Brain Tumors

Clinical Description 

A brain tumor is an abnormal growth of a person’s own cells inside the skull or cranium. There are many types of primary brain tumors depending on which cells they come from. Primary brain tumors come from an abnormal growth of brain cells including the nerve cells (neurons), glial cells (supporting cells of neurons), pituitary cells (hormone-secreting cells) and the meninges (the covering of the brain). It is important to differentiate between primary brain tumors and metastasis of a cancer to the brain, which is spread of cancer cells to the brain from a cancer that arises outside of the brain, such as breast cancer or lung cancer. 

There are over 50 different types of brain tumors. Some are slow growing and are benign, also called low-grade brain tumors, while others grow faster and are called high-grade or malignant brain tumors. The two most common primary brain tumors in adults are high-grade gliomas and meningiomas. 

Primary brain tumors can be classified into four general categories:

1. Gliomas

Gliomas are the most common type of brain tumor in adults, responsible for about 42% of all adult brain tumors. Gliomas are further characterized by the types of cells they affect:

Astrocytoma: Star-shaped cells that protect and support neurons. Tumors of these cells can spread from the primary site to other areas of the brain, but rarely spread outside the central nervous system. Astrocytomas are graded from I to IV depending on the speed of progression:

  • Grade I (pilocytic astrocytoma): Slow growing tumor, with little tendency to infiltrate surrounding brain tissue and most common in children and adolescents.
  • Grade II (diffuse astrocytoma): Fairly slow-growing tumor, with some tendency to infiltrate surrounding brain tissue and mostly seen in young adults.
  • Grade III (anaplastic astrocytoma): These tumors grow rather quickly and infiltrate surrounding brain tissue.
  • Grade IV (glioblastoma multiform, GBM): This is an extremely aggressive and lethal form of brain cancer. Unfortunately, it is the most common form of brain tumor in adults, accounting for 67% of all astrocytomas.

Oligodendroglioma: These cells make myelin, a fatty substance that forms a protective sheath around nerve cells. Oligodendrogliomas, which make up 4% of brain tumors, mostly affect people over 45 years of age. Some subtypes of this tumor are particularly sensitive to treatment with radiation therapy and chemotherapy. Half of patients with oligodendrogliomas are still alive after five years.

Ependymoma: These tumors affect ependymal cells, which line the pathways that carry cerebrospinal fluid throughout the brain and spinal cord. Ependymomas are rare and make up 2% of all brain tumors; however they are the most common brain tumor in children. They generally don’t affect healthy brain tissue and don’t spread beyond the ependyma. Although these tumors respond well to surgery, particularly those on the spine, ependymomas cannot always be completely removed. The five-year survival rate for patients over age 45 approaches 70%.

2. Meningiomas

These tumors affect the meninges, the tissue that forms the protective outer covering of the brain and spine. One-quarter of all brain and spinal tumors are meningiomas, and up to 85% of them are benign. Meningiomas can occur at any age, but the incidence increases significantly in people over age 65. Women are twice as likely as men to have meningiomas. They generally grow very slowly and often don’t produce any symptoms. Meningiomas can be successfully treated with surgery, but some patients, particularly the elderly, may be candidates for watchful waiting to monitor the disease. Others are also candidates for radiation therapy such as the Gamma Knife radiosurgery.

3. Acoustic Neuroma / Vestibular Schwannomas

Schwann’s cells are found in the insulating sheath that covers nerve cells. Vestibular schwannomas, more commonly known as acoustic neuromas, arise from the 8th cranial nerve, which is responsible for hearing and body stability. Specific symptoms of vestibular schwannoma include buzzing or ringing (tinnitus) in the ears, one-sided hearing loss and/or balance problems. Schwannomas are almost always benign and respond well to surgery. These tumors are also treated by Gamma Knife radiosurgery.

4. Medulloblastoma

This a common brain tumor in children, usually diagnosed before the age of 10. Medulloblastoma occurs in the cerebellum, which has a crucial role in coordinating muscular movements. Some experts believe that medulloblastomas arise from fetal cells that remain in the cerebellum after birth. Tumors grow quickly and can invade neighboring portions of the brain, as well as spreading outside the central nervous system and into the spinal fluid.

Symptoms of Brain Tumors

Different parts of the brain have different functions, so symptoms of brain tumor are usually related to the location of the tumor. Symptoms are caused by compression of normal brain tissue by the tumor, tissue destruction, swelling of tissues around the tumor, obstruction of the flow of fluid around the brain and spinal cord.

Some of the symptoms of brain tumors include:
• Headache
• Nausea/vomiting
• Seizures
• Speech problems
• Impaired vision
• Weakness in parts of the body
• Difficulty walking

Risk Factors for Developing Brain Tumors 

Most brain tumors are sporadic, meaning they have no known cause. The only known risk factors for primary brain tumors are environmental, such as ionizing radiation, or immune suppression. People with certain rare genetic disorders (von Hippel Lindau disease, neurofibromatosis type 2) also have an increased risk of developing certain brain tumors.

How Brain Tumors are Diagnosed

There are no screening tests to detect brain tumors early, and most are detected only once patient has symptoms. Diagnostic investigation begins with obtaining a thorough history and physical exam, followed by imaging studies (CT, MRI). PET scan is occasionally used. Although many brain tumors can be seen with a CT scan or MRI, a stereotactic biopsy is sometimes needed to confirm the diagnosis and type of tumor. A small hole is drilled into the skull and a needle is inserted to obtain a sample of the tumor for inspection under a microscope. 

Treatment Options for Brain Tumors at Tufts Medical Center

Given great diversity of primary brain tumors, treatments are complex and frequently require close consultation and coordination by specialists from neurosurgery, neuro-oncology, radiation oncology, neuroradiology and neuropathology. Treatment includes surgery, radiation therapy, and chemotherapy, often in combination.

Surgery is the most common treatment for brain tumors. It is the treatment of choice for any brain tumor that can be reached without causing damage to normal tissue. In case of more aggressive brain cancers, complete removal of the tumor is frequently not possible, and surgery is done to “debulk” or reduce the tumor as much as possible. Goals include improvement of neurologic function, relief of symptoms; extend in duration and quality of life.

Stereotactic surgery is performed either with a frame or without one. When a frame is used—a special lightweight metal ring is attached to the head with 4 small pins after the skin is anesthetized. The patient then gets an MRI scan in the frame. The MRI images are then sent to a special computer that will, under the surgeon’s direction, determine the exact location or coordinates of the tumor. Most often this is used for a needle biopsy of a brain lesion where high precision is required. The frameless stereotactic surgery is performed without a frame. A high resolution MRI is obtained and loaded onto a computer navigation system in the operating room. In the operating room the patient’s head is then matched with the MRI. Once this is done a wireless pen is then used to very accurately localize any structure on or in the patient’s head. With this the neurosurgeon can design a small incision and skull opening (craniotomy) right where it needs to be and find the shortest and safest route to remove the brain tumor with the least amount of brain disruption. 

Surgery may be combined with radiation therapy or followed with chemotherapy to destroy any remaining cancer cells.

Radiation therapy
New methods allow physicians to raise the dose of radiation delivered to a tumor, while minimizing the amount of radiation that reaches healthy tissue. 

Gamma Knife is “brain surgery without the knife”. Gamma knife applies extremely precise and focused radiation beams to the brain tumor, while the surrounding brain is spared the high doses of radiation. Gamma Knife is used to treat many conditions including brain metastases from all types of cancers, meningiomas, acoustic neuroma (vestibular schwannoma), pituitary adenomas, chordomas, chondrosarcomas, and some gliomas. The Gamma Knife is done as an outpatient procedure—the patient comes in the morning of the procedure and usually leaves in the afternoon. At Tufts Medical Center we have the only Gamma Knife unit in Massachusetts and Northern New England.

Very few chemotherapy drugs can go through the blood-brain barrier – a natural barrier that protects the brain by not allowing the toxins to reach the brain tissue. Temozolomide (Temodar), a pill given orally, is a targeted therapy that can overcome this obstacle. It interferes with cell division, slowing tumor growth. Temodar has been shown to prolong survival and improve quality of life in patients with Glioblastomas. 

Programs + Services

Neuro-Oncology Program

Discover the Neuro Oncology Cancer Treatment Program at Tufts Medical Center in Boston and learn more about brain tumor cancer treatment options.

Brain Tumor Center

The Brain Tumor Center at Tufts Medical Center offers Boston's most sophisticated brain tumor treatment options by a team of the world's top experts.

Doctors + Care Team

Carl B. Heilman, MD

Carl B. Heilman, MD

Title(s): Neurosurgeon-in-Chief; Chairman of Neurosurgery; Professor, Tufts University School of Medicine
Department(s): Neurosurgery
Appt. Phone: 617-636-5860
Fax #: 617-636-7587

Meningiomas, acoustic neuromas, skull base surgery, pituitary surgery, Chiari surgery

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John E. Mignano, MD, PhD

John E. Mignano, MD, PhD

Title(s): Radiation Oncologist; Clinic Director; Associate Professor, Tufts University School of Medicine
Department(s): Radiation Oncology, Pediatric Radiation Oncology
Appt. Phone: 617-636-6161
Fax #: 617-636-4513

Oncologic consultation for general radiotherapy and Gamma Knife, pediatric radiation oncology

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Julian K. Wu, MD

Julian K. Wu, MD

Title(s): Associate Chairman, Department of Neurosurgery; Chief, Division of Neurosurgical Oncology; Neurosurgery Residency Program Director; Professor, Tufts University School of Medicine
Department(s): Neurosurgery
Appt. Phone: 617-636-4500
Fax #: 617-636-7587

Neuro-oncology, Gamma Knife radiosurgery, meningiomas, pituitary tumors, gliomas, brain metastasis, trigeminal neuralgia

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Suriya Jeyapalan, MD, MPH

Suriya Jeyapalan, MD, MPH

Title(s): Neurologist
Department(s): Neurology
Appt. Phone: 617-636-6227
Fax #: 617-636-8199

Neuro-oncology, brain tumors, neurologic metastases

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Research + Clinical Trials

A071101: A Phase II Randomized Trial Comparing the Efficacy of Heat Shock Protein-Peptide Complex-96 (HSPPC-96) (NSC #725085, Alliance IND# 15380) Vaccine Given with Bevacizumab Versus Bevacizumab Alone in the Treatment of Surgically Resectable Recurrent Glioblastoma Multiforme (GBM)

The purpose of this study is to compare the effects of a vaccine called heat shock protein peptide complex 96 (HSPPC-96) given with a drug called bevacizumab to bevacizumab alone. HSPPC-96 is experimental and is made from tissue taken from the brain tumor. Specifically, HSPPC-96 is a protein (a naturally occurring substance) that is taken from a person's brain tumor tissue and given back to them in the form of a preparation called a vaccine that may work to help their body have a response against remaining brain tumor cells. Bevacizumab blocks a protein called VEGF (Vascular Endothelial Growth Factor), which is produced by normal cells but over produced by cancer cells. Bevacizumab has been approved by the Food and Drug administration for treating brain tumors that grow back. In this study, subjects will either get HSPPC-96 vaccine at the same time as bevacizumab, HSPPC vaccine first and then bevacizumab if their tumor comes back, or bevacizumab alone. The use of HSPPC-96 in combination with bevacizumab is also investigational

Randomized Phase II Trial of Hypofractionated Dose-Escalated Photon IMRT or Proton Beam Therapy Versus Conventional Photon Irradiation With Concomitant and Adjuvant Temozolomide in Patients With Newly Diagnosed Glioblastoma

The purpose of this study is to compare a different radiation schedule and higher radiation dose [higher dose group] to the standard dose of radiation [standard dose group]. Both groups will receive usual chemotherapy, temozolomide. The higher radiation dose could shrink brain cancer, but it could also cause side effects. This study will allow the researchers to know whether this higher dose is better, the same, or worse than the usual approach.

A Randomized, Placebo Controlled Phase 2b/3 Study of ABT-414 with Concurrent Chemoradiation and Adjuvant Temozolomide in Subjects with Newly Diagnosed Glioblastoma (GBM) with Epidermal Growth Factor Receptor (EGFR) Amplification (Intellance 1)

The main purposes of this study are to evaluate whether combining ABT-414 with usual RT and TMZ treatment controls GBM better than usual RT and TMZ without ABT-414, and whether ABT-414 makes patients live longer. This study will only include people whose tumors are tested and confirmed to have EGFR amplification.

Phase I/II Dose Escalation Trial to Assess Safety of Intrathecal Trastuzumab for the Treatment of Leptomeningeal Metastases in HER2 Positive Cancer

The purpose of this the study that you are now being asked to participate in is to determine how safe and effective the study drug, trastuzumab, is in patients with HER-2 positive cancer that has spread to the fluid around the brain and spinal cord.

Phase II Trial Of SMO/AKT/NF2 Inhibitors In Progressive Meningiomas With SMO/AKT/ NF2 Mutations

The purpose of this study is to test good and bad effects of two different drugs against meningioma tumors with altered genes. Today, therapy for meningioma is the same for all patients, and is not based on tumor genetic testing. This trial is trying to see if tumor genetic testing would be helpful at guiding treatment in meningioma patients. Researchers have looked at the DNA material (genes) that can be affected in meningioma and have found several genes that are altered, or mutated. These include the genes called SMO and NF2. When the SMO or NF2 genes are altered, it can cause a tumor to grow. There are drugs that target these 2 genes.

The study drug, vismodegib, blocks the SMO receptor. Vismodegib has already been FDA-approved to treat basal cell cancer, which is a type of skin cancer. Vismodegib could shrink cancer, but it could also cause side effects. The study drug, GSK2256098, blocks FAK, and seems to work better in tumors that have NF2-mutations. GSK2256098 has been tested in other cancers. Researchers hope to learn if either of the study drugs will shrink cancer.


A Randomized, Phase III Trial Of Memantine and Whole-Brain Radiotherapy With or Without Hippocampal Avoidance in Patients With Brain Metastases

The purpose of this study is to compare any good and bad effects of avoiding the hippocampus during whole-brain radiation plus memantine to using the usual whole-brain radiation plus memantine. The hippocampus is a brain structure that is important for memory. The addition of the hippocampal avoidance technique to the usual whole-brain radiation plus memantine will decrease the dose of radiation to your hippocampus. It is hoped hippocampal avoidance technique will decrease the chance of cognitive side effects, however it is possible hippocampal avoidance could have no impact on cognitive side effects and could even cause side effects. This study will allow the researchers to know whether this different approach is better, the same, or worse than the usual approach. Memantine is already FDA-approved for use in patients with dementia and is commonly used off-label (that is, for a purpose for which it is not FDA approved) for patients receiving whole-brain radiation therapy for cancer that has spread to the brain.

A221101: A Phase III Randomized, Double-Blind Placebo Controlled Study of Armodafinil (Nuvigil®) To Reduce Cancer-Related Fatigue in Patients with High Grade Glioma

The purpose of this study is to:  1) see if taking the study agent, armodafinil, at a dose of 150mg or 250mg, will improve problems with fatigue in subjects who have been diagnosed with cancer and are experiencing fatigue; and 2) see the effects (good and bad) of taking Armodafinil compared to placebo (an inactive agent) on cancer related fatigue. In this study, subjects will take either the study agent, armodafinil, or the placebo (inactive agent).  Subjects will not take both. Armodafinil (Nuvigil®) is a medicine that is currently FDA approved to promote wakefulness in people who have sleep disorders.   However, it is not been studied in people with cancer related fatigue.

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