Misael Cruz, M.D. | 01.22.

16 | INTERNAL MEDICINE

PRINCIPLES OF CANCER TREATMENT

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I.
II.
III.

LECTURE OUTLINE
Overview of Cancer
Goals of Cancer Treatment
Types of Cancer Treatment
a. Surgery
b. Radiation Therapy
c. Chemotherapy
d. Biologic Therapy

OVERVIEW OF CANCER
ORIGIN OF THE WORD CANCER
Came from the Father of Medicine, Hippocrates, a
Greek Physician.
Hippocrates used the Greek words, CARCINOS, to
describe tumors, thus calling cancer, KARKINOS
(crab or crayfish).
The Greek terms comes from the appearance of the
cut surface of a solid malignant tumor, with the veins
stretched on all sides as the animal has its feet along
the sides as well.
Crabs do not actually cause cancer but it is necessary
to limit the intake of seafoods, as well as any other
food in excess, due to possible accumulation of toxins,
which may or may not cause cancer.
OVERVIEW

Our bodies are well designed for homeostasis, for the

balancing of things within our bodies, and all of us have
mutations, several in reality, damaged, scarred cells we
cannot deny. These damaged cells, once exposed to
factors that either cause too much cellular proliferation or
alter factors that cause cell death, will have the high
chance of turning into malignant mutations, causing
cancer. These factors are nearly anything we live within
our times today, all facets of technology, which may
damage cells, allow alterations, cause reproduction of
several more mutated cells, clump together, and form
several malignant cells, and end up as cancer eventually.
THE FIRST DOCUMENTED CASE OF CANCER (two
versions)
1. The worlds oldest documented case of cancer from
ancient Egypt, in 1500 BC, recorded on a papyrus,
documenting 8 cases of tumors occurring on the
breast. It was treated by cauterization, a method to
destroy tissue with a hot instrument, called, Fire Drill.
2. Two of them, known as the Edwin Smith and
George Ebers papyri, contain descriptions of cancer
written around 1600 BC and are believed to date from
sources as early as 2500 BC.
CANCER THERAPY
1600 BC Surgery was written on papyri
17th Century Cancer surgery
1903 Radiation as treatment
1910 Chemotherapy
1928 Biologic Therapy
20th Century Gene Therapy

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INTERNAL MEDICINE | Principles of Cancer Treatment
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GOALS OF TREATMENT
The goal of cancer treatment is first to eradicate the
cancer.
If this primary goal cannot be accomplished, the goal
of cancer treatment shifts to palliation, the amelioration
of symptoms, and preservation of quality of life while
striving to extend life.
The dictum primum non nocere may not always be
the guiding principle of cancer therapy.
o When cure of cancer is possible, cancer
treatments may be considered despite the
certainty of severe and perhaps life-threatening
toxicities.

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Every cancer treatment has the potential to cause

harm, and treatment may be given that produces
toxicity with no benefit. The therapeutic index of
many interventions may be quite narrow, with
treatments given to the point of toxicity.
o Conversely, when the clinical goal is palliation,
careful attention to minimizing the toxicity of
potentially toxic treatments becomes a significant
goal.
Cure eradicate tumor cells
Control stabilize the disease without causing
symptoms
Palliate amelioration of symptoms, preserve the
quality of life.
Primum non nocere VS Primumm Succerrere. In
chemotherapeutics, we deal with the irony of initially
hastening the disease prior to managing the disease
itself.

TYPES OF CANCER TREATMENT

Types of Treatment:
1. Surgery
2. Chemotherapy
3. Radiation Therapy
4. Biologic Therapy

1.

2.

3.
4.

SURGERY
Prevention to prevent the progression of the disease.
a. Premalignant Lesions such as moles, familial
polyposis in the colon, etc.
b. HIGH RISK for Cancer:
i. Underlying disease
ii. Genetic predisposition
iii. Developmental anomaly
Diagnosis
a. Excisional biopsy get a small amount
b. Incisional biopsy cut a large amount
c. Core needle biopsy
d. Fine needle biopsy
*CNB and FNB most commonly used for diagnosis
of breast malignancies
Staging
Treatment
a. Primary in 40% of cases
b. Combined:
o Surgery, chemotherapy, radiation therapy
(multidisciplinary management)
o For local control
o Preservation of organ function
o Debulking or downsizing the tumor

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Can also be curative in some metastatic lesion (liver,

lung)
o Abscopal effect on rare occasions
o Ex: renal cancers, splenectomy in lymphoma
o For example, you have a patient with renal
carcinoma who developed a metastatic lesion in
the lungs. There is a possibility that when you do
nephrectomy, the metastatic lesion would also
disappear without treating it. This is called the
abscopal effect.
5. Palliation
a. Insertion of CV catheters
b. Removal of pericardial, pleural and ascetic fluid
c. Caval interruption for recurrent pulmonary emboli
d. Stabilization of weakened bone
e. Control of hemorrhage
f. Surgical bypass
g. Splenectomy
6. Rehabilitation
o Orthopedic procedures
o Breast reconstruction
o Plastic and reconstruction surgery
Evolution of Surgery
ANCIENT SURGERY

MANUAL EXCISION

LAPAROSCOPIC SURGERY

ROBOTICS SURGERY
CHEMOTHERAPY
Medical Oncology is a subspecialty of Internal Medicine
that deals with the use of drugs as treatment approach to
patients with cancer, alone or in conjunction with surgery
or radiation therapy.
Indications:
1. As adjuvant for local lesion
a. Organ preservation
b. Sensitize tumors
2. Tumor response (primary):
a. Complete total eradication/disappearance
b. Partial 50% eradication
c. Progression 25% increase
d. Stable no change
3. Palliation quality of life

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Eastern Cooperative Oncology Group Performance

Status (ECOG-PS):
0 Without symptom
1 Mild symptom, no treatment
2 Symptoms with treatment
3 Disabling symptoms with ambulation >50% of the day
4 Ambulation < 50%
Four (4) Broad Types:
1. Conventional Chemotherapy small molecules
could cause regression of experimental tumors in
animals
Target a large amount of molecules in the cells
causing a lot of side effects
Still being used nowadays
2. Targeted Agents small molecules interact with a
defined molecular target
Identify specific targets of molecule in the cell,
thereby preventing some side effects
Used nowadays
3. Hormonal Therapies targets the biochemical
pathways underlying estrogen and androgen function
4. Biologic Therapies with a particular target with a
capacity to orchestrate and regulate the host response
to kill the tumor
Mechanism of Action:
a. Direct DNA interactive agents
b. Indirect effects on DNA function
c. Mitotic spindle inhibitors
d. Hormonal effect
e. Targeted molecules
f. Biologic effect
Direct DNA Interactive Agents
1. Alkylating Agents phase non-specific; forms cross
linkage of DNA strands and appearance of breaks:
a. Nitrogen mustard aseptic thrombophlebitis
b. Cyclophosphamide

chemical
cystitis,
pulmonary fibrosis
c. Chlorambucil azoospermia, myelosuppression
d. Nitrosoureas bone marrow toxicity
e. Melphalan mucositis
f. Streptozotocin Fanconis syndrome, RTA
g. Procarbazine CNS effects, disulfiram like
syndrome
h. Cisplatin nephrotoxicity, neurotoxic
i. Carboplatin, temozolamide, oxaliplatin

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2. Antitumor
Antibiotics
and
Topoisomerase
Poisons produced by bacteria, bind directly to DNA
and generate free radicals
a. Doxorubicin cardiotoxicity
b. Bleomycin pulmonary fibrosis
c. Dactinomycin severe myelosuppression
d. Mitomycin C hemolytic uremic syndrome
e. Mitoxantrone

cardiotoxicity,
acute
promyelocytic leukemia
f. Etoposide myelosuppression
g. Camptothecin (Topotecan, CPT 11) mucositis
Indirect Effects to DNA Function:
1. Antimetabolites through misincorporation into
DNA, abnormal timing or progression through DNA
synthesis, altered function of purin and pyrimidine
synthesis
a. Methotrexate inhibits dihydrofolate reductase
b. 5 Flurouracil capecitabine (oral homologue)
c. Cytosine arabinoside gemcitabine
d. Fludarabine phosphate CNS dysfunction
e. Premetrexed folate directed antimetabolite
f. Asparaginase bacterial enzyme, stop DNA
synthesis
Mitotic Spindle Inhibitors prevent spindle formation;
cellular scaffolding; disaggregation of microtubules
1. Vincristine blocks growing cells in M phase;
neurotoxic
2. Vinblastine myelotoxic
3. Vinorelbine oral
4. Taxanes (Paclitaxel, Docetaxel) stabilize
microtubules and will function abnormally
5. Estramustine causes metaphase arrest
Hormonal Agents family of steroid hormone receptor
molecules that can alter gene transcription and apoptosis;
interacts with activity of hormones in the body
1. Glucocorticoids induces apoptosis; Cushing
syndrome
2. Tamoxifen partial estrogen receptor antagonist;
thromboembolic phenomenon and endometrial
carcinoma
3. Diethylstilbestrol down regulate LH to decreased
testosterone; CAD; not being used anymore
4. Luteinizing hormone releasing hormone agonist
leuprolide, goserelin
5. Aromatase Inhibitors catalyzes the formation of
estrogen
Anastrazole,
Ietrazole
(reversible),
Exemestane (irreversible)

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Targeted Therapies (Molecular)

Products of oncogenes and tumor suppressor gene
Regulators of cell death pathway
Mediators of cellular immortality
Molecules for microenvironmental molding
*Microenvironment house of tumor; within the cell;
within chromosome/mitochondria of cell
For hematopoietic neoplasm
1. Imatinib mesylate (Gleevec) CML
2. Tretinoin
3. Bortezomib
4. Vorinostat
5. Gemtuzumab
6. Ozogamicin
For solid neoplasm
1. Erlotinib
2. Lapatinib
3. Sorafenib
4. Sunitinib
Biologic Therapy
Goal: To manipulate the host-tumor interaction in
favour of the host
They differ from Molecular Targeted Therapy in that it
requires an active response on the part of the tumor or
host to allow the therapeutic effect
1. Cellular Mediated Immunity
Allogenic T cells
Autologous T cells
Tumor vaccines (HPV, Hepa B)
2. Antibodies
Antibodies against CD20
o Rituximab
o Trastuzumab
EGFR directed antibodies
o Cetuximab
o Panitumomab
Anti-VEGF antibodies
o Bevacizumab
3. Cytokines
Tumor Necrosis Factor (TNF)
Interferon (INF)
Chemokines
Note: Only interferon alpha, interleukin2 are
routinely used

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CHEMOTHERAPY

Effects of Chemotherapy
1. Myelosuppression
2. Nausea and vomiting
3. Diarrhea
4. Gonadal dysfunction
5. Alopecia
6. Mucositis
RADIATION THERAPY
Radiation Oncology
Clinical and scientific discipline devoted to
management of cancer and other disease by ionizing
radiation
Radiation Therapy
Clinical specialty dealing with the use of ionizing
radiation for the following goals:
o Curative
o Palliative
Applications:
o Definitive radiation
o In combination with surgery and chemotherapy:
Pre-op, Intra-op, Post-op
o Palliative radiation
Types of Ionizing Radiation
1. Electromagnetic Radiations
a. X-rays
b. Gamma rays
2. Particulate Radiations deeper types, not commonly
used in practice
Ex. Electrons, protons, neutrons, alpha particles,
heavily charged ions

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Biologic Effects of Radiation:

1. Direct Action: when gamma rays are absorbed in
biologic matter, some of the energy is converted to fast
electrons, which can interact directly with the critical
targets of the cell DNA. Beta rays are electrons and
may also react directly.
2. Indirect Action: the radiation may interact with other
atoms of molecules in the cell to produce free radicals
that are able to reach and damage the critical target
DNA.
Double Strand Break
Most important lesion produced in chromosome which
can cause cell killing mutations, and chromosomal
aberration
Types of Radiotherapy
1. Teletherapy far from the target organ
a. Conventional Roentgen Teletherapy
b. External Radiotherapy with High Energy
b.1. Cobalt uses gamma rays
b.2. Linear Accelerator uses x-rays
2. Internal Radiotherapy (Brachytherapy) near the
target organ
a. Intracavitary: placing the radioactive source
inside body cavity
b. Interstitial: implanting radioactive source
c. Transluminal: inserting the radioactive source
inside the lumen
d. Surface: applied directly to the skin or surface of
the target

Manual Plan

Manual planning is done when there is no available complex 3D

Planning. We measure the size of a lesion, put a mark at the center of
the target lesion.

2D Simulator Based

2D Plan and Cerrobend Blocks

Radiation Therapy

Cerrobend blocks are made of 10% lead.

Cobalt Therapy is available at PGH and Jose Reyes Memorial Medical

Center. Linear accelerator 2D is available at Chinese General Hospital.
3D-IMRT-IGRT is a more complex machine where you can apply the
function of CT Scan and evaluate the status of the lesion while treating
the patient. This is already available here at Sacred Heart Medical
Center. The latest is the tomotherapy which is like a CT Scan that
delivers the radiation around.

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3D Radiotherapy CT Based

Interstitial Brachytherapy (Tongue)

In here, we use needles. Those are where the radiation

passes through.
Interstitial Brachytherapy (Prostate)
Needles are inserted inside the prostate. It is CT guided.
Stereotactic Radiosurgery (SRS)

SRS is another complex form of radiotherapy for smaller brain lesions

where we only treat patients in a single session, target the affected
area, and so the rest of the brain parenchyma is not being treated.

Transluminal Brachytherapy (Lungs)

For endobronchial malignancies. We put a catheter inside
via bronchoscopy then we target the malignancy

Intracavitary Brachytherapy (Cervical)

As mentioned previously, brachytherapy is near the
patient. That is why we use this applicator for cervical
malignancies where radiation travels.

Intracavitary Brachytherapy (Nasopharynx)

We use these tubes, placed through the nostrils

Surface Brachytherapy (Skin)

Rarely used today. May cause secondary malignancies
like sarcoma of the hand because in the olden times,
patients just hold the radioactive material.
RADIATION THERAPY
Toxicities
Acute
o Occurring during the treatment and 3 months after
completion of radiation

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Fatigue, alopecia (depending on the area to be

treated) , skin discoloration, diarrhea, nausea,
vomiting, anorexia, esphagitis, xerostomia
The difference between the side effects of
radiation and chemotherapy is that chemotherapy
is systemic. It goes around the entire body so the
effect is generalized. In radiation therapy, the
effect is localized. (Ex. If you are treating the
abdomen, you will not expect alopeci.)
Chronic
o Occurring from 3 months onwards
o Cataract, stenosis, strictures, fibrosis, pericarditis,
enteritis, secondary tumors
These are not rarely being seen nowadays
because of the technology used.

Ex. Acupuncture for pain

COMPONENTS
o Surgery
o Pharmaceutical Drugs
o Herbal Medicine
o Nutritional Medicine
o Lifestyle and Behavior
o Mind/Body Medicine
o Energy Medicine
o Manipulative Therapies

Other forms of therapy:

1. Systemic Therapy
Uses radionucleotide targeted to a site of the tumor
Ex. Nulear medicines iodine 131, strontium 89
Nuclear medicine is different from radiation therapy and
radiation oncology. Nuclear medicine uses radioactive
isotopes for thyroid malignancies, strontium which is a
radioactive seed that they use for bone pain that cannot be
treated
with
conventional
or
extraconventional
management.
2. Photodynamic Therapy
Uses light (high energy) in a chemical structure form
and taken by cancer cells and produce free radicals
then die.
3. Cryotherapy
Uses very low temperature emissions for the treatment
of malignancy.
4. Gene Therapy
None have been approved for routine clinical use
Still under experimental studies.
Strategies being done:
1. Use of virus that cannot replicate
2. Virus that can replicate but only in the tumor cells
3. Virus that express antigen and promote host
mediated immune response
5. Integrative Therapy
This is accepted in oncology. It follows the principle
of yin and yang. It helps with whatever conventional/
western/ scientific medicine fails to do and it
complements it.
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INTERNAL MEDICINE | Principles of Cancer Treatment
PROPERTY OF AUFSOM Batch 2017
V3.2 s2015-2016

THINGS TO REMEMBER:
Cancer treatment goals include cure, control and
palliation
Cancer treatment includes surgery, radiation therapy,
chemotherapy, biologic therapy, integrative medicine,
gene therapy
Primum succerrere
o First, hasten to help.
o You hasten the disease first before you treat the
patient
Advancements are still experimental ongoing and still
on experimental stage

CANCER is a word, not a sentence. :)

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