Sunday, January 25, 2009
Study Points to Way of Stopping Lung Cancer Spread
Lung cancer cells produce a compound that helps the tumor spread to other parts of the body, a finding that could lead to a new way to prevent this dangerous development, researchers reported on Wednesday.
They said a protein called versican hijacks elements of the immune system, generating inflammation that can spur the growth and spread of lung cancer.
Michael Karin of the University of California, San Diego, and colleagues made the findings in experiments with mice, but said the protein is found in low levels in some normal human lung cells and other tissues.
Versican is made in large amounts by lung cancer cells, especially in aggressive tumors, they reported in the journal Nature.
Cancer becomes far more dangerous and hard to treat when it spreads from the original tumor site -- the lungs in this study -- to other parts of the body in a process called metastasis.
The researchers said their findings could lead to new treatments to limit the metastasis of lung cancer, perhaps by blocking the cancer cells from secreting the protein.
Versican was known to be involved in the development of embryos, and known to be active in some tumors, although its role was not clearly understood.
The study showed that versican causes the production of immune system proteins called cytokines, generating inflammation that fuels the growth and spread of the cancer.
"Our research showed that versican which (is) produced by cancer cells induced inflammatory response and this whole process enhances metastasis. This simply says that blocking versican or blocking the inflammatory response can reduce the metastatic incidence. However, it is not that easy," Sunhwa Kim, one of the researchers, said by e-mail.
The immune system's complexity is one hurdle, Kim said.
Kim, who previously worked in Karin's lab and now works for Johnson & Johnson, called the findings a good starting point for human studies focusing on this protein.
Worldwide, lung cancer is the leading cause of cancer death in men and the second leading cause of cancer death in women, with about 975,000 men and 376,000 women dying annually, according to the American Cancer Society. About 1.5 million new cases of lung cancer occur per year.
BRCA1 Influences Lung Cancer Chemotherapy
Carriers of certain haplotypes of the BRCA1 gene, which plays a central role in the DNA repair system, do not appear to respond to platinum-based chemotherapy for non-small-cell lung cancer, Korean researchers report in the Journal of Clinical Oncology published online ahead of print.
"Results from this study," senior investigator Dr. Jeong-Seon Ryu told Reuters Health, "show that lung cancer patients with two copies of AACC of BRCA1 do not benefit from platinum doublets -- gemcitabine/platinum, docetaxel/platinum or paclitaxel/platinum -- that are standard regimens worldwide for locally advanced or metastatic non-small-cell lung cancer."
Dr. Ryu of Inha University Hospital, Inchon, and colleagues came to this conclusion after studying the relationship of 4 tagging single-nucleotide BRCA1 polymorphisms and their haplotypes on the outcome of treatment in 300 patients. The five haplotypes studied were AACC, AACA, GCTC, GATC and AATC.
Median survival was 13 months and the researchers did not find any significant associations between any of the tagging polymorphisms and overall survival.
However, patients with two copies of the AACC (wild type) haplotype had significantly shorter survival than those with one or no copy (8.47 versus 14.57 months). This continued to be true after adjustment for factors including weight loss and second-line treatment (hazard ratio, 2.097).
This effect on survival was seen in patient with squamous cell carcinoma but not in those with adenocarcinomas.
"Therefore," concluded Dr. Ryu, "this result suggests that a new strategy is needed for these patients, especially in squamous cell carcinoma."
"Results from this study," senior investigator Dr. Jeong-Seon Ryu told Reuters Health, "show that lung cancer patients with two copies of AACC of BRCA1 do not benefit from platinum doublets -- gemcitabine/platinum, docetaxel/platinum or paclitaxel/platinum -- that are standard regimens worldwide for locally advanced or metastatic non-small-cell lung cancer."
Dr. Ryu of Inha University Hospital, Inchon, and colleagues came to this conclusion after studying the relationship of 4 tagging single-nucleotide BRCA1 polymorphisms and their haplotypes on the outcome of treatment in 300 patients. The five haplotypes studied were AACC, AACA, GCTC, GATC and AATC.
Median survival was 13 months and the researchers did not find any significant associations between any of the tagging polymorphisms and overall survival.
However, patients with two copies of the AACC (wild type) haplotype had significantly shorter survival than those with one or no copy (8.47 versus 14.57 months). This continued to be true after adjustment for factors including weight loss and second-line treatment (hazard ratio, 2.097).
This effect on survival was seen in patient with squamous cell carcinoma but not in those with adenocarcinomas.
"Therefore," concluded Dr. Ryu, "this result suggests that a new strategy is needed for these patients, especially in squamous cell carcinoma."
Young Patients with Lung Cancer Have Better Survival than Older Patients
The 5-year survival rate of patients with lung cancer is twice as high among those between the ages of 15 and 39 years as in those 40 years of age and older, according to data from the California Cancer Registry Database.
The findings of lung cancer prevalence, incidence and survival in the database between 1988 and 2006 were presented here by Dr. Laveena Chhatwani of the Stanford Cancer Center, California, during the 74th annual scientific assembly of the American College of Chest Physicians.
There were 2,728 patients with lung cancer who were between 15 and 39 years of age, comprising 0.08% of the lung cancer population. Dr. Chhatwani reported that the incidence of lung cancer in 15-39 year olds was 1.2 cases per 100,000, and in the 40-and-older age group it was 141 cases per 100,000.
Ethnic distribution was markedly different in the two age groups. In the young lung cancer patients, 55% were white, 19% were Hispanic, 12% were black and 12% were Asian. In contrast, 78% of lung cancer patients aged 40 years and older were white, 8% were Hispanic, 7% were black and 6% were Asian.
Distant disease was found at first diagnosis in 57% of the younger population compared with 51% of the older group.
Distribution of histologic subtypes differed by age, as well. Among younger patients, 39% had adenocarcinoma, 9% had squamous-cell carcinoma, 7% had small-cell carcinoma, 6% had large-cell carcinoma, 3% had bronchioloalveolar carcinoma and 35% had various other histologic subtypes.
Among older patients, 30% had adenocarcinoma, 19% had squamous-cell carcinoma, 13% had small-cell carcinoma and 28% had various other subtypes.
"Mean five-year cause-specific survival was 34% in the 15-39 year age group and 16% in the 40-and-older age group," Dr. Chhatwani reported. "At each disease stage, mean one- and five-year cause-specific survival rates were better in the younger group," she added.
"These findings suggest that lung cancer in the very young exhibits distinct clinical features," Dr. Chhatwani concluded. She attributed the better survival in the younger group to a higher prevalence of histologic subtypes that are associated with better survival.
The findings of lung cancer prevalence, incidence and survival in the database between 1988 and 2006 were presented here by Dr. Laveena Chhatwani of the Stanford Cancer Center, California, during the 74th annual scientific assembly of the American College of Chest Physicians.
There were 2,728 patients with lung cancer who were between 15 and 39 years of age, comprising 0.08% of the lung cancer population. Dr. Chhatwani reported that the incidence of lung cancer in 15-39 year olds was 1.2 cases per 100,000, and in the 40-and-older age group it was 141 cases per 100,000.
Ethnic distribution was markedly different in the two age groups. In the young lung cancer patients, 55% were white, 19% were Hispanic, 12% were black and 12% were Asian. In contrast, 78% of lung cancer patients aged 40 years and older were white, 8% were Hispanic, 7% were black and 6% were Asian.
Distant disease was found at first diagnosis in 57% of the younger population compared with 51% of the older group.
Distribution of histologic subtypes differed by age, as well. Among younger patients, 39% had adenocarcinoma, 9% had squamous-cell carcinoma, 7% had small-cell carcinoma, 6% had large-cell carcinoma, 3% had bronchioloalveolar carcinoma and 35% had various other histologic subtypes.
Among older patients, 30% had adenocarcinoma, 19% had squamous-cell carcinoma, 13% had small-cell carcinoma and 28% had various other subtypes.
"Mean five-year cause-specific survival was 34% in the 15-39 year age group and 16% in the 40-and-older age group," Dr. Chhatwani reported. "At each disease stage, mean one- and five-year cause-specific survival rates were better in the younger group," she added.
"These findings suggest that lung cancer in the very young exhibits distinct clinical features," Dr. Chhatwani concluded. She attributed the better survival in the younger group to a higher prevalence of histologic subtypes that are associated with better survival.
CT Screening May Detect Early Lung Cancer But Can Lead to Unneeded Surgery
New research indicates that while low-dose CT of the chest can identify lung cancer at an early, more treatable stage, it can also lead to major surgical procedures that uncover no cancer.
The Pittsburgh Lung Screening Study (PLuSS) represents the largest single-institution investigation of CT lung cancer screening in current and former cigarette smokers, according to the report in the November 1st issue of the American Journal of Respiratory and Critical Care Medicine.
The study included 3642 subjects, between 50 and 79 years of age, who were screened with low-radiation-dose CT. Repeat screening at 1 year was performed in 3423 of the subjects. To be eligible for the study, the subjects had to have smoked at least a half pack of cigarettes per day for 25 years or more and have no history of lung cancer.
A noncalcified lung nodule was identified in 40.6% of patients on the initial screening, Dr. David O. Wilson and colleagues, from the University of Pittsburgh, note. Prior to repeat screening, 55.6% of these patients underwent one or more diagnostic imaging studies.
During 3 years of follow-up, 80 subjects were found to have lung cancer, including 53 who had a tumor detected on initial screening.
Overall, 36 subjects (1%) who had an abnormality detected on the initial or repeat CT screen ended up having a major thoracic operation that resulted in a noncancer diagnosis. Of 82 subjects who underwent thoracotomy or video-assisted thorascopic surgery to rule out malignancy, 28 ultimately received a noncancer diagnosis.
Among 69 patients who had non-small cell lung cancer, 40 had stage 1 disease at diagnosis, the report indicates.
"Our challenge is how to reduce major surgery and morbidity from diagnostic procedures triggered by nodule discovery on CT," Dr. York E. Miller, from the University of Colorado, Denver, writes in a related editorial.
"Guidelines for the management of non-calcified pulmonary nodules have been suggested by several groups, with 'watchful waiting' the preferred option in some situations," Dr. Miller adds. These guidelines should be effective in reducing unnecessary surgical procedures if they are adhered to.
The Pittsburgh Lung Screening Study (PLuSS) represents the largest single-institution investigation of CT lung cancer screening in current and former cigarette smokers, according to the report in the November 1st issue of the American Journal of Respiratory and Critical Care Medicine.
The study included 3642 subjects, between 50 and 79 years of age, who were screened with low-radiation-dose CT. Repeat screening at 1 year was performed in 3423 of the subjects. To be eligible for the study, the subjects had to have smoked at least a half pack of cigarettes per day for 25 years or more and have no history of lung cancer.
A noncalcified lung nodule was identified in 40.6% of patients on the initial screening, Dr. David O. Wilson and colleagues, from the University of Pittsburgh, note. Prior to repeat screening, 55.6% of these patients underwent one or more diagnostic imaging studies.
During 3 years of follow-up, 80 subjects were found to have lung cancer, including 53 who had a tumor detected on initial screening.
Overall, 36 subjects (1%) who had an abnormality detected on the initial or repeat CT screen ended up having a major thoracic operation that resulted in a noncancer diagnosis. Of 82 subjects who underwent thoracotomy or video-assisted thorascopic surgery to rule out malignancy, 28 ultimately received a noncancer diagnosis.
Among 69 patients who had non-small cell lung cancer, 40 had stage 1 disease at diagnosis, the report indicates.
"Our challenge is how to reduce major surgery and morbidity from diagnostic procedures triggered by nodule discovery on CT," Dr. York E. Miller, from the University of Colorado, Denver, writes in a related editorial.
"Guidelines for the management of non-calcified pulmonary nodules have been suggested by several groups, with 'watchful waiting' the preferred option in some situations," Dr. Miller adds. These guidelines should be effective in reducing unnecessary surgical procedures if they are adhered to.
Outcomes Similar for Blacks and Whites with Lung Cancer When Surgery is Advised
Survival rates following a diagnosis of early-stage lung cancer tend to be lower among African American patients than among Caucasians. However, a study published in the January Archives of Surgery suggests that racial disparities in mortality are not seen when patients with health insurance are appropriately recommended surgical therapy, whether or not they actually undergo surgery.
According to Dr. David R. Flum, at the University of Washington in Seattle, and co-authors, "Health care system and provider biases and differences in patient characteristics are often thought to be predominant factors underlying racial disparities." They tested the theory that resection and survival rates would be similar regardless of race when patients with early-stage lung cancer were advised to have surgery.
They identified patients in the Surveillance, Epidemiology, and End Results-Medicare database who were diagnosed with stage I or II lung cancer between 1992 and 2002 and followed through the end of 2005. A total of 17,739 patients (median age 74 years; 89% white, 6% black) were recommended surgical therapy.
"Contrary to expectation, we observed a large...difference between black and white patients in the proportion of patients who actually underwent lung resection, even though all of the patients were recommended surgical therapy," the authors said. "Another surprising finding was that this large difference in receipt of optimal therapy did not appear to affect long-term survival."
Specifically, the researchers report, 69% of black patients and 83% of white patients underwent resection (p < 0.001). After adjustment for patient and cancer characteristics, black race was associated with lower odds of receiving surgery (hazard ratio 0.45).
In unadjusted analysis, black patients had a lower 5-year overall survival rate (36% vs 42%). However, after adjustment, there was no significant association between race and mortality (HR 1.03), or between race and lung cancer cause-specific mortality (HR 1.01).
These findings, the authors suggest, imply that factors such as perceptions and beliefs about lung cancer and its treatment, distrust of physicians, and limited access to subspecialty care may play a large role in racial health disparities.
On the other hand, they say, the absence of a survival difference could be explained "if white patients undergoing operations were at higher risk (defined by poorer pulmonary function) for death compared with black patients undergoing operations, counterbalancing the effect of more lung resections among white patients compared with black patients." Such a scenario could mean that surgery was overused in whites and/or underused in blacks.
Dr. Flum's team concludes: "Interventions designed to narrow gaps in health care should target structural aspects of care, providers, and patients and communities at risk for lung cancer and suboptimal care."
According to Dr. David R. Flum, at the University of Washington in Seattle, and co-authors, "Health care system and provider biases and differences in patient characteristics are often thought to be predominant factors underlying racial disparities." They tested the theory that resection and survival rates would be similar regardless of race when patients with early-stage lung cancer were advised to have surgery.
They identified patients in the Surveillance, Epidemiology, and End Results-Medicare database who were diagnosed with stage I or II lung cancer between 1992 and 2002 and followed through the end of 2005. A total of 17,739 patients (median age 74 years; 89% white, 6% black) were recommended surgical therapy.
"Contrary to expectation, we observed a large...difference between black and white patients in the proportion of patients who actually underwent lung resection, even though all of the patients were recommended surgical therapy," the authors said. "Another surprising finding was that this large difference in receipt of optimal therapy did not appear to affect long-term survival."
Specifically, the researchers report, 69% of black patients and 83% of white patients underwent resection (p < 0.001). After adjustment for patient and cancer characteristics, black race was associated with lower odds of receiving surgery (hazard ratio 0.45).
In unadjusted analysis, black patients had a lower 5-year overall survival rate (36% vs 42%). However, after adjustment, there was no significant association between race and mortality (HR 1.03), or between race and lung cancer cause-specific mortality (HR 1.01).
These findings, the authors suggest, imply that factors such as perceptions and beliefs about lung cancer and its treatment, distrust of physicians, and limited access to subspecialty care may play a large role in racial health disparities.
On the other hand, they say, the absence of a survival difference could be explained "if white patients undergoing operations were at higher risk (defined by poorer pulmonary function) for death compared with black patients undergoing operations, counterbalancing the effect of more lung resections among white patients compared with black patients." Such a scenario could mean that surgery was overused in whites and/or underused in blacks.
Dr. Flum's team concludes: "Interventions designed to narrow gaps in health care should target structural aspects of care, providers, and patients and communities at risk for lung cancer and suboptimal care."
Study Looks At Survival, Racial Disparities Among Lung Cancer Patients Who Undergo Surgery
"Racial Disparities Among Patients With Lung Cancer Who Were Recommended Operative Therapy," Archives of Surgery: Researchers led by Farhood Farjah of University of Washington's Surgical Outcomes Research Center examined 17,739 patients who were diagnosed with early stage lung cancer between Jan. 1, 1992, and Dec. 31, 2002, and were recommended to receive lung resection. Among those patients, 69% of blacks received the surgery, compared with 83% of whites. However, after making adjustments, researchers found no significant association between race and death, despite the 14% difference in the receipt of surgery. The findings suggest that "distrust, beliefs and perceptions about lung cancer and its treatment, and limited access to care (despite insurance) might have a more dominant role in perpetuating racial disparities than previously recognized," according to the study (Archives of Surgery, January 2009). Reprinted with kind permission from http://www.kaisernetwork.org. You can view the entire Kaiser Daily Health Policy Report, search the archives, or sign up for email delivery at http://www.kaisernetwork.org/dailyreports/healthpolicy. The Kaiser Daily Health Policy Report is published for kaisernetwork.org, a free service of The Henry J. Kaiser Family Foundation.
Smoking Linked To Most Male Cancer Deaths
The epidemiological analysis linked smoking to more than 70 percent of the cancer death burden among Massachusetts men in 2003. This percentage is much higher than the previous estimate of 34 percent in 2001.
"This study provides support for the growing understanding among researchers that smoking is a cause of many more cancer deaths besides lung cancer," said lead author Bruce Leistikow, a UC Davis associate adjunct professor of public health sciences. "The full impacts of tobacco smoke, including secondhand smoke, have been overlooked in the rush to examine such potential cancer factors as diet and environmental contaminants. As it turns out, much of the answer was probably smoking all along."
Leistikow used National Center for Health Statistics data to compare death rates from lung cancer to death rates from all other cancers among Massachusetts males. The assessment revealed that the two rates changed in tandem year-by-year from 1979 to 2003, with the strongest association among males aged 30-to-74 years.
Smoking is a known cause of most lung cancers, and the study authors concluded that the very close relationship over twenty-five years between lung and other cancer death rates suggests a single cause for both: tobacco smoke.
Leistikow, whose research is dedicated to uncovering the causes of premature mortality, said, "The fact that lung and non-lung cancer death rates are almost perfectly associated means that smokers and nonsmokers alike should do what they can to avoid tobacco smoke. It also suggests that increased attention should be paid to smoking prevention in health care reforms and health promotion campaigns."
The current study was funded by UC Davis, the Health Research Board (Ireland) and the National Cancer Institute.
Coauthors of the study were Zubair Kabir of the Harvard School of Public Health and the Research Institute for a Tobacco-Free Society (Ireland), Gregory Connolly and Hillel R. Alpert of the Harvard School of Public Health and Luke Clancy of the Research Institute for a Tobacco-Free Society.
"This study provides support for the growing understanding among researchers that smoking is a cause of many more cancer deaths besides lung cancer," said lead author Bruce Leistikow, a UC Davis associate adjunct professor of public health sciences. "The full impacts of tobacco smoke, including secondhand smoke, have been overlooked in the rush to examine such potential cancer factors as diet and environmental contaminants. As it turns out, much of the answer was probably smoking all along."
Leistikow used National Center for Health Statistics data to compare death rates from lung cancer to death rates from all other cancers among Massachusetts males. The assessment revealed that the two rates changed in tandem year-by-year from 1979 to 2003, with the strongest association among males aged 30-to-74 years.
Smoking is a known cause of most lung cancers, and the study authors concluded that the very close relationship over twenty-five years between lung and other cancer death rates suggests a single cause for both: tobacco smoke.
Leistikow, whose research is dedicated to uncovering the causes of premature mortality, said, "The fact that lung and non-lung cancer death rates are almost perfectly associated means that smokers and nonsmokers alike should do what they can to avoid tobacco smoke. It also suggests that increased attention should be paid to smoking prevention in health care reforms and health promotion campaigns."
The current study was funded by UC Davis, the Health Research Board (Ireland) and the National Cancer Institute.
Coauthors of the study were Zubair Kabir of the Harvard School of Public Health and the Research Institute for a Tobacco-Free Society (Ireland), Gregory Connolly and Hillel R. Alpert of the Harvard School of Public Health and Luke Clancy of the Research Institute for a Tobacco-Free Society.
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