Secondary tumor rate still elevated decades after Hodgkin cure

Last Updated: 2015-12-23

By Gene Emery

NEW YORK (Reuters Health) - Over the years, oncologists have cut back on the intensity of radiotherapy and chemotherapy in patients with Hodgkin lymphoma in hopes of reducing the incidence of secondary tumors that often develop after curative treatment.

A new cohort study of nearly 4,000 patients in the Netherlands has concluded that it hasn't worked, at least for solid tumors.

"We can actually show that the increased risks do not seem to go away even 40 years after treatment," the study's chief author, Dr. Michael Schaapveld, an epidemiologist with the Netherlands Cancer Institute told Reuters Health by phone. "We have to be aware of that and we have to do something to reduce the burden of disease in these patients."

"This is the kind of thing that haunts us a little bit," said Dr. Louis Frederic Diehl of Duke University School of Medicine, who was not involved in the study, which appears in the December 24 issue of the New England Journal of Medicine.

"We take a person who is young -- 25 years old -- we cure them of a fatal disease and X number of years later they get another fatal disease that seems to be related to our treatment," he told Reuters Health in a telephone interview. "That haunts us and makes us focused on getting better treatments up front."

The study "is going to engender a very hard look" at the scope of therapy, but he predicted that the analysis "is going to merge with the whole field of genetic analysis" to better attack such tumors.

Dr. Schaapveld and colleagues found that the likelihood of second solid cancers was not lower among patients treated between 1989 and 2000, when doctors were making an aggressive effort to avoid those secondary tumors compared to earlier periods.

"There were some lights at the end of the tunnel," the researcher said. "For breast cancer we did see that reducing radiation field size was associated with lower risk. But we didn't only change the radiation field, we also had changed the chemotherapy regimens."

The study, one of the few to look at cancer rates more than 25 years after treatment, tracked patients who had survived at least five years after initiation of Hodgkin therapy. The patients were divided into three treatment periods -- 1965 to 1976, 1977 to 1988, and 1989 to 2000. Just over 60% had received both radiation and chemotherapy; 27% had received radiation therapy only.

Forty years after treatment 48.5% of the people had developed a second tumor.

The rates at which second cancers developed were comparable over the three time periods.

The trend was also similar when only solid tumors were considered.

Differences were notable for women with lung and breast cancers. Among those patients, it took a bit longer for second tumors to appear for the women treated from 1965 to 1976. But that's because those patients got less extensive radiation than patients treated after 1976, Dr. Schaapveld said.

"In the 1970s we gave patients quite extensive fields, more extensive than even in the 1960s," he said. "In the 1980s to mid-1990s we reduced these field sizes again. We went from really extended field to involved field radiation."

Overall, Hodgkin patients were 4.6 times more likely to develop a second tumor than people in the general population were likely to develop an initial tumor.

Those odds were particularly elevated for developing non-Hodgkin lymphoma, thyroid cancer, mesothelioma, and soft-tissue sarcoma, all of which appeared at rates at least 10 times higher than the general population.

The rates were 5 to 10 times higher for leukemia, esophageal, stomach, lung, and pancreatic cancers.

Breast cancer rates were 4.7 times higher for women compared to the general population. Over 30 years, 16.6% of Hodgkin survivors developed a breast tumor.

"Breast cancer accounted for more than 40% of the excess risk of a second cancer among women in our cohort," the researchers wrote.

Lung cancer was the second most common tumor (20.2% of the excess risk in the cohort) with gastrointestinal tract cancer third (19.7%) and non-Hodgkin lymphoma fourth (13.1%).

As a result of the study, Dr. Schaapveld predicted, "doctors are going to be weighing more often the positive effects of giving radiation versus the possible harm it will cause. This will probably result in more individualized treatments."

"If you have a 20-year-old female before you, you might not want to give her radiation and you might choose to give her chemotherapy and avoid radiation if possible, at least radiation to the breast," he said. "It would be different if you had a 40-year-old sitting in front of you. The radiation might really cure her. The radiation risk is much lower for a 40-year-old. The breast is less sensitive."

The Dutch Cancer Society funded this research and supported one coauthor during the study.

SOURCE: http://bit.ly/1ULzHJ1

N Engl J Med 2015.