Comment on Hosmann et al. 5-ALA Fluorescence Is a Powerful Prognostic Marker during Surgery of Low-Grade Gliomas (WHO Grade II)—Experience at Two Specialized Centers. Cancers 2021, 13, 2540

Abstract BACKGROUND Maximizing extent of resection (EOR) improves outcomes in adults with World Health Organization (WHO) grade II low-grade gliomas (LGG). However, recent studies demonstrate that LGGs bearing a mutation in the isocitrate dehydrogenase 1 (IDH1) gene are a distinct molecular and clinical entity. It remains unclear whether maximizing EOR confers an equivalent clinical benefit in IDH mutated (mtIDH) and IDH wild-type (wtIDH) LGGs. OBJECTIVE To assess the impact of EOR on malignant progression-free survival (MPFS) and overall survival (OS) in mtIDH and wtIDH LGGs. METHODS We performed a retrospective review of 74 patients with WHO grade II gliomas and known IDH mutational status undergoing resection at a single institution. EOR was assessed with quantitative 3-dimensional volumetric analysis. The effect of predictor variables on MPFS and OS was analyzed with Cox regression models and the Kaplan–Meier method. RESULTS Fifty-two (70%) mtIDH patients and 22 (30%) wtIDH patients were included. Median preoperative tumor volume was 37.4 cm3; median EOR of 57.6% was achieved. Univariate Cox regression analysis confirmed EOR as a prognostic factor for the entire cohort. However, stratifying by IDH status demonstrates that greater EOR independently prolonged MPFS and OS for wtIDH patients (hazard ratio [HR] = 0.002 [95% confidence interval {CI} 0.000-0.074] and HR = 0.001 [95% CI 0.00-0.108], respectively), but not for mtIDH patients (HR = 0.84 [95% CI 0.17-4.13] and HR = 2.99 [95% CI 0.15-61.66], respectively). CONCLUSION Increasing EOR confers oncologic and survival benefits in IDH1 wtLGGs, but the impact on IDH1 mtLGGs requires further study.

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Interstitial radiosurgery of low-grade gliomas

Journal of Neurosurgery ◽

10.3171/jns.1995.82.3.0418 ◽

1995 ◽

Vol 82 (3) ◽

pp. 418-429 ◽

Cited By ~ 87

Author(s):

Friedrich W. Kreth ◽

Michael Faist ◽

Peter C. Warnke ◽

Reinhard Roβner ◽

Benedikt Volk ◽

...

Keyword(s):

Ct Scan ◽

Tumor Recurrence ◽

Survival Rates ◽

Low Grade ◽

Who Grade ◽

Content Type ◽

Low Grade Gliomas ◽

Interstitial Radiosurgery ◽

Grade Ii ◽

Fine Print

✓ The treatment of patients with low-grade gliomas remains a subject of controversy, especially with respect to new treatment modalities such as interstitial radiosurgery (brachytherapy), radiosurgery, and stereotactic radiotherapy. In a retrospective analysis conducted between 1979 and 1991, the authors studied the results of interstitial radiosurgery in 455 patients with low-grade gliomas (World Health Organization (WHO) Grade I + WHO Grade II) with regard to survival time, quality of life, the risk of malignant transformation, and the risk profile of the treatment concept. Interstitial radiosurgery with iodine-125 was performed using permanent (1979–1985) or temporary implants (after 1985) with low-dose rates (≤ 10 cGy/hr) and a reference dose of 60 to 100 Gy calculated to the outer rim of the tumor. The 5- and 10-year survival rates in patients with pilocytic astrocytomas (97 patients) were 84.9% and 83%, and in patients with WHO Grade II astrocytomas (250 patients) 61% and 51%, respectively. Five-year survival rates for patients with oligoastrocytomas (60 patients), oligodendrogliomas (27 patients), and gemistocytic astrocytomas (21 patients) were 49%, 50%, and 32%, respectively. In the group with WHO Grade II gliomas, young age and a good performance status were associated with a better prognosis. Unfavorable factors were midline shift, enhancement on computerized tomography (CT) scan, and tumor recurrence after previous radiotherapy or surgery. Tumor location had no influence on the prognosis (247 patients in this series had deep-seated tumors). Malignant transformation was the major cause of death. Important risk factors for malignancy were the patient's age, tumor enhancement in CT scan, and tumor recurrence after previous surgery or radiotherapy. Perioperative mortality was 0.9% and perioperative morbidity was 1.7%. Radiogenic complications were observed in 2.7% of all patients, most often in larger tumors and after using permanent implants. The authors conclude that interstitial radiosurgery represents a specific treatment modality for selected patients with unifocal circumscribed low-grade gliomas with a diameter of less than 4 cm in any location. The efficacy of this treatment lies in the same range as the best results after surgery and radiotherapy.

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Long-term outcome of stereotactic brachytherapy with temporary Iodine-125 seeds in patients with WHO grade II gliomas

Radiation Oncology ◽

10.1186/s13014-020-01719-9 ◽

2020 ◽

Vol 15 (1) ◽

Author(s):

Juliana Watson ◽

Alexander Romagna ◽

Hendrik Ballhausen ◽

Maximilian Niyazi ◽

Stefanie Lietke ◽

...

Keyword(s):

Prognostic Factors ◽

Low Grade ◽

Toxicity Profile ◽

Who Grade ◽

Low Grade Gliomas ◽

Stereotactic Brachytherapy ◽

Grade Ii ◽

Iodine 125

Abstract Background This long-term retrospective analysis aimed to investigate the outcome and toxicity profile of stereotactic brachytherapy (SBT) in selected low-grade gliomas WHO grade II (LGGII) in a large patient series. Methods This analysis comprised 106 consecutive patients who received SBT with temporary Iodine-125 seeds for histologically verified LGGII at the University of Munich between March 1997 and July 2011. Investigation included clinical characteristics, technical aspects of SBT, the application of other treatments, outcome analyses including malignization rates, and prognostic factors with special focus on molecular biomarkers. Results For the entire study population, the 5- and 10-years overall survival (OS) rates were 79% and 62%, respectively, with a median follow-up of 115.9 months. No prognostic factors could be identified. Interstitial radiotherapy was applied in 51 cases as first-line treatment with a median number of two seeds (range 1–5), and a median total implanted activity of 21.8 mCi (range 4.2–43.4). The reference dose average was 54.0 Gy. Five- and ten-years OS and progression-free survival rates after SBT were 72% and 43%, and 40% and 23%, respectively, with a median follow-up of 86.7 months. The procedure-related mortality rate was zero, although an overall complication rate of 16% was registered. Patients with complications had a significantly larger tumor volume (p = 0.029). Conclusion SBT is a minimally invasive treatment modality with a favorable outcome and toxicity profile. It is both an alternative primary treatment method as well as an adjunct to open tumor resection in selected low-grade gliomas.

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PO-0995: Estimation of radiobiology parameters of infiltrative low-grade gliomas WHO Grade II

Radiotherapy and Oncology ◽

10.1016/s0167-8140(17)31431-7 ◽

2017 ◽

Vol 123 ◽

pp. S549 ◽

Cited By ~ 1

Author(s):

S. Milyukov ◽

Y. Lysak ◽

G. Panshin ◽

N. Kharchenko ◽

Z. Tsallagova ◽

...

Keyword(s):

Low Grade ◽

Who Grade ◽

Low Grade Gliomas ◽

Grade Ii

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364 Tumor Compression Effect on White Matter Pathways Revealed by Local Connectome Fingerprint

Neurosurgery ◽

10.1093/neuros/nyx417.364 ◽

2017 ◽

Vol 64 (CN_suppl_1) ◽

pp. 284-285

Author(s):

Pinar Celtikci ◽

David Tiago Fernandes Cabral ◽

Yeh Fang-Cheng ◽

Sandip S Panesar ◽

Juan Carlos Fernandez-Miranda

Keyword(s):

White Matter ◽

Density Measurement ◽

High Angular Resolution ◽

Imaging Method ◽

Low Grade ◽

Who Grade ◽

Low Grade Gliomas ◽

Compression Effect ◽

Human Connectome Project ◽

Grade Ii

Abstract INTRODUCTION Low-grade gliomas (LGGs) are slow growing tumors that often cause infiltration and/or compression of the white matter pathways. Regular imaging modalities are no capable of revealing such a pathologic condition. Furthermore, up-to-date there is no reliable noninvasive imaging method to address this issue. Here we report that the local connectome fingerprint, an along track density measurement derived from diffusion MRI (dMRI), is capable of revealing the tumor compression effect on the surrounding white matter pathways. METHODS We acquired high angular resolution dMRI data on 16 patients diagnosed of LGG (WHO grade II). Peritumoral fiber tracts underwent qualitative and quantitative evaluation. Contralateral hemisphere counterparts were used for comparison. The local connectome fingerprint of peritumoral tract segment and their ratio to healthy side were visualized and calculated in comparison with 842 normal subjects from the Human Connectome Project. RESULTS >Our results showed significant increase in the ratios to the normal side among displaced tracts and decreases among the infiltrated tracts when compared to their healthy counterpart. Qualitative analysis of 65 peritumoral tracts revealed 9 (13.8%) unaffected, 24 (36.9%) displaced, 13 (20%) infiltrated and 19 (29.2%) tracts with a combination of displacement and infiltration. There were no disrupted tracts. The along tracks local connectome fingerprint further localizes the track segments with compression effect caused by the tumor mass. This feature cannot be observed in conventional tensor and diffusivity analysis. CONCLUSION The unique capability of local connectome fingerprint in revealing the compression and infiltration effect can provide potential diagnostic and prognostic applications in clinical intervention of patients with WHO grade-II low-grade gliomas.

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Multicentric Registry Study on Epidemiological and Biological Disease Profile as Well as Clinical Outcome in Patients with Low-Grade Gliomas: The LoG-Glio Project

Journal of Neurological Surgery Part A Central European Neurosurgery ◽

10.1055/s-0039-1693650 ◽

2019 ◽

Vol 81 (01) ◽

pp. 048-057 ◽

Cited By ~ 1

Author(s):

Andrej Pala ◽

Minou Nadji-Ohl ◽

Katharina Faust ◽

Stefan Rückriegel ◽

Constantin Roder ◽

...

Keyword(s):

Surgical Management ◽

Adjuvant Treatment ◽

Low Grade ◽

Inclusion Criteria ◽

Wild Type ◽

Who Grade ◽

Low Grade Gliomas ◽

Grade Ii ◽

Multicenter Registry

Abstract Background World Health Organization (WHO) grade II low-grade gliomas (LGGs) in adults are rare, and patients' mean overall survival (OS) is relatively long. Epidemiological data on factors influencing tumor genesis and progression are scarce, and prospective data on surgical management are still lacking. Because of the molecular heterogeneity of LGG, a comprehensive molecular characterization is required for any clinical and epidemiological research. Further, a detailed radiologic assessment is needed as the only established objective criterion for progressive disease. Both radiologic and molecular assessments have to be standardized to produce comparable data. The aim of the registry is to improve the evidence for surgical management of LGG patients by establishing a multicenter registry with a strong surgical and clinical focus including mandatory biobanking. Methods The LoG-Glio project is a prospective national observational multicenter registry that began on November 1, 2015. Inclusion criteria encompass all patients > 18 years of age with a radiologic suspicion of LGG. Patients with severe neurologic or psychiatric disorders that may interfere with their informed consent or if there is no possibility for further follow-up are excluded. Diagnosis of glioblastoma WHO grade IV isocitrate dehydrogenase (IDH) wild type leads to a secondary exclusion of patients. In addition to demographic data, results of the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire, add-on for patients with brain tumors, and National Health Institute Stroke Scale before and after surgery and during regular follow-ups are collected. At each time point a detailed recording of surgical and adjuvant treatment is performed. Radiologic assessment involves three-dimensional (3D) acquisition of T1, fluid-attenuated inversion recovery, and T2 sequences. For the final evaluation, a central detailed neuropathologic and molecular assessment of tumor samples and a radiologic evaluation of imaging sets are part of the study protocol. Results We report the first 100 consecutively registered patients for LoG-Glio. Three patients dropped out due to loss of follow-up. Of the remaining recruited patients, 8 were classified as wait and scan; 89 had surgery. Using the inclusion criteria described previously, 70 patients had an IDH-mutated glioma, 10 had miscellaneous rare LGGs, and 8 patients had an IDH wild-type WHO grade II or III glioma. Conclusion The LoG-Glio registry has been successfully implemented. Applied selection criteria result in an appropriately balanced patient cohort. Short-term outcome data on epidemiology as well as the influence of current surgical techniques and adjuvant treatment on patient outcomes are expected. In the long run, the aim of the registry is to validate the new molecular-based WHO classification and the influence of the extent of resection on progression-free survival and OS. The registry provides an open platform for future research projects benefiting patients with LGG.

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The molecular biology of WHO Grade II gliomas

Neurosurgical FOCUS ◽

10.3171/2012.12.focus12283 ◽

2013 ◽

Vol 34 (2) ◽

pp. E1 ◽

Cited By ~ 11

Author(s):

Nicholas F. Marko ◽

Robert J. Weil

Keyword(s):

Molecular Biology ◽

Tumor Biology ◽

Molecular Characteristics ◽

Low Grade ◽

Diffuse Astrocytoma ◽

Who Grade ◽

Low Grade Gliomas ◽

Molecular Features ◽

Grade Ii ◽

Who Grade Ii Gliomas

The WHO grading scheme for glial neoplasms assigns Grade II to 5 distinct tumors of astrocytic or oligodendroglial lineage: diffuse astrocytoma, oligodendroglioma, oligoastrocytoma, pleomorphic xanthoastrocytoma, and pilomyxoid astrocytoma. Although commonly referred to collectively as among the “low-grade gliomas,” these 5 tumors represent molecularly and clinically unique entities. Each is the subject of active basic research aimed at developing a more complete understanding of its molecular biology, and the pace of such research continues to accelerate. Additionally, because managing and predicting the course of these tumors has historically proven challenging, translational research regarding Grade II gliomas continues in the hopes of identifying novel molecular features that can better inform diagnostic, prognostic, and therapeutic strategies. Unfortunately, the basic and translational literature regarding the molecular biology of WHO Grade II gliomas remains nebulous. The authors' goal for this review was to present a comprehensive discussion of current knowledge regarding the molecular characteristics of these 5 WHO Grade II tumors on the chromosomal, genomic, and epigenomic levels. Additionally, they discuss the emerging evidence suggesting molecular differences between adult and pediatric Grade II gliomas. Finally, they present an overview of current strategies for using molecular data to classify low-grade gliomas into clinically relevant categories based on tumor biology.

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Quantitative analysis of 06-methylguanine-DNA methyltransferase (MGMT) promoter methylation in patients with low-grade gliomas

Journal of Clinical Oncology ◽

10.1200/jco.2009.27.15_suppl.2069 ◽

2009 ◽

Vol 27 (15_suppl) ◽

pp. 2069-2069

Author(s):

A. F. Ochsenbein ◽

A. D. Schubert ◽

E. Vassella ◽

L. Mariani

Keyword(s):

Promoter Methylation ◽

Tumor Response ◽

Methylation Status ◽

Mgmt Promoter Methylation ◽

Low Grade ◽

Who Grade ◽

Low Grade Gliomas ◽

Response To Chemotherapy ◽

Mgmt Promoter ◽

Grade Ii

2069 Background: Loss of heterozygosity (LOH) on the chromosomes 1p and 19q is associated with sensitivity to alkylating agents like temozolomide (TMZ) in patients with low-grade gliomas; whether methylation of the MGMT-promoter, a predictive factor in glioblastoma patients, also correlates with tumor response to TMZ in low-grade gliomas is unclear. Methods: We performed a retrospective analysis of patients with histologically verified low-grade gliomas (WHO Grade II) who were treated with TMZ for tumor progression at our hospital between November 1999 and November 2007. Objective tumor response was assessed by MRI at 6-month intervals. LOH of microsatellite markers on chromosomes 1p and 19q was determined by polymerase chain reaction (PCR) amplification of the matched pairs of blood and tumor DNA. A methylation-specific, primer extension based PCR method was developed to quanitatively assess the MGMT methylation status in the tumour tissue. Results: Twenty-two patients with a median age of 53 years (range 27–72) were included in the study; 59% were male. Seven patients had prior surgical resection of the tumor. Histological classification revealed 10 oligodendrogliomas, 7 oligoastrocytomas, and 5 astrocytomas. All patients were treated with TMZ 200mg/m2 day1–5 in a 4 wk cycle. Grade 3–4 hematological toxicity occurred in 32% of the patients (9% leucopenia, 23% thrombocytopenia). The progression free survival was 32 months. Combined LOH 1p and 19q was found in 14 pts; 1 patient had LOH 1p alone and 1 patient LOH 19q alone. The LOH status could not be determined in two patients and was normal in the remaining four. MGMT promoter methylation was detectable in 20 pts by conventional PCR and quantitative analysis revealed a methylation status between 12%-100%. The volumetric response to chemotherapy analyzed after 6 months by MRI correlated with the level of MGMT promoter methylation (p = 0.012). Conclusions: Quantitative methylation-specific PCR of the MGMT promoter correlates with radiological response to chemotherapy with temozolomide in WHO grade II gliomas. No significant financial relationships to disclose.

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