SOURCE: U.S. News and World Report. Authored by Marlene Cimons. Posted on November 19th, 2009.

Some patients with advanced melanoma survive for years after their cancer has spread, while others die quickly. Experts have never been able to predict who among those with this often fatal skin cancer will live longer than others. But this may be about to change.

Researchers at NYU’s Langone Medical Center, using a combination of tumor analysis and powerful computer chip technology, believe they have found a way to identify potential long-term survivors from within the patient group whose disease has metastasized beyond the skin to other organs. The researchers determined that patients with evidence of a stronger immune response are those likely to survive longer with the disease.

The information could point the way toward new targeted therapies for some patients, as well as spare others the toxic side effects of drugs unlikely to help them.

“It’s exciting, because we finally have some parameters that might help distinguish between these two stages in terms of survival,” said Nina Bhardwaj, director of the Tumor Vaccine Program at the NYU Cancer Institute and the study’s lead author.

“It’s potentially very important information that could make a difference in how melanoma patients will be treated,” she added.

Melanoma is an especially dangerous form of skin cancer. Risk factors include sunlight exposure, fair complexion, family history and numerous moles. An estimated 68,729 Americans will be diagnosed with melanoma this year, and about 8,650 people will die from previously detected tumors, according to the American Cancer Society.

Melanoma is highly curable when treated at its earliest stage, usually by surgery, before it has spread beyond the skin. There are few treatment options once the tumor has spread, although scientists are working on several experimental approaches. Many involve finding ways to boost the body’s immune system, including the development of a “therapeutic” vaccine.

Physicians typically assign melanoma to one of four stages, based on tumor size and location. Patients with stage I have the thinnest lesions and are the least likely to suffer a recurrence. The prognosis worsens as the tumor extends deeper into the skin.

By stage III – the focus of the study – the tumor generally has traveled to nearby lymph nodes, and five-year survival rates drop to below 69 percent. By the time a melanoma has spread to distant organs – stage IV – patients rarely survive more than a year.

But staging can be ambiguous. Patients in stage III are divided into three subgroups, depending on the extent of tumor growth in the lymph nodes. But, often, they all receive the same therapy.

“In stage IIIb, the five-year survival rate can be 50 percent, while stage IIIc drops substantially below 30 percent,” Bhardwaj said. “Yet, in many cases, these patients get enrolled in clinical trials as a group, even though there are significant differences between them. All the `threes’ get lumped into one group for treatment, or for experimental therapy. We are trying to break it down so that the appropriate therapy gets to the appropriate sub-group.”

With a clearer understanding of their survival prospects, physicians will be better equipped to tailor more specific treatments for individual patients. “This is leading the way toward more personalized medicine for melanoma treatment,” said Dusan Bogunovic, the graduate student who led the study. “There is no need to put someone on heavy-duty chemo if we know he or she won’t do well, or who might do better with another therapy. Not all end-stage melanoma patients are the same. They need to be treated differently.”

The study used a technique known as DNA-microarray to find 266 genes associated with shorter or longer survival among 38 patients whose melanomas had recurred after being surgically removed. The genes under study were those involved in immune response.

Microarray technology allows researchers to see how genes work in concert. Instead of looking at a single gene to characterize a cancer, scientists have the ability to look simultaneously at tens of thousands of genes. This technology enables them to pinpoint genetic similarities and differences among patients with the same type of cancer. DNA microarrays are created by robotic machines that arrange minuscule amounts of hundreds or thousands of gene sequences on a single microscope slide.

The researchers also analyzed the tumors themselves, including a simple test that measures the speed of dividing cells, called a mitotic index. In addition, they looked at other indicators of immune response, including white blood cells and the level of T cells within the tumors. Researchers combined this information with the genetic data produced by the microarray technology.

“The patients with reduced survival had genes that suggested the tumor was growing very fast,” which was confirmed by the mitotic index, Bhardwaj said. “The patients who survived longer had gene activity consistent with an immune response. The hope is that patients with a high immune response and a low mitotic index would be the ones who would benefit from some kind of therapeutic vaccine.”

The researchers stressed that the study results, which were published recently online in the Proceedings of the National Academy of Sciences, must be validated using a much larger independent group of patients.

The study’s co-authors include David W. O’Neill, Ilana Belitskaya-Levy, Sylvia Adams, Farbod Darvishian, Russell Berman, Richard Shapiro, Anna C. Pavlick, and Iman Osman from NYU Langone Medical Center; Vladimir Vacic and Stefano Lonardi from the University of California at Riverside; and Yi-Lo Yu from NYU and the University of Minnesota Medical School in Minneapolis.

The research was supported by grants from the National Science Foundation, the National Institutes of Health, the Cancer Research Institute, and the Emerald Foundation.