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Patients with cystic fibrosis (CF) recover from exacerbations equally well if they are treated at home or in a hospital, according to researchers from Johns Hopkins University. Furthermore, longer treatment with antibiotics does not appear to offer any additional benefit over shorter courses.
The study was published online ahead of the print edition of the American Thoracic Society’s American Journal of Respiratory and Critical Care Medicine.
“We undertook this research owing to the lack of clinical information of best practices in treating CF exacerbations available to physicians,” said J. Michael Collaco, M.D., assistant professor at Johns Hopkins.
In 2008 patients with CF had an average lifespan of only 37.4 years, and most died of the progressive pulmonary obstruction associated with the disease. The progression of the disease may be hastened by recurrent exacerbations.
“Traditional management includes aggressive airway clearance and antibiotics, the latter frequently administered intravenously, but despite effective symptomatic therapy, many patients may never completely recover their baseline lung function. Thus, it is crucial to determine the most effective means of therapy delivery for CF respiratory exacerbations,” said Dr. Collaco. “Unfortunately, due to the difficulty of performing randomized controlled trials, existing evidence is insufficient for many treatment issues, including the best site for delivery of care and the optimal duration of therapy.”
Outpatient intravenous antibiotic therapy has gained widespread acceptance because of its advantages over hospitalization including: fewer absences from school or work, less disruption of family life, decreased costs per treatment course, and high patient satisfaction. However, long-term costs may not be reduced in the outpatient setting if it precipitates the need for longer and more frequent courses of antibiotics, and quality of life may not always be better.
Dr. Collaco and colleagues from Johns Hopkins University used data from 1535 individuals in 755 families from the U.S. Cystic Fibrosis Twin-Sibling Study, a large, multi-center study directed by Garry Cutting, M.D., professor of genetics at Johns Hopkins. This analysis of the Twin-Sibling Study data compared levels of baseline lung function (forced expiratory volume in one second, or FEV1) to lung function at the end of treatment and over the year after treatment.
Dr. Collaco and colleagues found that exacerbations were followed by long-term declines in lung function regardless of whether antibiotics were administered in the hospital or at home, and no difference in intervals between courses of antibiotics was observed between hospital and home.
“This research indicates that intravenous antibiotic therapy for CF respiratory exacerbations administered in the hospital and in the home may be equivalent in terms of long-term FEV1 change and interval between courses of antibiotics,” said Dr. Collaco. “Furthermore, we found that, based on improvement of FEV1, optimal duration of therapy may be seven to 10 days, as opposed to between 10 and 21 days, as is seen in current practice.”
Patients who had a greater decline in lung function prior to starting therapy experienced steeper long-term declines following that course of therapy, indicating that more severe exacerbations have long-lasting effects, regardless of short-term treatment success. “This finding implies that patients with drastic drops in lung function with an exacerbation should be monitored more closely following treatment, for even with recovery of lung function, they remain at higher risk for greater long-term decline,” said Dr. Collaco.
Dr. Collaco acknowledged that subjects participating in the Twin-Sibling Study may be more motivated than the general CF population, and thus may have increased compliance with antibiotics and chest physiotherapy when treated at home. These subjects are also members of families where more than one sibling has CF, thus these families may be more adept with home care, which could have biased the outcome toward the benefit of home therapy.
“Ultimately,” he said, “given the decline in baseline FEV1 after an exacerbation, preventing exacerbations may be more important than the approach taken to treat the exacerbation. Taken together, our findings underscore the CF community’s need for determining an optimal approach to the treatment of pulmonary exacerbations. Large prospective studies are needed to answer these essential questions for CF respiratory management.”
Exposure to high levels of fungus may increase the risk of severe asthma attacks among people with certain chitinase gene variants, according to a study from Harvard Medical School, Harvard Pilgrim Health Care Institute and Brigham and Women’s Hospital.
The research was published online on the American Thoracic Society’s journal Web site ahead of the print edition of the American Journal of Respiratory and Critical Care Medicine.
“We found that the interaction between environmental mold exposure and certain variants of chitinase genes were positively associated with severe asthma exacerbations requiring hospitalization,” said lead researcher, Ann Wu, assistant professor at the at Harvard Medical School and Harvard Pilgrim Health Care Institute.
Chitinases break down chitin, a component in many fungi, and are induced during allergic inflammation. It has been suggested by past research that these could be biomarkers of inflammation. Moreover, certain variants of chitinase genes are known to be expressed more heavily in people with asthma.
The researchers used data from the Childhood Asthma Management Program, a multicenter trial that enrolled children between the ages of 5 and 12 with mild to moderate persistent asthma. Mold measures were taken in the subjects’ homes at the beginning of the study, and homes were classified as having greater or less than 25,000 mold colonies per gram of household dust.
“This level of mold in dust is high for a residential environment. However, it is not likely to be easily recognized. Studies have shown that homes that have problems with dampness (e.g. visible mold on walls/ceilings, water collection in basement, etc.) have higher levels of mold, but there is no specific level that is currently accepted to ’cause’ problems,” said Dr. Wu.
Finally, using blood samples, the researchers genotyped all the single nucleotide polymorphisms — SNPs, or variants in which just a single “letter” of the DNA code in a given gene is different — of chitinase genes and a chitinase-like gene within the study population.
They then analyzed the appearance of different variations of chitinase genes with level of mold exposure and number of hospital visits from severe asthma exacerbations. They found that certain variants of the chitinase gene CHIT1, in conjunction with high mold exposure, were associated with increased risk of severe asthma attacks.
“Our results support increasing evidence that CHIT1, which is primarily expressed in the lung, plays an important role in the pathophysiology of asthma in the proper environmental context of exposure to chitin, which was approximated by mold levels,” said Dr. Wu. “To our knowledge this was the first study to examine the effect of mold levels on the association of SNPs in the genes of both chitinases and chitinase-like proteins with asthma and allergy-related phenotypes.”
Chitinases may play a role in future targets for asthma therapy. Inhibition of chitinase enzymatic activity has been demonstrated to prevent hyper-responsiveness and inflammation in mice. It is plausible, said Wu, that therapeutics designed to block chitinase enzyme activity may prevent hyper-responsiveness and inflammation related to asthma.
“Future research should focus on expanding and replicating these findings,” she said. “The focus should be on mechanisms of chitinases and chitinase-like proteins in allergic inflammation. Additionally, finding other genes that may interact with mold exposure will also be important. We plan to find a population to replicate these findings. Additionally, we are preparing to perform a Genome-Wide Association Study in this same population to identify other genes that may interact with mold exposure.”
Daily use of probiotics reduced ventilator-associated pneumonia (VAP) in critically ill patients by almost half, according to new research from Creighton University School of Medicine in Omaha, Nebraska.
The study was published on the American Thoracic Society’s Web site ahead of the print edition of the American Journal of Respiratory and Critical Care Medicine.
It is estimated that VAP complicates the care of up to 30 percent of critical care patients receiving mechanical ventilation. “Patients with VAP have increased morbidity, mortality and hospital costs as well as prolonged intensive care unit (ICU) and hospital lengths of stay, and increased costs.”
“We chose to study probiotics in this context because VAP is increasingly caused by pathogens associated with antimicrobial resistance and the supply of novel antibiotics is essentially nonexistent for the foreseeable future,” said Lee E. Morrow, M.D., M.Sc., associate professor of medicine at Creighton University and lead author. “The implication is that novel methods of prevention must be our priority.”
Although previous studies have suggested that probiotics might be effective in reducing risk of VAP, the results have been limited by the quality of their design.
“We were unsure what to expect with this trial,” said Dr. Morrow. “Ultimately our hope was that upon completion of this ‘proof of concept’ study we could demonstrate two critically important points in a patient group at high risk for developing VAP: One, that properly selected probiotic agents can be safely administered to critically ill patients; and, two, when administered to the proper study population these agents also have efficacy in disease prevention. We felt that rigorously establishing these suppositions as facts was essential in order to continue to study probiotic agents in the intensive care unit setting.”
Dr. Morrow and colleagues included 138 critically ill patients from a single center to receive either placebo or probiotic therapy. Patients in the treatment arm received 2 x 109 colony-forming units of Lactobacillus rhamnosus twice daily — half the dose was administered as a slurry to the oropharynx and the remainder was given through nasogatsric tube. After almost 5 years, the researchers found that daily use of probiotics not only decreased VAP infections by about 50 percent compared to placebo, but also reduced the amount of antibiotics needed in comparison to placebo-treated patients. This reduction in antibiotic consumption led to significantly fewer Clostridium difficile infections in patients given probiotics. No side effects attributable to the probiotics were observed.
Meta analysis of similar studies shows an overall reduction in VAP of 39 percent with probiotics.
“Collectively, these data suggest that Lactobacillus may represent a novel, inexpensive (retail price, $2.13 per day for four tablets as administered per protocol), and non-antibiotic approach to prevention of nosocomial infections in properly selected ICU patients,” said Dr. Morrow.
Because the patients were carefully selected to reduce the risk of iatrogenic infection, and over 90 percent of patients in the ICU were deemed ineligible for the study, it is important to note, Dr. Morrow cautioned, that these findings are not applicable to all ICU patients and probiotics should not be used for VAP prophylaxis beyond the population that was included in this study.
“We strongly emphasize that these data should be viewed as preliminary in nature and cannot be generalized to the general ICU population given the prolonged period of enrolment, the rigorous inclusion criteria, the large number of exclusion criteria and the small number of patients included.
Other studies have found potentially harmful effects of probiotics, underscoring the need for meticulous monitoring of patients.
“Probiotic prophylaxis of VAP using Lactobacillus rhamnosus GG appears safe and efficacious in a select population with a very high risk of VAP,” concluded Dr. Morrow. “Ultimately, probiotics may fulfill a role in antimicrobial stewardship programs given the reductions in antibiotic consumption. Larger, multicenter clinical trials with more liberal inclusion criteria are needed to establish efficacy of probiotics and to allow for extrapolation to a larger at-risk population.”
PHOENIX, Ariz. — June 14, 2010 — Researchers at the Translational Genomics Research Institute (TGen), the Van Andel Research Institute (VARI) and the Virginia G. Piper Cancer Center at Scottsdale Healthcare have discovered a biomarker that could help in the treatment of patients with an aggressive type of lung cancer.
Using a particular biomarker, researchers might better predict which patients with small cell lung cancer are resistant to existing drug therapies, and which ones could benefit from new therapies tailored to their specific needs, according to a scientific paper published today in the Journal of Thoracic Oncology.
“There is a need for predictive biomarkers that can aid investigators in designing future clinical trials, to help identify treatments that might be effective for these patients who most likely will be resistance to existing drug therapies, ” said Dr. Glen J. Weiss, the paper’s senior author and Director of Thoracic Oncology at TGen Clinical Research Services at Scottsdale Healthcare. TCRS is a partnership between TGen and Scottsdale Healthcare that helps bring new therapies quickly to patients at the Virginia G. Piper Cancer Center in Scottsdale.
Nearly 220,000 Americans are diagnosed each year with lung cancer, which is by far the leading cause of cancer death in the U.S., annually killing nearly 160,000 patients.
Of all lung cancer patients, an estimated 33,000 are diagnosed with SCLC. This is a particularly aggressive disease that usually goes undetected until it is in an advanced stage and treatment options are limited. More than 95 percent of SCLC patients eventually die from the disease.
Researchers from TGen, VARI and the Virginia G. Piper Cancer Center at Scottsdale Healthcare focused on identifying microRNAs, which are single-stranded RNA molecules that regulate how genes and proteins control cellular development. Because microRNAs are so resilient, they are relatively easy to detect in tumor tissue and blood, which is often a limitation for other biomarkers.
“VARI provided bioinformatics support assembling all the different types of data into a cohesive data set for analysis to help identify the miRNA that play a role in the survival of the lung cancer patients,” said Dr. David Cherba, a VARI Bioinformatics Scientist.
Researchers profiled 34 tumor samples from patients with a median age of 69. They analyzed each tumor’s microRNAs, searching for those that might be associated with cancer survival.
They identified three microRNAs associated with SCLC. But one in particular, identified as miR-92-2*, was “significantly” linked to survival, the paper said.
This microRNA could be used in two significant ways:
“Our results demonstrate that higher tumor miR-92a-2* levels are associated with chemoresistance and with decreased survival in SCLC patients,” said the paper titled MicroRNA 92a-2*, a Biomarker Predictive for Chemoresistance and Prognostic for Survival in Small Cell Lung Cancer Patients.
This was one of the first scientific papers published since the completion of the TGen-VARI alliance and affiliation agreement, announced in February.
“The collaboration that occurred on this project highlights the synergies created by the VARI-TGen alliance,” said Dr. Craig Webb, a VARI Senior Scientific Investigator.
Dr. Jeffrey Trent, President and Research Director for TGen and VARI, said the new discoveries could have profound implications for the future of medicine.
“This advanced technology is exciting because of how these microRNA biomarkers could lead to improvements for patients. Hopefully, this will translate to new treatments and improved survival,” Dr. Trent said.
The next step in this research should be to attain further validation by analyzing additional independent samples, the paper concludes.
This study was funded by the American Cancer Society, a Sylvia Chase Pilot Grant and the IBIS Foundation of Arizona.
About the Virginia G. Piper Cancer Center at Scottsdale Healthcare
The Virginia G. Piper Cancer Center at Scottsdale Healthcare offers diagnosis, treatment, research, prevention and support in its facilities at the Scottsdale Healthcare Shea Medical Center, attracting patients from across Arizona and the U.S. Groundbreaking cancer research is conducted through its Scottsdale Healthcare Research Institute in collaboration with TGen and leading universities. Scottsdale Healthcare is the not-for-profit parent organization of the Scottsdale Healthcare Shea Medical Center, Scottsdale Healthcare Osborn Medical Center and Scottsdale Healthcare Thompson Peak Hospital, Virginia G. Piper Cancer Center, Scottsdale Healthcare Research Institute and Scottsdale Healthcare Foundation. For additional information, please visit www.shc.org.
Press Contact:
Keith Jones, Director of Public Relations
Virginia G. Piper Cancer Center at Scottsdale Healthcare
480-882-4412
[email protected]
About VARI
Established by Jay and Betty Van Andel in 1996, Van Andel Institute (VAI) is an independent research and educational organization based in Grand Rapids, Mich., dedicated to preserving, enhancing and expanding the frontiers of medical science, and to achieving excellence in education by probing fundamental issues of education and the learning process. The Van Andel Research Institute (VARI), the research arm of VAI, is dedicated to probing the genetic, cellular and molecular origins of cancer, Parkinson and other diseases and working to translate those findings into effective therapies. This is accomplished through the work of over 200 researchers in 18 on-site laboratories, in laboratories in Singapore and Nanjing, and in collaborative partnerships that span the globe.
Press Contact:
Joe Gavan
Vice President, Communications & Development
616-234-5390
About TGen
The Translational Genomics Research Institute (TGen) is a Phoenix-based non-profit organization dedicated to conducting groundbreaking research with life changing results. Research at TGen is focused on helping patients with diseases such as cancer, neurological disorders and diabetes. TGen is on the cutting edge of translational research where investigators are able to unravel the genetic components of common and complex diseases. Working with collaborators in the scientific and medical communities, TGen believes it can make a substantial contribution to the efficiency and effectiveness of the translational process. For more information, visit: www.tgen.org.
Press Contact:
Steve Yozwiak
TGen Senior Science Writer
602-343-8704
[email protected]
Researchers from Brigham and Women’s Hospital and the Harvard School of Public Health have established the first link between air pollution and sleep-disordered breathing (SDB), a known cause of cardiovascular diseases.
Antonella Zanobetti, Ph.D., Susan Redline, MD, MPH, Diane Gold, M.D., M.P.H. and colleagues explored the link between air pollution levels, temperature increases and sleep-disordered breathing using data from the Sleep Heart Health Study, which included more than 6,000 participants between 1995 and 1998, and EPA air pollution monitoring data from Framingham (Massachusetts), Minneapolis, New York City, Phoenix, Pittsburgh, Sacramento, and Tucson.
The study appears online ahead of the print edition of the American Journal of Respiratory and Critical Care Medicine on the American Thoracic Society’s Web site.
SDB affects up to 17 percent of U.S. adults, many of whom are not aware that they have a problem. Air pollution is also an endemic issue in many of the nation’s urban areas. Both SDB and pollution have been associated with a range of health problems, including increased cardiovascular mortality. “The influence of air pollution on SDB is poorly understood,” said Dr. Zanobetti. “Our hypothesis was that elevation in ambient air pollution would be associated with an increased risk of SDB and nocturnal hypoxia, as well as with reduced sleep quality.” The researchers further hypothesized that seasonal variations in temperature would exert an independent effect on SDB and sleep efficiency.
To test their hypotheses, the researchers used linear regression models that controlled for seasonality, mean temperature and other factors known to be associated with SDB, such as age, gender and smoking.
To examine the role of seasons, they performed a separate analysis, adding the interaction of season with the level of air pollution in the form of particulate matter under 10 μm, which is commonly associated with traffic. They evaluated long-term effects by computing the moving 365-day average of PM10.
In total, they included more than 3,000 individuals in their analysis.
“We found novel evidence for pollution and temperature effects on sleep-disordered breathing,” said Dr. Zanobetti. “Increases in apnea or hypopnea were associated with increases in short-term temperature over all seasons, and with increases in particle pollution levels in the summer months.”
Over all seasons, the researchers found that short-term elevations in temperature were associated with increased in Respiratory Disturbance Index (RDI), which was used to gauge the severity of SDB. In the summer, increases in PM10 were also associated with an increase in RDI (representing a 12.9 percent increase), as well as with an increase in the percent of time that blood oxygen saturation levels fell below 90 percent (representing a nearly 20 percent increase) and a decrease in sleep efficiency. There were no such statistically significant associations of particulate pollution with SDB in other seasons.
This is the first study to link pollution exposure and SDB.
“Particles may influence sleep through effects on the central nervous system, as well as the upper airways,” wrote Dr. Zanobetti. “ Poor sleep [associated with poor health outcomes] may disproportionately afflict poor urban populations. Our findings suggest that one mechanism for poor sleep and sleep health disparities may relate to environmental pollution levels.”
Other research has found an association between elevation in pollution and increased risk of sudden infant death syndrome (SIDS). There is a known overlap between etiologic factors for SIDS and SDB. Given the results of the current research, “the mechanisms that increase the risk of SIDS in associations with ambient pollutants may be similar to the mechanisms that underlie the risk of SDB ,[which] may include pollutant-associated effects on central or peripheral neurotransmitters that influence sleep-state stability,” said Dr. Zanobetti.
Several studies have also reported that temperature predicts mortality. “The association we found between short-term temperature and RDI could represent one possible mechanism by which changes across the range of temperature could predict mortality,” said Dr. Zanobetti.
Perhaps most importantly, the prevalence of SDB in the United States may increase as obesity rises. “While therapies are available for the disorder, the majority of adults with SDB are not being treated and many people are resistant to therapy,” said Dr. Zanobetti. “Along with reduction in obesity, these new data suggest that reduction in air pollution exposure might decrease severity of SDB and nocturnal hypoxia and may improve cardiac risk.”
John Heffner, M.D., past president of the American Thoracic Society observed, “This study gains even greater importance as scientists increasingly demonstrate the critical importance of sleep to health and well being. SDB increases risks for cardiovascular disease, strokes and other major health conditions. Air pollution is an independent contributor to most of these disorders and may produce its negative health effects by promoting SDB as an intermediary step in the pathway toward disease.”
This study was funded by the National Heart Lung and Blood Institute, the National Institute of Environmental Health Sciences and the Environmental Protection Agency.
Link to podcast: http://www.thoracic.org/newsroom/press-releases/journal/podcast/061510-zanobetti.mp3
Doctors have long known that snoring is hazardous to health for a number of reasons. In addition to restless nights and increased daytime sleepiness, sleep-disordered breathing (SDB) has a series of associated health problems, including increased risk of cardiovascular disease (CVD). While it is not always clear what the association between SDB and a given health problem is, new research exposes that at least one factor may help to explain the increased risk of cardiovascular problems that affects even people with mild to moderate SDB.
Researcher Reena Mehra, M.D., M.S., assistant professor of medicine at the Case Western Reserve School of Medicine in Cleveland, Ohio, and colleagues set out to investigate the morning and evening levels of three pro-thrombotic markers, plasminogen activator inhibitor-1 (PAI-1), fibrinogen and D-dimer, relative to the severity of SDB as defined by the apnea/hypopnea index (AHI) in 537 subjects.
The study appears online ahead of the print edition of the American Journal of Respiratory and Critical Care Medicine on the American Thoracic Society’s Web site.
After controlling for variables including body mass index (BMI), age, sex and co-morbidities, they found that for every 5-unit increase in AHI under 15, there was a corresponding significant increase of about 10 percent in PAI-1. Similarly, for every 5-unit increase in AHI under 15, fibrinogen significantly increased on average by about 8.4 mg/dL. There was no significant increase in D-dimer in relation to AHI, however.
“These data suggest that individuals with even modest levels of SDB (which describes a large proportion of the adult population) may have an enhanced pro-thrombotic biochemical profile, increasing their CVD risk,” said Dr. Mehra.
Increased morning PAI-1 remained significantly associated with SDB severity in those with mild to moderate SDB even after taking into account evening PAI-1, suggesting that morning may be a reflection of overnight SDB-related physiologic stress, and indicating that PAI-1 may be a good biomarker for assessing SDB stress. These diurnal findings were not noted with fibrinogen.
Interestingly, there was no association between either PAI-1 or fibrinogen at AHI above 15, which is generally the clinical cut-off between moderate and more sever SDB. “These data suggest that even at levels of SDB considered to be mild, there is an enhanced thrombotic state. Further research is needed to identify whether treatment of milder degree of SDB results in improvements in markers of thrombosis, a known contributor to cardiovascular disease,” said Dr. Mehra.
“In summary, these data suggest that, at low to modest levels of SDB, incremental increases in AHI are associated with increases in levels of two pro-thrombotic biomarkers associated with CVD. Future directions include exploring whether treatment of even mild to moderate levels of SDB improves biomarkers of thrombosis, and performing further work to understand the specific pathways and pathobiology of SDB-related increased risk of thrombosis.”
John Heffner, M.D., past president of the American Thoracic Society, commented, “This study joins so many others that paint a consistent picture of sleep as a fundamentally important physiologic process for health that can negatively impact multiple organ systems when disordered breathing occurs. This study provides an important insight into how sleep disruptions can trigger prothrombotic processes that may eventually lead to cardiovascular diseases and perhaps other conditions like strokes. Other investigators will now pursue the interaction of SDB with prothrombic states.”
This research was funded by the National Heart Lung Blood Institute.
HOUSTON – Oropharyngeal cancer patients whose tumors in the upper part of the throat test positively for the human papillomavirus (HPV) have better overall survival than patients with HPV-negative disease, researchers from The University of Texas MD Anderson Cancer Center report in a study published in the New England Journal of Medicine.
The study – the largest and most definitive to date completed in a joint effort with the Radiation Therapy Oncology Group (RTOG) – shows that tumor HPV status is a strong and independent prognostic factor for survival for these patients. Follow-up data from the study were presented today at the 44th annual meeting of the American Society of Clinical Oncology (Abstract #5510).
“This is the strongest prognostic factor we have ever identified for head and neck cancer patients,” said K. Kian Ang, M.D., Ph.D., professor in MD Anderson’s Department of Radiation Oncology and lead author on the paper. “Its value is stronger than other prognostic factors we have used such as the size of the tumor or presence of tumor in lymph nodes. Knowing that the tumor is associated with HPV is telling the patient that the prognosis is excellent with currently available treatments.”
The Phase III clinical trial established by the RTOG examined overall survival and progression-free survival in 323 patients with stage III-IV oropharyngeal cancer treated with a combination of radiation therapy and chemotherapy. Of these patients, 206 had HPV-positive tumors and 117 were HPV-negative. The three-year overall survival rate for patients with HPV-positive tumors was 82.4 percent compared to 57.1 percent with HPV-negative cancer. Progression-free survival rates were 73.7 percent and 43.4 percent, respectively.
When researchers adjusted for other significant determinants of survival, including patient age, race, tumor and nodal stage and tobacco use, patients with HPV-positive cancer had a 58 percent reduction in risk of death relative to patients with HPV-negative tumors. The study noted tobacco use substantially increased risk of death. Results will allow physicians to stratify patients enrolled in clinical trials into low, intermediate or high-risk of death based on HPV status, tobacco use and cancer stage. This information can then be used to better determine which patients are candidates for more intensive investigational therapies.
Oropharyngeal cancer develops in the part of the throat just behind the mouth. The American Cancer Society estimates that 28,500 people in the United States are diagnosed with cancer of the oral cavity and oropharynx each year. While the incidence of head and neck cancer has been declining during the past 30 years, the rate of HPV-positive oropharyngeal cancer is rapidly rising. Today, nearly 70 percent of oropharynx cancer cases are HPV-positive.
Ang credits the strength of the study to its size and the importance of collaboration among investigators. “Even large cancer centers like MD Anderson cannot do these types of studies alone. Working with our collaborators including, Maura Gillison, M.D., Ph.D., professor of medicine, epidemiology and otolaryngology at The Ohio State University, an experienced investigator on the role of HPV in head and neck cancer and co-author on the study, we were able to build on what smaller studies have suggested and produce numbers large enough to examine HPV status together with other prognostic factors.”
Head and neck tumors are routinely tested for HPV at MD Anderson and other large institutions. While it remains unclear why patients with HPV-positive tumors have better outcomes than those with HPV-negative tumors, researchers speculate it may be due to biologic and immunologic properties that render HPV-positive cancers inherently less malignant or better able to respond to treatment. Ang notes future studies are warranted to determine how the HPV vaccine, made available to the public in 2006, affects the incidence of HPV-related head and neck cancers.
In addition to Ang and Gillison, other authors on the study include: Randal Weber, M.D., Department of Head and Neck Surgery, David Rosenthal, M.D., Department of Radiation Oncology, Charles Lu, M.D., Department of Thoracic/Head and Neck Medical Oncology, all from MD Anderson; Jonathan Harris, M.S., RTOG Statistical Center; Richard Wheeler, M.D., Huntsman Cancer Institute; Phuc Nguyen-Tan, M.D., entra Hospitaler de L’Universite de Montreal; William Westra, M.D., The Johns Hopkins University; Christine Chung, M.D., Vanderbilt University School of Medicine; Richard Jordan, D.D.S., Ph.D., The University of California at San Francisco; Rita Axelrod, M.D., Thomason Jefferson University Hospital; Craig Silverman, M.D., University of Louisville, Kevin Redmond, M.D., University of Cincinnati College of Medicine.
The RTOG is a multi-institutional international clinical cooperative group funded primarily by National Cancer Institute grants CA21661 and CA37422. RTOG comprises 300 major research institutions in the United States, Canada and internationally.
About MD Anderson
The University of Texas MD Anderson Cancer Center in Houston ranks as one of the world’s most respected centers focused on cancer patient care, research, education and prevention. MD Anderson is one of only 40 comprehensive cancer centers designated by the National Cancer Institute. For six of the past eight years, including 2010, MD Anderson has ranked No. 1 in cancer care in “America’s Best Hospitals,” a survey published annually in U.S. News & World Report.
CHICAGO – Selenium, a supplement taken daily by millions in hopes of protection against cancer and a host of other diseases, has proven to be of no benefit in reducing a patient’s risk of developing lung cancer – either a recurrence or second primary malignancy, according to results of an international Phase III clinical trial.
Results from the decade-long study, initiated by the Eastern Cooperative Oncology Group, were presented today at the American Society of Clinical Oncology 2010 Annual Meeting by Daniel D. Karp, M.D., professor in the Department of Thoracic/Head and Neck Medical Oncology at The University of Texas MD Anderson Cancer Center.
“Several epidemiological and animal studies have long-suggested a link between deficiency of selenium and cancer development,” said Karp, the study’s principal investigator. “Interest and research escalated in the late 1990’s after a skin cancer and selenium study, published in 1996, found no benefit against the skin cancer, but did suggest an approximate 30 percent reduction of prostate and lung cancers. Our lung cancer research and another major study for the prevention of prostate cancer evolved from that finding.”
These large, follow-up clinical studies investigating the naturally occurring mineral, however, have since proven disappointing. In 2009, the National Cancer Institute (NCI) halted SELECT, an international study of more than 35,000 men investigating if either selenium or Vitamin E, alone or in combination, could reduce the risk of prostate cancer. Both supplements failed to show benefit.
According to the American Cancer Society, approximately 219,440 people were diagnosed with lung cancer in 2009 and 159,390 died from the disease, making it the leading cause of cancer death in both men and women. When caught as early as Stage I, and the tumor is surgically resectable, however, and can even be cured in about 80 percent of the cases. In this population, a chemoprevention agent would be desirable, as the risk of recurrence in Stage I patients after surgery accumulates by one to two percent annually. For example, a patient’s risk of developing a new cancer at 10 years is approximately 10-20 percent, said Karp.
From 2000 to 2009, the international NCI-sponsored Phase III study, enrolled 1,522 Stage I non-small cell lung cancer patients, all of whom had their tumors surgically removed and were cancer-free for at least six months post-surgery. Participants were randomized to receive either 200 micrograms of selenium or placebo. The study’s primary endpoints were reduction of development of a new cancer, or second primary, and/or recurrence of their initial cancer.
The study was halted early after an interim analysis revealed that the progression-free survival was superior in the placebo arm: 78 percent taking the placebo were alive without recurrence after five years, compared to 72 percent on selenium. A total of 216 secondary primary tumors developed, of which 84 (38.9 percent) were lung cancers. Of those taking selenium, 1.9 percent developed a second primary tumor after the first year, compared to 1.4 percent taking placebo. In total, 3.66 percent of participants in the selenium arm developed a secondary primary tumor of any type after one year, compared to 4.1 percent in the placebo group.
Side effects were minimal and no different in both groups: of those taking placebo, 38 percent had grade 1 or 2 toxicity, and 3 percent had grade 3, compared to 39 percent and 1 percent, respectively in those taking the supplement. The study was stopped by the independent Data and Safety Monitoring Committee due to futility.
The researchers did find that in a small group of the lung cancer patients who were never smoked, selenium did provide a small benefit; however, the size of the group of patients, 94, was too small to be statistically significant.
“Our results demonstrate that selenium is not an effective chemoprevention agent in an unselected group of lung cancer patients, and it’s not something we can recommend to our patients to prevent a second cancer from developing or recurring,” said Karp. “These findings also remind us that never smokers may represent a unique disease and should be an area for special consideration for research focus.
“Given our results and that of SELECT, physicians now can point to two large NCI-sponsored Phase III trials and tell patients that, at this time, the only definitive studies that have been conducted have been negative,” said Karp.
In addition to Karp, other authors on the study include: John Ruckdeschel, M.D.; Sandra Lee, ECOG; Gail Shaw, M.D.; Steven Keller, M.D.; Steven Belinsky, Ph.D.; Seena Aisner, M.D.; Omer Kucuk, M.D.; Jean MacDonald; and Mary Steele.
About M. D. Anderson
The University of Texas M. D. Anderson Cancer Center in Houston ranks as one of the world’s most respected centers focused on cancer patient care, research, education and prevention. M. D. Anderson is one of only 40 comprehensive cancer centers designated by the National Cancer Institute. For six of the past eight years, including 2009, M. D. Anderson has ranked No. 1 in cancer care in “America’s Best Hospitals,” a survey published annually in U.S. News & World Report.