phase II, including 10 patients, was continued with INC280 monotherapy only. Best response was stable disease in 30% of patients. In the selected patient population, enrollment was halted due to limited activity with INC280 monotherapy. In Phase Ib, the most common treatment-related AEs were fatigue (36.4%), nausea (30.3%) and increased alanine aminotransferase (30.3%). MTD was identified at INC280 Tab 300 mg twice daily + buparlisib 80 mg once daily. In Phase II, the most common AEs were headache (40.0%), constipation (30.0%), fatigue (30.0%) and increased lipase (30.0%). Conclusion The combination of INC280/buparlisib resulted in no clear activity in patients with recurrent PTEN-deficient glioblastoma. More stringent molecular selection strategies might produce better outcomes. Trial registration: NCT01870726.

    更新日期:2019-12-31
  • Effect of sensorineural hearing loss on neurocognitive and adaptive functioning in survivors of pediatric embryonal brain tumor
    J Neurooncol. (IF 3.129) Pub Date : 2019-11-28
    Andrew M. Heitzer, Alexandra M. Villagran, Kimberly Raghubar, Austin L. Brown, Miranda L. Camet, M. Douglas Ris, Jenny H. Hanning, M. Fatih Okcu, Arnold C. Paulino, Murali Chintagumpala, Lisa S. Kahalley

    Survivors of pediatric embryonal brain tumors (BT) are at high risk for sensorineural hearing loss (SNHL) associated with neurocognitive decline. However, previous studies have not assessed the relationship between SNHL and adaptive functioning. We examined neurocognitive and adaptive functioning in patients with and without SNHL.

    更新日期:2019-12-31
  • cMyc and ERK activity are associated with resistance to ALK inhibitory treatment in glioblastoma
    J Neurooncol. (IF 3.129) Pub Date : 2019-11-28
    Anne Berberich, Lara-Marie Schmitt, Stefan Pusch, Thomas Hielscher, Petra Rübmann, Nanina Hucke, Pauline Latzer, Bernd Heßling, Dieter Lemke, Tobias Kessler, Michael Platten, Wolfgang Wick

    Abstract Background Anaplastic lymphoma kinase (ALK) is expressed in ~ 60% of glioblastomas and conveys tumorigenic functions. Therefore, ALK inhibitory strategies with alectinib are conceivable for patients with glioblastoma. The aims of this preclinical study were to investigate efficacy as well as to understand and potentially overcome primary and acquired resistance mechanisms of alectinib in glioblastoma. Methods Efficacy of alectinib was analyzed dependent on ALK expression in different glioblastoma initiating cells and after lentiviral knockdown of ALK. Alectinib resistant cells were generated by continuous treatment with increasing alectinib doses over 3 months. M-RNA, phospho-protein and protein regulation were analyzed to decipher relevant pathways associated to treatment or resistance and specifically inhibited to evaluate rational salvage therapies. Results Alectinib reduced clonogenicity and proliferation and induced apoptosis in ALK expressing glioblastoma initiating cells, whereas cells without ALK expression or after ALK depletion via knockdown showed primary resistance against alectinib. High expression of cMyc and activation of the ERK1/2 pathway conferred resistance against alectinib in ALK expressing glioblastoma cells. Pharmacological inhibition of these pathways by cMyc inhibitor or MEK inhibitor, trametinib, overcame alectinib resistance and re-sensitized resistant cells to continued alectinib treatment. The combination of alectinib with radiotherapy demonstrated synergistic effects in inhibition of clonogenicity in non-resistant and alectinib resistant glioblastoma cells. Conclusion The data offer rationales for alectinib treatment in ALK expressing glioblastoma and for the use of ALK expression status as potential biomarker for alectinib treatment. In addition, the results propose MEK inhibition or radiotherapy as reasonable salvage treatments after acquired alectinib resistance.

    更新日期:2019-12-31
  • EGFR amplification is a real independent prognostic impact factor between young adults and adults over 45yo with wild-type glioblastoma?
    J Neurooncol. (IF 3.129) Pub Date : 2019-12-30
    Daniele Armocida, Alessandro Pesce, Alessandro Frati, Antonio Santoro, Maurizio Salvati

    Abstract Background In 2019 a group of University of Pennsylvania (Hoffman et al., J Neurooncol 145: 321–328, 2019) aimed to explore the prognostic impact of expression of epidermal growth factor receptor (EGFR), one of the most common genetic alterations in WT-GBM, in young adults with IDH-WT GBM, suggesting an inferior outcomes in young adults (< 45yo) with newly diagnosed, IDH-WT GBM. At the same time, our group were considering the dimension of this subpopulation treated in our centre, and we performed the same analysis, comparing datas with affected elderly adults. Methods We explore the prognostic impact of EGFR expression status in young adults with IDH-WT GBM, and compare this impact with the affected elderly adults. We therefore analyzed clinical characteristics, tumor genetics, and clinical outcomes in a cohort of adults aged 18–45 years with newly diagnosed WT GBM. We selected a total of 146 patients affected by newly diagnosed IDH-WT GBM who underwent surgery, radiation, and chemotherapy in our Institution in the period ranging between January 2014 and December 2016. We focused primarily on the prognostic impact of EGFR expression. Results We confirmed through a Bivariate Analysis that the Age of the Patients, the Volume of the lesions, were statistically strongly associated with the survival parameters; The general OS of the cohort presented a breakthrough point between the patients who were respectively younger and older than 45 years, EGFR mutation was per se not associated to a survival reduction in all the cohort patients. When analyzing exclusively the Survival parameters of the patients whose age was under 40, it was possible to outline a non statistically significant trend towards a lesser OS in younger patients harboring an EGFR expression. Conclusions Once again the main difference in terms of OS in GBM is shown in a EOR and in Age. To our knowledge, ours is the second study (Hoffman et al., J Neurooncol 145: 321–328, 2019) to evaluate the prognostic impact of EGFR CN gain specifically in young adults with IDH-WT GBM and in the era of modern radiation and Temozolomide, but is the first one to compares this impact with a population of adults over 45, and correlates this date with clinical onset, dimension and localization of disease between this groups. We suggest other centers to evaluate this important finding with a larger number of patients and we are inclined to accept collaborations to increase the power of this study.

    更新日期:2019-12-30
  • Socioeconomic factors affect treatment delivery for patients with low grade glioma: a Swedish population-based study
    J Neurooncol. (IF 3.129) Pub Date : 2019-12-27
    Louise Carstam, Isabelle Rydén, Sasha Gulati, Bertil Rydenhag, Roger Henriksson, Øyvind Salvesen, Anja Smits, Asgeir Store Jakola

    Despite aspirations to achieve equality in healthcare we know that socioeconomic differences exist and may affect treatment and patient outcome, also in serious diseases such as cancer. We investigated disparities in neurosurgical care and outcome for patients with low-grade glioma (LGG).

    更新日期:2019-12-27
  • Preclinical evaluation of binimetinib (MEK162) delivered via polymeric nanocarriers in combination with radiation and temozolomide in glioma
    J Neurooncol. (IF 3.129) Pub Date : 2019-12-24
    Fatima Bikhezar, Robin M. de Kruijff, Astrid J. G. M. van der Meer, Guzman Torrelo Villa, Susanne M. A. van der Pol, Gabriel Becerril Aragon, Ana Gasol Garcia, Ravi S. Narayan, Helga E. de Vries, Ben J. Slotman, Antonia G. Denkova, Peter Sminia

    Glioblastoma multiforme (GBM) is the most aggressive subtype of malignant gliomas, with an average survival rate of 15 months after diagnosis. More than 90% of all GBMs have activating mutations in the MAPK/ERK pathway. Recently, we showed the allosteric MEK1/2 inhibitor binimetinib (MEK162) to inhibit cell proliferation and to enhance the effect of radiation in preclinical human GBM models. Because the free drug cannot pass the blood–brain barrier (BBB), we investigated the use of nanocarriers for transport of the drug through the BBB and its efficacy when combined with radiotherapy and temozolomide (TMZ) in glioma spheroids.

    更新日期:2019-12-25
  • Targetable molecular alterations in congenital glioblastoma
    J Neurooncol. (IF 3.129) Pub Date : 2019-12-24
    Ahmed Gilani, Andrew Donson, Kurtis D. Davies, Susan L. Whiteway, Jessica Lake, John DeSisto, Lindsey Hoffman, Nicholas K. Foreman, B. K. Kleinschmidt-DeMasters, Adam L. Green

    Congenital glioblastomas (cGBMs) are uncommon tumors presenting in early infancy, variably defined as diagnosed at birth or at age less than 3 months by strict criteria, or more loosely, as occurring in very young children less than 12 months of age. Previous studies have shown that cGBMs are histologically indistinguishable from GBMs in older children or adults, but may have a more favorable clinical outcome, suggesting biological differences between congenital versus other GBMs. Due to the infrequency of cGBMs, especially when employing strict inclusion criteria, molecular features have not been sufficiently explored.

    更新日期:2019-12-25
  • The role of radiation and chemotherapy in adult patients with high-grade brainstem gliomas: results from the National Cancer Database
    J Neurooncol. (IF 3.129) Pub Date : 2019-12-24
    Panagiotis Kerezoudis, Anshit Goyal, Victor M. Lu, Mohammed Ali Alvi, Mohamad Bydon, Sani H. Kizilbash, Terry C. Burns

    Surgical resection of high-grade brainstem gliomas is challenging and treatment mostly involves radiation and chemotherapy. In this study, we utilized registry data to determine prognostic features and impact of chemotherapy and radiation on overall survival.

    更新日期:2019-12-25
  • DCE-MRI perfusion predicts pseudoprogression in metastatic melanoma treated with immunotherapy
    J Neurooncol. (IF 3.129) Pub Date : 2019-12-24
    Yoshie Umemura, Diane Wang, Kyung K. Peck, Jessica Flynn, Zhigang Zhang, Robin Fatovic, Erik S. Anderson, Kathryn Beal, Alexander N. Shoushtari, Thomas Kaley, Robert J. Young

    Abstract Purpose It can be challenging to differentiate pseudoprogression from progression. We assessed the ability of dynamic contrast enhanced T1 MRI (DCE-MRI) perfusion to identify pseudoprogression in melanoma brain metastases. Methods Patients with melanoma brain metastases who underwent immunotherapy and DCE-MRI were identified. Enhancing lesions ≥ 5mm in diameter on DCE-MRI and that were new or increased in size between a week from beginning the treatment, and a month after completing the treatment were included in the analysis. The 90th percentiles of rVp and rKtrans and the presence or absence of hemorrhage were recorded. Histopathology served as the reference standard for pseudoprogression. If not available, pseudoprogression was defined as neurological and radiographic stability or improvement without any new treatment for ≥ 2 months. Results Forty-four patients were identified; 64% received ipilimumab monotherapy for a median duration of 9 weeks (range, 1–138). Sixty-four lesions in 44 patients were included in the study. Of these, nine lesions in eight patients were determined to be pseudoprogression and seven lesions were previously irradiated. Forty-four progression lesions and eight pseudoprogression lesions were hemorrhagic. Median lesion volume for pseudoprogression and progression were not significantly different, at 2.3 cm3 and 3.2 cm3, respectively (p = 0.82). The rVp90 was smaller in pseudoprogression versus progression, at 2.2 and 5.3, respectively (p = 0.02), and remained significant after false discovery rate adjustment (p = 0.04). Conclusions Pseudoprogression exhibited significantly lower rVp90 on DCE-MRI compared with progression. This knowledge can be useful for managing growing lesions in patients with melanoma brain metastases who are receiving immunotherapy.

    更新日期:2019-12-25
  • Prediction of lower-grade glioma molecular subtypes using deep learning
    J Neurooncol. (IF 3.129) Pub Date : 2019-12-21
    Yutaka Matsui, Takashi Maruyama, Masayuki Nitta, Taiichi Saito, Shunsuke Tsuzuki, Manabu Tamura, Kaori Kusuda, Yasukazu Fukuya, Hidetsugu Asano, Takakazu Kawamata, Ken Masamune, Yoshihiro Muragaki

    Abstract Introduction It is useful to know the molecular subtype of lower-grade gliomas (LGG) when deciding on a treatment strategy. This study aims to diagnose this preoperatively. Methods A deep learning model was developed to predict the 3-group molecular subtype using multimodal data including magnetic resonance imaging (MRI), positron emission tomography (PET), and computed tomography (CT). The performance was evaluated using leave-one-out cross validation with a dataset containing information from 217 LGG patients. Results The model performed best when the dataset contained MRI, PET, and CT data. The model could predict the molecular subtype with an accuracy of 96.6% for the training dataset and 68.7% for the test dataset. The model achieved test accuracies of 58.5%, 60.4%, and 59.4% when the dataset contained only MRI, MRI and PET, and MRI and CT data, respectively. The conventional method used to predict mutations in the isocitrate dehydrogenase (IDH) gene and the codeletion of chromosome arms 1p and 19q (1p/19q) sequentially had an overall accuracy of 65.9%. This is 2.8 percent point lower than the proposed method, which predicts the 3-group molecular subtype directly. Conclusions A deep learning model was developed to diagnose the molecular subtype preoperatively based on multi-modality data in order to predict the 3-group classification directly. Cross-validation showed that the proposed model had an overall accuracy of 68.7% for the test dataset. This is the first model to double the expected value for a 3-group classification problem, when predicting the LGG molecular subtype.

    更新日期:2019-12-21
  • Identification and validation of a 21-mRNA prognostic signature in diffuse lower-grade gliomas
    J Neurooncol. (IF 3.129) Pub Date : 2019-12-18
    Lai-Rong Song, Jian-Cong Weng, Xu-Lei Huo, Liang Wang, Huan Li, Da Li, Zhen Wu, Jun-Ting Zhang

    Diffuse low-grade and intermediate-grade gliomas, also known as lower-grade gliomas (LGGs), are a class of central nervous system tumors. Overall survival varies greatly between patients, highlighting the importance of evaluating exact outcomes to facilitate individualized clinical management. We aimed to identify an mRNA-based prognostic signature to predict the survival of patients with LGGs.

    更新日期:2019-12-19
  • Preoperative predictive factors affecting return to work in patients with gliomas undergoing awake brain mapping
    J Neurooncol. (IF 3.129) Pub Date : 2019-12-18
    Akihito Yoshida, Kazuya Motomura, Atsushi Natsume, Lushun Chalise, Kentaro Iijima, Daisuke Hara, Izumi Kadono, Kenji Wakai, Toshihiko Wakabayashi

    This study aimed to investigate the preoperative predictive factors affecting return to work in patients with gliomas in the left cerebral hemisphere undergoing awake surgery.

    更新日期:2019-12-19
  • Advancing neuro-oncology of glial tumors from big data and multidisciplinary studies
    J Neurooncol. (IF 3.129) Pub Date : 2019-12-18
    Chin-Hsing Annie Lin, Mitchel S. Berger

    Multidisciplinary studies for glial tumors has produced an enormous amount of information including imaging, histology, and a large cohort of molecular data (i.e. genomics, epigenomics, metabolomics, proteomics, etc.). The big data resources are made possible through open access that offers great potential for new biomarker or therapeutic intervention via deep-learning and/or machine learning for integrated multi-omics analysis. An equally important effort to define the hallmarks of glial tumors will also advance precision neuro-oncology and inform patient-specific therapeutics. This review summarizes past studies regarding tumor classification, hallmarks of cancer, and hypothetical mechanisms. Leveraging on advanced big data approaches and ongoing cross-disciplinary endeavors, this review also discusses how to integrate multiple layers of big data toward the goal of precision medicine.

    更新日期:2019-12-19
  • The combination of stereotactic radiosurgery with immune checkpoint inhibition or targeted therapy in melanoma patients with brain metastases: a retrospective study
    J Neurooncol. (IF 3.129) Pub Date : 2019-12-14
    Filipe Martins, Luis Schiappacasse, Marc Levivier, Constantin Tuleasca, Michel A. Cuendet, Veronica Aedo-Lopez, Bianca Gautron Moura, Krisztian Homicsko, Adrienne Bettini, Gregoire Berthod, Camille L. Gérard, Alexandre Wicky, Jean Bourhis, Olivier Michielin

    Evidence pointing to a synergistic effect of stereotactic radiosurgery (SRS) with concurrent immunotherapy or targeted therapy in patients with melanoma brain metastases (BM) is increasing. We aimed to analyze the effect on overall survival (OS) of immune checkpoint inhibitors (ICI) or BRAF/MEK inhibitors initiated during the 9 weeks before or after SRS. We also evaluated the prognostic value of patients’ and disease characteristics as predictors of OS in patients treated with SRS.

    更新日期:2019-12-17
  • Patterns of seizure prophylaxis after oncologic neurosurgery
    J Neurooncol. (IF 3.129) Pub Date : 2019-12-13
    Brett E. Youngerman, Evan F. Joiner, Xianling Wang, Jingyan Yang, Mary R. Welch, Guy M. McKhann, Jason D. Wright, Dawn L. Hershman, Alfred I. Neugut, Jeffrey N. Bruce

    Evidence supporting routine postoperative antiepileptic drug (AED) prophylaxis following oncologic neurosurgery is limited, and actual practice patterns are largely unknown beyond survey data.

    更新日期:2019-12-17
  • Characterization of MGMT and EGFR protein expression in glioblastoma and association with survival
    J Neurooncol. (IF 3.129) Pub Date : 2019-12-10
    Lauren R. Schaff, Dongyao Yan, Sheeno Thyparambil, Yuan Tian, Fabiola Cecchi, Marc Rosenblum, Anne S. Reiner, Katherine S. Panageas, Todd Hembrough, Andrew L. Lin

    Understanding the molecular landscape of glioblastoma (GBM) is increasingly important in the age of targeted therapy. O-6-Methylguanine-DNA methyltransferase (MGMT) promoter methylation and EGFR amplification are markers that may play a role in prognostication, treatment, and/or clinical trial eligibility. Quantification of MGMT and EGFR protein expression may offer an alternative strategy towards understanding GBM. Here, we quantify baseline expression of MGMT and EGFR protein in newly diagnosed GBM samples using mass spectrometry. We correlate findings with MGMT methylation and EGFR amplification statuses and survival.

    更新日期:2019-12-11
  • Neurocognitive changes after awake surgery in glioma patients: a retrospective cohort study
    J Neurooncol. (IF 3.129) Pub Date : 2019-12-04
    Emma van Kessel, Tom J. Snijders, Anniek E. Baumfalk, Carla Ruis, Kirsten M. van Baarsen, Marike L. Broekman, Martine J. E. van Zandvoort, Pierre A. Robe

    Deficits in neurocognitive functioning (NCF) frequently occur in glioma patients. Both treatment and the tumor itself contribute to these deficits. In order to minimize the harmful effects of surgery, an increasing number of patients undergo awake craniotomy. To investigate whether we can indeed preserve cognitive functioning after state-of-the art awake surgery and to identify factors determining postoperative NCF, we performed a retrospective cohort study.

    更新日期:2019-12-04
  • Whole brain apparent diffusion coefficient measurements correlate with survival in glioblastoma patients
    J Neurooncol. (IF 3.129) Pub Date : 2019-12-03
    Aaron Michael Rulseh, Josef Vymazal

    Glioblastoma (GBM) is the most common malignant primary brain tumor, and methods to improve the early detection of disease progression and evaluate treatment response are highly desirable. We therefore explored changes in whole-brain apparent diffusion coefficient (ADC) values with respect to survival (progression-free [PFS], overall [OS]) in a cohort of GBM patients followed at regular intervals until disease progression.

    更新日期:2019-12-04
  • Tumor immune microenvironment is associated with the growth of intracranial germinomas
    J Neurooncol. (IF 3.129) Pub Date : 2019-11-26
    Masaaki Nishimoto, Kentaro Ohara, Dai Kamamoto, Ryota Tamura, Tomoru Miwa, Kazunari Yoshida, Hikaru Sasaki

    The role of immune checkpoint molecules and the tumor immune microenvironment in the development of intracranial germ cell tumors remains unclear.

    更新日期:2019-11-27
  • Correction to: Efficacy of Dabrafenib for three children with brainstem BRAF V600E positive ganglioglioma
    J Neurooncol. (IF 3.129) Pub Date : 2019-11-25
    Philippe Laflamme, Maria Kondyli, Tariq Aljared, Sofia Miconiatis, Christine Saint-Martin, Jean-Pierre Farmer, Roy W. Dudley, Sébastien Perreault, Nada Jabado, Valérie Larouche

    In the original article, the author names were published incorrectly. The names are correct in this publication.

    更新日期:2019-11-26
  • Transcription factors NFIA and NFIB induce cellular differentiation in high-grade astrocytoma
    J Neurooncol. (IF 3.129) Pub Date : 2019-11-23
    Kok-Siong Chen, Caitlin R. Bridges, Zorana Lynton, Jonathan W. C. Lim, Brett W. Stringer, Revathi Rajagopal, Kum-Thong Wong, Dharmendra Ganesan, Hany Ariffin, Bryan W. Day, Linda J. Richards, Jens Bunt

    Malignant astrocytomas are composed of heterogeneous cell populations. Compared to grade IV glioblastoma, low-grade astrocytomas have more differentiated cells and are associated with a better prognosis. Therefore, inducing cellular differentiation to alter the behaviour of high-grade astrocytomas may serve as a therapeutic strategy. The nuclear factor one (NFI) transcription factors are essential for normal astrocytic differentiation. Here, we investigate whether family members NFIA and NFIB act as effectors of cellular differentiation in glioblastoma.

    更新日期:2019-11-26
  • Multi-domain neurocognitive classification of primary brain tumor patients prior to radiotherapy on a prospective clinical trial
    J Neurooncol. (IF 3.129) Pub Date : 2019-11-23
    Roshan Karunamuni, Kathryn R. Tringale, Jeffrey Burkeen, Michelle D. Tibbs, Minh-Phuong Huynh-Le, Naeim Bahrami, Deborah Marshall, Tyler M. Seibert, Carrie R. McDonald, Jona A. Hattangadi-Gluth

    We investigated multi-domain baseline neurocognition of primary brain tumor patients prior to radiotherapy (RT), including clinical predictors of function and association between pre-RT and post-RT impairment on a prospective trial.

    更新日期:2019-11-26
  • Correction to: White matter changes in primary central nervous system lymphoma patients treated with high-dose methotrexate with or without rituximab
    J Neurooncol. (IF 3.129) Pub Date : 2019-11-22
    Fayez Estephan, Xiaobu Ye, Omar Dzaye, Nina Wagner-Johnston, Lode Swinnen, Douglas E. Gladstone, Rich Ambinder, David Olayinka Kamson, Sebastian Lambrecht, Stuart A. Grossman, Doris D. M. Lin, Matthias Holdhoff

    The following discrepancies and errors were found in the original publication:

    更新日期:2019-11-22
  • Nuclear receptor 4A2 (NR4A2) is a druggable target for glioblastomas
    J Neurooncol. (IF 3.129) Pub Date : 2019-11-21
    Keshav Karki, Xi Li, Un-Ho Jin, Kumaravel Mohankumar, Mahsa Zarei, Sharon K. Michelhaugh, Sandeep Mittal, Ronald Tjalkens, Stephen Safe

    The orphan nuclear receptor 4A2 (NR4A2) has been extensively characterized in subcellular regions of the brain and is necessary for the function of dopaminergic neurons. The NR4A2 ligand, 1,1-bis (31-indoly1)-1-(p-chlorophenyl)methane (DIM-C-pPhCl) inhibits markers of neuroinflammation and degeneration in mouse models and in this study we investigated expression and function of NR4A2 in glioblastoma (GBM).

    更新日期:2019-11-21
  • Brachytherapy with surgical resection as salvage treatment for recurrent high-grade meningiomas: a matched cohort study
    J Neurooncol. (IF 3.129) Pub Date : 2019-11-19
    Michael A. Mooney, Wenya Linda Bi, Jonathan M. Cantalino, Kyle C. Wu, Thomas C. Harris, Lucas L. Possatti, Parikshit Juvekar, Liangge Hsu, Ian F. Dunn, Ossama Al-Mefty, Phillip M. Devlin

    To evaluate surgical resection with brachytherapy placement as a salvage treatment in patients with recurrent high-grade meningioma who exhausted prior external beam treatment options.

    更新日期:2019-11-19
  • A multi-institutional analysis of clinical outcomes and patterns of care of 1p/19q codeleted oligodendrogliomas treated with adjuvant or salvage radiation therapy
    J Neurooncol. (IF 3.129) Pub Date : 2019-11-18
    Alexander J. Lin, Liam T. Kane, Jason K. Molitoris, Deborah R. Smith, Sonika Dahiya, Shahed N. Badiyan, Tony J. C. Wang, Tim J. Kruser, Jiayi Huang

    Practice patterns vary for adjuvant treatment of 1p/19q-codeleted oligodendroglioma patients. This study evaluates the outcomes of adjuvant (aRT) versus salvage radiation therapy (sRT) in a multi-institutional cohort.

    更新日期:2019-11-18
  • Radiation chronotherapy—clinical impact of treatment time-of-day: a systematic review
    J Neurooncol. (IF 3.129) Pub Date : 2019-11-15
    Dorela D. Shuboni-Mulligan, Ghislain Breton, DeeDee Smart, Mark Gilbert, Terri S. Armstrong

    Many brain tumor patients suffer from radiation-induced toxicities. Chronotherapy is a treatment modality that utilizes circadian rhythms to optimize the effect on tumor while minimizing negative outcomes on healthy tissue. This review aims to systematically examine the literature on the application of a radiation chronotherapeutic for all cancers and determine the possible advantages of incorporating a circadian-based fixed time-of-day for radiotherapy into CNS cancers.

    更新日期:2019-11-15
  • Analysis of CDKN2A gene alterations in recurrent and non-recurrent meningioma
    J Neurooncol. (IF 3.129) Pub Date : 2019-11-15
    Anne Guyot, Mathilde Duchesne, Sandrine Robert, Anne-Sophie Lia, Paco Derouault, Erwan Scaon, Leslie Lemnos, Henri Salle, Karine Durand, François Labrousse

    Assessment of the risk of recurrence is essential to determine the therapeutic strategy of meningioma treatment. Many relapsing or aggressive meningiomas show elevated mitotic and/or Ki67 indices, reflecting cell cycle deregulation. As CDKN2A is a key tumor suppressor gene involved in cell cycle control, we investigated whether CDKN2A alterations may be involved in tumor recurrence.

    更新日期:2019-11-15
  • Hypofractionated radiotherapy with temozolomide in diffuse intrinsic pontine gliomas: a randomized controlled trial
    J Neurooncol. (IF 3.129) Pub Date : 2019-11-14
    Yousra Izzuddeen, Subhash Gupta, K. P. Haresh, Dayanand Sharma, Prashanth Giridhar, Gour Kishore Rath

    Diffuse intrinsic pontine glioma (DIPG) is the most common form of brainstem glioma. The present study was performed to assess if hypofractionated radiotherapy completed in < 3 weeks with temozolomide improves survival in DIPG.

    更新日期:2019-11-14
  • Treatment-induced lesions in newly diagnosed glioblastoma patients undergoing chemoradiotherapy and heat-shock protein vaccine therapy
    J Neurooncol. (IF 3.129) Pub Date : 2019-11-14
    Paula Alcaide-Leon, Tracy L. Luks, Marisa Lafontaine, Janine M. Lupo, Hideho Okada, Jennifer L. Clarke, Javier E. Villanueva-Meyer

    Treatment-induced lesions represent a great challenge in neuro-oncology. The aims of this study were (i) to characterize treatment induced lesions in glioblastoma patients treated with chemoradiotherapy and heat-shock protein (HSP) vaccine and (ii) to evaluate the diagnostic accuracy of diffusion weighted imaging for differentiation between treatment-induced lesions and tumor progression.

    更新日期:2019-11-14
  • Delay in diagnosing patients with right-sided glioblastoma induced by hemispheric-specific clinical presentation
    J Neurooncol. (IF 3.129) Pub Date : 2019-11-11
    Claudia Baumann, Julia Tichy, Jan Hendrik Schaefer, Joachim P. Steinbach, Michel Mittelbronn, Marlies Wagner, Christian Foerch

    Cognitive functions are differentially represented in brain hemispheres. Aphasia is an “easy to recognize” symptom of diseases affecting the left side. In contrast, lesions in the right hemisphere cause subtle neuropsychological deficits such as neglect and anosognosia. We evaluated whether right-sided malignant brain tumors are on average larger at the time of first diagnosis as compared to left-sided tumors, and extrapolated the delay in diagnosing right-sided tumors compared to the left side.

    更新日期:2019-11-11
  • Microscopic brain invasion in meningiomas previously classified as WHO grade I is not associated with patient outcome
    J Neurooncol. (IF 3.129) Pub Date : 2019-11-11
    Annamaria Biczok, Christine Jungk, Rupert Egensperger, Andreas von Deimling, Bogdana Suchorska, Joerg C. Tonn, Christel Herold-Mende, Christian Schichor

    For meningiomas, the 2016 revision of the WHO classification introduced brain invasion per se as a sufficient condition to classify as grade II. We analyzed whether meningiomas previously graded as WHO grade I differ in prognosis depending on the presence of microscopic brain invasion.

    更新日期:2019-11-11
  • Fractionated stereotactic radiosurgery for malignant gliomas: comparison with single session stereotactic radiosurgery
    J Neurooncol. (IF 3.129) Pub Date : 2019-11-08
    Seung Won Choi, Kyung Rae Cho, Jung Won Choi, Doo-Sik Kong, Ho Jun Seol, Do-Hyun Nam, Jung-Il Lee

    Stereotactic radiosurgery (SRS) is feasible for malignant glioma; however, delivering the optimal radiation dose with sufficient large-volume coverage is a major concern. We aimed to investigate the clinical efficacy and safety of fractionated SRS (fSRS) versus single-session SRS (sSRS) for malignant gliomas.

    更新日期:2019-11-11
  • Weak MGMT gene promoter methylation confers a clinically significant survival benefit in patients with newly diagnosed glioblastoma: a retrospective cohort study
    J Neurooncol. (IF 3.129) Pub Date : 2019-11-07
    H. Pinson, G. Hallaert, J. Van der Meulen, F. Dedeurwaerdere, D. Vanhauwaert, C. Van den Broecke, J. Van Dorpe, D. Van Roost, J. P. Kalala, T. Boterberg

    Quantitative methylation specific PCR (qMSP) is a frequently used technique to assess MGMT gene promoter methylation in glioblastoma patients. The optimal technical cut-off value to distinguish methylated from unmethylated samples is nevertheless still undetermined. In literature, a “grey zone” of diagnostic uncertainty has been described.

    更新日期:2019-11-07
  • Correction to: Efficacy of initial temozolomide for high‑risk low grade gliomas in a phase II AINO (Italian Association for Neuro‑Oncology) study: a post‑hoc analysis within molecular subgroups of WHO 2016
    J Neurooncol. (IF 3.129) Pub Date : 2019-11-05
    Roberta Rudà, Alessia Pellerino, Andrea Pace, Carmine Maria Carapella, Cristina Dealis, Manuela Caroli, Marina Faedi, Lorenzo Bello, Enrica Migliore, Giulia Marchese, Luca Bertero, Paola Cassoni, Riccardo Soffietti

    The third and fourth authors' affiliation was incorrectly specified in the original publication. It is correctly shown here.

    更新日期:2019-11-06
  • Extent of surrounding edema does not correlate with acute complications after radiosurgery for melanoma brain metastases
    J Neurooncol. (IF 3.129) Pub Date : 2019-11-05
    Amelia Jardim, Justin Scott, Zachery Drew, Matthew C. Foote, Ananthababu P. Sadasivan, Bruce Hall, Sarah L. Olson, Mihir Shanker, Mark B. Pinkham

    To assess whether extent of surrounding edema correlates with acute adverse clinical outcomes within 3 months after stereotactic radiosurgery (SRS) for melanoma brain metastases (BM).

    更新日期:2019-11-06
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