11 Natural History and Management Options of Low-Grade Glioma low-grade gliomas (LGGs)

Abstract Background Optimum management of low-grade gliomas remains controversial, and widespread practice variation exists. This evidence-based meta-analysis evaluates the association of extent of resection, radiation, and chemotherapy with mortality and progression-free survival at 2, 5, and 10 years in patients with low-grade glioma. Methods A quantitative systematic review was performed. Inclusion criteria included controlled trials of newly diagnosed low-grade (World Health Organization Grades I and II) gliomas in adults. Eligible studies were identified, assigned a level of evidence for every endpoint considered, and analyzed according to Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines. The relative risk of mortality and of progression at 2, 5, and 10 years was calculated for patients undergoing resection (gross total, subtotal, or biopsy), radiation, or chemotherapy. Results Gross total resection was significantly associated with decreased mortality and likelihood of progression at all time points compared to subtotal resection. Early radiation was not associated with decreased mortality; however, progression-free survival was better at 5 years compared to patients receiving delayed or no radiation. Chemotherapy was associated with decreased mortality at 5 and 10 years in the high-quality literature. Progression-free survival was better at 5 and 10 years compared to patients who did not receive chemotherapy. In patients with isocitrate dehydrogenase 1 gene (IDH1) R132H mutations receiving chemotherapy, progression-free survival was better at 2 and 5 years than in patients with IDH1 wild-type gliomas. Conclusions Results from this review, the first to quantify differences in outcome associated with surgery, radiation, and chemotherapy in patients with low-grade gliomas, can be used to inform evidence-based management and future clinical trials.

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The management of incidental low-grade gliomas using magnetic resonance imaging: systematic review and optimal treatment paradigm

Neurosurgical FOCUS ◽

10.3171/2011.9.focus11219 ◽

2011 ◽

Vol 31 (6) ◽

pp. E12 ◽

Cited By ~ 14

Author(s):

Ashish H. Shah ◽

Karthik Madhavan ◽

Deborah Heros ◽

Daniel M. S. Raper ◽

J. Bryan Iorgulescu ◽

...

Keyword(s):

Systematic Review ◽

Mr Imaging ◽

Active Surveillance ◽

Case Series ◽

Treatment Decisions ◽

Low Grade ◽

Management Options ◽

Low Grade Gliomas ◽

Presenting Symptoms ◽

Radiological Evidence

Object The discovery of incidental low-grade gliomas (LGGs) on MR imaging is rare, and currently there is no existing protocol for management of these lesions. Various studies have approached the dilemma of managing patients with incidental LGGs. While some advocate surgery and radiotherapy, others reserve surgery until there is radiological evidence of growth. For neurosurgeons and radiologists, determining the course of action after routine brain imaging poses not only a medical but also an ethical dilemma. The authors conducted a systematic review of case reports and case series in hopes of enhancing the current understanding of the management options for these rare lesions. Methods A PubMed search was performed to include all relevant MR imaging studies in which management of suspected incidental LGG was reported. Comparisons were made between the surgical treatment arm and the active surveillance arm in terms of outcome, mode of discovery, reasons for treatment, and histology. Results Nine studies with 72 patients were included in this study (56 in the surgical arm and 16 in the active surveillance arm). Within the surgical arm, 49% remained deficit free after treatment, 25% showed evidence of tumor progression, 13% underwent a second treatment, and 7% died. The active surveillance group resulted in no unanticipated adverse events, with serial imaging revealing no tumor growth in all cases. Lesion regression was reported in 31% of this group. The surgical arm's mortality rate was 7% compared with 0% in the active surveillance arm. Conclusions Treatment decisions for incidental LGG should be individualized based on presenting symptoms and radiological evidence of growth. The asymptomatic patient may be monitored safely with serial MR imaging and occasionally PET scanning before treatment is initiated. In patients presenting with nonspecific symptoms or concurrent symptomatic lesions, treatment may be initiated earlier to reduce potential morbidity. All treatment decisions must be tempered by patient factors and expectations of anticipated benefit.

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PROGRESS IN CLINICAL NEUROSCIENCES: Advances in the Management of Low-Grade Gliomas

Canadian Journal of Neurological Sciences / Journal Canadien des Sciences Neurologiques ◽

10.1017/s0317167100016838 ◽

2005 ◽

Vol 32 (1) ◽

pp. 18-26 ◽

Cited By ~ 8

Author(s):

Warren P. Mason

Keyword(s):

Natural History ◽

Optimal Timing ◽

Low Grade ◽

Low Grade Gliomas ◽

Response Profile ◽

History Of ◽

Evidence Based Guidelines ◽

The Impact ◽

Extensive Surgery

The management of low-grade gliomas represents one of the most challenging and controversial areas in neuro-oncology. Many aspects of the treatment of low-grade gliomas are debated, including the optimal timing of surgery and radiotherapy, the benefit of extensive surgery, and the impact of these variables on the natural history of these indolent and generally incurable tumours. The recently published results of several large multicentre trials addressing the timing and dose of radiotherapy have provided solid evidence for delayed and reduced dose irradiation. These studies have also confirmed prognostic variables that can be used to guide management of individual patients. Among these variables is the observation that tumours with oligodendroglial features have a better natural history and response profile. The recognition that as many as two thirds of low-grade gliomas have oligodendroglial features, advances in molecular diagnostics making accurate pathologic diagnosis of oligodendroglial tumours possible, and the established chemosensitivity of malignant oligodendrogliomas, have raised new issues surrounding the potential value of chemotherapy for low-grade gliomas. This review will be restricted to low-grade diffuse astrocytomas, oligodendrogliomas, and low-grade mixed oligoastrocytomas in adults, and provide evidence-based guidelines for the management of these tumours, including the emerging role of chemotherapy as initial treatment.

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Natural History and Growth Patterns of Incidentally Discovered Diffusely Infiltrating Low-Grade Gliomas: A Volumetric Study

World Neurosurgery ◽

10.1016/j.wneu.2019.08.235 ◽

2019 ◽

Vol 132 ◽

pp. e133-e139 ◽

Cited By ~ 1

Author(s):

Michael Opoku-Darko ◽

Matthew E. Eagles ◽

Magalie Cadieux ◽

Albert M. Isaacs ◽

John J.P. Kelly

Keyword(s):

Natural History ◽

Growth Patterns ◽

Low Grade ◽

Low Grade Gliomas ◽

Volumetric Study

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SURG-08. AWAKE CRANIOTOMY WITH BRAIN MAPPING FOR DIFFUSE LOW-GRADE GLIOMA: CASE REPORT OF INSTITUTIONAL EXPERIENCE IN OVERCOMING HURDLES IN A LOW-RESOURCE SETTING

Neuro-Oncology ◽

10.1093/neuonc/noaa215.855 ◽

2020 ◽

Vol 22 (Supplement_2) ◽

pp. ii204-ii205

Author(s):

Kirby Manigos ◽

Kevin Paul Ferraris ◽

Joseph Erroll Navarro ◽

Kenny Seng ◽

Jose Carlos Alcazaren

Keyword(s):

Brain Mapping ◽

Diffusion Tensor ◽

Low Grade Glioma ◽

Awake Craniotomy ◽

Limited Resources ◽

Low Grade ◽

Low Grade Gliomas ◽

Neurologic Deficits ◽

Weighted Sequence ◽

Low Middle Income Countries

Abstract Maximal safe resection of low-grade gliomas located in functional areas of the cortex while avoiding postsurgical neurologic deficits can be achieved by awake craniotomy with brain mapping. The effectiveness of this surgical technique is fairly established in the developed world, however it remains to be routinely applied in low-middle income countries due to limited resources and lack of equipment. We present the case of a 44 year-old, right-handed male who had a 2-year history of focal aware motor seizures but was otherwise neurologically intact. Neuropsychological testing revealed no cognitive impairment. Cranial magnetic resonance imaging (MRI) revealed a non-enhancing, ill-defined tumor centered on the left insula and extending into the frontotemporal opercula, corona radiata, and posterior limb of the internal capsule—hypointense by T1-weighted sequence and hyperintense by T2-weighted sequence, thus radiographically consistent with diffuse low-grade glioma. Blood-oxygen-level-dependent functional MRI revealed left hemispheric language dominance in the cortex overlying the tumor, but with no motor cortex involvement. The patient underwent a protocol-driven awake craniotomy, intraoperative positive brain mapping using standard cortical stimulator, transsylvian and transcortical transopercular microsurgical approaches to achieve greater than 80% excision of the tumor. Postoperatively, the patient was seizure-free and with similar neurocognitive status prior to the surgery. The patient had been following up for standard adjuvant chemotherapy and radiotherapy. Avoidance of postsurgical neurologic deficits and maximal cytoreduction can still be achieved by awake craniotomy with brain mapping in settings with limited resources. Despite the lack of other perioperative tools and adjuncts such as diffusion tensor imaging, intraoperative ultrasonography, and even intraoperative MRI that are routinely available in high-resource settings, we illustrate in this case that comparable outcomes could be achieved by overcoming hurdles and aiming for the asymptote to the up-to-date and ideal neurosurgical treatment for diffuse low-grade gliomas.

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Paediatric Embryonal Tumours in Multilayered Rosettes Presenting as a Low Grade Glioma- An Unusual Case Report

JOURNAL FOR CLINICAL AND DIAGNOSTIC RESEARCH ◽

10.7860/jcdr/2020/45038.14089 ◽

2020 ◽

Author(s):

Sibhi Ganapathy ◽

Nikunj Godhani

Keyword(s):

Case Report ◽

Low Grade Glioma ◽

World Health ◽

Neurological Deficits ◽

Histopathological Analysis ◽

Low Grade ◽

Low Grade Gliomas ◽

Rare Differential Diagnosis ◽

Embryonal Tumours ◽

The Brain

Paediatric Embryonal Tumours in Multilayered Rosettes (ETMR) are rare aggressive tumours with poor survival statistics, defined in 2016 by World Health Organisation (WHO) classification of brain tumours. The tumours have a characteristic radiological appearance on Magnetic Resonance Imaging (MRI) of the brain, which is easily decipherable. This combined with a clinical picture of raised intracranial pressure symptoms, seizures and rapidly progressive new onset neurological deficits make the diagnosis fairly obvious. The final confirmation of the diagnosis is done by immunohistochemical analysis of the C19Myc gene alteration. Rarely, certain radiological presentations are uncharacteristic and resemble other more benign pathologies with overlapping clinical presentations. This can be misleading, as ETMRs require aggressive surgery followed by adjuvant chemotherapy and radiation to ensure best possible survival. We present such a case report of what appeared to be a low-grade glioma in the frontal lobe. This tumour presented with one episode of generalised tonic clonic seizures not unusual as a presenting complaint in low-grade gliomas per se. Surgical debulking under ultrasonic guidance was done and the specimen was sent to histopathological analysis. The histopathological analysis showed a surprise ETMR diagnosis which was sent for confirmation to two other centers. This case report highlights the need to keep ETMRs as a rare differential diagnosis for even low-grade gliomas of the brain, thereby allowing accurate prognostication only after histopathological and immunohistochemical assessment. We present a brief literature review on unusual presentations of ETMRs reported in literature to further illustrate the chimeric nature of this rare disease.

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NIMG-50. VOLUMETRIC ANALYSIS OF IDH-MUTANT LOW-GRADE GLIOMA: A NATURAL HISTORY STUDY OF TUMOR GROWTH RATES BEFORE AND AFTER TREATMENT

Neuro-Oncology ◽

10.1093/neuonc/nox168.624 ◽

2017 ◽

Vol 19 (suppl_6) ◽

pp. vi153-vi153 ◽

Cited By ~ 1

Author(s):

Ray Huang ◽

Robert J Young ◽

Benjamin Ellingson ◽

Harini Veeraraghavan ◽

Wei Wang ◽

...

Keyword(s):

Natural History ◽

Tumor Growth ◽

Growth Rates ◽

Volumetric Analysis ◽

Low Grade Glioma ◽

Low Grade ◽

Natural History Study ◽

Before And After

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A phase II study of temozolomide and oral VP-16 for adults with recurrent glioma—Final results

Journal of Clinical Oncology ◽

10.1200/jco.2006.24.18_suppl.1565 ◽

2006 ◽

Vol 24 (18_suppl) ◽

pp. 1565-1565 ◽

Cited By ~ 1

Author(s):

D. N. Korones ◽

M. Benita-Weiss ◽

T. Coyle ◽

P. Bushunow ◽

L. Mechtler ◽

...

Keyword(s):

Phase 1 ◽

Progression Free Survival ◽

Maximum Tolerated Dose ◽

Low Grade Glioma ◽

Recurrent Glioma ◽

Low Grade ◽

Entire Cohort ◽

Low Grade Gliomas ◽

Prior Therapy ◽

Anaplastic Gliomas

1565 Background: Although temozolomide has proven activity in patients with high and low grade gliomas, many patients do not respond, and for those who do, responses are often short-lived. We therefore undertook a trial of temozolomide in combination with oral VP-16 (etoposide) for patients with recurrent glioma. Methods: Patients were eligible for the study if they had recurrence of a glioma (glioblastoma [GBM], anaplastic glioma, or low-grade glioma), were ≥ 18 years of age, had a WHO score of 0–2, and had not received prior therapy with temozolomide or oral VP-16. All patients received temozolomide, 150 mg/m2/d days 1–5 and oral VP-16, 50 mg/m2/d days 1–12 (based on the maximum tolerated dose established in a previous phase 1 study [Cancer 2003, 97 (8); 1963–68.]). Cycles were repeated every 28 days for up to 12 cycles. All patients received prophylaxis for pneumocystis. Results: Fifty-one patients were enrolled - 32 with glioblastoma, 12 with anaplastic gliomas, and 7 with low-grade glioma. Median age was 52 years (21–76), and 67% were male. Forty-one were enrolled at first and 10 at second recurrence. Fifty had had prior radiation, and 30 of these 50 patients had also received prior chemotherapy. Of the 32 subjects with GBM, 4 had a PR (12.5%), 13 (41%) SD, 13 (41%) PD, and 2 were not evaluable because of deterioration prior to imaging. The median progression-free survival (PFS) was 2 mo. (0–51+ mo), and the 6 mo. PFS was 19%. Of the 12 patients with anaplastic gliomas, 2 had a PR (16%), 7 SD (58%), 2 PD (16%) and one was not evaluable. Their median PFS was 5.5 mo, and the 6 mo. PFS was 50%. Of the seven subjects with low grade gliomas, 4 had a PR, 2 SD, and 1 PD. Their median PFS was 5 mo. (0–12) and 6 mo. PFS was 57%. Of the entire cohort, two patients developed fever and neutropenia and died of pseudomonas sepsis. Another two patients were prematurely withdrawn from the study due to toxicity (one for grade 4 neutropenia and a second for grade 2 diarrhea). Conclusions: In this population of previously treated patients with recurrent glioma, the combination of oral VP-16 and temozolomide has only modest efficacy and significant toxicity. The results of this study suggest that in this setting, the combination offers no advantage over either agent used alone. [Table: see text]

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