jueves, 30 de junio de 2011

NIH-funded study shows 20 percent reduction in lung cancer mortality with low-dose CT compared to chest X-ray,June 29, 2011 News Release - National Institutes of Health (NIH)

Wednesday, June 29, 2011
5 p.m. EDT Contact:
NCI Office of Media Relations
(301) 496-6641


NIH-funded study shows 20 percent reduction in lung cancer mortality with low-dose CT compared to chest X-ray

Scientists have found a 20 percent reduction in deaths from lung cancer among current or former heavy smokers who were screened with low-dose helical computed tomography (CT) versus those screened by chest X-ray. The primary research results from the National Lung Screening Trial (NLST) were published online today in the New England Journal of Medicine.

This article provides a more extensive analysis of the original data reported in November 2010 while providing additional data to the public and research community without barriers to access. Sponsored by the National Cancer Institute (NCI), part of the National Institutes of Health, the NLST is a nearly decade-long study that establishes low-dose helical CT as the first validated screening test which can reduce mortality due to lung cancer.

“Today’s publication gives researchers, policy makers, and the public full access to primary findings from the NLST to guide the use of low-dose helical CT scanning by current and former smokers,” said Harold Varmus, M.D., NCI director. “The NCI marshaled the scientific and financial resources required for this expansive study, because only trials such as this allow us to say which methods of screening are effective, and how effective, in defined populations. Having a validated screening test that provides significant, but partial, protection against death from lung cancer complements — but should not be seen as replacing — ongoing efforts to control use of tobacco and to find other ways to prevent and treat lung cancer.”

The NLST was a randomized national trial involving 53,454 current and former heavy smokers ages 55 to 74. Participants were required to have a smoking history of at least 30 pack-years and were either current or former smokers without signs, symptoms, or history of lung cancer. Pack-years are calculated by multiplying the average number of packs of cigarettes smoked per day by the number of years a person has smoked.

Participants in the NLST were randomly assigned to receive three annual screens with either low-dose helical CT (often referred to as spiral CT) or standard chest X-ray. Helical CT uses X-rays to obtain a multiple-image scan of the entire chest, while a standard chest X-ray produces a single image of the whole chest in which anatomic structures overlie one another.

The paper published today provides important details about the number of screens that identified abnormalities potentially related to lung cancer (positive screens) and how many of those positive screens turned out to be false positives, meaning that the positive finding did not prove to be lung cancer upon follow-up. Over the three rounds of screening exams, 39.1 percent of the low-dose helical CT screens were positive and 16.0 percent of the chest X-rays were positive. In both arms of the trial, the majority of positive screens led to additional tests.

Across all three rounds, when a positive screening result was found, 96.4 percent of the low-dose helical CT tests and 94.5 percent of the chest X-ray exams were false positive. The vast majority of false positive results was probably due to the detection of normal lymph nodes or inflamed tissues. False positive results not due to lung cancer were typically confirmed by follow-up CT scans that showed no change in the finding over time.

The published results also provide insight into the type of lung cancers found by screening and the stages at which they were diagnosed. Adenocarcinomas, which begin in cells that line the lungs, and squamous cell carcinomas, which arise from the thin, flat fish-scale-like cells that line passages of the respiratory tract, were detected in the early stages of disease in both arms of the trial. Both types of carcinomas were detected more frequently at their earliest stage by low-dose helical CT compared to chest X-ray. Small-cell lung cancers, which are very aggressive tumors and grow in the tissues of the lung, were infrequently detected at early stages by low-dose helical CT or chest X-ray. Additional studies based on the complete NLST data set are ongoing and will include reports on cost-effectiveness of low-dose helical CT as well as the ability to use the data to develop models that may help indicate whether other groups of smokers, such as light smokers or younger smokers, would benefit from screening with low-dose helical CT. Other modeling studies are expected to examine the optimal frequency and duration of screening.

Adverse events, which are harms from the actual screening examinations, were few and relatively minor in the NLST. The rate of complications among people who underwent a diagnostic evaluation prompted by a positive screen was under 2 percent for either type of screening. Among those who did have complications, 16 people screened with low-dose helical CT (10 of whom had lung cancer) and 10 chest X-ray participants (all with lung cancer) died within 60 days of a follow-up invasive diagnostic procedure.

Invasive diagnostic procedures include bronchoscopy, where an instrument is inserted through the nose or mouth into the airways, and percutaneous lung needle biopsy, where a needle is inserted into the lung through the chest to remove a small piece of tissue for examination. While it is not known whether the diagnostic procedures caused these deaths, the low frequency of death within 60 days of an invasive procedure in the NLST suggests that death from evaluation of positive screens occurs rarely.

Radiation exposure associated with low-dose helical CT in the NLST is much lower than that associated with a regular diagnostic CT. The authors note any harm from exposure to radiation during the screenings could not be measured directly. Because the effect of such exposure is a long-term outcome, potential harms will need to be modeled in future studies.

It should also be noted that the population enrolled in this study, while ethnically representative of the U.S. population of smokers at high risk for lung cancer, was a highly motivated and primarily urban group that was screened at major medical centers. Thus, these results alone may not accurately predict the effects of recommending low-dose helical CT scanning for other populations.

“These primary findings from the NLST provide a valuable insight into how to potentially decrease death due to lung cancer. But the most important method of decreasing lung cancer rates remains for smokers to quit smoking and for those who don’t smoke to continue with their healthy behaviors,” said NLST co-investigator, Christine Berg, M.D., of the NCI.

The NLST was conducted by the American College of Radiology Imaging Network, a medical imaging research network focused on the conduct of multi-center imaging clinical trials, and the Lung Screening Study group, which was initially established by the NCI to examine the feasibility of the NLST.

For an updated Q&A on the NLST, please go to
http://www.cancer.gov/newscenter/qa/2002/nlstqaQA.

To view a video discussion of the design and outcomes of the NLST, please go to http://www.youtube.com/watch?v=hY6GQnO75Mo.

For more information on lung cancer and screening, please go to http://www.cancer.gov/cancertopics/types/lung.

NCI leads the National Cancer Program and the NIH effort to dramatically reduce the burden of cancer and improve the lives of cancer patients and their families, through research into prevention and cancer biology, the development of new interventions, and the training and mentoring of new researchers. For more information about cancer, please visit the NCI Web site at http://www.cancer.gov or call NCI's Cancer Information Service at 1-800-4-CANCER (1-800-422-6237).

About the National Institutes of Health (NIH): NIH, the nation's medical research agency, includes 27 Institutes and Centers and is a component of the U.S. Department of Health and Human Services. NIH is the primary federal agency conducting and supporting basic, clinical, and translational medical research, and is investigating the causes, treatments, and cures for both common and rare diseases. For more information about NIH and its programs, visit www.nih.gov.


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Reference: National Lung Screening Trial Research Team. Reduced Lung Cancer Mortality in the National Lung Screening Trial. NEJM. Online June 29, 2011. In print, August 4, 2011.
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NIH-funded study shows 20 percent reduction in lung cancer mortality with low-dose CT compared to chest X-ray,June 29, 2011 News Release - National Institutes of Health (NIH)

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jueves 30 de junio de 2011

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jueves 30 de junio de 2011
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Consultas acumuladas desde enero 2009 a la fecha: 382.572
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4. MÉXICO: 46.238 [12,1%]
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Cholera Epidemic, Haiti | CDC EID

EID Journal Home > Volume 17, Number 7–July 2011
Volume 17, Number 7–July 2011
Synopsis

Understanding the Cholera Epidemic, Haiti
Renaud Piarroux,
Robert Barrais, Benoît Faucher, Rachel Haus, Martine Piarroux, Jean Gaudart, Roc Magloire, and Didier RaoultAuthor affiliations: Université de la Méditerranée, Marseilles, France (R. Piarroux, B. Faucher, J. Gaudart, D. Raoult); Ministère de la Santé Publique et de la Population, Port-au-Prince, Haiti (R. Barrais, R. Magloire); Service de Santé des Armées, Paris, France (R. Haus); and Martine Piarroux Université de Franche-Comté, Besançon, France (M. Piarroux)

Suggested citation for this article

Abstract
After onset of a cholera epidemic in Haiti in mid-October 2010, a team of researchers from France and Haiti implemented field investigations and built a database of daily cases to facilitate identification of communes most affected. Several models were used to identify spatiotemporal clusters, assess relative risk associated with the epidemic's spread, and investigate causes of its rapid expansion in Artibonite Department. Spatiotemporal analyses highlighted 5 significant clusters (p<0.001): 1 near Mirebalais (October 16–19) next to a United Nations camp with deficient sanitation, 1 along the Artibonite River (October 20–28), and 3 caused by the centrifugal epidemic spread during November. The regression model indicated that cholera more severely affected communes in the coastal plain (risk ratio 4.91) along the Artibonite River downstream of Mirebalais (risk ratio 4.60). Our findings strongly suggest that contamination of the Artibonite and 1 of its tributaries downstream from a military camp triggered the epidemic.

On October 21, 2010, the Haitian Ministry of Public Health and Population (MSPP) reported a cholera epidemic caused by Vibrio cholerae O1, serotype Ogawa, biotype El Tor (1). This epidemic was surprising as no cholera outbreak had been reported in Haiti for more than a century (1,2). Numerous media rapidly related the epidemic to the deadly earthquake that Haiti had experienced 9 months earlier. However, simultaneously, a rumor held recently incoming Nepalese soldiers responsible for importing cholera, along with accusations of illegal dumping of waste tank contents (3). A cholera outbreak was indeed reported in Nepal's capital city of Kathmandu on September 23, 2010, shortly before troops left for Haiti (4,5). Two hypotheses then emerged to explain cholera in Haiti.

Some researchers posited the transmission of an environmental strain to humans (6). Reasoning by analogy with cholera epidemiology in South Asia, they hypothesized that weather conditions, i.e., the La Niña phenomenon, might have promoted the growth of V. cholerae in its environmental reservoir (6). The second hypothesis suggested importation of the disease from a cholera-endemic country. The sequencing of 2 isolates of V. cholerae supported this second hypothesis by establishing an exogenous origin, probably from southern Asia or eastern Africa (7). Responding to a request from Haitian authorities to the French Embassy for the support of epidemiologists, we conducted a joint French–Haitian investigation during November 7–November 27, 2010, to clarify the source of the epidemic and its unusual dynamic.
Morbidity and Mortality Survey

full-text:
Cholera Epidemic, Haiti CDC EID

Suggested Citation for this Article



Piarroux R, Barrais R, Faucher B, Haus R, Piarroux M, Gaudart J, et al. Understanding the cholera epidemic, Haiti. Emerg Infect Dis [serial on the Internet]. 2011 Jul [date cited]. http://www.cdc.gov/EID/content/17/7/1161.htm

DOI: 10.3201/eid1707.110059

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Renaud Piarroux, Université de la Méditerranée, UMR MD3, Faculte de Medecine de la Timone, 27 Boulevard Jean Moulin, CEDEX 05, Marseille 13385, France; email: renaud.piarroux@ap-hm.fr

R. parkeri Rickettsiosis, Argentina | CDC EID

EID Journal Home > Volume 17, Number 7–July 2011
Volume 17, Number 7–July 2011
Synopsis


Rickettsia parkeri Rickettsiosis, Argentina
Yamila Romer,
Alfredo C. Seijo, Favio Crudo, William L. Nicholson, Andrea Varela-Stokes, R. Ryan Lash, and Christopher D. PaddockAuthor affiliations: Hospital F.J. Muñiz, Buenos Aires, Argentina (Y. Romer, A.C. Seijo, F. Crudo); Centers for Disease Control and Prevention, Atlanta, Georgia, USA (W.L. Nicholson, C.D. Paddock); Mississippi State University, Mississippi State, Mississippi, USA (A. Varela-Stokes); and The University of Georgia, Athens, Georgia, USA (R.R. Lash)

Suggested citation for this article

Abstract
Rickettsia parkeri, a recently identified cause of spotted fever rickettsiosis in the United States, has been found in Amblyomma triste ticks in several countries of South America, including Argentina, where it is believed to cause disease in humans. We describe the clinical and epidemiologic characteristics of 2 patients in Argentina with confirmed R. parkeri infection and 7 additional patients with suspected R. parkeri rickettsiosis identified at 1 hospital during 2004–2009. The frequency and character of clinical signs and symptoms among these 9 patients closely resembled those described for patients in the United States (presence of an inoculation eschar, maculopapular rash often associated with pustules or vesicles, infrequent gastrointestinal manifestations, and relatively benign clinical course). Many R. parkeri infections in South America are likely to be misdiagnosed as other infectious diseases, including Rocky Mountain spotted fever, dengue, or leptospirosis.

Rickettsia parkeri, a tick-borne bacterium discovered in 1937, was considered nonpathogenic until 2004. Since 2004, >25 cases of R. parkeri rickettsiosis have been reported in persons living within the recognized range of the tick vector, Amblyomma maculatum, in the United States (1–4; Centers for Disease Control and Prevention, unpub. data). The clinical features of this newly recognized disease appear less severe than those produced by R. rickettsii bacteria, the agent of Rocky Mountain spotted fever (RMSF). For many years, investigators in several countries of South America, including Argentina, Brazil, and Uruguay, have recognized eschar-associated infections that clinically resemble R. parkeri rickettsiosis (5–7). These reports, and the discoveries of R. parkeri in A. triste ticks collected from these same countries, suggest that human infections with R. parkeri also occur in South America (8–10); to our knowledge, no confirmed cases of disease caused by this Rickettsia species have been reported from this continent.

The Paraná Delta, situated in the provinces of Buenos Aires and Entre Ríos in Argentina, represents the terminus of the Paraná River as it approaches and drains into the Uruguay River and subsequently into the Río de la Plata. This alluvial ecosystem, where braided river branches create a network of islands and wetlands, covers ≈14,000 km2 (5,405 mi2) and extends for ≈320 km (200 mi). This region also contains abundant populations of A. triste ticks (10). The Paraná Delta has always been a major agricultural and farming region. Recently, this area has become increasingly developed; roads have been built to allow greater access for tourism and recreational activities by many of the ≈14 million inhabitants of nearby Buenos Aires. In 2005, an eschar-associated febrile infection was diagnosed in a male beekeeper from the Paraná Delta; the infection was later confirmed as a spotted fever group (SFG) rickettsiosis by serology and immunohistochemistry (5). He had been bitten by a tick not far from several sites where R. parkeri was subsequently detected in A. triste ticks (10). We report confirmed cases of R. parkeri rickettsiosis in 2 patients in Argentina and describe additional suspected cases of this disease, or similar infections, in patients from the provinces of Buenos Aires, Chaco, and Entre Ríos.

full-text:
R. parkeri Rickettsiosis, Argentina CDC EID


Suggested Citation for this Article
Romer Y, Seijo AC, Crudo F, Nicholson WL, Varela-Stokes A, Lash RR, et al. Rickettsia parkeri rickettsiosis, Argentina. Emerg Infect Dis [serial on the Internet]. 2011 Jul [date cited].
http://www.cdc.gov/EID/content/17/7/1169.htm

DOI: 10.3201/eid1707.101857

Comments to the Authors
Please use the form below to submit correspondence to the authors or contact them at the following address:
Yamila Romer, Hospital F.J. Muñiz, Uspallata 2272, 1282 Buenos Aires, Argentina; email:
yromer@hotmail.com

Neurognathostomiasis | CDC EID

EID Journal Home > Volume 17, Number 7–July 2011
Volume 17, Number 7–July 2011

Synopsis
Neurognathostomiasis, a Neglected Parasitosis of the Central Nervous System
Juri Katchanov, Kittisak Sawanyawisuth, Verajit Chotmongkol, and Yukifumi Nawa
Author affiliations: Mahidol University, Bangkok, Thailand (J. Katchanov, Y. Nawa); and Khon Kaen University, Khon Kaen, Thailand (K. Sawanyawisuth, V. Chotmongkol)

Suggested citation for this article

Abstract
Gnathostomiasis is a foodborne zoonotic helminthic infection caused by the third-stage larvae of Gnathostoma spp. nematodes. The most severe manifestation involves infection of the central nervous system, neurognathostomiasis. Although gnathostomiasis is endemic to Asia and Latin America, almost all neurognathostomiasis cases are reported from Thailand. Despite high rates of illness and death, neurognathostomiasis has received less attention than the more common cutaneous form of gnathostomiasis, possibly because of the apparent geographic confinement of the neurologic infection to 1 country. Recently, however, the disease has been reported in returned travelers in Europe. We reviewed the English-language literature on neurognathostomiasis and analyzed epidemiology and geographic distribution, mode of central nervous system invasion, pathophysiology, clinical features, neuroimaging data, and treatment options. On the basis of epidemiologic data, clinical signs, neuroimaging, and laboratory findings, we propose diagnostic criteria for neurognathostomiasis.

Foodborne parasitic infections are common in the tropics, where many foodborne parasites are endemic and ingestion of raw shellfish and freshwater fish, as well as undercooked meat, is frequent among local populations (1). Increased international travel to areas endemic for these foodborne parasites and migration from tropical areas have led to the emergence of these diseases in temperate climates (2), where such infections are rarely seen by physicians and thus may not be considered in differential diagnoses.
Gnathostomiasis is a foodborne zoonotic helminthic infection caused by the third-stage larva of Gnathostoma spp. nematodes (Figure 1, panels A, B). At least 13 species have been identified (3), with 5 recorded in humans. G. spinigerum is the most common of these nematodes in Asia. Human infection with G. hispidum, G. doloresi, and G. nipponicum were found only in Japan (4). In the Americas, G. binucleatum is the only proven pathogenic Gnathostoma nematode in humans. Humans are infected primarily by eating raw or undercooked freshwater fish (Figure 1, panel C), frogs, and chicken. Humans are accidental unsuitable hosts; the parasite rarely develops to an adult worm, and the disease in humans is caused by the migrating larva.

Gnathostomiasis can be divided into cutaneous, visceral, and ocular forms, depending on the site of larval migration and subsequent signs and symptoms (2). The most common clinical presentation is the cutaneous one (Figure 1, panel D), which is characterized by localized, intermittent, migratory swellings of the skin and is often associated with localized pain, pruritus, and erythema (5,6). Visceral involvement can manifest in virtually any organ and any part of the body (3). The most severe manifestation of the visceral disease is involvement of the central nervous system (CNS), i.e., neurognathostomiasis.

Neurognathostomiasis has been reported only in G. spinigerum infections (3).

We found 24 reports describing a total of 248 patients with neurognathostomiasis published in English-language literature. In this article, we review epidemiology, mode of CNS invasion, pathophysiology, clinical features, neuroimaging data, and treatment options, and we propose diagnostic criteria for this emerging disease.

full-text:
Neurognathostomiasis CDC EID

Suggested Citation for this Article



Katchanov J, Sawanyawisuth K, Chotmongkol V, Nawa Y. Neurognathostomiasis, a neglected parasitosis of the central nervous system. Emerg Infect Dis [serial on the Internet]. 2011 Jul [date cited]. http://www.cdc.gov/EID/content/17/7/1174.htm

DOI: 10.3201/eid1707.101433

Comments to the Authors
Please use the form below to submit correspondence to the authors or contact them at the following address:
Yukifumi Nawa, Faculty of Tropical Medicine, Mahidol University, 420/6 Rajavithi Rd, Bangkok 10400, Thailand; email: yukifuminawa@fc.miyazaki-u.ac.jp

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NCI Launches International Clinical Trials Portal - NCI Cancer Bulletin for June 28, 2011 - National Cancer Institute

NCI Launches International Clinical Trials Portal

NCI has launched the International Collaboration in Clinical Trials portal, a site designed to strengthen international alliances in cancer clinical trials. The portal provides a central location for online resources that will help investigators outside the United States navigate the legal and regulatory issues that come with collaborating on clinical trials with U.S.-based research groups.

Legal, regulatory, logistical, and financial hurdles often delay international clinical trials, and clinical investigators from other countries sometimes need step-by-step guidance on launching a study protocol or joining a U.S. cooperative research group. Moreover, international cancer researchers typically have questions about NCI's role in clinical trials and how the U.S. clinical trials process works in general.
NCI conducted in-depth interviews with clinical cancer investigators from more than 11 countries to determine what should be included in the new portal. Based on those interviews, the portal provides background information on NCI-designated cancer centers, U.S.-based clinical trials cooperative groups, and NCI's international programs.

A section of the site is dedicated to answering common questions about biospecimen collection, clinical trial ethics, insurance, drug labeling and distribution, and quality assurance. As international investigators navigate through the portal, they will find links to registration forms and laws that regulate U.S. clinical trials.

"This new portal on Cancer.gov will help NCI's existing partners—and prospective new partners—navigate hurdles to keep up momentum of our clinical trial alliances," said Dr. Ted Trimble, acting director of NCI's Center for Global Health. "Collaborating internationally on cancer clinical trials enables progress in cancer treatment and screening. Completing larger trials across multiple countries can ensure that new methods have a global reach."

NCI Cancer Bulletin for June 28, 2011 - National Cancer Institute

Diabetes Drug May Increase Risk of Bladder Cancer - NCI Cancer Bulletin for June 28, 2011 - National Cancer Institute

Diabetes Drug May Increase Risk of Bladder Cancer

Use of the diabetes drug pioglitazone (Actos) for more than 1 year may increase the risk of developing bladder cancer, according to a June 15 safety announcement from the FDA.

The announcement is based on a 5-year interim analysis of a 10-year prospective cohort study of safety data being conducted by the drug’s manufacturer, Takeda Pharmaceuticals. The study includes more than 193,000 patients who are part of the Kaiser Permanente Northern California health plan. All patients in the study are 40 years of age or older and have been diagnosed with diabetes.

No overall increase in bladder cancer risk was seen in those using pioglitazone compared with those who had never taken the drug. Patients who had been taking the drug for 12 to 24 months, however, had a 40 percent higher risk of developing bladder cancer than people who had never taken it.

“Although there was no overall increased risk of bladder cancer with pioglitazone use, an increased risk of bladder cancer was noted among patients with the longest exposure to pioglitazone, and in those exposed to the highest cumulative dose of pioglitazone,” the FDA reported.

French health officials recently announced similar findings from a much larger retrospective study of 1.2 million patients taking pioglitazone. Based on the finding, health officials in France halted the use of pioglitazone. In addition, German health officials have ordered clinicians not to prescribe the drug to new patients.

The FDA has advised U.S. physicians not to prescribe pioglitazone for patients with bladder cancer and to use it “with caution” in those who have been treated previously for bladder cancer. “The benefits of blood sugar control with pioglitazone should be weighed against the unknown risks for cancer recurrence,” the agency stated.

NCI Cancer Bulletin for June 28, 2011 - National Cancer Institute

Potential Cardiac Risks Associated with Smoking Cessation Drug - NCI Cancer Bulletin for June 28, 2011 - National Cancer Institute

Potential Cardiac Risks Associated with Smoking Cessation Drug


The Food and Drug Administration (FDA) has updated the prescribing information label on the smoking-cessation drug varenicline (Chantix) to warn that the drug may increase the risk of certain cardiac events in people with underlying cardiovascular disease.

The change is based on findings from a clinical trial of 700 smokers who have cardiovascular disease, according to a safety announcement issued by the FDA on June 16. Trial participants were randomly assigned to receive varenicline or a placebo for 12 weeks and were then followed for an additional 40 weeks without treatment. Although cardiac events “were infrequent overall,” the agency noted that “certain events, including heart attack, were reported more frequently in patients treated with Chantix than in patients treated with placebo.”

Other cardiac events included small increased risks of chest pain, the need for coronary revascularization procedures, and peripheral vascular disease. The two most common events in patients taking varenicline were nonfatal heart attacks (7 versus 3 among those taking the placebo) and coronary revascularization procedures (8 versus 3). Five of the seven patients who required a revascularization procedure were from the same group of participants who had had a nonfatal heart attack.

Physicians should be aware of these risks and discuss the benefits and potential risks of varenicline with their patients who have heart disease, the agency stated in the announcement. In July 2009, the FDA added a “black box” warning about the increased risks of neuropsychiatric symptoms associated with their use to the labels of varenicline and another smoking cessation drug, bupropion (Zyban).

NCI Cancer Bulletin for June 28, 2011 - National Cancer Institute

Adding Targeted Therapy to Treatment for Esophageal Cancer - NCI Cancer Bulletin for June 28, 2011 - National Cancer Institute

Adding Targeted Therapy to Treatment for Esophageal Cancer
Name of the Trial
Phase III Randomized Study of Radiotherapy, Paclitaxel, and Carboplatin with versus without Trastuzumab in Patients with HER2-Overexpressing Esophageal Adenocarcinoma (RTOG-1010). See the protocol summary.

Dr. Howard Safran
Principal Investigator


Dr. Howard Safran, Radiation Therapy Oncology Group

Why This Trial Is Important Esophageal cancer that is confined to the esophagus and nearby lymph nodes (locally advanced disease) is often treated with a combination of chemotherapy, radiation therapy, and surgery (called trimodality therapy). Although trimodality therapy sometimes cures the disease, relapses are common, and many patients ultimately die from their disease. New strategies are needed to help prevent recurrences in patients with locally advanced esophageal cancer.

Samples of tumor tissue removed during biopsy or surgery indicate that about 20 percent to 30 percent of esophageal cancers express a growth factor receptor protein called HER2 (that is, the tumors are HER2 positive). Treatment with trastuzumab (Herceptin), a drug that targets HER2, improves the survival of women with HER2-positive metastatic breast cancer, and the drug markedly decreases cancer recurrence and improves the survival of women with earlier-stage HER2-expressing breast tumors. Doctors hope that trastuzumab may likewise reduce disease recurrence and improve the survival of people with HER2-positive esophageal cancer.

A recent phase III trial involving patients with advanced gastroesophageal and gastric cancers has bolstered the case for using trastuzumab in esophageal cancer. In that trial, patients with HER2-expressing tumors that could not be removed surgically (unresectable disease) were treated with chemotherapy and trastuzumab or with chemotherapy alone. Patients who received trastuzumab were more likely to respond to treatment and lived about 2.4 months longer.

In another trial, researchers at Brown University, led by Dr. Safran, conducted a pilot study of trastuzumab combined with chemotherapy and radiation therapy followed by surgery in 19 patients with locally advanced HER2-positive esophageal cancer and showed that the combined therapy was safe. They now want to see if adding trastuzumab to potentially curative therapy will help patients avoid disease recurrence and death.

In this phase III clinical trial, people with confirmed HER2-positive locally advanced adenocarcinoma of the esophagus will be randomly assigned to receive preoperative radiation therapy and chemotherapy, with or without trastuzumab. Following surgery, patients assigned to the trastuzumab arm of the study will receive maintenance therapy with trastuzumab for 1 year. The study is designed to determine whether the addition of trastuzumab improves disease-free survival and overall survival.

"The recurrence rate in locally advanced esophageal adenocarcinoma is very high, and we can only cure about 25 percent of the patients we treat with trimodality therapy," said Dr. Safran. "In [HER2-positive] breast cancer, trastuzumab reduces recurrence by about 50 percent. So one would hope that, in patients with esophageal cancer, it will have that same reduction in recurrence."

For More InformationSee the lists of entry criteria and trial contact information or call the NCI's Cancer Information Service at 1-800-4-CANCER (1-800-422-6237). The toll-free call is confidential.

An archive of "Featured Clinical Trial" columns is available at http://www.cancer.gov/clinicaltrials/featured.
NCI Cancer Bulletin for June 28, 2011 - National Cancer Institute

Imaging Boot Camp for Cancer Researchers - NCI Cancer Bulletin for June 28, 2011 - National Cancer Institute


This is the seventh article in a series of stories related to new technology in cancer research. You can read more articles in the series here.

Imaging Boot Camp for Cancer Researchers

Students at NCI's Cancer Research Imaging Camp get a lesson in using contrast to improve the visibility of a tumor on an MRI scan. (Photo by Sharon Reynolds)

In a basement lab, a group of students gently place a tumor-bearing mouse into the bore of a small-animal MRI machine to test several methods for distinguishing cancer from surrounding fat cells. Upstairs, another group of scientists rotates through three optical imaging stations, observing the different ways that visible and infrared light can be harnessed to visualize cancer cells in a mouse. At the ultrasound table, a young researcher uses a receiver to deliver a burst of energy to a small tumor in vivo, lighting up a contrast agent designed to bind to and highlight tumor blood vessels.

NCI's annual Cancer Research Imaging Camp, sponsored by the Cancer Imaging Program (CIP) and held June 19–24 this year at Washington University in St. Louis, provides a one-of-a-kind immersive experience for junior scientists eager to incorporate modern imaging methods into their research. Trainees can't possibly gain a comprehensive understanding of imaging technology in 6 days, but that's not the goal of the program, explained Dr. Kenneth Krohn, professor of radiology, radiation oncology, and chemistry at the University of Washington in Seattle and an instructor at Imaging Camp since its inception.

"What we want them to take away is that there are lots of evolving technologies, and that the most important thing is for them to formulate their research questions first and then find the best technology to answer those questions." What researchers should avoid, said Dr. Krohn, is using an imaging method in their research simply because they are familiar with it, or because it has been the only thing available to them.

Although some Imaging Camp participants have experience with one or more of the methods taught during the week, many are learning these methods for the first time.

By the third day of this year's program, Dr. Ashley Snider, an assistant professor of medicine and lipid researcher at the Medical University of South Carolina and the Ralph H Johnson VA Medical Center, and novice imager, had already picked up some ideas. She is working on a collaborative project with two senior cancer researchers, looking at how colon cancer forms in patients with ulcerative colitis. Dr. Snider plans to test some of the techniques she learned at Imaging Camp to monitor the overproduction of blood vessels and track drug delivery in the colon.

"I had never done in vivo imaging before camp," she said. "We'd seen in cells and in animals that an inflammation-associated lipid…contributes to carcinogenesis, but we want to take that work to the next level and monitor the response of tumors to inhibitors we're developing with in vivo imaging. That's why I'm here."

Setting Up Camp

The idea for Imaging Camp sprang from NCI's Imaging Integration and Implementation (I2) group, which was set up in 2004 to encourage greater use of imaging in cancer research. Early on, the group recruited Dr. Bonnie Sloane, distinguished professor and chair of pharmacology at Wayne State University, as a liaison to the CIP to help cancer biologists gain a better understanding of imaging techniques. She identified a basic lack of training as the main barrier to greater use of imaging in cancer biology.

Two Imaging Camp students watch a demonstration of a fluorescent probe used to highlight a tumor for optical imaging. (Photo by Sharon Reynolds)

"If you're trained, it's easy to use a technology. But if you don't understand the modalities and the pluses and minuses of each, you don't know how they could help answer your research questions," she explained. Conceived in 2005 and launched in 2007, Imaging Camp draws junior researchers from diverse disciplines that intersect with cancer biology and treatment.

"It's amazing how imaging has infiltrated this field completely," commented Dr. Suresh Mohla, associate director of NCI's Division of Cancer Biology, who co-chaired the Imaging I2 group. "More and more people are using whole-animal imaging to monitor tumor progression, to understand the behavior of tumors and surrounding cells. It's opened up a whole new perspective on how cancer develops in vivo that wasn't available before, and this program is contributing to training the next generation of cancer researchers in these innovative techniques," he continued.

"We hope that the Imaging Camp students will become the experts of the future, and train their own students. Since we can't train hundreds each year, we're trying to sow the seeds," Dr. Mohla explained.

Labor of Love

For its first 2 years, the camp was hosted by Duke University before the mantle was passed to Washington University in St. Louis in 2009. Beginning next year, the camp will be held at Vanderbilt University. Each year, the all-volunteer faculty members come from these and a dozen other institutions around the country to teach, and many have been instructors since the program began.

The planning—including logistics, recruiting new instructors, and managing the animal models required for the program—takes a good part of the preceding year, explained Drs. Joseph Ackerman and Joel Garbow of Washington University, who have served as the program hosts for the past 3 years.

"But it's such a labor of love for these faculty," said Dr. Anne Menkens, program director of the CIP's Molecular Imaging Branch and NCI coordinator of Imaging Camp. "We don't have to spend any time cajoling people into participating. Training the next generation is what drives them."

The student-to-faculty ratio is kept almost one-to-one; having only 25 students attend each year allows for nearly constant interaction between the imaging experts and the trainees. The faculty often learns new facts about cancer biology from the students, recounted Dr. Cristian Badea, a physicist and associate professor of radiology at Duke who has served as an instructor since Imaging Camp's first year.

"Every camp is a new experience. People bring all kinds of expertise, and I learn new things every year from the participants," he said. "I think the future of imaging is multidisciplinary, and while we're here we can start to break down the barriers of communication between the disciplines."

Through these conversations, "the students learn to talk to the imagers, the lingo, what to ask about their research," Dr. Sloane elaborated. "This is critically important because a lot of [imaging technology] is so sophisticated, a lot of junior people who haven't been exposed to it can be intimidated."

Creating Collaborations and Professional Relationships

Imaging Camp emphasizes collaboration and cooperation. The process begins on the first night, when participants present their current research and solicit ideas from the audience—both faculty and fellow students. Sharing continues in the halls as students are encouraged to swap papers and suggestions, many of which have led to collaborative projects among the trainees, said Dr. Menkens. The collaboration and cooperation continues in formal question-and-answer sessions designed to make sure that every question reaches the most appropriate experts.

The faculty also helps point the new imaging researchers toward potential mentors, bringing the trainees into their own extensive networks. "We encourage them to use the expertise of the camp to help them find a laboratory to work with that has that technology they need," said Dr. Krohn.

Sometimes those mentors are Imaging Camp faculty. Dr. Sloane has hosted a former Imaging Camp student who wanted more optical imaging experience. Dr. Samuel Achilefu, a professor of radiology at Washington University, who has run the optical imaging program at Imaging Camp for the past 4 years, is proud that several former students from Imaging Camp have collaborated with his group.

Some of these collaborations have turned into major projects. Dr. Garbow is participating in the first year of research on a grant won by Dr. Cheryl Jorcyk, an associate professor at Boise State University who attended Imaging Camp in 2009. "By chance we sat down next to each other at dinner, and when we stood up we had a research plan," remembered Dr. Garbow.

Their research project, funded by the Susan G. Komen for the Cure foundation, combines Dr. Jorcyk's expertise in the biology of breast cancer metastasis with Dr. Garbow's experience in imaging small-animal models of cancer. "I think our project is a model for the way collaborations might develop through this kind of training program," concluded Dr. Garbow.

Sharon Reynolds
Cancer Research Imaging Camp StudentsEvery year, 25 students are selected for the Cancer Research Imaging Camp. They come from diverse backgrounds, including chemistry, molecular biology, pharmacology, and even comparative oncology. Read profiles of three students and their interest in imaging training below.

Dr. Monique Spillman

Dr. Monique Spillman
Assistant Professor of Gynecologic OncologyUniversity of Colorado, Denver
For her research on the effects of estrogen and progesterone on ovarian cancer, Dr. Spillman had previously developed a mouse xenograft model and used fluorescence to detect cancer cells within the abdomen, but that technique "lacks sensitivity for deep lymph node metastases," which is an area of translational research she and her colleagues hope to explore, she explained. Lymph-node staging for women with early-stage ovarian cancer, which is vital for determining appropriate treatment, currently requires extensive surgical sampling. An in vivo imaging probe that recognizes deep metastases "would be less invasive and more informative," and could also be used in her laboratory to better understand the biology driving the spread of ovarian cancer to lymph nodes.


Dr. Vijay Ramakrishnan
Dr. Vijay Ramakrishnan
Postdoctoral Researcher in HematologyMayo Clinic
Dr. Ramakrishnan has been testing novel drugs and drug combinations on human multiple myeloma cell lines and in cells taken from patients, examining the role of bone marrow stromal cells and endothelial cells in disease progression. "We know that the bone marrow stromal cells and endothelial cells interact, but we don't understand how that interaction affects disease progression and response to chemotherapy," Dr. Ramakrishnan explained. He hopes to develop an animal model to monitor these interactions noninvasively in vivo. But before he attended Imaging Camp, Dr. Ramakrishnan had no experience with imaging. "[My colleagues and I] think both in vivo and live-cell imaging are going to be very informative as to how these cell-cell interactions are altered after treatment with particular chemotherapy agents," he said.



Dr. Jackie Wypij
Dr. Jackie Wypij
Assistant Professor of Veterinary Clinical MedicineUniversity of Illinois, Urbana-Champaign

As a member of the Comparative Oncology Trials Consortium, Dr. Wypij not only works on clinical trials of novel therapies for pets with cancer, she also looks for ways to translate her knowledge to human cancers. "There's a big black box between mouse and human research, and maybe our patients can fill this in. The genetics in some canine and feline cancers are quite close to some human cancers," she explained. "People are interested in having their pets participate in trials. They want to do it for their pets, but they also feel good about giving something back, that they might be helping people in the future as well." Her group does a lot of clinical imaging for dogs and cats, but "we don't yet incorporate the advanced research imaging methods into our research and trials, and that's what I'd like to do, particularly to look for biomarkers we can use for testing new treatments," she elaborated.


NCI Cancer Bulletin for June 28, 2011 - National Cancer Institute