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Thread: Introduction to Brain Cancers

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    Introduction to Brain Cancers

    Introduction to primary brain cancers and their treatment

    This introduction concerns primary brain tumors, which originate in the brain. It does not cover metastases of other cancers which spread to the brain (“brain mets”). Primary brain tumors do not metastasize to elsewhere in the body, except rarely to the spine, with the exception of a very rare type called a gliosarcoma.

    There are several types of primary brain cancers that occur in adults. This paper will focus on those that occur primarily in the cerebrum, the largest part of the brain.

    Grading System
    Brain tumors are graded from I to IV. Please note that brain cancers are spoken of in “grades” rather than “stages”.
    1. Grade I: Tumors classified as Grade I are low-grade tumors that grow very slowly. Often, people who have a Grade I tumor are thought to have been born with it. Grade I tumors are sometimes considered to be benign tumors. They account for around 50% of all brain tumors.
    2. Grade II: These tumors also grow slowly. However, they do have a greater tendency to recur and to spread into nearby tissue.
    3. Grade III: Grade III tumors grow rapidly.They are very likely to spread. Under a microscope, Grade III cells look very different from normal cells. Grades II and III account for around 25% of tumors
    4. Grade IV: Grade IV tumors grow and spread rapidly, often causing a midline shift. They grow so fast that they grow faster than their blood supply can support. Therefore, Grade IV brain cancers often have areas of necrotic cells. Prognosis is poor, although there are long term survivors. Grade IV accounts for around 25% of tumors.

    Grade II and Grade III tumors have a tendency to mutate to higher grades over time, although this does not always happen. Higher grade tumors have a tendency to recur after treatment, but this is not invariably the case.
    Last edited by Lboy; 02-21-2014 at 12:09 AM.
    Wife died from a GBM, November 2012. The full story in this thread

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    Types of Brain Tumors

    Astrocytomas (“Astros”)
    Astrocytes are a type of glial cell, so sometimes cancers formed from Astrocytes are called gliomas. The astrocytes, as well as other glial cells, are the structural cells of the brain. Like the iron work of a building, astrocytes serve as the structure of the cerebrum. There are a number of subtypes of Astrocytomas based on where they occur.
    1. Diffuse Astrocytomas (Grade II): Although Diffuse Astrocytomas grow slowly, they do tend to spread into nearby tissue. They also often change into higher grade tumors. Astrocytomas can occur in any part of the brain but usually occur in the cerebrum.
    2. Anaplastic astrocytoma (Grade III): Anaplastic tumors grow rapidly. They also will spread into nearby areas. It is common for Anaplastic tumors to change over time into Gliobastomas (Grade IV) tumors. Anaplastic astrocytoma is abbreviated to "AA" or “AA3” on most forums.
    3. Glioblastomas (Grade IV): Most glioblastomas grows extremely fast. They tend to extend tendrils into healthy brain tissue from a central tumor core. Gliobastomas are rare in children and young adults Gliobastoma is also known as glioblastoma multiforme. Glioblastoma is the most common form of brain cancer in adults. On the forum it is usually called GBM or GBM4.

    Oligodendroglioma Tumors
    (“Oligos”)
    Another type of glial cells that help maintain a healthy brain are the oligodendrocytes. Since oligodendrocytes are also glial cells, cancer formed from them are also called gliomas.
    • Oligodendroglioma (Grade II): An Oligodendroglioma grows and spreads slowly. Under a microscope, the Oligodendroglioma cells look almost like normal oligodendrocytes. They are given a classification of Grade II because they tend to spread and they do tend to upgrade with time.
    • Anaplastic Oligodendroglioma (Grade III): Cells of an Anaplastic Oligodendroglioma look significantly different from normal Oligodendrocytes. Unlike Astrocytomas, an Anaplastic Oligodendroglioma can either grow in one spot or in many spots in the brain.


    Mixed Gliomas

    A Mixed Glioma is quite literally formed from a mixture of astrocytes and oligodendrocytes and therefore shares characteristics of both.
    • Oligoastrocytoma (Grade II): These tumors are slow growing and slow spreading tumors. The cells look almost like normal ones.
    • Anaplastic Oligoastrocytoma (Grade III): Cells of an Anaplastic Oligoastrocytoma show significant changes from normal ones.
    Some doctors use the term "Mixed Grade Glioma" to characterize gliomas that contain 2 or more grades.

    Pineal Parenchymal Tumors

    A Pineal Parenchymal tumor is formed by parenchymal cells also called pineocytes. They often occur in adults and are relatively rare. They are divided into:
    • Pineocytomas (Grade II): This is a slow growing tumor that rarely occurs in children.
    • Pineoblastomas (Grade III): Pineoblastomas do spread. These tumors are rare and are more common in children.
    Although there are many other types of brain cancers, these are the major ones.
    Wife died from a GBM, November 2012. The full story in this thread

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    Causes
    The causes of brain tumors remain obscure. There are some known risk factors, but they explain relatively few cases. Here is a list of a few of the most common ones:
    • Exposure to vinyl chloride (not PVC, vinyl chloride is the substrate that PVC is made from)
    • Exposure to radiation
    • Infection by the Epstein-Barr virus
    • Genetic syndromes like neurofibromatosis, tuberous sclerosis, Von Hippel-Lindau disease, Li-Fraumeni sydrome, and Turcot syndrome
    Wife died from a GBM, November 2012. The full story in this thread

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    Symptoms
    Symptoms vary considerably from one individual to the next and are affected by type, size, and location of the tumor. Some common symptoms:
    • Seizures
    • Headaches
    • Nausea and vomiting
    • Dysfunction in vision, hearing or speech (aphasia)
    • Weakness on one side of the body
    • Balance problems
    • Personality changes
    • Rarely, a tumor may “bleed out” and cause a brain hemorrhage
    Please note that many of these symptoms are more likely to have some other cause, such as anxiety or sinus congestion. Beware of “Dr. Google!
    Last edited by Lboy; 02-25-2014 at 11:50 PM.
    Wife died from a GBM, November 2012. The full story in this thread

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    Diagnostic Tests
    • CT Scan: A CAT Scan, or Computed Tomography, is an imaging technique using X-Rays to produce a three dimensional image of an organ. X-rays and CT scans do not, however, provide tumor details and an MRI is required in order to confirm that a brain tumor is present.
    • MRI: An MRI, or Magnetic Resonance Imaging, is an imaging technique that uses a strong magnetic field rather than X-Rays. It takes advantage of the magnetic properties or water atoms in the body. Under a strong magnetic field, those atoms will align themselves with the magnetic field. This technique is also called NMRI (nuclear magnetic resonance imaging). An MRI produces a great contrast between soft tissues in the body so is ideal for brain scans. The details of a tumor are enhanced if a weakly radioactive tracer is injected, which lights up the tumor cells on an MRI. This is known as an MRI with contrast
    • Angiogram: An angiogram is used to study the blood flow to the tumor. This may be used in making a prediction of how fast the tumor might be able to grow and in decisions about doing surgery.
    • Biopsy: The only way to be 100% sure of a diagnosis is by examining under a microscope a sample of the abnormality. While this procedure is invasive, it is not very dangerous and almost always conducted, or a sample is taken from surgery to remove a tumor identified from an MRI. Most people recover very quickly with few if any side effects.
    o If the tumor is deemed operable, a craniotomy is performed by a neurosurgeon and as much of the tumor as possible is removed.
    o If the tumor is deemed inoperable, a needle biopsy will often be possible, in which tissue is removed for analysis.
    o In either case, the tissue is examined initially during the surgery, and then sent to a laboratory for further analysis. A pathology report will come back, usually within a week after the surgery, identifying the type of tumor.
    Wife died from a GBM, November 2012. The full story in this thread

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    Prognosis
    Prognosis is the statistical expectation of how long the patient is likely to live. Note that there is substantial and unpredictable variation and no definite figure can be given for an individual. Generally, survival times given are medians, not “averages”. Median survival time is the time from diagnosis at which 50% of initially diagnosed patients are still alive.

    Some factors that affect the prognosis are:
    • Specific type and grade of the tumor
    • Specific location of the tumor
    • The age of the patient
    • Size of the tumor
    • Whether or not a significant part of the tumor can be surgically removed.
    • Whether chemo methylates the DNA in a tumor (see treatment options section below)
    • Whether or not the 1p/19q genes are deleted for oligodendrogliomas (see standard treatment section below)
    • Whether or not the tumor is a recurrence of a previous tumor
    • Other health problems the patient might have
    Wife died from a GBM, November 2012. The full story in this thread

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    Treatment Options
    There are three basic types of treatment available to patients with brain cancers:
    Surgery: When surgery is possible, it is strongly advised. It is the best way to remove a significant portion of the tumor. From the patient's perspective, compared to other surgeries brain surgery is relatively easy. Recovery is often in less than one week. Most malignant tumors are diffuse with tendrils extending into healthy brain tissue, and thus cannot be wholly excised by surgery (this is most pronounced with grade IVs). Some tumors are inoperable because they are too deep in the brain, and surgery would cause excessive damage to brain functions. There are borderline candidates for surgery, in which case patients are advised to obtain at least two opinions from reputable neurosurgeons.

    Radiation Therapy: Radiation Therapy (RT) involves irradiating the brain or part of it with some type of radiation, usually X rays. There are several ways of doing this. The particular option chosen depends on the size and location of the tumor or area of concern. The total amount of radiation that a brain can receive during the life time of the patient is limited. This limit needs to be taken into account when making treatment decisions, and for this reason RT can usually only be administered once, unlike chemo or surgery.
    1. Whole Brain Radiation Therapy (WBRT): As the name implies, involves irradiation of the whole brain. It is hardly ever used with primary brain cancers, and because of potentially serious side effects is generally not recommended.
    2. Steriotactic Radiation: There are several forms of this therapy. All of them involve use of beams of X rays aimed only at the tumor or tumor bed, and defined margin of surrounding tissue to try to destroy invasive tendrils. Since the medical team can aim the beams from different directions, it is possible to use lower levels of radiation. Aimed at the tumor, this limits the amount of radiation to other parts of the brain. Maximum dosage is delivered where the beams cross at the tumor.
    3. Internal Radiation Therapy: This procedure involves using a catheter to place small radiation "seeds" into the middle of the cancer, or inserting wafers after surgery. This is not often used.
    4. Targeted radiotherapy (cyberknife). Highly focused radiotherapy, not usually used for brain tumors because of their diffuse nature, except for some inoperable grade I tumors and some well defined small tumors under 1cm diameter, usually at recurrence.
    5. Proton beam therapy. Uses protons instead of high energy photon (X ray) beams. In theory this does less damage to healthy tissues (the beam will stop at the tumor, unlike X rays), but there is little data to go on, as there are so few facilities worldwide due to the huge cost (upwards of $100 million for a single installation). Where available, use is prioritised for otherwise hard to reach and easily damaged locations, such as brain stem tumors.

    Chemotherapy: There are a number of oral and intravenous medications that can be used to treat brain cancers. The major problem is that many chemicals used for other cancers will not cross the brain-blood barrier. Special chemotherapy agents have been developed in order to do so.
    The most commonly used chemo is temozolomide (TMZ, called Temodar in the USA and Temodal elsewhere) which is given orally, in pill form. This acts by adding a methyl (CH3) radical to the tumor cell DNA, which inhibits cell division and thus tumor growth. Around 50% of people have a gene which partly undoes the methylation, and for them temozolomide is less effective, but they still benefit and it is the best treatment available. Older chemos are PCV, CCNU and BCNU, whose use is generally restricted to tumor recurrence if the tumor appears to have acquired resistance to temozolomide. There is some (inconclusive) evidence that PCV may be more effective for oligos.


    Other treatments
    Gliadel wafers. During surgery, after the tumor has been removed, wafers containing the chemo carnustine may be placed in the tumor bed. These then dissolve.

    Stereotactic laser ablation also known as LITT (llaser interstitial thermal therapy) . This is a new technique which involves inserting a fine wire into the tumour area, through which a laser beam is passed to heat the tumour cells to around 50 deg C which destroys them. This is normally done in real time in an MRI machine, in order to position the wire and monitor progress of tumour destruction. It is claimed that this can be used on tumours which are otherwise inoperable, and is less invasive than surgery.
    See: http://thejns.org/doi/full/10.3171/2014.9.FOCUS14471

    Antiangiogenic Agents that work by hindering the growth of blood vessels in the tumor The most common is Avastin, whose use is presently (2014) restricted to treating tumor recurrence. Avastin works by preventing blood vessel formation in GBM patients whose tumor expresses VEGF (vascular endothelial growth factor). It may halt tumor growth temporarily in about 40% of patients. Subject to insurance access (it is very expensive) it is routinely given at first recurrence in the US, sometimes prescribed at recurrence in Asia, Australia, and Canada, but rarely used in Europe.

    Targeted Vaccines. This is a new development still at the clinical trials stage, whereby a specially prepared sample of tumor, from biopsy or surgery, is used to prepare an individualized vaccine to boost the patient’s immune response to the cancer. It is usually restricted to newly diagnosed patients, although trials exist for recurrent GBM. Patients with a grade III or grade IV cancer may wish to see if they can take part in such a trial. Note that some trials are “double blind” and half the patients receive a placebo. Surgery must usually be performed at the hospital doing the research.

    Other drugs. There is some evidence that temozolomide is more effective when combined with other drugs; tumor cells are diverse, mutate rapidly, and some will inevitably be resistant to temozolomide, thus suggesting the need for several different agents. Suggested drugs include chloroquine, celebrex, and accutane, which could be combined in a drug cocktail. These and other anti-cancer agents which penetrate the blood –brain barrier are discussed by Ben Williams, a very long term glioblastoma survivor,, in this article:
    http://www.virtualtrials.com/williams.cfm

    which can be freely downloaded. Note that administering such combinations are not officially approved treatments and not part of standard treatment protocols, and would need to be discussed with your neuro-oncology team.

    another good reference to the 'cocktail' approach is http://astrocytomaoptions.com/

    Novocure. Not a drug, but a headgear worn by the patient which transmits electrical fields which allegedly disturb tumor cell division. Authorised by the FDA for clinical trials in the USA for:
    - recurrent glioblastoma, when other treatment options have been exhausted
    - recently for newly diagnosed glioblastoma, as a complement to temozolomide in the “maintenance” phase
    A recent clinical trial showed a promising increase in median survival times, 2 year survival rates were noticeably improved. This suggests that newly diagnosed patients would be well advised to enquire about its use as a complement to the standard radiotherapy+temozolomide treatment. Patients need to shave the scalp daily, and carry batteries around. There appear to be no side effects. Also authorised for use in the EU, Switzerland, Australia and Japan. Marketed as "Optune" in the USA.
    Last edited by NikosF; 05-19-2015 at 10:56 PM. Reason: added reference for LITT
    Wife died from a GBM, November 2012. The full story in this thread

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    Standard Treatment Protocols

    Note that these are standard treatments, and in individual cases neuro-oncologists may vary them.

    • Surgery, if feasible, is the first step for all tumors; cyberknife may be appropriate for some otherwise inoperable small tumors.

    • For glioblastomas and for grade 3 astrocytomas and mixed gliomas, the usual subsequent treatment (“Stupp protocol”) is six weeks of daily stereotactic radiotherapy (for 5 minutes or so) combined with a pill of temozolomide, usually a hour or two before the RT (the temozolomide acts to make the tumor cells more sensitive to the radiation). There is normally a 4-8 week gap after surgery to allow the brain to recover before commencing treatment. This treatment may be curtailed for patients in poor condition, but most stand up to it with relatively few side effects, mainly tiredness in the last few weeks of treatment and a few weeks after. Most patients need to take an anti-nausea pill before the temozolomide, and may need a low dose of steroids to counter brain swelling . Hair will usually be lost in patches where the radio beams are focused, it usually regrows but may be slow to do so.

    • After the initial treatment, patients are put on a “maintenance dose” of temozolomide 5 days a month, at a higher dose (typically 300mg), for six to twelve months or as long as blood counts can stand it. At this dose, temozolomide does hit the red and white blood cell count and these need to be carefully monitored. It is strongly recommended that grade III or grade IV patients have MRIs with contrast at least every three months to check progress and to monitor for recurrence.

    • For oligodendrogliomas, a key issue is whether two genes called 1p and 19q are absent in the tumor cells. If these have been deleted , which occurs in around 80% of cases, this makes the tumor cells very sensitive to chemo and improves prognosis. In these cases the normal procedure is to administer chemo (may be temozolomide or PCV) and keep RT in reserve in case of recurrence. This order may be reversed for patients without deletions.

    For grade II tumors, treatment may be more personalised. In some cases where the tumor is slow growing and causing few if any side effects patients may be put on “watch and wait” with regular MRIs.

    In approximately 70% of lower grade gliomas (grade II or grade III astrocytomas or mixed gliomas) two genes called IDH1 and IDH2 (isocitrate dihydrogenase) are mutated. This assists methylation of the tumor, making it more sensitive to chemo. In this case chemo (usually temozolomide) will usually be the first recourse when a grade II tumor reaches the size or symptoms requiring treatment.
    Last edited by Lboy; 02-25-2014 at 09:42 AM.
    Wife died from a GBM, November 2012. The full story in this thread

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    Other medications
    A variety of supporting medications may be needed to counter tumor effects. Two of the most common are:

    Dexamethasone (“Dex”, sometimes under the brand Decadron). This is a powerful steroid which is effective at countering brain pressure (and its effects) from a tumor. It does however have considerable side effects , which can include a surge in appetite, weight gain, muscle wastage , Cushing’s syndrome (“hamster cheeks”), a rise in blood sugar, and irritability. Doctors thus aim to provide the minimum dose to counter tumor effects, and reduce it wherever possible – but reduction must be done gradually to allow the body’s natural steroids to resume, as dex suppresses them . The natural herbal remedy boswellia reduces brain pressure without these side effects, but is less powerful than dex. Consult your neuro-oncologist before using boswellia.

    Levetiracetam (Keppra), the most commonly prescribed anti-epileptic to prevent seizures.
    Last edited by Lboy; 02-25-2014 at 09:30 AM.
    Wife died from a GBM, November 2012. The full story in this thread

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    Supplements
    At CancerForums we most strongly do not support the idea of solely relying on “natural” cures for cancer. Conventional medical treatment is best. However there may be some benefit to adding some harmless natural supplements with reputed anti-cancer properties to the conventional treatment, but this should be discussed with your neuro-oncology team. This is discussed in this thread and in the article by Ben Williams mentioned above. Most of these supplements can be readily purchased e.g in health food shops.
    Last edited by Lboy; 09-24-2014 at 09:37 AM.
    Wife died from a GBM, November 2012. The full story in this thread

 

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