Cancer therapy risks assessed.

Cancer therapy risks assessed

Survivors of childhood cancer have an increased risk of developing bone cancer later in life, primarily because of the use of radiation therapy and chemotherapy against the original cancer, a new study concludes. The study, published in the Sept. 3 NEW ENGLAND JOURNAL OF MEDICINE, is believed to be the most comprehensive analysis ever performed on the risks of cancer therapy for children.

Researchers from the National Cancer Institute and six cancer hospitals in the United States and Italy report that the risk of bone cancer among survivors of a variety of childhood cancers rises sharply with increasing exposure to radiation or certain chemotherapeutic agents, reaching 40-fold at some of the highest doses used. Unfortunately, says Margaret A. Tucker, senior researcher in the study, radiation and chemotherapy remain essential treatments for childhood cancers.

"Radiation doses are lower than they used to be, but they are still well within the range where they cause problems,' Tucker told SCIENCE NEWS. Moreover, she says, the research suggests that with chemotherapy use becoming more widespread, increasing numbers of chemotherapy-caused cancers can be expected to show up 15 or 20 years from now. Nevertheless, she says, "The risk of bone cancer is small compared to the enormous benefit the kids get from treatment at this point; if they aren't treated, then they die of their first tumor.'

Previous studies have documented, if somewhat sketchily, the risks of radiation therapy (SN: 6/22/85, p.127). But the new research goes to great lengths to measure such variables as dose levels relative to each patient's age and body surface-area, and the proximity of subsequent bone cancers to original radiation sites. Furthermore, in their measurements of dose levels for various skeletal components, the researchers took into account the radiation scatter patterns that are characteristic of various therapy machines, adjusting for differences in bone absorption associated with different types of energy beams used.

Using these and other factors, the retrospective study of more than 9,000 patients provides strong statistical evidence that approximately half of the secondary bone cancers observed can be blamed on radiation therapy or on chemotherapeutic alkylating agents such as the frequently prescribed cyclophosphamide. The study points to the difficulties that pediatric oncologists face in choosing a treatment regimen for children with cancer.

"The bottom line is that radiation has a profound effect on the likelihood of getting secondary bone tumors,' says Anna T. Meadows, chairperson of the Late Effects Study Group, a multicenter cancer research team that coordinated the current study. "The study provides evidence that with lower doses we can prevent at least some bone tumors. We don't want to give children anything but the minimum dose that would take care of the tumor.'

However, the study also suggests that hereditary factors may play a larger role in bone cancer development than was previously believed. Only one form of cancer, a rare eye cancer called retinoblastoma, has so far been linked to a specific genetic defect (SN: 1/5/85, p.10). But there is growing evidence that other childhood cancers have genetic roots as well, Tucker says. In the current study, for example, secondary bone cancer was reported in six patients who had received neither chemotherapy nor radiation therapy for their original cancers. Statistical analysis predicted that less than one such case would occur in the sample group. "It seems likely that heritable factors contribute to constellations of multiple childhood cancers, including bone [cancer],' the researchers conclude in their paper.

According to Tucker, the study may help physicians in calculating ideal radiotherapy and chemotherapy dosages, but in the long run an entirely new approach to cancer treatment may be needed. It's possible, she says, that as hereditary factors become better understood, some cancers may be more successfully managed on the gene therapy level.