Samenvatting
Samenvatting Oncology and Public Health
- Instelling
- Vrije Universiteit Amsterdam (VU)
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Voorbeeld van de inhoud
PUBLIC HEALTH ISSUES INONCOLOGY
There ae more cancer patients expected in upcoming years due to aging of population, better diagnostics
(screening for colon, breast and cervical cancer), more toxins in environment, etc. In 2020, there were 4
million new cases of cancer in Europe. In the Netherlands in 2021, 124.000 new cancer patients were
registered, which increases with 3.000 each year. In the Netherlands in 2021, 45.863 died of cancer, but
survival is increasing with 1% each year. The 5-year-survival has increased from 1990-2015 to 2015-2019
with 14% to 70% in women and with 14% to 66% in men. However, survival mostly increases in the
common cancers.
There are 260 types of cancer, of which 86% are rare cancers. The most common cancers (big 5) are
breast cancer, squamous cell carcinoma (skin), lung cancer, prostate cancer and colon cancer. The total
number of persons expected to be living with or after cancer in the Netherlands in 2032 is 1.400.000,
which is 1 in 13 persons. In the Netherlands, cancer is the leading cause of death. Around one third of
deaths from cancer are due to 5 leading behavioral and dietary risks, which are high BMI, low fruit and
vegetable intake, lack of physical activity, tobacco use and alcohol use.
Public health
Public health is the science and art of preventing disease, prolonging life and promoting health through
the organized efforts and informed choices of society, organizations, public and private, communities and
individuals. Health is a state of complete physical, mental and social wellbeing and not merely the
absence of disease or infirmity. In public health, the focus is on prevention by limiting risk factors for
cancer. Public health increases the health care capacity by making working in health care more attractive.
There is efficient organization of health care, digitalization, supporting the needs of patients and
survivors, but also increasing QoL and quality of end-of-life.
Public health refers to the collective actions to improve population health. According to WHO, it concerns
all organized measures (whether public or private) to prevent disease, promote health and prolong life
among the population as a whole.
Public health Medical science
Population Individual patients
Disease prevention Diagnosis
Health promotion Treatment
Interventions (environment/human behavior) Intervention (medical care)
Public health doesn’t only focus on cause of disease, but also on the cause of causes. This is for example
the surrounding of someone growing up (poor).
Examples of public health in environment are the sewage system, clean water, lowering speed limit, etc.
In human behavior, there are for example the pictures on cigarette packaging, promoting physical
activity, etc.
According to WHO, the main public health functions are:
Assessment and monitoring of the health of communities and populations at risk to identify
health problems and priorities
The formulation of public policies designed to solve identified local and national health problems
and priorities
Assure that all populations have access to appropriate and cost-effective care, including health
promotion and diseases prevention services
Major public health achievements are safer and healthier foods, healthier mothers and babies, family
planning, fluoridation of drinking water, motor-vehicle safety, recognition of tobacco use as a health
hazard, decline in deaths from coronary hearth disease and stroke, vaccinations, safer workplaces and
,control of infectious diseases. The improved sewage disposal and clean water supply systems are
considered the most important milestone.
Global burden of cancer
Cancer is the leading cause of death with 1 in 8 deaths worldwide. The global burden of cancer is
increasing due to an increasing global population, an increase in age, more cases found due to screening
and there is an increase in risk factors (smoking, obesity, etc.).
According to the RIVM, there are 3 forms of prevention:
1. Primary prevention Prevent the disease from occurring (vaccination, encourage healthy life)
2. Secondary prevention Detect and treat the disease in an early phase before symptoms occur
(screening programs)
3. Tertiary prevention Prevent damage and pain from the disease, slow down the disease and
prevent the disease from causing other problems (survivorship care, prevention of recurrence)
About one third of the most common cancers could be prevented through diet, weight and physical
activity. The overall recommendations are to be physically active, to eat a diet rich in wholegrains,
vegetables, fruit and pulses, to limit fast food consumption and other processed foods high in fat,
starches or sugar and to limit the consumption of sugar sweetened drinks.
Much of behavior are passive reflections of ‘upstream’ factors rather than active choice. Thus, the
effectiveness of behavioral change relies on policies that influence upstream factors and social norms
that determine people’s behaviors (causes of causes). Public health policy (i.e., laws, regulations,
guidelines), therefore, is an important and sometimes even critical determinant of population health.
INTRODUCTION IN
ONCOLOGY
55-year old male, heavy smoker, lives in Ijmuiden. He presents with shortness of breath, weight loss and
pain near his left hip. Tata-steel is located in Ijmuiden. No diagnosis based on CT-scan, so biopsy is taken.
Turns out to be lung cancer. Next step is staging, to see if there is tumor
tissue anywhere else in the body. This is done with PET-scan. There is fluid
injected, which will show parts where glucose is accumulated and tracer will
glow (radioactive). This is captured with a CT-scan. He turned out to have lung
cancer with bone metastasis (also needs to be confirmed with biopsy).
The first step of cancer spreading is via lymph nodes. From there to the blood
vessels and then anywhere in the body. A benign tumour does respect the
normal borders of the tissues. It will never metastasize. Depending on how it grows, patients usually have
had cancer for several years before it is detected or causes symptoms.
What is cancer?
Our bodies consist of about 30 trillion cells. These cells group together to form
tissue and organs. The organs work together. Cancer can arise in any of those
cells. Cancer comprises a large group of diseases characterized by abnormal
cells which continuously proliferate, invade local tissues and can spread to
other organs. The additional cells may form a mass of tissue called tumor. A
benign tumor is a slowly expanding mass that consists of relatively normal
cells and has a capsule to prevent tissue invasion. A malignant tumor has an irregular shape and surface,
necrosis, invasion of blood vessels, abnormal cells and tissue invasion.
,With 1.000.000 cancer cells, the tumor is the size of the head of a pin. With 1.000.000.000 cancer cells,
the tumor is the size of a small grape. A patient usually has had cancer for several years before it is
detected or causes symptoms.
There are different types of cancers. The main type of cancer is carcinoma (85%). This type is divided in
squamous cell carcinomas (comes from lining of esophagus) and adenocarcinomas (from more
underneath the surface). Other, less common types are:
Sarcoma: originates in bone and soft tissues
Glioma: originates in glial cells of the central nervous system
Melanoma: originates in melanocytes in the skin
Leukemia: originates in the blood-forming tissues of the bone marrow
Lymphoma and myeloma: originates in cells of the immune system
Normally, human cells grow and multiply to regenerate tissues. The DNA is exposed and replicated. This
results in 2 exact copies in DNA. The cells divide and each cell contains the same DNA. The process of
DNA replication is complex and vulnerable to random errors or damage by toxins, e.g. cigarette smoke
and asbestos. Direct damage by toxins to the cell (DNA change). It can also be indirect damage. In this
case, the damaged tissue needs to be replicated more to heal and this increases the chance on random
errors occurring during replication. These DNA changes are repaired or the cells go into apoptosis. When
they survive with changes, it is considered a genomic alteration.
Genomic alterations
These can be point mutations, deletions, insertions or translocations. A point mutation can lead to
different types of protein. Deletion leads to smaller protein. Insertion leads to larger protein. In
translocation, DNA of 2 chromosomes is being exchanged, which leads to abnormal protein.
The type and location of the genomic alteration is very important. There are 2 types of genes that can be
mutated in cancer, which are tumor suppressor genes or proto-oncogenes. Normally, proto-oncogenes
are involved in cell growth. In mutation, there is more protein, which leads to an increased cell
growth/division. For example, a growth factor receptor may send signals even when growth factors are
not there. These oncogenes can be targeted. HER2 is common in breast cancer and gastric/esophageal
cancer. B-RAF and MEK are important in development of melanoma.
P53 is a tumor suppressor gene involved in almost all cancer types. It binds damaged DNA and holds the
replication process. DNA repair is activated, when it doesn’t work, the cell goes into apoptosis. If P53
doesn’t function well, the DNA is not repaired. BRCA1 and BRCA2 are also tumor suppressor genes,
known for hereditary breast cancer.
New genomic alterations give cells a growth advantage. The normal suppression of growth and induction
of apoptosis is lost.
Hallmarks of cancer
Hallmarks of cancer is multi-hit model, so more are
happening at the same time. Due to (coincidence of)
specific genomic alterations, cancer cells can:
1. Stimulate their own growth (self-sufficiency in
growth signals)
2. Resist inhibitory signals that might otherwise stop
their growth (insensitivity to anti-growth signals)
3. Resist their programmed cell death (evading
apoptosis)
4. Multiply indefinitely (limitless replicative potential)
5. Stimulate the growth of (new) blood vessels to supply nutrients to the tumor (sustained
angiogenesis)
6. Invade local tissue and spread to distant sites (tissue invasion and metastasis)
7. Exploit abnormal metabolic pathways allowing them to survive
8. Evade the immune system (creating an immunosuppressive environment)
9. Show genome instability and mutation
10. Show tumor promoting inflammation
, In most common solid tumors, between 33 and 66 genes have mutations. Main outliers are some types of
lung cancer and melanomas, which have about 200 mutations. The more gene mutations, the more
foreign the tumor looks to the body and the easier for the immune system to get rid of these cells
(immunotherapy is applied). To date, studies have revealed +/- 140 genes that, when altered by
intragenic mutations, can promote or ‘drive’ tumorigenesis. A typical tumor contains 2 to 8 of these
‘driver gene’ mutations. The remaining mutations are passengers that confer no selective growth
advantage.
Approximately 30% of all cancer are caused by the way we live. +/- 20% of worldwide total cancer deaths
can be attributed to smoking. The carcinogenesis of smoking is that it delivers carcinogens directly to
tissues, which gives a risk of new mutations. Smoking causes irritation and inflammation, which increases
the cell replication. It also interferes with the body’s natural protective barriers.
Cumulative and repeated intense exposure to UV light increases the risk of melanoma (tanning booths
before 35). The UV radiation causes genetic mutations and interferes with cutaneous immune system.
A sedentary lifestyle is associated with 5% of cancer deaths. Physical activity stimulates the immune
system, angiogenesis and hormonal function, which happens less with a lack of exercise. In obese people,
there are higher hormone levels (estrogen, insulin and oxidative stress), which has a carcinogenic effect.
Also, 3,6% of cancers are associated with chronic alcohol drinking.
Environmental risks are second hand smoke, air pollution, industrial pollution and chemical exposures.
+/- 10% of all cancers are associated with viruses and bacteria, such as HPV, EBV and hepatitis B & C.
When hepatitis is not treated, it turns in chronic hepatitis, which is chronic inflammation of the liver. This
causes liver cirrhosis (scarring), in which hepatocellular carcinomas can form.
Also, +/- 10% of all cancers are inherited. Gene mutations are linked to some inherited cancers. These are
for example colon cancer (Lynch syndrome) and breast and ovarian cancer (BRCA).
CANCER DIAGNOSIS &
TREATMENT
Clinical and pathological staging of tumors happens based on TNM:
T = tumor = locally primary tumor (T1-T4)
N = node = lymph node involvement (N0-N3)
M = metastases = in distant organ or tissue (M0-M1)
T1-T4 classification can only be given after tumor is removed. The definite cancer diagnosis is based on
the pathological confirmation. The histology is determined based on the tissue biopsy (puncture or by
surgical removal).
Tests and examinations
A physical examination is done to test the performance score, lymphadenopathy (cervical, axillary and
inguinal), palpable liver or spleen, fluid accumulation in lungs or abdomen or pain upon compression of
bone or spine. This test is not specific, but will guide further investigations. Laboratory tests are carried
out to test bone marrow function (red and white blood cells, platelets), renal function, liver enzymes and
tumor markers.
There is made use of imaging in cancer for diagnosis, evaluation of response to treatment, evaluation for
complications or progression and evaluation of response with same modality as pre-treatment scan.
When patient comes to GP with enlarged lymph
nodes, they first do pathology to test whether it is
cancer or not. Then, there is looked at what type of
cancer it is, what stage and if it is curable.
Immunohistochemistry uses staining to test which
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