Fig. 25.1
Astrocytomas grade II. Axial MRI images show a lesion hyperintense in T2 sequences without mass effect (a), slightly hypointense in T1 sequences (b) without contrast enhancement (c) located in right posterior and inferior frontal lobe
MRI (diffusion weighted) can show higher apparent diffusion coefficient (ADC) due to low cellularity and low regional blood flow on perfusion imaging (rCBV). Metabolism and proliferation (assessed by MR spectroscopy or PET) are usually normal or lower than normal brain in LGG.
25.1.6 Treatment
The optimal treatment and the exact timing of treatment in LGG is still controversial, and the risks and benefits of therapies must be carefully balanced with the data available from limited prospective studies.
Symptoms management requires different therapeutic approaches.
The treatment is based on:
1.
Surgery
The objective is the maximal possible resection (patients with gross total resection have the longest survival), minimizing the postoperative deficits. Total resection improves seizure control, particularly in patients with a long epileptic history and insular tumors.
When surgery is not feasible, a biopsy is performed to obtain a histological diagnosis.
2.
Radiotherapy
The RT treatment after surgery is still a topic of debate, in particular regarding the optimal timing of treatment and the optimal radiation dose.
The lack of survival benefit with immediate adjuvant radiotherapy has been used as a justification to postpone radiation until disease progression.
Randomized trials showed no advantage for higher versus lower doses of RT (standard total RT dose of 50–54 Gy).
3.
Chemotherapy
It is an option for the initial treatment of patients with large residual tumors after surgery or unresectable tumors; it is also an option for patients with recurrence after surgery and radiation.
Observational studies indicate that chemotherapy may be effective in patients with oligodendroglial tumors; its role in diffuse low-grade astrocytomas is less clear.
PCV chemotherapy after radiation in high risk low-grade glioma could improve survival rates (median OS 13.3 years vs 7.8 years).
Due to its favorable toxicity profile, TMZ has been proposed as a therapeutic alternative to radiotherapy in first-line treatment, especially when patients are young, or tumor growth would require too extensive a field of radiation.
Prognostic biomarkers could be very important in therapeutic decisions.
25.1.7 Prognosis
5-year overall survival (OS) and progression-free survival (PFS) rates range from 58 to 72 % and 37 to 55 %, respectively.
Two biological characteristics prominently influence the prognosis of low-grade gliomas.
Positive prognostic factors that can influence survival include:
Histology: Oligodendrogliomas show a better prognosis than astrocytomas; the prognosis of patients with gemistocytic astrocytomas is worse than that of the average astrocytoma patient.
Younger age (<40 years).
Better performance status (KPS) at diagnosis and the absence of preoperative neurological deficits.
The lack of contrast enhancement on MRI, since tumor size or location is not universally accepted.
The extension of resection.
Molecular features: 1p deletion or 1p/19q codeletion is a favorable marker both in oligodendroglioma and oligoastrocytoma; IDH1 mutation has been recently suggested as an independent favorable prognostic factor [1].
25.2 High-Grade Gliomas
25.2.1 Definition
High-grade gliomas (HGGs) comprise: glioblastoma, World Health Organization (WHO) grade IV, anaplastic astrocytoma (WHO grade III), mixed anaplastic oligoastrocytoma (WHO grade III), and anaplastic oligodendroglioma (WHO grade III).
25.2.2 Epidemiology
The annual incidence of HGG is approximately 5/100,000. Glioblastomas (GBM) account for 60–70 % of HGG, anaplastic astrocytomas (AA) account for 10–15 %, and anaplastic oligodendrogliomas and anaplastic oligoastrocytomas account for 10 %.
HGGs are more common in men and twice as common in whites than in blacks. The median age at diagnosis is 64 years (GBM) and 45 years (AA)
No underlying cause has been identified for the majority of malignant gliomas. The only established risk factor is exposure to ionizing radiation.
Less than 5 % of patients affected by malignant gliomas have a family history of gliomas. Some of these familial cases are associated with rare genetic syndromes, such as neurofibromatosis 1 and 2.
25.2.3 Clinical Features
Symptoms of HGGs are the same of other brain tumors. Clinical manifestations include general symptoms due to increasing pressure in the brain (ICP) and focal symptoms and signs reflecting the size and location of the tumor.
In high-grade tumors, the incidence of epilepsy (30–40 %) is lower compared to low-grade gliomas (72–89 %).
Cognitive deficits are common and frequently may include slowed thinking, memory loss, and difficulty with multitasking.
25.2.4 Pathology
Gliomas arise from astrocytes, oligodendrocytes, or their precursors. Gliomas are graded, according to the four-tier WHO system (I to IV). Grading is based on pathologic features, endothelial proliferation, cellular pleomorphism, mitoses, and necrosis.
The high-grade gliomas are extremely invasive, with tumor cells often found up to 4 cm away, even on the contralateral side of the brain.
25.2.5 Radiographic Findings
MRI is the standard imaging. It is highly sensitive for a brain tumor but not specific (see Table 25.1).
Table 25.1
Main radiological features of LGG, HGG, brain metastases, meningiomas, and PNLS
LGG | GBM | Brain MTS | Meningiomas | PNSL | |
|---|---|---|---|---|---|
T1WI | Usually Iso/hypointense, well-defined mass | Irregular hypointense, isointense, necrosis cyst common. Ring enhancement surrounding central necrosis | Hypointense, isointense, hyperintense or mixed Strong enhancement, variable patterns | Extrassial lesions, isointense to cortex with homogeneus and strong enhancement | Homogenous iso/hypointense to cortex Strong homogenous contrast enhancement, (non-enhancing in less than 10 %) |
T2WI/FLAIR | Homogenous, hyperintense, no/little mass effect | Heterogenous, hyperintense, necrosis cyst, surrounding edema and infiltrating (nonenhancing) tumor | Variable, usually moderate hyperintense to cortex, surrounding edema | Iso-hyperintense to cortex | Homogenous iso/hypointense, may be heterogenous from necrosis |
DWI | No restricted diffusion | No restricted diffusion | Usually no restricted diffusion | Atypical and malignant variants show restricted diffusion | Restricted diffusion |
Perfusion | Low rCBV values | High rCBV in tumor and peritumoral region | High rCBV values | elevated rCBV values | Low rCBV values |
MRS | Low choline peak, low NAA, low values of Lac and lipids | Elevated choline peak, decrease in Cho/NAA and Cho/Cr ratios. High value of Lac and lipids | Strong Cho peak, NAA decreased, elevated lipid peaks without significant NAA/Cr and Cho/Cr ratios | Elevated choline and alanine peak | NAA decreased, elevated lipid peaks and high Cho/Cr ratios |
25.2.6 Differential Diagnosis
Brain Metastases
Primary CNS Lymphoma: usually shows homogeneous enhancing.
Cerebral Abscess: smooth and complete susceptibility-weighted imaging (SWI) low-intensity rim, central restricted diffusion is helpful.
Demyelinating tumefactive lesions (MS): younger patients, often open enhancement ring.
Subacute cerebral infarction: normal choline and rCBV.
25.2.7 Prognosis
The outcome for HHG remains dismal despite multimodality treatments, including surgery, chemo-radiotherapy.
Estimates of survival rates vary widely according to the type of tumor: the 5-year survival rate for GBMs is less than 5; 10 % for AA, and finally, for anaplastic oligodendroglioma and anaplastic oligoastrocytoma, the rate is 85 % or better.
Positive prognostic factors that can influence survival include:
Histology: Oligodendroglial tumors show a better prognosis than astrocytomas; the prognosis of patients with gemistocytic astrocytomas is worse than that of the average astrocytoma patient.
Younger age (<40 years).
Better performance status (KPS) at diagnosis and the absence of preoperative neurological deficits.
The extension of resection; tumor diameter <6 cm; tumor not crossing midline.
Molecular features: 25–50 % of anaplastic oligodendrogliomas and oligoastrocytomas harbor 1p/19q codeletion, which are favorable markers in oligodendroglioma and oligoastrocytoma. IDH1 mutation has been recently suggested as an independent favorable prognostic factor in these tumors.
O6-methylguanine-DNAmethyltransferase (MGMT): the epigenetic silencing of the MGMT DNA-repair gene by promoter methylation is an independent prognostic factor in patients with glioblastoma and has been associated with longer survival in patients who receive alkylating chemotherapies.
25.2.8 Treatment and Prognosis
Corticosteroids are extensively employed in HGG (usually dexamethasone, 4–16 mg/day) to relieve edema.
Antiepileptic drugs (AEDs) prophylaxis should not be routinely used. Moreover, some AEDs interfere with chemotherapeutic agents. Levetiracetam (1000–2000 mg/day) may be considered as a first-line agent; enzyme-inducing AEDs ( phenobarbital, carbamazepine, phenytoin) should be discouraged.
Surgery: for either diagnosis or tumor-debulking purpose. The general target is to remove more than 90 % of the tumor volume. Maximal cytoreduction without causing neurological deficits has critical prognostic value for patient outcome and survival.
For HGG located in eloquent areas of the brain or for patients with poor performance status, a biopsy of the tumor could be more appropriate.
Functional MRI is increasingly used in the planning of surgery in eloquent areas. Intraoperative MRI is now standard practice in some selected centers.
Radiotherapy: Fractionated focal radiotherapy (60 Gy, 30–33 fractions of 1.8–2 Gy) is the standard treatment after resection or biopsy. Ninety percent of tumors recur within a 2-cm margin. The current practice is to irradiate the tumor-involved tissue with an additional 2-cm margin.
Chemotherapy: After surgery, adjuvant radiotherapy combined with the DNA alkylating agent temozolomide should be considered in all glioblastomas. Temozolomide is administered orally (75 mg/m2), concomitantly with radiotherapy, followed by an adjuvant course (150–200 mg/m2 for 5 consecutive days every 28 days for 6 cycles).
Adjuvant and concomitant temozolomide combined with radiation gives significant improvements in median progression-free survival over radiation alone (6.9 vs 5 months), overall survival (14.6 vs 12.1 months), and the likelihood of being alive in 2 years (26 % vs 10 %).
Patients with glioblastomas displaying promoter methylation (MGMT) are more likely to benefit from the addition of temozolomide to radiotherapy.
The other first-line treatment approved by Food and Drug Administration (FDA) is biodegradable polymers containing the alkylating agent carmustine (Gliadel) implanted into the tumor bed after its resection.
According to the prospective randomized Radiation Therapy Oncology Group (RTOG) and EORTC trials on the role of PCV chemotherapy (procarbazine, CCNU, and vincristine) plus radiation in newly diagnosed anaplastic oligodendroglioma and oligoastrocytoma tumors, patients with 1p/19q codeletion survive much longer than patients with non-codeleted tumors (OS 123 vs 23 months in the EORTC study). Moreover, 1p/19q codeletion predicts sensitivity to PCV chemotherapy.
Many oncologists prefer temozolomide for anaplastic gliomas because it has fewer side effects than PVC and is easier to administer.
25.2.9 Treatment at Recurrence
All HGG patients experience disease recurrence. None of the existing salvage treatments has significantly improved their survival; some benefits have been observed only in selected patients.
A new tumor resection and cytoreduction could be considered for mass effect relief. At the moment, data concerning survival benefits are not conclusive
Salvage chemotherapy options include temozolomide rechallenge and nitrosoureas (in the US, Bevacizumab is a frequently used treatment for recurrent glioblastoma). Bevacizumab often results in rapid decrease of peritumoral edema, and it is an option for highly symptomatic patients, but survival benefits are less clear.
25.3 Gliomatosis
25.3.1 Definition and Pathology
The 2007 WHO classification defines gliomatosis cerebri (GC) as a subtype of diffuse glioma, considering it as a growth pattern of astrocytomas (most commonly), oligodendrogliomas, and oligoastrocytomas, in which invasion by glial neoplastic cells involves more than three lobes [7].
Molecular alterations found in GC are usually the same as in other low-grade tumors.
25.3.2 Epidemiology and Clinical Features
Same age and sex distribution of other gliomas; GC is usually found in the age group of 40–50 years and presents a slightly higher male prevalence
Symptoms might appear slowly and subtly and are variable and not specific
25.3.3 Diagnostic Markers
MRI is the first choice: T2 weighted images demonstrate the tumor involvement trough the white matter in multiple lobes with loss of distinction between grey and white matter
Contrast enhancement is not usually evident or minimal (if present, could indicate a malignant transformation)
25.3.4 Treatment and Prognosis
Prognosis is poor, probably due to the highly infiltrative activity of glioma cells. The survival rates at 1-, 2-, or 3 years are 48 %, 37 %, and 27 %, respectively [7], not very different from those of glioblastoma.
The optimal treatment of GC is still unclear [7]:
1.
The role of surgery is limited to histological diagnosis.
2.
Whole brain radiation therapy alone could affect clinical and radiological response rates positively, but its role on overall survival is questionable.
3.
Chemotherapy seems to be beneficial at least in some patients.
25.4 CNS Embryonal Tumors and Medulloblastoma
25.4.1 Definition
CNS embryonal tumors include a heterogeneous group of highly cellular, mitotically active, immature-appearing neoplasms.Related posts:
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