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Doctors study role of cures in new cancer

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More than 1 million Americans will learn they have cancer this year. For some, the news will be frighteningly familiar.

The most common cancer now reported in the country is the "second cancer," the malignancy that surfaces long after the first cancer vanishes. These cancers often do not occur in spite of treatment, but because of it. The same radiation and chemotherapy that cripples cancer cells can injure normal cells that are merely innocent bystanders. More than a decade later, a tumor can emerge from the wound.

For cancer patients, it's the cloud with their silver lining. The reason people get second cancers, said Dr. Lois Travis, "is because they've been cured of the first."

"As you have the very good news about the increasing relative survival rate for cancer," said Dr. Travis, of the National Cancer Institute, "then you have the concern about the long-term effects of therapy."

Because cancer survival rates continue to climb, doctors are turning more attention to the unintended consequences of their triumphs. On Monday, Dr. Travis and her colleagues will discuss second cancers during the annual American Society of Clinical Oncology meeting in New Orleans.

Although scientists have recognized second cancers since at least the 1970s, the field still has many more questions than answers for any given patient. It's not even clear what the risk may be. A second cancer depends on the type of treatment, the radiation dose, kind of cancer, age of the patient, genetic susceptibility and other variables. And some second cancers don't arise from the treatment, but rather from the cause, of the first cancer.

"There's no one answer,'' Dr. Travis said.

It is clear that the number of second cancers will rise. In 1973, she said, about 6.4 percent of all cancers were second cancers. In 1997, 15.3 percent of new cancer cases occurred among patients once cured of other malignancies. That made second cancers more common than prostate cancer, which accounted for 13.7 percent of cancers, or breast cancer, with 13.5 percent.

While a second cancer can appear after treatment for any type of cancer, researchers have focused their attention on those diseases that most often strike children and young adults. Young patients cured of lymphoma, leukemia or testicular cancer, for example, can expect decades of life ahead of them. On the other hand, a man in his 60s who develops prostate cancer may indeed develop a second cancer 20 years later, but chances are he might die from something else first.

Researchers studying young cancer survivors have found reason for concern. A watershed study of second cancers was published in 1997, in the Journal of the National Cancer Institute. That research, by Dr. Travis and her colleagues, found that among almost 29,000 survivors of testicular cancer, more than 1,400 of them had developed a second cancer. The number was about 40 percent higher than would be expected for the age and makeup of the group. And an increased risk was seen even among men who were cured more than 20 years earlier.

Dozens of other studies have found similar dangers.

A 1996 study examined 1,380 patients treated for Hodgkin's disease as children. Hodgkin's disease is a cancer of the lymphatic system. Of the original group, 79 had developed a malignancy 11 years later. With the size and characteristics of the population, doctors would have expected only about four patients to get cancer, the researchers explained in The New England Journal of Medicine.

But the risks have to be viewed in perspective, said one of the study's main authors, Dr. Anna Meadows of Children's Hospital of Philadelphia. While cancer survivors did have a cancer risk 18 times greater than their counterparts, it is also true that about 1,300 of them remained healthy during the course of the study.

"We're not talking about a lot of affected individuals," Dr. Meadows said. Also, many of the cancers that developed were thyroid and skin cancers, which generally have high cure rates.

If there is bad news, it's that the risk of second cancers does not appear to taper off as cancer survivors get older, said Dr. Dan Green of Roswell Park Cancer Institute in Buffalo, N.Y. Last month, he described a group of 182 patients who were treated for Hodgkin's disease in childhood or early teens. The study was significant, he said, because the doctors obtained data on all patients. One hazard in estimates of second cancers is that researchers - because they must retrieve old medical records - might miss patients who had no reason to see a doctor, making it seem as if the study group as a whole was sicker. Also, Dr. Green and his colleagues were able to track the average patient for more than 17 years, longer than many other studies.

At the end of the study, about one-fourth of the survivors had developed a second cancer, the researchers reported last month in the Journal of Clinical Oncology.

Studies like this aren't meant to scare patients who have been cured, Dr. Green said, but to make them aware that they should take good care of themselves. "The most important take-home message would be that they have to remain under medical surveillance," he said. They should be meticulous about screening for cancer. Women, for example, should get regular mammograms about 10 years after treatment, regardless of age, he said.

And of course, cancer survivors should stay away from known carcinogens, such as smoking and long hours of sunshine. Once patients have conquered cancer, he said, "we talk a lot about healthy lifestyle."

Scientists hope that more research into second cancers will mean that patients being treated today will have less risk than patients who were treated 20 years ago. Doctors are already working on ways to make certain that the cancer is cured with the lowest possible dose of radiation, or gentlest chemotherapy. But researchers have to be very careful before they start tinkering with the radiation used in cancer treatment.

"How can we alter our treatments to preserve the same cure rates, to prevent something that's going to happen in 20 years?" said Dr. Mary Gospodarowicz, a radiation oncologist at Princess Margaret Hospital in Toronto. "Whatever studies are done, need to be done very carefully." Patients need to be watched to make sure that a lower dose of radiation - or a different chemotherapy - still kills all stray cancer cells. A second cancer is only a theoretical risk. The current cancer is very real.

"If patients are not cured, they are at risk of dying of disease now," said Dr. Gospodarowicz, who will speak Monday in New Orleans. "You don't want to overreact and sacrifice the chance of cure now."

To better refine therapy, researchers also need to learn more about the mechanism that turns cancer treatment into cancer cause. Most tumors appear in parts of the body that were exposed to radiation, and radiation is a known carcinogen. But beyond that simple explanation, it isn't known whether certain people are just born uniquely sensitive to the power of radiation. And even less is known about how chemotherapy can cause cancer.

Most of all, Dr. Travis said, cancer survivors should be aware of their risks, but not consumed by a fear of developing the disease again. "For all we know, they will outlive us," she said. "They shouldn't have to be worried constantly."
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