Race Influences Decisions on Lung Cancer Surgery

African American patients who are offered surgery to treat early-stage lung cancer are far more likely than white patients to reject the offer, researchers at Henry Ford Health System (HFHS) are reporting. The finding is significant, the researchers write in the November 2005 issue of Chest, because chances of 5-year survival are as high as 50 percent in patients with early-stage disease who are treated with surgery, whereas the median survival is less than 1 year for those who decline surgery.

The result was consistent with previous studies indicating that African American lung cancer patients are less likely to undergo surgery; as a result, their mortality rates are higher than those among whites.

The study was a retrospective analysis of 97 African American patients and 184 white patients treated at the Josephine Ford Cancer Center in Detroit who were enrolled in the center's lung cancer registry. Data from patients enrolled in the HFHS pulmonary clinic between 1995 and 1998 were analyzed. Of those who were offered surgery, 18 percent of African American patients declined, compared with only 5 percent of white patients. Surgery was offered to 78 percent of white patients and 70 percent of African American patients. Of that group, 74 percent of white patients underwent the procedure, compared with 58 percent of African American patients.

"Knowing blacks decline surgery at a higher rate than whites is the first step to decreasing lung cancer mortality among this population," said the study's lead investigator, Dr. Bruno DiGiovine.

The authors hypothesized that, in addition to factors such as lack of trust in the health care system, the higher rate of decline may be linked to reports in previous studies, which found that African Americans are far more likely than whites to believe that surgery to treat lung cancer can actually cause the disease to metastasize.

Prevention Could Cut Worldwide Cancer Deaths by One-Third

Screening and treatment are the two primary approaches against cancer that receive the most money and attention, but a new global meta-analysis shows that about 2.5 million cancer deaths each year can be attributed either to modifiable behavior or environmental factors. If societies were able to implement changes at the population level, a substantial proportion of these deaths could be prevented.

Addictive substances - smoking and alcohol - were the most lethal of the nine modifiable risk factors examined. The other seven risk factors were grouped by diet/physical activity (excess weight, physical inactivity, and low consumption of fruits and vegetables); environmental risks (urban air pollution and indoor smoke, primarily from burning coal); unsafe sex (which transmits human papillomavirus [HPV] infections that cause cervical cancer); and contaminated injections in health care settings (which can cause liver cancer).

Working from published meta-analyses and systematic reviews, researchers determined that 35 percent of the 7 million global cancer deaths in 2001 were attributable to all of the risk factors combined, with more than two-thirds of these occurring in low- and middle-income regions. Nearly twice as many men as women died from preventable cancers. Of all cancer deaths, 41 percent of men's deaths were attributable to the modifiable risk factors, compared with 27 percent of women's deaths.

In high-income countries, the most prevalent causes of cancer are smoking, alcohol use, and overweight/obesity; 52 percent of preventable deaths are from lung cancer, followed by 6 percent each from esophageal and stomach cancer. In low- and middle-income countries, the most common preventable deaths are caused by lung cancer (31 percent), liver cancer (14 percent), and breast and esophageal cancer (13 percent each).

Smoking alone causes 21 percent of all cancer deaths worldwide. Analysis shows that modifying risk factors could reduce three types of cancer by more than 60 percent: esophageal cancer by 62 percent and lung cancer by 74 percent; cervical cancer could be completely eliminated if safe sex practices stopped the spread of HPV infections.

The study was published in the November 19 Lancet by Dr. Majid Ezzati and colleagues at the Harvard School of Public Health, and is the latest result from the Comparative Risk Assessment Collaborating Group (Cancers), a worldwide network of expert working groups that has previously published comparable analyses for other diseases.

Retinoid Resistance in Lung Cancer

Results from many laboratory studies suggested that retinoids - vitamin A and its natural and synthetic analogues - have potential anticarcinogenic activity. However, clinical trials using these compounds to prevent lung cancer have shown universally disappointing results. Loss of retinoic acid receptors (RAR) during carcinogenesis and disruption of the RA cellular signaling pathway may confer some of the observed resistance.

Expression of receptors in the RARβ family is frequently decreased in lung cancer cells. A study, conducted by researchers at Wake Forest and Dartmouth Universities, funded in part by NCI, and reported in the November 16 Journal of the National Cancer Institute, uncovered a previously unknown isoform of RARβ that may play a major roll in lung cancer retinoid resistance. This isoform, named RARβ1', was expressed in normal lung cells and in an RA-sensitive immortalized human bronchial epithelial (HBE) cell line, but not in RA-resistant HBE cells, lung cancer cell lines, or clinical lung cancer samples.

After transfection of an RA-resistant lung cancer cell line with RARβ1', RA treatment suppressed cell growth. Nontransfected cells were not affected by RA treatment. Treatment of another RA-resistant cell line with exogenous RARβ1' also led to growth suppression. Again, control cells were not affected by RA treatment. Investigators concluded that RARβ1' likely plays an important role in retinoid signaling and loss of the isoform that contributes to lung carcinogenesis.

"RARβ1' repression, despite RA treatment, offers a mechanistic explanation for clinical retinoid resistance that has been reported previously," wrote the investigators. "Identification of pharmacologic approaches that restore RARβ1' expression would provide a basis for future retinoid-based combination strategies for lung cancer therapy or chemoprevention."

Nanoparticles Track Cancer Vaccines

Nano-sized particles of iron oxide can be used as tags to label immune-stimulating cells for visualization with magnetic resonance imaging (MRI), according to a new report in the November Nature Biotechnology. The research promises to speed development of cancer vaccines and other immune-boosting strategies, according to an international team of researchers.

Since the debut of immunotherapy for cancer in the mid-1990s, researchers have struggled with delivering dendritic cells to lymph nodes, which is critical for their ability to enhance an immune response. Until now, there has been no accurate way to monitor their location. The team of investigators found that they were better able to assess advanced melanoma patients whose injected dendritic cells reached the target site, utilizing the FDA-approved iron-oxide nanoparticles and MRI, compared with utilizing standard scintigraphic imaging. Using this new procedure may facilitate studies to optimize inoculation procedures, immune response, and vaccination schedules.

"We show that magnetic resonance tracking of magnetically labeled cells is a clinically safe procedure that, because of its high resolution and excellent soft tissue contrast, appears ideally suited to monitor novel experimental cell therapies in patients," says the study's first author, Jolanda de Vries, from Radboud University Nijmegen Medical Center in The Netherlands.