SHOULD SMOKERS AND FORMER
SMOKERS
HAVE A LUNG SCAN?
Julie Weiner Buyon
( March 2003)
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
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.
Genetic Signatures
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]
Conclusion
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 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.
[iv] Ibid.
[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.
[xii] Ibid.
[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.
[xxvii] Ibid.
[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.
.
