Glioblastoma, the brain tumor that killed Senator Ted Kennedy, still mostly untreatable, say docs Read more: http://www.nydailynews.com/lifestyle/hea

BY Rosemary Black
DAILY NEWS STAFF WRITER

Tuesday, September 1st 2009, 11:00 AM

Ted Kennedy waged a battle against one of the most lethal of all brain tumors -- and at first, as the Massachusetts senator kept active seeing friends and going on his beloved sailboat, he almost seemed to have the upper hand.

But despite his access to the best medical treatment available, Kennedy lost the fight of his life just 15 months after his diagnosis.

Kennedy and others unlucky enough to learn they have glioblastoma receive a grim prognosis: about a year or a little more is the average life expectancy.

The outlook hasn’t changed all that much in the last 40 years, according to Dr. Eugene S. Flamm, chairman of neurosurgery at Montefiore Medical Center.

“It is a rapidly growing tumor that does not respond to treatment,” he says. “Even if you remove it surgically, the outcome is the same. The transformation of normal brain cells into tumor cells continues even after surgery.”

Despite the gloomy outlook, some doctors are more optimistic.

“It depends how you measure success,” says Dr. Alan Hirschfeld, chairman of neurosurgery at St. Vincent’s Hospital Manhattan. “If you measure it by extending life for two or three months, it’s successful. If you measure it in terms of curing the patient, no, we haven’t succeeded.”

“Survival time has increased very definitely,” says Dr. Michael Gruber, an oncologist at NYU Langone Medical Center. “How well a patient does depends on four indicators. Age is one. If you are over 50, your prognosis is worse than someone who is under 50. It also depends on the grade of tumor, whether it can be taken out, and a patient’s neurological status.”

In 2005, a drug called temozolomide was added to radiation therapy as the treatment for this type of tumor, and the median survival time was 14.6 months, according to the New York Times. Temozoliomide, which is taken orally and has fewer side effect than older drugs that were given intravenously, is now the go-to drug for treating glioblastoma.

Unfortunately, this rapidly growing tumor is virtually impossible to completely remove, says Hirschfeld.

“Although you can see something that looks very well defined on the MRI, the tumor extends well beyond those borders,” he says. “Even if you get 99.9 percent of it, you could still be left with 10 million cells that can grow and cause a recurrence.”

The cost of treating such a brain tumor is high -- from $100,000 to $500,000 is the figure experts at various medical centers tossed out, according to the New York Times.

When Kennedy was undergoing treatment, his own doctors couldn’t agree on whether he should have surgery, the Times reported. The senator flew to Duke for a three-plus hours operation in June that his doctors billed as “successful." But he lived just a few months longer.

Though there are no known risk factors for this type of tumor, it seems to strike people between the ages of 50 and 70 the most frequently, says Hirschfeld. It’s about equally common in men and women.

While new findings continue to extend the lives of patients with glioblastoma, for the moment, it remains one of the most dreaded diagnoses. For those who receive it, putting up a fight against the tumor may help.

“If you go to the Internet and do a search on outcomes in glioma, everyone will call it a terminal illness,” Dr. Henry Friedman, co-director of Duke’s brain tumor center, told the Times. “Your outcome is ‘dead on diagnosis.’ If you don’t have the philosophy that you can win, you have lost before you started.”

Newly Discovered Gene Could Be a Prime Target in the Most Lethal Brain Cancer

2/20/09
Duke Medicine News and Communications

Scientists at Duke University Medical Center and Johns Hopkins University have discovered mutations in two genes that could become therapeutic targets in malignant glioma, a dangerous class of brain tumors.

"The fact that the defective genes code for metabolic enzymes found only in malignant glioma, and not in normal tissue, could make the gene products therapeutic targets," says Hai Yan, MD, PhD, lead author, an assistant professor in the Duke Department of Pathology. The findings are published in the Feb. 19 issue of the New England Journal of Medicine.

These genetic flaws might also help distinguish between primary and secondary glioblastoma multiforme (GBM), two subtypes of especially deadly malignant gliomas, with survival of only months after their diagnosis. Patients that have mutation of the genes, isocitrate dehydrogenase 1, gene 1 and 2 (IDH1 and IDH2), also had a longer survival time.

Because the researchers found this genetic mutation in several different stages of glioma development, "the results suggested that the IDH mutations are the earliest genetic changes that start glioma progression," said Darell Bigner, MD, PhD, a co-author and director of the Preston Robert Tisch Brain Tumor Center at Duke University. Yet, patients with GBM or anaplastic astrocytoma who had the IDH mutations also were found to live longer than patients with those two cancers who lacked the mutations.

CMV: A virus in search of a vaccine

With the exception of the so-called cervical cancer vaccine, no shots have been approved specifically to prevent malignant tumors. But cervical cancer, which is caused by the sexually transmitted human papillomavirus (HPV), isn't the only tumor linked to a virus; another is cytomegalovirus (CMV), a usually harmless form of herpes that's the target of a possible therapeutic cancer vaccine for brain tumor patients.

As Scientific American reports this month, CMV has been found in the most common type of brain tumor, glioblastoma multiforme (GBM) — the cancer Massachusetts Democratic Sen. Edward Kennedy is battling. Duke University is recruiting 20 patients with these types of tumors for a combined phase 1/2 clinical trial (an early stage of testing that checks the safety and usefulness of a product) of an experimental vaccine treatment for these patients. It's also testing a similar version in another trial.

Duane Mitchell, the Duke University neuro-oncologist heading up the GBM vaccine treatment trials, is optimistic about them, telling Scientific American that creating a shot that goes after CMV "may be a radically new way to consider treating these tumors."

Pharma giant Novartis, meanwhile, is working on a CMV vaccine that would prevent infection with the virus. The company, headquartered in Basel, Switzerland, announced late last month that it expected to begin a phase 2 trial (which tests efficacy) of a preventive CMV vaccine this year. While CMV isn’t dangerous to most people, it infects 30,000 newborns in the U.S. annually, causing severe disability such as vision or hearing loss, seizures and cognitive problems in 8,000, according to the Centers for Disease Control and Prevention (CDC). It can also be deadly in people with weakened immune systems, such as AIDS patients.

Still, there are challenges. One researcher who tested a preventive CMV vaccine, University of Pennsylvania emeritus professor Stanley Plotkin, came up short when he found that it seemed to produce an immune response without actually preventing infection. "Is antibody sufficient, or do you need cellular immune responses? Or, are cellular immune responses sufficient and you don't need antibody? Those are unresolved issues," Plotkin told The Scientist in 2006, "that have somewhat hindered CMV vaccine development."

The FDA and the Tumor

By JOSEPH DOUGHERTY
June 13, 2008

Every morning I begin craving my cocktail — a drug cocktail. My life likely depends on it. I suspect Senator Kennedy will develop a similar appreciation for "drug cocktails" since his recent diagnosis with the same form of incurable brain cancer.

Kennedy surgeon a leader in neuro-oncology

By ESTES THOMPSON – 5 hours ago

RALEIGH, N.C. (AP) — Dr. John Sampson has spent most of his career studying brain tumors. And if diagnosed with the kind of cancer now faced by Sen. Edward Kennedy, he'd pick Duke University colleague Allan Friedman for a doctor.

"He's one of the best for this type of surgery in the world," Sampson said. "If someone had to choose, he would certainly be on the top of my list."

For the delicate task of removing the cancerous brain tumor that threatens his life, Kennedy went with Friedman, a 59-year-old Chicago native is a respected leader in the field of neuro-oncology who performs the majority of such surgeries at Duke University Medical Center.

Friedman "is one of the thought leaders" in the field of neuro-oncology, said Dr. Otis Brawley, the top doctor at the American Cancer Society. An internationally known tumor and vascular surgeon, he is responsible for more than 90 percent of tumor resections and biopsies at Duke.

ABC News: Vaccine Helps Man Survive Deadly Cancer

Ryan DeGrand Was Given Less Than Two Years to Live Before He Tried an Experimental Cancer Vaccine:

Developing an effective cancer vaccine has been a frustratingly elusive goal in medicine. Now researchers at Duke University Medical Center believe they might have one, harnessing the most effective and efficient of all disease fighters: the body's own immune system. Watch the story on "World News Tonight" at 6:30 p.m. ET. It appears to have helped Ryan DeGrand. DeGrand was living the American dream. Married with two children, he runs a successful golf equipment company in St. Louis,...

Isotope astatine-211 To Prolong Lives Of Brain Tumor Patients

Excerpt -

In a study to determine safe dosages of the isotope astatine-211 for treating patients with recurring brain tumors, researchers were pleasantly surprised to find that not only was the isotope's potency sufficient to kill residual cancer cells without damaging sensitive healthy brain cells, but the patients experienced longer survival rates.

"Astatine-211 has as much as five times or more cell-killing efficiency than the standard treatments of external beam radiation or beta-particle injection," said Michael R. Zalutsky, professor of radiology and biomedical engineering at Duke University Medical Center in Durham, N.C. The ability to deliver such a potent cancer killer without causing neurotoxicity (damage to the delicate neurological system that controls brain function) would be a tremendous step forward in combating this lethal disease, he said.

In the past, surgeons have been able to remove the tumor bulk, Zalutsky added, but were unable to see and thereby identify any residual cancerous cells that had escaped into the margins of the healthy tissue surrounding the tumor. It is these cells, however, that continue to grow into new tumors and eventually kill the patient. Scientists have long believed that radioimmunotherapy (RIT) could be the best way to destroy these cells, but demonstrating the feasibility of delivering a sufficiently potent radioactive isotope without harming healthy brain tissue has been heretofore impossible.

Don’t Tell Prominent Duke Doctor that Cancer Can’t Be Cured

By Rick Smith

Posted: Jan. 31, 2008

DURHAM — Dr. Henry Friedman, one of the world’s top researchers into brain tumors, scoffs at the idea that cancer isn’t curable. And Friedman’s work has been widely acknowledged, including two segments on the CBS program 60 Minutes.

“I believe you can be cured,” said Friedman, deputy director of the acclaimed Preston Robert Tisch Brain Tumor Center at Duke University. “The cancer may be in remission,” Friedman acknowledged, “but it can be in remission permanently.”

Duke, UNC Researchers Target ‘Achilles Heel’ in Brain Tumors

By Duke University News Service

Posted: Today at 7:10 a.m.

Editor’s note: This article is part of WRAL Local Tech Wire’s efforts to highlight research at universities across the Carolinas and Georgia.

DURHAM - Researchers at Duke University Medical Center and the University of North Carolina, Chapel Hill are exploiting an "Achilles Heel" of brain tumors that may selectively kill tumor cells while sparing surrounding brain tissue.

State-Of-The -Art Therapy for Glioblastoma Multiforme

This article was written by Dr. Henry Friedman. Henry S. Friedman, MD, is an internationally recognized neuro-oncologist with a career-long interest in the treatment of children and adults with brain and spinal cord tumors. He has written hundreds of articles on both the clinical and laboratory investigation of these neoplasms.