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MGH to use genetics to personalize cancer care

Mass. General's decision to make gene testing standard represents a major step in individualizing cancer treatment. Mass. General's decision to make gene testing standard represents a major step in individualizing cancer treatment. (Pat Greenhouse/ Globe Staff/ File 2004)
By Stephen Smith
Globe Staff / March 3, 2009
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Cancer doctors at Massachusetts General Hospital plan within a year to read the genetic fingerprints of nearly all new patients' tumors, a novel strategy designed to customize treatment.

The hope is to spare patients from the traditional hit-or-miss approach to cancer care, when expensive drugs with harmful side effects are often given without knowing whether they will work.

Doctors will hunt for 110 abnormalities, carried on 13 major cancer genes, that can predict whether drugs already on the shelf or in development might thwart a patient's tumor. They will use robots - and lab machines nicknamed John, Paul, George, and Ringo - that are capable of swiftly identifying genetic quirks in 5,000 to 6,000 patients a year, replacing labor-intensive techniques that had been used only selectively for a handful of cancers.

Mass. General's decision to make gene testing standard in cancer treatment - it's believed to be the first hospital in the nation to do so - represents a major step in delivering personalized medicine to the masses. But doctors acknowledge that it is unclear whether screening patients for an expanded library of tumor defects will actually save money on drugs, or whether it will translate into longer lives.

"Right now, as an oncologist, much of what we do is really barely educated guesswork in terms of what therapy is going to be the best for a particular patient," said Dr. Leif Ellisen, a Mass. General breast cancer specialist. "We needed a new way to think about cancer diagnosis and cancer therapy."

Routine tumor screening, which began with lung cancer patients this week, opens a window onto the frontier of cancer medicine, where doctors focus more on the genetic profile of a tumor and less on whether it's in the lung, breast, or prostate. The genes that reside inside the malignancy may prove vastly more important than its address.

The testing could be especially helpful to patients with rare tumors, cancers that stoke little interest among researchers or drug companies. That is because they may share genetic signatures with more common tumors already being successfully treated.

"What we've been trying to do is set the stage for this kind of personalized medicine," said Anna Barker, deputy director of the National Cancer Institute. "We'll be able to say, 'That drug will work well for you, that drug will not work well for you.' "

Still, cancer specialists from across the country - including at Mass. General - caution against vesting too much hope in any single approach to defeating a disease notorious for resisting medical advances.

Sometimes, they said, a tumor can harbor so many genetic abnormalities that no single test and no single drug proves sufficient.

"I'm one of the most enthusiastic people for molecular personalized medicine that you will find," said Dr. George Demetri, director of the Ludwig Center for Cancer Research at Dana-Farber Cancer Institute. "But the cancer field has sometimes been plagued by people saying, 'We're going to cure cancer next month.' "

Linnea Duff illustrates the promise of genetic fingerprinting. The 49-year-old mother was diagnosed with lung cancer in 2005 - "It felt like I was on a plane that was going down," she recalled.

One lung was partially removed, followed by chemotherapy. But by last summer, her lungs were speckled with small nodules. "I began to see a psychiatrist and a social worker at MGH to prepare for my death," said Duff, who lives in Meredith, N.H.

When Duff was initially diagnosed, doctors performed genetic screening, knowing that as a nonsmoker she might have a form of cancer susceptible to a particular drug. She didn't.

With the cancer spreading, testing was performed again - and, this time, it revealed that her tumors carried an abnormality called EML4-ALK, which had only recently been identified. And a drug company was testing a pill targeting this defect.

Duff began taking it in October. Within days, she began feeling better.

Mass. General expects to charge about $2,000 a test and will ask insurers to pay as part of basic care. But representatives of the state's three major health plans said they pay for gene testing only when it has proven medical benefits, meaning insurers may balk at paying for some of the new testing. In such cases, a top Mass. General cancer doctor said, the hospital might absorb the cost or, in some cases, seek payment from patients.

Other centers, including Dana-Farber, perform gene testing on select patients. For example, Dana-Farber patients with certain melanomas - under fingernails or inside the mouth - are genetically screened because doctors know those malignancies can carry abnormalities that are susceptible to certain drugs.

And at Memorial Sloan-Kettering Cancer Center in New York, most patients with lung cancer, the most lethal malignancy in the United States, will have their tumors genetically analyzed starting within weeks.

Eventually, said Dr. Marc Ladanyi, chief of Sloan-Kettering's Molecular Diagnostics Service, such screening during a visit to the oncologist will be as commonplace as tests performed during an annual physical.

"You can think of it a little bit like when you get your blood drawn," he said.

Some of the earliest clues about tumor genetics were yielded by breast cancer. Puzzled doctors noticed that despite giving patients the best treatments available, a substantial segment derived little benefit.

Research showed that about 1 in 4 breast cancer patients carry high levels of a protein called HER2, the result of a genetic abnormality in their tumors. When given the drug Herceptin, which blocks the protein, their survival prospects soared, but the drug does nothing for patients who didn't have HER2.

Similar findings were made regarding lung tumors. Then researchers discovered something that roiled the field even more: The same abnormal genes found in certain breast and lung tumors can also exist in other tumor types.

Those findings electrified Mass. General specialists, setting them on a course a year-and-a-half ago toward universal screening.

"If you don't go the extra mile to find those rare mutations, there are going to be some patients who don't get the right drug," said Dr. John Iafrate, a Mass. General pathologist who, with Ellisen, oversees the gene testing lab.

Scientists tinkered with robots and developed processes so that in seven hours, samples from 96 patients can undergo the laboratory equivalent of a car wash, reducing the cancer tissue to its most important constituent parts so genes can be easily read.

For Linnea Duff, there is now no evidence of cancer. How long the experimental drug will work, no one can say for sure. But she didn't expect to get this much time. "The thing with cancer is," she said, "if you can hold on, there is always the chance there will be a new discovery right around the corner."

Stephen Smith can be reached at stsmith@globe.com.

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