Brain Cancer

The brain and spinal column make up the central nervous system where vital functions such as thought, speech and bodily movement are controlled. A brain tumor begins when normal cells in the brain mutate and grow uncontrollably, forming a tumor. Brain tumors can be low grade (slow growing) or high grade (fast growing).

A brain tumor is an abnormal growth of tissue in the brain or central spine that can disrupt proper brain function. Doctors refer to a tumor based on where the tumor cells originated, and whether they are cancerous (malignant) or not (benign).

Benign: Benign tumors are the least aggressive type of brain tumor. They originate from cells within or surrounding the brain, do not contain cancer cells, grow slowly, and typically have clear borders that do not spread to other tissue.

Malignant: Malignant brain tumors contain cancer cells and often do not have clear borders. They are considered to be life threatening because they grow rapidly and invade surrounding brain tissue.

Primary: Primary brain tumors start in cells of the brain and are called primary brain tumors. Primary brain tumors may spread to other parts of the brain or to the spine, but rarely to other organs.

Metastatic: Metastatic brain tumors begin in another part of the body and then spread to the brain. These tumors are more common than primary brain tumors and are named by the location in which they begin.

Brain Cancers are categorized by the type of brain cell or by the location in the brain where it first develops. The most common primary brain tumors are gliomas, which originates in the glial tissue, which is a supportive cell in the brain. There are two main types of supportive cells: astrocytes and olidendrocytes. Most gliomas are either called astrocytoma or oligodendroglioma.

Astrocytomas develop from small, star shaped cells called astrocytes in the brain or spinal cord. They most often occur in the cerebrum, which is responsible for sensory imput, speech, and movement.

Oligodendrogliomas develop from oligodendrocyte cells, which are responsible for making the myelin, a protein and fat substance that surrounds the nerves.

Ependymomas are brain tumors that originate in the ependyma (a membrane lining the canal of the spinal chord and ventricles of the brain).

Brain Stem Gliomas are tumors which start in the glial cells of the brain stem.

Mixed Gliomas are tumors which include more than one type of glioma cell types.

Gliomas are given a grade, which is a measure of how close to normal cells the tumor looks under a microscope.

Grade I: Pilocytic Astrocytoma
Grade II: Diffuse Astrocytoma
Grade III: Anaplastic Astrocytoma
Grade IV: Glioblastoma (Glioblastoma multiforme GBM)
Brain Stem Gliomas originate in the brain stem, the lowest part of the brain, connecting the brain and spinal cord.

Acoustic Scwannoma is a tumor that begins in a nerve in the inner ear, called the Vestibular Nerve, and is usually benign.

Craniopharyngiomas are benign tumors that begins near the pituitary gland (at the base of the brain).

Medulloblastomas are rare cancers which originate in the cerebellum. Also called PNET, medulloblastomas often spread through the cerebrospinal fluid (CSF) to other locations in the brain and spine.

Meningiomas are the most common type of primary brain tumors. They begin in the meninges (the membranes that envelop and protect the central nervous system). They are generally non cancerous.

Pineal Gland and Pituitary Gland Tumors are abnormal growths that develop in and around the pineal gland (the small endocrine gland pituitary glands, and can cause excessive or abnormally low production of hormones that regulate important functions in the body.

Primary Central Nervous System Lymphoma Is a form of lymphoma that begins in the lymphatic system (a network of organs that carry a fluid called lymph throughout the body). Primary CNS Lymphoma begins when lymphocytes in the brain, spinal chord, meminges or eyes becomes malignant and begin to spread.

The treatment of brain cancer depends on the size and location of the tumor, and whether the cancer has spread within the central nervous system. The treatment options for primary brain cancer include:

Surgery
Surgery is usually the most effective first line of treatment for brain cancer, sometimes using GammaKnife and CyberKnife radiosurgery.

Radiation
Radiation therapy uses X-rays to kill cancer cells or slow their growth. Treatments include external radiation therapy and internal radiation therapy (which employs seeds or catheters containing radioactive compounds that are targeted to locations into or near the cancer), intensity modulated radiation therapy (IMRT), image guided radiation therapy (IGRT), and gamma knife radiosurgery.

Chemotherapy
Chemotherapy for glioblastomas and both high and low grade gliomas include Temozolomide (Temodar), Carmustine (BCNU) and Lomustine (CCNU), and for oligodendrogliomas, treatments may include Temozolomide or a combination of treatments called PCV (Procarbazine, CCNU, and vincristine).

Targeted Therapy
Targeted Therapy and new kinds of chemotherapy include angiogenesis inhibitors such as Bevacizumab (Avastin) which prevent the tumor to develop new blood vessels, growth factor inhibitors (EGRF) which block the growth receptors of tumors, and new drugs which target the specific gene changes in the tumor.

Immunotherapy Treatments
Immunotherapy use the patient’s own immune system to stop tumor growth, employing monoclonal antibodies which attach to proteins of cancer cells.

Brain metastases are cancer cells that have spread to the brain from primary tumors in other organs in the body. An estimated 24-45% of all cancer patients in the United States have brain metastases.

Treatment options depend on the primary tumor type, and the stage of the disease. Therapies include:
Radiation Therapy (WBRT whole brain radiation therapy, focal beam, and stereotactic radiation therapy)
Radiation therapy has become a mainstream therapy for brain metastasis. Radiation therapy includes WBRT and stereotactic radiosurgery. Stereotactic radiosurgery is a more preferred treatment modality for radiation resistant lesions such as non-small cell lung cancer, renal cell carcinoma, and melanoma. It is also frequently used in brain metastasis from breast cancer

Chemotherapy A variety of chemotherapeutic agents have been used to treat brain metastasis from lung, breast, and melanoma, including cisplatin, cyclophosphamide, etoposide, fluorouracil (5FU), ifosfamide, irinotecan, mitomycin, prednisone, temozolomide, teniposide, and vinorelbine

Most tumors that metastasize to the brain are not chemo-sensitive, though small-cell lung cancer, breast cancer, and lymphoma respond to chemotherapy. In most cases several therapeutic agents are used in combination and in conjunction with whole-brain radiation therapy

Combined Therapies In many cases, numerous agents are used in combination and in conjunction with whole-brain radiation therapy

Targeted Therapies Temozolomide has recently been used as a single agent to treat brain metastasis from breast cancer. Complete remission was achieved in 36% of patients, and an additional 58% had a partial response.
Tyrosine kinase inhibitors and monoclonal antibodies Gefitinib and erlotinib, epidermal growth factor receptor (EGFR) inhibitors have been used to treat non-small cell lung cancers that metastasize to the brain, especially if they have the EGFR mutation.

The use of lapatinib in combination with capecitabine has been used to treat HER2 positive brain metastasis, and vemurafenib is used in BRAF V600E–positive melanoma with brain metastasis. New research has suggested that sorafenib or sunitinib can lower the incidence of metastasis of renal cell carcinoma to the brain.

Monoclonal antibodies such as trastuzumab is commonly used to treat metastatic breast cancer, and Ipilimumab is administered to treat metastatic melanoma to the brain.

• National Cancer Institute Trials: The NCI, part of the National Institutes of Health, is the federal agency that provides funding for most U.S. cancer clinical trials. This site provides information on both open and closed cancer clinical trials that are funded by the government, as well as many sponsored by pharmaceutical companies, medical centers, and some international organizations.
http://www.cancer.gov/clinicaltrials/results/type/brain

• National Brain Tumor Society
http://braintumor.org

• Miles for Hope: Brain Tumor Vaccine Clinical Trials
www.milesforhope.org

• Musella Foundation
http://virtualtrials.com

• Brain Tumor Trials Collaborative
http://bttconline.org

• Trial Connect from the American Brain Tumor Association
www.emergingmed.com

• Center for Information and Study on Clinical Research Participation (CISCRP) CISCRP offers an online clinical trials search engine at SearchClinicalTrials.org.
www.SearchClinicalTreials.org

• Centerwatch This site helps people connect with clinical trials by offering a list of institutional review board (IRB)-approved clinical trials
www.centerwatch.com

• ClinicalTrials.gov This database of publicly and privately supported clinical trials is maintained by the National Library of Medicine at the NIH.
www.clinicaltrials.gov

• Coalition of Cancer Cooperative Groups This organization provides resources and information in order for patients to search for clinical trials.
www.cancertrialshelp.org

• WHO International Clinical Trials Registry Platform Search Portal The World Health Organization (WHO) coordinates health matters within the United Nations. This database allows people to search clinical trial registration information from many countries’ registries.
www.who.int/ictrp/en/

• Brain Cancer Clinical Trials-Is participation in a clinical trial right for you?
http://www.webmd.com/cancer/brain-cancer/brain-cancer-clinical- trials

• Educational Resources from the Brain Tumor Association
www.abta.org

• Brain Metastasis Information from MedScape
http://emedicine.medscape.com/article/1157902-overview

• Surviving “terminal” Brain Cancer Dr. Ben Williams (19 Year survivor of GBM)
http://www.virtualtrials.com/williams.cfm

• Brain Cancer (general information from Medicinenet)
http://www.medicinenet.com/brain_cancer/article.htm

Globe Study-Phase 3 Results Reveal Combination Therapy Does Not Improve Overall Survival in Glioblastoma
March, 2018
http://www.raredr.com/news/vb-111-combination-glioblastoma-fail

Globe Study-VBL Therapeutics (Nasdaq:VBLT), today reported top-line results from its pivotal Phase 3 GLOBE study in patients with recurrent glioblastoma (rGBM) which was designed to evaluate VB-111 in combination with bevacizumab (Avastin®), compared to the bevacizumab control arm.
March 08, 2018
http://www.raredr.com/news/vb-111-combination-glioblastoma-fail

UNC Tinkering with T-cells aims them at deadly brain cancer
March 1st, 2018
https://www.futurity.org/t-cells-glioblastoma-cspg4-1692572-2/

Recent Brain Cancer Updates from the 2014 ASCO Convention
http://blog.braintumor.org/897/

New tumor-targeting agents (APC) able to seek out and find solid tumors, even illuminating brain cancer stem cells that resist current treatments
Science Daily
June, 2014
http://www.sciencedaily.com/releases/2014/06/140611143653.htm

Journal of Clinical Cancer Research; Low Dose of Targeted Drug (bortezomib) might improve cancer-killing virus therapy
Science Daily
June 16, 2014
http://www.sciencedaily.com/releases/2014/06/140616204544.htm

New research in personalized treatments for brain cancer
Science Daily
May 21, 2014
http://www.sciencedaily.com/releases/2014/05/140521133123.htm

Harvard University: A potential solution for how to more effectively kill tumor cells using cancer-killing viruses has been discovered by researchers. The investigators report that trapping virus-loaded stem cells in a gel and applying them to tumors significantly improved survival in mice with glioblastoma multiform
May 16, 2014
http://www.sciencedaily.com/releases/2014/05/140516203342.htm

• NYU Brain Cancer Caregiver Support Group
http://cancer.med.nyu.edu/patients/patient-care/supportive-services/support-groups

• Voices Against Brain Cancer Support Groups
www.voicesagainstbraincancer.org

• Imerman Angels (to connect directly with another survivor or caregiver through an organization that creates personal, one-on-one connections among patients, survivors, and caregivers)
http://www.imermanangels.org

• Fighting Chance- free counseling service for cancer patients and caregivers.
http://fightingchance.org/resourceGuide.shtml