Should Smokers And Former Smokers Have A Lung Scan?
Posted by medconsumers on March 1, 2003
Should Smokers and Former Smokers Have a Lung Scan?
Julie Weiner Buyon
When asked to define healthy person, a doctor responded that it was someone who hadn’t received a thorough work up. In other words, no one is perfectly healthy and if you look hard enough, you’ll find something. And finding something is not always a good thing.
Screening, by definition, is done on healthy people. A persistent problem with screening for diseases is that screenings frequently uncover things that, if left alone, would probably not amount to much and have no impact on the person’s quality of life. Surprisingly enough, this includes cancerous tumors. Pathologists routinely find all sorts of disease during autopsies, disease that had nothing to do with the patient’s death and produced no symptoms during the patient’s lifetime.
But if you are not on the autopsy table and the screening turns up something, it demands some kind of response. Frequently, that response is invasive and painful and costly and may ultimately have been unnecessary.
So before undergoing a screening procedure, ask a few questions. What is the evidence that this test will benefit me? Can this test do harm? What will I gain by knowing I have this disease? How will the results of this screening, positive or negative, affect my quality of life? Who is recommending that I have this test and why?
This article addresses those questions regarding low-dose CT lung cancer screening.
Lung cancer is a pretty terrifying disease. Approximately 160,000 Americans will die of it this year. Most of them will have been diagnosed within the previous twelve months. Only 14% of lung cancer patients survive five years from time of diagnosis. This is because by the time lung cancer produces symptoms and is diagnosed, it has usually progressed past the point of effective treatment.
Doctors and researchers have been looking for an effective test to detect lung cancer at the treatable stage for several decades. X-rays, sputum tests, and blood markers are not yet technologically sophisticated enough to be effective. Spiral Computed Tomography (CT) produces a three dimensional image of the lung, which reveals about six times more resolution than an x-ray. Some physicians and researchers believe this screening technique will find cancer in the lung before it has spread and the disease is effectively treatable.
Common sense tells us that finding a cancerous tumor while it is very small will mean more effective treatment, if not cure, because it has not spread to other parts of the body (metastasis). Common sense, however, is not science, and science has not demonstrated that finding a cancerous lesion in the lung while it is still very small will definitely prolong life.
Currently, doctors use information about the size, shape and biology of a tumor to predict patient outcomes and recommend treatment. Large statistical analyses are performed to learn about correlations between patient outcomes and such factors as size, shape, and specific biological markers to provide doctors with predictive tools. Improved CT technology has provided a closer and more accurate look at size and shape. Some tumors are found when they are both small and localized (have not spread) and can be successfully treated by surgery. However, recent research indicates that tumor size at the time of diagnosis, even if that size is quite small, may not be the best predictor of outcome.
CT scans can find abnormalities smaller than a millimeter, but “No one knows the significance of a one-millimeter nodule”, says Dr. Larry Kessler, the Director of the Office of Surveillance and Biometrics at the FDA [i]. Research suggests that cancer may have spread to other parts of the body (metastasized) before it is detectable by any current method [ii].
What Are The Risks?
The Risk of a False-Positive
Many of the small abnormalities that are found during the highly sensitive CT scan will ultimately turn out to be nothing, or false-positives. Nonetheless, invasive, painful and costly diagnostic procedures may be the result. These unnecessary follow-up tests may present additional risks beyond the anxiety experienced undergoing tests and waiting for the results.
The most invasive of these diagnostic procedures is a thoracotomy, a surgical procedure in which the chest is explored for lung cancer. There are other kinds of biopsies that may be performed, depending on the individual patient’s circumstances. One is a bronchoscopy, in which a thin, lighted tube called a bronchoscope is placed into the patient’s mouth or nose to look into the breathing passages and retrieve a tissue sample. [iii] In a needle biopsy, a needle is inserted through the chest wall into the suspect tumor to remove tissue for analysis. Another procedure, thoracentesis, uses a needle to retrieve some fluid from around the lungs for analysis. [iv]
These procedures can be dangerous even if performed by a specialist, and most such procedures are not. “Eighty-five percent of thoracic surgery is done by non-thoracic specialists,” cautions Dr. James Mulshine of the National Cancer Institute [v]. “There is a one to three percent fatality rate for thoracic surgery at thoracic surgical centers.”
Bear in mind that most people undergoing these procedures are smokers or former smokers, whose lung tissue is already compromised. “You’re dealing with people who have damaged lungs because of the years of smoking and so biopsies may be dangerous for them. They’re more subject to infections – and they can be mortal infections. They can have parts of their lung removed or radiated and they already may have marginal lung status, so it may shorten their lives rather than extend their lives” says Dr. Barnett Kramer, Associate Director for Disease Prevention at The National Institutes of Health. [vi]
Additionally, it can be difficult to distinguish a slow-growing tumor that won’t amount to anything from one that will ultimately cause illness but is only in its early stages. CT scans are very good at detecting things that people die with, but not necessarily die from. [vii]
The Risk of Being a Patient Longer
In order to validate a screening method it is necessary to measure its effect on mortality, rather than on survival. Screening can result in an earlier diagnosis, but unless treatment is more effective at this earlier stage, all the earlier diagnosis has accomplished is making you a “patient” for a longer period of time.
For example, let’s say John and Judy both have lung cancer, but no symptoms yet. In September of 2000, John undergoes a screening, which detects a nodule that proves to be cancerous. John receives treatment and survives for two years following his diagnosis, but ultimately dies in September 2002 from lung cancer. Judy does not screen. Her cancer is diagnosed in March 2002, because she has been coughing up blood. Judy receives treatment, but also dies from lung cancer in September 2002. John’s two year “survival” statistic makes it seem that screening prolonged his life, when in reality it only prolonged the time he knew he was sick. This is known as lead-time bias and is why disease-specific mortality rates are used to validate screening methods.
The Risk of Radiation Exposure
Unnecessary exposure to radiation, such as during an unnecessary CT scan, slightly increases the possibility of developing a radiation induced cancer later on. According to the Food and Drug Administration (FDA), a CT examination with an effective dose of 10 millisieverts may be associated with an increase in the possibility of fatal cancer of approximately 1 chance in 2000, compared to the natural incidence of fatal cancer in America of 1 chance in 5 [viii]. While this increase seems awfully small, there are concerns that it can become a public health problem if large numbers of the population undergo increased numbers of CT procedures.
Additionally, a person should be concerned about the amount of radiation exposure over their lifetime. It is recommended that you keep your own records of your x-ray and CT history so that your physician can consider your past history in making an informed decision about the risks and benefits of a screening or diagnostic scan. [ix]
Dr. Stanley Stern of the FDA’s Radiation Programs Branch notes that “many facilities that offer CT screening use what they describe a ‘low dose’ techniques” [x], which can reduce effective dose by one quarter to one third of that associated with conventional diagnostic techniques. In theory, this should make the radiation dose received in a single scan fairly insignificant, but Dr. Stern is unaware of any specific study of doses associated with “low dose” techniques.
Not only are there no studies specific to low dose scans, but there are no regulations ensuring that the dose you receive in your scan is, indeed, low. There is only one national requirement for quality assurance (QA), and that is in mammography, according to Dr. Jill Lipoti of the New Jersey Department of Environmental Protection. “States are the regulatory body who have the authority to require facilities to have a QA program. Therefore, there is the potential for 50 different QA requirements in the 50 different states.” [xi]
The Conference of Radiation Control Program Directors, (comprised of the chief radiation protection officials in state and federal government agencies) is sufficiently concerned about self-referred CT screenings that it recently issued a formal resolution actively discouraging it. It also proposed a requirement that all CT scans be specifically ordered and authorized by a physician after a medical consultation. [xii]
Dr William Black, a radiologist at Dartmouth’s Hitchcock Medical Center, explains that “The radiation danger is very hard to quantify and there’s a lot of disagreement about whether or not this low level radiation is harmful. Some people actually contend now that low levels of radiation are good for you because they rev up your DNA repair mechanisms. We will probably never resolve this issue because if there’s a negative effect or a good effect they’re so small you’ll probably never be able to see them outside of doing some huge randomized trial of thousands of people.” [xiii] He feels that the harms incurred by false positives are far greater than the radiation.
While the radiation dose of a single scan is probably insignificant, the initial scan can trigger one or more diagnostic scans with much higher dosages of radiation. Something detected on the initial scan may be followed for months and even years, with both the radiation and the anxiety accumulating over time.
Who’s Recommending the Test – and Who Isn’t?
Because there have been no conclusive studies to determine whether or not spiral CT scanning for lung cancer actually saves lives, most physicians are not currently recommending it as a screening tool
Neither the American Cancer Society nor the American Lung Association is recommending the test, although the American Cancer Society is helping to fund screening studies as well as recruit participants.
Insurance companies won’t pay for an unproven test, so consumers are left with the options of joining a clinical trial or self-referral and paying for it themselves. Costs are typically several hundred dollars.
The scans are offered by private radiology clinics and hospitals – any facility with an expensive machine whose costs need to be amortized. Christine Blackett Schlank, author of Medicine and Money, explains that to attract patients and donors, hospitals have to have the newest and best technologies. “Once they have it they have to use it. They have to get their money back. So they’re making patients think that it’s something they want” [xiv].
CT scans are big business. There were an estimated 58 million CT examinations and procedures in the United States in 2000. Sales of multi-slice CT, which facilitate screening examinations, are expected to peak at more than $2.4 billion in five years. [xv]
Many imaging centers are aggressively marketing CT scans directly to consumers – full body scans, virtual colonoscopies, abdominal scans, and chest scans. The thing to remember, however, is that the technology is only as good as the radiologist reading the scan. “Screening for lung cancer should be done in a multi-disciplinary setting where everybody understands the problems with each of the tests, the subsequent tests, including biopsy, who then collaborate and come to a joint decision on what to do for that patient,” explains Dr. Claudia Henschke, Chair of the International Early Lung Cancer Action Project. [xvi] (See below.) Right now, that means getting a scan done at a hospital that is participating in a research study for lung cancer screening.
This recommendation is echoed by guidelines released in January 2003 by the American College of Chest Physicians, who recommend that screening with low dose CT should only be done in the context of well-designed clinical trials. [xvii] The guidelines were developed in collaboration with numerous other patient and professional associations, including the American Society for Clinical Oncology, the American Thoracic Society, the American College of Physicians and the American Cancer Society.
Current Screening Studies
The current studies regarding the positive effects of CT screening on lung cancer mortality rates have not been going on long enough to provide conclusions.
There are currently two large lung cancer-screening studies. One is the International Early Lung Cancer Action Project (I-ELCAP), which is part of an international consortium of health care institutions and professionals evaluating low-dose CT as a tool.
In the 1990’s, ELCAP studied 1000 high-risk individuals (smoker and former smokers, age 60 and older) who received a low-dose CT screening as well as a chest x-ray. None had any symptoms, yet the scans identified suspicious (non-calcified) nodules in 233 of the participants, compared to the 68 found by chest radiography.
To get a more detailed look at the suspicious nodules, the participants underwent a standard dose high-resolution diagnostic CT scan. Those with the largest nodules (20mm and larger) were immediately recommended for biopsy, as were participants whose nodules had other characteristics indicative of disease (roundness and non-smooth of edge of the nodules). Other participants with suspicious nodules were monitored for nodule growth with follow-up scans to determine if a biopsy was appropriate.
Malignant disease was ultimately identified in 27 individuals, nearly four times more than was found using chest x-ray. [xviii] Twenty-three of those diagnosed had Stage I lung cancer, the most treatable stage. The disease had not spread and required surgery for removal, but no further treatment such as radiation therapy or chemotherapy. [xix]
Key to increasing the accuracy of interpreting the scans is the concurrent development of sophisticated software to assist radiologists in overcoming ambiguities and delivering a precise measurement. This is especially crucial in tracking the growth of a suspicious nodule over time.
The principal investigator for ELCAP, Dr. Claudia Henschke, Division Chief of Chest Imaging at New York’s Cornell Medical Center, is optimistic about the benefits of screening using this technique. She and her co-investigators foresee the possibility of lung cancer survival rates skyrocketing from the current 12% to possibly 70% with so many tumors being found at the treatable stage. [xx].
Other experts are not as confident of the ultimate benefits of screening. “Even if the CT scan does prevent thirty percent of lung cancer deaths it may cause so much harm in everybody else that it’s still not worth it,” cautions Dartmouth radiologist William Black. “You have to have a very global assessment of not just the benefits to those who might be getting lung cancer or might otherwise die of lung cancer but to the entire population that’s going to be screened. The only way you can find that out is in a randomized trial.” [xxi]
ELCAP is an ongoing study and now involves some 19 medical centers internationally. It is not a randomized control trial. Critics of the study argue that all it proves is that “spiral CT is a promising technique that warrants investigation”. [xxii] Although 5-year survival statistics may increase, those numbers may be simply indicative of lead-time bias. In the absence of long-term follow-up of both a screened population and a control group that receives no CT screening, conclusions regarding CT screening’s effect on lung cancer mortality can only be guessed at.
“We can’t simply by logic work our way through to the right answer,” says Dr. Kramer of the NIH. “That’s the power of medical studies that put our own personal logic to the test– they actually give us hard evidence to test whether our logic is correct. The history of medicine has certainly taught us many, many times that logic can fail us.” [xxiii]
One of the problems with a long term study that is assessing a technology is that the technology and how it should be used can change while the study is still going on, raising the possibility that the trial is outdated even before it is completed.
“While we are accumulating data, we are constantly changing our protocol to accommodate new information and technology, which is something that is difficult to do within a randomized trial.” Explains Henschke. Indeed, concerns regarding a randomized trial articulated at the Second International Conference on Screening for Lung Cancer were that “the technology being evaluated by such a trial would be obsolete within a few years and high cost would not allow funds to be available for assessment of important innovations in lung cancer treatment and prevention.” [xxiv]
A randomized trial to assess CT screening’s impact on mortality was launched in September 2002: by the National Cancer Institute’s (NCI) National Lung Screening Trial (NLST). It will compare the efficacy of x-ray screening to low-dose spiral CT scan screening to determine which is better at reducing lung cancer deaths. Just as important, the trial will enable researchers to weigh the balance of harms and benefits for each technology.
50,000 asymptomatic current and former smokers are being recruited to participate in this trial, which will take place at 30 different sites around the country
The trial is a randomized, controlled study, which means that participants will be randomly assigned to receive either a chest x-ray or a low-dose spiral CT annually for three years. Researchers will monitor the health of participants through 2009.
However, given that we know that CT can finder smaller tumors than chest x-ray, why would anyone feel comfortable being in the xray side of the study? “The ethics are that you should feel that the person being randomized will, from the knowledge we have today, do equally well in both arms – that should be the underlying equipoise at the beginning” says Dr. Henshke. “We [ELCAP] say that randomization should not be done at the screening point but at the treatment point.”
Other experts disagree with the assumption that finding tumors when they are smaller is equivalent to a benefit. “The goal of screening asymptomatic people is not just to pick up things that you didn’t know about but to change the outcome and to improve life expectancy. And that’s a far different issue” asserts the NIH’s Barnett Kramer. He notes that bioethicists looked at the existing evidence before the NCI trial began and determined ” that not only is it ethically permissible but that it’s ethically indicated to do the randomized trial — otherwise we could incur a net harm without ever knowing it.” [xxv]
Participants in the NCI study will receive their screenings free of charge and must meet the following requirements:
· Are current or former smokers age 55 – 74
· Never had lung cancer and have not had any cancer within the past five years (except some skin cancers or in situ cancers)
· Are not currently enrolled in any other cancer screening or prevention trial
· Have not had a CT scan of the chest or lungs within the last 18 months.
The possible benefits for participants in the study is that their lung cancer may be detected at an early stage, which may reduce symptoms from cancer, result in milder treatment with fewer side effects, or prolong life. The study will help determine if early detection is possible with these techniques and if there are, in fact, benefits to early detection [xxvi].
The risks are those of overdiagnosis. Researchers expect, based on previous studies, that 25 percent to 60 percent of the CT scans will show abnormalities, most of which are not lung cancer but will probably require additional testing, such as biopsies or surgery. Additionally, researchers expect to find small tumors that would never have become life threatening, but may result in unnecessary treatments for cancer. Biopsies and surgeries carry their own risks, as do unnecessary treatments such as chemotherapy and radiation therapy [xxvii]. According to Dr. Denise R. Aberle, NLST co-director, “It could turn out that screening with spiral CT will result in more intrusive diagnostic and therapeutic procedures without reducing lung cancer deaths. The answer to this question is the goal of NLST” [xxviii].
The study, whose $200 million funding comes primarily from the NCI, will yield additional information. The effects of screening on smoking behaviors will be explored. In a study published last year, 23 percent of smokers said they quit after undergoing CT lung screening, and an additional 27 percent reported they were smoking less [xxix].
Researchers will explore the emotional effects of the screening process itself and the impact of positive screening results on the participant. “These are particularly important questions” says Dr. Aberle, “because there will be a large groups of individuals who will have positive screening tests for ultimately benign lesions, but in whom additional diagnostic tests will be indicated. Those individuals will be subjected to additional imaging studies, the possibility of biopsies, or even surgery. It’s important we measure the psychological consequences and the costs of these screening tests on the population being screened, not just those in whom lung cancer is found.” [xxx] Data will be collected to analyze the differential cost implications of the different screening methods.
Concurrent with a more precise and detailed ability to discover and view lung tumors, researchers are exploring ways of predicting whether or not individual tumors will turn out to be lethal. Hopefully, in the not too distant future (say a decade or so) doctors will be able to accurately distinguish between nodules found in the lung that require intervention and those that do not.
It appears that tumors have signatures – a pattern of activity involving many genes – that predict the ultimate behavior of the cancer. This is not the same thing as a gene that is associated with a propensity to develop a specific cancer (such as BRCA1 and BRCA2, the so-called “breast cancer genes”), but rather it is the individual combination of genetic mutations with existing inherited genes.
Researchers at theWhitehead Institute/MIT Center for Genome Research and the Dana Farber Cancer Institute have found that there seems to be a common genetic signature across several different types of cancer that presages metastatic potential in the primary tumor. [xxxi]
These signatures seem to indicate the lethality of tumors, regardless of size or other previously used determinants, suggesting that doctors will be able to use this information to individualize treatment plans in a much more sophisticated way. Tumor signatures will likely be able to predict which treatments will be effective or not, sparing many unnecessary treatment but also depriving others of hope of recovery. Yet this is still years away, as the findings of these studies of genetic signatures and tumor profiles need to be replicated and refined before they enter the mainstream of medical protocols.
“The key to cancer diagnosis and prognosis has been increasingly accurate discrimination among different types of tumors” explains Dr. Eric Lander, Director of the Whitehead Institute and member of the National Cancer Advisory Board. “But, still, this is little more than judging a book by its cover. The real promise of cancer research today comes from the ability to look under the hood, so to speak – to simultaneously monitor the activity level of each of the 30,000 genes in the genome. This rich description is a much closer description of the underlying biology of the tumor. Not surprisingly, it provides a much more powerful tool for classification and prediction. In the long run, this molecular description will completely reshape the taxonomy of cancer and form the foundation for all clinical studies.” [xxxii]
Screening is not yet proven to deliver a benefit, and may in fact cause harm in the form of unnecessary procedures, treatments and anxiety. Many healthcare professionals feel that a high rate of false positives make lung cancer screening prohibitively costly financially, physically and emotionally. Nonetheless, people at a higher risk for lung cancer want to avail themselves of any resources that may mitigate the ill effects of smoking. The most effective thing to do is to stop smoking now.
Individuals who want to be screened should first discuss it with their primary care physician. Then, if screening is the course decided upon, do your homework and find the best facility available, which will be one that is involved in a current study. You want to be at a multi-disciplinary facility staffed by lung cancer specialists – radiologists, pathologists, oncologists and surgeons whose specialty is lung cancer and are up-date on the latest research, protocols and technologies. The healthcare professionals at the cutting edge of this research are those involved in the ongoing studies described earlier.
To locate the nearest facility participating in International ELCAP got to http://www.ielcap.org/sites.html. To locate the NLST center nearest you, call 1-800-4-CANCER or log on to www:cancer.gov.nlst. If you don’t qualify for the study or are uncomfortable with being randomized to the x-ray arm of the NLST, you can probably just pay for the scan at most of these participating facilities.
Ultimately, what we know about cancer is dwarfed by what we don’t know. The best we can do is assess the current information and weigh its harms and benefits as we decide upon a course of action.
As Dr. Lander explains, “In the short run, we still have a pretty limited collection of data with which to work. It will likely take a decade before we have the sort of comprehensive data needed to draw truly solid conclusions. In the meanwhile, we will still be feeling our way – if not completely in the dark, then in the half-light.” [xxxiii]
Julie Weiner Buyon is a graduate student in Health Advocacy at Sarah Lawrence College. She lost her mother to lung cancer and her own cancer was detected through a routine screening.
[i] Dr. Larry Kessler. Quoted in Gina Kolata, “Cheaper Body Scans Spread, Despite Doubts”, The New York Times, 27 May, 2002, Section A, p1. Retrieved electronically through Lexis-Nexis, 9/20/02.
[ii] Dr. Thomas H. Lee and Dr. Troyen A. Brennan, “Direct-To-Consumer Marketing of High-technology Screening Tests,” The New England Journal of Medicine 346, no. 7 (February 14, 2002): 529 – 531, electronic version.
[iii] Lung Cancer Overview: Diagnosis, available from http://www.cancersource.com/LearnAboutCancer, accessed 5 December 2002.
[v] James Mulshine, MD, Head, Experimental Intervention Section, Cell and Cancer Biology Branch, Center for Cancer Research, National Cancer Institute, telephone interview with author, 19 December 2002.
[vi] Barnett Kramer, MD, Associate Director for Disease Prevention, National Institutes of Health, telephone interview with author, 5 February 2003.
[vii] Mary Ellen Butler, “Sensitive Lung Cancer Screens Challenge Treatment,” U.S. Medicine Information Central, accessed from http://www.usmedicine.com/article.cfm?articleID=359&issueID=36. Internet, accessed 5 October 2002.
[viii] Food and Drug Administration, “What are The Radiation Risks From CT?” available from http://www.fda.gov/cdrh/ct/risks.html; Internet; accessed 26 September 2002.
[ix] Radiation Safety, “X-rays over Your Lifetime” available from http://www.radiologyinfo.org/content/safety/xray_safety.htm, Internet, accessed 26 September 2002.
[x] Stanley Stern, Ph.D., Health Physicist, Radiation Programs Branch, Division of Mammography Quality and Radiation Programs, Office of Health and Industry Programs, Center for Devices and Radiological Health, U.S. Food and Drug Administration, personal correspondence, 23 September 2002.
[xi] Jill Lipoti, Ph.D., Assistant Director, Radiation Protection Programs, New Jersey Department of Environmental Protection, personal correspondence, 23 September 2002.
[xiii] William Black, MD, Department of Radiology, Dartmouth-Hitchcock Medical Center and the Department of Community and Family Medicine, Center for the Evaluative Clinical Sciences, Dartmouth Medical School, telephone interview with author, 7 February 2003.
[xiv] Christine Blackett Schlank. Quoted in Robert Finn, “Hospital Marketing Practices: When is It Appropriate to Advertise New Technology?”, Journal of the National Cancer Institute, 93, January 3 2001, 6-7. Retrieved electronically through Lexis-Nexis, 9/20/02.
[xv]Conference of Radiation Control Program Directors, “Resolution Relating to Computed Tomography Scanning”, May 8, 2002, available from http://www.crcpd.org/meetings.asp, Internet, accessed 19 September 2002.
[xvi]Claudia Henschke, MD, Division Chief of Chest Imaging, Weill Medical College of Cornell University; Chair, International Early Lung Cancer Action Project, interview with author, New York, NY, 17 December 2002.
[xvii] Peter B. Bach, MD and others, “Screening for Lung Cancer: The Guidelines”, Chest, 123 (January 2003), 83S-88S, accessed from http://www.chestjournal.org/cgi; Internet: accessed 30 January 2003.
[xviii] Claudia Henschke and others, “Early Lung Cancer Action Project: overall design and findings from baseline screening,” Lancet 354 (July 10, 1999), 99-105. Retrieved electronically through Lexis-Nexis, 9/20/02.
[xix] Denise Grady, “CAT Scan process Could Cut deaths from Lung Cancer,” The New York Times, 9 July 1999, p A1. Retrieved electronically through Lexis-Nexis, 20 September 2002.
[xx]Claudia Henschke and others, ibid.
[xxi] William Black, ibid.
[xxii] Steven Woloshin, Lisa M Schwartz, H. Gilbert Welch, “Tobacco Money: Up in Smoke?”, Lancet 359 (June 15, 2002), 2108-2111. Retrieved electronically through Lexis-Nexis, 9/17/02.
[xxiii] Barnett Kramer, ibid.
[xxiv] Consensus Statement, Second International Conference on Screening for Lung Cancer, Weill Medical College of Cornell University, New York, 25-27 February, 2000.
[xxv] Barnett Kramer, ibid.
[xxvi] National Cancer Institute, National Lung Screening trial Questions and Answers, available from http://newscenter.cancer.gov.pressreleases/NLSTQA.html: Internet; accessed 30 September 2002.
[xxviii] Lynn Cave, “Searching for a Lung Cancer Screening Test”, Bench Marks, 18 September 2002, available from http://newscenter.cancer.gov/BenchMarks/archives/2002_09/feature_print.html, Internet, accessed 30 September 2002.
[xxix] “Lung Screening Likely to Lead to Smoking Cessation, Study Finds,” AScribe Newswire, November 12, 2001, Retrieved electronically through Lexis-Nexis, 19 September 2002.
[xxx] Lynn Cave, ibid.
[xxxi] Sridhar Ramaswamy and others, “A molecular signature of metastasis in primary solid tumors”, Nature Genetics 33 (January 2003): 49-55.
[xxxii] Eric Lander, Ph.D., Director and Founder, Whitehead Institute/MIT Center for Genome Research, interview by author, Coral Gables, FL, 28 December 2002.
[xxxiii] Eric Lander, ibid.