Parisa Momtaz and Thomas J. Kaley
Definition
• Astrocytoma is the most common type of gliomas
• Classified under a grading system: Grade 1 (typically benign), grade 2 (low-grade astrocytomas), grade 3 (anaplastic), & grade 4 (glioblastoma multiforme)
Epidemiology/Risk Factors
• Grade 4 astrocytoma, glioblastoma multiforme, is the most common malignant 1° brain tumor, accounts for >50% of all gliomass
• Has been a/w type 1 neurofibromatosis, Turcot syndrome, LFS
• Polymorphisms in the CDKN2B & RTEL1 genes have been a/w greater risk
• Ionizing radiation
Clinical Manifestations
• Sx related to mass effect, parenchymal infiltration, hydrocephalus, tissue destruction
• HA (most common, 35%), sudden onset, more sev. in the AM
• Associated nausea, vomiting, focal neurologic deficits
• Seizures (30%), more common w/low-grade tumors
Diagnosis
• Mass may or may not enhance w/contrast on CT therefore MRI is more sensitive
• Grade II tumors typically nonenhancing, Grade IV tumor typically do enhance
• Ring enhancement is characteristic of glioblastoma multiforme
• PET & MRI spectroscopy remain under investigation
• Surgical bx or resection (careful attention to brainstem gliomas)
• Most remain localized therefore extensive staging procedures are not often necessary
Treatment Principles
Surgery
• Goal is to obtain histologic dx, reduce mass effect while preserving neurologic function, debulking; can be curative for benign tumors
• Stereotactic bx, open bx (primarily for tumors in critical areas where resection would lead to neurologic deficit)
• Debulking procedure, subtotal resection, maximal resection
• Post-op MRI should be obtained w/in 24–72 h to document extent of disease following surgery
RT
• EBRT: EBRT w/partial brain radiation is standard; is as effective as whole brain radiation while preserving nl brain tissue & reducing late neurotoxic effects
• Re-irradiate if progression free for >2 y since last RT, the new lesion is outside the target of the last RT, size of recurrence is small
• Complications: Radionecrosis (presents as a focal mass lesion w/contrast enhancement & mass effect), radiation-induced leukoencephalopathy (mos to y after, presents as diffused ↑ T2/FLAIR signal abnl on MRI w/assoc atrophy)
Chemotherapy
• Most commonly used agent is temozolomide as it penetrates the blood–brain barrier
• Nitrosoureas (eg, carmustine, lomustine), platinum-based therapies
• Procarbazine, Lomustine, Vincristine (PCV) for oligodendroglial tumors
• Limited benefit; used in combination w/surgery & radiation
Other therapeutic agents
• Corticosteroids, anticonvulsant agents, anticoagulation meds
Pathology/Grading Classification
• WHO classification as a four-tiered grading system based on key histologic features:
↑ cellularity, mitoses, endothelial proliferation, necrosis
Grade 1
• Typically benign. Eg, pilocytic astrocytoma, pleomorphic xanthoastrocytoma, subependymal giant cell astrocytoma
• Well circumscribed, rarely transform to higher grade astrocytomas, are often resectable, & typically cured by surgery alone & if incomplete resection can successfully tx w/RT
Grade 2: Low-grade Astrocytomas
• Diffuse infiltrating low-grade tumors w/only ↑ cellularity
• Poor Px factors: Age ≥40 y, tumor ≥6 cm, tumor crossing midline, presence of neurologic deficit prior to resection
• Typically are nonenhancing, low attenuation lesions on CT & MRI therefore T2-weighted or FLAIR MRI scans are preferred
• Poorly circumscribed, invasive & can transform to higher grade astrocytomas (50% pts will undergo anaplastic transformation in 5 y)
• Median survival is approx. 5 y
• Tx:
Surgery w/gross total excision w/o compromising function
No consensus on the timing of EBRT. Standard radiation dose is 45–54 Gy.
Limited data for temozolomide as adjuvant Rx.
Acceptable regimens for recurrence/progressive disease include temozolomide, nitrosourea, PCV (procarbazine, lomustine, vincristine) & platinum-based Rx (Shaw EG,Neuro Oncol 2008;10:884)
• Follow-up: MRI q3–6 mos for 5 y & then annually as late recurrences are common
Grade 3: Anaplastic Astrocytomas
• Presence of mitoses distinguishes anaplastic from low grade
• Can be both contrast enhancing & noncontrast enhancing on MRI
• High propensity to undergo transformation to glioblastoma multiforme
• Median survival 24 mos
• Tx:
Maximum surgical debulking w/o compromising function
Adjuvant RT prolongs survival
Adjuvant chemotherapy role unclear; single-agent carmustine & PCV have shown prolonged survival in some series & meta-analysis, temozolomide
Recurrence: Temozolomide (Yung WK J Clin Oncol 1999;17:2766) & nitrosourea-based regimens
Grade 4: Glioblastoma Multiforme
• Most common & most malignant of the 1° brain tumors
• Onset of sx is abrupt & due to mass effect
• Pathologic features: ↑ cellularity, endothelial proliferation, tumor necrosis
• EGFR amp & Mt or loss of PTEN are characteristic
• T1-weighted MRI scans w/the use of gadolinium show a ring-enhanced mass
• Tx:
Surgery followed by adjuvant RT w/concurrent & adjuvant temozolomide (Stupp R NEJM 2005;352:987)
Bev monotherapy approved for recurrence
Figure 21-1 GBM TI post-contrast MRI MSKCC. Courtesy of Dr. T. Kaley
Figure 21-2 Low-grade Astrocytoma T2 FLAIR MSKCC. Courtesy of Dr. T. Kaley