WASHINGTONThree cancer specialists offered a more optimistic
view for the future of lung cancer patients during a congressional
briefing. Despite the diseases dismal 5-year
survival statistics, advances in genetics, a new screening technique,
and treatment improvements promise earlier diagnosis and prolonged
life for some patients, they said.
Laurie Gaspar, MD, professor of radiation oncology, University of
Colorado Health Sciences Center, cited dramatic changes
during the 1990s in the treatment of lung cancer. I really
think that in the 10 years to come, my treatments will drastically
change from what I am doing today, she said.
The briefing, sponsored by the National Coalition for Cancer Research
(NCCR), focused on the toll of lung cancer in women, but much of the
material related to men as well as women.
Lung cancer replaced breast cancer as the leading cause of cancer
death in women in the early 1980s, and in 1999, some 68,000 women
will die of the disease in the United States, said Margaret R. Spitz,
MD, MPH, professor and chair of epidemiology, M.D. Anderson Cancer
Center. However, women diagnosed with lung cancer tend to fare better
than men, Dr. Gaspar noted. Women do slightly better, stage for
stage and at each time point, compared to men, for reasons that are
not entirely clear, she said.
Smokers and former smokers account for 85% of the lung cancer cases
diagnosed annually. Although more men than women smoke, men are
quitting at a far greater rate, Dr. Spitz said. We certainly
believe that there is a genetic link to nicotine addiction.
She noted that some people have variant genes that are associated
with a deficiency in the dopamine-reward pathway. For these people,
smoking creates a much greater reward effect from nicotine and causes
them to become addicted more readily. Dr. Spitz and her colleagues
have studied some of the variant genes.
In one example, we found that 25% of the never-smokers had the
variant gene, 57% of former smokers, and 78% of current smokers,
she said. Smokers with the variant gene began smoking at an average
age of 17 vs age 19 for smokers who did not have it, and those who
carried the variant found it harder to quit.
In the past, smoking cessation programs have treated all
smokers the same way, Dr. Spitz said. If we can begin to
study the genetic make-up of smokers, we will be able to develop
targeted interventions and find out which people do better with
Advances in Screening
Georgeann McGuinness, MD, associate professor of radiology, New
York University School of Medicine, stressed the value of developing
an effective screening technique to detect lung cancer in its
earliest stage. Five-year survival for lung cancer is 15%, but
when you break it down by stage, 5-year survival for stage I is
somewhere between 70% and 80%, with a steep drop off after stage
II, she said. But, she noted, relatively few lung cancers are
stage I when diagnosed.
Several clinical trials in the 1970s found no benefit to screening
for lung cancer with a combination of chest x-rays and sputum
samples, and thus screening of even high-risk, asymptomatic patients
has not been recommended. However, these findings have recently been
called into question by a reanalysis that suggested flaws in the
design and interpretation of the studies, Dr. McGuinness said.
A strong argument has been developed that, in fact, periodic
screening chest x-rays may downstage the distribution of cancers at
detection, with improved resectability and survival, she said.
Therefore, early detection efforts in asymptomatic, high-risk
individuals are justified.
Dr. McGuinness is a co-investigator in the multicenter Early Lung
Cancer Action Project (ELCAP), which is led by Claudia Henschke, MD,
PhD, of Weill Medical College, Cornell University. Dr. McGuinness
recapped the preliminary findings of this low-dose spiral CT scanning
trial aimed at screening for lung cancer in asymptomatic smokers and
former smokers over age 60. The ELCAP team reported its preliminary
results in The Lancet in July. [See ONI, August 1999, page 1.]
Of the 1,000 persons screened (54% male, 46% female), CT scanning
detected from one to six noncalcified nodules in 233 patients, and
conventional chest x-rays found nodules in 68 patients. Twenty-seven
cancers were detected by CT, only 7 of which were detected by chest
x-ray. Of these 27 cancers, 23 were diagnosed as stage I.
In our study, 85% of the cancers we detected were stage I at
presentation as compared to a general nonscreened population
presenting to their doctors, where stage I lung cancer is a rarity,
on the order of 12% to 14%, Dr. McGuinness said.
Spiral CT scans allow volumetric measurement of irregularly shaped
nodules. We can also view the lesion with infinite viewing
angles and, by so doing, detect even subtle changes in its shape and
contour, she said.
Dr. McGuinness suggested that if screening could reduce lung cancer
mortality by even 20%, applied to the current 160,000 US lung cancer
deaths annually, this would translate into 32,000 lives saved,
which is the equivalent of curing all lymphomas, or two thirds of
breast or colon cancers.
Dr. Gaspar focused on the progress in recent years in treating lung
cancer and the potential for the future. We are better at
identifying patients who will benefit from our treatments, she
said. We now have a standard way of combining radiation and
chemotherapy for patients who arent eligible for surgery. We
have many new chemotherapy agents available and a number of new
technological developments in radiation therapy.
She said that chemotherapy has really come a long way. There
are drugs that have direct cytotoxicity, drugs that prevent
metastasis, and drugs that make radiation therapy more effective or
protect the normal tissues from drug side effects.
She also noted the increasing number of patients, particularly women,
who now use complementary and alternative therapies. Because
our patients are taking these drugs, it would probably be wise of us
in the future to study them, she said.
Radiation oncologists are increasingly treating lung cancer patients
with conformal radiation therapy, which is mapped out with the aid of
CT scans to tighten the area to which radiation is delivered, Dr.
Gaspar said. By giving radiation treatments from many, many
angles, the radiation field can be shaped to be just a little bit
larger than the lung cancer, she said. Using this
technique, we can give a higher dose, with a higher chance of
controlling the tumor and less chance of side effects.
The treatment advances of the 1990s are but a prelude to future
improvements that will reduce lung cancer morbidity and mortality,
Direction of Future Studies: An Interview With Dr. James Mulshine
To get a sense of the cost-effectiveness of lung cancer screening,
Thus, algorithms must be developed to guide management after a
Attendees at the First International Conference on Screening for Lung
There is pressure to initiate trials quickly, Dr. Mulshine noted,
Several trials are already in the late planning stage, and the