Imagine a war zone where the entire army has shown up to fight the enemy but for some reason won’t shoot.  For this war to be won, whatever is keeping the soldiers from fighting needs to be found and stopped.  This is the situation researchers have recently discovered in their fight against  malignant gliomas, a common type of brain tumor.  Dr. Richard C. E. Anderson from the Pediatric Neurosurgery Center recently presented this research at the American Society of Pediatric Neurosurgeons‘ Annual Meeting.

According to Dr. Anderson, the impetus for this research is the difficulty in treating this kind of cancer.  He says, “despite surgery, radiation, and chemotherapy, the prognosis can still be poor.”

He and a multicenter group of researchers have found that the presence of glioma tumor cells does trigger a large immune response in the body.  However, at some point in the tumor’s development, the immune cells sent in to fight become inhibited, leaving the deadly tumor to grow unrestricted.  He and his colleagues are trying to find out why, and exactly how, this is happening in the hopes of  somehow bolstering the patient’s own immune system to fight this deadly invader.

The troops used by the immune system to fight this cancer are specific white blood cells called Tumor Associated Microglia/Monocytes or TAMs.  According to Anderson, “They are found at a much higher frequency than any other immune cell in the presence of malignant gliomas” and inherently they are, “capable of destroying these tumor cells.”  But in laboratory tests, “TAMS are significantly impaired in the presence of malignant gliomas.”  If fully functional, the TAMS would secrete a cancer cell destroying agent called TNF-alpha.  Instead, they sit there like soldiers who have been ordered not to release any bullets.

Dr. Anderson explains further, “The TAMs do not secrete the TNF-alpha in the presence of glioma cells, not simply because the entire system is blocked, but rather there is some specific pathway to cause this, and that is what we’re trying to figure out!”

He and his colleagues have found a specific gene within the TAMs that is activated, or up-regulated, when these kinds of tumor cells are present.  When a gene is up-regulated, it becomes more sensitive or develops more receptors to be effected by an agent acting on it.  What that agent is, researchers are trying to find out.

As they know more, Anderson says they can, “attempt to reverse functional impairment of TAMs by using siRNA, blocking antibodies, or medications to inhibit up-regulation of these genes.”

Dr. Anderson is hopeful.  He says, “these initial findings are a huge clue in the continuing fight against this deadly cancer.” He and his fellow researchers now know that the soldiers are there, it’s just a matter of freeing up the troops to do battle.

People involved in this research are: at Columbia University, Richard Anderson, Shinji Shimato, Benjamin Kennedy, Mike Castelli, Peter Canoll, and Jeffrey Bruce; at Harvard University, David Anderson and Alex Kostianovsky; and at Erinyes Biotechnologies, Lisa Maier.

The vaccine is called Oncophage® and it was named the best therapeutic vaccine by the World Vaccine Congress in April of last year.  It is a unique cancer treatment in that it is made from material taken from the patient’s own tumor.  It is then used to stimulate their immune system to specifically go after cancer cells and leave their healthy cells alone.

This new study follows the successful completion of the Phase 1 Trial started by Andrew T. Parsa, MD, PhD, Associate Professor of Neurological Surgery at the University of California, San Francisco (UCSF), where the first trial was completed.  He had this to say:

We are encouraged by the preliminary results generated by (the) Phase One study, which treated the most challenging patients with at least one recurrence.  In this patient population, treatment with Oncophage extended overall medical survival to approximately 10.5 months, with a favorable side effect profile.
Dr. Andrew Parsa

Dr. Bruce has joined Dr. Parsa’s efforts by conducting phase 2 trials here at the Department of Neurosurgery.  This is not their first time working together, as Dr. Parsa completed his residency here at Columbia and was part of the Bartoli Brain Tumor Laboratory with Dr. Bruce.  About the trials being carried out at his center Dr. Bruce said, “The expansion of the Phase 2 clinical trial will enable us to learn more quickly about the potential of brain tumor vaccines in this setting,”  He is excited about this drug’s potential.

Dr. Bruce is currently recruiting patients with high-grade gliomas for this trial and some have already received the vaccine.  A glioma is a type of tumor that derives from glial cells in the brain or spine.  Glial cells make up some of the supporting structure in the brain and protect the neurons.

Doctors grade gliomas as High or Low.  When a glioma is Low-Grade, it means it is benign (not cancerous).  A High-Grade glioma is malignant which means that it is cancerous and can spread.  These tumors need to be removed, but depending on their location and rate of growth, it may be difficult to get all of the cancer.  For this reason, High-Grade gliomas are often also treated with chemotherapy and radiation.

This vaccine could be an incredible boon for those with cancer.  Engaging the patients own immune system to fight the cancer on a cellular level creates highly specific targeting with less damage to surrounding tissue than conventional treatments.  That means, potentially, that not only will more people survive, but they will survive with a better quality of life.

The recent article in the Journal of the National Cancer Institute details a retrospective comparison of the rates of brain tumors in Scandinavia with the rise of cell phone use since the 90′s.  In particular, they looked to see if the incidence of gliomas and meningiomas, two types of brain tumor,  increased between 1974 and 2003. Here is what they found:

From 1974 to 2003, brain tumor incidence rates in Denmark, Finland, Norway, and Sweden were stable, decreased, or continued a gradual increase that started before the introduction of mobile phones. No change in incidence trends was observed from 1998 to 2003, the time when possible associations between mobile phone use and cancer risk would be informative about an induction period of 5–10 years. JNCI

Similarly, Dr. Bruce and his colleagues performed a retrospective study in 2002 that compared 90 people who were diagnosed with Acoustic Neuromas, tumors near the ear, against a group of 86 without.  They gathered information from each person like: whether they even used a cell phone, how many minutes they talked per month, how long they had the phone, and which ear did they normally hold the phone to. Not only was there no correlation between those that had tumors and any cell phone use but there was a tendency for people to have tumors on the other side of the head than they usually held their phone.

As more time passes, the use of cell phones increases, and more research is done, then perhaps a connection will be made but by then it is quite possible that a newer technology will have developed for us to worry about.  Besides, with hands-free and texting who is going to be holding their phone to their ear anyway?

*See Dr. Bruce‘s and his colleagues’ paper: Handheld cellular telephones and risk of acoustic neuroma in Neurology 2002;58:1304-1306

Astrocytomas, ependymomas and oligodendrogliomas are all types of glioma and they are named after the cells from which they originate: astrocytes, ependymal cells and oligodendrocytes.

A mixed glioma is a malignant tumor that contains more than one of these cell types. The most common site for a mixed glioma is the cerebrum, the main part of the brain. Like other malignant tumors it may spread to other parts of the brain.

Symptoms

The initial symptoms of brain tumors, such as headache and nausea, usually are the result of increased intracranial pressure caused by the bulk of the tumor or a backup of the cerebrospinal fluid that surrounds the brain and spinal cord.

Glial cells are widely distributed throughout the central nervous system, so these tumors can occur in a wide variety of locations, and therefore can cause a wide variety of other symptoms. A tumor of the frontal lobe of the brain may cause gradual changes in mood and personality. There may also be paralysis on one side of the body (known as hemiparesis). A tumor in the temporal lobe of the brain may cause problems with coordination and speech and may affect your memory. If the parietal lobe of the brain is affected, writing and other such activities may be difficult. Hemiparesis may also be present.

Diagnosis

Imaging studies are the key component in the diagnosis of most brain tumors. Currently, magnetic resonance imaging (MRI) is the best available imaging modality. Computed tomography (CT) scans also are used. For either study, an agent that provides contrast in the image is administered intravenously so neurological surgeons can visualize the tumor against the normal brain in the background. In some cases, neurological surgeons may employ an MRI scan with frameless stereotactic guidance. For this study, a contrast MRI is performed after special markers (called fiducials) are placed on the patientís scalp. The fiducials are processed by a computer, which calculates the location of the tumor and creates a three-dimensional reconstruction. This image then is used at the time of surgery to help locate the tumor precisely, maximize tumor removal, and minimize injury to the surrounding brain.

To give an exact diagnosis, a biopsy (sample of cells from the tumor) is sometimes taken, then looked at under a microscope. The biopsy involves an operation. Your doctor will discuss with you whether this is necessary in your case, and what the operation involves.

Treatment

Where possible, surgery is the first form of treatment for a mixed glioma. Surgery involves the resection of the tumor to decrease the pressure it exerts. The aim of surgery is to remove as much of the tumor as possible without damaging the surrounding brain tissue.

Depending on the size, location and spread of the tumor, it may not be possible to remove it completely and further treatment may be given as a follow up to surgery.

For most gliomas, however, surgery will not provide a cure by itself. When a tumor is removed, it can be examined under a microscope to provide an accurate diagnosis so the next steps in treatment, which may include radiation therapy or chemotherapy, can be determined. In addition, some smaller tumors may be treated effectively with stereotactic radiosurgery, which involves the use of a highly focused beam of radiation to target the cancer cells specifically and leave the surrounding brain unaffected. The choice of treatment usually is made based on the grade of the tumor, which is a measure of the tumor’s malignancy.

Some tumors, particularly those that are high-grade, cannot be treated by surgery and these are referred to as inoperable. If surgery is not possible your doctor will discuss other forms of treatment with you.