CARCINOGENESIS By- Dr. Chirag Patil chiragpatil1275@gmail.com M.D.S in Oral & Maxillofacial Surgery

1. CARCINOGENESIS
By – Dr. Chirag Patil
M.D.S in Oral and Maxillofacial
Surgery

2. Carcinogenesis or oncogenesis or
tumorigenesis means mechanism of induction
of tumours (pathogenesis of cancer); agents
which can induce tumours are
called carcinogens
A mass of tissue formed as a result of
abnormal,excessive,uncordinated,
autonomous and purposeless proliferation of
cell even after cessation of stimulus for
growth which caused it is called Neoplasia

3. Etiology and pathogenesis of cancer is discussed
under the following 4 broad headings:
• A. Molecular pathogenesis of cancer (genes and
cancer)
• B. Chemical carcinogens and chemical
carcinogenesis
• C. Physical carcinogens and radiation carcinogenesis
• D. Biologic carcinogens and viral oncogenesis.

5. A. MOLECULAR PATHOGENESIS OF CANCER
(GENETIC MECHANISMS OF CANCER)
• Basic Concept of Molecular Pathogenesis:
• How a normal cell is transformed to a cancer cell-

6. • 1. Monoclonality of tumours- most human cancers arise from a
single clone of cells by genetic transformation or mutation.
• 2. Field theory of cancer- In an organ developing cancer, in the
normal cells, limited number of cells only grow into cancer
after undergoing sequence of changes under the influence of
etiologic agents.
• 3. Multi-step process of cancer growth and progression
• Gradual multi-step process involving many generations of cells.
The various causes act on the cell one after another (multi-hit
process).
• Further progression of the tumour.
• Ultimately, the cells transformed having features of
malignancy—excessive growth, invasiveness and distant
metastasis

7. • 4. Genetic theory of cancer.
• Cell growth of normal as well as abnormal types is under
genetic control.
• In cancer, there are either genetic abnormalities in the cell,
or there are normal genes with abnormal expression.
• The abnormalities may be from inherited or induced
mutations (carcinogenic agents: chemicals, viruses,
radiation).
• The mutated cells transmit their characters to the next cells
and result in cancer.

8. • 5. Genetic regulators of normal and abnormal mitosis.
• Regulatory genes control mitosis & cell aging,
terminating in cell death by apoptosis.
• 4 regulatory genes:
• Oncogenes- Mutated form of normal protooncogenes
in cancer
• i) Proto-oncogenes are growth-promoting genes
• ii) Anti-oncogenes are growth-inhibiting or growth
suppressor genes.
• iii) Apoptosis regulatory genes control the programmed
cell death.
• iv) DNA repair genes, that has occurred during mitosis
and also control the damage to proto-oncogenes and
antioncogenes.

9. • In cancer,
- Abnormal cell growth due to genetic damage
Abnormalities in 4 cell regulatory genes are as under:
i) Activation of growth-promoting oncogenes
ii) Inactivation of cancer-suppressor genes
iii) Abnormal apoptosis regulatory genes
iv) Failure of DNA repair genes

10. Cancer-related Genes and Cell Growth
(Hallmarks of Cancer)

11. 1. EXCESSIVE AND AUTONOMOUS GROWTH:
GROWTH PROMOTING ONCOGENES
• protooncogenes become activated oncogenes by
following mechanisms:
• Mutation in the protooncogene which alters its structure
and function.
• Retroviral insertion in the host cell.
• Damage to the DNA sequence that normally regulates
growth-promoting signals of protooncogenes resulting in
its abnormal activation.
• By formation of extra copies of protooncogene causing
overproduction that promotes excessive cellular
proliferation.

12. Transformation of proto-oncogene to oncogenes occur
by three mechanisms:
• i) Point mutations- alteration of a single base in the DNA chain
• ii) Chromosomal translocations- transfer of a portion of one
chromosome carrying proto-oncogene to another chromosome and
making it independent of growth controls.
• iii) Gene amplification - increasing the number of copies of DNA
sequence in proto-oncogene leading to increased mDNA and thus
increased or over expressed gene product.

13. Growth factors (GFs).
• GFs were the first proto-oncogenes to be discovered for
cell proliferation cascade.
• Bind to cell surface receptors to activate cell proliferation
cascade within the cell.
• However, a cancer cell may synthesise a GF and respond to
it as well,
• cancer cells acquire growth self-sufficiency.
• Growth factor genes are not altered or mutated .
• large secretion of GFs which stimulate cell proliferation.

14. Mechanisms of activation of proto-oncogenes to
form growth promoting oncogenes.

15. REFRACTORINESS TO GROWTH INHIBITION:
GROWTH SUPPRESSING ANTI-ONCOGENES
• Mutated anti-oncogenes behave like growth-promoting oncogenes
Important Tumour-suppressor Anti-oncogenes
•Retinoblastoma protein (RB Gene)
•P53 gene
•Transforming growth factor- ß (TGF- ß) and its receptors
•Adenomatous polyposis coli(APC) gene & ß-catein protein
•Von-hippel-lindau (VHL)
•Willms tumour(WT gene)
•Neurofibroma gene

16. Oncogenes versus Antioncogenes.

17. ESCAPING CELL DEATH BY APOPTOSIS:
GENES REGULATING APOPTOSIS AND CANCER
• Another mechanism of tumour growth is escaping cell death by
apoptosis.
• Apoptosis in normal cell is by cell death receptor (CD95), resulting in
DNA damage.
• other pro-apoptotic factors (BAD, BAX, BID and p53)
• apoptosis-inhibitors (B-Cell Lymphoma 2, BCL-X).
• In cancer cells, the function of apoptosis is interfered due to
mutations in BCL2 & CD95

18. AVOIDING CELLULAR AGEING:
TELOMERES AND TELOMERASE IN CANCER
• After each mitosis (cell doubling)
there is progressive shortening of
telomeres which are the terminal
tips of chromosomes.
• Telomerase is the RNA enzyme
• helps in repair of such damage to
DNA and maintains normal
telomere length in successive cell
divisions.
• after repetitive mitosis for a
maximum of 60 to 70 times,
telomeres are lost in normal cells
and the cells cease to undergo
mitosis.
• Cancer cells ,telomere length is
maintained.
• cancer cells avoid aging,mitosis
does not slow down or cease

19. CONTINUED PERFUSION OF CANCER:
TUMOUR ANGIOGENESIS
• Cancers can only survive if the
cancer cells are adequately
nourished and perfused, as
otherwise they cannot grow
further.
• Neovascularisation in the cancers
not only supplies the tumour with
oxygen and nutrients, but the
newly formed endothelial cells
also elaborate a few growth
factors for progression of primary
as well as metastatic cancer.

20. CONTINUED PERFUSION OF CANCER:
TUMOUR ANGIOGENESIS
• The stimulus for angiogenesis is provided by the release of
various factors:
• i) Promoters of tumour angiogenesis-
-vascular endothelial growth factor (VEGF)
- basic fibroblast growth factor (bFGF).
ii) Anti-angiogenesis factors- thrombospondin-1,
- angiostatin,
-endostatin
-vasculostatin
• Mutated form of p53 gene in various cancers results in removal
of anti-angiogenic role thus favouring continued angiogenesis

21. INVASION AND DISTANT METASTASIS:
CANCER DISSEMINATION

22. DNA DAMAGE AND REPAIR SYSTEM:
MUTATOR GENES AND CANCER
• Normal cells during complex mitosis suffer from minor damage to the
DNA which is detected and repaired before mitosis is completed so
that integrity of the genome is maintained.
• small mutational damage to the cell by exogenous factors (e.g. by
radiation,chemical carcinogens etc) is also repaired. p53 gene is
responsible for detection and repair of DNA damage.
• If system of DNA repair is defective as happens in some inherited
mutations (mutator genes), the defect in unrepaired DNA is passed to
the next progeny of cells and cancer results.

23. CANCER PROGRESSION AND HETEROGENEITY:
CLONAL AGGRESSIVENESS
• Biology of cancers is that with passage of time cancers become more
aggressive;(tumour progression).
Clinical parameters of cancer progression are:
- increasing size of the tumour,
- higher histologic grade
- areas of tumour necrosis
- invasiveness and distant metastasis.

24. CANCER PROGRESSION AND HETEROGENEITY:
CLONAL AGGRESSIVENESS
• molecular biology, passage of time cancer cells acquire more
and more heterogeneity.
• cancer cells remain monoclonal in origin, they acquire more
and more mutations which, in turn, produce multiple-
mutated subpopulations of more aggressive clones of cancer
cells (i.e. heterogeneous cells) in the growth which have
tendency to invade, metastasise

25. CANCER—A SEQUENTIAL MULTISTEP MOLECULAR
PHENOMENON: MULTISTEP THEORY
• cancer occurs several sequential steps of abnormalities in
the target cell-
 Initiation
 promotion
 Progression
multiple steps are involved at genetic
level by which cell proliferation of cancer cells is activated-
 activation of growth promoters
 loss of growth suppressors
 inactivation of intrinsic apoptotic mechanisms
 escaping cellular aging

26. MICRORNAs IN CANCER: ONCOMIRS
• MicroRNAs (miRNAs) are evolutionally conserved, endogenous,
noncoding single stranded RNA molecules with a length of 22
nucleotides only.
• Normally, miRNAs function as the regulators of cell
proliferation, differentiation and survival.
• miRNAs have an oncogenic role in initiation and progression of
cancer and are termed as oncogenic
microRNAs, abbreviated as oncomiRs.
• oncomiRs can perform various functions:
- tumour suppressor
- tumour promoter
-pro-apoptotic.

27. • CHEMICAL CARCINOGENESIS

28. Stages in Chemical Carcinogenesis
1. INITIATION OF CARCINOGENESIS
2. PROMOTION OF CARCINOGENESIS
3. PROGRESSION OF CARCINOGENESIS

29. Stages in Chemical Carcinogenesis
1. INITIATION OF CARCINOGENESIS
• first stage in carcinogenesis induced by initiator chemical
carcinogens.
• The change can be produced by a single dose of the initiating agent
for a short time, though larger dose for longer duration is more
effective.
• The change so induced is sudden, irreversible and permanent.

30. • Chemical carcinogens acting as initiators of
carcinogenesis can be grouped into 2 categories.
– Direct-acting carcinogens
– Indirect - acting carcinogens

31. 1. Direct-acting carcinogens.
• These are a few chemical substances (e.g. alkylating
agents, acylating agents) which can induce cellular
transformation without undergoing any prior metabolic
activation
a) Alkylating agents
• Anti-cancer drugs
(e.g. cyclophosphamide, chlorambucil,
busulfan, melphalan, nitrosourea etc)
• β-propiolactone -Lymphomas
• Epoxides -AML
b) Acylating agents –(Bladder cancer)
• Acetyl imidazole
• Dimethyl carbamyl chloride

32. 2. Indirect-acting carcinogens or
procarcinogens
• These require metabolic conversion within the body so as to
become ‘ultimate’ carcinogens having carcinogenicity
• e.g. -polycyclic aromatic hydrocarbons,
- aromatic amines,
- azo dyes,
- naturally-occurring products and others.
In either case, the following steps are involved in transforming ‘the
target cell’ into ‘the initiated cell’:

33. INDIRECT-ACTING CARCINOGENS
(PROCARCINOGENS)
a) Polycyclic, aromatic hydrocarbons
(in tobacco, smoke, fossil fuel, soot, tar,
minerals oil, smoked animal foods, industrial -Lung cancer
and atmospheric pollutants) -Skin cancer
• Anthracenes (benza-, dibenza-, dimethyl benza-) -Cancer of upper
aerodigestive tract
• Benzapyrene
• Methylcholanthrene
b) Aromatic amines and azo-dyes
•β-naphthylamine -Bladder cancer
• Benzidine
• Azo-dyes (e.g. butter yellow, scarlet red etc) -Hepatocellular
carcinoma

34. c) Naturally-occurring products
• Aflatoxin B 1
• Actinomycin D
• Mitomycin C -Hepatocellular carcinoma
• Safrole
• Betel nuts
d) Miscellaneous
• Nitrosamines and nitrosamides- Gastric carcinoma
• Vinyl chloride monomer -Angiosarcoma of liver
• Asbestos - Bronchogenic carcinoma, mesothelioma
• Arsenical compounds - Cancer, skin, lung
• Metals (e.g. nickel, lead, cobalt, chromium etc) - Lung cancer
• Insecticides, fungicides (e.g. aldrin, dieldrin, chlordane etc) - Cancer
in experimental animals
• Saccharin and cyclomates

35. Sequential stages in chemical carcinogenesis (left) in evolution of cancer (right).

36. 2. PROMOTION OF CARCINOGENESIS
• Promotion is the next sequential stage in the chemical
carcinogenesis. Promoters of carcinogenesis are
substances such as phorbol esters, phenols, hormones,
artificial sweeteners and drugs like phenobarbital.
– They differ from initiators in the following respects:
i) They do not produce sudden change.
ii) They require application or administration, for sufficient time and
in sufficient dose.
iii) The change induced may be reversible.
iv) They do not damage the DNA per se and are thus not mutagenic
but instead enhance the effect of direct-acting carcinogens or
procarcinogens.
v) Tumour promoters

37. 3. PROGRESSION OF CARCINOGENESIS
– Progression of cancer is the stage when mutated proliferated
cell shows features of malignancy. These features pertain to
morphology, biochemical composition and molecular
features of malignancy.
– features appear only when the initiated cell starts to
proliferate rapidly and in the process acquires more and
more mutations.
– The new cells develops after such repetitive proliferation
inherits genetic and biochemical characteristics of
malignancy.

38. B. PHYSICAL CARCINOGENESIS
• Divided into 2 groups:
1. Radiation- ultraviolet light and ionising
radiation - carcinogenic agent.
2. Non-radiation- Non-radiation physical agents
are the various forms of injury

39. • The main source of UV radiation-
- sunlight
-UV lamps
-welder’s arcs.
• UV light penetrates the skin for a few millimetres that
its effect is limited to epidermis.
• can cause various forms of skin cancers—
-squamous cell carcinoma
- basal cell carcinoma
-malignant melanoma.

40. MECHANISM-

41. ULTRAVIOLET LIGHT.
a) Xeroderma pigmentosum is predisposed to skin cancers at
younger age (under 20 years of age).
b) Ataxia telangiectasia is predisposed to leukaemia.
c) Bloom’s syndrome is predisposed to all types of cancers.
d) Fanconi’s anaemia with increased risk to develop cancer.

42. IONISING RADIATION.
• Ionising radiation - X-rays,
- Alpha,
- beta
- Gyama-rays,
- Radioactive isotopes
- Protons and neutrons can cause cancer in man.
• Radiation-induced cancers-
- leukaemias (except chronic lymphocytic leukaemia);
- thyroid (most commonly papillary carcinoma),
-skin, breast, ovary, uterus, lung, myeloma, and salivary glands
The risk is increased by higher dose and with high LET (linear
energy transfer) such as in neutrons and Alpha-rays than with
low LET as in X-rays and gyama-rays

43. • Mechanism.
Radiation damages the DNA of the cell by
one of the 2 possible mechanisms:
a) It may directly alter the cellular DNA.
b) It may dislodge ions from water and other molecules of the cell
and result in formation of highly reactive free radicals that may
bring about the damage.
• Damage DNA resulting in mutagenesis
• May cause chromosomal breakage, translocation, or point
mutation.
• Effect depends upon a number of factors such as type of
radiation, dose, dose-rate, frequency and various host factors
such as age, individual susceptibility, immune competence,
hormonal influences and type of cells irradiated.

44. BIOLOGIC CARCINOGENESIS
• Parasites.
• Schistosoma haematobium infection of the urinary bladder -
squamous cell carcinoma of the urinary bladder
• Clonorchis sinensis, lives in the hepatic duct cause
cholangiocarcinoma.
• Fungus.
• Aspergillus flavus - hepatocellular carcinoma
• Bacteria.
• Helicobacter pylori - chronic gastritis and peptic ulcer;
its prolonged infection may lead to gastric lymphoma and
gastric carcinoma.

45. Viral Carcinogenesis
• 20% of all cancers worldwide are due to
persistent virus infection.
• oncogenic viruses with neoplasia was first
observed by an Italian physician Sanarelli in
1889.
• The contagious nature of the common human
wart was first established in 1907. .

46. Oncogenic Viral Infections: General
Aspects
• viral infections (including oncogenic viruses) can be
transmitted by one of the 3 routes:
i) Horizontal transmission-
viral infection passes from one to another-
- Direct contact
- Ingestion of contaminated water or food
- Inhalation.
Most of these infections begin on the epithelial surfaces,
spread into deeper tissues, and then through
haematogenous or lymphatic or neural route disseminate
to other sites in the body.

47. ii) By parenteral route -by inter-human spread and
from animals and insects to humans.
iii) Vertical transmission- when the infection is
genetically transmitted from infected parents to
offsprings.
• oncogenic viruses fall into 2 broad groups:
-DNA oncogenic virus
-RNA oncogenic viruse or retroviruses.

48. Both types of oncogenic viruses usually have 3 genes
and are abbreviated according to the coding
pattern by each gene:
i) gag gene: codes for group antigen.
ii) pol gene: codes for polymerase enzyme.
iii) env gene: codes for envelope protein.

49. • Primary viral infections- majority of the common
viral infections lasts for a few days to a few weeks and
produce clinical manifestations. generally cleared by
body’s innate immunity and specific immune
responses. immunocompetent host is generally
immune to the disease or reinfection by the same
virus.
However, body’s immune system is not effective
against surface colonization or deep infection or
persistence of viral infection.
• Persistence of viral infection or latent infection some
viruses may occur by acquiring mutations in viruses
which resist immune attack by the host, or induces
immunosuppression in the host such as HIV.

50. oncogenesis by each group of DNA and RNA
oncogenic viruses is briefly considered below:
1.Mode of DNA viral oncogenesis.
2. Mode of RNA viral oncogenesis.

51. 1.Mode of DNA viral
oncogenesis.
A, Replication:
Step 1. The DNA virus invades the host cell.
Step 2. Viral DNA is incorporated into the host
nucleus and T-antigen is expressed
immediately after infection.
Step 3. Replication of viral DNA occurs and
other components of virion are formed.
The new virions are assembled in the cell
nucleus.
Step 4. The new virions are released,
accompanied by host cell lysis.
B, Integration : Steps 1 and 2 are similar as in
replication.
Step 3. Integration of viral genome into the
host cell genome occurs
which requires essential presence of
functional T-antigen.
Step 4. A ‘transformed (neoplastic) cell’ is
formed.

52. 2. Mode of RNA viral
oncogenesis.
Step 1. The RNA virus invades the host
cell. The viral envelope fuses
with the plasma membrane of the host
cell; viral RNA genome as well as
reverse transcriptase are released into
the cytosol.
Step 2. Reverse transcriptase acts as
template to synthesise single strand of
matching viral DNA which is then copied
to form complementary DNA resulting in
double-stranded viral DNA (provirus).
Step 3. The provirus is integrated
into the host cell genome producing
‘transformed host cell.’
Step 4.Integration of the provirus brings
about replication of viral components
which are then assembled and released
by budding.

53. DNA Oncogenic Viruses.
Virus Associated Tumour
1. PAPOVAVIRUSES
Human papilloma virus
Cervical cancer and its precursor lesions,
squamous cell carcinoma at other sites
Skin cancer in epidermodysplasia
verruciformis Papillomas (warts) on skin,
larynx, genitals (genital warts)
HERPESVIRUSES
Epstein-Barr virus
Burkitt’s lymphoma
Nasopharyngeal carcinoma
Human herpesvirus(Kaposi's sarcoma
herpesvirus)
Kaposi’s sarcoma
Pleural effusion lymphoma
POXVIRUSES Molluscum contagiosum, papilloma
HEPADNAVIRUSES
Hepatitis B virus
Hepatocellular carcinoma

54. RNA Oncogenic Viruses.
Virus Associated Tumour
HUMAN T-CELL LYMPHOTROPIC VIRUS (HTLV)
HTLV-I
Adult T-cell leukaemia lymphoma (ATLL)
HTLV-II T-cell variant of hairy cell leukaemia
HEPATITIS C VIRUS
HCV
Hepatocellular carcinoma

55. FIELD CANCERIZATION
• “field cancerization” was first introduced by Slaughter et al. in
1953
• Braakhuis et al. (2003) Defined
“The presence of one or more areas consisting of epithelial cells that
have genetic alterations. A field lesion (or shortly ‘field’) has a
monoclonal origin, and does not show invasive growth and
metastatic behavior, the hallmark criteria of cancer.”

56. • studying the presence of histologically abnormal tissue surrounding
oral squamous cell carcinoma.
• Development of multiple primary tumors and locally recurrent
cancer.
• Organ systems in which field cancerization has been described since
then are: head and neck (oral cavity, oropharynx and larynx), lung,
vulva, esophagus, cervix, breast, skin, colon and bladder.

57. • Genetically altered cells plays a central role.
• Initial phase - stem cell acquires genetic alterations and forms a
“patch,” a clonal unit of altered daughter cells.
• Mutations in TP53 and have been reported for head and neck, lung,
skin and breast cancer.
• Conversion of a patch into an expanding field is the next logical and
critical step in epithelial carcinogenesis. (Additional genetic alteration
are reqiured)
• Proliferating field gradually displaces the normal mucosa.

58. In the mucosa of the head and neck & esophagus, such
fields have been detected with dimensions of greater
than 7 cm in diameter (not detected by routine
diagnostic techniques )
leads to the development of one or more tumors within
a contiguous field of preneoplastic cells
fields often remain after surgery of the primary tumor
lead to new cancers “a second primary tumor” or “local
recurrence,” depending on the exact site and time
interval

59. Three phenomena:
• A wide field of aerodigestive mucosa that tends to be
affected by pre-malignant disease
• The frequent occurrence of multiple primary tumors in
epithelial areas affected by widespread pre-malignant
disease
• The possibility of distant related primary tumors in the
upper aerodigestive tract.

60. Implications for Therapy-
• Care should be taken about screening and directed biopsies in these
patients.
• Frequent examination for high-risk patients.
• Clonal patches that are unable to be detected grossly and are beyond
the initial scope of surgical excision including chemotherapy or
radiotherapy

61. APPLIED ASPECT
• CHEMOTHERAPY
• TARGET CHEMOTHERAPY
• RADIOTHERAPY

62. CHEMOTHERAPY
• A chemotherapeutic agent affects a cell in its
dividing cycle and induces irreparable damage
to the DNA to induce cell death.

63. Classification according to phase-
specific toxicity
• PHASE SPECIFIC CHEMOTHERAPY-
• Methotrexate- Antimetabolite that binds to dihydrofolate
reductase preventing DNA synthesis in S-phase. (similar to the
action of the ionizing radiations)
• Vinca alkaloids -preventing polymerization to form microtubules
and is M-phase specific
• Vinblastine – arrest cell mitosis
Kills proliferating cells during the cell cycle
These synchronized cell enter into a phase of cell cycles that killed by
the cytotoxic agents

64. • CELL- CYCLE SPECIFIC CHEMOTHERAPY-
• Most chemotherapeutic agents are cell cycle-specific (cells that
actively divides)
• Only proliferating cells remain fully sensitive to drug induced
cytotoxicity
• To increase cell kill – increase the duration of exposure rather than
increasing the drug dose
• CELLS CYCLE- NONSPECIFIC CHEMOTHERAPY-
• Alkylating agents & paltanium derivatives have an equal effect on
tumour & normal cells whether they are proliferating or resting phase
• Linear dose response curve (greater the dose of drug grater the
fractional cell kill)

65. TRAGETED SMALL MOLECULES AGAIST
EPIDERMAL GROWTH FACTOR RECEPTORS
• Gifitinib & erlotinib are orally active (EGFR-TKI) epidermal
growth factor receptors tyrosine kinase inhibitor
Blocks EGFR signaling
• Inhibits- growth, proliferation & survival of many solid tumors
Side effects of drug- acneiform rash

66. RADIATION THERAPY
• The ionizing radiations are known to induce
damage to the nucleotide chains of DNA and
induce cell death. When a single chain is
damaged, the damage is repairable, but when
the double stranded damage occurs the cell
death results.

67. • Oxygenated cells are more susceptible to radiation than hypoxic cells
• Cell death occurs with proliferation, therefore, rapidly growing
tumors are more susceptible to injury.
• intrabony tumors are relatively radioresistant than the soft tissue
tumors.
CELL CYCLE & RADIATION INJURY-
M Phase- mitosis very sensitive to radiation injury
G1 phase- resting phase, moderately resistant
S phase- DNA synthesis, moderately resistant to radiation
G2 Phase- resting phase, sensitive
G0 non cycling cells- moderate resistance

68. Radiation Strategies
• Shrinking fields: Selective radiation dosing to varying region
depending on primary size and shape (e.g. 7,000 cGy to primary site
as primary therapy, 5,000–5,500 cGy to N0 neck or adjuvant
treatment)
• Brachytherapy: Delivery of radiation to malignant tissue by
placement of permanent radioisotopes intraoperatively

69. • Three-dimensional multiple treatment beam therapy: Utilizes CT
and MRI imaging, multiple treatment fields arranged to maximize
radiation dose to target area yet achieve maximum normal tissue
sparing
• Hyperfractionated radiation therapy
• Rationale: To allow normal cells to proliferate and to suppress the
tumor cells in between the fractions.
• Dose: 1 Gy twice daily, for total dose of 60 to 70 Gy over a period of 7
weeks.

70. THANK YOU