Nipping Lung Cancer Early Trumps Treatment Advances

Lung cancer management is undergoing a  molecular-profiling makeover, but how much does it matter?

An oncogenic revolution is redefining advanced-stage lung cancer as a heterogeneous collection of fundamentally different tumors types, each distinguished by a specific oncogenic driver, specifications that, in turn, help define the drugs that best control the cancer’s growth. For example, based on newly reported findings from the Lung Cancer Mutation Consortium, roughly 17% of stage IV lung cancer tumors have a mutation in their epidermal growth factor receptor (EGFR) gene as their major oncogenic driver, making these tumors prime candidates for treatment with erlotinib or gefitinib. In another 10% of tumors the driver is an ALK gene change that makes the cancers very responsive to crizotinib.

heart and lungs, courtesy Gray's Anatomy, 1918; Wikimedia Commons

The program at the biennial World Conference on Lung Cancer earlier this month in Amsterdam teemed with reports like these. The Consortium’s data have so far linked 54% of advanced lung cancers to any one of 10 different oncogenic drivers, a genetic alphabet soup that includes ALK, MET, MEK, HER2, etc. Testing for mutations like these, and targeting therapy accordingly was the talk of the meeting, it’s elegant and cutting edge, and, alas, it’s a strategy ultimately doomed to fail.

The nasty truth about advanced-stage, stage IV lung cancer is that it won’t sit still and fully submit to even the best-targeted, genetically appropriate agents. Inevitably, be it after 6 months or 6 years, the cancer will develop drug resistance and recur and will need treatment with a new drug or it will grow unchecked, spread, and kill. Molecular profiling and targeted therapies are stopgaps, not solutions.

Two real solutions to advanced stage lung cancer also had their moments in the spotlight at the World Conference. Both solutions depend on preventing people from ever developing advanced-stage lung cancer, either by avoiding lung cancer formation, or by detecting it early so that it’s treated at stage I or II.

How do people not develop lung cancer? Simple: Don’t smoke. Epidemiologic records from the past half century,  discussed at the meeting by Oxford statistician Sir Richard Peto, put it in clear terms: U.S. cigarette smoking peaked in about 1960, and by 2009 the annual smoking rate had dropped by about half from that high level. The result: U.S. lung cancer incidence rates hit their apex in 1980, and by 2009 the rate had fallen by about 1/3. The numbers told it all: less smoking followed by less lung cancer. The sharp drop in U.S. smoking since 1960 is a lung-cancer success story.

And if lung cancer develops, find it sooner, before it’s at an advanced stage. The crux of this strategy–using annual CT lung scans to identify potential early-stage lung cancer in high-risk, heavy smokers–received its validation in a New England Journal of Medicine report just before the World Conference got underway, and just in time for the meeting’s organizing group, the International Association for the Study of Lung Cancer, to issue an endorsement of routine CT screening for people with a history of heavy smoking.

Improved insights into the genetic drivers of lung cancer, and better treatment of tumors with more targeted, less toxic drugs are meaningful advances, but even better is leveraging smoking avoidance and early diagnosis to minimize the number of patients with advanced lung cancer.

—Mitchel Zoler (on Twitter @mitchelzoler)

Smoking Scenes in Youth-Rated Movies Decline, But More Work Remains

iStockphoto

For the fifth year in a row, the number of smoking scenes in major youth-rated movies has declined, according to a report by the Centers for Disease Control and Prevention. In addition, the percentage of top-grossing movies with no tobacco incidents were the highest in 2010 compared with the last 20 years.

The report, Smoking in Top-Grossing Movies – United States 2010,  showed that the number of onscreen tobacco incidents in youth-rated movies (G, PG, or PG-13) dropped from 2,093 in 2005 to 595 in 2010. That’s almost a 72% decrease.

That’s the good news.

The bad news is that one in five high school students still smoke and “there’s still a substantial amount of smoking in youth-related films,” said Stanton A. Glantz, Ph.D., one of the study authors and director of Smoke Free Movies, in a news conference.

Several studies have indicated that smoking in movies increases the odds smoking initiation among youth.

Physicians ought to be educating parents that this is a real problem and that they should not let their youth watch movies that have smoking in them, said Dr. Glantz in a phone interview. His Web site lists the smoking status of top-grossing movies every week.

The report is also the first to look at the impact of policy. Three of the six major studios which have adopted a smoking-reduction policies between 2004 and 2007 had lowered their on-screen smoking incidents much more than those studios with no policy in place.

“The data find that three major movie studios (Comcast/Universal, Disney and Time Warner/Warner Bros.) have almost eliminated tobacco from their youth-rated movies, reducing the number of tobacco incidents per film (G/PG/PG13) by 96 percent.  In contrast, studios without policies as well as independent companies (News Corporation/Twentieth Century Fox, Sony/Columbia/Screen Gems and Viacom/Paramount) reduced tobacco depictions in youth-rated movies by an average of only 42 percent over the same period,” according to a news release by the Legacy for Longer Healthier Lives, which hosted a news conference following the report’s release.

The authors admit that implementation of policy won’t affect youths exposure to older movies and that youths do watch R-rated movies, but they recommend several solutions.

They suggest anti-tobacco ads before the movies that have smoking scenes. They also recommend expanding the R rating to include movies with smoking as one way to reduce adolescent exposure to on-screen smoking.

“And if you want to get politically involved,” said Dr. Glantz, “work with your state to stop subsidizing movies with smoking in them.” Almost all states offer movie producers subsidies in the form of tax credit or cash rebates to attract movie production to their states, according to the CDC report. “The 15 states subsidizing top-grossing movies with tobacco incidents spent more on these productions in 2010 ($288 million) than they budgeted for their state tobacco-control programs in 2011 ($280 million),” the authors write.

The authors used data from the Thumbs Up! Thumbs Down! project, which counts occurrences of tobacco incidents in U.S. top-grossing movies each year, to update their 2010 report.

By Naseem S. Miller (@ReportingBack)

European Parliament Members Weigh in on NCDs

With the United Nations summit on noncommunicable disease less than a year away, Members of the European Parliament (MEPs) have now contributed to a growing number of voices worldwide calling for urgent action to address the chronic disease epidemic.

Image by Pacopus via Flickr Creative Commons

In a statement sent this week to the Presidency of the European Union, four MEP groups wrote, “Chronic non-communicable diseases account for 86% of deaths in the WHO European Region. They include heart disease, stroke, hypertension, diabetes, kidney disease, cancers, respiratory and liver diseases. Because most are treatable but not always curable, they generate an enormous financial burden due to treatment costs, care costs and loss of productivity.”

Signatories are the MEP Heart Group, the EU Diabetes Working Group, the MEP Group for Kidney Health and MEPs Against Cancer, informal groups of parliament members engaged in fighting the diseases and conditions in those health areas.

The MEPs note that chronic noncommunicable diseases (NCDs) affect more than a third of Europe’s population, comprising over 100 million citizens, and that four preventable health determinants – tobacco use, poor diet, alcohol consumption, and lack of physical activity – account for most of chronic illness and death in Europe. Prevention costs less than disease management and treatment, yet 97% of health expenses currently are spent on treatment and only 3% invested in prevention.

The statement advises EU member states to follow recommendations from a policy paper entitled “A Unified Prevention Approach.” That 20-page document was issued in July by the Chronic Disease Alliance, a coalition of 10 separate European nonprofit professional medical organizations, including those representing hepatology, oncology, cardiology, nephrology, respiratory medicine, and diabetology.

The Alliance’s recommendations include a call for harmonization of tobacco taxation across Europe, standardization of cigarette packaging with 80% of the package devoted to pictorial health warnings, and a ban of tobacco sales via the Internet and vending machines.

They also recommend a ban of added trans fat to foods, introduction of a traffic light color coding system to food labels (with green being the most healthful and red the least), increased access to affordable fresh fruit and vegetables, and EU measures to prohibit marketing of unhealthful food to children. Other recommendations address the promotion of physical activity and the reduction of alcohol consumption and dependence.

According to the Alliance, “Simple policies could save millions of lives and cut billions of euros in direct and indirect costs…By acting now, the European Commission will be doing something that transcends anything else it may accomplish.”

–Miriam E. Tucker (@MiriamETucker on Twitter)

Selling Health & Cigarettes?

  The American Medical Association doesn’t believe medical services should be served up next to an array of tobacco products in retail outlets, and it appears that the American Osteopathic Association agrees.

Meeting this week in Chicago, representatives of the nation’s more than 67,000 osteopathic physicians will consider a policy that calls on legislators to ban or discourage placement of medical practices in retail settings that promote or sell tobacco products.

 The placement of medical clinics in these settings convey a message contrary to the efforts of health care providers, said Dr. Joseph Yasso, D.O., chair of the AOA’s bureau of state government affairs.

 “These types of clinics are proliferating rather rapidly and since that is the case, we certainly don’t want these popping up in areas where a patient comes in to see a nurse practitioner and is diagnosed with acute bronchitis or a respiratory infection and is advised not to smoke and they walk out the door past a counter that sells cigarettes,” he said.

 That ship has likely sailed, with Walgreens Take Care clinics alone treating more than 300,000 cases of acute respiratory conditions from 2008 to 2009, according to a press release announcing that patients with respiratory illnesses, ages 2 years and up, can seek nebulizer treatments year round at these clinics.

 The Convenient Care Association has developed quality and safety standards for its roughly 1,200 retail health care clinic members that include providing patients with health promotion and disease prevention education, but they do not tackle the issue of tobacco sales.

While store-based health clinics provide a service to patients,  should there be conditions on where they’re placed or the products sold in the next aisle? If so, where does one draw the line? What do you think?

— Patrice Wendling (on Twitter @pwendl)

Smoking, Genes, and Volcanos – Oh My!

Dr. Thorgeirsson's slide on the Icelandic volcanos. (Photo by Sherry Boschert)

From the annual meeting of the American Society of Addiction Medicine.

The lives of thousands of physicians, reporters, and others have been disrupted by a volcano whose name they can barely pronounce. Can you say Eyjafjallajokull? Does it even help to see a phonetic spelling (EYE-a-fyat-la-jo-kutl)? For me, not so much. For more giggles, try pronouncing the name of the glacier next to it—Myrdalsjokull—which covers the even larger Katla volcano that very well may go off within the next couple of years, causing even more travel mayhem.

During a talk on the genetics of nicotine addiction, Thorgeir E. Thorgeirsson, Ph.D., director of medical genetics at the University of California, Santa Cruz, diverged briefly to talk about the big, bad smokers in his native Iceland. Take a listen:

The genetics involved in the other kind of smoking—the kind that involves cigarettes and nicotine addiction—also will likely have a huge effect on lives, though its applications aren’t quite ready for clinical practice. Dr. Thorgeirsson noted that “For the price of a fancy car, you can have your genome sequenced. The price is dropping rapidly.” Although he acknowledged that researchers are “still stumbling in the darkness” trying to understand the genetic influences on addiction, they’re starting to learn enough that he suggested, “Perhaps our definitions of nicotine dependence need to be addressed” to incorporate genetic underpinnings.

Individuals respond differently to drugs of abuse because innate differences protect or predispose them to addiction, added another speaker in the same session, Dr. Laura Bierut of Washington University, St. Louis. She and other researchers already have identified gene variants that appear to contribute to nicotine or cocaine dependency, but some startling findings make them wonder how these might eventually prove useful clinically.

“We were shocked” to find that each time a gene variant was identified as a risk factor for nicotine dependence, it appeared to be protective against cocaine dependence, and vice versa, she said. The implications raise concerns about possibly designing gene-based treatments to reduce one kind of dependency and having it boomerang by increasing the risk of another kind of dependence.

So far, the only clinically useful knowledge in this area is the risk of addiction within families. If parents have substance dependence or addiction problems, their children are highly likely to have the same vulnerabilities. Young patients need to hear this, and pediatricians need to know if a parent is addicted in order to best help their patients, she said.

–Sherry Boschert (@sherryboschert on Twitter)

A Preventable Threat to Global Development

Sir George Alleyne / Photo taken at the UN by Miriam E. Tucker

On a global scale, noncommunicable diseases such as diabetes, cancer, and heart disease don’t just threaten health, but also development. 

That’s how speakers framed the discussion at a World Health Organization panel on noncommunicable disease (NCD), held at the United Nations as a side session during the 43rd Session of the Commission on Population and Development (CPD). 

Sir George Alleyne, director emeritus of the Pan American Health Organization, led off by calling NCDs a “major burden in terms of morbidity and mortality” in the developing world and a “neglected disease priority.” 

Yet, 80% of NCDs can be controlled or prevented by reducing common risk factors such as tobacco use, unhealthful diets, and inactivity, measures addressed in the WHO’s 2008-2013 Action Plan for the Global Strategy for the Prevention and Control of Noncommunicable Diseases. 

Dr. Rachel A. Nugent, deputy director for global health at the Center for Global Development, said that unlike infectious disease, which hits children and the elderly the hardest, NCDs primarily affect adults of working age. This in turn leads to reduced productivity and economic loss in developing nations. 

A 2007 study found that a 10% increase in cardiovascular disease mortality among the working-age population decreases the per capita income growth rate by about 1 percentage point. Between 2006 and 2015, that loss is projected to total $84 billion (in U.S. dollars) worldwide. 

“Even if health and social losses aren’t enough to compel us to action—and they are—the potential economic losses should move us to action,” Dr. Nugent said. 

Dr. Gauden Galea of the WHO’s chronic disease division outlined the links between NCDs and infectious disease. For example, people with diabetes have a threefold increased risk for developing active tuberculosis, slightly more than the relative risk for active smokers. 

According to a recent study, a 10% reduction in the death rate from NCDs would have a similar impact on progress toward TB eradication goals as would a rise in gross national product corresponding to at least a decade of growth in low-income countries. 

Dr. Laurent Huber, director of the Framework Convention Alliance, an international antitobacco coalition, said his organization has joined forces with several international health groups and nongovernmental organizations to push for action on NCDs. 

The coalition has two main priorities. One is inclusion of NCD indicators in the UN’s Millennium Development Goals (MDGs). Currently, the MDGs—the blueprint for world development that guides funding decisions—don’t even mention NCDs. An MDG Review Summit is slated for September 2010. 

The other priority—also endorsed by the Commonwealth of Nations and the Caribbean Community—is a September 2011 UN General Assembly Special Session (UNGASS) on NCDs to raise political awareness of the issue, just as a 2001 UNGASS did for HIV/AIDS. 

Dr. Alleyne, a Barbados-born physician who was knighted by Queen Elizabeth in 1990, sees the NCD UNGASS not just as a priority but a necessity. “This has to happen,” he told me when I spoke with him briefly after the session ended. “We need a push. This has to happen.” 

-Miriam E. Tucker (@MiriamETucker on Twitter)

ACIP’s Smoking Gun

From the joint annual meeting of the Interscience Conference on Antimicrobial Agents and Chemotherapy and the Infectious Diseases Society of America

Do you smoke?  That’s now reason enough for you to receive the pneumococcal polysaccharide vaccine, according to the latest recommendations–approved just last week–from the Center for Disease Control and Prevention’s Advisory Committee on Immunization Practices (ACIP) http://www.cdc.gov/vaccines/recs/acip/default.htm.

I heard some some buzz about this new recommendation while covering the joint annual meeting of the Interscience Conference on Antimicrobial Agents and Chemotherapy and the Infectious Diseases Society of America, affectionately known as ICAAC/IDSA.

Dr. Pekka Nuorti of the CDC dropped this potential bombshell into his talk about tools to prevent pneumococcal disease in adults.

Dr. Nuorti conducted a study published in 2000 which found that smokers accounted for more than half of the pneumococcal disease cases in adults younger than 65 years. The new indication for the vaccine represents a risk-based approach to reducing pneumococcal disease, compared to an age-based approach, he noted. In addition, ACIP is now recommending the vaccine for all adults with asthma. The previous recommendation was age-based, and simply recommended vaccination for all adults aged 65 years and older.

This change would increase the number of people who would need the pneumococcal polysaccharide vaccine, and the question and answer session here at ICAAC/IDSA included questions about the possible need for boosters for younger adults, and whether those who are exposed to secondhand smoke eventually would become targets for vaccination. Also, a new pneumococcal vaccine for adults may be available in less than 5 years, so is it worth it to vaccinate large numbers of adults, only to possibly re-vaccinate them in the near future? And what if someone has only recently quit smoking?

Dr. Nuorti was just the messenger, and he didn’t have the answers to these questions, which will likely be ongoing. Certainly members of this audience, which included clinicians and research scientists, were debating the pros and cons of these new indications among themselves.

—Heidi Splete