Newsweek article - on lung cancer


"One solution is for radiologists to perform a follow-up scan when they
find a suspicious lesion, and for doctors to biopsy only those that change
or grow over time."
"They're awaiting the results of a large federal study, launched in 2002
and scheduled to wrap up in 2009, that is designed to clarify the risks
and benefits. Early results could come out as soon as next year."

The Deadliest Cancer
Lung cancer kills more Americans than any other type of malignancy?and
some of the victims never smoked. But despite grim statistics there is
some good news: fresh research offers hope for earlier diagnosis and
more-effective treatments.
By Geoffrey Cowley and Claudia Kalb
Newsweek

Aug. 22, 2005 issue - With the news last week that former smoker Peter
Jennings had succumbed to lung cancer at 67 and Dana Reeve, who never
smoked, was diagnosed with the disease at 44, millions of Americans
grasped a terrible truth?the deadliest form of cancer doesn't strike just
the pack-a-day crowd. Suddenly lung cancer was everyone's concern. And
rightly so. Lung cancer may not inspire walkathons or pink-ribbon
awareness campaigns, but after three decades of the War on Cancer and four
decades of surgeon generals' reports, it remains the most devastating of
all malignancies. The disease kills some 160,000 Americans a year?more
than breast cancer, colon cancer and prostate cancer combined. The burden
has grown steadily in recent decades, thanks to the rising incidence among
women, and survival rates have scarcely budged. Nearly 60 percent of
patients still die within a year of diagnosis, and 85 percent die within
five.

Genes aside, growing evidence suggests that women are uniquely vulnerable
to lung cancer. Most of the 600 percent increase they've suffered over the
past eight decades can be tied directly to smoking. But when researchers
look at the minority of lung cancers involving nonsmokers, a curious
disparity emerges. Whereas nonsmokers account for just 10 percent of lung
cancer among men, they account for twice that fraction among women. What
could explain the discrepancy? Hypotheses abound, but one of the most
compelling centers on estrogen, a female reproductive hormone with
well-known links to breast and ovarian cancer. Cells taken from lung
tumors are covered with estrogen receptors, and the tumor cells
proliferate faster when exposed to the hormone in test tubes. Jill
Siegfried, a pharmacologist at the University of Pittsburgh Cancer
Institute, has documented the same effect in lab mice, and she suspects
that something similar is happening in young women's bodies. If she's
right, drugs that suppress estrogen could open a new frontier in treatment
and even prevention, just as they have in breast cancer.

For people at high risk of lung cancer, the more immediate challenge: to
spot the disease at earlier, more-treatable stages. Even today, patients
diagnosed with small, localized tumors enjoy a five-year survival rate of
nearly 50 percent, but few are so lucky. Lung cancer tends to develop
silently, causing none of the classic symptoms (hoarseness, wheezing,
coughing, chest pain), until the tumors are large and dispersed. By the
time they get a diagnosis, at least three out of four patients already
have metastatic disease. Routine chest X-rays have never been found to
improve survival rates, but experts are now hoping that a new
technique?the so-called spiral CT scan?will succeed where old methods have
failed. The machine itself is a wonder. Instead of simply snapping a flat
picture of the lungs, it spins around the chest, assembling as many as 400
images into a 3-D model that can illuminate even the tiniest lesions in
lung tissue. "On a chest X-ray you can see tumors when they're one to two
centimeters," says Dr. Claudia Henschke of New York Weill Cornell Medical
Center. "On a CT scan, you can see them as small as two millimeters."

The spiral CT has performed well in early trials, picking up operable
tumors that traditional X-rays missed and enabling doctors to excise them
safely. In a recent international study, Henschke and her colleagues
reported that 81 percent of the lung tumors detected through spiral CT
screening were successfully removed at early stages?and that 96 percent of
the treated patients were still alive eight years later. So why not start
screening everyone? With more than 90 million current and former smokers
in the United States alone, isn't this a clear opportunity to save lives?
In truth, it's too early to tell. No one knows exactly how the tiny tumors
detected by spiral CT would behave if they were left untreated. As two NIH
experts observed in The New England Journal of Medicine recently, "the
apparently longer survival with screening may represent the indolent
nature of the tumors that were detected rather than a benefit of screening
itself."

You might argue that it's better to be safe than sorry, but widespread
screening could pose hazards of its own. A test this sensitive turns up
all kinds of suspicious lesions, but it can't readily distinguish the 10
percent that are cancerous from the 90 percent that are not. That can
require invasive follow-up tests, in which doctors use needles or scopes
to excise lung tissue for analysis. "You end up finding a lot of noise,"
says Dr. Nasser Altorki, one of Henschke's colleagues at Cornell. "We have
to figure out how to zero in on those 10 percent of patients who actually
have the problem, without doing harm to the large majority of other
patients." One solution is for radiologists to perform a follow-up scan
when they find a suspicious lesion, and for doctors to biopsy only those
that change or grow over time.

Some physicians now urge the highest-risk patients to consider annual CT
exams. At Vanderbilt, for example, Johnson recommends annual screenings
for people over 50 who have smoked a pack a day for 30 years (or two packs
a day for 15) and who have an underlying lung condition. But health
agencies and professional groups have yet to endorse routine screening.
They're awaiting the results of a large federal study, launched in 2002
and scheduled to wrap up in 2009, that is designed to clarify the risks
and benefits. Early results could come out as soon as next year.

Timely detection is a critical step toward saving lives, but it's only
part of the challenge. Though patients diagnosed early fare better than
those diagnosed late, half of them still suffer hard-to-treat recurrences
within five years. Fortunately, their odds are improving. Recent studies
suggest that traditional chemotherapy, administered after surgery, can
boost five-year survival to nearly 70 percent. In the past, says Dr.
Frances Shepherd of Toronto's Princess Margaret Hospital, patients were
sent home after surgery to hope for the best. Today the best cancer
centers are urging them to consider chemo.

Meanwhile, newer drugs are targeting tumors in more specific ways. Melissa
Zagon?a nonsmoking, 37-year-old mother, wife and lawyer?had little cause
for hope when her cancer was diagnosed in 2000. The tumor in her lung had
already seeded three more in her brain, one of them the size of a golf
ball. But after enduring surgery, radiation and chemo, she lucked into a
clinical trial of a new drug called Iressa. And shortly after that drug
stopped working last fall, a more potent one called Tarceva reached the
market. Though she still has tumors in her body, the $2,000-a-month
treatment is now holding them at bay. "Nothing is shrinking, but nothing
is growing," she says. "I just hope there will be something new the next
time the disease progresses."

It's not an impossible dream. Tarceva and Iressa (which is now being
phased out) are just the first in a new generation of treatments that home
in specifically on cancer cells, disrupting the molecular signals that
sustain them. Tarceva works by blocking a protein called EGFR (epidermal
growth factor receptor). And though it rarely sends tumors into remission,
a recent study from the National Cancer Institute of Canada found that it
could boost the one-year survival rate from 22 percent to 31 percent in
patients who had already received conventional treatments. "They lived
longer, they lived better, and the drug was well tolerated," says
Shepherd, the study's lead author. "That's a triple crown, isn't it?"

It's certainly progress. On average, the patients on Tarceva lived only
two months longer than those who got a placebo. But that record could
improve as researchers learn to combine it with other therapies.
Siegfried, the University of Pittsburgh researcher studying estrogen's
effects on lung tumors, is about to start testing Tarceva in combination
with Faslodex, an estrogen-blocking drug approved for breast cancer, to
see if the two work synergistically. Other combinations are showing
promise, too. Avastin, the first in a new class of cancer drugs designed
to starve tumors of blood, is now approved only for colon cancer, but
researchers recently reported that it slowed lung-cancer progression when
combined with traditional chemo.

Lung cancer won't be beaten in a single breakthrough. Improving today's
dismal survival rates will require time, money and commitment?provisions
that this disease has traditionally lacked. Unlike the people with AIDS or
breast cancer, those affected by lung cancer have struggled vainly to
mobilize public opinion?partly because there are too few survivors to take
to the streets. Only a handful of charities, most of them local, have
focused on raising money for research. "It's not like going out and
raising money for a kids' cause," says Joel Massel of the Chicago-based
LUNGevity Foundation, a group that Zagon founded with six other
lung-cancer patients in 2000. "We've tried desperately to get a celebrity
spokesman, but it's been extremely difficult." After more than 30
attempts, the group still lacks one. Public funding has been skewed, too.
Last year the National Cancer Institute spent twice as much on breast
cancer as on lung cancer?even though lung cancer took four times the toll.
But change is in the wind. Late last week the NCI unveiled a new $80
million research initiative aimed at improving early detection, developing
new therapies and combating the use of tobacco. "There's been a
blame-the-victim mentality for lung cancer," says Dr. Margaret Spitz, the
outside adviser who spearheaded the new initiative. "Obviously, we have to
do more."

Improving life for today's patients is of course critical. But the world's
deadliest cancer won't be beaten by CT scanners and targeted therapies
alone. In a tobacco-free world, lung cancer would be an orphan disease,
not a pandemic. The ultimate challenge, says Cheryl Healton of the
American Legacy Foundation, "is to create a world in which young people
reject tobacco, and anyone who wants to quit can." Though smoking rates
have declined in recent decades, a quarter of America's kids are still
getting hooked by the time they leave high school. Critics insist it's no
accident. Last week, just days before the NCI announced its new
lung-cancer initiative, the Federal Trade Commission reported that the
tobacco industry spent $15.2 billion marketing cigarettes in the United
States in 2003 (the most recent year on record)?up from $12.7 billion in
2002 and $6.7 billion in 1998. Studies suggest the money is all too
effective, and health advocates despair of countering its impact. "We're
spending at best a thousandth of what they are," says Healton, whose
tobacco-control foundation grew out of the industry's 1998 settlement of
lawsuits brought by the states. The misfortunes of an anchorman and a
celebrity widow won't change that dynamic, but giving lung cancer an
overdue moment in the spotlight is a start.

© 2005 Newsweek, Inc.

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