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IM 3B ONCOLOGY

FINALS

PRINCIPLES OF
CANCER TREATMENT

1. True of cancer growth:


a. Cancer is very different from a normal organ attempting to
regulate its own growth. FALSE. IT CAN MIMICS AN ORGAN.
b. Cancers have set an appropriate limit on how much growth
should be permitted. FALSE. IT HAS NOT SET AN APPROPRIATE
LIMIT ON HOW MUCH GROWTH SHOULD BE PERMITTED

c. Cancer cells that are not dividing are heterogeneous. TRUE.


d. Some cancer cells have not sustained too much genetic damage
to replicate but have defects in their death pathways that permit
their survival. FALSE. SOME CANCER CELLS HAVE SUSTAINED TOO
MUCH GENETIC DAMAGE.

Cancer growth
cancer mimics an organ attempting to regulate its
own growth
cancers have not set an appropriate limit on how
much growth should be permitted

Some have sustained too much genetic damage to


replicate but have defects in their death pathways
that permit their survival

NORMAL ORGANS

& CANCERS

(1) a population of cells in cycle and actively renewing


(2) a population of cells not in cycle
cells that are not dividing are
heterogeneous
some have sustained too much genetic
damage to replicate but have defects in
their death pathways that permit their
survival

Severely damaged and starving cells are unlikely to kill the


patient

PROBLEM
Cells that are reversibly not in cycle are capable
of replenishing tumor cells physically removed
or damaged by radiation and chemotherapy
which includes cancer stem cells
The stem cell fraction may define new targets
for therapies that will retard their ability to reenter the cell cycle.

2. True of Gompertzian tumor


growth
a. The growth rate of a tumor peaks the moment it is clinically
detectable. FALSE. IT PEAKS BEFORE ITS CLINICALLY
DETECTABLE.
b. Tumor becomes detectable at a burden of about 103 cm3
and kills the patient at a tumor burden about 1kg. FALSE. ITS
109(1 cm ) cells
3

c. Efforts to treat the tumor and reduce its size can result in an
increase in the growth fraction and an increase in growth
rate . TRUE.

ANSWER: C

Tumors follow a Gompertzian


growth curve, with the apparent
growth fraction of a neoplasm
being high with small tumor
burdens and declining until, at
the time of diagnosis, with a
tumor burden of 15 109
tumor cells [kills the patient at a
tumor cell burden of about 1012
(1 kg)], the growth fraction is
usually 14% for many solid
tumors. By this view, the most
rapid growth rate occurs before
the tumor is detectable.

Specific cellular mechanisms promote entry or withdrawal


of tumor cells from the cell cycle. For example, when a
tumor recurs after surgery or chemotherapy, frequently its
growth is accelerated and the growth fraction of the tumor
is increased. This pattern is similar to that seen in
regenerating organs.
Partial resection of the liver results in the recruitment of
cells into the cell cycle, and the resected liver volume is
replaced. Similarly, chemotherapy-damaged bone marrow
increases its growth to replace cells killed by chemotherapy.
However, cancers do not recognize a limit on their
expansion.

3. True of Gompertzian tumor


growth:
a. the growth fraction of a tumor increases exponentially over time.
FALSE. IT DECLINES EXPONENTIALLY W/ TIME
b. the growth rate of a tumor peaks before it is clinically detectable.
TRUE
c. tumor size increases dramatically then slows down as the tumor
reaches the size at which limitation of nutrients or auto or host
regulatory influences can occur. FALSE. TUMOR SIZE INCREASES
SLOWLY NOT DRAMATICALLY.
d. tumor becomes detectable at a burden of about 10^3 cells and kills
the patient at a tumor cell burden of about 10^43. FALSE. IT IS
DETECTABLE AT 10^9, & KILL THE PATIENT AT 10^12(1KG)

Gompertzian tumor growth:


Growth fraction
starts at 100% with the
first transformed cell
declines exponentially
over time until at the time
of diagnosis

Tumor size
increases slowly
goes through an exponential phase
slows again as the tumor reaches the size at
which limitation of nutrients or auto- or host
regulatory influences can occur

Growth rate

Tumor cell burden

peaks before it is clinically detectable


The maximum growth rate occurs at 1/e, the
point at which the tumor is about 37% of its
maximum size (marked with an X )

detectable at about 109


(1 cm 3 ) cells
kills the patient at about
1012 (1 kg)

TRUE OR FALSE.
Tumors follow a Gompertzian growth curve.
ANSWER: TRUE
IT FOLLOWS A
GOMPERTZIAN GROWTH
CURVE

4. TRUE OR FALSE. Peak growth rate of the


tumor happens once tumor is clinically
detectable.
ANSWER: FALSEThe most rapid growth rate occurs before the tumor is detectable. An
alternative explanation for such growth properties may also emerge
from the ability of tumors at meta- static sites to recruit circulating
tumor cells from the primary tumor or other metastases. An additional
key feature of a successful tumor is the ability to stimulate the
development of a new supporting stroma through angiogenesis and
production of proteases to allow invasion through basement membranes
and normal tissue barriers. The maximum growth rate occurs at 1/e,
the point at which the tumor is about 37% of its maximum size
(marked with an X in the graph).

5. True of Gompertzian tumor


growth:
a. The growth of a tumor increases exponentially over time
FALSE. IT DECLINES EXPONENTIALLY OVER TIME
a. The growth rate of a tumor peaks before it is clinically detectable
b. Tumor size increases dramatically then slows down as the tumor
reaches the size at which initiation of nutrients or auto or host
regulatory influences can occur.
FALSE. TUMOR SIZE INCREASES SLOWLY NOT DRAMATICALLY
c. Tumor becomes detectable at a burden of about 103cells and kills the
patient at a tumor cell burden of about 1012.
FALSE. TUMOR BECOMES DETECTABLE AT A BURDEN OF ABOUT
109CELLS NOT 103CELLS

Gompertzian growth curve


The growth fraction of a tumor declines exponentially over time
The growth rate of a tumor peaks before it is clinically
detectable
Tumor size increases slowly, goes through an exponential phase,
and slows again as the tumor reaches the size at which limitation
of nutrients or auto- or host regulatory influences can occur.
The maximum growth rate occurs at 1/e, the point at which the
tumor is about 37% of its maximum size (marked with an X).
DETECTABLE
10^9 (1 cm3) cells

KILL
10^12 (1 kg).

GOAL OF CANCER TREATMENT


PRIMARY: ERADICATE CANCER
IF NOT MET: SHIFT TO PALLIATION
AMELIORATION OF SYMPTOMS
PRESERVATION OF QUALITY OF LIFE(MOST IMPORTANT)

WHEN CURE OF CA IS POSSIBLE, CANCER TREATMENTS MAY


BE UNDERTAKEN DESPITE THE CERTAINTY OF SEVERE AND
LIFE THREATENING TOXICITIES

GUIDING PRINCIPLE
PRIMUM SUCCERRERE
FIRST HASTEN TO HELP

PRIMUM NON NOCEREFIRST DO NO HARM


NOT A GUIDING PRINCIPLE

6. Systemic form of cancer


treatment:
A. Surgery
B. Radiation therapy
C. Biologic therapy
D. Brachytherapy

FOUR MAIN TYPES OF CANCER


TREAMENT
LOCAL
*EFFECTS CAN INFLUENCE THE
BEHAVIOR OF TUMOR AT
REMOTE SITES
1. SURGERY

2. RADIATION THERAPYINCLUDES PHOTODYNAMIC

SYSTEMIC

3. CHEMOTHERAPY- INCLUDES
HORMONAL AND MOLECULAR
TARGETED THERAPY
4. BIOLOGIC THERAPY- INCLUDES
IMMUNOTHERAPY & GENE
THERAPY

KEY FEATURE OF SUCCESSFUL


TUMOR
ability to stimulate the development of a new
supporting stroma through:
Angiogenesis
Production of proteases
to allow invasion through basement membranes
and normal tissue barriers

Specific cellular mechanisms promote


entry or withdrawal of tumor cells from
the cell cycle.
E.g. when a tumor recurs after surgery or chemotherapy,
frequently its growth is accelerated and the growth fraction of
the tumor is increased.
Chemotherapy-damaged bone marrow increases its growth
to replicated cells killed by chemotherapy.

This pattern is similar to that seen in regenerating organs.


Partial resection of the liver results in the recruitment of cells
into the cell cycle.

PRINCIPLES OF
CANCER SURGERY

CANCER PREVENTION

7. Surgery is used in cancer prevention of


pre- malignant lesion in:
A. Breast
B. Colon- also includes skin & cervix
C. Ovary
D. Lung

Also can be prevented in people who


have:
1. An underlying disease
2. The presence of
genetic lesions

3. The presence of a
developmental anomaly

Colectomy in those with pancolonic


involvement with ulcerative colitis
Colectomy for familial polyposis
Thyroidectomy for multiple endocrine
neoplasm type 2
Bilateral mastectomy or oophorectomy for
familial breast or ovarian cancer syndrome
Orchiectomy
- with an undescended testis

8. Surgical procedure that has systemic


antitumor effect on some malignancy:
A. Colectomy
B. Orchiectomy- also includes oophorectomy
& adrenalectomy
C. Mastectomy
D. Cholecystectomy

9. True of use of Surgery as


prophylaxis.
a. Colectomy for multiple endocrine neoplasia type 2 . FALSE.
COLECTOMY IS FOR THOSE W/ PANCOLONIC ULCERATIVE COLITIS
WHILE MEN2 IS AN INDICATION FOR THYROIDECTOMY.
b. Hysterectomy for familial breast or ovarian cancer syndromes.
FALSE. IT IS OOPHORECTOMY NOT HYSTERECTOMY FOR FAMILIAL
BREAST OR OVARIAN CANCER SYNDROMES.
c. Orchiectomy in those with prostate cancer. FALSE. IT IS FOR
THOSE W/ UNDESCENDED TESTIS.
d. in some cases, prophylactic surgery is more radical than the
surgical procedures used to treat the cancer after it develops

Cancer Prevention/ Prophylaxis


Those who are at
risk of cancer from
either
an underlying disease

Prevention/Prophylaxis

the presence of genetic


lesions

Colectomy

the presence of a
developmental anomaly

Colectomy

thyroidectomy
bilateral
mastectomy or
oophorectomy
orchiectomy

Pancolonic involvement w/
ulcerative colitis
familial polyposis
MEN type 2
familial breast or
ovarian cancer syndromes
w/an undescended testis

Surgery can also be associated with systemic


antitumor effects in the setting of hormonally
responsive tumors.
Oophorectomy and/or adrenalectomy
May eliminate estrogen
Hormones that drive certain
production
breast cancer
Orchiectomy
May reduce androgen
Hormones that drive all
production
prostate cancers

*Both have effects on metastatic tumor growth

10. Which is the correct statement


regarding Surgery as prophylaxis:
A. Colectomy for multiple endocrine neoplasia type 2
INCORRECT. COLECTOMY IS FOR THOSE WITH PANCOLONIC
INVOLVEMENT W/ ULCERATIVE COLITIS.
B. Hysterectomy for familial breast or ovarian cancer syndromes
INCORRECT. BILATERAL MASTECTOMY OR OOPHORECTOMY NOT
HYSTERECTOMY.
C. Orchiectomy in those with prostate cancer
INCORRECT. IT IS FOR THOSE WITH UNDESCENDED TESTIS, NOT
FOR PROSTATE CANCER.
D. Prophylactic surgery is more radical than surgical procedures
used to treat the cancer after it develops

PROPHYLAXIS

In some cases, prophylactic surgery is


more radical than the surgical procedures
used to treat the cancer after it develops.
The assessment of risk involves many factors and
should be undertaken with care before advising a
patient to undergo such a major procedure.
*However, patient fears play a major role in
defining candidates for cancer prevention surgery.
Counseling and education may not be enough to
allay the fears.

DIAGNOSIS

11. Immunologic detection of proteins


is more effective in fresh frozen tissue
rather than in formaldehyde fixed
tissue
True
False

12. Correct about core needle biopsy


a) Usually obtains considerably less tissue, but this
procedure often provides enough information to plan a
definitive surgical procedure
b) Wedge of tissue is removed and an effort is made to
include the majority of the cross sectional diameter of the
tumor in the biopsy to minimize sampling error. FALSE.
THE STATEMENT REFERS TO AN INCISIONAL BIOPSY.
c) Both A and B

ANSWER: A
Core-needle biopsy usually obtains considerably less tissue,
but this procedure often provides enough information to
plan a definitive surgical procedure.
If an excisional biopsy cannot be performed, incisional biopsy
is the procedure of second choice. A wedge of tissue is
removed, and an effort is made to include the majority of
the cross- sectional diameter of the tumor in the biopsy to
minimize sampling error.

TYPES OF BIOPSY PROCEDURE

TYPES OF BIOPSY PROCEDURE

13. Which of the following statements is


correct regarding different kinds of
biopsy?
a. Excisional biopsy, the entire tumor mass is removed
without getting a portion of normal tissue. FALSE. IT IS
REMOVED W/ A SMALL MARGIN OF NORMAL TISSUE
SURROUNDING IT.
b. Incisional biopsy, a wedge of tissue is removed, and an
effort is made to include majority of the cross sectional
diameter of the tumor in the biopsy to minimize sampling
error. This procedure has less risk of facilitating the spread of
the tumor. FALSE. BECAUSE, AN EFFORT IS MADE TO
MAN=XIMIZE SAMPLING ERROR NOT MINIMIZE.

c. Core needle biopsy, usually obtains considerably less


tissue, but this procedure
often provides enough
information to plan a definitive surgical procedure. TRUE.
d. Fine needle aspiration generally obtains only a
suspension of cells from within a mass and can provide
sufficient tissue in searching for genetic abnormalities and
protein expression patterns, such as hormone receptor
expression in breast cancers. FALSE. IF (+) FOR CANCER, IT
MAY ALLOW GIVING SYSTEMIC TREATMENT WHEN
METASTATIC DISEASE IS EVIDENT. ALSO, IT CAN PROVIDE
BASIS FOR PLANNING A METICULOUS AND EXTENSIVE
PROCEDURE.

TREATMENT

4. Benefits of neoadjuvant
chemotherapy
a) Downgrade the tumor. FALSE. ONLY REDUCE THE SIZE NOT
DOWNGRADE.
b) Clinically control undetected metastatic disease. TRUE
c) Both A and B
*After an initial diagnostic biopsy, chemotherapy and/or radiation
therapy is delivered to reduce the size of the tumor and clinically
control undetected metastatic disease. Such therapy is followed
by a surgical procedure to remove residual masses; this is called
neoadjuvant therapy.

15. Surgery may be curative in the


following
a) Patients with lung metastases from breast cancer may be cured
by resection of the lung lesions. FALSE. IT SHOULD BE LUNG METS
FR. OSTEOSARCOMA.
b) Patients with an ulcerating breast mass with bone metastases
undergoes mastectomy

c) Patients with colon cancer who have fewer than five liver
metastases restricted to one lobe and no extrahepatic
metastases

ANSWER: C
Surgery may be curative in a subset of patients with
metastatic dis- ease.
Patients with lung metastases from osteosarcoma may
be cured by resection of the lung lesions.
In patients with colon cancer who have fewer than five
liver metastases restricted to one lobe and no
extrahepatic metastases
Hepatic lobectomy may produce long-term disease-free
survival in 25% of selected patients.

16. True regarding use of surgery and


its systemic effect antitumor effects
a) If resection of the primary lesion takes place in the presence
of metastases, acceleration of metastatic growth may occur.
TRUE
b) Removal of both breasts may prevent breast cancer spread to
other organs . FALSE. IT OOPHORECTOMY/ADRENALECTOMY
THAT CAN REDUCE BREAST CA BECAUSE IT ELIMINATES
ESTROGEN PRODUCTION
c) Orchiectomy in male ER (+) breast cancer can prevent
recurrence . FALSE. IT REDUCE ANDROGEN, THEREFORE CAN
PREVENT PROSTATE CANCERBUT NOT BREAST CA.

ANSWER: A
Surgery can also be associated with systemic antitumor effects. In
the setting of hormonally responsive tumors, oophorectomy
and/or adrenalectomy may eliminate estrogen production, and
orchiectomy may reduce androgen production, hormones that
drive certain breast and all prostate cancers, respectively; both
procedures can have useful effects on metastatic tumor growth.
If resection of the primary lesion takes place in the presence of
metastases, acceleration of metastatic growth has also been
described in certain cases, perhaps based on the removal of a
source of angiogenesis inhibitors and mass-related growth
regulators in the tumor.

17. The following statements describes


the sentinel node approach
a) Useful for all malignancies

b) The first draining lymph node a spreading tumor


would encounter is defined by injecting a dye into
the tumor site at operation and then dissecting
the first node to turn blue
c) Provides reliable information regarding stage of
breast cancer but risk of lymphedema
lymphangioedema is increased

ANSWER: B
Lymph node spread may be assessed using the sentinel node
approach, in which the first draining lymph node a spreading
tumor would encounter is defined by injecting a dye or
radioisotope into the tumor site at operation and then resecting
the first node to turn blue or collect label.

The sentinel node assessment is continuing to undergo clinical


evaluation but appears to provide reliable information without
the risks (lymphedema, lymphangiosarcoma) associated with
resection of all the regional nodes.

18. True of surgical treatment of


cancer:
a. Surgery is the most effective means of treating all
metastatic cancer . FALSE. JUST 40% OF METASTATIC CANCER,
60% NOT ACCESSIBLE FOR REMOVAL.
b. Cancer surgery aiming for cure is usually planned to excise
the tumor completely with an adequate margin of normal
tissue. TRUE
c. surgery has systemic antitumor effects. TRUE
d. B and C only

19. TRUE OR FALSE. Surgery is the first


treatment modality of choice in Stage III
breast cancer.
ANSWER: FALSEIn some settings (e.g., bulky testicular cancer or stage III breast cancer), surgery is not the first treatment modality used. After an initial
diagnostic biopsy, chemotherapy and/or radiation therapy is
delivered to reduce the size of the tumor and clinically control
undetected metastatic disease. Such therapy is followed by a
surgical procedure to remove residual masses; this is called
neoadjuvant therapy. Because the sequence of treatment is critical to
success and is different from the standard surgery-first approach,
coordination among the surgical oncologist, radiation oncologist, and
medical oncologist is crucial.

20. True of surgical treatment of


cancer

a. surgery is the most effective means of treating all


metastatic cancer. FALSE. IT IS MOST EFFECTIVE MEANS
IN TREATING CANCER IN GENERAL.
Only 40% metastatic cancer are cured by surgery
60% have metastatic disease that is not accessible for
removal
b. cancer surgery aiming for cure is usually planned to
excise the tumor completely with an adequate margin of
normal tissue
c. surgery has systemic antitumor effects
d. B and C only

Cancer surgery aiming for cure is usually planned


to excise the tumor completely with an adequate margin of
normal tissue
safe margin varies with the tumor and the anatomy
touching the tumor as little as possible to prevent vascular and
lymphatic spread
minimizing operative risk
Surgery can also be associated with systemic antitumor effects
In the setting of hormonally responsive tumors, oophorectomy
and/or adrenalectomy may control estrogen production
orchiectomy may reduce androgen production; both have effects
on metastatic tumor growth.

SURGERY
Most effective means of treating cancer.
about 40% of cancer patients are cured by surgery.
Unfortunately, a large fraction of patients with solid tumors have
metastatic disease that is not accessible for removal (60%)
Benefits even when the disease is not curable by surgery alone
local control of tumor,
preservation of organ function,
debulking that permits subsequent therapy to work better, and
staging information on extent of involvement

Patients with colon cancer who have lung


metastases restricted to one lung and no
extrapulmonary metastases may have long
term disease-free survival in 25% if they
undergo pneumonectomy.
True

False
In patients with colon cancer who have fewer than five liver
metastases restricted to one lobe and no extrahepatic
metastases, hepatic lobectomy may produce long-term diseasefree survival in 25% of selected patients.

21. TRUE OR FALSE. Surgery is the first


treatment modality of choice in Stage III
Breast cancer.
Rationale:
Answer False
In some settingse.g., bulky testicular cancer or stage III
breast cancersurgery is not the first treatment modality

PALLIATION

22. Surgery as palliation can be


applied to the following cause/s:
a) Limb-sparing surgery followed by adjuvant
radiation in therapy and chemotherapy for
osteosarcoma. a form of treatment
b) Axillary lymph dissection in breast cancer. a form
of treatment
c) Inferior vena cava filter for recurrent pulmonary
emboli . a form of palliation

Surgery is used in a number of ways for palliative or supportive care


of the cancer patient, not related to the goal of curing the cancer.
These include insertion and care of central venous catheters, control
of pleural and pericardial effusions and ascites, caval interruption for
recurrent pulmonary emboli, stabilization of cancer-weakened
weight- bearing bones, and control of hemorrhage, among others.
Surgical bypass of gastrointestinal, urinary tract, or biliary tree
obstruction can alleviate symptoms and prolong survival. Surgical
procedures may provide relief of otherwise intractable pain or reverse
neurologic dysfunction (cord decompression).
Splenectomy may relieve symptoms and reverse hypersplenism.
Intrathecal or intrahepatic therapy relies on surgical placement of
appropriate infusion portals.

23. Surgery employed as supportive


care (palliation) except:
a. insertion of central venous catheters. PALLIATION

b. control of pleural and pericardial effusions and


ascites, caval interruption for recurrent pulmonary
emboli. PALLIATION
c. Stabilization of cancer weakened weight -bearing
bones. PALLIATION
d. Modified radical mastectomy for breast cancer
stage 2. TREATMENT

Palliation
Insertion of central
venous catheters
Caval interruption
Stabilization

-control of pleural and pericardial


effusions and ascites
-for recurrent pulmonary emboli
-cancer-weakened weight-bearing
bones
Surgical bypass of GIT, -alleviate symptoms
urinary tract, or biliary -prolong survival
tree obstruction

Palliation
Cord decompression
Splenectomy
Surgical placement of
appropriate infusion
portals
Correct other
treatment related
toxicities

-relief of otherwise intractable pain


-reverse neurologic dysfunction
-relieve symptoms
reverse hypersplenism
-Used in intrathecal or intrahepatic
therapy
-Such as adhesions or strictures

24. TRUE OR FALSE. In patients with colon


cancer who have fewer than five liver
metastases restricted to one lobe and no
extrahepatic metastases, hepatic lobectomy
(metastectomy) may produce longterm diseasefree survival in 25% of selected patients.
Answer true

PRINCIPLES OF
RADIATION THERAPY

25. Which of the following statements


regarding radiation therapy is/are
correct?
a. Radiation is a physical form of treatment that
damages any tissue in its path
b. Radiation causes breaks in DNA and generates free
radicals from cell water that may damage cell
membranes, proteins and organelles.
c. Radiation damage is augmented dependent on only
oxygen, hypoxemic cells are more resistant

d. all of the above

26. Radiation:
A. Damage cause is dependent on the formation of radicals.
FALSE. DAMAGE IS DEPENDENT ON OXYGEN
B. Its selectivity for cancer cells may be due to defects in cancer
cells ability in repair defective RNA and other damage. FALSE. IT
IS REPAIR OF DEFECTIVE DNA NOT RNA.
C. A physical form of treatment that damages any tissue in its
path. TRUE.
D. Its selectivity for cancer cells may be due to defects in host
cells ability to repair sublethal RNA and other damage. FALSE. IT
IS THE CANCER CELLS ABILITY TO REPAIR, BUT NOT OF THE
HOST.

PHYSICAL PROPERTIES AND


BIOLOGIC EFFECTS
Exposure to ionizing radiation
is constant
Sources of radiation
- The sun and other cosmic
sources
- The ground
- The air we breathe
- The food we ingest
- From within our bodies

Radiation is a physical form


of treatment that damages
any tissue in its path
Selectivity for cancer cells
may be due to defects in a
cancer cells ability to repair
sublethal DNA and other
damage

PHYSICAL PROPERTIES AND


BIOLOGIC EFFECTS
Radiation causes breaks in
DNA and generates free
radicals from cell water that
may damage cell membranes,
proteins, and organelles
Radiation
damage
is
augmented dependent on
oxygen
Hypoxemic cells are more
resistant

Augmentation of oxygen
presence is one basis for
radiation sensitization
Sulfhydryl
compounds
interfere with free radical
generation and may act as
radiation protectors.
Most radiation-induced cell
damage is due to the
formation of hydroxyl radicals

PHYSICAL PROPERTIES AND


BIOLOGIC EFFECTS
The dose-response curve for cells have both linear and
exponential components
Linear component

Exponential
component

From double-stranded DNA


breaks produced by single hit
Represents breaks produced by
multiple hits

27. Cells in the phase of cell cycle are


more resistant to radiation
A. Early G1
B. Late G1 - & S PHASE
C. Early G2
D. Late G2

THE FACTORS THAT INFLUENCE


TUMOR CELL KILLING
Do of the tumor the dose required to deliver an
average of one lethal hit to all cells in a population.
Dq of the tumor the threshold dose; a measure of
the cells ability to repair sublethal damage
Hypoxia
Tumor mass
Growth fraction
Cell cycle time and phase (cells in late G1 and S are
more resistant)

28. Inverse square law:


A. Radiation from any source increases in intensity as a function
of the square of distance from the source. FALSE. IT DECREASES.
B. Radiation from any source increases in intensity as a function
of the square of the source. FALSE. IT DECREASES.
C. Radiation from any source decreases in intensity as a
function of the square of the distance from the source
D. Radiation from any source is constant in intensity as a function
of the distance from the source.. FALSE. IT DECREASES.

Inverse Square Law


Radiation from any source decreases in intensity as a
function of the square of the distance from the source
If the radiation source is 5 cm above the skin surface and the
tumor is 5 cm below the skin surface, the intensity of
radiation in the tumor will be 52/102 or 25% of the intensity
at the skin
If the radiation source is moved to 100 cm from the patient,
the intensity of radiation in the tumor will be 1002/1055, or
91% of the intensity at the skin

29. Most radioresistant organ:


A. Bone
B. Heart
C. Skeletal muscle
D. Nerve

Principles of radiation therapy


Most sensitive
Male testis
Female ovary
Bone marrow

Sensitive

Resistant

Hematopoietic
Heart
system
Skeletal muscle
Mucosal lining of
Nerves
the intestinal tract
Any bone marrow in
Organs with less
a radiation field will Organs with more
need for cell renewal
be eradicated by
self-renewal as a
*Bone is among the
therapeutic
part of normal
most radioresistant
irradiation.
homeostasis
organ

30. Acute toxicity of radiation:


A. Radiation enteritis
B. Mucositis
C. Dental caries
D. Thyroid failure

Acute toxicities
Often these can be alleviated by interruption of treatment:
Mucositis
Skin erythema (ulceration in severe cases)
Bone marrow toxicity

Chronic toxicities more Serious


Cause

Effect

Radiation of the head and neck region Thyroid failure


Cataracts and retinal damage
Blindess
Salivary glands stop making saliva
Dental caries, and poor dentition
Taste and smell
Mediastinal irradiation

Can be affected
Threefold increase risk of fatal
myocardial infarction

Other effects/toxicities
Other late vascular effects
Chronic constrictive
pericarditis
Lung fibrosis
Viscus stricture
Spinal cord transection
Radiation enteritis

A serious late toxicity


Development of second solid
tumors in or adjacent to the
radiation fields
Such tumors can develop in any
organ or tissue and occur at a rate of
about 1% per year beginning in the
second decade after treatment

31. Correct about radioactive


therapy
a) Its selectivity for cancer cells may be due to defects in a
cancer cells ability to repair sublethal DNA and other
damage.
b) Radiation damage is dependent on oxygen, hypoxemic
cells are more sensitive. FALSE. HYPOXEMIC CELLS ARE
MORE RESISTANT NOT SENSITIVE.
c) Augmentation of oxygen is the basis for radiation
resistance. FALSE. IT IS ONE OF THE BASIS FOR RADIATION
SENSITIZATION NOT RESISTANCE.

ANSWER: A
The selectivity of radiation for causing cancer cell
death may be due to defects in a cancer cells ability
to repair sublethal DNA and other damage.
Ionizing radiation causes breaks in DNA and
generates free radicals from cell water that may
damage cell membranes, proteins, and organelles.
Radiation damage is augmented by oxygen; hypoxic
cells are more resistant. Augmentation of oxygen
presence is one basis for radiation sensitization.

32. Determinants of radiation dose


a) Type of malignancy
b) Type of machine
c) Total rad

ANSWER: C
Radiation effect is influenced by three
determinants:
total absorbed dose (total rad)
number of fraction
time of treatment

RADIATION
QUANTITATED ON THE BASIS OF THE AMOUNT OF RADIATION
ABSORBED IN THE PATIENT; NOT BASED ON THE AMOUNT OF
RADIATION GENERATED BY THE MACHINE.
RAD(RADIATION ABSORBED DOSE)
DEF. 100 ERG OF ENERGY PER GRAM OF TISSUE.

INTERNATIONAL SYSTEM(SI) UNIT FOR RAD= GRAY(Gy); 1 Gy=100 rad.


RADIATION DOSE IS MEASURED BY PLACING DETECTORS AT THE BODY
SURFACE OR CALCULATING THE DOSE BASED ON RADIATING PHNATOMS
THAT RESEMBLE HUMAN FORM & SUBSTANCE.

Drugs used in cancer treatment that


may also act as radiation sensitizers
COMPOUNDS THAT
DNA SYNTHESIS
INCORPORATE INTO DNA INHIBITOR
& ALTER ITS
STEREOCHEMISTRY
HALOGENATED
HYDROXYUREA
PYRIMIDINES
CISPLATIN

COMPOUNDS THAT
DEPLETE THIOLS

BUTHIONINE
SULFOXIMINE

These are important adjuncts to the local treatment of certain tumors, such as
squamous head and neck, uterine cervix, and rectal cancers.
HYPOXIA-MAJOR FACTOR THAT INTERFERES W/ RADIATION EFFECTS

33. TRUE OR FALSE. Cisplatin and


Hydroxyurea are both radiosensitizing
agents.
Rationale:
Answer is true
Certain drugs used in cancer treatment may also act as
radiation sensitizers. For example, compounds that
incorporate into DNA and alter its stereochemistry (e.g.,
halogenated pyrimidines, cisplatin) augment radiation effects,
as doeshydroxyurea, another DNA synthesis inhibitor.
Harrisons Principles of Internal Medicine 18th edition

34. Development of second solid tumors


in or adjacent to the radiation fields
a) Acute toxicity of radiation
b) Development is dependent on dose of radiation received
c) Occur at a ratio of about 1% per year beginning in the
second decade after treatment

ANSWER: C
A serious late toxicity is the development of second solid tumors in or
adjacent to the radiation fields. Such tumors can develop in any organ
or tissue and occur at a rate of about 1% per year beginning in the
second decade after treatment. Some organs vary in susceptibility to
radiation carcinogenesis.

No data suggest that a threshold dose of therapeutic radiation exists


below which the incidence of second cancers is decreased.
*HIGH RATES OF SECOND TUMORS OCCUR IN PEOPLE WHO RECEIVES
AS LITTLE AS 1000 cGy.

35. TRUE OR FALSE. X-rays are generated by


linear accelerations, gamma rays are generated
from decay of atomic nuclei in radioisotopes
such as cobalt and radium
True

False

ANSWER: TRUE
X-rays and gamma rays are the forms of ionizing radiation
most commonly used to treat cancer.
They are both electromagnetic, nonparticulate waves that
cause the ejection of an orbital electron when absorbed.
This orbital electron ejection is called ionization.
X-rays are generated by linear accelerators; gamma rays
are generated from decay of atomic nuclei in radioisotopes
such as cobalt and radium.
These waves behave biologically as packets of energy, called
photons.

36. In treating mycosis fungoides, electron


beam are used because of its low tissue
penetrance.
True
False
HARRISON
Electron beams are a
particulate form of radiation
that, in contrast to photons and
protons, have a very low tissue
penetrance and are used to
treat cutaneous tumors.

POWERPOINT
Electron beams have a very
low tissue penetrance and are
used to treat skin conditions
such as mycosis fungoides

37. The maximum dose in the target volume is


often the cause of complications to tissues in
the transit volume.
True
False
The maximum dose in the target volume is often the
cause of complications to tissues in the transit volume,
and the

Minimum dose in the target volume influences the


likelihood of tumor recurrence. Dose homogeneity in
the target volume is the goal.

38. Radiation is quantitated based on the


amount of radiation generated by the linear
acceleration
True
False
*Radiation is quantitated based on the amount of
radiation absorbed by the tumor in the patient; it is
not based on the amount of radiation generated by
the machine.

39. Acute radiation toxicities, except:


a. Radiation enteritis
b. Mucositis
c. skin erythema/ulceration
d. bone marrow toxicity

Acute toxicities
Mucositis
skin erythema
(ulceration in severe cases)
bone marrow toxicity

Chronic toxicities
are more serious
Radiation of the head and neck region thyroid
failure.
Cataracts and retinal damage blindness.
Salivary glands stop making saliva dental caries
and poor dentition
Taste and smell can be affected
Mediastinal irradiation 3-fold risk of fatal MI
Often these can be
Other late vascular effects
alleviated by interruption of chronic constrictive pericarditis
treatment.
lung fibrosis
viscus stricture
spinal cord transection
radiation enteritis

40. Most radiation sensitive organs,


except:
a. testis
b. bone
c. bone marrow
d. ovaries

PRINCIPLES OF RADIATION THERAPY


Most sensitive
1. male testis
organs
2. female ovary
3. bone marrow
Any bone marrow in a radiation field will be
eradicated by therapeutic irradiation
Sensitive
Organs with more self-renewal
as a part of normal homeostasis
1. hematopoietic system
2. mucosal lining of the intestinal tract
Resistant to
radiation effects

Organs with less need for cell renewal


1. Heart
2. Skeletal muscle
3. Nerves

41. TRUE OR FALSE.Most radiation-induced cell


damage is due to the formation of hydroxyl radicals.
ANSWER- TRUE
Therapeutic radiation is ionizing; it damages any tissue in its
path.
The selectivity of radiation for caus- ing cancer cell death may be
due to defects in a cancer cells ability to repair sublethal DNA
and other damage.
Ionizing radiation causes breaks in DNA and generates free
radicals from cell water that may damage cell membranes,
proteins, and organelles.
Radiation damage is augmented by oxygen; hypoxic cells are
more resistant.

Augmentation of oxygen presence is one basis for radiation


sensitization. Sulfhydryl compounds interfere with free radical
generation and may act as radiation protectors.
Most radiation-induced cell damage is due to the formation
of hydroxyl radicals from tissue water:
Ionizingradiation+H2OH2O+ +e
H2O+ + H2O H3O+ + OH
OH cell damage

42. TRUE OR FALSE. Radiation is


quantitated based on the amount of
radiation generated by the machine.
ANSWER: FALSE- Radiation is quantitated based on
the amount of radiation absorbed by the tumor in
the patient; it is not based on the amount of radiation
generated by the machine. Radiation dosage is defined
by the energy absorbed per mass of tissue. Radiation
dose is measured by placing detectors at the body
surface or based on radiating phantoms that resemble
human form and substance, containing internal
detectors.

43. TRUE OR FALSE. Cisplatin and Hydroxyurea


are both radiosensitizing agents.
TRUE- Certain drugs used in cancer treatment may
also act as radiation sensitizers. For example,
compounds that incorporate into DNA and alter its
stereochemistry (e.g., halogenated pyrimidines,
cisplatin) augment radiation effects at local sites, as
does hydroxyurea, another DNA synthesis inhibitor.
These are important adjuncts to the local treatment of
certain tumors, such as squamous head and neck,
uterine cervix, and rectal cancers.

44. TRUE OR FALSE. Brachytherapy can be


used to treat cervical and prostate
cancers.
TRUE- Brachytherapy involves placing a sealed source of
radiation into or adjacent to the tumor and withdrawing the
radiation source after a period of time. Advantage: used to
treat prostate and cervical cancer
Disadvantage: short range of radiation effects (the inverse
square law); the inability to shape the radiation to fit the
target volume.
Adverse effects due to toxic exposure to the radiation of
normal tissue: concomitant radiation enteritis or cystitis in
cervix cancer; brain injury in brain tumors.

45. Brachytherapy can be used to


treat cervical and prostate cancers.
A. Total absorbed dose
B. Amount generated by machine
C. Number of fractions
D. Time

-Radiation effect is influenced by three determinants: total


absorbed dose, number of fractions, and time of treatment.
-A frequent error is to omit the number of fractions and the
duration of treatment.
-Thus, a typical course of radiation therapy should be described
as 4500 cGy delivered to a particular target (e.g., mediastinum)
over 5 weeks in 180-cGy fractions.
-Most curative radiation treatment programs are delivered
once a day, 5 days a week, in 150- to 200-cGy fractions.

46. In radiation-resistant organs like the


heart, this is the most sensitive component.
A. Vascular endothelium
B. Muscle
C. Connective tissue
D. All components are equally resistant

RATIONALE:

Bone is among the most radio-resistant organs, with


radiation effects being manifested mainly in children
through premature fusion of the epiphyseal growth plate.
By contrast, the male testis, female ovary, and bone
marrow are the most sensitive organs. Any bone marrow
in a radiation field will be eradicated by therapeutic
irradiation.
Organs with less need for cell renewal, such as heart,
skeletal muscle, and nerves, are more resistant to
radiation effects.

RATIONALE
In radiation-resistant organs, the vascular endothelium
is the most sensitive component.
Organs with more self-renewal as a part of normal
homeostasis, such as the hematopoietic system and
mucosal lining of the intestinal tract, are more sensitive.
Acute toxicities include mucositis, skin erythema
(ulceration in severe cases), and bone marrow toxicity.
Often these can be alleviated by interruption of
treatment.

47. True regarding development of


second solid tumors after radiation.
A. Occur at a rate of about 1% per year beginning 5
years after treatment.
FALSE. A serious late toxicity is the development of
second solid tumors in or adjacent to the radiation
fields. Such tumors can develop in any organ or
tissue and occur at a rate of about 1% per year
beginning in the second decade after treatment.
Some organs vary in susceptibility to radiation
carcinogenesis.

48. True regarding development of


second solid tumors after radiation.
B .A woman who receives mantle field radiation
therapy for Hodgkins disease at age 35 years has
comparable in magnitude to genetic breast cancer
syndromes.
FALSE. A woman who receives mantle field radiation
therapy for Hodgkins disease at age 25 years has a
30% risk of developing breast cancer by age 55 years.
This is comparable in magnitude to genetic breast
cancer syndromes. Women treated after age 30 years
have little or no increased risk of breast cancer.

49. True regarding development of


second solid tumors after radiation.
C. High rates of second tumors occur in people who
receive as little as 1000 cGy. TRUE.

50. True of principles of radiation


therapy, except:
a.Augmentation of oxygen is the basis for radiation
sensitization. TRUE
b.Most radiation-induced cell damage is due to the
formation of hydroxyl radicals. TRUE
c. Can be used alone or together with chemotherapy to
produce cure of localized tumors however of no use in
tumors that have disseminated. FALSE. IT HAS USE TO
TUMORS THAT HAVE DISSEMINATED
d.Teletherapy is the most commonly used form of radiation
therapy. TRUE

51. Which of the following statement/s


regarding radiation therapy is/are correct?
a.Radiation is a physical form of treatment that damages
any tissue in its path
b.Radiation causes breaks in DNA and generates free
radicals from cell water that may damage cell
membranes, proteins and organelles
c. Radiation damage is augmented dependent on only
oxygen; hypoxemic cells are more resistant
d.All of the above

Radiation
Physical form of treatment that damages any tissue
in its path
Selectivity for cancer cells may be due to defects in a
cancer cell's ability to repair sublethal DNA and
other damage
Causes breaks in DNA and generates free radicals
from cell water that may damage cell membranes,
proteins and organelles.

Radiation

Radiation damage is augmented dependent on


oxygen. Hypoxemic cells are more resistant.
Augmentation of oxygen presence is one basis fo
radiation sensitization.
Sulfhydryl compounds interfere with free radical
generation and may act as radiation protectors.
Most radiation-induced cell damage is due to the
formation of hydroxyl radicals

DOSE RESPONSE CURVE


LINEAR COMPONENT EXPONENTIAL COMPONENT
FROM DOUBLE
REPRESENTS BREAK
STARNDED DNA
PRODUCED BY
BREAKS PRODUCED MULTIPLE HITS
BY SINGLE HIT

52. Most radiation sensitive organs


except:
a.Testis
b.Bone
c.Bone marrow
d.Ovaries

Bone - most radio-resistant organs


Radiation effects being manifested mainly in
children through premature fusion of the
epiphyseal growth plate.
*Most sensitive organs: Testis, Ovary and
Bone marrow
*Any bone marrow in a radiation field will be
eradicated by therapeutic irradiation

53. TRUE OR FALSE. Most radiationinduced cell damage is due to the


formation of hydroxyl radicals
Rationale:
Answer - true

54. TRUE OR FALSE. Radiation is


quantified based on the amount of
radiation generated by the machine
Rationale:
Answer - false
Radiation is quantitated on the basis of the amount of
radiation absorbed in the patient; it is not based on the
amount of radiation generated by the machine.
Harrisons Principles of Internal Medicine 18th edition

PRINCIPLES OF
CHEMOTHERAPY

ENDPOINTS OF DRUG ACTION


1. The existence of compounds that would be magic bullets
that might bind to tumors, owing to the affinity of the agent for
the tumor Paul Ehrich
2. Observed toxic effects of certain mustard gas derivatives on
the bone marrow during World War I lead to the idea that
smaller doses of these agents might be used to treat tumors of
marrow-derived cells
3. Certain tumors from hormone-responsive tissues, e.g. breast
tumors, could shrink after oophorectomy-->endogenous
substances promoting the growth of a tumor might be
antagonized

55. Advanced cancer with possible


cure with chemotherapy:
A. Small cell lung CA
B. Breast CA
C. Melanoma
D. Bladder CA

56. Advanced cancers with possible


cure, except:
a. Hodgkin's disease
b. Seminoma
c. Ewing's sarcoma

d. Pancreatic carcinoma

Advanced Cancers with Possible Cure


Acute lymphoid and acute myeloid
leukemia (pediatric/ adult)
Germ cell neoplasms
Embryonal carcinoma
Teratocarcinoma
Seminoma or dysgerminoma
Choriocarcinoma
Hodgkins disease (pediatric/
adult)
Squamous carcinoma (anus)

Pediatric neoplasms
Wilms tumor
Embryonal rhabdomyosarcoma
Ewings sarcoma
Peripheral neuroepithelioma
Neuroblastoma
Ovarian carcinoma
Non-small-cell lung carcinoma
(stage III)
Lymphomascertain types
(pediatric/adult)
Gestational trophoblastic
neoplasia
Small-cell lung carcinoma

57. Cancers possibly cured with chemotherapy


as adjuvant to surgery, EXCEPT:
a. Breast carcinoma
b. Hepatocellular carcinoma
c. Colorectal carcinoma
d. Osteogenic sarcoma

CANCERS POSSIBLY CURED WITH CHEMOTHERAPY AS ADJUVANT TO


SURGERY (BCROS)
BREAST CARCINOMA
OSTEOGENIC SARCOMA
COLORECTAL CARCINOMA
SOFT TISSUE SARCOMA
TUMORS POORLY RESPONSIVE IN ADVANCE STAGES TO
CHEMOTHERAPY
PANCREATIC CARCINOMA
PROSTATE CARCINOMA
BILIARY TRACT NEOPLAS
MELANOMA(SUBSETS)
THYROID CARCINOMA
HEPATOCELLULAR
CARCINOMA OF VULVA
CARCINOMA
NON-SMALL CELL LUNG CA
SALIVARY GLAND CANCER

58. Advanced cancer possibly cured


by chemo and radiation
A. Squamous carcinoma of Anus

B. Carcinoma of Uterine Cervix


C. Relapsed lymphoma
D. all of the above
E. A & B

Advanced Cancers Possibly Cured by Chemotherapy and Radiation


Squamous carcinoma (head and neck)
Breast carcinoma
Squamous carcinoma (anus)
Small-cell lung carcinoma
Carcinoma of the uterine cervix
Non-small-cell Lung Ca(stage
III)

Cancer Possibly Cured with High-Dose Chemotherapy with Stem Cell


Support 25
Relapsed leukemias, lymphoid and myeloid
Relapsed lymphomas, Hodgkins and non-Hodgkins
Chronic myeloid leukemia
Multiple myeloma

CANCERS RESPONSIVE W/ USEFUL PALLIATION BUT NOT CURE, BY


CHEMOTHERAPY
BLADDER CARCINOMA
ENDOMETRIAL CARCINOMA
CML
SOFT TISSUE SARCOMA
HAIRY CELL LEUKEMIA
HEAD & NECK CANCER
CLL
ADENOCORTICAL
LYMPHOMA(CERTAIN TYPES)
CARCINOMA
MULTIPLE MYELOMA
ISLET CELL NEOPLASM
GASTRIC CARCINOMA
BREAST CARCINOMA
CERVIX CARCINOMA
COLORECTAL CARCINOMA
RENAL CARCINOMA

USES OF CHEMOTHERAPY AGENTS


1. Treatment of active, clinically apparent cancer
2. Employed after the failure of surgery or radiation therapy
to eradicate a local tumor
3. Part of multimodality approaches to offer primary
treatment to a clinically localized tumor
- Allow organ preservation when given with radiation, as in
the larynx or other upper airway sites

- Sensitive tumors to radiation when given, e.g., to patients


concurrently receiving radiation for lung or cervix cancer

KARNOFSKY
Carefully quantitating its effect on tumor size
Using these measurements to objectively decide the basis for further
treatment of a particular patients or further clinical evaluation of a
drugs potential

NEWER EVALUATION SYSTEMRECIST


Utilize unidimensional measurement
Intent is similar in rigorously defining evidence for the activity
of the agent in assessing its value to the patient
PARTIAL RESPONSE
PROGRESSIVE DISEASE

30% decrease in the sums of the


longest diameters of lesions
increase of 20% in the sums of the
longest diameters
by RECIST

PATIENT TREATED W/ PALLIATIVE


INTENT
Should be aware of their diagnosis

Aware of limitations of the proposed treatments


Have access to supportive care
Have suitable performance status, according to
assessment algorithms such as the one developed by
Karnofsky or by the Eastern Cooperative Oncology
Group (ECOG)

PRINCIPLES OF DRUG
USE

RESPONSE
Defined as tumor shrinkage, is but the most immediate indicator of
drug effect

To be clinically valuable, responses must translate into clinical benefit


This is conventionally established by a beneficial effect on overall
survival, or at least an time to further progression of disease

Active efforts are being made to quantitate effects of anticancer agents


on quality of life

CANCER DRUG CLINICAL TRIALS

VALUABLE OUTCOMES OF CANCER


TREATMENT
Induce cancer cell death, resulting in tumor shrinkage
with corresponding improvement in patient survival,
or the time until the disease progresses
Induce cancer cell differentiation or dormancy with
loss of tumor cell replicative potential &
reacquisition of phenotypic properties resembling
normal cells

59. Extrinsic pathway of apoptosis:


A. Inactivated by a variety of noxious stimuli like DNA damage
B. Caspase 8 is activated in this pathway
C. Release of apoptosis-inducing protein is inhibited by BH3only family
members
D. Initiated by release of cytochrome C and SMAC from the
mitochondrial intermembrane space

Extrinsic pathway of apoptosis


activated by cross-linking members of the tumor necrosis factor (TNF)
receptor superfamily, such as CD95 (Fas) and death receptors DR4 and
DR5, by their ligands, Fas ligand or TRAIL (TNF-related apoptosisinducing ligand), respectively
This induces the association of FADD (Fas-associated death domain)
and procaspase-8 to death domain motifs of the receptors

Caspase-8 is activated and then cleaves and activates effector


caspases-3 and -7, which then target cellular constituents (including
caspase-activated DNAse, cytoskeletal proteins, and a number of
regulatory proteins), inducing the morphologic appearance
characteristic of apoptosis, which pathologists term karyorrhexis

60. Intrinsic pathway of apoptosis


A. Inactivated by a variety of noxious stimuli like DNA damage
B. Caspase 8 is activated in this pathway
C. Release of apoptosis-inducing protein is inhibited by BH3only family
members
D. Initiated by release of cytochrome C and SMAC from the
mitochondrial intermembrane space

Intrinsic pathway of apoptosis


Initiated by the release of cytochrome c and SMAC (second
mitochondrial activator of caspases) from the mitochondrial
intermembrane space in response to a variety of noxious stimuli,
including DNA damage, loss of adherence to the extracellular matrix
(ECM), oncogene-induced proliferation, and growth factor deprivation
Upon release into the cytoplasm, cytochrome c associates with dATP,
procaspase-9, and the adaptor protein APAF-1, leading to the
sequential activation of caspase-9 and effector caspases
SMAC binds to and blocks the function of inhibitor of apoptosis
proteins (IAP), negative regulators of caspase activation.

61. True of apoptosis


a) The proapoptoticprotein bcl2 attenuates mitochondrial
toxicity and its overexpression in certain lymphomas
conveys good prognosis.
b) The antiapoptotic gene product bax antagonize this action
of bcl2.

c) Apoptosis is characterized by chromatin condensation;


cell shrinkage.
d) In living animals, phagocytosis by surrounding stromal cells
is heralded by inflammation.

ANSWER: C
Apoptosis, or programmed cell death, refers to a highly ordered
process whereby cells respond to defined stimuli by dying, and it
recapitulates the necessary cell death observed during the
ontogeny of the organism. Cancer chemotherapeutic agents can
cause both necrosis and apoptosis. Apoptosis is characterized
by chromatin condensation (giving rise to apoptotic bodies),
cell shrinkage, and, in living animals, phagocytosis by
surrounding stromal cells without evidence of inflammation.
The antiapoptotic protein bcl2 attenuates mitochondrial
toxicity, while proapoptotic gene products such as bax
antagonize the action of bcl2.

62. Upregualtion of Bcl2


oversuppression is observed in:
A. Pancreatic cancer
B. Brain cancer
C. Melanoma
D. Liver cancer

The release of apoptosis-inducing proteins from the mitochondria


is regulated by pro- and antiapoptotic members of the Bcl-2 family
Antiapoptotic members (e.g., Bcl-2, Bcl-XL, and Mcl-1) associate
with the mitochondrial outer membrane via their carboxyl termini,
exposing to the cytoplasm a hydrophobic binding pocket composed
of Bcl-2 homology (BH) domains 1, 2, and 3 that is crucial for their
activity
Overexpression of Bcl-2 as a result of the t(14;18) translocation
contributes to follicular lymphoma
Upregulation of Bcl-2 expression - observed in:
Prostate CA
Breast CA
Lung CA
Melanoma

63. Characteristic of apoptosis in


living cells EXCEPT
A. Chromatin condensation
B. Cell shrinkage
C. Phagocytosis with inflammation

RATIONALE: Apoptosis is characterized by chromatin


condensation (giving rise to apoptotic bodies), cell
shrinkage, and, in living animals, phagocytosis by
surrounding stromal cells without evidence of inflammation.

64. This is characterized by chromatin condensation, cell


shrinkage and in living animals, phagocytosis by
surrounding stromal cells without evidence of
inflammation.
a.Necrosis
b.Autophagy
-cellular response to injury where the cell does not
initially die but catabolizes itself in a way that can lead to
loss of replicative potential
c. Anoikis
d.Apoptosis

APOPTOSIS
Programmed
Highly ordered process whereby cells respond to defined
stimuli by dying and it recapitulates the necessary cell
death observed during ontogeny of the organism
Chromatin condensation->apoptoic bodies
Cell shrinkage, phagocytosis by surrounding stroma
without evidence of inflammation(in living cells)
Signal transduction system or specific cell-surface
receptors

CELL DEATH
*

*CANCER CHEMOTHERAPEUTIC AGENT CAN CAUSE BOTH NECROSIS & APOPTOSIS

COMBINATION CHEMOTHERAPY
Refers to the use of regimens where different drugs are
combined with the goal of achieving at least an additive &
hopefully supra-additive effect
Component drugs in such regimens ideally have distinct,
nonoverlapping toxicities to the host

Are each individually active


Have been shown in a clinical trial to be tolerable & convey
clinical value in contrast to the use of single agents

CHEMOTHERAPEUTIC
DRUGS

65. Refer to small molecules or biological designed


and developed to interact with a defined molecular
target important in either maintaining the malignant
state or selectively expressed by the tumor cells.
A. Conventional chemotherapy
B. Targeted agents
C. Hormonal therapies
D. Biologic therapies

66. Often macromolecules that have a


particular target or may have the capacity to
orchestrate or regulate the host immune
responses to kill tumor cells
A. Conventional chemotherapy
B. Targeted agents
C. Hormonal therapies
D. Biologic therapies

CANCER DRUG TREATMENTS ARE OF


4 BROAD TYPES
1. CONVENTIONAL CHEMOTHERAPY AGENTS
historically derived by the empirical observation that these small
molecules could cause major regression of experimental tumors growing
in animals
mainly target DNA structure or segregation of DNA as chromosomes in
mitosis
3. HORMONAL THERAPIES
The 1st form of targeted therapy
Capitalize on the biochemical pathways underlying estrogen & androgen
function & action

2. TARGETED AGENTS
Refer to small molecules or biologicals
- Generally macromolecules such as antibodies or cytokines
Designed & developed to interact with a defined molecular target
- Important in either maintaining the malignant state, or
- selectively expressed by the tumor cells
Targeted therapies seek to capitalize on the biology behind the aberrant
cellular behavior as a basis for therapeutic effects
4. BIOLOGIC THERAPIES
Are often macromolecules that have a particular target
e.g., antigrowth factor or cytokine antibodies
May have the capacity to regulate growth of tumor cells
Induce a host immune response to kill tumor cells
Include not only antibodies but cytokines & gene therapies

CONVENTIONAL
CHEMOTHERAPY

A. DIRECT DNA-INTERACTIVE
AGENTS- ALKYLATING
ALKYLATING AGENTS
CYCLOPHOSPHAMIDE
FOSFOMIDE
NITROGEN MUSTARD
CHLORAMBUCIL
MALPHALAN
PROCARBAZINE
DACARBAZINE
TEMOZOLAMIDE
CISPLATIN
CARBOPLATIN
OXALIPLATIN

ANTI-TUMOR ANTIBIOTICS OF
TOPOISOMERASE POISONS
DOXORUBICIN
DAUNORUBICIN
IDARUBICIN
BLEOMYCIN
MITOXANTRONE
ETOPOSIDE
CAMPTOTHECIN
TOPOTECAN
CPT-11/IRINOTECAN

67. True of alkalyting agents


A. Stabilizes microtubules preventing cell division
B. May cause second neoplasm
C. Cell cycle specific agents

ALKYLATING AGENTS
Alkylating agents as a class are cell cycle phasenonspecific agents.
They break down, either spontaneously or after normal organ or tumor
cell metabolism, to reactive intermediates that covalently modify bases
in DNA.
This leads to cross-linkage of DNA strands or the appearance of breaks
in DNA as a result of repair efforts.
Broken or cross-linked DNA is intrinsically unable to complete
normal replication or cell division; in addition, it is a potent activator of
cell cycle checkpoints and further activates cell-signaling pathways that
can precipitate apoptosis.

As a class, alkylating agents


share similar toxicities:
myelosuppression, alopecia,
gonadal
dysfunction,
mucositis, and pulmonary
fibrosis.They differ greatly in
a spectrum of normal organ
toxicities.
As a class, they share the
capacity to cause second
neoplasms,
particularly
leukemia, many years after
use, particularly when used
in low doses for protracted
periods.

68. Cyclophosphamide is inactive unless


metabolized
by
the
liver
to
4hydroxycyclophosphamide which decomposes
into an alkylating species as well as to this
chemical which causes chemical cystitis
a) Chlorocetaldehyde
b) Ifosfamide
c) 2-mercaptoethanesulfonate
d) Acrolein

CYCLOPHOSPHAMIDE
An inactive drug unless
metabolized by the liver to
4-hydroxy-cyclophosphamide,
which decomposes into an
alkylating species, as well
as to chloroacetaldehyde
and acrolein. The latter
causes chemical cystitis;
therefore,
excellent
hydration
must
be
maintained while using
cyclophosphamide

69. Toxicity of doxorubicin


a) Causes chronic cardiotoxicity in the form of atrial and
ventricular dysrhythmias.
FALSE. IT IS ACUTE CARDIOTOXICITY.
a) Cardiotoxicity has been related to topoisomerase action.
FALSE. It is related to iron-catalyzed oxidation and reduction of
doxorubicin not to topoisomerase action.
a) Doxorubicins cardiotoxicity is increased when given together
with trastuzumab (Herceptin), the anti-HER2/neu antibody.
TRUE
b) Powerful vesicant with no known antidote to extravasation.
FALSE. IT HAS A KNOWN ANTIDOTE- Dexrazoxane

70. Cardiotoxicity of Doxuribicin is related to:


A. Topoisomerase II action
*related to iron catalyzed oxidation and reduction
B. Peak serum concentration

C. Coadministration with cyclophosphamide


*coadministration w/ trastuzumab

71. Toxicity of Doxorubicin:


A. Causes chronic cardiotoxicity in the form of atrial and
ventricular dysrhythmias
B. Cardiotoxicity has been related to topoisomerase action
C. Doxorubicins cardiotoxicity is increased when given
together with Trastuzumab (Herceptin), the anti-HER2/neu
antibody.
D. Powerful vesicant with no known antidote to extravasation

Answer: C Rationale:
Letter A - it causes acute cardiotoxicity in the form of atrial
and ventricular dysrhythmias
Letter B - Cardiotoxicity has been related to iron-catalyzed
oxidation and reduction of doxorubicin, and not to
topoisomerase action

Letter D - The drug is a powerful vesicant yet Dexrazoxane is


an antidote to doxorubicin-induced extravasation.

72. True of Doxorubicin, EXCEPT:


a. Doxorubicin can intercalate into DNA structure, replication,
and topoisomerase II function

b. Doxorubicin can undergo reduction reactions by accepting


electrons into the quinone ring system, with the capacity to
undergo reoxidation to form reactive oxygen radicals after
reoxidation
c.Doxorubicin causes unpredictable myelosuppression,
alopecia, nausea, and mucositis precluding its use.
FALSE- IT IS PREDICTABLE.
d. Cardiotoxicity has been related to iron catalyzed oxidation and
reduction of doxorubicin and not to topoisomerase action

DOXORUBICIN
It can intercalate into DNA, thereby altering DNA structure,
replication, and topoisomerase II function.
It can also undergo reduction reactions by accepting
electrons into its quinone ring system, with the capacity to
undergo reoxidation to form reactive oxygen radicals after
reoxidation.
It causes predictable myelosuppression, alopecia, nausea,
and mucositis. In addition, it causes acute cardiotoxicity in
the form of atrial and ventricular dysrhythmias, but these
are rarely of clinical significance.

DOXORUBICIN
In contrast, cumulative doses >550 mg/m2 are associated with a
10% incidence of chronic cardiomyopathy.
The incidence of cardiomyopathy appears to be related to schedule
(peak serum concentration), with low-dose, frequent treatment or
continuous infusions better tolerated than intermittent higher-dose
exposures.
Cardiotoxicity has been related to iron-catalyzed oxidation and
reduction of doxorubicin, and not to topoisomerase action.
Cardiotoxicity is related to peak plasma dose; thus, lower doses and
continuous infusions are less likely to cause heart damage.

DOXORUBICIN
Doxorubicins cardiotoxicity is increased when given together with
trastuzumab (Herceptin), the anti-HER2/neu antibody. Radiation
recall or interaction with concomitantly administered radiation to
cause local site complications is frequent. The drug is a powerful
vesicant, with necrosis of tissue apparent 47 days after an
extravasation; therefore, it should be administered into a rapidly
flowing intravenous line.
Dexrazoxane is an antidote to doxorubicin-induced extravasation.
Doxorubicin is metabolized by the liver, so doses must be reduced
by 5075% in the presence of liver dysfunction.

MOA

Can intercalate into DNA, thereby altering


o DNA structure & replication
o Topoisomerase II function
- Can also undergo reduction reactions then reoxidation to form reactive oxygen radicals.

TOXICITY

Predictable myelosuppression, alopecia, nausea & mucositis


- Acute cardiotoxicity in the form of atrial & ventricular dysrhythmias (rarely of clinical
significance)
- Cumulative doses >550 mg/m2 are associated with a 10% incidence of chronic
cardiomyopathy (appears to be related to schedule peak serum concentration)
- CARDIOTOXICITY related to iron-catalyzed oxidation and reduction of doxorubicin , and
not to topoisomerase action
o Related to peak plasma dose -> lower doses and continuous infusions are less likely to
cause damage
o DOXORUBICIN + TRASTUZUMAB (Herceptin), an anti-HER2/neu antibody
CARDIOTOXICITY
- Radiation recall/ interaction with concomitantly admin. radiation local site
complications
- Powerful vesicant with tissue necrosis 4-7 days after extravasation
o Administered in rapidly flowing IV line
o Antidote: DEXRAZOXANE

73. True of Cisplatin, except:


a.Requires administration with adequate hydration
b.Can cause hypomagnesemia and hypocalcemia
c. Neurotoxicity with stocking and glove sensory
neuropathy without motor neuropathy.
FALSE. IT HAS MOTOR NEUROPATHY (SENSORIMOTOR)
a.Intensely emetogenic

CISPLATIN
was discovered fortuitously by observing that bacteria
present in electrolysis solutions could not divide
Only the cisdiamine configuration is active as an antitumor
agent
Requires administration with adequate hydration
HYPOMAGNESEMIA can lead to hypocalcemia&tetany
Neurotoxicity with stocking-&-glove sensorimotor
neuropathy
Ototoxicity
Intensely emetogenic
Less evident myelosupression than with others

74. Vesicant chemotherapeutic agents


EXCEPT
A. Paclitaxel
B. Doxorubicin
C. Vincristine
D. Meclorethamine

VESICANT DRUG
Doxorubicin
Daunorubicin
Vincristine
Vinblastine
Vinorelbine
Meclorethamine
Mitoxantrone(mild)
Dactinomycin

75. Platinum agent with prominent neurotoxicity and


activity against GI cancers
A. Cisplatin
B. Oxaliplatin
C. Carboplatin

CISPLATIN
- Gradual decrease in kidney function is
common even with hydration
- HYPOMAGNESEMIA can lead to
hypocalcemia & tetany
- Neurotoxicity with stocking-and-glove
sensorimotor neuropathy
- Ototoxicity in 50% of patients treated
with conventional doses
- Intensely emetogenic, thus requiring
prophylactic antiemesis
-Myelosuppression less evident than
with other alkylating agents
--Chronic vascular toxicity (Raynauds
phenomenon, coronary artery disease)
is a more unusual toxicity.

Oxaliplatin
A platinum analogue with note- worthy
activity in colon cancers refractory to
other treatments. It is prominently
neurotoxic.
Carboplatin
Displays less nephro-, oto-, and
neurotoxicity. However,
myelosuppression is more frequent, and
because the drug is exclusively cleared
through the kidney, adjustment of dose
for creatinine clearance must be
accomplished through use of various
dosing nomograms.

B. INDIRECT EFFECTORS OF DNA


FUNCTION-ANTIMETABOLITE
METHOTREXATE

DEOXYCOFORMYCIN

PEMETREXED

6-MERCAPTOPURINE (6-MP)

5-FU
LEUCOVORIN

6-THIOGUANINE

CYTOSINE ARABINOSIDE

2-CHLORODEOXYADENOSINE

GEMCITABINE

HYDROXYUREA

FLUDRABINE PHOSPHATE

AZATHIOPRINE

76. Mode of action of 5-fluorouracil


(5FU)
a) 5FU is metabolized in cells to 5F-dUMP, which inhibits
thymidylate synthetase.
b) 5FU is metabolized by dihydropyridine dehydrogenase, and
deficiency of this enzyme can lead to increased response
rate from 5FU.

c) Both A and B are correct.

5FU is metabolized in cells


to 5 FdUMP, which inhibits
thymidylate synthetase (TS).
In addition,
misincorporation can lead to
single-strand breaks, and
RNA can aberrantly
incorporate FUMP. 5FU is
metabolized by
dihydropyrimidine
dehydrogenase, and
deficiency of this enzyme
can lead to excessive
toxicity from 5FU.

77. Prolonged intravenous 5-fluorouracil


(5FU) prominent toxicity:
a. Stomatitis
b. Bone marrow suppression
c. CNS Dysfunction
d. Pulmonary Embolism

5FU
Oral bioavailability varies unreliably, but orally administered analogues
of 5FU such as capecitabine have been developed that allow at least
equivalent activity to many parenteral 5FU-based approaches.
Intravenous administration of 5FU leads to
bone marrow suppression after short infusions
stomatitis after prolonged infusions.

Leucovorin augments the activity of 5FU by promoting formation of the


ternary covalent complex of 5FU, the reduced folate, and TS.
Less frequent toxicities include CNS dysfunction, with prominent
cerebellar signs, and endothelial toxicity manifested by thrombosis,
including pulmonary embolus and myocardial infarction.

C. MITOTIC SPINDLE INHIBITORS


VINCA ALKALOIDS

TAXANES

VINCRISTINE

DOCETAXEL

VINBLASTINE

PACLITAXEL

78. True of mitotic spindle inhibitors


a) Docetaxel binds to tubulin dimer with the result that
microtubules are disaggregated resulting to block of
growing cells in M-phase. FALSE. IT IS VINCRISTINE THAT
BINDS TO TUBULIN DIMER NOT DOCETAXEL.
b) Vincristine is a powerful vesicant, and infiltration can be
treated by cold compress. FALSE. IT IS TREATED W/ LOCAL
HEAT NIT COLD COMPRESS
c) The taxanes stabilize microtubules against
depolymerisation.

ANSWER: C
Vincristine (not docetaxel) binds to the tubulin dimer with the result that
microtubules are disaggregated. This results in the block of growing cells in
M-phase; however, toxic effects in G1 and S-phase are also evident,
Vincristine is metabolized by the liver, and dose adjustment in the presence
of hepatic dysfunction is required. It is a powerful vesicant, and infiltration
can be treated by local heat and infiltration of hyaluronidase.
The taxanes include paclitaxel and docetaxel. These agents differ from the
vinca alkaloids in that the taxanes stabilize microtubules against
depolymerization. The stabilized microtubules function abnormally and
are not able to undergo the normal dynamic changes of microtubule
structure and function necessary for cell cycle completion.

VINCRISTINE

VINBLASTINE

MOA:
1. Binds to the tubulin dimer with the result that microtubules are disaggregated
2. Block of growing cells in M-phase
(toxic effects in G1 & S-phase are also evident)
KINETICS
- Metabolized by the liver
o Dose adjustment in hepatic dysfunction is required

ADMIN
- Powerful vesicant
o Infiltration can be treated by local heat & infiltration of hyaluronidase
Clinically used IV doses neurotoxicity in the
MORE myelotoxic with more frequent
form of glove-and-stocking neuropathy is
thrombocytopenia
frequent
- MORE mucositis & stomatitis
- Acute neuropathic effects include jaw pain,
paralytic ileus, urinary retention, & the
syndrome of inappropriate antidiuretic hormone
secretion
- Myelosuppression is NOT seen

79. True of mitotic spindle inhibitors:


a. Vinca alkaloids like vincristine stabilizes microtubules against depolymerization.
FALSE. IT IS TAXANES THAT STABILIZES MICROTUBULES AGAINST
DEPOLYMERISATION.
b. Premedication with dexamethasone and diphenhydramine and cimetidine
completely eliminate the risk of hypersensitivity reactions to the paclitaxel
vehicle.
FALSE. PREMEDICATION IS DECREASES THE RISK BUT NOT ELIMINATE.
c. Paclitaxel may cause hypersensitivity reactions, myelosuppression,
neurotoxicity in the form of glove-and-stocking numbness and paresthesia
d. Cardiac rhythm disturbances were observed in phase I and II trials of taxanes,
most common of which is symptomatic bradycardia.
FALSE. IT IS ASYMPTOMATIC BRADYCARDIA

HORMONAL THERAPY

ESTROGEN
RECEPTOR
ANTAGONIST

PROGESTATIO
NAL AGENTS

AROMATASE
INHIBIOTRS

ANDROGEN
DEPRIVATION

TESTICULAR
ANDROGEN
SUPRESSION

TAMOXIFEN

MPA
ANDROGENS(
HALOTESTIN)
ESTROGENS

IRREVERSIBLE DIETHYLSTILBE LEUPROLIDE


-EXEMESTANE STROL
GOSERELIN
REVERSIBLE
ANASTROZOLE
-LETROZOLE

80. Aromatase Inhibitors:


a. family of enzymes that catalyze the formation of estrogen
exclusively in the ovaries
b. are of two types, the irreversible steroid analogues such as
anastrozole and the reversible inhibitors such as exemestane
c. superior to tamoxifen n the adjuvant treatment of breast
cancer in postmenopausal patients with estrogen receptorpositive tumors
d. protective against osteoporosis

Answer: C

Aromatase refers to a family of enzymes that catalyze the formation of


estrogen in various tissues, including the ovary and peripheral adipose
tissue and some tumor cells.
Aromatase inhibitors are of two types, the irreversible steroid analogues
such as exemestane and the reversible inhibitors such as anastrozole or
letrozole.

Anastrozole is superior to tamoxifen in the adjuvant treatment of breast


cancer in postmenopausal patients with estrogen receptorpositive
tumors.
Letrozole treatment affords benefit following tamoxifen treatment.
Adverse effects of aromatase inhibitors may include an increased risk of
osteoporosis.

TARGETED THERAPY

Diagnostically Guided Protein


Kinase Antagonists

Multikinase
inhibitors

Proteasome
Inhibitors

Histone
Deacetylase
Inhibitors

mTOR Inhibitors

IMATINIB
NILOTINIB
DASATINIB
BOSUTINIB
PONATINIB
GEFITINIB

SORAFINIB
&SUNITINIB
PAZOPANIB
REGORAFENIB
VANDETANIB
CABOZANTINIB
AXITINIB

BORTEZOMIB
CARFILZOMIB

VORINOSTAT
ROMIDEPSIN

TEMSIROLIMUS
EVEROLIMUS

ERLOTINIB
AFATINIB
CRIZOTINIB
VEMURAFENIB
DABRAFENIB
TRAMETINIB

HEMATOPOITEIC NEOPLASM
-IMATINIB
-NILOTINIB
-DASATINIB
-BORTEZOMIB
-VORINOSTAT

SOLID TUMORS
-GEFITINIB
-ERLOTINIB
-LAPATINIB
-SORAFINIB &SUNITINIB (MULTTITARGETED
KINASE ANTAGONISTS)
-TEMSIROLIMUS & EVEROLIMUS (mTOR)

PERSONALIZED CANCER TREATMENT


- all patients undergoing initial diagnostic evaluation for breast cancer should
have their tumour tested for ER, PR, & the c-erbB2 (HER2; HER2/neu)
oncoprotein
- patients expressing the ER &/or PR are candidates for adjuvant hormone
receptor-directed therapies
-Patients with evidence of abundant HER2 expression or HER2 gene amplification
will likely derive benefit from TRASTUZUMAB

81. Which of the following drugs is an


inhibitor of vascular endothelial growth
factor (VEGF) receptors and can modulate
tumor blood vessel function through its
action on endothelial cells?
a) Lapatinib
b) Sorafenib
c) Cetuximab

d) Tratuzumab

SORAFENIB
- for solid tumors , Multitargetd kinase antagonist
-Drugs of this type with prominent activity against the vascular endothelial
growth factor receptor (VEGFR) tyrosine kinase have activity in renal cell
carcinoma.
- Sorafenib is a VEGFR antagonist with activity against the raf serinethreonine protein kinase, and regorafenib is a closely related drug with
value in relapsed advanced colon cancer.
Other Multitargted Kinase anatagonists
1. SUNITINIB-anti VEGFR, anti-PDGRF, anti-c-kit

Lapatinib
-targeted, solid tumors
HER2/NEU Combined EGF receptor & erbB2 tyrosine kinase
antagonist with activity in breast cancers refractory to
anti-erbB2 antibodies
Cetuximab -biologic, EGFR-directed antibodies
EGFR
-Colorectal cancers(refractory) with wild-type Ki-ras
oncoprotein;
-head and neck cancers treated with radiation;
MOA
-direct effects, antiproliferative, stimulated immune cell
or complement mediated response
Side effects
-rash, diarrhea, infusion reactions

Trastuzumab
HER2/NEU

Biologic therapy, antibodies


Active in breast cancer and GI cancers expressing
HER2/neu;
SIDE EFFECTS: cardiotoxicity, particularly in setting
of prior anthracyclines, requires monitoring;
infusion reactions

82. Agent targeting EGFR receptors in


Adenocarcinoma of the lung:
A. Sunitinib
B. Imatinib
C. Erlotinib
D. Trastuzumab

Erlotinib
- For solid tumors
-EGF receptor tyrosine kinase antagonist
-With somewhat superior outcome in clinical trials in NonSmall Cell Lung Cancer (NSCLC)
- Even patients with wild-type EGF receptors may benefit from
erlotinib treatment
-The presence of EGF receptor tyrosine kinase mutations has
recently been shown to be a basis for recommending erlotinib
and afatinib for first-line treatment of advanced NSCLC.

SUNITINIB

IMATINIB

ERLOTINIB

TRASTUZUMAB

Renal cell
carcinoma
Pancreatic
neuroendocrine
tumor
GI stromal
tumor

Bcr-Abl fusion
protein (CML/ALL)
c-kit mutants
PDGFR
variants (GI
stromal tumor)
eosinophilic
syndromes

First-line
treatment of
NSCLC with ATP
site mutation of
EGFR;
second-line
treatment of
wild-type EGFR
NSCLC

HER2/neu
For breast cancer &
GI cancer

BIOLOGIC THERAPY

CELL MEDIATED IMMUNITY

ANTIBODIES

CYTOKINES

Allogeneic T cells are transferred RITUXIMAB(ANTI CD20) INTERFERON


to cancer-bearing hosts in three TRASTUZUMAB(ANTIIL-2
major settings
HER-2 NEU)
ANTIBODIES TO CD52
Autologous T cells are removed EGFR-DIRECTED Ab
from the tumor-bearing host,
-CETUXIMAB
manipulated in several ways in
&PANITUMUMAB
vitro, and given back to the
ANTI-VEGF Ab
patient
-BEVACIZUMAB
Tumor vaccines are aimed at
boosting T cell immunity

ACUTE
COMPLICATIONS OF
CANCER TREATMENT

83. Primary prophylaxis administration of G-CSF is


indicated in the following patient/s
A. 35 year old patient with breast cancer stage III who
received dose dense Doxurubicin, and cyclophosphamide
B. Patient NL, who has neutropenia ANC of 1200, on day 7 of
Paclitaxel/Carboplatin, asymptomatic
C. Patient ST, who is on day 8 of radiation therapy for Stage III
Laryngeal cancer

84. Primary CSF administration is


indicated
A. Routinely to prevent Grade 3 neutropenia
B. In a patient given 1st line treatment for metastatic breast
cancer using agent Taxane
C. In a patient with preexisting neutropenia

D. in a patient wth ECOG PS 0 who received a targeted agent


against Her2

85. Indicated clinical indication for G-CSF administration


for purposes of preventing neutropenia in cancer
patients undergoing chemotherapy:
a. Needed routinely for first cycle of chemotherapy for patients
with ECOG PS 0
*NOT ROUTINE, POOR PERFORMANCE STATUS
b. Needed routinely for patients who had febrile neutropenia in
previous cycle
c. Needed routinely for patients with age > 65 years being
treated for lymphoma with palliative intent to be given on the
first cycle
*CURATIVE INTENT NOT PALLIATVE
d. All of the above

86. If indicated as primary prophylaxis, GCSF should be started agent against Her2
A. Right after chemotherapy
*in primary prophylaxis given shortly after completing chemo
B. 1 day after chemotherapy
*secondary prophylaxis -24-72hrs after
C. 1 day before chemotherapy
D. 1 hour prior to chemotherapy
*NOT SURE, PLEASCE CHECK

87. Her condition improved after 3 days.


Repeat CBC showed ANC of 900/uL.
When do you stop G-CSF administration?
A. Continue until absolute neutrophil count is 10,000/uL
B. Continue until her next cycle of chemotherapy which will
be in 11 days

C. Should stop after 24 hours of first G-CSF administration


D. Continue daily injections concurrently with chemotherapy

When Should Therapy Begin


and End?
When indicated, start2472h afterchemotherapy
Continue until absolute neutrophilcountis 10,000/l
Do notuseconcurrentlywithchemotherapy or radiationtherapy

88. Myelosuppression after


chemotherapy:

a. Maximal neutropenia occurs 48 hours after conventional doses of


anthracyclines, antifolates and antimetabolites
FALSE. IT OCCURS 6-14 DAYS.
b. Alkylating agents like doxorubicin can display delayed marrow
toxicity, first appearing 6 weeks after dosing.
FALSE. IT INCLUDES Nitrosoureas, DTIC, and procarbazine ONLY.
c. Febrile neutropenia refers to the clinical presentation of fever in a
neutropenic patients in a patient undergoing treatment with a
cytotoxic agent.
d. Mortality from uncontrolled infection is directly proportional with
the neutrophil count.
FALSE. INVERSELY PROPORTIONAL

CASE

A, a 40 year old female diagnosed to have


invasive ductal carcinoma stage IIB L, s/p modified
radical mastectomy L, is admitted for 2nd cycle of
adjuvant
chemotherapy
using
docetaxel,
Doxorubicin and Cyclophosphamide. During her first
cycle, she had an episode of fever and neutropenia
for which she was given IV antibiotics and stayed in
the hospital for 1 week.

89. Based on the case above, when do you start


G-CSF administration?
a. 2 hours after chemotherapy
b. If patient is febrile
c. 24 hours after chemotherapy
d. While on docetaxel infusion

Answer: B
Most patients, however, receive regimens that do not have such a high
risk of expected febrile neutropenia, and therefore most patients
initially should not receive G-CSF or GM-CSF.
Special circumstancessuch as a documented history of febrile
neutropenia with the regimen in a particular patient or categories of
patients at increased risk, such as patients older than age 65 years with
aggressive lymphoma treated with curative chemotherapy regimens;
extensive compromise of marrow by prior radiation or chemotherapy;
or active, open wounds or deep-seated infectionmay support primary
treatment with G-CSF or GM-CSF.

90. AA was not given G-CSF and was eventually admitted


the following week due to fever, chills and difficulty of
breathing. Her ANC on administration is 0. CXR showed
pneumonia. She was given IV antibiotics and G-CSF. When
do you stop G-CSF administration?
a. Continue until absolute neutrophil count is 10,000/ul
b. Continue until her next cycle of chemotherapy

c. Stop after 24 hours of first G-CSF administration


d. Will not stop, daily G-CSF with dose of 5mg/kg per day
subcutaneously so that chemotherapy will not be delayed.

FEBRILE NEUROPENIA

FEBRILE NEUROPENIA

THROMBOCYTOPENIA

THROMBOCYTOPENIA

THROMBOCYTOPENIA

ANEMIA

ANEMIA

OTHERS(NOT SURE IF
INCLUDED)

91. Facilitates INVASION OF CANCER


CELLS
A. Activation of transduction pathways
B. Repair of DNA damage
C. Activation of suicide pathway
D. Loss of gap junction and cadherins
Invasion
Loss of cell-cell contacts
Gap junctions, Cadherins
Increased production of matrix metalloproteinases (MMPs)
Often takes the form of epithelial-to-mesenchymal transition (EMT),
with anchored epithelial cells becoming more like motile fibroblasts

92. Phase of cell cycle, during which the


fidelity of DNA replication is assessed and
errors are corrected:
A. M phase
B. Gap 1
C. S phase

D. Gap 2

93. Phosphorylation of pRB:


A. Occurs in early G1 phase at the restriction point
B. Requires CDK4/cyclin D complex for full phosphorylation
C. Determines whether a cell will enter S phase D. Results to
light complex with E2F/DP1

Cell cycle checkpoints


The progression of a cell through the cell division cycle is regulated at a number
of checkpoints by a wide array of genes

G1
first phase
preparations are made to replicate the genetic material
The cell stops before entering the DNA synthesis phase, or S phase, to take
inventory
Are we ready to replicate our DNA?
Is the DNA repair machinery in place to fix any mutations that are detected?
Are the DNA replicating enzymes available?
Is there an adequate supply of nucleotides?
Is there sufficient energy?

Cell cycle checkpoints


Retinoblastoma protein, Rb
-main brake on the process is the retinoblastoma protein, Rb
When the cell determines that it is prepared to move ahead,
sequential activation of cyclin-dependent kinases (CDKs) results in
the inactivation of the brake, Rb, by phosphorylation

Phosphorylated Rb releases the S phaseregulating transcription


factor, E2F/DP1, and genes required for S phase progression are
expressed

THANK YOU!
YANNIE SAN-ANTONIO
KAT KABIGTING
KIMPOY SEVILLA
FRECHELLE DY
FARA LUIS
JONATHAN DE LUNA