-
Journal of Neuro-oncology Dec 2015Should patients with imaging suggestive of low grade glioma (LGG) undergo observation versus treatment involving a surgical procedure?
QUESTION
Should patients with imaging suggestive of low grade glioma (LGG) undergo observation versus treatment involving a surgical procedure?
TARGET POPULATION
These recommendations apply to adults with imaging suggestive of a WHO grade 2 glioma (oligodendroglioma, astrocytoma, or oligo-astrocytoma).
RECOMMENDATIONS
Surgical resection is recommended over observation to improve overall survival for patients with diffuse low-grade glioma (Level III) although observation has no negative impact on cognitive performance and quality of life (Level II).
QUESTION
What is the impact of extent of resection on progression free survival (PFS) or overall survival (OS) in LGG patients?
TARGET POPULATION
These recommendations apply to adults with imaging suggestive of a WHO grade 2 glioma (oligodendroglioma, astrocytoma, or oligo-astrocytoma).
RECOMMENDATIONS
IMPACT OF EXTENT OF RESECTION ON PFS:
LEVEL II
It is recommended that GTR or STR be accomplished instead of biopsy alone when safe and feasible so as to decrease the frequency of tumor progression recognizing that the rate of progression after GTR is fairly high.
LEVEL III
Greater extent of resection can improve OS in LGG patients.
QUESTION
What tools are available to increase extent of resection in LGG patients?
TARGET POPULATION
These recommendations apply to adults with imaging suggestive of a WHO grade 2 glioma (oligodendroglioma, astrocytoma, or oligo-astrocytoma).
RECOMMENDATIONS
INTRAOPERATIVE MRI DURING SURGERY:
LEVEL III
The use of intraoperative MRI should be considered as a method of increasing the extent of resection of LGGs.
QUESTION
What is the impact of surgical resection on seizure control and accuracy of pathology in low grade glioma patients?
TARGET POPULATION
These recommendations apply to adults with imaging suggestive of a WHO grade 2 glioma (oligodendroglioma, astrocytoma, or oligo-astrocytoma).
RECOMMENDATIONS
SURGICAL RESECTION AND SEIZURE CONTROL:
LEVEL III
After taking into account the patient's clinical status and tumor location, gross total resection is recommended for patients with diffuse LGG as a way to achieve more favorable seizure control.
LEVEL III
Taking into account the patient's clinical status and tumor location, surgical resection should be carried out to maximize the chance of accurate diagnosis.
QUESTION
What tools can improve the safety of surgery for LGGs in eloquent locations?
TARGET POPULATION
These recommendations apply to adults with imaging suggestive of a WHO grade 2 glioma (oligodendroglioma, astrocytoma, or oligo-astrocytoma).
RECOMMENDATIONS
PREOPERATIVE IMAGING:
LEVEL III
It is recommended that preoperative functional MRI and diffusion tensor imaging be utilized in the appropriate clinical setting to improve functional outcome after surgery for LGG.
LEVEL III
Intraoperative mapping is recommended for patients with diffuse LGGs in eloquent locations compared to patients with non-eloquently located diffuse LGGs as a way of preserving function.
Topics: Humans; Brain; Brain Neoplasms; Evidence-Based Medicine; Glioma; Neoplasm Grading; Neurosurgical Procedures
PubMed: 26530265
DOI: 10.1007/s11060-015-1867-1 -
Journal of Neuro-oncology Dec 2015What is the optimal imaging technique to be used in the diagnosis of a suspected low grade glioma, specifically: which anatomic imaging sequences are critical for most...
QUESTION
What is the optimal imaging technique to be used in the diagnosis of a suspected low grade glioma, specifically: which anatomic imaging sequences are critical for most accurately identifying or diagnosing a low grade glioma (LGG) and do non-anatomic imaging methods and/or sequences add to the diagnostic specificity of suspected low grade gliomas?
TARGET POPULATION
These recommendations apply to adults with a newly diagnosed lesion with a suspected or histopathologically proven LGG.
LEVEL II
In patients with a suspected brain tumor, the minimum magnetic resonance imaging (MRI) exam should be an anatomic exam with both T2 weighted and pre- and post-gadolinium contrast enhanced T1 weighted imaging. CRITICAL IMAGING FOR THE IDENTIFICATION AND DIAGNOSIS OF LOW GRADE GLIOMA:
LEVEL II
In patients with a suspected brain tumor, anatomic imaging sequences should include T1 and T2 weighted and Fluid Attenuation Inversion Recovery (FLAIR) MR sequences and will include T1 weighted imaging after the administration of gadolinium based contrast. Computed tomography (CT) can provide additional information regarding calcification or hemorrhage, which may narrow the differential diagnosis. At a minimum, these anatomic sequences can help identify a lesion as well as its location, and potential for surgical intervention. IMPROVEMENT OF DIAGNOSTIC SPECIFICITY WITH THE ADDITION OF NON-ANATOMIC (PHYSIOLOGIC AND ADVANCED IMAGING) TO ANATOMIC IMAGING:
LEVEL II
Class II evidence from multiple studies and a significant number of Class III series support the addition of diffusion and perfusion weighted MR imaging in the assessment of suspected LGGs, for the purposes of discriminating the potential for tumor subtypes and identification of suspicion of higher grade diagnoses.
LEVEL III
Multiple series offer Class III evidence to support the potential for magnetic resonance spectroscopy (MRS) and nuclear medicine methods including positron emission tomography and single-photon emission computed tomography imaging to offer additional diagnostic specificity although these are less well defined and their roles in clinical practice are still being defined.
QUESTION
Which imaging sequences or parameters best predict the biological behavior or prognosis for patients with LGG?
TARGET POPULATION
These recommendations apply to adults with a newly diagnosed lesion with a suspected or histopathologically proven LGG.
RECOMMENDATION
Anatomic and advanced imaging methods and prognostic stratification
LEVEL III
Multiple series suggest a role for anatomic and advanced sequences to suggest prognostic stratification among low grade gliomas. Perfusion weighted imaging, particularly when obtained as a part of diagnostic evaluation (as recommended above) can play a role in consideration of prognosis. Other imaging sequences remain investigational in terms of their role in consideration of tumor prognosis as there is insufficient evidence to support more formal recommendations as to their use at this time.
QUESTION
What is the optimal imaging technique to be used in the follow-up of a suspected (or biopsy proven) LGG?
TARGET POPULATION
This recommendation applies to adults with a newly diagnosed low grade glioma.
LEVEL II
In patients with a diagnosis of LGG, anatomic imaging sequences should include T2/FLAIR MR sequences and T1 weighted imaging before and after the administration of gadolinium based contrast. Serial imaging should be performed to identify new areas of contrast enhancement or significant change in tumor size, which may signify transformation to a higher grade.
LEVEL III
Advanced imaging utility may depend on tumor subtype. Multicenter clinical trials with larger cohorts are needed. For astrocytic tumors, baseline and longitudinal elevations in tumor perfusion as assessed by dynamic susceptibility contrast perfusion MRI are associated with shorter time to tumor progression, but can be difficult to standardize in clinical practice. For oligodendrogliomas and mixed gliomas, MRS may be helpful for identification of progression.
Topics: Adult; Humans; Brain; Brain Neoplasms; Evidence-Based Medicine; Glioma; Neoplasm Grading; Neuroimaging
PubMed: 26530262
DOI: 10.1007/s11060-015-1908-9 -
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 2015Adult patients (older than 18 years of age) with newly diagnosed World Health Organization (WHO) Grade II gliomas (Oligodendroglioma, astrocytoma, mixed...
TARGET POPULATION
Adult patients (older than 18 years of age) with newly diagnosed World Health Organization (WHO) Grade II gliomas (Oligodendroglioma, astrocytoma, mixed oligoastrocytoma).
QUESTION
Is there a role for chemotherapy as adjuvant therapy of choice in treatment of patients with newly diagnosed low-grade gliomas?
LEVEL III
Chemotherapy is recommended as a treatment option to postpone the use of radiotherapy, to slow tumor growth and to improve progression free survival (PFS), overall survival (OS) and clinical symptoms in adult patients with newly diagnosed LGG.
QUESTION
Who are the patients with newly diagnosed LGG that would benefit the most from chemotherapy?
LEVEL III
Chemotherapy is recommended as an optional component alone or in combination with radiation as the initial adjuvant therapy for all patients who cannot undergo gross total resection (GTR) of a newly diagnosed LGG. Patient with residual tumor >1 cm on post-operative MRI, presenting diameter of >4 cm or older than 40 years of age should be considered for adjuvant therapy as well.
QUESTION
Are there tumor markers that can predict which patients can benefit the most from initial treatment with chemotherapy?
LEVEL III
The addition of chemotherapy to standard RT is recommended in LGG patients that carry IDH mutation. In addition, temozolomide (TMZ) is recommended as a treatment option to slow tumor growth in patients who harbor the 1p/19q co-deletion.
QUESTION
How soon should the chemotherapy be started once the diagnosis of LGG is confirmed?
RECOMMENDATION
There is insufficient evidence to make a definitive recommendation on the timing of starting chemotherapy after surgical/pathological diagnosis of LGG has been made. However, using the 12 weeks mark as the latest timeframe to start adjuvant chemotherapy is suggested. It is recommended that patients be enrolled in properly designed clinical trials to assess the timing of chemotherapy initiation once diagnosis is confirmed for this target population.
QUESTION
What chemotherapeutic agents should be used for treatment of newly diagnosed LGG?
RECOMMENDATION
There is insufficient evidence to make a recommendation of one particular regimen. Enrollment of subjects in properly designed trials comparing the efficacy of these or other agents is recommended so as to determine which of these regimens is superior.
QUESTION
What is the optimal duration and dosing of chemotherapy as initial treatment for LGG?
RECOMMENDATION
Insufficient evidence exists regarding the duration of any specific cytotoxic drug regimen for treatment of newly diagnosed LGG. Enrollment of subjects in properly designed clinical investigations assessing the optimal duration of this therapy is recommended.
QUESTION
Should chemotherapy be given alone or in conjunction with RT as initial therapy for LGG?
RECOMMENDATION
Insufficient evidence exists to make recommendations in this regard. Hence, enrollment of patients in properly designed clinical trials assessing the difference between chemotherapy alone, RT alone or a combination of them is recommended.
QUESTION
Should chemotherapy be given in addition to other type of adjuvant therapy to patients with newly diagnosed LGG?
RECOMMENDATION
Level II: It is recommended that chemotherapy be added to the RT in patients with unfavorable LGG to improve their progression free survival.
Topics: Humans; Brain Neoplasms; Evidence-Based Medicine; Glioma; Neoplasm Grading
PubMed: 26530261
DOI: 10.1007/s11060-015-1931-x -
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