Tag Archives: NCI-designated Cancer Center

Risk of Death Doubles For Early Stage Ovarian Cancer Patients Who Are Not Checked For Lymph Node Metastases

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University of California Davis Cancer Center and California Cancer Registry researchers determined that the risk of death doubles for those women with apparent early stage ovarian cancer who are not checked for lymph node metastases.

Dr. Gary Leiserowitz, Chief of Gynecologic Oncology at the UC Davis Cancer Center & Rosemary Cress, Research Program Director at the California Cancer Registry, reported that early-stage ovarian cancer patients had nearly twice the risk of death if they were not tested for lymph node metastases.

A team of University of California (UC) Davis Cancer Center and California Cancer Registry researchers determined that more than a quarter of women with apparent early ovarian cancer do not receive lymph node biopsies, which have been shown to improve patient survival.

For the study, the researchers identified patients diagnosed with apparent early-stage epithelial ovarian cancer between 1998 and 2000 from cancer registries in New York and California, then collected detailed information from patient medical records on the types of surgical staging procedures performed on 721 of the patients.

The study set forth the critical findings below.

  • Approximately 90 percent of patients had removal of the omentum and evaluation of the bowel serosa and mesentery.  In contrast, only 72 percent of patients with presumed early-stage disease had lymph nodes from the pelvis and abdomen tested for signs of cancer spread, despite the existence of published, professional guidelines for proper staging of the disease.
  • Only lymph node assessment (as well as node assessment combined with washings and omentectomy) had a statistically significant association with improved survival.
  • The five-year survival for women with early-stage disease who had the node biopsies was 84 percent, compared with 69 percent of those who did not have the tests.
  • Patients who did not have lymph node assessment had nearly twice the risk of death as those who did.
  • Stratification of patients based upon receipt of chemotherapy revealed that lack of lymph node sampling had an effect only on patients who also received no chemotherapy.  Thus, only when patients did not have the lymph nodes tested did chemotherapy improve survival, a finding the researchers attribute to the role chemotherapy likely plays in killing cancer cells that have spread beyond the ovaries.
  • Gynecologic oncologists were nearly six-and-a-half times more likely to perform lymph node biopsies than other surgical specialists, and nearly four times more likely to perform all recommended staging biopsies. (See “Additional Information” below for prior medical study findings, regarding the importance of gynecologic oncologists in the evaluation and treatment of ovarian cancer.)

The study results were published online last week in the journal Gynecology Oncology and will be published in the journal’s April print edition.

“Early-stage patients had nearly twice the risk of death if they didn’t have the lymph nodes tested,” said Rosemary Cress, who is an epidemiologist and research program director at the California Cancer Registry, associate adjunct professor in the Department of Public Health Sciences at UC Davis, and the study’s lead author. “Hopefully, this should raise the awareness among physicians that it’s really important to do lymph node biopsies in these patients.”

Why some surgeons don’t remove lymph nodes during ovary surgery for early-stage cancer patients is a matter of speculation, said Gary Leiserowitz, M.D., chief of Gynecologic Oncology at the UC Davis Cancer Center, who is the senior author of the study. But the tests are important, he said, because patients with positive lymph nodes are given a more advanced stage diagnosis and prescribed follow-up chemotherapy treatment.

“Depending on the knowledge and expertise of the surgeon doing the operation, they may not know they need to do all the biopsies,” said Dr. Leiserowitz. “The literature is pretty consistent in showing that the people who have specialized knowledge in this – gynecological oncologists – are much more likely to follow the guidelines.”

Another reason some surgeons may not perform the lymph node biopsies, he said, is that they don’t believe the patient would benefit, either because of advanced age or because they have other serious illnesses, or both.

“If we have a patient who is medically unsuitable because of their age or medical conditions and is not a candidate for chemotherapy, you wouldn’t do all the staging biopsies,” said Dr. Leiserowitz. “But for a woman, say in her 40’s who is otherwise healthy, it turns out to be critical, because chemotherapy could be lifesaving.”

Leiserowitz said he hopes the results of the study will help educate the medical community and patients about the value of appropriate cancer treatment.

“If you are going to treat someone with a cancer, you really have an obligation to understand what the published practice guidelines are, and adhere to them as well as you can, or refer the patient to someone else who will,” he said.

The study was paid for with a grant from the U.S. Centers for Disease Control and Prevention.

About University of California Davis Cancer Center

University of California (UC) Davis Cancer Center is the only National Cancer Institute- designated center serving the Central Valley and inland Northern California, a region of more than 6 million people. Its top specialists provide compassionate, comprehensive care for more than 9,000 adults and children every year, and offer patients access to more than 150 clinical trials at any given time. Its innovative research program includes more than 280 scientists at UC Davis and Lawrence Livermore National Laboratory. The unique partnership, the first between a major cancer center and national laboratory, has resulted in the discovery of new tools to diagnose and treat cancer. Through the Cancer Care Network, UC Davis is collaborating with a number of hospitals and clinical centers throughout the Central Valley and Northern California regions to offer the latest cancer-care services. For more information, visit cancer.ucdavis.edu.

About the California Cancer Registry

The California Cancer Registry (CCR) is a program of the California Department of Public Health’s Cancer Surveillance and Research Branch (CSRB), and works in collaboration with the Public Health Institute, regional cancer registries, health care providers, cancer registrars, and cancer researchers throughout California and the nation. CSRB collects, analyzes, and disseminates information on cancer incidence and mortality. The statewide population-based cancer surveillance system monitors the incidence and mortality of specific cancers over time and analyzes differential cancer risks cancer by geographic region, age, race/ethnicity, sex, and other social characteristics of the population. It gathers cancer incidence data through CCR, and conducts and collaborates with other researchers on special cancer research projects concerning the etiology, treatment, risk factors, and prevention of specific cancers. In addition, the system is designed to monitor patient survival with respect to the type of cancer, extent of disease, therapy, demographics, and other parameters of prognostic importance. In general, data generated from CCR are utilized as set forth below.

  • Monitor the amount of cancer and cancer incidence trends by geographic area and time in order to detect potential cancer problems of public health significance in occupational settings and the environment, and to assist in their investigation.
  • Provide information to stimulate the development and targeting of resources to benefit local communities, cancer patients, and their families.
  • Promote high-quality epidemiologic and clinical research by enabling population-based studies to be performed that can provide better information for cancer control.
  • Inform health professionals and educate citizens regarding specific health risks, early detection, and treatment for cancers known to be elevated in their communities.
  • Respond to public concerns and questions about cancer.

For more information, visit http://www.ccrcal.org/.

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Additional Information — The Role of Gynecologic Oncologists and Their Impact on Survival:

Peptide Being Tested for Atherosclerosis Inhibits Ovarian Cancer Growth; Clinical Trial Planned

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A drug in testing to treat atherosclerosis significantly inhibited growth of ovarian cancer in both human cell lines and mouse models, marking the first such report of a peptide being used to fight malignancies, according to a study by researchers at UCLA’s Jonsson Comprehensive Cancer Center.

A drug in testing to treat atherosclerosis significantly inhibited growth of ovarian cancer in both human cell lines and mouse models, marking the first such report of a peptide being used to fight malignancies, according to a study by researchers at UCLA’s Jonsson Comprehensive Cancer Center.

The study follows a previous discovery by the same group showing that a protein called apolipoprotein A-I (apoA-I) may be used as a biomarker to diagnose early stage ovarian cancer in patients, when it typically is asymptomatic and much easier to treat. These earlier findings could be vital to improving early detection, as more than 85 percent of ovarian cancer cases present in the advanced stages, when the cancer has already spread and patients are more likely to have a recurrence after treatment, said Dr. Robin Farias-Eisner, chief of gynecologic oncology and co-senior author of the study with Dr. Srinu Reddy, a professor of medicine.

Robin Farias-Eisner, M.D., Ph.D., Chief of Gynecologic Oncology, UCLA Jonsson Comprehensive Cancer Center

“The vast majority of ovarian cancer patients are diagnosed with advanced disease and the vast majority of those, after surgery and chemotherapy, will eventually become resistant to standard therapy,” Farias-Eisner said. “That’s the reason these patients die. Now, with this peptide as a potential therapy, and if successful in clinical trials, we may have a novel effective therapy for recurrent, chemotherapy-resistant ovarian cancer, without compromising the quality of life during treatment.”

The study was published Nov. 1, 2010 in the early online edition of the peer-reviewed journal Proceedings of the National Academy of Sciences.

In their previous work, Farias-Eisner, Reddy and their research teams identified three novel biomarkers that they used to diagnose early stage ovarian cancer. In September 2009, the U.S. Food and Drug Administration cleared the first laboratory test that can indicate the likelihood of ovarian cancer, OVA1™ Test, which includes the three biomarkers identified and validated by Farias-Eisner, Reddy and their research teams.

They observed that one of the markers, apoA-I, was decreased in patients with early stage disease. They wondered why the protein was decreased and set out to uncover the answer. They speculated that the protein might be protective, and may be preventing disease progression.

The protein, apoA-I, is the major component of HDL [high-density lipoprotein], the good cholesterol, and plays an important role in reverse cholesterol transport by extracting cholesterol and lipids from cells and transferring it to the liver for extraction. The protein also has anti-inflammatory and antioxidant properties. Because lipid transport, inflammation and oxidative stress are associated with the development and progression of cancer, Farias-Eisner and Reddy hypothesized that the reduced levels of apoA-I in ovarian cancer patients may be causal in disease progression.

Mice that were engineered to have many copies of human apoA-I gene showed very little cancer development when induced with ovarian cancer, while the mice without the extra copies of apoA-I showed much more disease. The mice with extra copies of the apoA-I gene also lived 30 to 50 percent longer than those who didn’t receive it.

Farias-Eisner and Reddy wanted to treat the mice that had more cancer with the protein apoA-I, but it was too large to conveniently administer, having 243 amino acids. The researchers then turned to apoA-I mimetic peptides—only 18 amino acids in length—that are being tested for cardiovascular diseases. That project had been ongoing for a number of years at UCLA, said Reddy, who is also a part of the cardiovascular research team led by Dr. Alan M. Fogelman, executive chair of the Department of Medicine.

Srinivasa T. Reddy, Ph.D., M.Sc., Professor, Division of Cardiology, Depart. of Molecular & Medical Pharmacology, David Geffen School of Medicine, University of California at Los Angeles

“The smaller peptides mimic the larger apoA-I protein and provided us with agents we could give to the mouse to see if it was effective in fighting ovarian cancer,” said Reddy. “One of the peptides was being tested as an experimental therapy for atherosclerosis, so we already have some information on how it’s being tolerated in humans, which would be vital information to have if we progressed to human studies in ovarian cancer.”

The peptide, thus far, has caused little to no side effects in atherosclerosis patients, Reddy said, a hopeful sign that it might be well tolerated in ovarian cancer patients.

The mice that were given the peptide by injection had about 60 percent less cancer than the mice that did not receive the peptide, Farias-Eisner said. The peptide also was given in drinking water or in mouse food and proved to be as effective when administered that way.

“It was an exciting result,” Farias-Eisner said. “It looked like we had something that could be ingested or injected that might be very effective against ovarian cancer progression.”

Farias-Eisner said the peptide avidly binds oxidized lipids, one of which is known to stimulate cancer cells to survive and multiply. In the mouse studies, the mice that received peptide had significantly lower levels of this cancer promoting lipid.

An early phase clinical trial is being planned testing the peptide in patients with aggressive ovarian cancers that are resistant to chemotherapy, a group of patients whose median survival is just 40 months. Farias-Eisner hopes the study will be started and completed within two years.

The study was funded by the Womens Endowment, the Carl and Roberta Deutsch Family Foundation, the Joan English Fund for Women’s Cancer Research, the National Institutes of Health and the West Los Angeles Veterans Affairs Medical Center.

UCLA’s Jonsson Comprehensive Cancer Center has more than 240 researchers and clinicians engaged in disease research, prevention, detection, control, treatment and education. One of the nation’s largest comprehensive cancer centers, the Jonsson center is dedicated to promoting research and translating basic science into leading-edge clinical studies. In July 2010, the Jonsson Cancer Center was named among the top 10 cancer centers nationwide by U.S. News & World Report, a ranking it has held for 10 of the last 11 years. For more information on the Jonsson Cancer Center, visit our website at http://www.cancer.ucla.edu.

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