National Cancer Institute NCI Cancer Bulletin: A Trusted Source for Cancer Research News
March 9, 2010 • Volume 7 / Number 5

Cancer Research Highlights

Internal Radiation Effectively Reduces Local Recurrence of Some Endometrial Cancers

In a large, randomized clinical trial of women with high-intermediate risk endometrial cancer, vaginal brachytherapy (VBT) was as effective at reducing the rate of cancer recurrence in the vagina as external-beam radiation therapy (EBRT), and VBT had fewer side effects. These results from the PORTEC-2 trial, led by Dr. Remi Nout from Leiden University Medical Center in the Netherlands, were published March 6 in the The Lancet.

A previous trial, PORTEC-1, had shown that EBRT reduced the rate of local or regional cancer recurrence from more than 20 percent to 5 percent for women at high-intermediate risk of recurrence. However, more than a quarter of these women reported side effects in the first 2 years after treatment, mostly in the gastrointestinal tract (such as diarrhea).

To test whether VBT would be as effective as EBRT but less toxic, the researchers enrolled 427 women in the PORTEC-2 trial. After surgery to remove the uterus, ovaries, and fallopian tubes, 214 women received EBRT and 213 received VBT as low-, medium-, or high-dose-rate treatment according to the treating center’s discretion. After a median follow-up of 45 months, four women in the EBRT group and three women in the VBT group had a vaginal recurrence. The estimated 5-year vaginal recurrence rates were 1.6 percent after EBRT and 1.8 percent after VBT. No significant differences in disease-free survival or overall survival were seen between the groups.

More than four times as many women reported gastrointestinal side effects at completion of EBRT (53.8 percent) as those who received VBT (12.6 percent). This difference between groups decreased over time and was no longer statistically significant 2 years after treatment. One woman in the EBRT group and four women in the VBT group reported high-grade atrophy of the vaginal mucosa, a condition in which the skin lining the vagina becomes thin and can cause uncomfortable symptoms. Rates of sexual activity after treatment were not significantly different between the two groups.

“VBT achieves excellent vaginal control and rates of locoregional recurrence, overall survival, and disease-free survival that are similar to EBRT, and quality of life and gastrointestinal toxic effects are significantly better with VBT. VBT should be the adjuvant treatment of choice for patients with endometrial carcinoma of high-intermediate risk,” the authors concluded.

Extensive Lymph Node Removal May Improve Survival in Some Women with Endometrial Cancer

The systematic removal of lymph nodes around the pelvis and along the aorta in the abdomen may improve overall survival in women with endometrial cancer who are at an increased risk of the disease returning after surgery, according to a new study by Japanese researchers. Their findings were published online February 25 in The Lancet.

The retrospective cohort study included 671 women treated at two hospitals in Japan, where the care of women with endometrial cancer—including lymph node removal—is highly standardized. There was a 66 percent improvement in overall survival in women at intermediate or high risk of recurrence who received both a pelvic and para-aortic lymphadenectomy along with a hysterectomy, compared with women who only had the pelvic lymph nodes removed after hysterectomy. There was no improvement in overall survival associated with more extensive lymph node removal in women who were considered to be at low risk of recurrence. Recurrence risk was based on a widely used international risk categorization system for endometrial cancer. The study also showed that, along with para-aortic lymphadenectomy, post-surgical chemotherapy independently improved overall survival in women who had a higher recurrence risk.

The findings run counter to those of two earlier clinical trials (reported in The Lancet and Journal of the National Cancer Institute) that showed no survival improvement after lymph node removal, Dr. Yukiharu Todo and colleagues from the Hokkaido Cancer Center explained. But they noted that both trials included only a small number of patients who had an increased risk of cancer that had spread to the lymph nodes. “Both pelvic and para-aortic lymph nodes must be removed to eradicate microscopic and macroscopic tumor involvement and achieve sufficient therapeutic effect in patients at risk of lymph node metastasis,” the researchers concluded.

Although the study was retrospective, its design limited the bias that can hinder such studies, wrote Drs. Sean Dowdy and Andrea Marini from the Division of Gynecologic Surgery at the Mayo Clinic in an accompanying editorial. They concurred with the Japanese researchers that the findings must be validated in a randomized clinical trial, which is needed to help establish a standard of care “for the surgical treatment of endometrial cancer. Such a standard is long overdue.”

Children and Teens Less Likely Than Young Adults to Die of Non-Hodgkin Lymphoma

Young adults diagnosed with non-Hodgkin lymphoma (NHL) between the ages of 20 and 29 are about twice as likely to die from the disease as adolescents and children, researchers from the CDC reported in the March Archives of Pediatrics and Adolescent Medicine. A number of factors may contribute to this disparity, including the fact that young adults with this disease have much lower participation rates in clinical trials than children and teens, the researchers suggested.

To compare survival rates, Dr. Eric Tai and his colleagues analyzed data on 2,442 patients with NHL from 13 SEER cancer registries. The patients included 1,455 young adults and 987 teens and children diagnosed between 1992 and 2001.

Even after taking into account the subtype of the disease and the stage at diagnosis, young adults were still more likely to die within 5 years compared with children and teens. The study found that 87 percent of children and teens survived 24 months compared with 79 percent of young adults; the 5-year survival rates were 85 percent for children and teens and 75 percent for young adults.

Although survival in NHL has increased over time, the gains have been smaller among young adults than among children and adolescents, the researchers noted. They suggested that “differences in underlying conditions known to increase the incidence of NHL, differences in treatment, lack of participation in clinical trials, potential long-term or late effects on mortality, and lack of optimal follow-up” may all play a role. Future efforts to address survival should include increasing the number of clinical trials for young adults, encouraging them to enroll in the trials, and promoting improved access to care for this population, the investigators concluded.

Older Women Are at Low Risk of New HPV Infections, Infections that Progress to Cervical Cancer

ALSO IN THE JOURNALS

A report published online March 2 in the British Medical Journal by researchers from NCI’s Division of Cancer Epidemiology and Genetics, led by Dr. Sholom Wacholder, examined the risk of miscarriage following HPV vaccination with Cervarix in two multicenter phase III clinical trials, one sponsored by GlaxoSmith-Kline (GSK) and the other by NCI in Costa Rica. Participants in the NCI trial were randomly assigned in a masked fashion to receive either Cervarix or the hepatitis A vaccine Havrix. In both trials, the vaccination schedule for both arms included three doses administered over the course of 6 months.

“Overall, there is no evidence for an association between HPV vaccination and risk of miscarriage,” the authors concluded.

They noted that there was a slight but not statistically significant increase in the rate of miscarriage during the first 3 months after any dose of HPV vaccination compared with the hepatitis A vaccine, 14.7 percent versus 9.1 percent. Based in part on these findings, the FDA has requested that GSK conduct further research to assess the risk of miscarriage in women who become pregnant around the time of Cervarix administration.

Data from a large cohort of women in Costa Rica have clarified the natural history of human papillomavirus (HPV) infections among older women. The data indicate that risk of infection declines markedly with age and suggest that frequent HPV DNA screening to find new infections or vaccinating middle age women against newly-transmitted HPV provides very little benefit. The analysis appeared March 3 in the Journal of the National Cancer Institute.

New infections with cancer-causing strains of HPV are mainly transmitted sexually at young ages. At any age, new infections typically don’t lead to cancer; only infections that persist in a detectable state for years are likely to progress.

For 7 years, a team of researchers from NCI’s Division of Cancer Epidemiology and Genetics, Division of Cancer Prevention, and collaborators in Costa Rica and the United States followed a cohort of women age 18 and older who enrolled in a long-term, population-based study of almost 10,000 participants. Approximately one-third of these women were actively followed with cervical screening every 6 to 12 months to determine their HPV infection status, to look for abnormal cell changes using conventional and liquid-based Pap tests, and to examine the visual appearance of the cervix. Women with abnormal tests suggesting precancer (equivocal or definite cervical squamous intraepithelial neoplasia 3) or cancer were diagnosed with colposcopy and biopsy and treated as needed. The remaining two-thirds of the women in the study, who were at low-risk for cervical cancer, received a follow-up screening 5 to 7 years after the initial screening at enrollment (passively followed).

For all women in the study, new infections were unlikely to persist or lead to the development of precancerous lesions. Infections of long duration were associated with the highest risk of further persistence and precancer diagnosis. But newly detected infections among older women (some of which might have been re-appearances from a latent state) were just as benign as those in young women.

Explaining the natural history of HPV infections and the propensity for the body to clear them at any age, the authors stated that “a focus on HPV persistence, and avoidance of overreaction to HPV infections that are likely to resolve spontaneously, is essential for a rational introduction of HPV testing into cervical cancer screening programs.” They cautioned that, “Vaccination and screening programs must specify clearly what kind of infections they are targeting to avoid mistaken conclusions.”

People Continue to Trust Physicians, Despite Increasing Health Information Online

According to a recent NCI survey, the public’s trust in their physicians has continued to rise in spite of the fact that people report turning to the Internet first for their health information needs. In contrast, trust in the Internet and other more traditional sources such as television has been on the decline. The survey also showed a consistent increase in the number of Americans who communicate with their doctors through e-mail. A letter about the findings from staff who oversee NCI’s Health Information National Trends Survey (HINTS) appeared March 4 in the New England Journal of Medicine.

HINTS is the only national survey that examines how people access and use cancer-related information. NCI researchers surveyed approximately 5,000 to 6,000 adults in waves during 2003, 2005, and 2008. The findings build on earlier trends observed in the first two waves of the survey.

“Despite a decade’s worth of exposure to health information on the Internet, the public’s trust in physicians as their preferred source of health information has remained high, and if anything, increased from 2002 to 2008,” wrote Drs. Bradford Hesse and Rick Moser of NCI’s Division of Cancer Control and Population Sciences.

People have experienced data overload, Dr. Hesse suggested, and, because the clarity of online health information is not guaranteed, it can be confusing to them. At the same time, Dr. Hesse said, “we know reputable sites don’t always put information online that’s understandable to the general public.”

The next HINTS will be administered in 2011, and will include items designed to track Healthy People 2020 goals for meaningful use of health information technology.