Researchers have developed a model for estimating a woman's risk of developing breast cancer after being treated with large-field chest radiotherapy for Hodgkin lymphoma (HL). Using the model, they determined that the cumulative absolute risk of breast cancer among female HL survivors increases with age at the end of follow-up, time since diagnosis, and radiation dose.
Breast cancer is the most common solid tumor among young women who survive HL, but individualized risk projections of cumulative absolute risk had not previously been developed. Projections could be used to counsel HL survivors and plan long-term management and prevention strategies.
To create the model, a team led by Drs. Lois B. Travis and Mitchell H. Gail of NCI analyzed data from an international population-based, case-control study of nearly 3,800 female HL survivors who were diagnosed at age 30 or younger. Among the survivors, 105 developed breast cancer, according to findings in the October 5 Journal of the National Cancer Institute.
Because the study included women diagnosed from 1965 through 1994, the model is most appropriate for survivors who received HL treatments commonly used in the past. The researchers urge caution in applying the findings to women treated with newer therapies, such as limited-field radiotherapy or ovary-sparing chemotherapy.
Gains in long-term survival provided by radiation therapy and chemotherapy should always be balanced against the associated risks of secondary cancers and other late sequelae, the researchers note. The risk projections will "serve as a unique and valuable resource for the large number of current HL survivors given therapeutic regimens of the past," they write.
A new regimen that had previously been tested only in mice has proved effective in helping humans avoid graft-versus-host disease (GVHD). Results of a study by researchers at Stanford University appear in the September 29 New England Journal of Medicine.
Normally, people with lymphoid malignant diseases or acute leukemia can be treated with bone marrow transplants after being prepped with high doses of chemotherapy. But 20 to 65 percent of bone marrow transplant patients develop acute GVHD, an illness in which the new, transplanted immune cells attack recipients' skin, intestines, and liver. GVHD causes nearly half of deaths among those who never relapse.
In this study, researchers gave 37 transplant recipients 10 doses of total lymphoid irradiation at 80 cGy per day, starting 11 days before their transplants. The patients then received antithymocyte globulin, as well as immunosuppressive therapy with cyclosporine and mycophenolate mofetil.
After a mean follow-up of 446 to 482 days, only 2 of the 37 patients developed acute GVHD. This incidence is much lower than that cited in the medical literature. It is also striking in that 14 of the participants received transplants from unrelated donors, a situation that normally results in GVHD more than half of the time. In addition, nearly all of the patients who entered the trial in partial remission ended up in full remission after receiving the treatment.
While gene therapy originally showed great promise for cancer treatment, the difficulty in delivering therapeutic genes to the growing tumor has hamstrung this technique. Now, a team from the Mayo Clinic reports that hitchhikers can help. By attaching these genetically modified viruses to immune T cells, the team obliterated tumors in mice.
"We use immune cells to home in on the tumors," said Dr. Richard Vile, lead author on the paper published September 18 in Nature Medicine online. "There they can deliver whatever therapeutic genes we want."
Dr. Vile explained that as the body defends itself against a growing tumor, T cells begin to recognize and target cancer cells. Ideally, clinicians could remove these cells from the blood, attach beneficial viruses, and return hundreds of thousands of the hitchhiker-rich T cells to the patient.
As a proof of concept, the team generated T cells designed to home in on a particular type of laboratory-grown mouse tumor similar to melanoma. They then attached a variety of viruses to the T cells and returned the cells to the mice. Between 5 and 14 percent of the injected T cells homed in on the tumors, a rate that Dr. Vile described as "very promising." All of the mice receiving hitchhiker viruses engineered to produce interleukin-12 - a growth factor that boosts the immune system - were cured of their tumors.
Because the viruses ride into the tumor on immune system cells, they enjoy a "privileged status" that prevents them from being recognized and destroyed by other immune cells.
A large chemoprevention study of phytoestrogens - plant-derived compounds found in many foods - has shown that high intake of the compounds decreases the risk of lung cancer. In the September 28 Journal of the American Medical Association, investigators reported that study participants who ate the most phytoestrogens reduced their lung cancer risk by 46 percent compared with those who ate the lowest amount.
Dr. Margaret Spitz, the lead investigator of the study at the University of Texas M.D. Anderson Cancer Center, said that phytoestrogens latch onto estrogen receptors in lung tissue, which, via biomolecular machinery, may explain the reduction in lung cancer risk. But she could not say why women, in general, seemed to benefit less than men from phytoestrogens or why former smokers seemed to benefit less than people who never smoked.
Between 1995 and 2003, the research team enrolled 1,674 patients treated for lung cancer and 1,735 healthy controls. The participants answered detailed questions about their diet for the year before their enrollment or their cancer diagnosis.
The researchers then analyzed consumption of categories of foods that contain different kinds of phytoestrogens: isoflavones (soybeans and soy products, chickpeas, and red clover), lignans (rye grains, linseeds, carrots, spinach, broccoli, and other vegetables), and coumesterol (beans, peas, clover, spinach, and sprouts).
The investigators cautioned that much more research is needed to prove a definitive chemoprevention effect. For example, for reasons not fully understood, high consumption of phytoestrogens did not reduce lung cancer risk in those people studied who had smoked and then quit. "We are just at the beginning of our work to explore the connection between these nutrients and lung cancer risk," said Dr. Spitz.
NCI has launched a national clinical trial designed to collect blood samples from patients after successful treatment of advanced ovarian cancer in order to develop an approach for detecting ovarian cancer at an early stage if the disease returns. The trial, led by the Center for Cancer Research (CCR), NCI's intramural research program, will involve 10 additional institutions where a series of blood samples will be collected from women with advanced-stage ovarian cancer who show no signs of cancer after completing their first program of chemotherapy treatment.
"If we can harness all of the protein information in the blood in our patients' samples, we may have a strong lead on how to detect ovarian cancer at an early stage when it can be most effectively treated," said the study's principal investigator, Dr. Elise Kohn of CCR.
Currently the only approved test to determine ovarian cancer recurrence is CA-125 (a test for a protein that is detectable in 80 percent of advanced-stage patients with epithelial ovarian cancer). But the CA-125 test fails to reliably diagnose women who have no signs of recurrence. Advanced-stage cancer has a high likelihood of returning within 3 years of initial treatment, even in the absence of symptoms of recurrence.
The long-term goal of the trial - which will enroll 400 women over 24 months - is to develop an approach to predict the presence of early-stage ovarian cancer using new technology that looks for protein patterns or protein fragments in blood.
"A pilot study launched in 2000 gave us a better understanding of the complexities of protein analysis and reinforced the importance of collecting and analyzing a large number of blood samples and their protein patterns," Dr. Kohn said.
For additional information, go to http://www.cancer.gov/newscenter/pressreleases/OvarianMultiInstituteTrial.