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Journal of Clinical Oncology : Official... Feb 2022To provide guidance to clinicians regarding therapy for diffuse astrocytic and oligodendroglial tumors in adults.
PURPOSE
To provide guidance to clinicians regarding therapy for diffuse astrocytic and oligodendroglial tumors in adults.
METHODS
ASCO and the Society for Neuro-Oncology convened an Expert Panel and conducted a systematic review of the literature.
RESULTS
Fifty-nine randomized trials focusing on therapeutic management were identified.
RECOMMENDATIONS
Adults with newly diagnosed oligodendroglioma, isocitrate dehydrogenase (IDH)-mutant, 1p19q codeleted CNS WHO grade 2 and 3 should be offered radiation therapy (RT) and procarbazine, lomustine, and vincristine (PCV). Temozolomide (TMZ) is a reasonable alternative for patients who may not tolerate PCV, but no high-level evidence supports upfront TMZ in this setting. People with newly diagnosed astrocytoma, IDH-mutant, 1p19q non-codeleted CNS WHO grade 2 should be offered RT with adjuvant chemotherapy (TMZ or PCV). People with astrocytoma, IDH-mutant, 1p19q non-codeleted CNS WHO grade 3 should be offered RT and adjuvant TMZ. People with astrocytoma, IDH-mutant, CNS WHO grade 4 may follow recommendations for either astrocytoma, IDH-mutant, 1p19q non-codeleted CNS WHO grade 3 or glioblastoma, IDH-wildtype, CNS WHO grade 4. Concurrent TMZ and RT should be offered to patients with newly diagnosed glioblastoma, IDH-wildtype, CNS WHO grade 4 followed by 6 months of adjuvant TMZ. Alternating electric field therapy, approved by the US Food and Drug Administration, should be considered for these patients. Bevacizumab is not recommended. In situations in which the benefits of 6-week RT plus TMZ may not outweigh the harms, hypofractionated RT plus TMZ is reasonable. In patients age ≥ 60 to ≥ 70 years, with poor performance status or for whom toxicity or prognosis are concerns, best supportive care alone, RT alone (for promoter unmethylated tumors), or TMZ alone (for promoter methylated tumors) are reasonable treatment options. Additional information is available at www.asco.org/neurooncology-guidelines.
Topics: Astrocytoma; Brain Neoplasms; Clinical Decision-Making; Consensus; Evidence-Based Medicine; Humans; Medical Oncology; Oligodendroglioma; Predictive Value of Tests; Randomized Controlled Trials as Topic; Time Factors; Treatment Outcome
PubMed: 34898238
DOI: 10.1200/JCO.21.02036 -
Neurologia Medico-chirurgica Apr 2022Malignant progression of diffuse low-grade glioma (LGG) is a critical event affecting patient survival; however, the incidence and related factors have been inconsistent... (Meta-Analysis)
Meta-Analysis
Malignant progression of diffuse low-grade glioma (LGG) is a critical event affecting patient survival; however, the incidence and related factors have been inconsistent in literature. According to the PRISMA guidelines, we systematically reviewed articles from 2009, meta-analyzed the incidence of malignant progression, and clarified factors related to the transformation. Forty-one articles were included in this study (n = 7,122; n, number of patients). We identified two definitions of malignant progression: histologically proven (Htrans) and clinically defined (Ctrans). The malignant progression rate curves of Htrans and Ctrans were almost in parallel when constructed from the results of meta-regression by the mean follow-up time. The true transformation rate was supposed to lie between the two curves, approximately 40% at the 10-year mean follow-up. Risk of malignant progression was evaluated using hazard ratio (HR). Pooled HRs were significantly higher in tumors with a larger pre- and postoperative tumor volume, lower degree of resection, and notable preoperative contrast enhancement on magnetic resonance imaging than in others. Oligodendroglial histology and IDH mutation (IDHm) with 1p/19q codeletion (Codel) also significantly reduced the HRs. Using Kaplan-Meier curves from eight studies with molecular data, we extracted data and calculated the 10-year malignant progression-free survival (10yMPFS). The 10yMPFS in patients with IDHm without Codel was 30.4% (95% confidence interval [95% CI]: 22.2-39.0) in Htrans and 38.3% (95% CI: 32.3-44.3) in Ctrans, and that with IDHm with Codel was 71.7% (95% CI: 61.7-79.5) in Htrans and 62.5% (95% CI: 55.9-68.5) in Ctrans. The effect of adjuvant radiotherapy or chemotherapy could not be determined.
Topics: Brain Neoplasms; Glioma; Humans; Incidence; Isocitrate Dehydrogenase; Mutation
PubMed: 35197400
DOI: 10.2176/jns-nmc.2021-0313 -
European Journal of Medical Research Jan 2023Primary central nervous system (CNS) tumors are a heterogeneous group of neoplasms, including benign and malignant tumors. Since there are many heterogeneities in the... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Primary central nervous system (CNS) tumors are a heterogeneous group of neoplasms, including benign and malignant tumors. Since there are many heterogeneities in the prevalence reported in previous studies on this type of tumor, this study was performed to determine the overall prevalence of different primary CNS tumors.
METHOD
The study was conducted as a systematic review and meta-analysis by searching international databases, including PubMed, Scopus, Science Direct, Web of science, and the Google Scholar search engine until August 2020. After transferring the studies to information management software (EndNote) and eliminating duplicate studies, the remaining studies were reviewed based on inclusion and exclusion criteria according to three stages of primary and secondary evaluation and qualitative evaluation. Comprehensive Meta-Analysis software, Begg, Mazumdar, and I tests were used for data analysis, publication bias analysis, and heterogeneity analysis, respectively.
RESULTS
After performing the systematic review steps, 80 studies were included for final analysis. Based on 8 studies, the prevalence of brain tumors was 70.9%. Also, studies on 7 other studies showed that the prevalence of spinal tumors was 12.2%. A review of 14 studies showed that the prevalence of neuroepithelial tumors was 34.7%. The analysis of 27 studies reported a prevalence of glioma tumors of 42.8%. Analyses performed on other studies showed that the prevalence of pituitary adenomas was 12.2%, embryonal tumors 3.1%, ependymal tumors 3.2%, meningiomas 24.1%, glial tumors 0.8%, astrocytic 20.3%, oligodendroglial 3.9%, glioblastoma 17.7%, schwannoma 6.7%, medulloblastoma 7.7% and Polycystic astrocytomas 3.8%.
CONCLUSION
As a result, it can be stated that brain tumors are the most common type of primary CNS tumors. It was also observed that tumors involving neuroepithelial cells are more common in patients than other types of tumors.
Topics: Humans; Prevalence; Central Nervous System Neoplasms; Brain Neoplasms; Glioblastoma
PubMed: 36670466
DOI: 10.1186/s40001-023-01011-y -
World Neurosurgery Jan 2020With the 2016 update of the World Health Organization (WHO) Classification of Tumors of the Central Nervous System incorporating molecular subtyping to histology, WHO...
Effect of Treatment Modalities on Progression-Free Survival and Overall Survival in Molecularly Subtyped World Health Organization Grade II Diffuse Gliomas: A Systematic Review.
BACKGROUND
With the 2016 update of the World Health Organization (WHO) Classification of Tumors of the Central Nervous System incorporating molecular subtyping to histology, WHO grade II diffuse astrocytic and oligodendroglial tumors are subcategorized by distinct molecular markers. There are no reported systematic reviews quantifying differences in progression-free survival (PFS) and overall survival (OS) on the basis of molecular subtypes of WHO grade II diffuse gliomas, against the background of administered treatments.
METHODS
Using the PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analyses) guidelines and the Cochrane Handbook of Systemic Reviews of Interventions, we conducted a systematic review through MEDLINE, Embase, and CENTRAL (Cochrane Central Register of Controlled Trails).
RESULTS
For OS, the first quartile (25%), median (50%), third quartile (75%), and 95% confidence interval, respectively, were identified (in months): astrocytoma-wild-type WHO II (A-wt II): 22.8, 32.2, 40.7, and 21.6-61.2; astrocytoma-mutant WHO II (A-mt II): 69.85, 115.2, 128.4, and 55.4-164.0; oligodendroglioma WHO II (OD-II): 106.3, 163.7, 213.3, and 67.3-235.4 (P value = 0.0002). For PFS, the 25th, 50th, and 75th percentiles, and 95% confidence interval, respectively, are as follows (in months): A-wt II: 6.90, 17.45, 19.57, and 3.00-23.69; A-mt II: 37.20, 43.20, 55.63, and 35.7-60.0; OD-II: 47.42, 59.2, 88.28, and 46.3-91.2 (P value = 0.015).
CONCLUSIONS
This seems to be the first systematic review of OS and PFS in patients with WHO grade II low-grade gliomas (LGGs), against treatment modalities, in molecularly stratified subsets introduced by the WHO 2016 classification of central nervous system tumors. Overall, A-wt II was confirmed to have a significantly shorter OS than did A-mt II; no significant difference was found between OS of OD-II with A-wt II and A-mt II. In addition, all 3 molecular subtypes were found to have statistically significant differences between PFS, with OD-II having a statistically better PFS than A-mt II. These data can provide valuable prognostic insight to patients and clinicians. In addition, assessing survival differences enhances understanding of treatment recommendations against molecular markers and may facilitate future clinical trial design.
Topics: Brain Neoplasms; Glioma; Humans; Neoplasm Grading; Progression-Free Survival; Survival Rate
PubMed: 31473344
DOI: 10.1016/j.wneu.2019.08.111 -
Neuroradiology Mar 2021Molecular parameters have become integral to glioma diagnosis. Much of radiogenomics research has focused on the use of advanced MRI techniques, but conventional MRI...
PURPOSE
Molecular parameters have become integral to glioma diagnosis. Much of radiogenomics research has focused on the use of advanced MRI techniques, but conventional MRI sequences remain the mainstay of clinical assessments. The aim of this research was to synthesize the current published data on the accuracy of standard clinical MRI for diffuse glioma genotyping, specifically targeting IDH and 1p19q status.
METHODS
A systematic search was performed in September 2019 using PubMed and the Cochrane Library, identifying studies on the diagnostic value of T1 pre-/post-contrast, T2, FLAIR, T2*/SWI and/or 3-directional diffusion-weighted imaging sequences for the prediction of IDH and/or 1p19q status in WHO grade II-IV diffuse astrocytic and oligodendroglial tumours as defined in the WHO 2016 Classification of CNS Tumours.
RESULTS
Forty-four studies including a total of 5286 patients fulfilled the inclusion criteria. Correlations between key glioma molecular markers, namely IDH and 1p19q, and distinctive MRI findings have been established, including tumour location, signal composition (including the T2-FLAIR mismatch sign) and apparent diffusion coefficient values.
CONCLUSION
Consistent trends have emerged indicating that conventional MRI is valuable for glioma genotyping, particularly in presumed lower grade glioma. However, due to limited interobserver testing, the reproducibility of qualitatively assessed visual features remains an area of uncertainty.
Topics: Adult; Brain Neoplasms; Glioma; Humans; Isocitrate Dehydrogenase; Magnetic Resonance Imaging; Neoplasm Grading; Reproducibility of Results
PubMed: 32840682
DOI: 10.1007/s00234-020-02532-7 -
Journal of Neuro-oncology Nov 2018Gliomatosis cerebri (GC) is a rare fatal widespread infiltrating CNS tumor. As consistent disease features have not been established, the tumor comprises a diagnostic...
INTRODUCTION
Gliomatosis cerebri (GC) is a rare fatal widespread infiltrating CNS tumor. As consistent disease features have not been established, the tumor comprises a diagnostic challenge.
METHODS
We conducted a systematic literature search for published case reports and case series on patients with histologically confirmed GC. Clinical, diagnostic, neuroimaging, histopathological, and molecular data on individual or summary patient level were extracted and analyzed.
RESULTS
A total of 274 studies were identified, including 866 patients with individual-level data and 782 patients with summary data (58.9% males, mean age 43.6 years). Seizures (49.8%) were the most common presenting symptom followed by headache (35.9%), cognitive decline (32.2%), and focal motor deficits (32%). Imaging studies showed bilateral hemisphere involvement in 65%, infratentorial infiltration in 29.9% and a focal contrast-enhanced mass (type II GC) in 31.1% of cases. MRI (extensive hyperintensities in T2/FLAIR sequences) and MR spectroscopy (elevated choline, creatinine, and myoinositol levels; decreased NAA levels) showed highly consistent findings across GC patients. Low-grade and anaplastic astrocytoma were the most prevalent diagnostic categories, albeit features of any histology (astrocytic, oligodendroglial, oligoastrocytic) and grade (II-IV) were also reported. Among molecular aberrations, IDH1 mutation and MGMT promoter methylation were the most commonly reported. Increasing time elapsed from symptom onset to diagnosis comprised the only independent determinant of the extent of CNS infiltration.
CONCLUSION
A distinct clinical, neuroimaging, histopathological, or molecular GC phenotype is not supported by current evidence. MRI and MR spectroscopy are important tools for the diagnosis of the tumor before confirmation with biopsy.
Topics: Central Nervous System Neoplasms; Humans; Neoplasms, Neuroepithelial; Neuroimaging
PubMed: 30117023
DOI: 10.1007/s11060-018-2976-4 -
Journal of Neuro-oncology Dec 2015Adult patients (age ≥18 years) who have suspected low-grade diffuse glioma.
TARGET POPULATION
Adult patients (age ≥18 years) who have suspected low-grade diffuse glioma.
QUESTION
What are the optimal neuropathological techniques to diagnose low-grade diffuse glioma in the adult?
RECOMMENDATION
LEVEL I: Histopathological analysis of a representative surgical sample of the lesion should be used to provide the diagnosis of low-grade diffuse glioma.
LEVEL III
Both frozen section and cytopathologic/smear evaluation should be used to aid the intra-operative assessment of low-grade diffuse glioma diagnosis. A resection specimen is preferred over a biopsy specimen, to minimize the potential for sampling error issues.
TARGET POPULATION
Patients with histologically-proven WHO grade II diffuse glioma.
QUESTION
In adult patients (age ≥18 years) with histologically-proven WHO grade II diffuse glioma, is testing for IDH1 mutation (R132H and/or others) warranted? If so, is there a preferred method?
LEVEL II
IDH gene mutation assessment, via IDH1 R132H antibody and/or IDH1/2 mutation hotspot sequencing, is highly-specific for low-grade diffuse glioma, and is recommended as an additional test for classification and prognosis.
TARGET POPULATION
Patients with histologically-proven WHO grade II diffuse glioma.
QUESTION
In adult patients (age ≥18 years) with histologically-proven WHO grade II diffuse glioma, is testing for 1p/19q loss warranted? If so, is there a preferred method?
LEVEL III
1p/19q loss-of-heterozygosity testing, by FISH, array-CGH or PCR, is recommended as an additional test in oligodendroglial cases for prognosis and potential treatment planning.
TARGET POPULATION
Patients with histologically-proven WHO grade II diffuse glioma.
QUESTION
In adult patients (age ≥18 years) with histologically-proven WHO grade II diffuse glioma, is MGMT promoter methylation testing warranted? If so, is there a preferred method?
RECOMMENDATION
There is insufficient evidence to recommend methyl-guanine methyl-transferase (MGMT) promoter methylation testing as a routine for low-grade diffuse gliomas. It is recommended that patients be enrolled in properly designed clinical trials to assess the value of this and related markers for this target population.
TARGET POPULATION
Patients with histologically-proven WHO grade II diffuse glioma.
QUESTION
In adult patients (age ≥18 years) with histologically-proven WHO grade II diffuse glioma, is Ki-67/MIB1 immunohistochemistry warranted? If so, is there a preferred method to quantitate results?
LEVEL III
Ki67/MIB1 immunohistochemistry is recommended as an option for prognostic assessment.
Topics: Humans; Brain; Brain Neoplasms; Disease Management; Evidence-Based Medicine; Glioma; Neoplasm Grading
PubMed: 26530263
DOI: 10.1007/s11060-015-1909-8 -
Journal of Neuro-oncology Dec 2015(1) What is the optimal role of external beam radiotherapy in the management of adult patients with newly diagnosed low-grade glioma (LGG) in terms of improving outcome...
QUESTIONS
(1) What is the optimal role of external beam radiotherapy in the management of adult patients with newly diagnosed low-grade glioma (LGG) in terms of improving outcome (i.e., survival, complications, seizure control or other reported outcomes of interest)? (2) Which radiation strategies (dose, timing, fractionation, stereotactic radiation, brachytherapy, chemotherapy) improve outcomes compared to standard external beam radiation therapy in the initial management of low grade gliomas in adults? (3) Do specific factors (e.g., age, volume, extent of resection, genetic subtype) identify subgroups with better outcomes following radiation therapy than the general population of adults with newly diagnosed low-grade gliomas?
TARGET POPULATION
These recommendations apply to adults with newly diagnosed diffuse LGG.
RECOMMENDATIONS
OUTCOMES IN ADULT PATIENTS WITH NEWLY DIAGNOSED LOW GRADE GLIOMA TREATED WITH RADIOTHERAPY: Level I Radiotherapy is recommended in the management of newly diagnosed low-grade glioma in adults to prolong progression free survival, irrespective of extent of resection. Level II Radiotherapy is recommended in the management of newly diagnosed low grade glioma in adults as an equivalent alternative to observation in preserving cognitive function, irrespective of extent of resection. Level III Radiotherapy is recommended in the management of newly diagnosed low grade glioma in adults to improve seizure control in patients with epilepsy and subtotal resection. Level III Radiotherapy is recommended in the management of newly diagnosed low-grade glioma in adults to prolong overall survival in patients with subtotal resection. Level III Consideration of the risk of radiation induced morbidity, including cognitive decline, imaging abnormalities, metabolic dysfunction and malignant transformation, is recommended when the delivery of radiotherapy is selected in the management of newly diagnosed low-grade glioma in adults. STRATEGIES OF RADIOTHERAPY IN ADULT PATIENTS WITH NEWLY DIAGNOSED LOW GRADE GLIOMA: Level I Lower dose radiotherapy is recommended as an equivalent alternative to higher dose immediate postoperative radiotherapy (45-50.4 vs. 59.4-64.8 Gy) in the management of newly diagnosed low-grade glioma in adults with reduced toxicity. Level III Delaying radiotherapy until recurrence or progression is recommended as an equivalent alternative to immediate postoperative radiotherapy in the management of newly diagnosed low-grade glioma in adults but may result in shorter time to progression. Level III The addition of chemotherapy to radiotherapy is not recommended over whole brain radiotherapy alone in the management of low-grade glioma, as it provides no additional survival benefit. Level III Limited-field radiotherapy is recommended over whole brain radiotherapy in the management of low-grade glioma. Level III Either stereotactic radiosurgery or brachytherapy are recommended as acceptable alternatives to external radiotherapy in selected patients. PROGNOSTIC FACTORS IN ADULT PATIENTS WITH NEWLY DIAGNOSED LOW GRADE GLIOMA TREATED WITH RADIOTHERAPY: Level II It is recommended that age greater than 40 years, astrocytic pathology, diameter greater than 6 cm, tumor crossing the midline and preoperative neurological deficit be considered as negative prognostic indicators when predicting overall survival in adult low grade glioma patients treated with radiotherapy. Level II It is recommended that smaller tumor size, extent of surgical resection and higher mini-mental status exam be considered as positive prognostic indicators when predicting overall survival and progression free survival in patients in adult low grade glioma patients treated with radiotherapy. Level III It is recommended that seizures at presentation, presence of oligodendroglial histological component and 1p19q deletion (along with additional relevant factors-see Table 1) be considered as positive prognostic indicators when predicting response to radiotherapy in adults with low grade gliomas. Level III It is recommended that increasing age, decreasing performance status, decreasing cognition, presence of astrocytic histological component (along with additional relevant factors (see Tables 1, 2) be considered as negative prognostic indicators when predicting response to radiotherapy.
Topics: Humans; Brain Neoplasms; Disease Management; Evidence-Based Medicine; Glioma; Neoplasm Grading
PubMed: 26530266
DOI: 10.1007/s11060-015-1948-1