Download Emergencias Oncologicas

Cancer
Prevention and Screening
Mauricio Burotto MD
National Cancer Institute
National Institutes of Health
Rudolph Ludwig Karl Virchow
1821- 1902
Virchow’s Accomplishment
• Defined cancer as a disease involving
uncontrolled cell growth
• The initial description of leukemia
• Defined cancer using a light microscope
on specimens obtained on autopsy
Adenocarcinoma
Cancer is uncontrolled cell growth,
uncontrolled mitoses
Virchow’s Accomplishments
The definition of cancer used in 2015 is largely that of Virchow with minor
modifications
More than 160 years later, we still use his definitions using a light
microscope.
There is clear evidence that some early detected cancers do not
pose a threat and do not need to be treated
Hallmarks of Cancer
Different approches
• Integrative or complex perspective
– For basic and translational cancer research
• Operational perspective
– For medical (public health, provider) intervention
Operational perspective
Operational perspective
Definitions
• Primary prevention
Prevention
• Secondary prevention
Screening
• Tertiary prevention
Treatment
Concept Message
• The number of new cancer cases is expected to
rise by more than 50% in US and more than
double worldwide by 2030, it is estimated that
more than half of all cancers can be prevented
by applying what we already know.
Prevention in Cancer
• Avoid exposures
– Tobacco
– Alcohol
• Interventions
– Behavioral
• Decrease obesity
– Pharmacological
– Vaccines
Prevention in Cancer
• Avoid exposures
– Tobacco***
– Alcohol
• Interventions
– Behavioral
• Decrease obesity**
– Pharmacological
– Vaccine
Copyright 1964, U.S. Department of Health, Education, and Welfare
Basis of more than 7,000 articles relating to smoking
and disease already available at that time in the
biomedical literature, the Advisory Committee
concluded that smoking is:
• A cause of lung and laryngeal cancer in men
• A probable cause of lung cancer in women
• The most important cause of chronic bronchitis
Copyright 1964, U.S. Department of Health, Education, and Welfare
Tobacco
• Tobacco accounts for approximately one third of
all cancer deaths, more than any other risk
factor
• Obesity is now the risk factor with the highest
attributable cancer mortality (14% to 20%) after
tobacco
Overweight and obesity
By the evidence
• Definitively associated with an increased risk of
six cancers
– Breast, CRC, Esophagus (ADC), Pancreas,
Endometrial and RCC
• Associated with increased death rates in
– The same as before plus ovarian and prostate
cancers
Diet modification and vitamins
for cancer prevention
Diet and Cancer Prevention
Evidence in cancer prevention
Observational studies
More
Publication Bias to positives findings
Randomized studies
Less
Expensive
Longer follow-up
American Cancer Society Recommendations
Presented By Jeffrey Meyerhardt at 2014 ASCO Annual Meeting
Toxicity: What does it take to
recognize small increases in risk?
-carotene
-ATBC
29,133 smokers
-CARET
18,314 at-risk
NEJM 330:1029, 1994
Prevention acting on infectious risk factor
Prevention acting on infectious risk factor
Approved agents for cancer chemoprevention
Approved agents for cancer chemoprevention
Ideal target for chemoprevention
Requires:
• Abnormal level of expression in early,
preinvasive human neoplasia relative to normal
epithelium
• Clear biological contribution to the initiation,
maintenance, or progression of a preinvasive
neoplasm to cancer
Ideal target for prevention
• Pharmacologic accessibility :
– Its modulation cause reductions in neoplastic
incidence
–Cancer mortality
– Pathological evidence of improvement
• Specificity for neoplasia, rather than the
normal tissue from which cancers arise
Oral Oncology 2014
Effect of PPARγ Agonists on NSCLC:
Treatment Animal Models (Lung)
-tumor volume ↓ 66.7%
-growth delay 104 days
Keshamouni et al. Oncogene 2004
PRINCIPLES OF SCREENING
THE BASICS
The Basics
Cancer Screening
• Screening is doing a test to determine if
cancer might be present in an asymptomatic
individual.
• Diagnostic tests are used when there are
symptoms to cause a clinical suspicion of
disease.
Principles of Screening
Finding disease is not a measure of success in
screening*
Increased survival is not a legitimate measure of
success outside of a randomized clinical trial
Reduction of cancer specific mortality in a
randomized trial is the only true proof of effective
screening
Cancer Screening
• A series of tests with some uncertainties:
– some known proven harms
– some possible benefits
– some proven benefits
Lead-time bias
Length Bias
Cancer diagnosed in between scheduled screens
is more aggressive than those diagnosed at
scheduled screenings. Those diagnosed at
initial screening are least aggressive of all.
SCREENING RECOMMENDATIONS
By Cancer Site
Comments
Cancer Screening
Well designed clinical studies have consistently
demonstrated the mortality reduction through:
– Mammography for Breast Cancer
– Stool Blood Testing, Sigmoidoscopy and
Colonoscopy for Colorectal Cancer
– Pap and Visual Screening for Cervical Cancer
– Low Dose Spiral CT for those at high risk of Lung
Cancer
CERVICAL CANCER
A Comment about Cervical
Screening
American Cancer Society recommends annual
cytological screening (Pap testing) beginning at age
21 and women who have three consecutive normal
should be screened every three years.
HPV testing is becoming common in US practices
Visual Examination of the Cervix with Vinegar is
effective especially in third world countries.
Colon Cancer
Colorectal Cancer Mortality 1975-2010
Age Adjusted Mortality Rate
per 100,000
NCI SEER 2012
Colon Cancer Mortality
• Decline due to:
– Improvements in treatment
– Screening with stool blood examination, sigmoidoscopy,
colonoscopy
– Awareness of symptoms and early presentation
Lung Cancer (NSCLC)
1975
1977
1979
1981
1983
1985
1987
1989
1991
1993
1995
1997
1999
2001
2003
2005
2007
2009
age-adjusted rate per 100,000
Lung Cancer Mortality 1975-2010
100
90
80
70
60
50
Male
40
Female
30
20
10
0
The National Lung Screening Trial
• Nearly 54,000,
– age 55 and above.
– 30 pack year or greater history of smoking. If quit, did so less than 15 years
prior to trial entry.
– Reasonable health.
• Prospectively randomized to PA Chest Xray or Low Dose spiral CT
yearly x 3.
– Done at 30 sites with lung cancer expertise.
– Analysis 10 years from start of screening showed 20% relative risk
reduction.
The National Lung Screening Trial
(one view of the 20 percent reduction in mortality)
Comparing the two groups (ten years from the start of screening)
– 80 to 90 lung cancer deaths were prevented in the screened group (87 less
deaths).
– About 350 still died of lung cancer.
– 16 died due to interventions caused by screening (six did not have cancer).
Science January 2015
“Here we show that the lifetime risk of cancers of many
different types is strongly correlated (0.81) with the total
number of divisions of the normal self-renewing cells”
“The majority is due “bad luck”, that is, random mutations
arising during DNA replication of normal stem cells”
Science January 2015
What about cervix
and gastric ???
Message
• Avoiding exposures tobacco and “healthy life”
are the most effective measure of cancer control
• We are still learning which are the best
screening methods
• Which is better for US or Europe is not
necessarily the best for our countries
• Be critical about scientific and medical literature
NCI-NIH
Clinical Research Center