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

2019 ◽  
Vol 81 (01) ◽  
pp. 048-057 ◽  
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.

scholarly journals The Role of Extent of Resection in IDH1 Wild-Type or Mutant Low-Grade Gliomas

Neurosurgery ◽  
2017 ◽  
Vol 82 (6) ◽  
pp. 808-814 ◽  
Author(s):  
Toral Patel ◽  
Evan D Bander ◽  
Rachael A Venn ◽  
Tiffany Powell ◽  
Gustav Young-Min Cederquist ◽  
...  
Keyword(s):  
Cox Regression ◽  
Extent Of Resection ◽  
World Health ◽  
Low Grade ◽  
Wild Type ◽  
Who Grade ◽  
Cox Regression Analysis ◽  
Low Grade Gliomas ◽  
Grade Ii ◽  
The Impact

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.

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

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.

scholarly journals Seizure response to temozolomide chemotherapy in patients with WHO grade II oligodendroglioma: a single-institution descriptive study

2018 ◽  
Vol 6 (3) ◽  
pp. 203-208 ◽  
Author(s):  
Aya Haggiagi ◽  
Edward K Avila
Keyword(s):  
Disease Progression ◽  
Seizure Frequency ◽  
World Health ◽  
Low Grade ◽  
Inclusion Criteria ◽  
Who Grade ◽  
Seizure Reduction ◽  
Grade Ii ◽  
Health Organization

Abstract Background Tumor-related epilepsy (TRE) is common in patients with low-grade oligodendrogliomas. TRE is difficult to control despite multiple antiepileptic drugs (AEDs) in up to 30% of patients. Chemotherapy has been used for treatment to avoid potential radiotherapy-related neurotoxicity. This study evaluates the effect of temozolomide on seizure frequency in a homogeneous group with World Health Organization (WHO) grade II oligodendrogliomas. Methods A retrospective analysis was conducted of adult patients with WHO grade II oligodendrogliomas and TRE followed at Memorial Sloan Kettering between 2005 and 2015 who were treated with temozolomide alone either as initial treatment or for disease progression. All had seizures 3 months prior to starting temozolomide. Seizure frequency was reviewed every 2 cycles and at the end of temozolomide treatment. Seizure reduction of ≥50% compared to baseline was defined as improvement. Results Thirty-nine individuals met inclusion criteria. Median follow-up since starting temozolomide was 6 years (0.8-13 years). Reduction in seizure frequency occurred in 35 patients (89.7%). Improvement was independent of AED regimen adjustments or prior antitumor treatment in 16 (41%); of these, AED dosage was successfully reduced or completely eliminated in 10 (25.6%). Twenty-five patients (64.1%) remained on a stable AED regimen. The majority (n = 32, 82%) had radiographically stable disease, 5 (12.8%) had objective radiographic response, and 2 (5.2%) had disease progression. Conclusions Temozolomide may result in reduced seizure frequency, and permit discontinuation of AEDs in patients with WHO II oligodendroglioma. Improvement was observed irrespective of objective tumor response on MRI, emphasizing the importance of incorporating seizure control in assessing response to tumor-directed therapy.

IDH wild-type WHO grade II diffuse low-grade gliomas. A heterogeneous family with different outcomes. Systematic review and meta-analysis

2018 ◽  
Vol 43 (2) ◽  
pp. 383-395 ◽  
Author(s):  
Davide Tiziano Di Carlo ◽  
Hugues Duffau ◽  
Federico Cagnazzo ◽  
Nicola Benedetto ◽  
Riccardo Morganti ◽  
...  
Keyword(s):  
Systematic Review ◽  
Meta Analysis ◽  
Low Grade ◽  
Wild Type ◽  
Who Grade ◽  
Low Grade Gliomas ◽  
Grade Ii

scholarly journals Huge heterogeneity in survival in a subset of adult patients with resected, wild-type isocitrate dehydrogenase status, WHO grade II astrocytomas

2019 ◽  
Vol 130 (4) ◽  
pp. 1289-1298 ◽  
Author(s):  
Gaëtan Poulen ◽  
Catherine Gozé ◽  
Valérie Rigau ◽  
Hugues Duffau
Keyword(s):  
Radiation Therapy ◽  
Malignant Transformation ◽  
Isocitrate Dehydrogenase ◽  
Adult Patients ◽  
World Health ◽  
Wild Type ◽  
Who Grade ◽  
Grade Ii ◽  
The Individual

OBJECTIVEWorld Health Organization grade II gliomas are infiltrating tumors that inexorably progress to a higher grade of malignancy. However, the time to malignant transformation is quite unpredictable at the individual patient level. A wild-type isocitrate dehydrogenase (IDH-wt) molecular profile has been reported as a poor prognostic factor, with more rapid progression and a shorter survival compared with IDH-mutant tumors. Here, the oncological outcomes of a series of adult patients with IDH-wt, diffuse, WHO grade II astrocytomas (AII) who underwent resection without early adjuvant therapy were investigated.METHODSA retrospective review of patients extracted from a prospective database who underwent resection between 2007 and 2013 for histopathologically confirmed, IDH-wt, non–1p19q codeleted AII was performed. All patients had a minimum follow-up period of 2 years. Information regarding clinical, radiographic, and surgical results and survival were collected and analyzed.RESULTSThirty-one consecutive patients (18 men and 13 women, median age 39.6 years) were included in this study. The preoperative median tumor volume was 54 cm3 (range 3.5–180 cm3). The median growth rate, measured as the velocity of diametric expansion, was 2.45 mm/year. The median residual volume after surgery was 4.2 cm3 (range 0–30 cm3) with a median volumetric extent of resection of 93.97% (8 patients had a total or supratotal resection). No patient experienced permanent neurological deficits after surgery, and all patients resumed a normal life. No immediate postoperative chemotherapy or radiation therapy was given. The median clinical follow-up duration from diagnosis was 74 months (range 27–157 months). In this follow-up period, 18 patients received delayed chemotherapy and/or radiotherapy for tumor progression. Five patients (16%) died at a median time from radiological diagnosis of 3.5 years (range 2.6–4.5 years). Survival from diagnosis was 77.27% at 5 years. None of the 21 patients with a long-term follow-up greater than 5 years have died. There were no significant differences between the clinical, radiological, or molecular characteristics of the survivors relative to the patients who died.CONCLUSIONSHuge heterogeneity in the survival data for a subset of 31 patients with resected IDH-wt AII tumors was observed. These findings suggest that IDH mutation status alone is not sufficient to predict risk of malignant transformation and survival at the individual level. Therefore, the therapeutic management of AII tumors, in particular the decision to administer early adjuvant chemotherapy and/or radiation therapy following surgery, should not solely rely on routine molecular markers.

Interstitial radiosurgery of low-grade gliomas

1995 ◽  
Vol 82 (3) ◽  
pp. 418-429 ◽  
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.

scholarly journals NCOG-30. ADJUVANT VERSUS SALVAGE MANAGEMENT FOR IDH-MUTANT LOW GRADE GLIOMA

2020 ◽  
Vol 22 (Supplement_2) ◽  
pp. ii135-ii135
Author(s):  
Martin Tom ◽  
Deborah Park ◽  
Surabhi Tewari ◽  
Wei Wei ◽  
Samuel Chao ◽  
...  
Keyword(s):  
Adjuvant Treatment ◽  
Salvage Treatment ◽  
Low Grade Glioma ◽  
Postoperative Treatment ◽  
Management Approach ◽  
Low Grade ◽  
Free Survival ◽  
Grade Ii ◽  
Postoperative Observation

Abstract PURPOSE Timing of postoperative treatment in low-grade glioma (LGG) remains controversial. We sought to evaluate outcomes between adjuvant versus salvage management among patients with IDH-mutant molecularly-defined LGG. METHODS We analyzed a single-institutional database of adults diagnosed with LGG (grade II) with an IDH-mutation and either 1p19q-codeletion (oligodendroglioma) or 1p19q-intact (astrocytoma). Cox multivariable analysis (MVA) accounting for age, sex, and extent-of-resection, was used to compare adjuvant versus salvage approaches on overall survival (OS), progression free survival (PFS), next-intervention free survival (NIFS, defined as intervention subsequent to either adjuvant or salvage treatment), and malignant-transformation free survival (MTFS). Adjuvant treatment was defined as immediate postoperative treatment with radiotherapy (RT) and/or temozolomide (TMZ) prior to progression. Salvage management was defined as postoperative observation followed by surgery or RT and/or TMZ at progression. RESULTS Of 162 patients with oligodendroglioma, median follow-up was 8.5 years (range, 0.03-25.7). Adjuvant treatment was given to 97 (59.9%) patients, with 65 (40.1%) undergoing a salvage approach. On MVA, adjuvant treatment was not associated with OS, PFS, NIFS, or MTFS (p > 0.05 each). Among 82 patients with astrocytoma, median follow-up was 6.1 years (range, 0.5–25.7), and adjuvant treatment was administered to 41 (50.0%) patients, while 41 (50.0%) received salvage management. On MVA, adjuvant treatment was associated with improved PFS (HR 0.42, 95% CI 0.24-0.73, p < 0.001) and NIFS (HR 0.35, 95% CI 0.18–0.65, p < 0.001), but was not associated with OS or MTFS (p > 0.05 each). CONCLUSIONS Among grade II, IDH-mutant oligodendrogliomas, initial postoperative observation followed by salvage treatment at progression may be appropriate, as immediate adjuvant therapy was not associated improved outcomes. However, a more individualized postoperative management approach is required for grade II, IDH-mutant astrocytomas, as adjuvant treatment was associated with improved PFS and NIFS, but not OS. Further validation and prospective studies are required.

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

2017 ◽  
Vol 123 ◽  
pp. S549 ◽  
Author(s):  
S. Milyukov ◽  
Y. Lysak ◽  
G. Panshin ◽  
N. Kharchenko ◽  
Z. Tsallagova ◽  
...  
Keyword(s):  
Low Grade ◽  
Who Grade ◽  
Low Grade Gliomas ◽  
Grade Ii

scholarly journals RADT-38. ADJUVANT RADIOTHERAPY FOR INTRACRANIAL ATYPICAL AND MALIGNANT MENINGIOMAS IN ADULT PATIENTS

2020 ◽  
Vol 22 (Supplement_2) ◽  
pp. ii189-ii190
Author(s):  
Ansley Unterberger ◽  
Aditya Kondajji ◽  
Daniel Kulinich ◽  
Courtney Duong ◽  
Isaac Yang
Keyword(s):  
Median Time ◽  
Primary Brain Tumor ◽  
Adjuvant Radiation ◽  
High Grade ◽  
Inclusion Criteria ◽  
Who Grade ◽  
Time To Recurrence ◽  
Grade Ii ◽  
Grade Iii

Abstract BACKGROUND Meningiomas, the most common primary brain tumor, account for more than one third of all primary CNS tumors. High-grade meningiomas, WHO grade II and III, comprise between 16%-24% of total meningiomas and are more aggressive, recur more frequently, and portend a worse prognosis than WHO grade I meningiomas. Adjuvant radiation of high-grade meningiomas, while not uncommon, remains variably described in current literature. To assess our institution’s radiation protocol, we examined our cohort of over 200 high-grade meningiomas. METHODS We queried our hospital’s EHR system for surgically resected meningiomas from January 2013 to December 2019. Of 286 results identified, 24 patients met the inclusion criteria: 1) histologically confirmed WHO grade II or III meningioma, 2) primary resection coupled with adjuvant radiation therapy, and 3) no chemotherapy. Only one WHO grade III meningioma met inclusion criteria. Patients with NF2 were excluded. Patient demographics, radiation dosage, fraction number, and dates of surgery, radiation onset, recurrence, and most recent follow-up were recorded. RESULTS Median age at surgery was 56.2 years (± 11.1, range 37.8 – 81.7), and males comprised 70.8% (n = 17) of the population. Only FSRT or IMRT were employed. The most frequent dosage was 55.8 Gy across 31 fractions with a median time to radiation of 2.7 months (± 3.0, range 1.0 – 12.6). 5 out of 24 patients experienced recurrence, which did not include the WHO III tumor. Median time to recurrence was 3.0 years (± 2.0, range .3 – 5.8). Median follow up was 3.5 years (± 2.2, range .3 – 9.3). CONCLUSIONS A fraction of our population experienced recurrence, regardless of grade II or grade III pathology. FSRT remains a safe and effective adjuvant therapy for high-grade meningioma after surgical resection. Future prospective studies comparing differing radiation modalities should be conducted.

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

Neurosurgery ◽  
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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