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Radiotherapy advance points way to noninvasive brain cancer treatment

With an equal rate of incidence and mortality-the number of those who get it, and the number of those who die from it-Glioblastoma Multiforme (GBM) is a brain cancer death sentence.

Of the approximately 12,000 people who are diagnosed with GBM annually in the U.S., half will die within a year, and the rest within 3 years. Currently, the only treatments that stretch survival limits are exceptionally invasive surgeries to remove the tumor and radiation treatment with the maximum tolerated dose - all of which leads to a painfully low quality of life. Because of this, researchers are racing to find better therapies to stop or slow GBM.

In the Jan. 1, 2006 issue of the journal Clinical Cancer Research, Gelsomina "Pupa" De Stasio, professor of physics at the University of Wisconsin-Madison, and her colleagues report on research into using a new radiotherapy technique for fighting GBM with the element gadolinium. The approach might some day lead to less invasive treatment and possibly a cure of this disease.

"It's the most lethal cancer there is. The only good thing about it is that, if left untreated, death is relatively quick and pain-free, since this tumor does not form painful metastases in other parts of the body," says De Stasio. The therapy, called Gadolinium Synchrotron Stereotactic Radiotherapy (GdSSR), requires a gadolinium compound to find tumor cells and penetrate them, down into their nuclei, while sparing the normal brain. Then, the patient's head is irradiated with x-rays. For these x-ray photons the whole brain is transparent, while gadolinium is opaque. Then, where gadolinium is localized-in the nuclei of the cancer cells only-what's known as "the photoelectric effect" takes place.

"Exactly 100 years after Einstein first explained this effect, we have found a way to make it useful in medicine," De Stasio says. "In this effect, atoms absorb photons and emit electrons. The emitted electrons are very destructive for DNA, but ha ve a very short range of action. Therefore, to induce DNA damage that the cancer cells cannot repair, and consequently cell death, gadolinium atoms must be localized in the nuclei of cancer cells."

De Stasio adds that, for the treatment to be effective, gadolinium must be absent from normal cells and be present in the majority of the cancer cell nuclei. The first condition is well demonstrated by MRI, while the second was recently demonstrated using microscopy techniques at the Synchrotron Radiation Center (SRC) in Stoughton.

De Stasio, the first to introduce this technique into the biological and medical fields, is working to develop the therapy to treat GBM. In the current article, she and her colleagues prove that gadolinium reaches more than 90 percent of the cancer cell nuclei, using four different kinds of human glioblastoma cells in culture.

De Stasio developed and oversees the X-ray PhotoElectron Emission spectroMicroscopy (X-PEEM) program at UW Madison's SRC, where she also serves as interim scientific director.

The technology necessary for eventual treatment would involve miniature synchrotron light sources, which could be similar in size and cost to an MRI machine. De Stasio says the next steps will include animal and possibly human clinical trials.

"If we do see that we can cure animals from their cancers, then it's worth investigating the molecular biology of this drug and seeing what the uptake mechanism is," she says. "But first, you want to know that it works and that it really has potential for saving lives."

Because of the deadly nature of GBM, De Stasio says an alternative is desperately needed to current therapies that offer little promise for extending life. De Stasio says it will be a year before it is known whether the treatment works in animal models, and likely another five to ten years before clinical trials and available treatments would emerge.

While the human health payoff seems fa r away, De Stasio says she is committed to the timetable needed for success. "(Fighting cancer) is the type of work that makes you feel good about being a scientist," she says. "If you can really contribute to humanity and do something that's useful for people, for sick people, it's really incredibly gratifying."

John Morgan, (608) 877-2357, jmorgan@wisc.edu
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Source:University of Wisconsin-Madison


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