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Darlix, Amélie, Emmanuel Mandonnet, Christian F. Freyschlag, Daniel Pinggera, Marie-Therese Forster, Martin Voss, Joachim Steinbach et al. "Chemotherapy and diffuse low-grade gliomas: a survey within the European Low-Grade Glioma Network". Neuro-Oncology Practice 6, n. 4 (13 dicembre 2018): 264–73. http://dx.doi.org/10.1093/nop/npy051.
Abstract (sommario):
Abstract Background Diffuse low-grade gliomas (DLGGs) are rare and incurable tumors. Whereas maximal safe, functional-based surgical resection is the first-line treatment, the timing and choice of further treatments (chemotherapy, radiation therapy, or combined treatments) remain controversial. Methods An online survey on the management of DLGG patients was sent to 28 expert centers from the European Low-Grade Glioma Network (ELGGN) in May 2015. It contained 40 specific questions addressing the modalities of use of chemotherapy in these patients. Results The survey demonstrated a significant heterogeneity in practice regarding the initial management of DLGG patients and the use of chemotherapy. Interestingly, radiation therapy combined with the procarbazine, CCNU (lomustine), and vincristine regimen has not imposed itself as the gold-standard treatment after surgery, despite the results of the Radiation Therapy Oncology Group 9802 study. Temozolomide is largely used as first-line treatment after surgical resection for high-risk DLGG patients, or at progression. Conclusions The heterogeneity in the management of patients with DLGG demonstrates that many questions regarding the postoperative strategy and the use of chemotherapy remain unanswered. Our survey reveals a high recruitment potential within the ELGGN for retrospective or prospective studies to generate new data regarding these issues.
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Mansouri, Alireza, Karanbir Brar e Michael D. Cusimano. "Considerations for a surgical RCT for diffuse low-grade glioma: a survey". Neuro-Oncology Practice 7, n. 3 (12 novembre 2019): 338–43. http://dx.doi.org/10.1093/nop/npz058.
Abstract (sommario):
Abstract Background Diffuse low-grade gliomas (DLGGs) are heterogeneous tumors that inevitably differentiate into malignant entities, leading to disability and death. Recently, a shift toward up-front maximal safe resection of DLGGs has been favored. However, this transition is not supported by randomized controlled trial (RCT) data. Here, we sought to survey the neuro-oncology community on considerations for a surgical RCT for DLGGs. Methods A 21-question survey focusing on a surgical RCT for DLGGs was developed and validated by 2 neurosurgeons. A sample case of a patient for whom management might be debatable was presented to gather additional insight. The survey was disseminated to members of the Society for Neuro-Oncology (SNO) and responses were collected from March 16 to July 10, 2018. Results A total of 131 responses were collected. Sixty-three of 117 (54%) respondents thought an RCT would not be ethical, 39 of 117 (33%) would consider participating, and 56 of 117 (48%) believed an RCT would be valuable for determining the differing roles of biopsy, surgery, and observation. This was exemplified by an evenly distributed selection of the latter management options for our sample case. Eighty-three of 120 (69.2%) respondents did not believe in equipoise for DLGG patients. Quality of life and overall survival were deemed equally important end points for a putative RCT. Conclusions Based on our survey, it is evident that management of certain DLGG patients is not well defined and an RCT may be justified. As with any surgical RCT, logistic challenges are anticipated. Robust patient-relevant end points and standardization of perioperative adjuncts are necessary if a surgical RCT is undertaken.
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Silva, Melissa, Catalina Vivancos e Hugues Duffau. "The Concept of «Peritumoral Zone» in Diffuse Low-Grade Gliomas: Oncological and Functional Implications for a Connectome-Guided Therapeutic Attitude". Brain Sciences 12, n. 4 (15 aprile 2022): 504. http://dx.doi.org/10.3390/brainsci12040504.
Abstract (sommario):
Diffuse low-grade gliomas (DLGGs) are heterogeneous and poorly circumscribed neoplasms with isolated tumor cells that extend beyond the margins of the lesion depicted on MRI. Efforts to demarcate the glioma core from the surrounding healthy brain led us to define an intermediate region, the so-called peritumoral zone (PTZ). Although most studies about PTZ have been conducted on high-grade gliomas, the purpose here is to review the cellular, metabolic, and radiological characteristics of PTZ in the specific context of DLGG. A better delineation of PTZ, in which glioma cells and neural tissue strongly interact, may open new therapeutic avenues to optimize both functional and oncological results. First, a connectome-based “supratotal” surgical resection (i.e., with the removal of PTZ in addition to the tumor core) resulted in prolonged survival by limiting the risk of malignant transformation, while improving the quality of life, thanks to a better control of seizures. Second, the timing and order of (neo)adjuvant medical treatments can be modulated according to the pattern of peritumoral infiltration. Third, the development of new drugs specifically targeting the PTZ could be considered from an oncological (such as immunotherapy) and epileptological perspective. Further multimodal investigations of PTZ are needed to maximize long-term outcomes in DLGG patients.
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Darlix, Amélie, Valérie Rigau, Julien Fraisse, Catherine Gozé, Michel Fabbro e Hugues Duffau. "Postoperative follow-up for selected diffuse low-grade gliomas with WHO grade III/IV foci". Neurology 94, n. 8 (22 gennaio 2020): e830-e841. http://dx.doi.org/10.1212/wnl.0000000000008877.
Abstract (sommario):
ObjectiveDiffuse low-grade gliomas (DLGG) are defined by continuous growth and an almost unavoidable malignant transformation. Foci of malignant glioma can be found within DLGG samples obtained from surgical resections. As the medical management of patients is classically based on the higher tumor grade, an immediate adjuvant treatment is usually proposed. To determine whether postponing the medical treatment in selected patients is feasible, we conducted a single-center retrospective study.MethodsThis was a single-center retrospective analysis of a consecutive series of DLGG managed with this conservative strategy. Inclusion criteria were at least 1 focus of malignant tumor (grade III–IV, WHO 2016), no previous chemotherapy or radiotherapy, no less than a subtotal resection of the fluid-attenuated inversion recovery tumor volume, no intention of treating with immediate adjuvant therapy, and minimum 2 years of follow-up. The time interval to the following oncologic medical treatment was analyzed, as well as the functional and survival results.ResultsForty-four patients met the inclusion criteria (median age 36, median time interval from diagnosis 7 months). Most tumors (88%) were IDH-mutant and 1p19q intact (59%); 9 presented with grade IV foci. With a median follow-up of 6.7 years, 75% of patients received a subsequent medical treatment, after a median time of 3.4 years since surgery. At the time of analysis, 9 patients (20.0%) had died (5- and 7-year survival rates: 95% and 67.0%). Most surviving patients were still active professionally, without seizures.ConclusionsPostponing the medical treatment in DLGG with foci of malignant tumor following total or subtotal resection should be considered in selected patients.
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Zhang, Kai, Dingyang Liu, Zhuanyi Yang, Xuejun Li, Zhiquan Yang e Xinghui He. "Resective surgery for patients with frontal lobe diffuse low-grade glioma-related epilepsy: predictors of seizure outcomes". Therapeutic Advances in Chronic Disease 13 (gennaio 2022): 204062232211418. http://dx.doi.org/10.1177/20406223221141856.
Abstract (sommario):
Background: Diffuse low-grade gliomas (DLGGs) are prone to invade the frontal lobes, with seizures being the most common symptom. However, limited attention has been paid to surgical outcomes and their predictors in patients with frontal DLGG-related epilepsy. Objective: This study aimed to analyze predictors of postoperative seizure outcomes in patients with frontal DLGG-related epilepsy. Design: This is a single-center retrospective study. Methods: This study retrospectively collected data of 115 patients with frontal DLGG-related epilepsy who underwent resective surgery between January 2014 and January 2021. Patients were categorized into favorable and unfavorable seizure outcome groups based on the International League Against Epilepsy (ILAE) classification. Univariate and multivariate analyses were used to identify potential predictors of seizure outcomes. Results: The mean follow-up was 4.11 ± 2.06 years, and 77.4% (89 of 115) of patients were seizure-free. Permanent neurological deficits were observed in 7.0% (8 of 115) of patients. Univariate and multivariate analyses revealed that total tumor removal [odds ratio (OR), 0.31; 95% confidence interval (CI), 0.12–0.82; p = 0.018] and older age at seizure onset (OR, 0.96; 95% CI, 0.93–0.99; p = 0.042) were independent predictors of favorable seizure outcomes. Conclusion: Surgical resection is an effective treatment for frontal DLGG-related epilepsy. Favorable seizure outcomes are more likely to be achieved in patients with complete tumor removal and those with older age at seizure onset.
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Alvarez de Eulate-Beramendi, Sayoa, Valérie Rigau, Luc Taillandier e Hugues Duffau. "Delayed leptomeningeal and subependymal seeding after multiple surgeries for supratentorial diffuse low-grade gliomas in adults". Journal of Neurosurgery 120, n. 4 (aprile 2014): 833–39. http://dx.doi.org/10.3171/2013.10.jns131512.
Abstract (sommario):
Object Diffuse WHO Grade II glioma (diffuse low-grade glioma [DLGG]) is an infiltrative brain tumor that usually migrates along the white matter fibers. The delayed CSF dissemination of supratentorial DLGGs is an exceptional complication and is rarely described in adults. Here, the authors report outcomes in a surgical series of 9 patients with DLGGs with subsequent leptomeningeal and/or subependymal seeding (LMSS) following multiple incomplete resections. Methods The authors performed a retrospective review of patients who underwent surgery for histopathologically confirmed WHO Grade II gliomas between 1998 and 2012 and experienced a secondary CSF spread. Information regarding clinical features, surgical procedures, histopathological results, adjuvant treatment, and clinical outcomes was collected and analyzed. Results Nine consecutive patients were included in this study. There were 6 men and 3 women whose mean age was 35.5 years (range 22–59 years) at the time of initial symptom onset. All patients underwent surgery with the aid of intraoperative mapping, with incomplete tumor removal because of invasion of eloquent structures. The neuropathological examination diagnosed a DLGG in all cases (7 oligodendrogliomas, 1 astrocytoma, and 1 oligoastrocytoma). Five patients had a 1p19q codeletion. Because of tumor regrowth, the 9 patients underwent reoperation (2 surgeries in 6 cases and 3 surgeries in 3 cases), again with incomplete resection. There were no surgical complications. Adjuvant therapy (radiotherapy and chemotherapy) was administered in all patients because of progression to a higher grade of malignancy that was histopathologically confirmed in all tumors. The patients suddenly worsened, and the diagnosis of LMSS was made with a mean delay of 77 months (range 27–140 months) after the initial symptom onset. Six patients benefited from salvage chemotherapy while palliative care was chosen in 3 cases. The median survival in the 6 patients who underwent LMSS treatment was significantly longer than that in the 3 patients who did not receive salvage chemotherapy (p = 0.03). Indeed, all patients died, with a mean delay between the diagnosis of LMSS and death of 11 months (range 2–38 months) and with a mean delay between the initial symptom onset and death of 88 months (range 34–144 months). Conclusions Cerebrospinal fluid dissemination of DLGG is a rare but possible event. It can occur throughout the progression of WHO Grade II oligodendrogliomas, oligoastrocytomas, and astrocytomas, regardless of 1p19q status. This complication seems to appear in patients who have undergone multiple incomplete resections. Salvage therapy can be considered in patients with good neurological status. However, LMSS is associated with a decreased overall survival. Therefore, this rare entity deserves further multicenter studies to better understand its pathophysiology and to adapt therapeutic strategies.
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Levine, Adrian, Cyril Li, Joseline Haizel-Cobbina, Liana Nobre, Julie Bennett, Michael Dewan, Uri Tabori e Cynthia Hawkins. "LGG-12. CLINICAL AND MOLECULAR FEATURES OF DISSEMINATED PEDIATRIC LOW-GRADE GLIOMA". Neuro-Oncology 25, Supplement_1 (1 giugno 2023): i58. http://dx.doi.org/10.1093/neuonc/noad073.222.
Abstract (sommario):
Abstract Although most pediatric LGG (PLGG) have excellent long-term survival, there is a subset of cases that disseminate throughout the neuraxis (DLGG) that have very poor outcomes. The reason for this aggressive behavior is unknown but we hypothesize that distinct and specific biological mechanisms underlie the metastatic ability. The methylation-based class of diffuse leptomeningeal glioneuronal tumor (DLGNT) is characterized by MAPK pathway activating fusions with chromosome 1p loss, 19q loss, and/or 1q gain. However, it is unknown what proportion of DLGG match the DLGNT group, and which other methylations classes are at risk of metastasis. To improve our understanding of this rare patient population, we created an international DLGG consortium. Data from the first 68 cases shows a broad age distribution and no sex predilection. As expected, DLGG has much worse prognosis than the overall PLGG population. Virtually all DLGG progress at 5 years, compared to a quarter of other PLGG, and DLGG are 5-times more likely to die at 10 years. We observe three patterns of dissemination – 35% present with a localized mass and have secondary dissemination, 50% with disseminated tumor and a clear dominant mass, and 15% with disseminated disease without a dominant mass. In 47 patients with molecular testing, BRAF fusions accounted for 64% of driver alterations. Additional alterations were identified less frequently, including BRAF V600E (9%), FGFR1 alterations (9%), and KRAS mutations (4%). In 25 patients with methylation profiling, 10 (40%) successfully classified with a calibrated score above 0.8, illustrating that many cases do not fit a defined methylation group. The most common methylation classification was pilocytic astrocytoma (5 patients), and surprisingly only two patients classified as DLGNT. In sum this study illustrates the variable clinical behaviour associated with metastasis in PLGG and expands the range of molecular driver alterations, including ones previously unreported in DLGNT.
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Ali Khan, Ahsan, Mohammad Hamza Bajwa, Noman Khan, Muhammad Usman Khalid, Fatima Mubarak e Syed Ather Enam. "NIMG-76. DISCRETE LOWER-GRADE GLIOMA (DLGG) VERSUS INFILTRATIVE LOWER-GRADE GLIOMA (ILGG): CORRELATION OF RADIOLOGICAL CHARACTERISTICS WITH CLINICAL OUTCOMES". Neuro-Oncology 23, Supplement_6 (2 novembre 2021): vi146—vi147. http://dx.doi.org/10.1093/neuonc/noab196.573.
Abstract (sommario):
Abstract INTRODUCTION Lower grade gliomas encompass grade 2 and 3 tumors. However, this term is more generalized and does not include the spectrum of radiological and tumor morphological patterns seen. Here we have established two distinct patterns of radiographic appearance seen within lower grade gliomas: ILGG and DLGG. Imaging plays a vital role in diagnosis, surveillance, characterization, and monitoring of intracranial tumors. Of particular importance is the differentiation of tumor features to reliably predict malignancy, tumor grade, possible molecular or genetic features, disease progression and recurrence, potential for malignant transformation, and postoperative outcomes. Our study will look at these radiographic characteristics of diffuse and infiltrating lower grade gliomas and discuss their predictive value. Understanding the distinct nature of these varieties of LGG will help us in surgical decision-making, prognostication, biopsy target and precision medicine. METHODS Pre-operative and post-operative MRI images of Grade 2 and 3 tumors were identified and analyzed in order to extract radiographic data, and correlated with patient demographics, clinical outcomes, extent of surgical resection, and molecular genetic analysis. RESULTS Out of 35 patients evaluated, 22 (62.9%) were labeled ILGGs and 13 (37.1%) were deemed DLGGs according to the pre-defined criteria. T2 habitat was higher in ILGG (mean = 2162) than DLGG (mean = 1482) as well as size, in cm (6.02 vs. 4.92). ADC habitat, lesion ADC, and percentage of the lesion that showed contrast-enhancement were similar. T2-FLAIR mismatch was significantly higher in ILGG (p = 0.02). Post-operative KPS scores were significantly higher in the DLGG group (p = 0.03). CONCLUSION T2-FLAIR mismatch can be a significant classifier for lower-grade gliomas. Our study shows there are differences in tumor morphology of diffuse and infiltrative lower-grade gliomas which can be correlated to outcomes after surgery. *Indicates corresponding author.
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Hamidi, Nima, Ajay Fernandez, Kyle Tuohy e Alireza Mansouri. "QOLP-09. HEALTH ECONOMIC EVALUATION OF LOW-GRADE GLIOMA MANAGEMENT: A SYSTEMATIC REVIEW". Neuro-Oncology 22, Supplement_2 (novembre 2020): ii176. http://dx.doi.org/10.1093/neuonc/noaa215.734.
Abstract (sommario):
Abstract BACKGROUND Diffuse low-grade gliomas (DLGGs, WHO Grade II gliomas) comprise 13-16% of all primary brain tumors. Although there has been a paradigmatic shift toward upfront maximal safe resection (MSR) for these heterogeneous tumors, it is important to consider the health economic perspective of this approach, compared with the traditional watch-and-wait approach, as well. OBJECTIVE To conduct a systematic review of the health economic literature on the range of DLGG management options. METHODS Following the PRISMA guidelines, Medline, EMBASE, The Central Registration Depository (CRD), EconPapers, and EconLit were searched for ‘cost-effectiveness’, ‘health economics’ and ‘Low-grade glioma’. Grade I tumors were excluded. Pre-specified variables were extracted. All currencies were converted to USD. RESULTS Among 258 abstracts, 28 were selected for full-text screening, and 3 were selected for this review. A European study evaluated the role of intraoperative electrical stimulation (IES). Although IES was associated with higher direct costs upfront ($38,662.70 vs $32,116.10), this was offset by less long-term indirect costs ($12,222.30 vs $31,927.10; p=0.023), greater QALY (4.8 vs 2.9; p=0.001), and an incremental cost-effectiveness ratio (ICER) of $1,842.50. Another study evaluated the cost-effectiveness of adjuvant PCV+RT vs RT alone, finding greater QALY for the former (9.94 vs 5.17) and an ICER of $10,186 per QALY gained. A third study evaluated the cost-effectiveness of adding 18F-fluoroethyl-L-tyrosine (FET) PET to MRI, compared to preoperative MRI alone. This resulted in an ICER of $7,193.58 for the baseline scenario (lowest reimbursement) and $10,236.12 for the morbidity-adjusted reimbursement rate scenario (highest reimbursement). There were no studies evaluating the health economics of maximal upfront surgical resection to the watch-and-wait approach. CONCLUSION We found a limited number of studies reporting on the health economics of DLGGs. Given the paradigmatic transition toward more aggressive upfront surgical resection, DLGG-specific health economic analyses are underway.
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Zetterling, Maria, Kenney R. Roodakker, Shala Ghaderi Berntsson, Per-Henrik Edqvist, Francesco Latini, Anne-Marie Landtblom, Fredrik Pontén, Irina Alafuzoff, Elna-Marie Larsson e Anja Smits. "Extension of diffuse low-grade gliomas beyond radiological borders as shown by the coregistration of histopathological and magnetic resonance imaging data". Journal of Neurosurgery 125, n. 5 (novembre 2016): 1155–66. http://dx.doi.org/10.3171/2015.10.jns15583.
Abstract (sommario):
OBJECTIVE Magnetic resonance imaging tends to underestimate the extent of diffuse low-grade gliomas (DLGGs). With the aim of studying the presence of tumor cells outside the radiological border, the authors developed a method of correlating MRI findings with histological data in patients with suspected DLGGs in whom en bloc resections were performed. METHODS Five patients with suspected DLGG suitable for en bloc resection were recruited from an ongoing prospective study. Sections of the entire tumor were immunostained with antibodies against mutated IDH1 protein (IDH1-R132H). Magnetic resonance images were coregistered with corresponding IDH1 images. The growth pattern of tumor cells in white and gray matter was assessed in comparison with signal changes on corresponding MRI slices. RESULTS Neuropathological assessment revealed DLGG in 4 patients and progression to WHO Grade III glioma in 1 patient. The tumor core consisted of a high density of IDH1-R132H–positive tumor cells and was located in both gray and white matter. Tumor cells infiltrated along the peripheral fibers of the white matter tracts. In all cases, tumor cells were found outside the radiological tumor border delineated on T2-FLAIR MRI sequences. CONCLUSIONS The authors present a new method for the coregistration of histological and radiological characteristics of en bloc–removed infiltrative brain tumors that discloses tumor invasion at the radiological tumor borders. This technique can be applied to evaluate the sensitivity of alternative imaging methods to detect scattered tumor cells at tumor borders. Accurate methods for detection of infiltrative tumor cells will improve the possibility of performing radical tumor resection. In future studies, the method could also be used for in vivo studies of tumor invasion.
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Fahlström, M., S. Mirza e F. Latini. "P15.09.B ALONG-TRACT ANALYSIS OF DTI PARAMETERS TO DETECT EXTENSION AND DIRECTION OF WHITE MATTER ABNORMALITIES IN PATIENTS WITH DIFFUSE LOW GRADE DIFFUSE GLIOMAS". Neuro-Oncology 25, Supplement_2 (1 settembre 2023): ii111. http://dx.doi.org/10.1093/neuonc/noad137.373.
Abstract (sommario):
Abstract BACKGROUND Diffuse Low-grade gliomas (DLGG) show extensive infiltration through white matter (WM) tracts. Diffusion tensor tractography with along-tract analysis (ATA) has been used to non-invasively assess the microstructural integrity of WM pathways. The possibility to detect the extension and direction of WM infiltration using local DTI-based parameters in DLGG has been investigated with different techniques but displayed inconsistent results. The aim of this study was to use ATA analysis to compare DTI parameters in white matter pathways invaded/spared by DLGGs. MATERIAL AND METHODS Fourteen patients with a diagnosis of DLGG were included. DLGGs were manually segmented based on 3D-FLAIR images spatially normalised to MNI space. DTI was acquired for all the subjects using a single-shot echo-planar sequence on a 3T with 48 sampling directions. DTI data was reconstructed within MNI space using q-space diffeomorphic reconstruction (QSDR) in DSI studio. Five bilateral sets of WM pathways were reconstructed based on the HCP-1021 template. ATA was performed for FA, AD and RD for all five bilateral WM pathways. In short, all WH pathways were stretched to the same length of 100 indices, FA, RD and AD were sampled for each index. An overlay of tumour 3D reconstruction was used to detect contact with WM pathways . Not affected WM pathways were considered normal and included as normal data. All WM pathways were compared individually and per index to the normal data using a z-test. RESULTS Eight patients had an IDH-mutated grade 2 astrocytoma, 6 had a 1p19q co-deleted grade 2 Oligodendroglioma. ATA analysis displayed a clear difference between invaded and non-invaded WM pathways in all the DTI parameters. In infiltrated pathways, the z-test displayed: 1) significant lower FA only within a limited tumoral area but not along the all infiltrated segment; 2) RD was significantly higher compared with normal data in a larger area even beyond the tumour borders; 3) AD was significant lower in the infiltrated WM pathways beyond the tumour borders. CONCLUSION s: ATA analysis is a sensitive and reliable method to detect the extension and the direction of diffusion abnormalities within and beyond the DLGG extension. Our results support other studies suggesting that FA is not an enough sensitive index to detect gliomas related WM abnormalities. A wider use of this method may be valuable to better plan the surgical resection of patients with DLGG or to tailor radiotherapy planning according to WM invasion.
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Still, Megan E. H., Alexandre Roux, Gilles Huberfeld, Luc Bauchet, Marie-Hélène Baron, Denys Fontaine, Marie Blonski et al. "Extent of Resection and Residual Tumor Thresholds for Postoperative Total Seizure Freedom in Epileptic Adult Patients Harboring a Supratentorial Diffuse Low-Grade Glioma". Neurosurgery 85, n. 2 (5 novembre 2018): E332—E340. http://dx.doi.org/10.1093/neuros/nyy481.
Abstract (sommario):
Abstract BACKGROUND Epileptic seizures impair quality of life in diffuse low-grade glioma (DLGG) patients. Tumor resection significantly impacts postoperative seizure control, but the precise extent of resection (EOR) required for optimal seizure control is not clear yet. OBJECTIVE To identify the EOR and residual tumor volume that correlated to postoperative seizure control, defined as a total seizure freedom (Class 1A in reference to Engel classification system) with and without antiepileptic drugs in patients undergoing surgical resection of supratentorial DLGG. METHODS A retrospective review was conducted of all patients who underwent first-line surgical resection of supratentorial DLGG who presented with preoperative seizures without adjuvant oncological treatment. EOR and residual tumor volume were quantified from pre- and post-operative magnetic resonance imagings. Receiver operating characteristic curves were plotted to determine the EOR and residual tumor volume that corresponded to optimal postoperative seizure control. RESULTS Of the 346 included patients, 65.5% had controlled seizures postoperatively, with higher age at resection (adjusted OR per unit, 1.03 [95% confidence interval:1.01-1.06], P = .043) and higher percentage of resection (adjusted OR per unit, 1.02 [95% confidence interval:1.00-1.03], P < .001) found as independent predictors of postoperative seizure control. Optimal EOR was ≥91% and optimal residual tumor volume was ≤19 cc to improve postoperative seizure control. CONCLUSION Postoperative seizure control is more likely when EOR is ≥91% and/or when residual tumor volume is ≤19 cc in supratentorial DLGG gliomas who present with seizures. Resected peritumoral cortex should, however, be taken into account in future studies.
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Darlix, A., H. Duffau, V. Rigau e C. Gozé. "P04.14 Loss of oligodendroglial features at recurrence in five diffuse low-grade glioma patients treated with repeated surgery". Neuro-Oncology 21, Supplement_3 (agosto 2019): iii31—iii32. http://dx.doi.org/10.1093/neuonc/noz126.109.
Abstract (sommario):
Abstract BACKGROUND Diffuse low-grade gliomas (DLGG) are characterized by a continuous growth and an unavoidable anaplastic transformation. IDH mutation and 1p19q codeletion have been integrated to the 2016 WHO classification to define the oligodendroglioma entity. Whenever feasible, neurosurgical resection is the first treatment option. At recurrence, a second surgical resection is proposed in selected cases. The consistency of molecular patterns (IDH mutation, 1p19q codeletion) at recurrence has been poorly studied in DLGG. MATERIAL AND METHODS We conducted a retrospective study on consecutive DLGG patients treated at our institution with repeated surgery (2006–2017). Clinical and biological data were collected for both the initial and subsequent surgery. Additional immunohistochemistry (including tumor morphology, ATRX and p53) and genetic analyses (TERT promoter mutation, CIC mutation, CGHa) were also performed on tumors with joint loss of IDH mutation and of 1p19q codeletion at recurrence. RESULTS A total of 71 patients were identified. Analyses were carried out on 56 patients (molecular data missing: n=15). Nine patients (16.1%) presented with a loss of their IDH mutation at second surgery. Five of them (8.9%) had an additional loss of their 1p19q codeletion. These five cases (3 men, median age 36.6 years) were all treated with surgery as the first oncological treatment. The first surgery revealed in all cases tumors with morphological oligodendroglial features, IDH mutation and 1p19q codeletion. Further molecular analysis strengthened the diagnosis of oligodendroglioma (TERT promoter and CIC mutations, no ATRX loss, no expression of p53). Four patients were followed-up after the first surgery; one patient received Temozolomide 14 months later due to FLAIR tumor volume growth. Because of the regrowth of the residual FLAIR tumor volume, a second surgery was performed in all patients, after a median time of 38.9 months. The morphological oligodendroglial features were lost, and the genetic analyses revealed in all cases no IDH mutation, no 1p19q codeletion, no ATRX loss and no expression of p53. No evidence of anaplasia was found histologically or by CGHa analysis in these recurrent tumors. CONCLUSION We describe five DLGG patients with a shared histo-molecular evolution characterized by the loss of the initial IDH mutation and of oligodendroglial features at second surgery. While rare, this possible evolution must be acknowledged as it can impact the subsequent therapeutic strategy. This observation is the first of a loss of founder alterations in DLGG genesis (i.e. IDH mutation and 1p19q codeletion); the involved mechanism likely differs from the previously described oligoclonal selection caused by spontaneous tumor genetic drift and/or pressure of chemotherapy, and could be linked with the Darwinian selection of a subpopulation of tumor cells after the first surgery.
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Darlix, A., V. Rigau, J. Fraisse, C. Gozé, M. Fabbro e H. Duffau. "P04.02 Postponing the medical treatment is possible in selected cases of diffuse low-grade glioma with foci of WHO grade III-IV after total or subtotal resection". Neuro-Oncology 21, Supplement_3 (agosto 2019): iii28—iii29. http://dx.doi.org/10.1093/neuonc/noz126.097.
Abstract (sommario):
Abstract BACKGROUND Diffuse low-grade gliomas (DLGG) are defined by a continuous growth and an unavoidable malignant transformation. Foci of malignant transformation may be found within DLGG samples obtained from surgical resections. As the medical management is classically based on the higher tumor grade, an immediate adjuvant treatment is usually proposed (radiotherapy [RT] with Temozolomide or PCV), whatever the extent of resection. Yet, early RT has no impact on overall survival compared with late RT, and is associated with cognitive toxicity. An alternative approach consists in postponing the medical treatment in selected patients. MATERIAL AND METHODS We conducted a monocentric retrospective analysis of a consecutive series of patients managed with this conservative approach. Inclusion criteria were: DLGG (WHO 2016 grade II) with at least one focus of malignant transformation (grade III-IV); no previous chemotherapy or RT; no less than a subtotal resection of the FLAIR tumor volume; no intention of treating with immediate adjuvant therapy; at least two years of postoperative follow-up. The time interval to the next medical treatment (chemotherapy and/or radiotherapy) was assessed, as well as the functional and survival results. RESULTS Forty-five DLGG patients, of median age 36.5 years, were included in the analysis (median time interval from diagnosis: 7.3 months). The histo-molecular diagnosis was diffuse astrocytoma, IDH mutant in 46.7% of cases, astrocytoma, IDH wild-type in 13.3% and oligodendroglioma, IDH mutant and 1p/19q codeleted in 40.0%. Ten tumors presented with grade IV foci. The quality of resection was subtotal (FLAIR tumor residue ≤15 cm3) in 73.3%, total (no FLAIR tumor residue) in 24.4% and supratotal in 2.2%. After surgery, patients were managed with regular clinical and radiological follow-up. With a median postoperative follow-up of 6.3 years, 75.5% of patients received a subsequent medical treatment, after a median time interval of 3.7 years. The first treatment after surgery consisted of repeated surgery in 11 patients, Temozolomide in 28 patients, RT in one patient. At the time of analysis, 19 patients (42.2%) had been treated with RT, after a median time interval of 9.5 years. Nine patients (20.0%) had died (median overall survival not reached, 5-years and 7-years survival rates: 95.2% and 67.0%). Most surviving patients were still active professionally (69.4%), with a median Karnofsky performance status of 90, and no or rare seizures. CONCLUSION In this series, total or subtotal resection of DLGG with a least one focus of grade III-IV glioma radically changed the natural history of these tumors and allowed delaying the following medical treatment by several years. This strategy is feasible in selected patients and should be considered on a case-by-case basis in patients with foci of malignant transformation following total or subtotal resection.
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Acharya, Shami, Priya Sekhon, Jose Pedro Lavrador, Ravindran Visagan, Vijay Narbad, Josephine Jung, Richard Gullan, Francesco Vergani, Ranj Bhangoo e Keymours Ashkan. "Diffuse Low Grade Glioma - A 10-year single institution case series". Neuro-Oncology 21, Supplement_4 (ottobre 2019): iv15. http://dx.doi.org/10.1093/neuonc/noz167.064.
Abstract (sommario):
Abstract Objectives To study clinical features and treatment options between 2007–2018 in a population of diffuse low grade glioma (DLGG) patients (WHO Grade2). Methods Single centre retrospective cohort study. Variables reviewed: demographics, extent of resection (biopsy – Bx, subtotal resection – STR, gross total resection – GTR), molecular genetics and outcome. Results N=104.M=61 F=43, average age, 41.8 yrs. For their first surgery, 40.4% underwent a Bx, 32.7% STR, 26.9% GTR. 50.9% of patients had a second procedure due to clinical progression (13.8% Bx, 38.85% STR, 47.2% GTR). We were more surgically aggressive at the second sitting (p=0.0021). After 2014, we were more aggressive in terms of achieving a resection over a biopsy alone (pre 2013: 26 Bx, 24 resection, post 2013: 15 Bx, 28 resection). 35% had 1p19q co-deletion, 70% had 1DH1 mutation and 44.6% with MGMT methylated. There was no difference in survival and extent of resection in 1p19 co-deletions (HR 0.35), however there was in the IDH 1 group (HR 1.25. Post operatively, 37.9% patients had chemotherapy and 57.3 % radiotherapy. 80.5% (Bx 65,9% alive, resection 95% alive) of patients are still alive (longest survival 11.6 yrs). Amongst those who died, the mean overall survival was 4.0 (range 0–7 - 5 years): Of these 14% had undergone a Bx and 6% STR/GTR. The adjusted analysis revealed that EOR is the only revelant factor for survival in the population when adjusted for IDH, 1p19q, tumour volume, age, gender and surgery year (p=0.44). Conclusion Our data emphasises the importance of achieving maximal resection when possible.
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Duffau, H. "A new philosophy in surgery for diffuse low-grade glioma (DLGG): Oncological and functional outcomes". Neurochirurgie 59, n. 1 (febbraio 2013): 2–8. http://dx.doi.org/10.1016/j.neuchi.2012.11.001.
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Chan-Seng, Emilie, Sylvie Moritz-Gasser e Hugues Duffau. "Awake mapping for low-grade gliomas involving the left sagittal stratum: anatomofunctional and surgical considerations". Journal of Neurosurgery 120, n. 5 (maggio 2014): 1069–77. http://dx.doi.org/10.3171/2014.1.jns132015.
Abstract (sommario):
Object Preserving function while optimizing the extent of resection is the main goal in surgery for diffuse low-grade glioma (DLGG). This is particularly relevant for DLGG involving the sagittal stratum (SS), where damage can have severe consequences. Indeed, this structure is a major crossroad in which several important fascicles run. Thus, its complex functional anatomy is still poorly understood. Subcortical electrical stimulation during awake surgery provides a unique opportunity to investigate white matter pathways. This study reports the findings on anatomofunctional correlations evoked by stimulation during resection for gliomas involving the left SS. Surgical outcomes are also detailed. Methods The authors performed a review of patients who underwent awake surgery for histopathologically confirmed WHO Grade II glioma involving the left SS in the neurosurgery department between August 2008 and August 2012. Information regarding clinicoradiological features, surgical procedures, and outcomes was collected and analyzed. Intraoperative electrostimulation was used to map the eloquent structures within the SS. Results Eight consecutive patients were included in this study. There were 6 men and 2 women, whose mean age was 41.7 years (range 32–61 years). Diagnosis was made because of seizures in 7 cases and slight language disorders in 1 case. After cortical mapping, subcortical stimulation detected functional fibers running in the SS in all patients: semantic paraphasia was generated by stimulating the inferior frontooccipital fascicle in 8 cases; alexia was elicited by stimulating the inferior longitudinal fascicle in 3 cases; visual disorders were induced by stimulating the optic radiations in 5 cases. Moreover, in front of the SS, phonemic paraphasia was evoked by stimulating the temporal part of the arcuate fascicle in 5 patients. The resection was stopped according to these functional limits in the 8 patients. After a transient postsurgical worsening, all patients recovered to normal results on examination, except for the persistence of a right superior quadrantanopia in 5 cases, with no consequences for quality of life. The 8 patients returned to a normal social and professional life. Total or subtotal resection was achieved in all cases but one. Conclusions The authors suggest that the use of intrasurgical electrical mapping of the white matter pathways in awake patients opens the door to extensive resection of DLGG within the left SS while preserving the quality of life. Further anatomical, clinical, radiological, and electrophysiological studies are needed for a better understanding of the functional anatomy of this complex region.
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Buvarp, Dongni, Isabelle Rydén, Katharina S. Sunnerhagen, Thomas Olsson Bontell, Tomás Gómez Vecchio, Anja Smits e Asgeir Store Jakola. "Preoperative Patient-Reported Outcomes in Suspected Low-Grade Glioma: Markers of Disease Severity and Correlations with Molecular Subtypes". Journal of Clinical Medicine 10, n. 4 (8 febbraio 2021): 645. http://dx.doi.org/10.3390/jcm10040645.
Abstract (sommario):
This prospective study aims to determine the overall health-related quality of life (HRQoL), functioning, fatigue, and psychological distress preoperatively in patients with suspected diffuse low-grade glioma (dLGG). We were particularly interested if these parameters differed by molecular tumor subtypes: oligodendroglioma, IDHmut astrocytoma and IDHwt astrocytoma. Fifty-one patients answered self-assessed questionnaires prior to operation (median age 51 years; range 19–75; 19 females [37%]). Thirty-five (69%) patients had IDH-mutated tumors, of which 17 were 1p/19q codeleted (i.e., oligodendroglioma) and 18 non-1p/19q codeleted (i.e., IDHmut astrocytoma). A lower overall generic HRQoL was associated with a high level of fatigue (rs = −0.49, p < 0.001), visual disorder (rs = −0.5, p < 0.001), motor dysfunction (rs = −0.51, p < 0.001), depression (rs = −0.54, p < 0.001), and reduced functioning. Nearly half of the patients reported high fatigue (23 out of 51 patients) and anxiety (26/51 patients). Patients with IDHwt had worse generic HRQoL, worse functioning, and more severe fatigue, though differences were not statistically significant between the molecular subtypes. In conclusion, fatigue and anxiety are prominent self-assessed symptoms of patients with suspected dLGG in a preoperative setting, but do not seem to be a reliable method to make assumptions of underlying biology or guide treatment decisions.
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Darlix, A., M. Fabbro, M. Monnier, F. Castan, L. Coutant, E. Denis, M. Carriere et al. "P01.15.A Longitudinal assessment of neurocognition and quality of life in low-grade glioma patients receiving first-line Temozolomide". Neuro-Oncology 24, Supplement_2 (1 settembre 2022): ii27. http://dx.doi.org/10.1093/neuonc/noac174.087.
Abstract (sommario):
Abstract Background While maximal safe resection is the first therapeutic option in patients with newly-diagnosed diffuse low-grade glioma (DLGG), the timing and choice of further treatments (chemotherapy, radiation therapy or combinations of both) remain controversial. Because the expected survival is long in these young patients, the oncological impact of treatments must be balanced with the possible side effects, in particular regarding neurocognitive functioning and quality of life (QoL). Temozolomide (TMZ), an alkylating agent, is widely used in this setting. Here we aimed at evaluating the feasibility of a longitudinal neurocognitive and QoL assessment in DLGG patients receiving TMZ. Material and Methods We conducted a prospective study including adult DLGG patients receiving TMZ as first-line treatment after surgical resection(s) or biopsy. Neurocognition and QoL were evaluated longitudinally until progression. The feasibility was evaluated in terms of participation and compliance of a complete neurocognitive and QoL assessment (defined as the completion of these assessments at baseline, 6 months and 12 months). Secondary objectives were the description of the proportion of patients with changes in neurocognitive or QoL scores on TMZ. Results Of 29 eligible patients, 26 accepted to enter the study (participation rate 86.7%): 57.7% men, median age 45y. Tumor type was distributed as follows: astrocytoma, IDH-mutant 13/26, astrocytoma, IDH wild-type 1/26 and oligodendroglioma, IDH mutant and 1p19q codeleted 12/26. The compliance rate was 95.6% (evaluable in 23 patients as 3 patients had tumor progression within the first 12 months of TMZ). After TMZ, 13.6% of patients experienced a decline of the MoCA score as compared to baseline (from normal to abnormal). Cognitive complaints according to the FACT-COG assessment were stable for 90.9%. The complete cognitive and QoL evaluations (baseline and after 12 months of TMZ) will be presented. Conclusion Our data shows that a longitudinal evaluation of cognition and QoL is feasible in low-grade glioma patients. It suggests that first-line TMZ does not negatively affect neurocognition and QoL. These results must be evaluated in the long-term setting (evaluations ongoing) and confirmed in a larger, multicenter cohort.
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Tilling, Elliot, Simon Lammy, Elsie Bridgman, Hannah Johnson, Alexandru Stan, Aaron Taylor e Athanasios Grivas. "The Changing Landscape of Diffuse Low Grade Glioma (DLGG) Management in the West of Scotland: A Single Centres 10-Year Experience". Neuro-Oncology 24, Supplement_4 (1 ottobre 2022): iv21. http://dx.doi.org/10.1093/neuonc/noac200.095.
Abstract (sommario):
Abstract AIMS Management strategies for patients diagnosed with diffuse low grade glioma (DLGG) remain controversial. Current evidence favours resection over biopsy. This has resulted in more aggressive intervention. We examined management trends in the West of Scotland over a 10 year period. METHOD Patients diagnosed with DLGG between 2010 and 2019 were included and grouped according to time of diagnosis: 1) 2010-2012, 2) 2013-2016 and 3) 2017-2019. Clinical characteristics, management and overall survival (OS) were investigated and comparatively analysed. Survival between resection and biopsy groups was also analysed. RESULTS 84 patients were included (n=25 in Group 1, n=35 in Group 2 and n=24 in Group 3). Biopsy was less commonly performed in Group 2 (17%) and Group 3 (21%) compared to Group 1 (56%) p=0.014. The frequency of post-operative seizures: G1: n=3 (12%), G2: n=1 (2.9%), G3: n=2 (8.3%) (p=0.385) and focal neurological deficit: G1: n=4 (16%), G2: n=8 (22.9%), G3: n=6 (25) (p=0.718) and mean length of stay (LoS) in days: G1: 7.7, G2: 8.8, G3: 7.4 (p = 0.548) were similar across the groups. Survival analysis revealed no significant difference between groups: G1 52%, G2 69%, G3 75% (p=0.172). Patients managed by resection (n=58) versus biopsy (n = 26) observed improved survival (resection OS 70% compared to biopsy OS 39% (p= 0.005)). CONCLUSION Resection results in improved survival over biopsy. This has resulted in an institutional change over time. But no significant difference was observed in OS between different time periods.
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Latini, F., M. Fahlström, A. Beháňová, I. Sintorn, M. Hodik, K. Staxäng e M. Ryttlefors. "P11.62.A The link between gliomas infiltrationandwhite matter architecture investigated with electron microscopy and diffusion tensor imaging". Neuro-Oncology 24, Supplement_2 (1 settembre 2022): ii72. http://dx.doi.org/10.1093/neuonc/noac174.251.
Abstract (sommario):
Abstract Background Diffuse low-grade gliomas (DLGG) display different preferential locations in eloquent and secondary associative brain areas. The reason for this tendency is still unknown. We hypothesized that the intrinsic architecture and water diffusion properties of the white matter bundles in these regions may facilitate gliomas infiltration. Material and Methods Magnetic resonance imaging of sixty-seven diffuse low-grade gliomas patients were normalized to/and segmented in MNI space to create three probabilistic infiltration weighted gradient maps according to the molecular status of each tumor group (IDH mutated, IDH wild-type and IDH mutated/1p19q co-deleted). Diffusion tensor imaging (DTI)- based parameters were derived for five major white matter bundles, displaying regional differences in the grade of infiltration, averaged over 20 healthy individuals acquired from the Human connectome project (HCP) database. Transmission electron microscopy (TEM) was used to analyze fiber density, fiber diameter and g-ratio in 100 human white matter regions, sampled from cadaver specimens, reflecting areas with different gliomas infiltration in each white matter bundle. Histological results and DTI-based parameters were compared in anatomical regions of high- and low grade of infiltration (HIF and LIF) respectively. Results We detected differences in the white matter infiltration of five major white matter bundles in three groups. IDHm infiltrated left fronto-temporal subcortical areas. IDHwt were detected in the posterior-temporal and temporo-parietal regions bilaterally. IDHm/1p19q infiltrated anterior subcortical regions of the frontal lobes bilaterally. Regional differences within the same white matter bundles were detected by both TEM- and DTI analysis linked to different topographical variables. Our multimodal analysis showed that HIF regions, common to all the groups, displayed a smaller fiber diameter, lower FA and higher RD compared with LIF regions. Conclusion Our results suggest that the both morphological features and diffusion parameters of the white matter may be different in regions linked to the preferential location of DLGG.
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Ng, Sam, Pablo Andres Valdes, Sylvie Moritz-Gasser, Anne-Laure Lemaitre, Hugues Duffau e Guillaume Herbet. "207 Intraoperative Functional Re-mapping Unveils Evolving Patterns of Cortical Plasticity". Neurosurgery 70, Supplement_1 (aprile 2024): 54–55. http://dx.doi.org/10.1227/neu.0000000000002809_207.
Abstract (sommario):
INTRODUCTION: Diffuse low-grade gliomas (DLGG) induce a compensatory modulation of the anatomo-functional architecture, making this kind of brain tumours an ideal lesion model to study the dynamics of neuroplasticity. Direct electrostimulation (DES) mapping is a well-tried procedure used during awake resection surgeries to spare cortical epicenters which are critical for a range of functions. Because DLGG is a chronic disease, it inevitably relapses years after the initial surgery, and thus requires a second surgery to reduce tumour volume again. METHODS: We capitalized on a series of 101 DLGG patients who benefited from two DES-guided neurosurgeries usually spaced several years apart, resulting in a DES dataset of 2082 cortical sites. We used a multi-step approach to generate probabilistic neuroplasticity maps that reflected the dynamic rearrangements of cortical mappings from one surgery to another, both at the population and individual-level. RESULTS: Voxel-wise neuroplasticity maps revealed regions with a high potential of evolving reorganizations, including the supplementary motor area (SMA), the dorsolateral prefrontal cortex (dlPFC), the anterior ventral premotor cortex (vPMC) and the middle superior temporal gyrus (STG). Parcel-wise neuroplasticity maps confirmed this potential for the dlPFC, the anterior and the ventral precentral gyrus. A series of clustering analyses revealed a topological migration of clusters, especially within the left dlPFC and STG (language sites); the left vPMC (speech arrest/dysarthria sites) and the right SMA (negative motor response sites). At the individual level, these dynamic changes were confirmed for the dlPFC (bilateral), the left vPMC and the anterior left STG (threshold free cluster enhancement, 5000 permutations, family-wise-error-corrected). CONCLUSIONS: Our results provide a critical insight into the dynamic potential of DLGG-induced continuing rearrangements of the cerebral cortex, with considerable implications for re-operations.
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Ius, Tamara, Giada Pauletto, Barbara Tomasino, Marta Maieron, Riccardo Budai, Miriam Isola, Daniela Cesselli, Christian Lettieri e Miran Skrap. "Predictors of Postoperative Seizure Outcome in Low Grade Glioma: From Volumetric Analysis to Molecular Stratification". Cancers 12, n. 2 (8 febbraio 2020): 397. http://dx.doi.org/10.3390/cancers12020397.
Abstract (sommario):
The importance of the extent of resection (EOR) has been widely demonstrated as the main predictor for survival, nevertheless its effect on tumor related epilepsy is less investigated. A total of 155 patients were enrolled after a first-line surgery for supratentorial Diffuse Low Grade Gliomas (DLGGs). Postoperative seizure outcome was analyzed stratifying the results by tumor volumetric data and molecular markers according to 2016 WHO classification. Receiver operating characteristic (ROC) curves were computed to asses EOR, residual tumor volume, and ΔT2T1 MRI index (expressing the tumor growing pattern) corresponding to optimal seizure outcome. A total of 70.97% of patients were seizure-free 18 months after surgery. Better seizure outcome was observed in IDH1/2 mutated and 1p/19q codeleted subgroup. At multivariate analysis, age (p = 0.014), EOR (p = 0.030), ΔT2T1 MRI index (p = 0.016) resulted as independent predictors of postoperative seizure control. Optimal parameters to improve postoperative seizure outcome were EOR ≥ 85%, ΔT2T1 MRI index ≤ 18 cm3, residual tumor volume ≤ 15 cm3. This study confirms the role of EOR and tumor growing pattern on postoperative seizure outcome independently from the molecular class. Higher ΔT2T1 MRI index, representing the infiltrative component of the tumor, is associated with worse seizure outcome and strengthens the evidence of common pathogenic mechanisms underlying tumor growth and postoperative seizure outcome.
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Wong, D., Y. Shen, A. B. Levine, T. Hoon Lee, E. Pleasance, M. Jones, B. Thiessen et al. "29 Unraveling molecular drivers of brain cancers at the clinical setting". Canadian Journal of Neurological Sciences / Journal Canadien des Sciences Neurologiques 45, S3 (giugno 2018): S15. http://dx.doi.org/10.1017/cjn.2018.302.
Abstract (sommario):
Brain tumor behavior is driven by aberrations in the genome and epigenome. Many of these changes, such as IDH mutations in diffuse low-grade glioma (DLGG), are common amongst the same class of tumour and can be incorporated into the diagnostic criteria. However, any given tumor may have other, less common genomic aberrations that are essential for its biological behavior and may inform on underlying aberrant cellular pathways, and potential therapeutic agents. Precision oncology is a genomics-based approach which profiles these alterations to better manage cancer patients and has established itself within the practice of oncology and is slowly making its way into neuro-oncology. The BC Cancer’s Personalized OncoGenomics (POG) program has profiled 16 adult tumours originating from the central nervous system using whole genome and transcriptome analysis (WGTA), for the first time, within a meaningful clinical timeframe/setting. As expected, primary genomic drivers were consistent with their respective diagnoses, though secondary drivers were found to be unique to each tumour. Although these analyses did not result in altered clinical management for these patients, primarily due to availability of drug or clinical trials, they highlight the heterogeneity of secondary drivers in cancers and provide clinicians with meaningful biological information. Lastly, the data generated by POG has highlighted the frequency and complexity of novel driver fusions which are predicted to behave similarly to canonical driver events in their respective tumours. The information available to clinicians through POG has provided paramount knowledge into the biology of each unique tumour.
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Dénes, Anna, Thomas Olsson Bontell, Hanna Barchéus, Sandra Ferreyra Vega, Helena Carén, Cecilia Lindskog, Asgeir S. Jakola e Anja Smits. "The clinical value of proneural, classical and mesenchymal protein signatures in WHO 2021 adult-type diffuse lower-grade gliomas". PLOS ONE 18, n. 5 (16 maggio 2023): e0285732. http://dx.doi.org/10.1371/journal.pone.0285732.
Abstract (sommario):
Objectives Accumulating evidence shows that mesenchymal transition of glioblastomas is associated with a more aggressive course of disease and therapy resistance. In WHO2021-defined adult-type diffuse gliomas of lower grade (dLGG), the transition of the tumor phenotype over time, has not been studied. Most efforts to correlate proneural, classical or mesenchymal phenotype with outcome in dLGG were made prior to the WHO 2021 classification. Here, we set out to investigate if phenotype predicted survival and tumor recurrence in a clinical cohort of dLGGs, re-classified according to the 2021 WHO criteria. Methods Using a TMA-based approach with five immunohistochemical markers (EGFR, p53, MERTK, CD44 and OLIG2), we investigated 183 primary and 49 recurrent tumors derived from patients with previously diagnosed dLGG. Of the 49 relapses, nine tumors recurred a second time, and one a third time. Results In total, 71.0% of all tumors could be subtyped. Proneural was most dominant in IDH-mut tumors (78.5%), mesenchymal more common among IDH-wt tumors (63.6%). There was a significant difference in survival between classical, proneural and mesenchymal phenotypes in the total cohort (p<0.001), but not after molecular stratification (IDH-mut: p = 0.220, IDH-wt: p = 0.623). Upon recurrence, proneural was retained in 66.7% of the proneural IDH-mut dLGGs (n = 21), whereas IDH-wt tumors (n = 10) mainly retained or gained mesenchymal phenotype. No significant difference in survival was found between IDH-mut gliomas remaining proneural and those shifting to mesenchymal phenotype (p = 0.347). Conclusion Subtyping into classical, proneural and mesenchymal phenotypes by five immunohistochemical markers, was possible for the majority of tumors, but protein signatures did not correlate with patient survival in our WHO2021-stratified cohort. At recurrence, IDH-mut tumors mainly retained proneural, while IDH-wt tumors mostly retained or gained mesenchymal signatures. This phenotypic shift, associated with increased aggressiveness in glioblastoma, did not affect survival. Group sizes were, however, too small to draw any firm conclusions.
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Terakawa, Yuzo, Yordanka N. Yordanova, Matthew C. Tate e Hugues Duffau. "Surgical management of multicentric diffuse low-grade gliomas: functional and oncological outcomes". Journal of Neurosurgery 118, n. 6 (giugno 2013): 1169–75. http://dx.doi.org/10.3171/2013.2.jns121747.
Abstract (sommario):
Object Multicentric diffuse low-grade gliomas (DLGGs) are defined as widely separated lesions in different lobes or hemispheres where there is no anatomical continuity between lesions. This condition is rare and its clinicopathological characteristics have been scarcely described in the literature. Here, the authors report the first consecutive surgical series of multicentric DLGGs with functional and oncological outcomes. Methods A retrospective review of patients surgically treated for histopathologically confirmed multicentric DLGGs between 2000 and 2012 was performed. Information regarding clinical features, surgical procedures, histopathological results, and clinical outcomes was collected and analyzed. Results Five consecutive patients were included in this study. There were 3 men and 2 women, whose mean age was 27.4 years (range 23–35 years). The mean follow-up period after surgery was 46 months (range 11–138 months). Gross-total or subtotal resection was achieved in all cases, using a single surgery in 3 patients and a 2-stage surgery in 2 patients. There was no mortality or permanent morbidity associated with surgery. The Karnofsky Performance Scale score ranged between 90 and 100 in all cases. Adjuvant chemotherapy was administered in 2 patients because of tumor regrowth with no malignant transformation. Conclusions Multicentric DLGGs can be removed safely without inducing severe permanent neurological deficits. Interestingly, a single-stage resection of multiple lesions within different lobes may be performed if tumors are located in the same hemisphere. Therefore, the authors suggest considering surgery as the first therapeutic option for multicentric DLGGs, as in solitary DLGGs.
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Dénes, A., T. Olsson Bontell, H. Barchéus, S. Ferreyra Vega, H. Carén, C. Lindskog, A. S. Jakola e A. Smits. "P02.15.A PRONEURAL, CLASSICAL AND MESENCHYMAL PROTEIN SIGNATURES LACK PROGNOSTIC VALUE IN WHO 2021 ADULT TYPE DIFFUSE LOWER-GRADE GLIOMAS". Neuro-Oncology 25, Supplement_2 (1 settembre 2023): ii33. http://dx.doi.org/10.1093/neuonc/noad137.100.
Abstract (sommario):
Abstract BACKGROUND Mesenchymal transformation in glioblastomas is associated with therapy resistance and increased aggressiveness. In WHO 2021-defined adult-type diffuse gliomas of lower grade (dLGG), the transition between phenotypic states, has not been studied. Most reports correlating proneural, classical or mesenchymal signatures with outcome in dLGG were made prior to the WHO 2021 classification. Here, we set out to investigate if phenotype as well as the transition of phenotype predicted survival in a clinical cohort of WHO 2021 defined dLGGs. MATERIAL AND METHODS We used a TMA-based approach and five immunohistochemical markers (EGFR, p53, MERTK, CD44 and OLIG2) to examine 183 primary and 49 recurrent tumors from patients with previously diagnosed dLGG. Of the 49 recurrent tumors, nine tumors relapsed a second time, and one a third time. RESULTS In total, 71.0% of all tumors could be subtyped into proneural, classical or mesenchymal. Proneural was the predominant subtype among IDH-mut tumors (78.5%), while in IDH-wt tumors mesenchymal was more common (63.6%). A significant difference in survival was found between subtypes (proneural, classical and mesenchymal) in the total cohort (p<0.001), but not when molecularly stratified (IDH-mut: p=0.220, IDH-wt: p=0.623). Upon relapse, proneural signature was retained in 66.7% of the proneural IDH-mut dLGGs (n=21), whereas IDH-wt tumors (n=10) mainly retained or gained mesenchymal phenotype. There was no significant difference in survival between IDH-mut gliomas remaining proneural and those switching to mesenchymal signature (p=0.347). CONCLUSION Subtyping into proneural, classical and mesenchymal phenotypes by five immunohistochemical markers, was possible for the majority of tumors, but statistical significance between phenotypes and survival was lost after molecular stratification according to the WHO 2021 criteria. IDH-mut tumors mainly remained proneural at recurrence, while IDH-wt tumors mostly retained or gained mesenchymal phenotype. This phenotypic shift, which in glioblastoma is associated with increased aggressiveness, did not affect survival. Sample sizes were, however, too small to draw any firm conclusions on whether this negative finding is due to lack of statistical power or reflects a true biological difference from glioblastomas.
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Ramakrishnan, Piravin, Saad Moughal, William Bolton, John Gooden, Paul Chumas e Ryan Mathew. "SURG-29. CAN NEOADJUVANT CHEMOTHERAPY INCREASE EXTENT OF RESECTION IN DIFFUSE LOWER-GRADE GLIOMA?" Neuro-Oncology 24, Supplement_7 (1 novembre 2022): vii258. http://dx.doi.org/10.1093/neuonc/noac209.994.
Abstract (sommario):
Abstract INTRODUCTION Maximal safe surgical resection remains front-line treatment for diffuse lower-grade gliomas (DLGGs). Greater extent of resection (EOR) can delay transformation, control seizures, and improve survival. EOR is limited by the infiltrative nature of DLGGs and eloquent brain location preponderance. We investigated the role of neoadjuvant chemotherapy in tumour volume reduction (TVR) for cases in which a meaningful EOR was deemed unachievable. METHODS Retrospective review (2000-2020) of patients in a large tertiary UK brain tumor centre who serendipitously underwent management that did or could mimic a neoadjuvant chemotherapy pathway. Inclusion criteria: >18 years at diagnosis; histologically-proven WHO grade 2 supratentorial glioma; received chemotherapy alone after biopsy then +/- debulking. Tumour volume delta +/- EOR were calculated on serial MRI T2/FLAIR sequences using a semi-automated quantitative analysis tool (Smartbrush, BrainLab® AG). RESULTS Group 1 (neoadjuvant chemotherapy and then surgery, n=4): debulking was considered unachievable initially but then possible post-chemotherapy. Median TVR post-chemotherapy was 16.90% (range 0.45–64.90%). Mean EOR was 68.67% (33.72–100%). Median overall survival (OS) and progression free survival (PFS) were 85 (18–154) and 62 (13–153) months, respectively. Group 2 (biopsy followed by chemotherapy alone, n=7): debulking was considered unachievable initially. Median TVR post-chemotherapy was 25.68% (-294.95–46.02%, one patient progressed during chemotherapy). Median OS and PFS were 92 (6–135) and 27 (3–80) months, respectively. On re-review, and based on Group 1 results, some Group 2 patients may have been able to undergo debulking with meaningful EOR post-chemotherapy. CONCLUSIONS Chemotherapy can have a significant impact on reducing tumour volumes, such that cases initially deemed unsuitable for debulking may be converted into those in which a meaningful EOR can be achieved. Larger, multicentre, retrospective studies, and prospective trials are needed to determine the role of chemotherapy as a neoadjuvant tool in the management of DLGGs.
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Pallud, Johan, e Guy M. McKhann. "Diffuse Low-Grade Glioma-Related Epilepsy". Neurosurgery Clinics of North America 30, n. 1 (gennaio 2019): 43–54. http://dx.doi.org/10.1016/j.nec.2018.09.001.
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Dellaretti, Marcos, Gustavo Touzet, Nicolas Reyns, François Dubois, Sebastião Gusmão, Júlio Leonardo Barbosa Pereira e Serge Blond. "Correlation among magnetic resonance imaging findings, prognostic factors for survival, and histological diagnosis of intrinsic brainstem lesions in children". Journal of Neurosurgery: Pediatrics 8, n. 6 (dicembre 2011): 539–43. http://dx.doi.org/10.3171/2011.9.peds1167.
Abstract (sommario):
Object The aim of this study was to compare MR imaging characteristics with histopathological findings of intrinsic brainstem lesions and also to show the prognostic factors in patients with diffuse brainstem glioma. Methods Between February 1988 and August 2007, 44 brainstem biopsies were performed at the Roger Salengro Hospital in Lille, France, in children with intrinsic brainstem lesions not amenable to excision. Twenty-six were female and 18 male, and the mean age was 6 years. Results Histological evaluation revealed diffuse brainstem glioma in all patients with diffuse nonenhancing brainstem lesions. Diffuse brainstem glioma was found in 18 patients (90%) with diffuse enhancing brainstem lesions. Pathological entities different from diffuse glioma were verified in 2 patients (10%)—1 with ependymoma and 1 with ganglioglioma. In 4 of 5 patients with a focal nonenhancing brainstem lesion, the histopathological diagnosis was diffuse low-grade glioma. In 6 of 10 patients with focal enhancing brainstem lesion, the diagnosis was diffuse brainstem glioma, and pathological entities different from diffuse brainstem glioma were verified in 2 (20%), both with pilocytic astrocytoma. The mean 1-year actuarial survival rates for patients classified with low-grade and high-grade glioma were 80.4% ± 0.08% and 48.6% ± 0.14%, respectively. Conclusions The impact of stereotactic biopsy on intrinsic brainstem lesions was greater in patients with MR imaging–documented enhancing lesions in whom the diagnosis of diffuse glioma was less frequent. Patients with low-grade glioma seem to have longer survival than those with high-grade glioma.
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Surbeck, W., G. Herbet e H. Duffau. "Sexuality after surgery for diffuse low-grade glioma". Neuro-Oncology 17, n. 4 (19 febbraio 2015): 574–79. http://dx.doi.org/10.1093/neuonc/nou326.
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Dellaretti, Marcos, Nicolas Reyns, Gustavo Touzet, François Dubois, Sebastião Gusmão, Júlio Leonardo Barbosa Pereira e Serge Blond. "Diffuse brainstem glioma: prognostic factors". Journal of Neurosurgery 117, n. 5 (novembre 2012): 810–14. http://dx.doi.org/10.3171/2012.7.jns111992.
Abstract (sommario):
Object Brainstem gliomas were regarded as a single entity prior to the advent of MRI; however, several studies investigating MRI have recognized that these lesions are a heterogeneous group, and certain subgroups have a better prognosis for long-term survival. The aim of this study was to conduct a retrospective analysis of prognostic factors of patients with brainstem gliomas confirmed by histopathological diagnosis, particularly regarding assessment of whether histological grade, age, and MRI findings are prognostic factors for patient survival. Methods The study evaluated 100 patients diagnosed with brainstem glioma. There were 63 adults (40 men and 23 women; age range 18–75 years, mean 41 years) and 37 children (19 boys and 18 girls; age range 2–12 years, mean 6.9 years). Results The mean overall survival of this population, measured from the date of biopsy, was 57 months for diffuse low-grade glioma and 13.8 months for diffuse high-grade glioma (p < 0.001). The mean survival among patients with nonenhancing contrast lesions on MRI was 54.2 months, whereas for patients with enhancing lesions, it was 21.7 months (p < 0.001). Comparisons between the Kaplan-Meier survival curves of adults and children revealed similar median survival periods of 25 and 16 months, respectively (p > 0.05). The multivariate analysis (Cox proportional hazards regression) revealed that only histological grade was a significant prognostic factor (p < 0.001). Conclusions The study revealed that histological grade and MRI features were significant prognostic factors for survival in these patients, but in multivariate analysis, only histological grade remained a significant factor.
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Mandonnet, Emmanuel, Michel Wager, Fabien Almairac, Marie-Helene Baron, Marie Blonski, Christian F. Freyschlag, Fabio Barone et al. "Survey on current practice within the European Low-Grade Glioma Network: where do we stand and what is the next step?" Neuro-Oncology Practice 4, n. 4 (17 gennaio 2017): 241–47. http://dx.doi.org/10.1093/nop/npw031.
Abstract (sommario):
Abstract Diffuse low-grade glioma form a rare entity affecting young people. Despite advances in surgery, chemotherapy, and radiation therapy, diffuse low-grade glioma are still incurable. According to current guidelines, maximum safe resection, when feasible, is the first line of treatment. Apart from surgery, all other treatment modalities (temozolomide, procarbazine-CCNU-vincristine regimen, and radiation therapy) are handled very differently among different teams, and this in spite of recent results of several phase 3 studies. Based on a European survey, this paper aimed to get a picture of this heterogeneity in diffuse low-grade glioma management, to identify clinically relevant questions raised by this heterogeneity of practice, and to propose new methodological frameworks to address these questions.
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Nishikawa, Ryo. "Low-grade Glioma: Management Issues(Treatment of Diffuse Astrocytoma Grade 2)". Japanese Journal of Neurosurgery 18, n. 6 (2009): 418–22. http://dx.doi.org/10.7887/jcns.18.418.
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Prener, Martin, Giske Opheim, Helle Juhl Simonsen, Christina Malling Engelmann, Morten Ziebell, Jonathan Carlsen e Olaf B. Paulson. "Delineation of Grade II and III Gliomas Investigated by 7T MRI: An Inter-Observer Pilot Study". Diagnostics 13, n. 8 (7 aprile 2023): 1365. http://dx.doi.org/10.3390/diagnostics13081365.
Abstract (sommario):
Purpose: Diffuse low-grade gliomas (DLGGs) are low-malignancy brain tumors originating from the glial cells of the brain growing continuously and infiltratively along the neural axons and infiltrating the surrounding brain tissue. DLGGs usually transform into higher malignancy, causing progressive disability and premature death. MRI scans are valuable when assessing soft tissue abnormalities, but, due to the infiltrative properties of DLGGs, delineating the tumor borders is a challenging task. Therefore, the aim of this study was to explore the difference in gross tumor volume (GTV) of DLGGs delineated from 7 Tesla and 3 Tesla MRI scans. Method: Patients were recruited at the department of neurosurgery and were scanned in both a 7T and a 3T MRI scanner prior to the operation. Two observers delineated the tumors using semi-automatic delineation software. The results from each observer were blinded to the other observer’s delineation. Results: Comparing GTVs from 7T and 3T, the percentage difference varied up to 40.4% on the T2-weighted images. The percentage difference in GTV varied up to 15.3% on the fluid-attenuated inversion recovery (FLAIR) images. On the T2-weighted images, most cases varied by approximately 15%; on the FLAIR sequence, half of the cases varied by approximately 5% and the other half by approximately 15%. The overall inter-observer agreement was near perfect, with an intraclass correlation of 0.969. The intraclass correlation was better on the FLAIR sequence than on the T2 sequence. Conclusion: Overall, the GTVs delineated from 7T images were smaller. The increase in field strength improved the inter-observer agreement only on the FLAIR sequence.
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Li, Gaigai, Yanyan Li, Yang Hu, Qian Wu, Haihan Yu, Hong Deng e Zhouping Tang. "Diffuse low-grade glioma mimicking ischaemic infarct: a case report". International Journal of Neuroscience 128, n. 9 (19 febbraio 2018): 886–90. http://dx.doi.org/10.1080/00207454.2018.1435537.
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Nahed, Brian V., Navid Redjal, Daniel J. Brat, Andrew S. Chi, Kevin Oh, Tracy T. Batchelor, Timothy C. Ryken, Steven N. Kalkanis e Jeffrey J. Olson. "Management of patients with recurrence of diffuse low grade glioma". Journal of Neuro-Oncology 125, n. 3 (3 novembre 2015): 609–30. http://dx.doi.org/10.1007/s11060-015-1910-2.
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Mandonnet, Emmanuel, Philip de Witt Hamer, Johan Pallud, Luc Bauchet, Ian Whittle e Hugues Duffau. "Silent diffuse low-grade glioma: Toward screening and preventive treatment?" Cancer 120, n. 12 (11 marzo 2014): 1758–62. http://dx.doi.org/10.1002/cncr.28610.
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Kumar, Nikhil, Denise Malicki, Michael Levy e John Ross Crawford. "Unusual paediatric-type diffuse low-grade glioma in a toddler". BMJ Case Reports 16, n. 3 (marzo 2023): e254490. http://dx.doi.org/10.1136/bcr-2022-254490.
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Agnihotri, Sameer, Kenneth D. Aldape e Gelareh Zadeh. "Isocitrate dehydrogenase status and molecular subclasses of glioma and glioblastoma". Neurosurgical Focus 37, n. 6 (dicembre 2014): E13. http://dx.doi.org/10.3171/2014.9.focus14505.
Abstract (sommario):
Diffuse gliomas and secondary glioblastomas (GBMs) that develop from low-grade gliomas are a common and incurable class of brain tumor. Mutations in the metabolic enzyme glioblastomas (IDH1) represent a distinguishing feature of low-grade gliomas and secondary GBMs. IDH1 mutations are one of the most common and earliest detectable genetic alterations in low-grade diffuse gliomas, and evidence supports this mutation as a driver of gliomagenesis. Here, the authors highlight the biological consequences of IDH1 mutations in gliomas, the clinical and therapeutic/diagnostic implications, and the molecular subtypes of these tumors. They also explore, in brief, the non-IDH1–mutated gliomas, including primary GBMs, and the molecular subtypes and drivers of these tumors. A fundamental understanding of the diversity of GBMs and lower-grade gliomas will ultimately allow for more effective treatments and predictors of survival.
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Somma, Teresa, Cinzia Baiano, Laura Santi, Giovanni Sabatino, Giuseppe Maria della Pepa, Giuseppe La Rocca, Paolo Cappabianca, Alessandro Olivi, Miran Skrap e Tamara Ius. "Diffuse low grade glioma and pregnancy: Practical considerations and clinical tips". Clinical Neurology and Neurosurgery 198 (novembre 2020): 106110. http://dx.doi.org/10.1016/j.clineuro.2020.106110.
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Onishi, Shumpei, Fumiyuki Yamasaki, Motoki Takano, Ushio Yonezawa, Kazuhiko Sugiyama e Kaoru Kurisu. "NI-17 T2-FLAIR MISMATCH SIGN IN DIFFUSE GLIOMA AND DYSEMBRYOPLASTIC NEUROEPITHELIAL TUMOR". Neuro-Oncology Advances 1, Supplement_2 (dicembre 2019): ii28. http://dx.doi.org/10.1093/noajnl/vdz039.128.
Abstract (sommario):
Abstract BACKGROUND T2-FLAIR mismatch sign was reported as a specific imaging marker for diffuse astrocytoma with IDH-mutant and 1p/19q non-codeletion. However, most of the previous studies for T2-FLAIR mismatch were confirmed only among low grade glioma. The purpose of this study is to assess the T2-FLAIR mismatch sign in supratentorial diffuse glioma, diffuse midline glioma and dysembryoplastic neuroepithelial tumor (DNT) to unveil the exception rules of the sign. METHODS In total, 51 patients were included in this study; 33 supratentorial diffuse glioma (18 diffuse astrocytoma with IDH mutant (IDHmut-Noncodel), 12 oligodendroglioma with IDH-mutant and 1p19q codeletion (IDHmut-Codel), 3 diffuse astrocytoma with IDH wildtype (IDHwt)), 18 diffuse midline glioma and 11 DNT. The tumors were evaluated by 2 independent reviewers to assess presence or absence of T2-FLAIR mismatch sign. RESULT Ten out of 18 cases of IDHmut-Noncodel presented T2-FLAIR mismatch sign. None of the other supratentorial diffuse glioma (IDHmut-Codel and IDHwt) presented T2-FLAIR mismatch. The T2-FLAIR mismatch sign for IDHmut-Noncodel presented 100% positive predictive values among supratentorial diffuse glioma. However, 8 out of 18 cases of diffuse midline glioma and 8 out of 11 cases of DNT also presented the T2-FLAIR mismatch. CONCLUSION The T2-FLAIR mismatch sign was specific marker for IDHmut-NonCodel among supratentorial diffuse glioma. Physicians need to be aware that diffuse midline glioma and DNT could present the T2-FLAIR mismatch sign.
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Oberheim Bush, Nancy Ann, e Susan Chang. "Treatment Strategies for Low-Grade Glioma in Adults". Journal of Oncology Practice 12, n. 12 (dicembre 2016): 1235–41. http://dx.doi.org/10.1200/jop.2016.018622.
Abstract (sommario):
Diffuse low-grade gliomas include oligodendrogliomas and astrocytomas. The recent 2016 WHO classification has now updated the definition of these tumors to include molecular characterization, including the presence of isocitrate dehydrogenase mutation and 1p/19q codeletion. In this new classification, the histologic subtype of grade II mixed oligoastrocytoma has been eliminated. Treatment recommendations are currently evolving, mainly because of a change in the prognostic factors that are based on molecular and cytogenetic features. Standard of care includes maximal safe surgical resection. Prior randomized clinical trials stratified treatment arms on the basis of extent of resection and age, with patients stratified into low risk (age younger than 40 years and gross total resection) and high risk (age older than 40 years or subtotal resection). Patients who are low risk may undergo routine magnetic resonance imaging surveillance after resection. On the basis of recently published data, it is now recommended that high-risk patients undergo a combination of both radiation and chemotherapy after surgery. These studies, however, do not address the management of patients with low-grade gliomas in the era of genomic medicine. These treatments can also have great impact on quality of life, and therefore treatment recommendations should be done on an individual basis taking into account the current pathology classification, age, extent of resection, quality of life, and patient preference.
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van den Bent, Martin J., Marion Smits, Johan M. Kros e Susan M. Chang. "Diffuse Infiltrating Oligodendroglioma and Astrocytoma". Journal of Clinical Oncology 35, n. 21 (20 luglio 2017): 2394–401. http://dx.doi.org/10.1200/jco.2017.72.6737.
Abstract (sommario):
The new 2016 WHO brain tumor classification defines different diffuse gliomas primarily according to the presence or absence of IDH mutations ( IDH-mt) and combined 1p/19q loss. Today, the diagnosis of anaplastic oligodendroglioma requires the presence of both IDH-mt and 1p/19q co-deletion, whereas anaplastic astrocytoma is divided into IDH wild-type ( IDH-wt) and IDH-mt tumors. IDH-mt tumors have a more favorable prognosis, and tumors with low-grade histology especially tend evolve slowly. IDH-wt tumors are not a homogeneous entity and warrant further molecular testing because some have glioblastoma-like molecular features with poor clinical outcome. Treatment consists of a resection that should be as extensive as safely possible, radiotherapy, and chemotherapy. Trials of patients with newly diagnosed grade II or III glioma have shown survival benefit from adding chemotherapy to radiotherapy compared with initial treatment using radiotherapy alone. Both temozolomide and the combination of procarbazine, lomustine, and vincristine provide survival benefit. In contrast, trials that compare single modality treatment of chemotherapy alone with radiotherapy alone did not observe survival differences. Currently, for patients with grade II or III gliomas who require postsurgical treatment, the preferred treatment consists of a combination of radiotherapy and chemotherapy. Low-grade gliomas with favorable characteristics are slow-growing tumors. When deciding on the timing of postsurgical treatment with radiotherapy and chemotherapy, both clinical and molecular factors should be taken into account, but a more conservative approach can be considered initially in some of these patients. The factor that best predicts benefit of chemotherapy in grade II and III glioma remains to be established.
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Dasgupta, Pushan, Veerakumar Balasubramanyian, John F. de Groot e Nazanin K. Majd. "Preclinical Models of Low-Grade Gliomas". Cancers 15, n. 3 (18 gennaio 2023): 596. http://dx.doi.org/10.3390/cancers15030596.
Abstract (sommario):
Diffuse infiltrating low-grade glioma (LGG) is classified as WHO grade 2 astrocytoma with isocitrate dehydrogenase (IDH) mutation and oligodendroglioma with IDH1 mutation and 1p/19q codeletion. Despite their better prognosis compared with glioblastoma, LGGs invariably recur, leading to disability and premature death. There is an unmet need to discover new therapeutics for LGG, which necessitates preclinical models that closely resemble the human disease. Basic scientific efforts in the field of neuro-oncology are mostly focused on high-grade glioma, due to the ease of maintaining rapidly growing cell cultures and highly reproducible murine tumors. Development of preclinical models of LGG, on the other hand, has been difficult due to the slow-growing nature of these tumors as well as challenges involved in recapitulating the widespread genomic and epigenomic effects of IDH mutation. The most recent WHO classification of CNS tumors emphasizes the importance of the role of IDH mutation in the classification of gliomas, yet there are relatively few IDH-mutant preclinical models available. Here, we review the in vitro and in vivo preclinical models of LGG and discuss the mechanistic challenges involved in generating such models and potential strategies to overcome these hurdles.
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Mobark, Nahla Ali, Musa Alharbi, Yasser S. Bayoumi, Aymn Albanyan, Ali Abdullah O. Balbaid, Wael abdel Rahman Aljabarat e Malak Abedalthagafi. "DIPG-35. Personalized treatment for molecularly heterogeneous Diffuse midline glioma, H3 k27-altered Paediatric case". Neuro-Oncology 24, Supplement_1 (1 giugno 2022): i26. http://dx.doi.org/10.1093/neuonc/noac079.092.
Abstract (sommario):
Abstract Diffuse midline glioma, H3 k27-altered (DMG) is a type of Paediatric- type diffuse high grade gliomas according to the 2021 WHO CNS tumors Classification. Diffuse intrinsic pontine glioma (DIPG) is another acceptable related term when it located in the pons with fatal prognosis. The combination of H3K27M with BRAF V600 mutations rarely reported in DMG although more commonly in Paediatric-type low grade gliomas (Diffuse low-grade glioma, MAPK pathway-altered). We present a twenty-month-old boy, previously healthy, presented with 2 weeks history of unsteady gait, drooling, cranial nerves palsy MRI imaging showed diffuse pontine mass with classic radiological features of DIPG. 2.6 x 1.6 x 3.2 (AP x TV x CC) with no evidence for spinal metastases. Patient underwent right retro sigmoid approach and open biopsy of lesion he received focal Radiation Therapy 54GY/30fx as stander of care of DIPG with mild neurogical improvement Pathological & molecular Diagnosis was Diffuse midline glioma, H3 k27-altered with Co-occurrence BRAF V600E mutation. Two months after end of radiation, he presented with vomiting, and neurological deterioration with new right-side hemiplegia. Imaging studies showed interval increase in the pontine lesion with increased edema causing narrowing of the fourth ventricle, no active hydrocephalus. He was started on combination therapy BRAF inhibitor Dabrafenib and MEK Inhibitor Trametinib as maintenance therapy the patient gradually showed Marked neurological and clinical improvement. A 6-month MRI after start of targeted therapy showed favorable treatment response with complete resolution of the previous diffusion restriction, reduced tumor volume on MR perfusion ,reduced perilesional edema otherwise almost stabilization of nonenhancing pontine lesion. The poor prognosis of recurrent DIPG is well known but our patient is clinically and radiologically stable with excellent quality of life and well tolerating the therapy . Our case show that personalized treatment approach that address molecular heterogeneity of H3K27M glioma are safe and feasible
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Almairac, Fabien, Jeremy Deverdun, Jérôme Cochereau, Arthur Coget, Anne-Laure Lemaitre, Sylvie Moritz-Gasser, Hugues Duffau e Guillaume Herbet. "Homotopic redistribution of functional connectivity in insula-centered diffuse low-grade glioma". NeuroImage: Clinical 29 (2021): 102571. http://dx.doi.org/10.1016/j.nicl.2021.102571.
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Jooma, Rashid, Muhammad Waqas e Inamullah Khan. "Diffuse low-grade glioma – Changing concepts in diagnosis and management: A review". Asian Journal of Neurosurgery 14, n. 2 (2019): 356. http://dx.doi.org/10.4103/ajns.ajns_24_18.
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Ma, Yipo, Jinfeng Zhang, Ying Wen, Jinghua Chen, Lei Yuan, Xuechun Jiang, Dan Xu e Kefu Liu. "Diffuse low-grade glioma misdiagnosed as acute cerebral infarction: A case report". Medicine 101, n. 35 (2 settembre 2022): e30378. http://dx.doi.org/10.1097/md.0000000000030378.
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Shatara, Margaret, Sandeep Sood, Janet M. Poulik, Deniz Altinok, Steven Miller, Xuehui Liu e Zhihong Wang. "DIPG-59. LOW GRADE DIFFUSE INTRINSIC PONTINE GLIOMA? A SINGLE INSTITUTION EXPERIENCE". Neuro-Oncology 20, suppl_2 (giugno 2018): i61. http://dx.doi.org/10.1093/neuonc/noy059.152.