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 
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.

Chemotherapy
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. 

Doctors + Care Team

Carl B. Heilman, MD

Carl B. Heilman, MD

Accepting New Patients

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

Accepting New Patients

Title(s): Associate Chairman, Neurosurgery; Chief, 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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Marie Roguski, MD, MPH

Marie Roguski, MD, MPH

Accepting New Patients

Title(s): Neurosurgeon; Assistant Professor, Tufts University School of Medicine
Department(s): Neurosurgery
Appt. Phone: 617-636-5878
Fax #: 617-636-7587

Neurosurgical oncology, degenerative spinal disorders, brain and spinal tumors, including primary, metastatic, and benign conditions (glioma, metastasis, meningioma, schwannoma), degenerative spinal disorders, including myelopathy, herniated spinal discs, and lumbar stenosis, and their treatment with minimally invasive spinal surgery, spinal fusion, and microdiscectomy,

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Mina Safain, MD

Mina Safain, MD

Accepting New Patients

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

Pituitary tumors, brain tumors, meningiomas, minimally invasive spine surgery, complex and reconstructive spine surgery, spinal microsurgery, spinal trauma

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Suriya Jeyapalan, MD, MPH

Suriya Jeyapalan, MD, MPH

Accepting New Patients

Title(s): Neuro-Oncologist
Department(s): Neurology; Cancer Center
Appt. Phone: 617-636-5848
Fax #:

Neuro-oncology, brain tumors, neurologic metastases

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Research + Clinical Trials


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

This randomized phase III trial studies armodafinil to see how well it works in reducing cancer-related fatigue in patients with high grade glioma. Armodafinil may help relieve fatigue in patients with high grade glioma. 
More information about research and clinical trials


A Phase III Trial Of Stereotactic Radiosurgery Compared With Whole Brain Radiotherapy (WBRT) For 5-15 Brain Metastases

This is an international multi-centre, open-label, randomized phase III trial comparing stereotactic radiosurgery (SRS) to whole brain radiotherapy (WBRT) in patients with 5 to 15 brain metastases.

Primary Objectives

• To compare the overall survival in patients with five to fifteen brain metastases who receive SRS compared to patients who receive WBRT.

• To compare the neurocognitive progression-free survival in patients with five to fifteen brain metastases who receive SRS compared to patients who receive WBRT.

 

Secondary Objectives

Patient/treatment Related Secondary Outcomes

• To compare time to central nervous system (CNS) failure (local, distant, and leptomeningeal) in patients who receive SRS compared to patients who receive WBRT.

• To evaluate if there is any difference in CNS failure patterns (local, distant, or leptomeningeal) in patients who receive SRS compared to patients who receive WBRT.

• To evaluate number of salvage procedures following SRS in comparison to WBRT.

• To evaluate the individual cognitive test results following SRS in comparison to WBRT.

• To tabulate and descriptively compare the post-treatment adverse events associated with the interventions.

• To evaluate the time delay to (re-)initiation of systemic therapy in patients receiving SRS in comparison to WBRT.

• To prospectively validate a predictive nomogram for distant brain failure [Ayala-Peacock 2014].

Economic Endpoints

• To compare the estimated cost of brain-related therapies in patients who receive SRS compared to patients who receive WBRT:

- Comparison based on payer rates (Medicare for US / provincial heath authorities in Canadian jurisdictions with activity-based funding).

Quality of Life Endpoints

• To evaluate patient’s quality of life, as assessed by the EORTC QLQ-C30 + BN20, EQ-5D, ECOG performance status, for those who receive SRS compared to those who receive WBRT.

Translational Endpoints

• Collect plasma to evaluate whether detectable somatic mutations in liquid biopsy can enhance prediction of the overall survival and development of new brain metastases.

• Analysis of serum samples for inflammatory biomarker C-reactive protein and brain-derived-neurotrophic factor (BDNF) to elucidate molecular/genomic mechanisms of neurocognitive decline and associated radiographic changes.

Imaging/Dosimetric Endpoints

• Collect whole-brain dosimetry in SRS patients to be prospectively correlated with cognitive toxicity, intracranial control and radiation necrosis (hippocampal dosimetry will be retrospectively assessed).

• Collect imaging parameters and workflow details relating to the radiosurgery planning MRIs (including timing of MR prior to radiosurgery, magnet field strength, contrast type/dose/timing, use of image post-processing, and formal reviewed by radiology) to be prospectively correlated with tumour control outcomes (local control, intracranial control).

• Evaluate serial changes in imaging features found in routine MRI images (T2w changes, morphometry) that may predict tumour control and/or neurocognitive outcomes


More information about research and clinical trials


Pivotal, Open-label, Randomized Study of Radiosurgery With or Without Tumor Treating Fields (TTFields) (150kHz) for 1-10 Brain Metastases From Non-small Cell Lung Cancer (NSCLC)

The study is a prospective, randomized controlled phase III trial, to test the efficacy, safety and neurocognitive outcomes of advanced NSCLC patients, following stereotactic radiosurgery (SRS) for 1-10 brain metastases, treated with NovoTTF-100M compared to supportive treatment alone. The device is an experimental, portable, battery operated device for chronic administration of alternating electric fields (termed TTFields or TTF) to the region of the malignant tumor, by means of surface, insulated electrode arrays
More information about research and clinical trials

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