Patients who test positive for the EGFR gene may live twice as long as those who are EGFR- when given the a combination of chemotherapy and cetuximab—a drug that blocks a key pathway particular gene-driven tumors use to grow and spread—as their first-line treatment, the study shows.

“The results of this study could very well change the way lung cancer patients are treated in the future, similarly to how screening for estrogen-driven breast cancer changed how patients with HER2+ breast tumors are treated,” said Fred Hirsch, MD, PhD, professor of Medicine at University of Colorado Denver and the paper’s lead author.

The paper, published in the July issue of the prestigious Journal of Clinical Oncology, is from a phase II randomized study out of the Southwest Oncology Group, a consortium of cancer researchers. It comes on the heels of the large, randomized European FLEX study, which showed that some advanced non-small-cell lung cancer patients who got the combination therapy lived longer than others who got the same therapy.

“We needed a tool to tell us which patients to put on cetuximab, because it does not make sense to give an expensive drug that has side effects for someone it will not help,” Hirsch said. “We believe that EGFR FISH is that tool.”

The EGFR FISH test, which was developed at the University of Colorado Cancer Center, is available in most laboratories, so lung cancer patients around the world could be quickly screened in the future to see if they would benefit from cetuximab plus chemotherapy. They will soon begin a 1,000-patient phase III trial to validate the findings, and they anticipate FDA approval of the tool to select patients for EGFR inhibitors in the near future.

“When we give patients the right drugs for their exact tumor type, we can help them live a longer, more comfortable life with the disease,” said Paul A. Bunn, Jr., MD, UCCC director and professor of Medicine at UC Denver, who co-authored the study. “I am already using this test to screen my patients for this gene, and if they test positive, I am giving them the combination therapy. They are doing very well on it. We are hopeful that this test will shift how we choose which therapies to give to each individual patient, which is key to getting the best results.”

In the UCCC study, EGFR+ patients lived an average of 15 months after diagnosis with the combination therapy, compared to an average of 7 months for EGFR- patients. EGFR+ patients’ tumors also shrunk twice as much on the combination therapy.

The Colorado group, which includes Hirsch, Bunn, and UC Denver professors of Medicine Wilbur Franklin, MD, and Marileila Varella-Garcia, PhD, previously found similar results using the EGFR FISH test to predict which patients would do well on Tarceva (erlotinib), another EGFR inhibitor drug. EGFR also plays a role in colorectal cancer, so the test could also be used to predict which of those patients may benefit from EGFR-blocking drugs.

Approximately 215,000 people in the United States will be diagnosed with lung cancer in 2008, according to the American Cancer Society. Only about 40 percent will be alive one year later, and only about 15 percent will be alive five years later. Because there is no effective screening test for lung cancer, most people are diagnosed when the disease has spread beyond the lung. Lung cancer kills more adults in the United States than any other cancer.

By: University of Colorado Hospital – Thu, 07/17/2008 – 13:46

Researchers from four leading cancer centers have confirmed that an analysis involving a panel of genes can be used to predict which lung cancer patients will have the worst survival. The finding could one day lead to a test that would help determine who needs more aggressive treatment.

The study on lung cancer and survival is the largest of its kind and appears online in Nature Medicine.

The researchers looked at 442 lung cancer tissue samples collected from six cancer hospitals in North America. They tested the cancer samples to look at the expression of hundreds of genes, and factored in clinical predictors such as tumor stage and the patients’ gender and age. The results showed that the lung cancers could be divided into groups with better and worse survival rates.

Typically, lung cancer patients receive chemotherapy after surgery to reduce the risk of the cancer coming back. But specialists know that some patients with stage I disease, the earliest stage, have an aggressive disease with poor prognosis while some patients with more advanced stage II disease have a relatively good prognosis. The question is how to identify which patients need the additional therapy and which patients could potentially avoid it.

“We found that looking at clinical data along with gene expression can be a more reliable indicator. Gene expression is not just a black box approach – which a lot of researchers think it is. Sometimes knowing the context actually helps you use that information more efficiently,” says study author David Beer, Ph.D., professor of surgery and radiation oncology at the University of Michigan Medical School and co-director of the Cancer Genetics Program at the U-M Comprehensive Cancer Center.

Lung cancer is particularly complex, with multiple types and subtypes, most of which are directly related to smoking. There are many genetic alterations induced by tobacco smoke exposure. To be able to offer one simple gene test for the disease, scientists would need to accurately model the known cellular diversity and the potential differences underlying the aggressiveness between lung cancers.

“Our findings suggest that there is a potential for successfully predicting lung cancer prognosis based on gene expression, but it is likely to be more difficult to develop a clinically useful test than has been suggested by previous studies. It’s going to require more assay standardization and a large prospective study to identify a signature that is ready for clinical use,” says study author Kerby Shedden, Ph.D., associate professor of statistics at U-M.

The researchers will continue to refine this process, identifying the important genes and testing them on tissue samples. They also plan in the future to test their predictors in a prospective trial, enrolling patients as they are diagnosed and following their progress. Enrollment for this trial has not begun.

Four institutions formed a consortium with support from the National Cancer Institute, to develop and validate gene expression signatures of lung cancers. The four institutions are the University of Michigan Comprehensive Cancer Center, H. Lee Moffitt Cancer Center and Research Institute in Tampa, Fla., Memorial Sloan-Kettering Cancer Center in New York, and Dana-Farber Cancer Institute in Boston.

The researchers collected lung cancer tissue samples from six centers and grouped them into four sets based on the laboratories where the samples were processed. Two sets served as the “training set,” in which researchers looked at several possible gene expression methods to determine whether they could be predictive of patient outcome. They then looked at the other two additional tumor sets for which all outcome data had remained unknown and blinded to the researchers, called “validation sets,” to assess whether the outcome of the training set could be duplicated.

By: University of Michigan Health System – Mon, 07/21/2008 – 15:43

Etzel and colleagues analyzed data from 491 African Americans with lung cancer and 497 African Americans without lung cancer to identify risk factors for the disease. They then compared these risk factors with a previously established risk prediction model for whites.

What was unique to African Americans was the risk associated with chronic obstructive pulmonary disease. African American men with a prior history of chronic obstructive pulmonary disease had a more than sixfold increased risk of lung cancer, similar to that seen with smoking. This is approximately two-fold higher than the risk typically seen from chronic obstructive pulmonary disease among whites.

“The one size fits all risk prediction clearly does not work,” said Carol Etzel, Ph.D., assistant professor of epidemiology at the University of Texas M.D. Anderson Cancer Center.

As with whites, smoking was a significant risk factor for lung cancer. Current smokers had a more than sixfold increased risk of lung cancer, and former smokers had a more than threefold increased risk. This decreased risk was confined to those who had quit smoking more than ten years prior to diagnosis; these patients had a 58 percent decreased risk compared with patients who had quit within the previous ten years.

Researchers also found that hay fever, previously shown to be protective among whites, was also protective among African Americans. Specifically, African Americans with hay fever were 44 percent less likely to develop lung cancer, a rate that had been previously seen among whites.

African American males have a higher risk of lung cancer incidence at 110.6 per 100,000 compared with 81 per 100,000 among white males. Mortality is also higher among African American men at 95.8 per 100,000 compared with 72.6 among whites. Lung cancer incidence and mortality rates among women are comparable.

Etzel said the risk prediction model detailed in Cancer Prevention Research is part of an ongoing project to establish risk models among different ethnic groups; a model for Hispanics is currently under development.

“What we hope is that a doctor can use these models to encourage their patients to take steps to prevent lung cancer. Even if they are never smokers, they can be at risk,” said Etzel.

By: American Association for Cancer Research – Fri, 09/05/2008 – 07:27

Lung cancer risk prediction models are enhanced by taking into account risk factors by race and by measuring DNA repair capacity, according to research teams led by epidemiologists at The University of Texas M. D. Anderson Cancer Center in two complementary papers appearing in the September issue of Cancer Prevention Research.

In the first study to focus on African-Americans, researchers found unique results based on increased exposure to certain risks. Based upon these findings, a specific model was developed to further refine the predictability of lung cancer in this population, according to lead author Carol Etzel, Ph.D., assistant professor in M. D. Anderson’s Department of Epidemiology.

“African-Americans have similar risk factors for lung cancer as Caucasians, but the risks tend to be higher, and there is a stronger association with occupational exposures, such as wood dust and asbestos, than we have previously observed for whites,” said Etzel. “Additionally, we determined the risks associated with Chronic Obstructive Pulmonary Disease (COPD) are substantially higher than those noted in Caucasian subjects.” COPDs, such as emphysema, raise a person’s risk for lung cancer.

The study focused on those who self-reported as being black, and who represented approximately 14 percent of the overall study population. Study participants were recruited from M. D. Anderson Cancer Center and the Michael E. DeBakey VA Medical Center in Houston, TX. The control population, which was matched on the basis of age, sex and ethnicity, was recruited from Houston-area community centers and the Kelsey-Seybold Clinic, Houston’s largest multi-specialty physician group practice. The African-American model was validated on an independent sample of African-American lung cancer cases and controls from two lung cancer studies being conducted in metropolitan Detroit.

“The challenge for us is to try to predict which of the United States’ estimated 45 million current smokers and 46 million former smokers are at highest risk for developing lung cancer. Accurate prediction models may identify subgroups of these smokers who will benefit most from intensive screening programs and behavioral interventions,” said Margaret Spitz, M.D., senior author and professor in M. D. Anderson’s Department of Epidemiology.

The previously published Spitz lung cancer risk prediction model was based solely on lung cancer cases and controls among Caucasian subjects. Internal and external validation results showed the predictive power of the new African-American group-specific model to approach 79 percent, versus 66 percent for the original model.

“The predictive abilities are much improved with the new model and underscore the need for further race-specific modeling,” said Spitz.

Expanding the Original Model

In the second paper, Spitz, the lead author, demonstrates that the predictive capability of her original model which incorporates clinical and risk factor data, was improved by adding two measures of DNA repair capacity.

The original Spitz model measured the following smoking intensity variables: Pack-years of smoking for current smokers and the age at which former smokers stopped smoking, physician-diagnosis of hay fever and emphysema, exposure to asbestos and dusts, and family history of cancer.

Suboptimal DNA repair capacity is associated with up to twofold statistically significant increased lung cancer risks. By adding these measures of repair capacity into expanded former smokers and current smokers models’ equations, the sensitivity of each were statistically significantly better than the baseline models. However, the sensitivity of these expanded models remains modest and further refining is planned by incorporating data on nutrition and common genetic variation into even more sophisticated models.

According to the authors, “While the uniform advice for any smoker is immediate cessation, reliable prediction models could be helpful in the context of both screening and prevention trials.”

The data for both studies were derived from a long-term 17-year study of the epidemiology of lung cancer at M. D. Anderson funded by the National Cancer Institute and led by Spitz. This research was supported by grants from the National Cancer Institute, and the Flight Attendant Medical Research Institute.

Participants of both studies were defined as “never smokers,” or those who had smoked fewer than 100 cigarettes in their lifetimes; “former smokers,” who had not smoked in more than a year; and “current smokers,” which included individuals who had quit smoking within the past 12 months. Smokers were also asked to report their use of mentholated cigarettes, and former smokers the age at which they stopped smoking.

Lung Cancer Facts

Over 85 percent of all lung cancers occur in current or former smokers. Lung cancer causes more deaths than any other cancer, killing more than 160,000 Americans annually and millions worldwide. According to the American Cancer Society, the incidence of lung cancer is close to 40 percent higher in African-American men, the death rate approximately 30 percent higher and the five-year survival rate is 12 percent versus 15 percent for whites.

Spitz added, “The team is working on a similar model targeting the Hispanic population. Our goal is to ultimately develop an interactive risk assessment tool, much like the Gail breast cancer risk assessment tool, to make lung cancer prediction in various populations accessible for treating physicians.”

By: University of Texas M. D. Anderson Cancer Center – Sun, 09/07/2008 – 14:32

A study by researchers from American Cancer Society looked at the data of lifelong nonsmokers living North America, Europe, and Asia. The data comes from 13 large-scale studies conducted during the period between 1960 and 2004. It includes examining more than 630,000 men who have lung cancer cases and 1.8 million men with death cases associated with the lung cancer. The data also includes information on women living in 10 countries and reporting to 22 cancer registries.

The study found that lung cancer among lifelong nonsmokers occurs as frequently as brain and central nervous system cancers do. Nonsmoking men were found to be at 1.1% risk of dying from lung cancers prematurely, while women were at 0.8% risk. The risk was especially high among African American and Asian men. This shows a significant difference between nonsmokers and smokers, who are at 22.1% (for men) and 11.9% (for women) risk of dying earlier.

Comparing lung cancer cases and death cases between smokers and nonsmoker, researchers concluded that from 10% to 15% (from 16000 to 24000 cases annually) of disease cases are caused by other factors, while for the rest of cases tobacco is responsible. For smokers lung cancer is the number one cause leading to premature death, while for nonsmokers it is only from seventh to ninth cancer causing early deaths.

Researchers also found that lung cancer cases remained stable among nonsmokers for a rather long period of time, since 1930. Overall, the number of nonsmokers is increasing, meaning that more needs to be done to help nonsmokers fight the the risk of lung cancer.

By: Ruzanna Haroutiunyan for eMaxHealth – Tue, 09/09/2008 – 11:56

For the study, lead researcher Carol Etzel of the University of Texas M.D. Anderson Cancer Center and colleagues developed a risk assessment model to help predict blacks’ risk for lung cancer. Researchers analyzed data on 491 blacks with lung cancer and 497 blacks without the disease to develop the tool and then compared it with the existing risk models for whites. Researchers said that blacks’ high risk for COPD prompted them to develop the risk assessment model to help doctors better predict lung cancer risk.

The new model found that black men with a history of COPD had a more than sixfold increased risk of developing lung cancer, which is about the same risk for those who smoke. According to Reuters, both black and white smokers have a risk of lung cancer six times higher than that of non-smokers. Smoking is the leading cause of COPD, but pollution, and other environmental factors also play a role, Reuters reports.

Etzel said, “What we hope is that a doctor can use these models to encourage their patients to take steps to prevent lung cancer. Even if they are never smokers, they can be at risk.” The researchers now are working on a risk model for Hispanics (Reuters, 9/4).

Reprinted with permission from kaisernetwork.org. You can view the entire Kaiser Weekly Health Disparities Report, search the archives, and sign up for email delivery at kaisernetwork.org/email . The Kaiser Weekly Health Disparities Report is published for kaisernetwork.org, a free service of The Henry J. Kaiser Family Foundation. © 2007 Advisory Board Company and Kaiser Family Foundation. All rights reserved.

By: kaisernetwork.org – Wed, 09/10/2008 – 16:08

To evaluate empathic opportunities and physician responses, we conducted a qualitative thematic analysis of 20 audiorecorded, transcribed consultations between patients with lung cancer and their thoracic surgeons or oncologists, from a larger observational study of 137 patients in a Veterans Affairs hospital in the southern United States. Using qualitative analysis, we collaboratively developed themes and subthemes until saturation. Then, each transcript was coded, using grounded theory methods, until consensus was achieved, counting and sequentially analyzing patient empathic opportunities and physician responses.

Subthemes regarding patients’ statements about lung cancer included (1) morbidity or mortality concerns, (2) cancer-related symptoms, (3) relationship to smoking, (4) decisions about treatment, (5) beliefs about or mistrust of medical care, (6) factors limiting ability to treat cancer, and (7) confusion regarding cancer status and treatment. We identified 384 empathic opportunities and found that physicians had responded empathically to 39 (10%) of them. Otherwise, physicians provided little emotional support, often shifting to biomedical questions and statements. We defined this phenomenon as missed opportunities for “interval empathy.”

When empathy was provided, 50% of these statements occurred in the last one-third of the encounter, whereas patients’ concerns were evenly raised throughout the encounter.

The study concluded that doctors rarely responded empathically to the concerns raised by patients with lung cancer, and empathic responses that did occur were more frequently in the last third of the encounter. Our results may provide a typologic approach to help physicians recognize empathic opportunities and with further development may aid in improving physicians’ communication skills.

By: Archives of Internal Medicine Sept. 22 Abstract – Tue, 09/23/2008 – 04:46

Paul Newman had been battling lung cancer since June 2008. He pulled out of directing a stage production of John Steinbeck’s Of Mice and Men in Connecticut because of unspecified health problems. His lung cancer put the disease in spotlight.

Lung cancer is the uncontrolled growth of abnormal cells in one or both lungs. These abnormal cells do not carry out the functions of normal cells and do not develop into healthy lung tissue. Researchers have found that it takes a series of genetic changes to create a lung cancer cell. Before becoming fully cancerous, cells can be precancerous, which means they have some irregularities (mutations) but still function as lung cells.

Lung Cancer Society reports that the signs and symptoms of lung cancer can take years to develop and they may not appear until the disease is advanced. Some symptoms of lung cancer that are in the chest can be coughing, especially if it persists or becomes intense, pain in the chest, shoulder, or back unrelated to pain from coughing. Other signs of lung cancer include a change in color or volume of sputum, shortness of breath and changes in the voice or being hoarse.

Harsh sounds with each breath (stridor), recurrent lung problems, such as bronchitis or pneumonia and coughing up blood are other known symptoms of lung cancer.

“People respond in different ways when they learn they have been diagnosed with cancer. Some people want to learn all they can about their disease, while others try not to think too much about it. Most health care professionals want you to be an active partner with them in making decisions. They know that you will better be able to cope with the challenges of treatment if you have a sense of control over the process,” writes Lung Cancer Society.

Because environmental factors other than smoking can increase your risk of lung cancer, it is important to reduce or eliminate those factors. Examples of environmental factors include asbestos, radon, and secondhand smoke. If you have been exposed to asbestos or radon, you can take steps to decrease or eliminate those exposures.

By: eMaxHealth and Lung Cance Society – Sat, 09/27/2008 – 17:39

Mr. Newman was an icon of the American stage and film, loved by audiences around the world. He and his devoted and equally talented wife, Joanne Woodward, changed the lives of people in the United States and around the world through their many philanthropic projects.

Two months ago reports began to appear in the press that Mr. Newman was undergoing treatment for lung cancer. Those reports were unconfirmed and respecting the family’s privacy we made no public comment at that time, even though we were dismayed at how callously Mr. Newman was being described as a “former chain smoker” with all the insinuations about lung cancer inherent in that label.

Mr. Newman was first and foremost a great man and that is how he should be remembered. We do not know what cancer took his life. We do know that a wonderful man is gone and we mourn his passing.

The stigma and blame associated with lung cancer has added to the burden that all lung cancer patients, and their families, must bear whether they smoked or not.

Over 215,000 people will be diagnosed with lung cancer this year, and the majority will die within 12 months. More people die from lung cancer than breast, prostate, colon, kidney, melanoma and liver cancers combined. Over half of them are former smokers many of whom quit decades ago and do not even realize that they will always be at higher risk. Another 15% have never smoked at all.

Our commitment to all who have died and to all those families that have been hurt by this deadly disease is: We will change this.

Lung Cancer Alliance (www.LungCancerAlliance.org) is the only national non-profit organization dedicated exclusively to patient support and advocacy for those living with or at risk for lung cancer.

By: Lung Cancer Alliance – Tue, 09/30/2008 – 04:04

“Most people are not aware that lung cancer among non-smokers has such an enormous impact,” said Lung Cancer Alliance (LCA) President %26amp; CEO Laurie Fenton Ambrose today. The heavy burden of lung cancer in non-smokers contradicts the common belief that lung cancer is a disease that strikes only smokers.

Whether non-smokers are being diagnosed with lung cancer at an increasing rate and whether that rate is higher in women than men is under debate. An American Cancer Society (ACS) study released earlier this week added fuel to that debate by claiming the rate is not increasing, and that men and women who have never smoked have similar rates of lung cancer.

“Our primary concern is real people,” said Fenton Ambrose. “The statistical debate over rates will continue to play out but we must not lose sight of the actual numbers of people – smokers, former smokers and never smokers – who are dying from this stigmatized and underfunded cancer.”

According to National Cancer Institute (NCI) estimates, 161,840 people – smokers, former smokers and non-smokers – will die of lung cancer in the U.S. in 2008. That is more people than the combined total of the next four biggest cancer killers: colon cancer (49,960 deaths), breast cancer (40,930 deaths), pancreatic cancer (34, 290 deaths) and prostate cancer (28,660).

The generally accepted estimate – and the estimate used in the ACS paper – is that never smokers account for 10% to 15% of all lung cancer deaths.

With the 15% number, 24,276 non-smokers will die in 2008, making non-smoking lung cancer the sixth largest cancer killer, ahead of leukemia (21,710 deaths), lymphoma (20,510 deaths), liver cancer (18,410 deaths) and ovarian cancer (15,520).

At the lower estimate of 10%, 16,189 non-smokers will die of lung cancer in 2008, making it the ninth most lethal cancer. (See attached table.)

LCA Board member, Deborah Morosini MD, the sister of Dana Reeve, a never smoker, whose death from lung cancer in 2006 brought public attention to the full impact of the disease, called the numbers on smoking-related and non-smoking-related lung cancers “staggering.”

“With smoking-related lung cancer the most lethal cancer and with non-smoking related lung cancer the sixth highest or even the ninth highest, it is clear that we must make lung cancer a national public health priority,” she said.

“This is not an ‘either or situation’,” she said. “We must address lung cancer period.”

In a press release on Monday, ACS claimed its study showed that “over the last 50 to 70 years, there has been no increase in lung cancer among people who have never smoked.”

However, state and regional cancer registries, which monitor the occurrence of cancer cases throughout the United States, do not routinely collect information on patient smoking history. As a result, there remains a lack of clear evidence regarding trends in non-smoking-related cancers over the last several decades.

A 2007 Stanford University study found that in adults aged 40-79 years; non-smoking women had a higher rate of lung cancer than non-smoking men. The ACS study found similar results with a higher ratio of non-smoking women to men in the 40-59 year age bracket, and similar gender specific rates in the 60-79 year age bracket. It was only among adults aged 80 years and older that women had a lower incidence rate than men in the ACS study.

The Stanford study, headed by Heather A. Wakelee MD, was prompted by clinicians who were seeing an increasing number of lung cancer patients, especially women, who had never smoked

“I commend Dr. Wakelee for opening up this critical area to research. The bottom line is that both these papers point out the urgent need for more accurate and better collection of data on smoking history and other risk factors for lung cancer and I hope we can move forward quickly ,” said Dr. Morosini.

Table 1:1

Estimated Cancer Deaths in 2008

Lung Cancer (smoking related) 137,564

Colon Cancer 49,960

Breast Cancer 40,930

Pancreatic Cancer 34,290

Prostate Cancer 28,660

Leukemia 21,710

Lymphoma 20,510

Liver Cancer 18,410

Ovarian Cancer 15,520

Lung Cancer (never smoker 15%) 24,276

Lung Cancer (never smoker 10%) 16,184

Source: 2008 SEER Cancer Facts and Figures

By: Lung Cancer Alliance – Tue, 09/30/2008 – 04:20