Smoking
The adverse health effects from cigarette smoking account for 440,000 deaths, or nearly 1 of every 5 deaths, each year in the United States. More deaths are caused each year by tobacco use than by all deaths from human immunodeficiency virus (HIV), illegal drug use, alcohol use, motor vehicle injuries, suicides, and murders combined.
Cancer
Cardiovascular Disease (Heart and Circulatory System)
By Gina Kolata : NY Times article : Oct 26, 2006
Researchers in New York report that millions of lives could be saved by detecting lung cancer early with annual CT scans and treating it immediately, when it can still be cured.
The stakes are high: while death rates for other cancers have fallen, lung cancer is the leading cause of cancer deaths in this country, killing more than 160,000 people a year.
For years, doctors have thought there was little they could do for lung cancer, but now with more sensitive scans, many are rethinking that view.
“You could prevent 80 percent of deaths,” said the study’s lead author, Dr. Claudia Henschke, a professor of radiology and cardiothoracic surgery at Weill Cornell Medical College.
But the report is controversial. Some medical experts and a patient advocacy group say that because this study is so much bigger than previous studies and so carefully done, it should change the testing landscape, while others say that it did not include comparison groups to demonstrate clearly that there is any benefit from annual CT exams.
The study, by researchers at NewYork-Presbyterian/Weill Cornell hospital and published today in The New England Journal, involved more than 31,000 people in seven countries. The participants included smokers and former smokers, but also included people in Japan who had never smoked but had the scans as part of annual physical exams.
The scans found 484 lung cancers, 412 of which were at a very early stage. Then the researchers tracked those cancer patients for an average of about three years after the cancer was detected. After three years, most patients were still alive. The researchers projected that more than 80 percent of those with early-stage cancer would live at least 10 years after their cancer was diagnosed.
Supporters of the findings include Dr. James Mulshine, a professor of internal medicine at Rush University Medical Center in Chicago. The study design may not have been perfect, he said, and there is more to be learned from other studies that are now under way, but he said the data from this one was convincing.
“This is a profoundly important report,” Dr. Mulshine said. “It is a remarkable result.”
Members of an advocacy group for lung cancer patients, the Lung Cancer Alliance, agreed. “This is the most important breakthrough for the lung cancer community,” Laurie Fenton, the group’s president, said in a news release.
And, says Dr. Henschke’s colleague Dr. David Yankelevitz, it makes sense that early detection can save lives. Lung cancer screening is analogous to screening for breast cancer, Dr. Yankelevitz said. In both situations, he added, “treatment is easier and the outcomes are better when the tumor is small.”
But mammograms are endorsed by many national groups, whereas lung cancer screening is not. And while praising the new study’s careful accumulation of data, representatives of groups like the American Cancer Society, the American Society of Clinical Oncology, the International Association for the Study of Lung Cancer and the U.S. Preventive Services Task Force, say the study is unlikely to persuade them to recommend screening as a public policy.
One reason is that everyone in Dr. Henschke’s study had CT scans. And so, researchers say, with no comparison group of people who did not have scans, they are left wondering: Does screening, in the end, save lives?
“Intuitively, it makes sense,” said Dr. Stephen Swensen, a professor of radiology at the Mayo Clinic who conducted a study that was similar to Dr. Henschke’s but smaller.
Dr. Swensen added, “It makes sense that if you find a cancer earlier you will save lives.”
But “the science hasn’t backed that up yet,” he said.
Cancer specialists have long known that there are cancers of all types — and lung cancers are no exception — that stop growing on their own, or that grow so slowly that they never cause problems. So, some ask, how many of the people said to be cured were never in danger? And how often will people have operations that can involve removing part of a lung, which is risky in itself, when their cancer was not lethal?
The problem, as with other cancer scans, is that science cannot always tell the difference between cancers that will stop and those that will not.
The researchers also ask another question: How often did the scans find cancers early but without affecting the person’s life expectancy?
“Everyone knows we can pick up things better with screening,” said Dr. Elliott Fishman, a professor of radiology and oncology at Johns Hopkins Hospital in Baltimore. “But is picking up the same thing as curing? If I pick up a tumor that is one centimeter today and you live five years or I pick it up four years later and you live one year, it’s the same thing.”
Even evaluating patients with suspicious CT results can be risky, more dangerous, say, than evaluating women with suspicious lumps on a mammogram, said Dr. David Johnson, deputy director of the cancer center at Vanderbilt University and a past president of the American Society of Clinical Oncology.
In Dr. Henschke’s study, doctors investigated more than 4,000 nodules in patients, finding about 400 early-stage cancers.
“This is not sticking a needle in a breast,” Dr. Johnson said. “It is sticking a needle in the chest, where it can collapse a lung.” In some cases, that is followed by surgery to further evaluate a lump. “How many people do we subject to needless evaluations?” Dr. Johnson asked.
It is not even clear, some researchers said, whether the patients in Dr. Henschke’s study really would survive 10 years on average. The investigators used a statistical model to estimate how long patients would be expected to live after most had survived about three years.
“Ten years should be 10 years,” Dr. Fishman said. “It’s being guesstimated out. Let’s look in 10 years and see what happens.”
More definitive answers about the value of CT testing may come in a few years when another study, by the National Cancer Institute, is over. It randomly assigned its nearly 55,000 participants, smokers or former smokers, to have annual CT scans or, for comparison, chest X-rays. Based on previous studies, many researchers consider chest X-rays largely ineffective for early diagnosis of the cancer, so it can serve as a placebo control in this study.
Another institute study is assessing chest X-rays by randomly assigning participants to have an annual X-rays or to have no screening.
In the meantime, cancer specialists say doctors and their patients must decide, on an individual basis, what to do. They could wait for the clinical trials to be completed, or they could decide to have scans now, while the data may not be ideal.
And the scans can be expensive. Dr. Howard Forman, a professor of diagnostic radiology at Yale, says that Yale charges $802.39 for the scan and the doctor’s interpretation.
And while many insurers do not pay for CT lung cancer screening tests, that may change, Dr. Forman said. He said he did not find this study to be convincing — like others, he said he needed to see control group data. But Dr. Forman, who is on the Medical Policy and Technology Assessment Committee for Wellpoint, an insurance company, said it would be hard to deny paying for the test now that the data were in The New England Journal of Medicine.
“The New England Journal of Medicine is a de facto Good Housekeeping seal of approval,” Dr. Forman said.
“It is not proof that screening saves lives,” he said. But, he added, “proof for a lot of medicine is not there.”
For now, said Dr. Robert Smith, director of cancer screening at the American Cancer Society, it may make sense for smokers or former smokers to have scans for early lung cancer detection.
Patients, Dr. Smith added, should discuss the test with their doctors first, going over potential benefits and potential dangers. And they should be careful to go to a center that has the expertise and experience to do the scans and any follow-up medical procedures properly.
But, he said, the new study adds to the information that CT scans might save lives.
“There is a lot of promise here,” he said. And so, he said, “it is not at all unreasonable for individuals at high risk of lung cancer to seek testing on their own.”
Others, like Dr. Ned Patz, a professor of radiology, pharmacology and cancer biology at Duke University Medical Center, say they suspect that patients’ desire for the tests may cool once they know of the risks.
“A lot of patients ask about it,” Dr. Patz said. “We counsel them and tell them what the data are. Then they are not interested.”
Study Raises Doubts About Lung Cancer Screening ....argument AGAINST CT scanning
By Gina Kolata : NY Times article ; March 6, 2007
Lung cancer screening with CT scans does not appear to save lives, and it exposes people to serious risks of injury and even death from needless surgery, researchers are reporting.
The results are a disappointment, the researchers say. Lung cancer is the leading cause of cancer deaths among men and women and kills more Americans than the four next most deadly cancers combined. For decades, cancer specialists have hoped to show that early detection and treatment can save lives.
The first attempts, using chest X-rays, were disappointing. But many hoped that the more sensitive CT scans could find cancers early enough to make a difference.
“When we took this study on, we were expecting that CT might do the job where chest X-rays couldn’t,” said Dr. Peter B. Bach, the study’s lead author and a lung specialist and epidemiologist at Memorial Sloan-Kettering Cancer Center.
But, he said, his hopes were dashed.
“We don’t think there is a hint of a benefit,” Dr. Bach said.
The new study’s conclusions, to be published Wednesday in The Journal of the American Medical Association, come just a few months after another study concluded that early detection with CT scans could save lives.
The main difference between the two studies, cancer researchers say, is the question of what counts as evidence of effectiveness — a decline in the death rate from lung cancer or an increase in survival time after being diagnosed. Estimating survival, as the previous study did, can be misleading, a number of researchers said, which is why they place less credence in it.
But the debate is unlikely to be settled until a more conclusive study, now under way and involving more than 50,000 people, is concluded. That study, sponsored by the National Cancer Institute, randomly assigned people to have CT scans or not and asked whether the death rate from lung cancer was lower in those who had scans. It will be several years until its results are known. In the meantime, Dr. Bach stresses that neither his study nor the previous one is definitive.
In the study to be published Wednesday, researchers from the Mayo Clinic in Rochester, Minn., the H. Lee Moffitt Cancer Center & Research Institute in Tampa, Fla., the Instituto Tumori in Milan, and Memorial Sloan-Kettering Cancer Center in New York, screened and analyzed data from 3,246 people with no symptoms of lung cancer. All were smokers or had smoked for an average of 39 years. And all were screened with CT scans of their lungs.
The scans detected lung cancer in 144 people. That, the researchers calculated, is about 300 percent more than would be expected without screening. And there was a concomitant thousand percent increase in surgical treatment. But, they note, the number who died from lung cancer — 38 — was about the same as it would have been without screening.
The researchers used a statistical model to estimate the expected number of cancers and the expected death rate without screening.
One reason more cancers were found and treated but the death rate was the same, researchers propose, is that screening led to the detection and treatment of cancers that did not need to be treated — they would not have grown enough in the person’s lifetime to cause any harm. And many of the deadly cancers that were treated still ended up killing patients. The extra surgical treatment prompted by screening can be harmful, the researchers noted. The death rate from lung cancer surgery is 5 percent. In addition, 20 to 40 percent of people who have lung cancer surgery have serious complications, like heart attacks, large blood clots in their lungs, pneumonia that requires time on a ventilator, and infections leading to repeat operations.
The new study’s conclusions are very different from those reached in the previous study of CT scans. There, researchers, led by Dr. Claudia Henschke, a professor of radiology and cardiothoracic surgery at Weill Cornell Medical College, reported that more than 80 percent of lung cancer deaths could be prevented with CT scans.
But Dr. Henschke’s did not attempt to compare mortality rates in people who were screened to the rates in those who were not.
Instead, in her analysis, she assumed everyone with lung cancer would die of it without treatment. Then she followed some patients for a median of three years after their cancer was detected and from that estimated the 10-year survival of screened patients. Survival rates, however, raise a very different question from death rates, many noted.
Dr. Henschke says the survival rate is the only question that is significant to patients. “I can calculate a case fatality rate, but that is meaningless to people,” she said. “What is meaningful is that when I screen, my long-term cure rate is 80 percent. That means when you are diagnosed, regardless of the stage of your cancer, you have an 80 percent chance of living for 10 years. And if you find it in stage one and promptly have surgery, your chance is as high as 92 percent.”
She added that the new study and hers had similar data. The difference, she said, “is that they were reporting it every step of the way in the most negative way.”
Dr. William Black, a radiologist at Dartmouth-Hitchcock Medical Center, who wrote an editorial accompanying the new paper, said the flaw in Dr. Henschke’s reasoning is her assumption that every untreated lung cancer is ultimately fatal.
Lung cancer, he said, like every other cancer, is a mixture of types. Some tumors are pretty much harmless: they would never spread and kill and they would have gone undetected were it not for the screening. The result of screening, though, will be a cancer diagnosis, treatment, and a “cure.”
Others are deadly no matter when they are found and treated, so finding them early only means more time with the cancer diagnosis. A person, for example, might die five years after symptoms are apparent, no matter what treatment is provided. If the cancer is detected five years before symptoms emerge, the person will survive 10 years after diagnosis as opposed to surviving five years after diagnosis if the cancer is not found until there are symptoms.
“As soon as you advance the date of diagnosis with any screening test you will improve the apparent survival,” said Dr. Barnett Kramer, who is associate director for disease prevention at the National Institutes of Health.
A final concern, Dr. Black said, is that Dr. Henschke may have missed the most deadly cancers. People who seemed fine after their last CT scan were only followed for a year. If they developed a fast-growing lung cancer and died of it soon after, they would not be counted in the lung cancer survival rate.
Dr. Kramer and Dr. Black, are members of the executive committee overseeing the National Cancer Institute’s National Lung Screening Trial, the randomized study of lung cancer screening.
Screening tests are worthwhile, these researchers say, if the death rate in the screened group is lower than the rate in people who are not screened.
“Survival is a meaningless statistic,” said Dr. Ned Patz, a professor of radiology at Duke University Medical Center who is an investigator in the National Cancer Institute study. “What we want to do is reduce the number of people who die from lung cancer. And that is mortality. What we all want to know is mortality.”
In fact, he added, the patients in the new study had exactly the same survival rate as those in Dr. Henschke’s study. Yet their death rate, apparently, was not affected by screening.
Dr. Bach said he knew that his study’s message, that lung cancer screening may do more harm than good, is difficult. But, he said, he hopes people will take it to heart and not have the screening test unless the randomized trial shows it reduces the death rate.
“It’s tricky,” Dr. Bach said. . “It’s far easier to take the paradigm — catch it early — and apply it to all cancers. But that clearly is not an apt model for all cancers.”
Essay: Trying to reconcile two different study results
H. Gilbert Welch, Steven Woloshin and Lisa M. Schwartz
NY Time Article : March 13, 2007
Of all the forms of cancer, lung cancer is by far the deadliest. So doctors have long hoped to come up with a screening test that would find it early, before it can grow and become untreatable.
Last fall, The New England Journal of Medicine published a study concluding that spiral CT screening (a kind of three-dimensional chest X-ray) would make most lung cancers curable. It sounded like wonderful news. For proponents of screening, it was a call to action: the Lung Cancer Alliance is starting an advertising campaign featuring sports celebrities trying to persuade you to make the “right call” and get screened.
But just last week The Journal of the American Medical Association published a study concluding that spiral CT screening is not only ineffective, but may actually be harmful, prompting unnecessary surgery that carries risks of its own.
How could these two studies — in the country’s two most prestigious medical journals — arrive at diametrically opposite conclusions? An answer requires a clear understanding of the goal of cancer screening.
That goal is to save lives — or, in scientific terms, reduce mortality. Simply finding cancer early is not enough.
Finding cancer early saves lives only if two conditions are met: the cancers detected are the ones that kill people; and early treatment prevents these deaths.
It is not enough to increase survival. While that may seem to be the mirror image of mortality, it can be a terribly misleading measure of the value of screening.
In the 1970s and ’80s, there was great interest in screening smokers for lung cancer using conventional chest X-rays. The question was seen as so important that it was examined using the gold standard of medical studies, a randomized trial. Half the participants were randomly selected to receive regular chest X-rays; half did not and served as the control group.
Three such randomized trials were conducted, and all three showed that screening did not reduce mortality. In fact, two reported slightly higher death rates in the group receiving chest X-rays.
The most famous of these trials, at the Mayo Clinic, showed how misleading survival can be. Although the 10-year survival rate doubled with screening, mortality was not reduced; indeed, screening may have increased it. The Mayo trial also showed that more than a decade after screening was stopped, there were still more cancers in the screened group. This shouldn’t happen: in two large randomly selected groups, there should be the same number of cancers in both. The chest X-rays must have detected some lung cancers that were never destined to cause symptoms or death — a phenomenon known as overdiagnosis.
This phenomenon challenges our conventional view of cancer as an inexorably progressive disease. Research in screening has demonstrated that what pathologists call cancer encompasses a broad spectrum of disorders: some cancers rapidly progress to death, some do so more slowly, and some don’t progress at all (or may even regress).
Overdiagnosis is even more of a concern for spiral CT, because it can detect far more abnormalities than chest X-rays. In fact, a screening program in Japan found about 10 times as many lung cancers with spiral CT as had been found in the same population using chest X-rays. More remarkably, the chance of having lung cancer detected by spiral CT was almost the same in nonsmokers and smokers.
This flies in the face of everything we know about lung cancer and smoking — 50 years of research showing that smokers are 10 to 20 times as likely as nonsmokers to die from lung cancer. This is powerful evidence that spiral CT detects some lung cancers that will never affect patients.
Because all lung cancer patients get treated, overdiagnosis means some people receive treatment that can’t help them (because they do not need it) and can only cause harm. Most patients given diagnoses of early lung cancer undergo surgery to remove part of a lung, a major operation from which about 5 percent die within a month.
With this background, let’s look at the two recent studies on screening.
The New England Journal study reported screening about 31,000 people with spiral CTs and finding 484 with lung cancer. These patients had a 10-year survival of 80 percent — compared with 10 percent for current lung cancer patients in the United States. The JAMA study reported screening about 3,200 people and finding 144 with lung cancer. (The detection rate was higher because this study had older patients and longer follow-up.) Of 3,200 people, 38 died from lung cancer — the same mortality rate expected for people of similar age and smoking history in the absence of screening.
In short, The New England Journal reported increased survival; JAMA reported no difference in mortality.
Most of us interpret “increased survival” to mean fewer deaths. But it does not, because survival is subject to two powerful distortions.
The first is called lead-time bias. Simply advancing the time of diagnosis (as with CT screening) will always increase survival.
Imagine two patients with lung cancer. Even if both die at age 70, a patient with cancer diagnosed by spiral CT screening at age 59 has a longer survival than one with cancer diagnosed because of symptoms (cough, weight loss and so on) at age 67. The first patient survives 11 years; the second 3 years. But both died at the same age. Survival is increased, but mortality is the same.
A second source of distortion results from overdiagnosis, when screening finds cancers that were never destined to progress and cause death. Overdiagnosis bias can also drastically inflate survival statistics, even if mortality is unchanged.
To understand why, you need to understand the definition of the two statistics. Both are fractions. Survival is calculated over a fixed period, for example 5 or 10 years.
Overdiagnosis inflates both the numerator of the survival statistic (number alive at a specified time) and the denominator (number of diagnoses). For the mortality statistic, overdiagnosis has no effect on the numerator (number of deaths) or the denominator (number studied). Perhaps the easiest way to understand this is to imagine if we told all the people in the country that they had lung cancer today: lung cancer mortality would be unchanged, but lung cancer survival would skyrocket.
The goal of lung cancer screening is to reduce mortality — to save lives. Because the New England Journal study examines only survival, it cannot tell us whether any lives are saved. Because the JAMA study examines mortality, it is the more valid study. It also corroborates the Mayo trial finding that a significantly increased survival rate can coexist with no difference in mortality.
The JAMA study also highlights the tradeoffs involved in lung cancer screening. The findings show that compared with no screening, if 1,000 people are screened over five years there would be 48 more lung cancer diagnoses, 46 more lung cancer operations (which would be expected to cause 2 deaths) and no lung cancer deaths prevented. The study data are consistent with as many as eight deaths prevented by screening, or eight extra deaths caused by it.
But neither study is definitive, because neither was a randomized trial. And both required assumptions. Given the potential benefit (so many people die from lung cancer) and the potential harms (some die from treatments), no one should have to assume anything.
Luckily, two randomized trials are under way — one a Dutch-Belgian collaboration, the other sponsored by the National Cancer Institute. Recent experience, notably with hormone replacement in postmenopausal women, has demonstrated how presuming benefits in the absence of randomized trials can cause real harm. To avoid repeating these mistakes, we should not screen for lung cancer unless the trials demonstrate a reduction in mortality.
This essay is by H. Gilbert Welch, Steven Woloshin and Lisa M. Schwartz. Dr. Welch is the author of “Should I Be Tested for Cancer? Maybe Not and Here’s Why” (University of California Press). He, Dr. Schwartz and Dr. Woloshin are senior research associates at the VA Outcomes Group in White River Junction, Vt.
Cancer
- The risk of dying from lung cancer is more than 22 times higher among men who smoke cigarettes, and about 12 times higher among women who smoke cigarettes compared with never smokers.
- Cigarette smoking increases the risk for many types of cancer, including cancers of the lip, oral cavity, and pharynx; esophagus; pancreas; larynx (voice box); lung; uterine cervix; urinary bladder; and kidney.
- Rates of cancers related to cigarette smoking vary widely among members of racial/ethnic groups, but are generally highest in African-American men.
Cardiovascular Disease (Heart and Circulatory System)
- Cigarette smokers are 2–4 times more likely to develop coronary heart disease than nonsmokers.
- Cigarette smoking approximately doubles a person’s risk for stroke
- Cigarette smoking causes reduced circulation by narrowing the blood vessels (arteries). Smokers are more than 10 times as likely as nonsmokers to develop peripheral vascular disease.
- Cigarette smoking is associated with a ten-fold increase in the risk of dying from chronic obstructive lung disease. About 90% of all deaths from chronic obstructive lung diseases are attributable to cigarette smoking.
- Cigarette smoking has many adverse reproductive and early childhood effects, including an increased risk for infertility, preterm delivery, stillbirth, low birth weight, and sudden infant death syndrome (SIDS).
- Postmenopausal women who smoke have lower bone density than women who never smoked. Women who smoke have an increased risk for hip fracture than never smokers.
By Gina Kolata : NY Times article : Oct 26, 2006
Researchers in New York report that millions of lives could be saved by detecting lung cancer early with annual CT scans and treating it immediately, when it can still be cured.
The stakes are high: while death rates for other cancers have fallen, lung cancer is the leading cause of cancer deaths in this country, killing more than 160,000 people a year.
For years, doctors have thought there was little they could do for lung cancer, but now with more sensitive scans, many are rethinking that view.
“You could prevent 80 percent of deaths,” said the study’s lead author, Dr. Claudia Henschke, a professor of radiology and cardiothoracic surgery at Weill Cornell Medical College.
But the report is controversial. Some medical experts and a patient advocacy group say that because this study is so much bigger than previous studies and so carefully done, it should change the testing landscape, while others say that it did not include comparison groups to demonstrate clearly that there is any benefit from annual CT exams.
The study, by researchers at NewYork-Presbyterian/Weill Cornell hospital and published today in The New England Journal, involved more than 31,000 people in seven countries. The participants included smokers and former smokers, but also included people in Japan who had never smoked but had the scans as part of annual physical exams.
The scans found 484 lung cancers, 412 of which were at a very early stage. Then the researchers tracked those cancer patients for an average of about three years after the cancer was detected. After three years, most patients were still alive. The researchers projected that more than 80 percent of those with early-stage cancer would live at least 10 years after their cancer was diagnosed.
Supporters of the findings include Dr. James Mulshine, a professor of internal medicine at Rush University Medical Center in Chicago. The study design may not have been perfect, he said, and there is more to be learned from other studies that are now under way, but he said the data from this one was convincing.
“This is a profoundly important report,” Dr. Mulshine said. “It is a remarkable result.”
Members of an advocacy group for lung cancer patients, the Lung Cancer Alliance, agreed. “This is the most important breakthrough for the lung cancer community,” Laurie Fenton, the group’s president, said in a news release.
And, says Dr. Henschke’s colleague Dr. David Yankelevitz, it makes sense that early detection can save lives. Lung cancer screening is analogous to screening for breast cancer, Dr. Yankelevitz said. In both situations, he added, “treatment is easier and the outcomes are better when the tumor is small.”
But mammograms are endorsed by many national groups, whereas lung cancer screening is not. And while praising the new study’s careful accumulation of data, representatives of groups like the American Cancer Society, the American Society of Clinical Oncology, the International Association for the Study of Lung Cancer and the U.S. Preventive Services Task Force, say the study is unlikely to persuade them to recommend screening as a public policy.
One reason is that everyone in Dr. Henschke’s study had CT scans. And so, researchers say, with no comparison group of people who did not have scans, they are left wondering: Does screening, in the end, save lives?
“Intuitively, it makes sense,” said Dr. Stephen Swensen, a professor of radiology at the Mayo Clinic who conducted a study that was similar to Dr. Henschke’s but smaller.
Dr. Swensen added, “It makes sense that if you find a cancer earlier you will save lives.”
But “the science hasn’t backed that up yet,” he said.
Cancer specialists have long known that there are cancers of all types — and lung cancers are no exception — that stop growing on their own, or that grow so slowly that they never cause problems. So, some ask, how many of the people said to be cured were never in danger? And how often will people have operations that can involve removing part of a lung, which is risky in itself, when their cancer was not lethal?
The problem, as with other cancer scans, is that science cannot always tell the difference between cancers that will stop and those that will not.
The researchers also ask another question: How often did the scans find cancers early but without affecting the person’s life expectancy?
“Everyone knows we can pick up things better with screening,” said Dr. Elliott Fishman, a professor of radiology and oncology at Johns Hopkins Hospital in Baltimore. “But is picking up the same thing as curing? If I pick up a tumor that is one centimeter today and you live five years or I pick it up four years later and you live one year, it’s the same thing.”
Even evaluating patients with suspicious CT results can be risky, more dangerous, say, than evaluating women with suspicious lumps on a mammogram, said Dr. David Johnson, deputy director of the cancer center at Vanderbilt University and a past president of the American Society of Clinical Oncology.
In Dr. Henschke’s study, doctors investigated more than 4,000 nodules in patients, finding about 400 early-stage cancers.
“This is not sticking a needle in a breast,” Dr. Johnson said. “It is sticking a needle in the chest, where it can collapse a lung.” In some cases, that is followed by surgery to further evaluate a lump. “How many people do we subject to needless evaluations?” Dr. Johnson asked.
It is not even clear, some researchers said, whether the patients in Dr. Henschke’s study really would survive 10 years on average. The investigators used a statistical model to estimate how long patients would be expected to live after most had survived about three years.
“Ten years should be 10 years,” Dr. Fishman said. “It’s being guesstimated out. Let’s look in 10 years and see what happens.”
More definitive answers about the value of CT testing may come in a few years when another study, by the National Cancer Institute, is over. It randomly assigned its nearly 55,000 participants, smokers or former smokers, to have annual CT scans or, for comparison, chest X-rays. Based on previous studies, many researchers consider chest X-rays largely ineffective for early diagnosis of the cancer, so it can serve as a placebo control in this study.
Another institute study is assessing chest X-rays by randomly assigning participants to have an annual X-rays or to have no screening.
In the meantime, cancer specialists say doctors and their patients must decide, on an individual basis, what to do. They could wait for the clinical trials to be completed, or they could decide to have scans now, while the data may not be ideal.
And the scans can be expensive. Dr. Howard Forman, a professor of diagnostic radiology at Yale, says that Yale charges $802.39 for the scan and the doctor’s interpretation.
And while many insurers do not pay for CT lung cancer screening tests, that may change, Dr. Forman said. He said he did not find this study to be convincing — like others, he said he needed to see control group data. But Dr. Forman, who is on the Medical Policy and Technology Assessment Committee for Wellpoint, an insurance company, said it would be hard to deny paying for the test now that the data were in The New England Journal of Medicine.
“The New England Journal of Medicine is a de facto Good Housekeeping seal of approval,” Dr. Forman said.
“It is not proof that screening saves lives,” he said. But, he added, “proof for a lot of medicine is not there.”
For now, said Dr. Robert Smith, director of cancer screening at the American Cancer Society, it may make sense for smokers or former smokers to have scans for early lung cancer detection.
Patients, Dr. Smith added, should discuss the test with their doctors first, going over potential benefits and potential dangers. And they should be careful to go to a center that has the expertise and experience to do the scans and any follow-up medical procedures properly.
But, he said, the new study adds to the information that CT scans might save lives.
“There is a lot of promise here,” he said. And so, he said, “it is not at all unreasonable for individuals at high risk of lung cancer to seek testing on their own.”
Others, like Dr. Ned Patz, a professor of radiology, pharmacology and cancer biology at Duke University Medical Center, say they suspect that patients’ desire for the tests may cool once they know of the risks.
“A lot of patients ask about it,” Dr. Patz said. “We counsel them and tell them what the data are. Then they are not interested.”
Study Raises Doubts About Lung Cancer Screening ....argument AGAINST CT scanning
By Gina Kolata : NY Times article ; March 6, 2007
Lung cancer screening with CT scans does not appear to save lives, and it exposes people to serious risks of injury and even death from needless surgery, researchers are reporting.
The results are a disappointment, the researchers say. Lung cancer is the leading cause of cancer deaths among men and women and kills more Americans than the four next most deadly cancers combined. For decades, cancer specialists have hoped to show that early detection and treatment can save lives.
The first attempts, using chest X-rays, were disappointing. But many hoped that the more sensitive CT scans could find cancers early enough to make a difference.
“When we took this study on, we were expecting that CT might do the job where chest X-rays couldn’t,” said Dr. Peter B. Bach, the study’s lead author and a lung specialist and epidemiologist at Memorial Sloan-Kettering Cancer Center.
But, he said, his hopes were dashed.
“We don’t think there is a hint of a benefit,” Dr. Bach said.
The new study’s conclusions, to be published Wednesday in The Journal of the American Medical Association, come just a few months after another study concluded that early detection with CT scans could save lives.
The main difference between the two studies, cancer researchers say, is the question of what counts as evidence of effectiveness — a decline in the death rate from lung cancer or an increase in survival time after being diagnosed. Estimating survival, as the previous study did, can be misleading, a number of researchers said, which is why they place less credence in it.
But the debate is unlikely to be settled until a more conclusive study, now under way and involving more than 50,000 people, is concluded. That study, sponsored by the National Cancer Institute, randomly assigned people to have CT scans or not and asked whether the death rate from lung cancer was lower in those who had scans. It will be several years until its results are known. In the meantime, Dr. Bach stresses that neither his study nor the previous one is definitive.
In the study to be published Wednesday, researchers from the Mayo Clinic in Rochester, Minn., the H. Lee Moffitt Cancer Center & Research Institute in Tampa, Fla., the Instituto Tumori in Milan, and Memorial Sloan-Kettering Cancer Center in New York, screened and analyzed data from 3,246 people with no symptoms of lung cancer. All were smokers or had smoked for an average of 39 years. And all were screened with CT scans of their lungs.
The scans detected lung cancer in 144 people. That, the researchers calculated, is about 300 percent more than would be expected without screening. And there was a concomitant thousand percent increase in surgical treatment. But, they note, the number who died from lung cancer — 38 — was about the same as it would have been without screening.
The researchers used a statistical model to estimate the expected number of cancers and the expected death rate without screening.
One reason more cancers were found and treated but the death rate was the same, researchers propose, is that screening led to the detection and treatment of cancers that did not need to be treated — they would not have grown enough in the person’s lifetime to cause any harm. And many of the deadly cancers that were treated still ended up killing patients. The extra surgical treatment prompted by screening can be harmful, the researchers noted. The death rate from lung cancer surgery is 5 percent. In addition, 20 to 40 percent of people who have lung cancer surgery have serious complications, like heart attacks, large blood clots in their lungs, pneumonia that requires time on a ventilator, and infections leading to repeat operations.
The new study’s conclusions are very different from those reached in the previous study of CT scans. There, researchers, led by Dr. Claudia Henschke, a professor of radiology and cardiothoracic surgery at Weill Cornell Medical College, reported that more than 80 percent of lung cancer deaths could be prevented with CT scans.
But Dr. Henschke’s did not attempt to compare mortality rates in people who were screened to the rates in those who were not.
Instead, in her analysis, she assumed everyone with lung cancer would die of it without treatment. Then she followed some patients for a median of three years after their cancer was detected and from that estimated the 10-year survival of screened patients. Survival rates, however, raise a very different question from death rates, many noted.
Dr. Henschke says the survival rate is the only question that is significant to patients. “I can calculate a case fatality rate, but that is meaningless to people,” she said. “What is meaningful is that when I screen, my long-term cure rate is 80 percent. That means when you are diagnosed, regardless of the stage of your cancer, you have an 80 percent chance of living for 10 years. And if you find it in stage one and promptly have surgery, your chance is as high as 92 percent.”
She added that the new study and hers had similar data. The difference, she said, “is that they were reporting it every step of the way in the most negative way.”
Dr. William Black, a radiologist at Dartmouth-Hitchcock Medical Center, who wrote an editorial accompanying the new paper, said the flaw in Dr. Henschke’s reasoning is her assumption that every untreated lung cancer is ultimately fatal.
Lung cancer, he said, like every other cancer, is a mixture of types. Some tumors are pretty much harmless: they would never spread and kill and they would have gone undetected were it not for the screening. The result of screening, though, will be a cancer diagnosis, treatment, and a “cure.”
Others are deadly no matter when they are found and treated, so finding them early only means more time with the cancer diagnosis. A person, for example, might die five years after symptoms are apparent, no matter what treatment is provided. If the cancer is detected five years before symptoms emerge, the person will survive 10 years after diagnosis as opposed to surviving five years after diagnosis if the cancer is not found until there are symptoms.
“As soon as you advance the date of diagnosis with any screening test you will improve the apparent survival,” said Dr. Barnett Kramer, who is associate director for disease prevention at the National Institutes of Health.
A final concern, Dr. Black said, is that Dr. Henschke may have missed the most deadly cancers. People who seemed fine after their last CT scan were only followed for a year. If they developed a fast-growing lung cancer and died of it soon after, they would not be counted in the lung cancer survival rate.
Dr. Kramer and Dr. Black, are members of the executive committee overseeing the National Cancer Institute’s National Lung Screening Trial, the randomized study of lung cancer screening.
Screening tests are worthwhile, these researchers say, if the death rate in the screened group is lower than the rate in people who are not screened.
“Survival is a meaningless statistic,” said Dr. Ned Patz, a professor of radiology at Duke University Medical Center who is an investigator in the National Cancer Institute study. “What we want to do is reduce the number of people who die from lung cancer. And that is mortality. What we all want to know is mortality.”
In fact, he added, the patients in the new study had exactly the same survival rate as those in Dr. Henschke’s study. Yet their death rate, apparently, was not affected by screening.
Dr. Bach said he knew that his study’s message, that lung cancer screening may do more harm than good, is difficult. But, he said, he hopes people will take it to heart and not have the screening test unless the randomized trial shows it reduces the death rate.
“It’s tricky,” Dr. Bach said. . “It’s far easier to take the paradigm — catch it early — and apply it to all cancers. But that clearly is not an apt model for all cancers.”
Essay: Trying to reconcile two different study results
H. Gilbert Welch, Steven Woloshin and Lisa M. Schwartz
NY Time Article : March 13, 2007
Of all the forms of cancer, lung cancer is by far the deadliest. So doctors have long hoped to come up with a screening test that would find it early, before it can grow and become untreatable.
Last fall, The New England Journal of Medicine published a study concluding that spiral CT screening (a kind of three-dimensional chest X-ray) would make most lung cancers curable. It sounded like wonderful news. For proponents of screening, it was a call to action: the Lung Cancer Alliance is starting an advertising campaign featuring sports celebrities trying to persuade you to make the “right call” and get screened.
But just last week The Journal of the American Medical Association published a study concluding that spiral CT screening is not only ineffective, but may actually be harmful, prompting unnecessary surgery that carries risks of its own.
How could these two studies — in the country’s two most prestigious medical journals — arrive at diametrically opposite conclusions? An answer requires a clear understanding of the goal of cancer screening.
That goal is to save lives — or, in scientific terms, reduce mortality. Simply finding cancer early is not enough.
Finding cancer early saves lives only if two conditions are met: the cancers detected are the ones that kill people; and early treatment prevents these deaths.
It is not enough to increase survival. While that may seem to be the mirror image of mortality, it can be a terribly misleading measure of the value of screening.
In the 1970s and ’80s, there was great interest in screening smokers for lung cancer using conventional chest X-rays. The question was seen as so important that it was examined using the gold standard of medical studies, a randomized trial. Half the participants were randomly selected to receive regular chest X-rays; half did not and served as the control group.
Three such randomized trials were conducted, and all three showed that screening did not reduce mortality. In fact, two reported slightly higher death rates in the group receiving chest X-rays.
The most famous of these trials, at the Mayo Clinic, showed how misleading survival can be. Although the 10-year survival rate doubled with screening, mortality was not reduced; indeed, screening may have increased it. The Mayo trial also showed that more than a decade after screening was stopped, there were still more cancers in the screened group. This shouldn’t happen: in two large randomly selected groups, there should be the same number of cancers in both. The chest X-rays must have detected some lung cancers that were never destined to cause symptoms or death — a phenomenon known as overdiagnosis.
This phenomenon challenges our conventional view of cancer as an inexorably progressive disease. Research in screening has demonstrated that what pathologists call cancer encompasses a broad spectrum of disorders: some cancers rapidly progress to death, some do so more slowly, and some don’t progress at all (or may even regress).
Overdiagnosis is even more of a concern for spiral CT, because it can detect far more abnormalities than chest X-rays. In fact, a screening program in Japan found about 10 times as many lung cancers with spiral CT as had been found in the same population using chest X-rays. More remarkably, the chance of having lung cancer detected by spiral CT was almost the same in nonsmokers and smokers.
This flies in the face of everything we know about lung cancer and smoking — 50 years of research showing that smokers are 10 to 20 times as likely as nonsmokers to die from lung cancer. This is powerful evidence that spiral CT detects some lung cancers that will never affect patients.
Because all lung cancer patients get treated, overdiagnosis means some people receive treatment that can’t help them (because they do not need it) and can only cause harm. Most patients given diagnoses of early lung cancer undergo surgery to remove part of a lung, a major operation from which about 5 percent die within a month.
With this background, let’s look at the two recent studies on screening.
The New England Journal study reported screening about 31,000 people with spiral CTs and finding 484 with lung cancer. These patients had a 10-year survival of 80 percent — compared with 10 percent for current lung cancer patients in the United States. The JAMA study reported screening about 3,200 people and finding 144 with lung cancer. (The detection rate was higher because this study had older patients and longer follow-up.) Of 3,200 people, 38 died from lung cancer — the same mortality rate expected for people of similar age and smoking history in the absence of screening.
In short, The New England Journal reported increased survival; JAMA reported no difference in mortality.
Most of us interpret “increased survival” to mean fewer deaths. But it does not, because survival is subject to two powerful distortions.
The first is called lead-time bias. Simply advancing the time of diagnosis (as with CT screening) will always increase survival.
Imagine two patients with lung cancer. Even if both die at age 70, a patient with cancer diagnosed by spiral CT screening at age 59 has a longer survival than one with cancer diagnosed because of symptoms (cough, weight loss and so on) at age 67. The first patient survives 11 years; the second 3 years. But both died at the same age. Survival is increased, but mortality is the same.
A second source of distortion results from overdiagnosis, when screening finds cancers that were never destined to progress and cause death. Overdiagnosis bias can also drastically inflate survival statistics, even if mortality is unchanged.
To understand why, you need to understand the definition of the two statistics. Both are fractions. Survival is calculated over a fixed period, for example 5 or 10 years.
Overdiagnosis inflates both the numerator of the survival statistic (number alive at a specified time) and the denominator (number of diagnoses). For the mortality statistic, overdiagnosis has no effect on the numerator (number of deaths) or the denominator (number studied). Perhaps the easiest way to understand this is to imagine if we told all the people in the country that they had lung cancer today: lung cancer mortality would be unchanged, but lung cancer survival would skyrocket.
The goal of lung cancer screening is to reduce mortality — to save lives. Because the New England Journal study examines only survival, it cannot tell us whether any lives are saved. Because the JAMA study examines mortality, it is the more valid study. It also corroborates the Mayo trial finding that a significantly increased survival rate can coexist with no difference in mortality.
The JAMA study also highlights the tradeoffs involved in lung cancer screening. The findings show that compared with no screening, if 1,000 people are screened over five years there would be 48 more lung cancer diagnoses, 46 more lung cancer operations (which would be expected to cause 2 deaths) and no lung cancer deaths prevented. The study data are consistent with as many as eight deaths prevented by screening, or eight extra deaths caused by it.
But neither study is definitive, because neither was a randomized trial. And both required assumptions. Given the potential benefit (so many people die from lung cancer) and the potential harms (some die from treatments), no one should have to assume anything.
Luckily, two randomized trials are under way — one a Dutch-Belgian collaboration, the other sponsored by the National Cancer Institute. Recent experience, notably with hormone replacement in postmenopausal women, has demonstrated how presuming benefits in the absence of randomized trials can cause real harm. To avoid repeating these mistakes, we should not screen for lung cancer unless the trials demonstrate a reduction in mortality.
This essay is by H. Gilbert Welch, Steven Woloshin and Lisa M. Schwartz. Dr. Welch is the author of “Should I Be Tested for Cancer? Maybe Not and Here’s Why” (University of California Press). He, Dr. Schwartz and Dr. Woloshin are senior research associates at the VA Outcomes Group in White River Junction, Vt.
Not Starting Means Never Having to Quit
By Jane E. Brody : NY Times : June 19, 2010
My husband’s fate was sealed at age 11, when he smoked his first cigarette. As he put it, “I got hooked that very day.” Although he tried repeatedly to quit, he rarely abstained from nicotine longer than a tortured week or two.
Finally, with the help of a hypnotist and nicotine gum, at age 61 he quit for good. But 50 years of smoking, emphysema limited his stamina for a decade, and lung cancer killed him 15 years after he smoked his last cigarette.
That’s the bad news. The good news is that he repeatedly told our sons, “Learn from my mistake — if you never start, you’ll never have to quit,” and they never started. Nicotine is a legal but pernicious addictive drug, likened in its tenacity to heroin and cocaine. Recent studies have shown how it hooks so many people — especially adolescents — and why those who smoke have such a hard time giving it up, even when they know the risks all too well. One woman I know has had lung cancer twice and is still smoking.
After several decades of decline in the prevalence of smoking, fostered largely by clean-air regulations and public stigma, it has now leveled off at around 20 percent of Americans 18 and older, said Dr. Neal L. Benowitz of the University of California, San Francisco, author of a recent report on nicotine addiction in The New England Journal of Medicine. As older smokers quit or die, Dr. Benowitz said in an interview, more youngsters start. That keeps the number of smokers at 45 million, and the number of smoking-related deaths at 435,000 a year.
An Early Start
The studies have clearly shown that those who first smoke as adolescents (or younger) are more likely to become regular and heavier smokers as adults. Furthermore, studies in adolescent animals found that nicotine can induce “permanent structural and chemical changes in the brain that affect behavior and foster addiction,” Dr. Benowitz said.
Still, the improved understanding of nicotine addiction, including evidence of a genetic influence, has offered new avenues for prevention and treatment. First and foremost, of course, is to keep youngsters from starting. Those who make it to 18 without inhaling cigarette smoke are least likely to become regular smokers.
As Dr. Chyke A. Doubeni and colleagues at the University of Massachusetts Medical School reported in June
Those who inhaled tobacco smoke at least once a month, the researchers reported, were 10 times as likely as less frequent smokers to develop symptoms of nicotine dependence, including a strong desire to smoke, withdrawal symptoms, feeling addicted and having difficulty controlling their smoking.
The more often they smoked, the more dependent they became, and vice versa. Even one symptom of dependency was enough to lead to daily smoking.
Dr. Benowitz expects that New York’s new $4.35-a-pack cigarette tax (by far the highest in the nation) will deter adolescent smoking by raising the full price to about $10. But more can be done through taxation, especially if tax dollars are directed toward tobacco control.
In The New England Journal of Medicine this month, Dr. Steven A. Schroeder and Kenneth E. Warner note that European tobacco taxes tend to be much higher; in Norway, for example, they exceed $11 a pack. The writers suggested extending smoke-free zones to vehicles in which children ride, apartments and condominiums, and public parks and beaches, as well as more public financing of cessation programs.
Nicotine’s Hook
Nicotine provides a quick fix. With each inhalation, it is carried into the lungs, where it rapidly enters the circulation and moves quickly to the brain. There it binds to receptors and facilitates the release of various brain chemicals, especially dopamine, which induces feelings of pleasure that in turn reinforce the desire for more nicotine.
Dr. Benowitz explained that over the course of a day, as the brain continues to be exposed to nicotine, partial tolerance develops and each subsequent cigarette produces less of an effect. But during sleep, nicotine comes off the receptors and smokers awaken with an intense craving for a cigarette.
“That first cigarette in the morning has the biggest kick,” he said, and the vicious cycle resumes. He reported that as tolerance develops, the number of binding sites for nicotine in the brain increases, enhancing symptoms of craving and withdrawal and the desire for the next cigarette.
New drugs, like varenicline (Chantix), have been developed that block nicotine receptors and make smoking less satisfying; other drugs under development have nicotinelike effects that can lessen withdrawal symptoms. A nicotine vaccine is also being tested.
To be sure, cravings for nicotine go beyond its chemistry. As Dr. Benowitz reported: “Nicotine induces pleasure and reduces stress and anxiety. Smokers use it to modulate levels of arousal and to control mood. Smoking improves concentration, reaction time, and performance of certain tasks.”
He added, however, that “relief from withdrawal symptoms is probably the primary reason for this enhanced performance and heightened mood.” In other words, if they had never started smoking, most people would never know the difference.
The main exception, perhaps, may be people who suffer from depression, other mental ills, and substance abuse disorders. They are more likely to smoke and much less likely to quit because nicotine acts as a form of self-medication.
When addicted smokers try to quit, they experience irritability, depressed mood, restlessness and anxiety, symptoms typical of psychiatric patients. Many in withdrawal say they feel that there is little pleasure left in life.
Added to the brain effects of nicotine withdrawal are behavioral and environmental cues to smoke — the feel and taste of a cigarette; the association with certain moods and activities like drinking, partying, or relaxing after a meal; a habit of smoking on the job, or being with someone who is smoking — and you can see why it can be so hard for a smoker to quit.
Dr. Benowitz noted that women who smoke are more strongly influenced than men by “conditioned cues” and negative emotions. Women also metabolize nicotine more quickly, which can make them more dependent on nicotine and explain in part why it is more difficult for women to quit.
“If we understand the reasons different people smoke, we can provide specific behavioral skills to deal with them instead of smoking,” he said. “Smoking cessation has to be individualized.”
By Jane E. Brody : NY Times : June 19, 2010
My husband’s fate was sealed at age 11, when he smoked his first cigarette. As he put it, “I got hooked that very day.” Although he tried repeatedly to quit, he rarely abstained from nicotine longer than a tortured week or two.
Finally, with the help of a hypnotist and nicotine gum, at age 61 he quit for good. But 50 years of smoking, emphysema limited his stamina for a decade, and lung cancer killed him 15 years after he smoked his last cigarette.
That’s the bad news. The good news is that he repeatedly told our sons, “Learn from my mistake — if you never start, you’ll never have to quit,” and they never started. Nicotine is a legal but pernicious addictive drug, likened in its tenacity to heroin and cocaine. Recent studies have shown how it hooks so many people — especially adolescents — and why those who smoke have such a hard time giving it up, even when they know the risks all too well. One woman I know has had lung cancer twice and is still smoking.
After several decades of decline in the prevalence of smoking, fostered largely by clean-air regulations and public stigma, it has now leveled off at around 20 percent of Americans 18 and older, said Dr. Neal L. Benowitz of the University of California, San Francisco, author of a recent report on nicotine addiction in The New England Journal of Medicine. As older smokers quit or die, Dr. Benowitz said in an interview, more youngsters start. That keeps the number of smokers at 45 million, and the number of smoking-related deaths at 435,000 a year.
An Early Start
The studies have clearly shown that those who first smoke as adolescents (or younger) are more likely to become regular and heavier smokers as adults. Furthermore, studies in adolescent animals found that nicotine can induce “permanent structural and chemical changes in the brain that affect behavior and foster addiction,” Dr. Benowitz said.
Still, the improved understanding of nicotine addiction, including evidence of a genetic influence, has offered new avenues for prevention and treatment. First and foremost, of course, is to keep youngsters from starting. Those who make it to 18 without inhaling cigarette smoke are least likely to become regular smokers.
As Dr. Chyke A. Doubeni and colleagues at the University of Massachusetts Medical School reported in June
Those who inhaled tobacco smoke at least once a month, the researchers reported, were 10 times as likely as less frequent smokers to develop symptoms of nicotine dependence, including a strong desire to smoke, withdrawal symptoms, feeling addicted and having difficulty controlling their smoking.
The more often they smoked, the more dependent they became, and vice versa. Even one symptom of dependency was enough to lead to daily smoking.
Dr. Benowitz expects that New York’s new $4.35-a-pack cigarette tax (by far the highest in the nation) will deter adolescent smoking by raising the full price to about $10. But more can be done through taxation, especially if tax dollars are directed toward tobacco control.
In The New England Journal of Medicine this month, Dr. Steven A. Schroeder and Kenneth E. Warner note that European tobacco taxes tend to be much higher; in Norway, for example, they exceed $11 a pack. The writers suggested extending smoke-free zones to vehicles in which children ride, apartments and condominiums, and public parks and beaches, as well as more public financing of cessation programs.
Nicotine’s Hook
Nicotine provides a quick fix. With each inhalation, it is carried into the lungs, where it rapidly enters the circulation and moves quickly to the brain. There it binds to receptors and facilitates the release of various brain chemicals, especially dopamine, which induces feelings of pleasure that in turn reinforce the desire for more nicotine.
Dr. Benowitz explained that over the course of a day, as the brain continues to be exposed to nicotine, partial tolerance develops and each subsequent cigarette produces less of an effect. But during sleep, nicotine comes off the receptors and smokers awaken with an intense craving for a cigarette.
“That first cigarette in the morning has the biggest kick,” he said, and the vicious cycle resumes. He reported that as tolerance develops, the number of binding sites for nicotine in the brain increases, enhancing symptoms of craving and withdrawal and the desire for the next cigarette.
New drugs, like varenicline (Chantix), have been developed that block nicotine receptors and make smoking less satisfying; other drugs under development have nicotinelike effects that can lessen withdrawal symptoms. A nicotine vaccine is also being tested.
To be sure, cravings for nicotine go beyond its chemistry. As Dr. Benowitz reported: “Nicotine induces pleasure and reduces stress and anxiety. Smokers use it to modulate levels of arousal and to control mood. Smoking improves concentration, reaction time, and performance of certain tasks.”
He added, however, that “relief from withdrawal symptoms is probably the primary reason for this enhanced performance and heightened mood.” In other words, if they had never started smoking, most people would never know the difference.
The main exception, perhaps, may be people who suffer from depression, other mental ills, and substance abuse disorders. They are more likely to smoke and much less likely to quit because nicotine acts as a form of self-medication.
When addicted smokers try to quit, they experience irritability, depressed mood, restlessness and anxiety, symptoms typical of psychiatric patients. Many in withdrawal say they feel that there is little pleasure left in life.
Added to the brain effects of nicotine withdrawal are behavioral and environmental cues to smoke — the feel and taste of a cigarette; the association with certain moods and activities like drinking, partying, or relaxing after a meal; a habit of smoking on the job, or being with someone who is smoking — and you can see why it can be so hard for a smoker to quit.
Dr. Benowitz noted that women who smoke are more strongly influenced than men by “conditioned cues” and negative emotions. Women also metabolize nicotine more quickly, which can make them more dependent on nicotine and explain in part why it is more difficult for women to quit.
“If we understand the reasons different people smoke, we can provide specific behavioral skills to deal with them instead of smoking,” he said. “Smoking cessation has to be individualized.”
....and you thought doctors were smart!
