Frontiers

There are few walk-a-thons, golf tournaments, wine tastings or gala fund-raisers held for the Invisible Cancer. Celebrities don’t step forward to draw attention to it, and the media rarely run stories addressing it. Yet, the Invisible Cancer will kill some 160,440 Americans this year alone—more than malignancies of the breast, colon, prostate and cervix combined.

People with the Invisible Cancer usually don’t live long enough to hold marches or letter-writing campaigns, so they have little support in Congress. And while colored ribbons are used to raise awareness of other illnesses, a clear ribbon trimmed in gold represents the Invisible Cancer. The gold recognizes the value of each survivor.

The disease earned the name “Invisible Cancer” because it often develops without specific signs or symptoms that reveal its presence until later, when cure is unlikely or impossible. The overall five-year survival rate for the Invisible Cancer is only 15 percent for the general population and only 11 percent for African Americans. These rates haven’t changed much in 30 years. The Invisible Cancer is, of course, lung cancer.

Clearly, this disease needs more research (see Commentary). But the National Cancer Institute’s (NCI) Lung Cancer Progress Review Group reports that money for lung-cancer research falls “far below the levels that characterize other common malignancies and far out of proportion to its massive public health impact.”

Furthermore, the NCI is virtually the only source of dollars for lung cancer research. Most other cancers have foundations, advocacy groups and organizations that supplement NCI funding. The Department of Defense, for example, funds research on cancers of the breast, prostate and ovaries and on chronic myelogenous leukemia through its Congressionally Directed Medical Research Program. But it has no research program for lung cancer. Yet, Veterans Administration hospitals treat more than 6,000 lung cancer cases annually.

This lack of awareness-raising events and spokespersons, and low levels of research funding relative to the number who die of the disease suggest a national lack-of-concern for the America’s leading cancer killer. Why the bias?

The explanation may boil down to a little three-word question asked of almost everyone with lung cancer: Did you smoke?

Some 87 percent of lungcancer cases are caused by smoking. The link between the two was first convincingly thrust forward by the U.S. Surgeon General in 1964, and it is now beyond dispute. Tobacco smoke contains 3,500 chemicals, 20 of which are cancer-causing. The

About 1 in 10 heavy smokers develop lung cancer. That some heavy smokers live into their 90s and never get cancer strongly suggests that a person’s genetic make-up influences lungcancer risk. Research suggests that women may be more susceptible to lung cancer than men.

As the evidence grew linking smoking and lung cancer, the number of U.S. adult smokers
dropped from 42.4 percent in 1965 to 22 percent in 2003.

Today, smoking is scorned by most of society, and popular opinion regards lung cancer as a self-inflicted disease. But that view is too simplistic, say those who study smoking and lung cancer.

Janet Healy is director of the Alliance for Lung Cancer Advocacy, Support and Education (ALCASE), a national advocacy group for people with lung cancer. The did-you-smoke question is a sensitive one for people with lung cancer who call the ALCASE hotline.

“They see it as an attempt to affix blame or at least causation,” Healy says. “To them, it implies fault. It implies even a certain willful ignorance on their part: ‘How could they not know cigarettes are harmful, and if they continue to smoke, why are they surprised to get lung cancer?’

“On the personal level, this attitude contributes to clinical depression and can lead to a sense of isolation and selfblame. So you get this sort of whirlpool of shame within the person who has lung cancer.” Depression occurs in more than one-third of people with lung cancer, Healy says.

This attitude of blame stigmatizes those with lung cancer and heaps more suffering onto people who are coping with a devastating disease and in need of compassion. The question ‘did you smoke?’ is particularly vexing for the 12-13 percent of people with lung cancer who never smoked. Some of these cases are due to second-hand smoke, some to unknown causes and some to on-the-job exposure to cancer-causing substances such as asbestos, radon, nickel, chromium, arsenic and other chemicals.

Lung cancer’s long road often begins in childhood

Mary Ellen Wewers, RN, PhD, MPH, Mildred E. Newton Professor of Nursing and a specialist in smoking cessation, has great sympathy for smokers with lung cancer. “Most smokers begin as children, and most think they will have quit by the time they leave high school, she says. “But 95 percent don’t. They become dependent on nicotine and its biological effects.” Society’s readiness to stigmatize smokers also overlooks the socioeconomic factors of smoking and the persuasive, targeted marketing of the tobacco companies, she says.

Nationally, 80 percent of smokers begin smoking before age 18, and 22 percent of young people begin smoking before age 13. A University of Michigan study found that 85 percent of high school seniors who smoked occasionally believed that they would not be smoking in five years, as did 32 percent of those smoking one pack a day.

A follow-up study done five to six years later found that only 13 percent of the pack-a-day smokers had quit and that 69 percent smoked one pack a day or more. Of those who smoked one to five cigarettes a day as seniors, only 30 percent had quit—60 percent had expected to do so—and 44 percent had increased their cigarette consumption.

Some 20 to 30 percent of smokers with lung cancer don’t want to quit even after their diagnosis, Wewers says. It happens, she says, because they have a poor prognosis, they already have cancer, or because they can’t quit.

Research also shows that tobacco use is influenced by education level and socioeconomic status. In 2001, 22 percent of Americans over age 25 smoked. Of those, 59 percent had a high school education or less, 22 percent had some college and 11 percent had a Bachelor’s degree or higher.

“Disadvantaged people are more likely to smoke and get lung cancer than privileged people,” Wewers says. Children in both lower and upper socioeconomic groups start smoking at the same rate, she says. “But as they grow into adulthood, those with more options can get help quitting, or they replace nicotine with other activity or with medication. But the disenfranchised and underserved don’t have those opportunities.”

Cool images negate written warnings

“The tobacco industry also used highly effective marketing campaigns to target young people, poorer minorities and whites and other vulnerable groups,” Wewers says.

A 1999 editorial in the New England Journal of Medicine (NEJM) noted that during the 1990s, tobacco advertising heavily targeted African-American teenagers, and that during the decade the prevalence of teenage African- American smokers rose from 13 percent to 23 percent, an 80 percent increase.

A 2001 NEJM study showed that even the 1998 Master Settlement Agreement, which prohibits tobacco marketing to people under 18 years of age, has done little to reduce the exposure of young people to cigarette advertising in magazines. “In short,” says an accompanying editorial, “the Master Settlement Agreement by itself will do little to change the fact that 400,000 Americans die every year of tobacco-related diseases and that more than 3,000 children become regular smokers every day.”

Tobacco company marketing strategies minimize risks and negate the warnings printed on advertisements and tobacco products. “Many studies show that if risk statements are juxtaposed with messages that show positive experiences, the perception of the risk is diminished,” says Neal L. Benowitz, MD, chief of clinical pharmacology and experimental therapeutics, University of California San Francisco.

“Teenagers see cool people in movies and healthy, sexy people in advertisements, and that undermines the risk,” he says. “The truth is, one of every two lifelong smokers dies an average 10 years sooner than nonsmokers, but teenagers don’t know that.”

Addiction keeps the small fires burning

Industry stratagems, peer pressure, rebelliousness and wanting a personal identity can trick teens to start smoking. But nicotine addiction keeps them going.

“Addiction is a risk that is not understandable, or it’s underestimated, by someone who is not addicted,” says Benowitz, a national authority on nicotine addiction. “Most kids sort of understand the concept, but they figure they’re different. It won’t happen to them. But most become addicted and can’t quit.”

Adolescents who begin occasional tobacco use can show signs of nicotine dependence within days to weeks, he says. Nicotine works on the brain and changes a person’s psychological state. The drug attaches to proteins on brain cells known as receptors. “People with certain receptor types are more susceptible to the drug than others,” Benowitz says.

Nicotine works like acetylcholine, a hormone-like substance produced by brain cells that is involved in pleasure, mood and arousal. Some people use the nicotine in cigarettes to help get through the day, Benowitz says.

“When they wake up in the morning, a cigarette helps them get going; when they feel stressed, a cigarette helps them relax; when they get depressed, a cigarette makes them feel better; when they’re lethargic, a cigarette stimulates them; a cigarette at bedtime helps them relax.”

“I can’t turn back the clock for me, but people need to be made aware of just what a killer lung cancer is.”  — Lung cancer survivor Rich Shapiro.

When regular smokers do try to quit smoking, they have uncomfortable withdrawal symptoms. “They can’t focus, they can’t concentrate, they feel lethargic and depressed,” Benowitz says. “People find it very disabling.”

Why some people can quit smoking with little difficulty and others cannot isn’t completely understood, but some of it is in a person’s genes. “Genetics helps determine if a person smokes 10 cigarettes a day or 40,” Benowitz says.

Years pass, then decades. Many of the high schoolers who took their first puffs on a lark are now adult, long-term smokers. Their lung cells suffer cancer-causing smoke damage, and in some the Invisible Cancer gains a silent start. Some of these smokers will quit cigarettes for good, but the disease process continues. About 40 percent of people with lung cancer are former smokers.

A case in point

Rich Shapiro, 57, was one of those. Shapiro began smoking at age 11 and quit at age 40, about 18 years ago. “But it wasn’t soon enough,” he says. For most of that time he smoked two packs a day. “One problem is that the result of smoking is so far in the future, it’s hard to really believe that a threat exists.”

Lung cancer has four possible stages, with stage four being the latest and most deadly. Shapiro was diagnosed with early stage three lung cancer on Dec. 18, 2002. “A day that will live in infamy,” he says.

He was treated at OSU’s James Cancer Hospital by thoracic surgeon Patrick Ross, MD. Ross removed the upper lobe of Shapiro’s left lung. Shapiro also received 28 radiation treatments. Shapiro expected to survive 18 months, but he’s now made it some weeks beyond that, and he feels good.

“I can’t turn back the clock for me, but people need to be made aware of just what a killer lung cancer is,” he says. “The statistics are really scary: 170,000 people died last year of lung cancer. That’s the equivalent of about eight 747s crashing each week with all on board lost. And the response by society is practically nil. What kind of reaction could we expect from government and society if we lost a 747 every day of the week and two on Sunday? Here’s something we do voluntarily, we know it causes lung cancer, and the tobacco companies are still in business with little or no regulation. Just a little warning on a pack.”

The diagnosis and beyond

Shapiro had already quit smoking at the time of his diagnosis, but 13-20 percent of people with lung cancer are current smokers, and that can create stresses in a family, says Kristine K. Browning, a clinical nurse practitioner at OSU’s James Cancer Hospital and Solove Research Institute, who works closely with people being treated for lung cancer.

“The spouse, father, mother or child may want the patient to quit smoking, cold turkey, right there, when they learn of the diagnosis. They’ll say, ‘If you can’t quit smoking all of this is worthless, you might as well not continue the treatment.’

“We always advise patients to quit smoking; it’s beneficial at all stages of the disease,” she says. “Quitting lowers their risk of developing a second cancer. It helps them breathe better during anesthesia and surgery, and afterward during chemotherapy and radiation, when patients often experience mucous production and increased coughing.

“Yes, the person should quit smoking, but psychologically that’s really hard on the person, too,” she says. “They also need to think about the diagnosis and getting through treatment. They know they need to stop smoking. But adding the blame that this is all their fault doesn’t help the patient succeed. This is an addiction, and these individuals need extra help to quit. We start patients on nicotine replacement therapy, drug therapy or both, to begin treating the addiction, with the goal of helping the patient to successfully quit.”

Why lung cancer is deadly

When doctors diagnose lung cancer early, patients have a 49 percent chance of cure, according to the ACS. But only 16 percent of lung cancers are found early. It usually happens by accident, during examinations for other problems.

Survival rates for lung cancer would likely rise if a method were available for early detection. Early detection methods exist for other common cancers: mammography for breast cancer, Pap tests for cervical cancer, rectal exams and PSA levels for prostate cancer, and colonoscopy and the stool tests for colorectal cancer. “But no reliable screening test exists yet for lung cancer,” says Miguel A. Villalona, MD, a medical oncologist and associate professor of medicine at OSU’s James Cancer Hospital.

“X-rays were tried, but they weren’t accurate,” Villalona says. A new technique, known as low-dose spiral computerized tomography (CT) scan is being tested for early detection of lung cancer, but the findings so far are debatable, Villalona says. “Spiral CT can detect tumors early, but it also detects spots that are not cancer. Such false positives create problems of their own.”

Improvements in surgical techniques over the past 25 years have helped improve survival of early disease. But current treatments for later-stage lung cancer—radiation therapy and chemotherapy—fall short of what is needed, says OSU’s Patrick Ross.

Ross describes himself as an optimistic physician who doesn’t give up on people with latestage lung cancer. “I’ve had a number of patients who came to me after being told that they had three, six or nine months to live. Some of those patients are coming back one, three or five years after their surgery. Also, we can now do more to control the symptoms of advanced disease.”

Shapiro, a patient of Ross’, agrees. “The fact is, oncology is getting better, and people with cancer are living longer. The goal of every cancer patient is to survive long enough for a cure to be found. And although there is still no absolute cure, new medications are being found that keep us alive longer. The intermediate goal is to treat cancer as a long-term illness rather than a fatal disease, and that’s where lung cancer survivors are now.”

At the same time, researchers at OSU and elsewhere are working to improve lung-cancer treatment. For example, Gregory A. Otterson, MD, a medical oncologist who specializes in lung cancer, leads a study examining whether a drug used to treat lung cancer will work better when patients inhale it.

“When given intravenously, as it normally is, this drug is quite toxic,” Otterson says. “Most patients stop taking it early. But the same drug is tolerated very well by patients when inhaled.” Otterson and his colleagues believe administering the drug this way may also improve its effectiveness.

A number of researchers at the Comprehensive Cancer Center- A rthur G. James Cancer Hospital and Richard J. Solove Research Institute are also doing chemoprevention studies for lung cancer (see “Pills to Prevent Cancer?”).

Lung-cancer research elsewhere suggests that a therapeutic vaccine may reverse or slow the progress of one type of lung cancer, while still other researchers are closing in on a gene that may make some people more susceptible to lung cancer. And data is now being analyzed from a recent clinical trial testing the use of spiral CT scan to detect lung cancer early. The study will help determine if use of the technology will save lives.

Preventing lung cancer is the surest way to lower the death rate from the disease. That means avoiding second hand smoke and other airborne carcinogens, and for smokers, it means stopping all tobacco use.

“Quitting smoking is hard,” Shapiro says. “But the more times you try, the more likely you are to beat it. I made it after three tries. For someone having a hard time, maybe the fifth time will be the charm. “At some point, it will get easier. If at first you don’t succeed…you have to keep trying."  ■