Oligodendroglioma
Encyclopedia
Oligodendrogliomas are a type of glioma
that are believed to originate from the oligodendrocytes of the brain
or from a glial precursor cell. They occur primarily in adults (9.4% of all primary brain and central nervous system tumors) but are also found in children (4% of all primary brain tumors). The average age at diagnosis is 35 years.
of oligodendrogliomas is unknown. Some studies have linked oligodendroglioma with a viral cause. A 2009 Oxford Neurosymposium study illustrated a 69% correlation between NJDS gene mutation and the tumor initiation shown by Kevin Smith. A single case report has linked oligodendroglioma to irradiation of pituitary adenoma.
NEJM 867-5309, ed 6, p112-116, Kevin Smith etal
activity. They occur mainly in the frontal lobe
thus affecting personality.
Headaches combined with increased intracranial pressure
are also a common symptom of oligodendroglioma. Depending on the location of the tumor, any neurological deficit can be induced, from visual loss, motor weakness and cognitive decline. A Computed Tomography
(CT) or Magnetic Resonance Imaging
(MRI) scan is necessary to characterize the anatomy of this tumor (size, location, heter/homogeneity). However, final diagnosis of this tumor
, like most tumors, relies on histopathologic examination (biopsy
examination).
is the only method of definitive diagnosis. Oligodendrogliomas recapitulate the appearance of the normal resident oligodendroglia of the brain. (Their name derives from the Greek roots 'oligo' meaning “ few” and 'dendro' meaning “trees”.) They are generally composed of cells with small to slightly enlarged round nuclei with dark, compact nuclei and a small amount of eosinophilic cytoplasm. They are often referred to as "fried egg" cells due to their histologic appearance. They appear as a monotonous population of mildly enlarged round cells infiltrating normal brain parenchyma
and producing vague nodules. Although the tumor may appear to be vaguely circumscribed, it is by definition a diffusely infiltrating tumor.
Classically they tend to have a vasculature of finely branching capillaries that may take on a “chicken wire” appearance . When invading grey matter structures such as cortex, the neoplastic oligodendrocytes tend to cluster around neurons exhibiting a phenomenon referred to as “perineuronal satellitosis”. Oligodendrogliomas may invade preferentially around vessels or under the pial
surface of the brain.
Oligodendrogliomas must be differentiated from the more common astrocytoma
. Non-classical variants and combined tumors of both oligodendroglioma and astrocytoma differentiation are seen, making this distinction controversial between different neuropathology
groups. In the US, in general, neuropathologists trained on the West Coast are more liberal in the diagnosis of oligodendroliomas than either East Coast or Midwest trained neuropathologists who render the diagnosis of oligodendroglioma for only classic variants. Molecular diagnostics may make this differentiation obsolete in the future.
Other glial
and glioneuronal tumors with which they are often confused due to their monotonous round cell appearance include pilocytic astrocytoma
, central neurocytoma, the so-called dysembryoplastic neuroepithelial tumor, or occasionally ependymoma
.
(WHO) guidelines. Oligodendrogliomas are generally dichotomized into grade II (low grade) and grade III (high grade) tumors. The designation of grade III oligodendroglioma (high grade) generally subsumes the previous diagnoses of anaplastic or malignant oligodendroglioma.
Unfortunately, the WHO guidelines include subjective criteria in differentiating grade II and grade III tumors including the appreciation of “significant” hypercellularity and pleomorphism in the higher grade lesion. In addition, the presence of low mitotic activity, vascular proliferation and necrosis, including pseudopallisading necrosis are insufficient by themselves to elevate the grade of these tumors. This leads to inevitable interobserver variability in diagnosis by pathologists. The ultimate responsibility for making treatment decisions and interpretation of these diagnoses lies with the oncologist in consultation with the patient and their family.
It has been proposed that WHO
guidelines should contain a category for grade IV oligodendrogliomas which essentially appear to be glial neoplasms with overwhelming features of glioblastoma multiforme
(GBM) arising from known lower grade oligodendrogliomas or GBM with a significant proportion of oligodendroglial differentiation. The diagnostic utility of this latter category is uncertain as these tumors may behave either like glioblastoma or grade III oligodendrogliomas. As such, this is an exceptionally unusual diagnosis.
The updated WHO guidelines published in 2007 recommends classifying such tumors for the time being as ‘glioblastoma with oligodendroglioma component’. It remains to be established whether or not these tumors carry a better prognosis than standard glioblastomas.
report for oligodendrogliomas. The status of the 1p/19q loci can be detected by FISH, loss of heterozygosity (LOH) analysis or virtual karyotyping
. Virtual karyotyping has the advantage of assessing the entire genome in one assay, as well as the 1p/19q loci. This allows assessment of other key loci in glial tumors, such as EGFR and TP53 copy number status.
Whereas the prognostic relevance of 1p and 19q deletions is well established for anaplastic oligodendrogliomas and mixed oligoastrocytomas, the prognostic relevance of the deletions for low-grade gliomas is more controversial. In terms of low-grade gliomas, a recent study also suggests that 1p/19q co-deletion may be associated with a (1;19)(q10;p10) translocation which, like the combined 1p/19q deletion, is associated with superior overall survival and progression-free survival in low-grade glioma patients. Oligodendrogliomas show only rarely mutations in the p53 gene, which is in contrast to other gliomas. Epidermal growth factor receptor
amplification and whole 1p/19q codeletion are mutually exclusive and predictive of completely different outcomes, with EGFR amplification predicting poor prognosis. There is a strong correlation between 1p/19q codeletion and the expression of proneural genes, suggesting that gliomas with a 1p19q codeletion represent a subgroup of proneural gliomas.
survival times for oligodendrogliomas were 11.6 years for grade II and 3.5 years for grade III.
However, such figures can be misleading since they do not factor in the types of treatment nor the genetic signature of the tumors. A recent study analyzed survival based on chromosomal deletions and the effects of radiation or chemotherapy as treatment, with the following results (both low-grade and anaplastic oligodendrogliomas): 1p/19q deletion with radiation = 121 months (mean), 1p/19q deletion with chemotherapy = over 160 months (mean not yet reached), no 1p/19q deletion with radiation = 58 months (mean), and no 1p/19q deletion with chemotherapy = 75 months (mean). Another study divided anaplastic oligodendrogliomas into the following four clinically relevant groups of histology with the following results: combined 1p/19q loss = median survival was >123 months (not yet reached), 1p loss only = median survival was 71 months, 1p intact with TP53 mutation = median survival 71 months, and 1p intact with no TP53 mutation = median survival was 16 months.
Because of the indolent nature of these tumors and the potential morbidity associated with neurosurgery
, chemotherapy
and radiation therapy
, most neurooncologists
will initially pursue a course of watchful waiting
and treat patients symptomatically. Symptomatic treatment often includes the use of anticonvulsants for seizures and steroids
for brain swelling. PCV chemotherapy (Procarbazine
, CCNU
and Vincristine
) has been shown to be effective and was the most commonly used chemotherapy regimen used for treating anaplastic oligodendrogliomas, but is now being superseded by a newer drug: Temozolomide. Temozolomide
is a common chemotherapeutic drug to which oligodendrogliomas appear to be quite sensitive. It is often used as a first line therapy, especially because of its relatively mild side effects when compared to other chemotherapeutic drugs.
Nevertheless, a retrospective study on 1054 patients with anaplastic oligodendroglioma, presented during the 2009 ASCO Annual Meeting, suggests that PCV therapy may be superior in efficacy to the newer temozolomide therapy. Median time to progression for patients with 1p19q co-deletion was longer following PCV alone (7.6 years) than with temozolomide alone (3.3 years); median overall survival was also longer with PCV treatment versus temozolomide treatment (not reached, vs. 7.1 years).
The standard dosing schedule of temozolomide is 5 consecutive days of daily dosing during 28 day cycles. However, different dosing schedules may produce better results, such as continuous daily dosing using lower amounts of drug (e.g. 21 day dosing during 28 day cycles). As an example of an altered dosing schedule, promising results have been shown using lower daily doses on each day for 7 weeks, followed by a 4 week off periods. Regarding the duration of dosing, for oligodendrogliomas the duration prescribed by oncologists varies considerably and seems to range from 6 cycles to over 32 cycles (i.e. over 3 years). In one study, researchers compared patients who received temozolomide for at least 12 months on the 5/28 day cycle, dividing such patients into two groups: "short term" patients receiving temozolomide for 12-18 cycles and those "long term" patients receiving 19 or more cycles (range was 19 to 32 cycles). Researches found that there was a statistically significant advantage for "long term" treatment (median progression free survival for "short term" patients was 95 weeks (follow up of 73 weeks), but for "long term" patiets the median progression free survival was not yet reached (follow up of 134 weeks)).
Because of their diffusely infiltrating nature, oligodendrogliomas cannot be completely resected and are not curable by surgical excision
. If the tumor mass compresses adjacent brain structures, a neurosurgeon
will typically remove as much of the tumor as he or she can without damaging other critical, healthy brain structures. Surgery may be followed up by chemotherapy
, radiation
, or a mix of both, but recent studies suggest that radiation does not improve overall survival (even when age, clinical data, histological grading, and type of surgery are considered), and should be avoided when treating oligodendrogliomas. However, it is possible that radiotherapy may prolong the overall time to progression.
Oligodendrogliomas, like all other infiltrating gliomas, have a very high (almost uniform) rate of recurrence and gradually increase in grade over time. Recurrent tumors are generally treated with more aggressive chemotherapy and radiation therapy. Recently, stereotactic surgery
has proven successful in treating small tumors that have been diagnosed early.
Long-term survival is reported in a minority of patients. With aggressive treatment and close monitoring, it is possible to outlive the typical life expectancies for both low grade and high grade oligodendrogliomas. Westergaard’s
study (1997) showed that patients younger than 20 years had a median survival of 17.5 years. Another study shows a 34% survival rate after 20 years. However, as discussed above, such figures can be misleading since they do not factor in the types of treatment nor the genetic signature of the tumors. As well, such historic data loses significance due to the relatively long survival of patients (compared to other types of brain tumors) and the introduction of newer treatment options over time.
Glioma
A glioma is a type of tumor that starts in the brain or spine. It is called a glioma because it arises from glial cells. The most common site of gliomas is the brain.-By type of cell:...
that are believed to originate from the oligodendrocytes of the brain
Brain
The brain is the center of the nervous system in all vertebrate and most invertebrate animals—only a few primitive invertebrates such as sponges, jellyfish, sea squirts and starfishes do not have one. It is located in the head, usually close to primary sensory apparatus such as vision, hearing,...
or from a glial precursor cell. They occur primarily in adults (9.4% of all primary brain and central nervous system tumors) but are also found in children (4% of all primary brain tumors). The average age at diagnosis is 35 years.
Etiology
The etiologyEtiology
Etiology is the study of causation, or origination. The word is derived from the Greek , aitiologia, "giving a reason for" ....
of oligodendrogliomas is unknown. Some studies have linked oligodendroglioma with a viral cause. A 2009 Oxford Neurosymposium study illustrated a 69% correlation between NJDS gene mutation and the tumor initiation shown by Kevin Smith. A single case report has linked oligodendroglioma to irradiation of pituitary adenoma.
NEJM 867-5309, ed 6, p112-116, Kevin Smith etal
Symptoms
In anywhere from fifty to eighty percent of cases, the first symptom of an oligodendroglioma is the onset of seizureSeizure
An epileptic seizure, occasionally referred to as a fit, is defined as a transient symptom of "abnormal excessive or synchronous neuronal activity in the brain". The outward effect can be as dramatic as a wild thrashing movement or as mild as a brief loss of awareness...
activity. They occur mainly in the frontal lobe
Frontal lobe
The frontal lobe is an area in the brain of humans and other mammals, located at the front of each cerebral hemisphere and positioned anterior to the parietal lobe and superior and anterior to the temporal lobes...
thus affecting personality.
Headaches combined with increased intracranial pressure
Intracranial pressure
Intracranial pressure is the pressure inside the skull and thus in the brain tissue and cerebrospinal fluid . The body has various mechanisms by which it keeps the ICP stable, with CSF pressures varying by about 1 mmHg in normal adults through shifts in production and absorption of CSF...
are also a common symptom of oligodendroglioma. Depending on the location of the tumor, any neurological deficit can be induced, from visual loss, motor weakness and cognitive decline. A Computed Tomography
Computed tomography
X-ray computed tomography or Computer tomography , is a medical imaging method employing tomography created by computer processing...
(CT) or Magnetic Resonance Imaging
Magnetic resonance imaging
Magnetic resonance imaging , nuclear magnetic resonance imaging , or magnetic resonance tomography is a medical imaging technique used in radiology to visualize detailed internal structures...
(MRI) scan is necessary to characterize the anatomy of this tumor (size, location, heter/homogeneity). However, final diagnosis of this tumor
Tumor
A tumor or tumour is commonly used as a synonym for a neoplasm that appears enlarged in size. Tumor is not synonymous with cancer...
, like most tumors, relies on histopathologic examination (biopsy
Biopsy
A biopsy is a medical test involving sampling of cells or tissues for examination. It is the medical removal of tissue from a living subject to determine the presence or extent of a disease. The tissue is generally examined under a microscope by a pathologist, and can also be analyzed chemically...
examination).
Microscopic Appearance
Oligodendrogliomas cannot currently be differentiated from other brain lesions solely by their clinical or radiographic appearance. As such, a brain biopsyBiopsy
A biopsy is a medical test involving sampling of cells or tissues for examination. It is the medical removal of tissue from a living subject to determine the presence or extent of a disease. The tissue is generally examined under a microscope by a pathologist, and can also be analyzed chemically...
is the only method of definitive diagnosis. Oligodendrogliomas recapitulate the appearance of the normal resident oligodendroglia of the brain. (Their name derives from the Greek roots 'oligo' meaning “ few” and 'dendro' meaning “trees”.) They are generally composed of cells with small to slightly enlarged round nuclei with dark, compact nuclei and a small amount of eosinophilic cytoplasm. They are often referred to as "fried egg" cells due to their histologic appearance. They appear as a monotonous population of mildly enlarged round cells infiltrating normal brain parenchyma
Parenchyma
Parenchyma is a term used to describe a bulk of a substance. It is used in different ways in animals and in plants.The term is New Latin, f. Greek παρέγχυμα - parenkhuma, "visceral flesh", f. παρεγχεῖν - parenkhein, "to pour in" f. para-, "beside" + en-, "in" + khein, "to pour"...
and producing vague nodules. Although the tumor may appear to be vaguely circumscribed, it is by definition a diffusely infiltrating tumor.
Classically they tend to have a vasculature of finely branching capillaries that may take on a “chicken wire” appearance . When invading grey matter structures such as cortex, the neoplastic oligodendrocytes tend to cluster around neurons exhibiting a phenomenon referred to as “perineuronal satellitosis”. Oligodendrogliomas may invade preferentially around vessels or under the pial
Pia mater
Pia mater often referred to as simply the pia, is the delicate innermost layer of the meninges, the membranes surrounding the brain and spinal cord. The word finds its roots in Latin, meaning literally "tender mother." The other two meningeal membranes are the dura mater and the arachnoid mater....
surface of the brain.
Oligodendrogliomas must be differentiated from the more common astrocytoma
Astrocytoma
Astrocytomas are a type of neoplasm of the brain. They originate in a particular kind of glial-cells, star-shaped brain cells in the cerebrum called astrocytes. This type of tumor does not usually spread outside the brain and spinal cord and it does not usually affect other organs...
. Non-classical variants and combined tumors of both oligodendroglioma and astrocytoma differentiation are seen, making this distinction controversial between different neuropathology
Neuropathology
Neuropathology is the study of disease of nervous system tissue, usually in the form of either small surgical biopsies or whole autopsy brains. Neuropathology is a subspecialty of anatomic pathology, neurology, and neurosurgery...
groups. In the US, in general, neuropathologists trained on the West Coast are more liberal in the diagnosis of oligodendroliomas than either East Coast or Midwest trained neuropathologists who render the diagnosis of oligodendroglioma for only classic variants. Molecular diagnostics may make this differentiation obsolete in the future.
Other glial
Glioma
A glioma is a type of tumor that starts in the brain or spine. It is called a glioma because it arises from glial cells. The most common site of gliomas is the brain.-By type of cell:...
and glioneuronal tumors with which they are often confused due to their monotonous round cell appearance include pilocytic astrocytoma
Pilocytic astrocytoma
Pilocytic astrocytoma or juvenile pilocytic astrocytoma or cystic cerebellar astrocytoma is a neoplasm of the brain that occurs more often in children and young adults...
, central neurocytoma, the so-called dysembryoplastic neuroepithelial tumor, or occasionally ependymoma
Ependymoma
Ependymoma is a tumor that arises from the ependyma, a tissue of the central nervous system. Usually, in pediatric cases the location is intracranial, while in adults it is spinal. The common location of intracranial ependymoma is the fourth ventricle...
.
Histopathological Grading
The histopathologic grading of oligodendrogliomas is controversial. Currently the most commonly used grading schema is based on year 2007 World Health OrganizationWorld Health Organization
The World Health Organization is a specialized agency of the United Nations that acts as a coordinating authority on international public health. Established on 7 April 1948, with headquarters in Geneva, Switzerland, the agency inherited the mandate and resources of its predecessor, the Health...
(WHO) guidelines. Oligodendrogliomas are generally dichotomized into grade II (low grade) and grade III (high grade) tumors. The designation of grade III oligodendroglioma (high grade) generally subsumes the previous diagnoses of anaplastic or malignant oligodendroglioma.
Unfortunately, the WHO guidelines include subjective criteria in differentiating grade II and grade III tumors including the appreciation of “significant” hypercellularity and pleomorphism in the higher grade lesion. In addition, the presence of low mitotic activity, vascular proliferation and necrosis, including pseudopallisading necrosis are insufficient by themselves to elevate the grade of these tumors. This leads to inevitable interobserver variability in diagnosis by pathologists. The ultimate responsibility for making treatment decisions and interpretation of these diagnoses lies with the oncologist in consultation with the patient and their family.
It has been proposed that WHO
World Health Organization
The World Health Organization is a specialized agency of the United Nations that acts as a coordinating authority on international public health. Established on 7 April 1948, with headquarters in Geneva, Switzerland, the agency inherited the mandate and resources of its predecessor, the Health...
guidelines should contain a category for grade IV oligodendrogliomas which essentially appear to be glial neoplasms with overwhelming features of glioblastoma multiforme
Glioblastoma multiforme
Glioblastoma multiforme is the most common and most aggressive malignant primary brain tumor in humans, involving glial cells and accounting for 52% of all functional tissue brain tumor cases and 20% of all intracranial tumors. Despite being the most prevalent form of primary brain tumor, GBMs...
(GBM) arising from known lower grade oligodendrogliomas or GBM with a significant proportion of oligodendroglial differentiation. The diagnostic utility of this latter category is uncertain as these tumors may behave either like glioblastoma or grade III oligodendrogliomas. As such, this is an exceptionally unusual diagnosis.
The updated WHO guidelines published in 2007 recommends classifying such tumors for the time being as ‘glioblastoma with oligodendroglioma component’. It remains to be established whether or not these tumors carry a better prognosis than standard glioblastomas.
Molecular genetics
By far, the most common structural deformity found is co-deletion of chromosomal arms 1p and 19q. The high frequency of co-deletion is a striking feature of this glial tumour and is considered as a "genetic signature" of oligodendroglioma. Allelic losses on 1p and 19q, either separately or combined, are more common in classic oligodendrogliomas than in either astrocytomas or oligoastrocytomas. In one study, classic oligodendrogliomas showed 1p loss in 35 of 42 (83%) cases, 19q loss in 28 of 39 (72%), and these were combined in 27 of 39 (69%) cases; there was no significant difference in 1p/19q loss of heterozygosity status between low-grade and anaplastic oligodendrogliomas. 1p/19q co-deletion has been correlated with both chemosensitivity and improved prognosis in oligodendrogliomas. The gene products lost as a consequence of this codeletion may include mediators of resistance to genotoxic therapies. Alternatively, 1p/19q loss might be an early oncogenic lesion promoting the formation of glial neoplasms, which retain high sensitivity to genotoxic stress. Most larger cancer treatment centers routinely check for the deletion of 1p/19q as part of the pathologyPathology
Pathology is the precise study and diagnosis of disease. The word pathology is from Ancient Greek , pathos, "feeling, suffering"; and , -logia, "the study of". Pathologization, to pathologize, refers to the process of defining a condition or behavior as pathological, e.g. pathological gambling....
report for oligodendrogliomas. The status of the 1p/19q loci can be detected by FISH, loss of heterozygosity (LOH) analysis or virtual karyotyping
Virtual Karyotype
Virtual karyotype detects genomic copy number variations at a higher resolution level than conventional karyotyping or chromosome-based comparative genomic hybridization .-Background:...
. Virtual karyotyping has the advantage of assessing the entire genome in one assay, as well as the 1p/19q loci. This allows assessment of other key loci in glial tumors, such as EGFR and TP53 copy number status.
Whereas the prognostic relevance of 1p and 19q deletions is well established for anaplastic oligodendrogliomas and mixed oligoastrocytomas, the prognostic relevance of the deletions for low-grade gliomas is more controversial. In terms of low-grade gliomas, a recent study also suggests that 1p/19q co-deletion may be associated with a (1;19)(q10;p10) translocation which, like the combined 1p/19q deletion, is associated with superior overall survival and progression-free survival in low-grade glioma patients. Oligodendrogliomas show only rarely mutations in the p53 gene, which is in contrast to other gliomas. Epidermal growth factor receptor
Epidermal growth factor receptor
The epidermal growth factor receptor is the cell-surface receptor for members of the epidermal growth factor family of extracellular protein ligands...
amplification and whole 1p/19q codeletion are mutually exclusive and predictive of completely different outcomes, with EGFR amplification predicting poor prognosis. There is a strong correlation between 1p/19q codeletion and the expression of proneural genes, suggesting that gliomas with a 1p19q codeletion represent a subgroup of proneural gliomas.
Prognosis & treatment
Oligodendrogliomas are generally felt to be incurable using current treatments. However compared to the more common astrocytomas, they are slowly growing with prolonged survival. In one series, medianMedian
In probability theory and statistics, a median is described as the numerical value separating the higher half of a sample, a population, or a probability distribution, from the lower half. The median of a finite list of numbers can be found by arranging all the observations from lowest value to...
survival times for oligodendrogliomas were 11.6 years for grade II and 3.5 years for grade III.
However, such figures can be misleading since they do not factor in the types of treatment nor the genetic signature of the tumors. A recent study analyzed survival based on chromosomal deletions and the effects of radiation or chemotherapy as treatment, with the following results (both low-grade and anaplastic oligodendrogliomas): 1p/19q deletion with radiation = 121 months (mean), 1p/19q deletion with chemotherapy = over 160 months (mean not yet reached), no 1p/19q deletion with radiation = 58 months (mean), and no 1p/19q deletion with chemotherapy = 75 months (mean). Another study divided anaplastic oligodendrogliomas into the following four clinically relevant groups of histology with the following results: combined 1p/19q loss = median survival was >123 months (not yet reached), 1p loss only = median survival was 71 months, 1p intact with TP53 mutation = median survival 71 months, and 1p intact with no TP53 mutation = median survival was 16 months.
Because of the indolent nature of these tumors and the potential morbidity associated with neurosurgery
Neurosurgery
Neurosurgery is the medical specialty concerned with the prevention, diagnosis, treatment, and rehabilitation of disorders which affect any portion of the nervous system including the brain, spine, spinal cord, peripheral nerves, and extra-cranial cerebrovascular system.-In the United States:In...
, chemotherapy
Chemotherapy
Chemotherapy is the treatment of cancer with an antineoplastic drug or with a combination of such drugs into a standardized treatment regimen....
and radiation therapy
Radiation therapy
Radiation therapy , radiation oncology, or radiotherapy , sometimes abbreviated to XRT or DXT, is the medical use of ionizing radiation, generally as part of cancer treatment to control malignant cells.Radiation therapy is commonly applied to the cancerous tumor because of its ability to control...
, most neurooncologists
Oncology
Oncology is a branch of medicine that deals with cancer...
will initially pursue a course of watchful waiting
Watchful waiting
Watchful waiting is an approach to a medical problem in which time is allowed to pass before medical intervention or therapy is used. During this time, repeated testing may be performed....
and treat patients symptomatically. Symptomatic treatment often includes the use of anticonvulsants for seizures and steroids
Glucocorticoid
Glucocorticoids are a class of steroid hormones that bind to the glucocorticoid receptor , which is present in almost every vertebrate animal cell...
for brain swelling. PCV chemotherapy (Procarbazine
Procarbazine
Procarbazine Procarbazine Procarbazine (Matulane (US), Natulan (Canada), Indicarb (India) is an antineoplastic chemotherapy drug for the treatment of Hodgkin's lymphoma and certain brain cancers (such as Glioblastoma multiforme). It is a member of a group of medicines called alkylating agents. It...
, CCNU
Lomustine
Lomustine is an alkylating nitrosourea compound used in chemotherapy. It is in the same family as streptozotocin. This is a highly lipid soluble drug, and thus crosses the blood brain barrier. This property makes it ideal for treating brain tumors, and is its primary use...
and Vincristine
Vincristine
Vincristine , formally known as leurocristine, sometimes abbreviated "VCR", is a vinca alkaloid from the Catharanthus roseus , formerly Vinca rosea and hence its name. It is a mitotic inhibitor, and is used in cancer chemotherapy.-Mechanism:Tubulin is a structural protein that polymerizes to...
) has been shown to be effective and was the most commonly used chemotherapy regimen used for treating anaplastic oligodendrogliomas, but is now being superseded by a newer drug: Temozolomide. Temozolomide
Temozolomide
Temozolomide Temozolomide Temozolomide (brand names Temodar and Temodal is an oral alkylating agent which can be used for the treatment of Grade IV astrocytoma — an aggressive brain tumor, also known as glioblastoma multiforme as well as melanoma, a form of skin cancer...
is a common chemotherapeutic drug to which oligodendrogliomas appear to be quite sensitive. It is often used as a first line therapy, especially because of its relatively mild side effects when compared to other chemotherapeutic drugs.
Nevertheless, a retrospective study on 1054 patients with anaplastic oligodendroglioma, presented during the 2009 ASCO Annual Meeting, suggests that PCV therapy may be superior in efficacy to the newer temozolomide therapy. Median time to progression for patients with 1p19q co-deletion was longer following PCV alone (7.6 years) than with temozolomide alone (3.3 years); median overall survival was also longer with PCV treatment versus temozolomide treatment (not reached, vs. 7.1 years).
The standard dosing schedule of temozolomide is 5 consecutive days of daily dosing during 28 day cycles. However, different dosing schedules may produce better results, such as continuous daily dosing using lower amounts of drug (e.g. 21 day dosing during 28 day cycles). As an example of an altered dosing schedule, promising results have been shown using lower daily doses on each day for 7 weeks, followed by a 4 week off periods. Regarding the duration of dosing, for oligodendrogliomas the duration prescribed by oncologists varies considerably and seems to range from 6 cycles to over 32 cycles (i.e. over 3 years). In one study, researchers compared patients who received temozolomide for at least 12 months on the 5/28 day cycle, dividing such patients into two groups: "short term" patients receiving temozolomide for 12-18 cycles and those "long term" patients receiving 19 or more cycles (range was 19 to 32 cycles). Researches found that there was a statistically significant advantage for "long term" treatment (median progression free survival for "short term" patients was 95 weeks (follow up of 73 weeks), but for "long term" patiets the median progression free survival was not yet reached (follow up of 134 weeks)).
Because of their diffusely infiltrating nature, oligodendrogliomas cannot be completely resected and are not curable by surgical excision
Surgery
Surgery is an ancient medical specialty that uses operative manual and instrumental techniques on a patient to investigate and/or treat a pathological condition such as disease or injury, or to help improve bodily function or appearance.An act of performing surgery may be called a surgical...
. If the tumor mass compresses adjacent brain structures, a neurosurgeon
Neurosurgery
Neurosurgery is the medical specialty concerned with the prevention, diagnosis, treatment, and rehabilitation of disorders which affect any portion of the nervous system including the brain, spine, spinal cord, peripheral nerves, and extra-cranial cerebrovascular system.-In the United States:In...
will typically remove as much of the tumor as he or she can without damaging other critical, healthy brain structures. Surgery may be followed up by chemotherapy
Chemotherapy
Chemotherapy is the treatment of cancer with an antineoplastic drug or with a combination of such drugs into a standardized treatment regimen....
, radiation
Radiation
In physics, radiation is a process in which energetic particles or energetic waves travel through a medium or space. There are two distinct types of radiation; ionizing and non-ionizing...
, or a mix of both, but recent studies suggest that radiation does not improve overall survival (even when age, clinical data, histological grading, and type of surgery are considered), and should be avoided when treating oligodendrogliomas. However, it is possible that radiotherapy may prolong the overall time to progression.
Oligodendrogliomas, like all other infiltrating gliomas, have a very high (almost uniform) rate of recurrence and gradually increase in grade over time. Recurrent tumors are generally treated with more aggressive chemotherapy and radiation therapy. Recently, stereotactic surgery
Stereotactic surgery
Stereotactic surgery or stereotaxy is a minimally invasive form of surgical intervention which makes use of a three-dimensional coordinates system to locate small targets inside the body and to perform on them some action such as ablation, biopsy, lesion, injection, stimulation, implantation,...
has proven successful in treating small tumors that have been diagnosed early.
Long-term survival is reported in a minority of patients. With aggressive treatment and close monitoring, it is possible to outlive the typical life expectancies for both low grade and high grade oligodendrogliomas. Westergaard’s
study (1997) showed that patients younger than 20 years had a median survival of 17.5 years. Another study shows a 34% survival rate after 20 years. However, as discussed above, such figures can be misleading since they do not factor in the types of treatment nor the genetic signature of the tumors. As well, such historic data loses significance due to the relatively long survival of patients (compared to other types of brain tumors) and the introduction of newer treatment options over time.
External links
- Clinical Trials and Noteworthy Treatments for Brain Tumors
- Brain and Spinal Tumors: Hope Through Research (National Institute of Neurological Disorders and Stroke)
- SDBTT Astro Fund: funding research and offering support to those affected by low-grade oligodendrogliomas
- CT and MR Scans Classic Radiology Imaging of Oligodendroglioma