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Long-Term Survivors Offer Clues to Cancer Therapies : Medicine: At least 50% of patients with the disease will be cured. Scientists are asking why some beat the odds.


WASHINGTON — "Make the next six months the best of your life," the doctor told Jerilyn Ross.

It was August, 1979. Ross, 33, had just learned the grim news: Cancer cells from a malignant melanoma surgically removed seven months earlier had migrated to a lymph node under her arm. Her doctors were pessimistic. Melanoma, a skin cancer that often starts as a black mole, does not respond to drugs or radiation, and can be deadly once it spreads.

More than 15 years later--and about to celebrate her 48th birthday--Ross is cancer-free.

In 1974, Natalie Spingarn, 52, was diagnosed with breast cancer. By 1977, it had metastasized, or spread, to her spine. By 1979, it was in her bones. In 1982, she developed cancer in the other breast. "You have one year, maybe two," her doctor told her in 1982.

Twelve years later--and 20 years after her initial diagnosis--she is still going strong.

An estimated 8 million Americans have survived cancer, and at least 50% of those who develop the disease will be cured. To be sure, most of these are people in whom the cancer is detected early. Stories of spontaneous remission are extremely rare, and cases of long-term survival after metastasis also are much less common.

Nevertheless, they exist.

The question is, why? Why do some people beat the odds while others with similar medical profiles succumb? In recent years, scientists have begun paying greater attention to the question, believing the answers could provide valuable insights into the body's response to cancer--and to cancer therapies--and help lead to new approaches to fighting the disease.

"There are some very interesting clues that come out of chance observations in medicine, particularly from these long-term survivors who have beaten the odds," said Dr. Harmon Eyre, an oncologist who is chief medical officer for the American Cancer Society. "They should never be overlooked."

Scientists now are examining all of these questions in trying to design strategies against a disease that is the second-leading cause of death among Americans--after heart disease--but probably the one dreaded the most.

The field "is exploding," said Dr. Steven A. Rosenberg, a National Cancer Institute researcher who has devoted virtually his entire career to seeking ways to use and strengthen the body's own defenses against cancer. "I think it's become one of the most exciting areas in cancer research."

In some of these success stories, the reason for a good outcome could be as basic as the skill of the medical team--the surgeon who operates, the chemotherapist who calculates the doses of drugs and administers them or the radiologist who delivers the radiation. It could also depend on the destination sites of metastasized cells--if they spread to the bones, for example, an individual can live for many years with cancer; if they end up in vital organs, death can be swift.

But some of the answers also may be found in the complexities of the body's genetic makeup or its immune system--that is, how the body's defenses respond to the presence of alien cells. Or answers may come from how the body tolerates chemotherapy; doses can be made strong enough to kill tumors if the patient can withstand the onslaught of a drug's often-toxic side effects.

"There is a subset of people who have an unusually good response under usually unfavorable circumstances," said Dr. Sam Broder, NCI director.

As to why this happens, "it's a complicated question," Broder said. "Experts have postulated that some have better immune systems that can synergize with the chemotherapy or hormones that are used. Or that they are resistant to (drug) side effects. Or, by the luck of the draw, the tumor is just unusually sensitive to the (drug) agents. . . . Every person's response is variable."

But, he adds in a note of caution, "the biologies of different cancers are different. A diagnosis of lung or pancreatic cancer is a very bad diagnosis. It is important to have no illusions about this. Basically there are certain cancers that are very difficult--or impossible--to treat."

Lately, a growing emphasis has been placed on trying to home in on the various ways in which the body naturally responds to cancer and in seeking ways to strengthen those responses. Most researchers believe that the body almost always tries to mount some kind of a response, but the battle often typically favors the cancer.

In recent years, scientific and medical journals periodically have reported research that reveals intriguing clues about the body's relationship to the onset and spread of cancer.

Late last month, for example, Dr. Michael O'Reilly and Dr. Judah Volkman, researchers at Children's Hospital in Boston, announced they had identified a hormone-like factor in animals that appears to check the growth of secondary tumors formed by metastasizing cells, often the tumors that ultimately cause death. They have also found preliminary evidence that this chemical exists in humans.

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