1

Introduction to Cancer and

Cancer
Treatments

By: Girma T
 Introduction
2

 Cancer (neoplasm, tumor, or malignancy) is a

group of more than 100 different diseases that
are characterized by uncontrolled cellular
growth, local tissue invasion and spread of cells
from the site of origin (primary site) to other
sites in the body through blood or lymphatic
system (Metastasis)
 Intro………………..
3

Characteristic of a cancer cells:

 Unregulated cell growth/Uncontrolled cell
proliferation
 Cancer cells do not respond to the normal processes;
cell growth, proliferation and survival.
 Cancer cells cannot carry out the physiologic functions of
their normal differentiated (mature) counterparts. They
are often described as poorly differentiated (immature).
 Loss of apoptosis---immortal cell: do not undergo
4

Tissue invasion/metastasis
 They are also able to invade adjacent normal
tissues and break away from primary tumor site
and travel through blood or lymph to form new
tumors (metastases) at a distant site
Angiogenesis
 Their ability to stimulate formation of new blood
vessels and their endless replication potential
further contribute to their continued growth and
survival.
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6
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 Epidemiology in Ethiopia
8

 In Ethiopia, cancer accounts for about 5.8% of total

national mortality.
 No population-based data
 Estimated annual incidence of cancer is around
60,960 cases and the annual mortality over 44,000.
 The most prevalent cancers in Ethiopia among the
entire adult population are breast cancer (30.2%),
cancer of the cervix (13.4%) and colorectal cancer
(5.7%).
Cancer usually causes somatic
mutations
9

 Somatic cells: All the body cells except reproductive

(germ) cells.
 Germ cells: Either the egg or sperm cell; a
reproductive cell.
 Almost all of the mutations identified in tumor cells are
somatic mutations. These mutations are not passed on
to the next generation.
 Only germline mutations will be passed on to offspring.
10
 Cancer Etiology
11
 Normal healthy cells are strictly regulated, with
stimulatory and inhibitory signals in a delicate
balance
 For normal cells to become cancer cells:
 It is believed that a physical, chemical or
biological agent damage the cell and cause
a genetic alteration
 The malignant phenotype often requires
12
 Carcinogenesis

13

 A cancer is thought to develop from a cell in

which the normal mechanisms that control cell
growth and proliferation are altered
 Carcinogenesis is multistage process that is

genetically regulated
 It may occur in the following steps: initiation,

promotion, transformation, and

progression.
Initiation: exposure of normal cells to
carcinogens
 These carcinogens produce genetic alterations
14

Promotion: carcinogens or other factors alter

the environment to favour growth of the altered
cell population compared to normal cells

Transformation (conversion): cancerous cell

or altered cells

Progression: further genetic alterations that

lead to increased cell proliferation
 Include invasion into local tissues and
 Environmental exposures
15

Risk Factors Associated Cancers

Leukemia
Thyroid cancer
Ionizing radiation
Breast cancer
Lung cancer

Ultraviolet radiation Melanoma

Leukemia and Lymphoma

Viral causes Nasopharyngeal cancer
(EBV, HPV, Hepatitis) Cervical cancer
Liver cancer
 Environmental exposures……
16

 Kaposi’s sarcoma: which requires

immunosuppressive conditions (AIDS) is
predominant
 Benezene-Leukemia
 Smoking: Smoking causes lungs cancer; the
main cancer worldwide. It is also implicated in
pancreatic, bladder, kidney, mouth, stomach,
and liver cancer.
 Lifestyle risks
17

Risk Factors Associated Cancers

Head and Neck cancers

Alcohol Liver cancer
Stomach cancer

Colorectal cancer
Breast cancer
Diet and Obesity
Endometrial, esophageal, and kidney
cancers

Lung cancer
Tobacco Head and Neck cancers
Bladder cancers
 Genetic predisposition
18

Syndrome Genes Associated Cancers

Hereditary Breast & Breast, Ovarian, Prostate,

Ovarian Cancers BRCA1 and BRCA2 Pancreatic cancers

Soft tissue and osteo-sarcoma

Breast cancer
Li-Fraumeni Syndrome BRCA2, p53, CHEK2
Leukemias
Brain tumors
Breast and endometrial cancers
Cowden Syndrome PTEN
Thyroid cancer
Lynch Syndrome Colon, endometrial, ovarian,
MLH1, MSH2, MSH6 pancreatic, stomach cancers
(HNPCC)

Von Hippel-Lindau Renal Cell Carcinoma

VHL
Syndrome Pheochromocytoma
 Drug exposure
19

Risk Factors Associated Cancers

Estrogens and Tamoxifen Endometrial cancer

Vaginal cancer
Diethylstilbestrol (DES)
(in female offspring)
Leukemia
Alkylating agents
Bladder cancers
Immunosuppressants
Lymphoma
(adalimumab, infliximab)
20
 Cancer Genetics
21

 Two major classes of genes involved in cancer:

oncogenes and tumor-suppressor genes.
 Oncogene: is a gene that has the potential to
cause cancer.
 In tumor cells, they are often mutated and/or expressed
at high levels.
 Most normal cells will undergo a programmed form
of rapid cell death (apoptosis) when critical
functions are altered and malfunctioning.
22

 Proto-oncogenes: normal genes involved in cell

growth and proliferation or inhibition of apoptosis.
 A tumor suppressor gene(anti-oncogene): is
a gene that protects a cell from one step on the
path to cancer.
 When this gene mutates to cause a loss or reduction in
its function, the cell can progress to cancer, usually in
combination with other genetic changes.
 Cancer Genetics

23

 The p53 gene is one of the most common

tumor-suppressor genes.
 Numerous cellular changes occur in the
genetic material of cancer cell so that
programmed cell death, or apoptosis, does
not occur.
 Proliferation of cancer cells goes unregulated.
 Q
24

1. What is cancer and describe characteristics of

cancer?

2. What is the difference between benign and

malignant tumor

3. What is the difference between hematologic

and solid tumor?

4. Describe in detail etiology and carcinogenesis?

 Principles of Tumor Growth

25
 Diagnosis takes about 109 cancer cells (1 g mass, 1 cm in
diameter) for a cancer to be clinically detectable by
palpation or radiography
 Malignant cell growth occurs many times before a mass may
be palpated (undergone about 30 doublings in cell number).
 The cell kill hypothesis states that a certain percentage of
cells will be killed with each treatment course.
 Cancers consisting of less than 104 cells are believed to be
small enough for elimination by host factors, including
immunologic mechanisms
Gompertzian kinetics tumor-growth curve:
relationship to symptoms, diagnosis, and
various treatment regimens.
26
 Classification of cancer
27

 Cancers can arise in any tissue in the body

 Carcinomas: cancer starts in cells that make up the
skin or tissue lining organs such as liver, breast, lung---
Cancers of epithelial cells. They constitute
approximately 85% of all cancers.
 Sarcomas: Cancers of mesoderm cells (e.g. bone,
muscle)
 Adenocarcinomas: Cancers of glandular tissue (e.g.
28
Diagnosis and staging of cancer

29

 Standardized staging for tumor burden at the

time of diagnosis is important both for
determining prognosis and for making
decisions about treatment.
 The American Joint Committee on Cancer
(AJCC) has developed a simple classification
scheme that can be incorporated into a form
for staging and universally applied.
 Cont.……..
30

 Appropriate laboratory tests, radiologic

scans, and tissue samples are necessary.
 The sample of tissue may be obtained by a
biopsy, fine-needle aspiration (FNA),
 Staging of Cancer
31

 Following a pathologic diagnosis, cancers should be

staged to determine extent or spread of the disease
(i.e, tumor location and size) before starting treatment
 This influences both treatment selection & prognosis.
 Determining stage of cancer requires tests that can
physically or radiographically measure the size of
primary tumor (e.g., radiographs, CT scan, or MRI),
biopsies, LP, examine regional LNs, & variety of lab
tests including appropriate tumor markers
32
 Staging of Cancer
33
 The most common staging system for solid
tumors is TNM system
 The untreated primary Tumor (T) will gradually
increase in size, leading to regional lymph node
involvement (N) and, finally, distant metastases
(M).
 Tumors are described by size of primary mass and
ranges from T1 to T4.
 Nodes are described by extent of the spread of
regional lymph nodal involvement (N0 to N3).
 Metastases are generally scored on their presence
or absence (M0 or M1).
34
35

 The assigned TNM rating translates into a particular

stage classification ( staged as stage I-IV).
 Stage I usually indicates localized tumor(T1)
 Stage II and III represent local and regional spread of
disease, and
 Stage IV denotes the presence of distant metastases
 E.g., T3N1M0 describes a moderate-to-large-sized
primary mass, with regional LN involvement & no
distant metastases, for most cancers it is stage III.
 Staging of Cancer
36

 TNM staging is used clinically to indicate the

extension of cancer before definitive therapy
begins.
 Certain types of tumors, such as lymphomas
and leukemia are usually staged by a different
classification scheme that reflects the
natural history of this type of tumor spread and
helps to direct treatment decisions.
 Staging Criteria for
Esophageal Cancer
37
Primary Tumor (T)
T1: Invasion of lamina propria or submucosa
T2: Invasion of muscularis propria
T3: Invasion of adventitia
T4: Invasion of adjacent structures
Regional Lymph Nodes
N0: No regional lymph node involvement
N1: Regional lymph node involvement
Distant Metastasis (M)
M0: No metastasis
M1: Distant metastasis
M1a: Cervical or celiac lymph nodes
M1b: Other distant metastasis
Based upon these parameters, the tumor is classified as:
Stage I: T1, N0, M0
Stage IIA: T2 or T3, and N0, M0
Stage IIB: T1 or T2, and N1, M0
Stage IIIA: T3, N1, M0
Stage IIIB: T4, Any N, M0
Stage IVA: Any T, Any N, M1a
Stage IVB: Any T, Any N, M1b
 Treatment modalities
38
 Three modalities are used to treat cancer:
 Surgery
 Radiation
 Systemic anticancer agents (Chemotherapy,

hormonal therapy and targeted therapy)

 Surgery remains the treatment of choice for
most early stage cancers
 Surgery typically involves removal of the primary
tumor and adjacent lymph nodes
 Radiation therapy can be used alone for
localized cancer or for cancer that may
encompass a single radiation field
39
 Systemic anticancer agents include chemotherapy,
hormonal, targeted drugs, and biologic therapies
 In general, systemic anticancer agents destroy
cancer cells while minimizing effects to healthy
cells
 A cancer may be treated with multiple modalities.
 Systemic anticancer agents are often administered
to patients with local disease (i.e, early stage)
following surgery or radiation therapy
 Q
40

1. How do you understand cancer cell growth?

2. How do we diagnosis ca and staging

3. What is the importance of staging cancer?

4. What is TNM staging system and describe its

importance?

5. Describe the cancer treatment modalities?

The Language of Cancer Response
41

CURE
 Is when patient is entirely free of disease and
has the same life expectancy as someone
without cancer
 The patient is alive 5 years from the time of
diagnosis without disease recurrence
 Although breast cancer and melanoma
patients are still at significant risk of relapse
after 5 years.
 Con’t……..
42

Complete Response
 When a patient experiences
 Complete disappearance of all cancer cells

without evidence of new disease for at least

one month after treatment
 The cancer is completely gone

Partial Response
 When a patient experiences
 30% or greater decrease in tumor diameter
along with no new disease for 1 month
 Con’t
43

Progressive Disease
 When a patient experiences an increase in tumor size
or they develop new lesions while receiving treatment
 At least a 20% increase in the sum of the longest
diameter of target lesions from baseline

Stable Disease
 When a patient's tumor neither grows nor shrinks
 It is the zone between partial response and
 Case study
44

 G.K. is a 67-year-old woman who was recently diagnosed with

metastatic breast cancer. Her symptoms include widespread
pain, anorexia, and fatigue. She began receiving a
combination chemotherapy regimen and has received three
cycles of treatment.

Based on the case:

 A recent CT scan of her breast showed no change in tumor size
 A recent CT scan of her breast showed no cancer cell
 A recent CT scan of her breast showed increase size of tumor
 Con’t
45

Clinical Benefit
 When a patient experiences subjective
improvement
 Decrease in pain or improved quality of life or
functional status without an objective
response
 Examples of objective response with diseases
such as leukemia or multiple myeloma:
 elimination of abnormal cells;
 return to normal hematologic values and
bone marrow function ;
 return of tumor markers to normal levels; or,
 Con’t
46

Survival Endpoints
 Disease-free survival: how long a
patient survives without the cancer
 Progression-free survival: how long a
patient survives without disease
progression
47
Q
Which of the following is TRUE about
cancer response?
A. Cancer is considered cured when a patient
has no evidence of cancer for 2 years.
B. A complete response is the same as a cure.
C. When a patient's tumor has grown
significantly it's considered progressive
disease.
D. Disease-free survival is how long a patient
survives without disease progression.
48

1. The zone between partial response and

progression is called: ________________
2. If there is a decrease in the size of the prostate
on digital rectal exam in a patient who received
treatment for prostate cancer, it is called:
a. Cure c. Complete Response
b. Partial response d. Progressive
3. How long a patient survives without disease
progression is called
c. Clinical benefit
d. Disease-free survival
e. Progression-free survival
 Principles of Chemotherapy
49
 The main goals of treatment with
chemotherapy are determined by:
 Cancer type
 Stage
 Goals
 To cure the cancer : for local or regional
disease
 To control the cancer: to patients with
metastatic disease to slow the progression of
cancer
 To relieve symptoms caused by the cancer
(Palliative therapy):
 Adjuvant therapy (AT)
 Case : F.R., a 58-year-old woman with no other
medical problems, recently underwent surgical
resection for stage III ovarian cancer and she was
take 4 cycle of chemo before surgery. She has been
told that she currently has no evidence of cancer;
however, she also is told that she should now
receive 6 cycle of chemotherapy.
 Why would chemotherapy recommended before
surgery
 Why would chemotherapy be recommended now
when she has no detectable disease?
 The goal of therapy for F.R is?
 Why chemo is given in cycle?
 51

Neoadjuvant chemotherapy
 Giving chemotherapy before surgery to de-bulk the tumor, making its
removal easily
 given before the primary treatment (surgery or radiation) in patients who
present with locally advanced tumors that are unlikely to be cured with
primary therapy alone

Adjuvant chemotherapy
When the most appropriate course of action is surgery but when it is followed
by chemotherapy
The goal with adjuvant therapy is to prevent recurrence by administering
chemotherapy to kill Micrometastases or residual disease not removed during
surgery or those that traveled to other parts of the body as a result of
 Cont.……..
52

Primary induction chemotherapy

 When surgery isn't an option and
chemotherapy will be administered on
its own
Consolidation or intensification
chemotherapy
 Chemotherapy that is given to sustain
a remission once a remission is
Cont.……..
53

Maintenance chemotherapy
 Is chemo given at lower doses to assist
in prolonging remission
 It is only used for certain types of
cancer...
 E.g. acute lymphocytic leukemia and
acute promyelocytic leukemia
 Chemotherapy Cycles
54
 There are a wide variety of chemotherapy
regimens
 Their usefulness varies depending on the
type of cancer and patient factors
 Generally chemotherapy doses are
administered in cycles
 Cycles are courses of chemotherapy and
are usually defined by number of days
 It gives the patient time to recover from
the toxicities (nadir time)
 Cycles may be the same each time or vary
based on toxicity concerns or the protocol
being used
55
 Con’t
56

Dose-Dense Chemotherapy (DDC)

 Shortens the time between cycles
 Shorten the overall time of therapy and
 Decrease the amount of time that the
tumor can grow between cycles
 But it usually requires the use of colony-
stimulating factors (CSFs) to shorten the
length of neutropenia
Dose-Intense Chemotherapy (DIC)
 Involves increasing the total dose of
chemo given during a fixed cycle period
 Con’t
57

 Single drugs at tolerable doses rarely able to cure

cancers
 Combinations of chemotherapeutic agents
 Are often used to take advantage of different
mechanisms of action to avoid resistance, different
toxicity profiles, and possible synergistic actions
 Drugs with non-overlapping mechanisms of action
and toxicities are preferable for combination use
 Basic Principles of Combination
Chemotherapy
58

 All drugs must be active alone

 Adding an ineffective drug simply to try and take
advantage of a synergistic effect rarely works
 Drugs are chosen based on non-overlapping toxicities.
 This minimizes the risk for permanent organ damage or
lethal toxicity caused by overloading individual organs.
 Drugs should have different mechanisms of action.
 Attacking multiple targets is better than risking the
selection of resistant clones.
59

Which of the following are TRUE about

the design of chemotherapy regimens?
A. They are always designed with a cure in
mind.
B. Combination therapy is the standard of
care for most types of cancer.
C. Using drugs with the same mechanism of
action is better than hitting multiple targets.
D. Dose-intense chemotherapy means
shortening the time between chemo cycles.
 Calculating Chemo Doses
60

 In the early days most chemotherapy was

given at fixed doses or doses based on body
weight.
 Today, most chemotherapeutic agents are
dosed by body surface area as an estimate of
blood volume, cardiac output, and resulting
drug distribution to the kidneys and liver.
 Body Surface Area
61

Mosteller equation for BSA:

DuBois and DuBois equation for

BSA:
BSA(m2) = 0.007184 x weight (kg)0.425 x height
(cm)0.725
62

 E.g
Cisplatin 50 mg/m2 administered once
every 3 weeks
 Measurements Necessary to
Administer Chemotherapy
63

 White blood cell count (WBC)

 >2,500 cells/mm3 or ANC of >1,000
cells/mm3
 Platelet count: >75,000 cells/mm3
 However, these parameters may not apply
when the cancer is of the bone marrow
such as with leukemia.
 Con’t
64

Renal Function
 Creatinine clearance is the most often used
measure to estimate glomerular filtration rate
(GFR) and estimate renal function.
 The Cockcroft-Gault equation is arguably still
the most common equation used to calculate
creatinine clearance for drug dosing, although
some use the Jelliffe equation instead.
 Renal Function
65 Calculations
 Cockcroft-Gault equation for CrCl:
CrCl (mL/min) = [(140-age) x (weight in
kg)]
[(72) x (serum creatinine in
mg/dL)] x 0.85 if female

 Jelliffe equation for CrCl:

Male CrCl (mL/min/1.73 m2) = 98 - 0.8 (age
in years - 20)
serum creatinine in
mg/dL

Female CrCl (mL/min/1.73 m2)= 88 - 0.7 (age

 Cumulative Dosing
66
 In some chemo drugs, toxicity increases as their
cumulative dose increases
 The cumulative dose of all anthracyclines has to be
taken into consideration and tracked.
 Anthracyclines
 Doxorubicin, Daunorubicin, Epirubicin, Idarubicin or
Mitoxantrone
 Direct toxicity to cardiac muscle in a cumulative dose
 Risk for cardiomyopathy and congestive heart failure.
 The damage is permanent & changing to a different
anthracycline won't help prevent it.
 Cumulative Dosing
67

 With cumulative doses of doxorubicin over 450 to 550 mg/m2

 Incidence of CHF is significant, and at higher doses incidence
climbs steeply.
 Factors:
 Age
 Both very young children and the elderly are at higher risk
even with lower cumulative doses
 Delayed toxicity …..children (extended lifespan).
 Continued monitoring after completion for all pediatric
patients that have received anthracyclines.
 Combinations
 Paclitaxel increases exposure to doxorubicin when it is
administered immediately before doxorubicin.
 Cancer
68 Prevention
Lung Cancer
 Smoking cessation!!!
 Tobacco is related to lung, head and neck,
esophagus, pancreas, bladder, kidney,
stomach and possibly colon and uterine
cancers
 Second hand smoke has been shown to be
risk factor for lung cancer
Smoking Cessation-Pharmacotherapy
69

 Design to ameliorate symptoms of nicotine

withdrawal:
 Anxiety, dysphoria or depressive
symptoms, insomnia, increased
appetite/weight gain
 Includes Nicotine gum, patches, nasal spray,
inhaler
 Prevention Con’t
70

Breast Cancer
Tamoxifen therapy
 Shown to be beneficial in women who have at least
a 1.7% absolute risk of developing the disease over
the subsequent 5-year period
 At 20 mg/day for 5 years decreased risk for
invasive and noninvasive cancer of up to 50%
 Caution when using tamoxifen
 Increased risk for endometrial cancer
 Increased risk for life-threatening
thromboembolic events
 Con’t
71

Colon Cancer
 Possible benefit with NSAID use (specifically
in patients with familial adenomatous
polyposis)-but not yet recommended
routinely.

Gastric Cancer
 Antibiotic eradiation of Helicobacter pylori
 Possible: -carotene, vitamin E, selenium
Con’t
72

Prostate cancer
 Finasteride
 A 5- reductase inhibitor
 Blocks conversion of testosterone to
dihydrotestosterone.
 Show to decrease the risk for prostate cancer in
men aged 55 years and older but mortality after
disease occurrace was equal
 Decreased urinary symptoms with finasteride
 Cancer Prevention - Diet
73

 Increase intake of fruits and vegetables

have been found to decrease
cardiovascular disease
 There has been also enough and
significant benefit seen in cancer
prevention with fruits/vegetables.
74
75
 Cancer Screening
76

Cervical Cancer
 Pap Smear
 Beginning when patient becomes sexually
active until age 65 (or until total
hysterectomy)
 At least every 3 years.
 Insufficient evidence to screen routinely for
human papillomavirus (HPV)
 HPV-DNA testing as follow-up if low-grade
atypia or other abnormalities found
 Con’t
77

Breast Cancer
 Mammogram
 Once every 1 to 2 years age 40-49 years
 Annual mammogram for age ≥ 50
 Clinical Breast Exam
 Either performed by patient or provider has not
been found to have any effect on outcome.
78

Five Steps of a Breast Self-

Exam (BSE)
Step 1: Begin by looking at your breasts in the mirror
with your shoulders straight and your arms on your hips.
79

 Here's what you should look for:

 breasts that are their usual
size, shape, and color
 breasts that are evenly shaped
without visible distortion or
swelling
 If you see any of the following
changes, bring them to your
doctor's attention:
 dimpling, wrinkle, or bulging of the
skin
 a nipple that has changed position
or an inverted nipple (pushed
inward instead of sticking out)
 redness, soreness, rash, or swelling
80

 Step 2: Now,
raise your
arms and look
for the same
changes.
 81
 Step 3: While you're at the mirror, gently squeeze
each nipple between your finger and thumb and check
for nipple discharge (this could be a milky or yellow
fluid or blood).
 Step 4: Next, feel your breasts while lying down, using
your right hand to feel your left breast and then your
left hand to feel your right breast. Use a firm, smooth
touch with the first few fingers of your hand, keeping
the fingers flat and together.
 Cover the entire breast from top to bottom, side to side
82
83

 Step 5: Finally, feel your

breasts while you are
standing or sitting. Many
women find that the
easiest way to feel their
breasts is when their skin
is wet and slippery, so
they like to do this step in
the shower. Cover your
entire breast, using the
same hand movements
described in Step 4.
 Cont.……..
84

Colon Cancer
 Beginning at age ≥ 50
 Colonoscopy, flexible sigmoidoscopy,
fecal occult blood testing, Barium enema
 Alone or in combination are equally
effective.
 If family history of colon cancer in first
degree relative
 First colonoscopy 10 years prior to
his/her age at diagnosis
 Con’t
85

Prostate Cancer
 PSA and Digital rectal exams : Not specific however
Skin Cancer
 Routine screening for skin cancer using a total body
skin exam not recommended.
Ovarian Cancer
 Does not recommend vaginal ultrasound or CA-125
measurement
Lung Cancer
 No established guidelines yet for the use of
screening CT of the chest
 Match
86

1. Tamoxifen
a. Gastric ulcer
2. NSAID
3. CT of the chest b. Colon CA
4. Antihelicobacter
c. Lung cancer
5. Finasteride
6. PSA d. Prostate CA
7. Plant based diet e. Cervical CA
8. Pap smear
9. HPV Vaccine f. Breast CA
10. Mamogram g. All type of
Sigmoidoscopy
11.
cancers
87

The
End!!