HOUSTON, June 8 — More than a decade after the government urged scientists to enroll more women in clinical research projects, females were still significantly under-represented in clinical trials involving nonsex-specific cancers, a review of more than 600 studies showed.

Women accounted for less than 40% of patients in these trials and were significantly lacking in trials involving six of seven nonsex-specific cancers, Reshmi Jagsi, M.D., D.Phil., of the University of Michigan in Ann Arbor, and colleagues reported online in Cancer.

The researchers also found that trials with government funding had significantly more women than privately funded studies.

• Explain to patients that this study showed the fewer women were represented in published high-impact studies of cancer than would be predicted by the sex distribution of the cancer.
• The authors did not address potential reasons for the disparity.

“Only by understanding the forces affecting the sex distribution of study subjects can we as a society succeed in ensuring that our medical research efforts are inclusive and to the benefit of all,” the authors concluded.

The Revitalization Act of 1993 emphasized the need to include women in clinical research projects. In a 2001 report, the Institute of Medicine identified gender as a basic variable in the design and analysis of clinical studies.

Whether women are adequately represented in clinical trials remains an unresolved issue, Dr. Jagsi and colleagues said.

For example, a review of federally funded studies published in medical journals in 2004 showed that women constituted 37% of participants in nonsex-specific trials.

Studies of participation in cancer-specific research have yielded conflicting results.

So, to update the current status of women’s representation in clinical cancer studies, the authors reviewed articles published in 2006 in eight major journals.

They identified 1,534 cancer research articles, including 661 pertaining to prospective clinical studies involving a total of 1,096,098 participants. The prospective studies formed the basis for the primary analyses.

The authors analyzed the studies with respect to seven nonsex-specific cancer types: central nervous system, gastrointestinal, head and neck, hematologic, lung, sarcoma, and urinary.

They compared women participants in the studies to the number of females that would be expected on the basis of sex distribution for that that type of cancer.

The estimated incidence of specific cancers in women was based on data from the U.S. Bureau of Census and the National Cancer Institute.

“For six of seven cancer types analyzed, the overall percentage of women among treatment study participants was significantly (P<0.001) lower than the percentage expected based on general population incidence data,” the authors said.

Overall, women accounted for 38.8% of participants in studies of nonsex-specific cancers. Studies focusing on treatment had an even lower percentage of women compared with studies focusing on other aspects of cancer (36.9% versus 42.2%, P=0.004).

Female participation was higher in government-funded studies: 41.3% versus 36.9% in studies funded by other sources (P=0.005).

Studies whose first or senior author was a woman also had a higher proportion of female participants than studies led by males (41.3% versus 37.3%, P=0.01).

In a multivariate analysis, lack of government funding and a focus on cancer treatment were independent predictors of a lower percentage of female participants (P=0.03).

Limitation of the study included focus on high-impact published studies in a single year, assessment of participants in published articles rather than trial enrollment, inability to evaluate other factors such as race and socioeconomic status, and inclusion of both study as a whole and individual participants as units of measure.

The authors reported no potential conflicts of interest.

Primary source: Cancer

Source reference:
Jagsi R, et al “Under-representation of women in high-impact published clinical cancer research” Cancer 2009; DOI: 10.1002/cncr.24366.

Ortho Biotech Oncology Research & Development, a unit of Centocor Research & Development, Inc., has announced that it has entered into a five-year Cooperative Research and Development Agreement (CRADA) with the National Cancer Institute (NCI), with Steven A. Rosenberg, M.D., Ph.D., chief, Surgery Branch, serving as the NCI principal investigator, to research and develop novel cell therapy technologies as potential treatments for a variety of cancers. These adoptive immunotherapy technologies are designed to work by helping the immune system fight cancer. Standard cancer treatments still have not progressed much beyond surgery, radiation and chemotherapy, which are effective at killing tumor cells but also can harm or kill healthy tissues. Adoptive immunotherapies have the potential to spare healthy tissue because they are designed to directly find and destroy cancerous tumor cells using a patient’s own immune system T cells.

Dr. Rosenberg has been a pioneer in the field of adoptive immunotherapy of cancer for decades. His group developed Tumor Infiltrating Lymphocytes (TILs), T cells obtained from a patient’s tumor, expanded and then re-administered to actively seek and destroy cancer cells. Remarkable responses to this therapy have been observed in patients with malignant melanoma, a type of skin cancer that ranks sixth among U.S. men and seventh in U.S. women for the most commonly diagnosed cancer, according to the NCI. In recent years, Dr. Rosenberg’s team pioneered a new technology in which T cells obtained from a patient’s blood are genetically engineered to express receptors that give them specific immunity against cancer cells and then re-administered.

Researchers at Ortho Biotech Oncology Research & Development independently developed a different and proprietary adoptive immunotherapeutic approach that uses tumor antigens and other materials to stimulate T cells from a patient’s blood to become Cytotoxic T Lymphocytes (CTLs), which recognize and attack tumor cells. Early clinical results show that this technology holds promise in melanoma patients and also has the potential to work in other types of cancers.

Under the CRADA, Dr. Rosenberg’s lab will conduct a clinical trial in melanoma patients using Ortho Biotech Oncology Research & Development’s proprietary technology. It is hoped that the technology will be effective in other types of cancer, as well. The other part of the CRADA will focus on a collaborative effort on a T-Cell Receptor (TCR) research program.

“This public-private partnership represents an extraordinary opportunity to bring together complementary and substantial expertise and resources from two groups with the common goal of advancing a highly promising new modality of therapy for patients with cancer,” says Jay P. Siegel, M.D., chief biotechnology officer of Johnson & Johnson’s Pharmaceuticals and Medical Devices & Diagnostics businesses.

“Dr. Rosenberg and NCI have extensive experience in the development of immunotherapies for melanoma and other cancers, as well as a strong track record in conducting early phase clinical studies. We look forward to collaborating with NCI to optimize technologies and to begin testing of our immunotherapy technology in melanoma patients by the end of 2009, with the possibility of additional studies for other types of cancer and other technologies in years to come,” adds William N. Hait, M.D., Ph.D., senior vice president and worldwide head of oncology research and development, who with Dr. Siegel will direct the Ortho Biotech Oncology Research & Development team under the collaboration.

Melanoma:


Skin cancer is the most common form of cancer in the United States, and Melanoma, its most deadly form, accounts for 4 percent of all diagnosed skin cancers, according to NCI. Melanoma, which usually begins in cutaneous melanocytes - the cells that produce the pigment melanin - is more likely to spread to other body parts, known as metastatic melanoma. In 2008 in the United States, an estimated 68,000 people were diagnosed with melanoma and 8,420 people died. The percentage of people in the United States who develop melanoma has more than doubled in the last 30 years. When detected early, melanoma can be successfully treated with surgery; however, more advanced disease has limited treatment options, with a poor prognosis. Treatment of patients with melanoma in the United States costs about $1.5 billion annually, NCI reports.

Source:
William Foster, J&JPRD

Porter Novelli

CHICAGO, June 4 — Optical analysis during colonoscopies can accurately distinguish benign growths from dangerous precancerous polyps that need removal, a British researcher reported here.

If widely adopted, such methods could reduce bleeding and perforations associated with removal of polyps that turn out to be benign, said Ana Ignjatovic, B.M.B.Ch., of St. Mark’s Hospital in London.

Moreover, if precancerous polyps are simply snipped and left in the colon to be eliminated naturally, colonoscopy efficiency could be boosted substantially, she said here at a Digestive Disease Week press briefing.

Her report was based on a prospective study called DISCARD, directly comparing optical analysis of polyps in situ with conventional laboratory histopathology findings.

• Explain to interested patients that technologies are available to analyze polyps visually during the colonoscopy to determine whether they are dangerous or not.
• Explain that optical performance relative to pathology methods, which require that polyps be removed and taken for lab analysis, is an important issue.
• Explain that unnecessary polyp removal carries a risk of bleeding and perforations.
• Note that this study was published as an abstract and presented orally at a conference. These data and conclusions should be considered to be preliminary until published in a peer-reviewed journal.

In the study, which is still ongoing, colonoscopies were performed in 126 patients, with 355 polyps seen.

Endoscopists first examined them with standard, commercial optical technologies including high-definition white light, narrow-band imaging, or chromoendoscopy.

The polyps were then removed and retrieved for laboratory analysis as in conventional colonoscopies.

Of 194 identified as adenomas by lab analysis, 182 (94%) were correctly diagnosed by the optical method.

The accuracy for non-neoplastic growths was 90%, with 52 of 58 benign polyps correctly identified with the optical technology.

Dr. Ignjatovic said the optical method was somewhat less accurate for smaller polyps, 5 mm or less, and especially those found to be benign by lab pathology.

Non-neoplastic, small polyps were correctly diagnosed at a rate of 85% by the optical methods, compared with 100% of larger polyps (P=0.04).

Adenomatous polyps were correctly diagnosed with the optical methods for 93% of these small polyps, compared with 98% of those 6 to 9 mm (P=0.47).

The experience of the endoscopist was also a significant factor in the accuracy of optical analysis, mainly in diagnosis of polyps ultimately determined to be adenomas.

Clinicians rated as nonexpert, who examined 50 of the study patients, had an accuracy rate of 87% with the optical technologies, compared with 96% for expert endoscopists (P=0.04).

Because the study was conducted at a single academic medical center, Dr. Ignjatovic recommended that a broader comparative study be conducted in a broader array of clinical sites.

Kenneth Wang, M.D., a gastroenterologist at the Mayo Clinic in Rochester, Minn., said the findings were encouraging.

“I liked Dr. Ignjatovic’s concept of using available technology,” said Dr. Wang, who moderated the briefing.

“This isn’t anything special,” he said, referring to the optical devices used, including off-the-shelf, Olympus high-definition white light system.

“It’s a small study, so obviously it needs to be reproduced,” he added.

But if the findings are confirmed, it would almost certainly improve the patient experience with colonoscopies, Dr. Wang said.

“[We could] give patients all the information they want right there, at the time of the procedure. That delay, with the waiting for pathology and contacting the patient . . . causes some problems,” said Dr. Wang.

“It would be nice to wrap things up at that visit and not make the patient wait.”

No commercial funding for the study was reported. Dr. Ignjatovic reported no potential conflicts of interest. Dr. Wang reported research funding from AstraZeneca Pharmaceuticals, BARRX Medical, Fujinon, Olympus America, and Spectra Science.

Primary source: Digestive Disease Week

Source reference:
Ignjatovic A, et al “Optical biopsy at colonoscopy: are we ready? DISCARD study: early results” DDW 2009; Abstract 721.