National Cancer Institute NCI Cancer Bulletin: A Trusted Source for Cancer Research News
February 21, 2012 • Volume 9 / Number 4

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Cancer Research Highlights

Contrary to Evidence, Some Doctors Recommend Ovarian Cancer Screening

One in three doctors believes that screening for ovarian cancer is effective, according to a recently published survey of practicing physicians, even though substantial evidence to the contrary exists. The findings, published February 7 in the Annals of Internal Medicine, suggest that some women may be exposed to the risks of screening, such as unnecessary surgeries and procedures that result from false-positive tests, and may incur unnecessary costs.

No professional organization supports ovarian cancer screening, regardless of a woman’s risk. Moreover, the U.S. Preventive Services Task Force has recommended against routine screening for ovarian cancer since 2004, and more evidence against screening for ovarian cancer emerged last year. Transvaginal ultrasound, the CA-125 blood test, or both are used to screen for ovarian cancer.

In the new study, family physicians, general internists, and obstetrician-gynecologists answered a questionnaire that included a vignette about a woman’s annual examination. Overall, 65 percent reported that they “sometimes” or “almost always” offered or ordered ovarian cancer screening tests for medium-risk women, and 29 percent did so for low-risk women. Moreover, 24 percent routinely (almost always) ordered or offered tests for medium-risk women, and 6 percent did so even for low-risk women. Physicians were more likely to report that they ordered screening tests when the patient in the vignette requested it.

“These findings are cause for concern, given that the risks of ovarian cancer screening outweigh the benefits,” said lead investigator Dr. Laura-Mae Baldwin of the University of Washington. “Sometimes physicians are enthusiastic about cancer screening before the [scientific] evidence shows that the benefits outweigh the risks.”

As with all surveys, this study included potential sources of bias, noted Dr. Barnett Kramer, director of NCI’s Division of Cancer Prevention and editor-in-chief of the NCI Physician Data Query (PDQ) Screening and Prevention Editorial Board. Nonetheless, he echoed concerns about how often doctors do not follow current screening recommendations and the “prevalence of faith in the effectiveness of screening.”

“A substantial proportion of the health professionals who responded to the survey may have been unaware that the only randomized controlled trial of ovarian cancer screening, published last year, showed no reduction in risk of dying from ovarian cancer in the general population,” Dr. Kramer wrote in an e-mail. “But the study did show harms associated with screening.”

The survey, he continued, shows the need for “enhanced educational efforts for the professional community regarding what is known about the balance of benefits and harms associated with ovarian cancer screening.”

Lynch Syndrome Tied to Increased Risk of Breast and Pancreatic Cancers

The first prospective cohort study of families with Lynch syndrome provides the strongest evidence to date that people with this inherited condition have an increased risk of breast cancer and pancreatic cancer. The study is also the first to show that, within Lynch syndrome families, relatives who lack gene mutations that cause this syndrome have no higher risk of cancer than people in the general population, suggesting that these individuals do not require more intense cancer screening. In addition, the study confirms that affected individuals have an increased risk of several cancers previously thought to be associated with the syndrome. The study results were published February 13 in the Journal of Clinical Oncology.

Lynch syndrome is caused by inherited mutations in one of four DNA mismatch repair (MMR) genes, which are involved in fixing errors in DNA that are made when a cell’s genetic material is copied in preparation for cell division. People with these mutations are known to have a higher-than-normal risk for colorectal cancer and a variety of other cancers, and they are generally diagnosed with these cancers at a younger age (see related article).

But previous studies had yielded inconsistent evidence on the risk of pancreatic cancer and “only weak or circumstantial evidence” of increased breast cancer risk in these individuals, senior study author Dr. Mark Jenkins of the University of Melbourne, Australia, noted in an e-mail message.

Dr. Jenkins, Dr. Aung Ko Win, and their colleagues followed MMR-mutation carriers and their non-carrier relatives from NCI’s Colon Cancer Family Registry to provide estimates of carriers’ future risk for numerous cancers, including breast, colorectal, endometrial, kidney, ovarian, pancreatic, and stomach cancer. They found that carriers had from 4 to 30 times the normal risk, depending on the cancer type.

People with Lynch syndrome are usually advised to undergo colonoscopy at an earlier age and more often than the general population. “Further clarification of the risk of breast cancer for a range of ages is needed to determine the recommended ages for mammographic screening or whether methods such as MRI are warranted for women with Lynch syndrome,” Dr. Jenkins wrote.

Radiation Therapy after Surgery for Lung Cancer May Not Improve Survival

Radiation treatment after surgery does not appear to improve the survival of some elderly patients with lung cancer, according to results from an NCI-supported study. The study looked specifically at patients ages 65 and older with stage III non-small cell lung cancer (NSCLC) that had spread to nearby lymph nodes. There was no difference in survival between patients in the study who received postoperative, or adjuvant, radiation therapy and those who did not. The study was published online February 13 in Cancer.

The study’s authors, led by Dr. Juan Wisnivesky of the Mount Sinai School of Medicine in New York, acknowledged that they could not determine from their work—a retrospective analysis of data on more than 1,300 patients in NCI’s SEER-Medicare database—whether adjuvant radiation therapy improved progression-free survival or quality of life.

Long-term survival is substantially decreased in patients with NSCLC that has spread to nearby lymph nodes, the authors noted, but there are no data from clinical trials to show that adjuvant radiation therapy improves survival in such patients, Dr. Wisnivesky noted in an interview.

Yet in this study, he continued, more than half of the patients received postoperative radiation therapy. The findings were the same even when the analysis was limited to patients in certain subgroups, such as those who also received postoperative chemotherapy or who were treated during different time periods. (The study covered patients treated from 1992 to 2005.)

“We were expecting that radiation therapy would be associated with improved survival. But we’ve shown that this is not the case, to the extent that we could with our data,” Dr. Wisnivesky said. “And [radiation] treatments are not without costs or risks.”

Because the study is retrospective with incomplete data, the findings should be interpreted with caution, stressed Dr. Giuseppe Giaccone of NCI’s Center for Cancer Research. Nevertheless, he said, the data support the idea that if there are any survival differences from adjuvant radiation, “they are likely to be small.”

A phase III clinical trial being conducted in Europe, called Lung ART, is testing whether post-surgical radiation in this same patient population improves overall survival.

High Platelet Levels Linked with Poor Survival in Ovarian Cancer

Excessively high platelet levels are associated with poor survival in women with ovarian cancer, according to findings from a new study. Funded in part by NCI, the study showed that women with elevated platelet levels (thrombocytosis) had substantially worse progression-free survival and overall survival, and were more likely to have advanced cancer at diagnosis, than women with normal platelet levels. The findings were published February 16 in the New England Journal of Medicine.

The researchers identified the association between thrombocytosis and survival through an analysis of blood samples from more than 600 women with ovarian cancer. Experiments using mouse models of ovarian cancer confirmed the findings and suggested a potential mechanism by which tumors can cause platelet levels to climb.

According to the study’s senior author, Dr. Anil Sood of the University of Texas M. D. Anderson Cancer Center, the findings point to potential new treatment avenues for ovarian cancer and suggest that platelet levels could possibly serve as diagnostic and prognostic markers. “We need to do much more work to further evaluate all of these findings and develop them,” he cautioned.

Researchers found that thrombocytosis was also associated with increased levels of thrombopoietin, a hormone that regulates platelet production, and the cytokine interleukin-6 (IL-6), which can increase thrombopoietin production.

In the mouse model experiments, the research team found that IL-6 secreted by tumor cells and thrombopoietin are critical components of a “feed-forward loop” that promotes thrombocytosis and tumor growth. They also showed that an investigational monoclonal antibody that targets IL-6 called siltuximab slowed ovarian tumor growth in mice, and that siltuximab was even more effective when used in combination with the chemotherapy drug paclitaxel.

In a small clinical trial that was part of the larger multi-institutional study, 3 weeks of siltuximab treatment substantially reduced platelet levels in 18 women with ovarian cancer.

Additional studies are ongoing, Dr. Sood explained, including those focused more closely on how platelets may promote tumor growth. Additional early stage clinical trials to test anti-IL-6 treatment in women with ovarian cancer are being planned, he noted.

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