LECTURES ON

RADIOTHERAPY AND
ONCOLOGY
B.SC RADIOGRAPHY
PROGRAM,

RDG 508
Lecture 1

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 Clinical modality dealing wih the use of ionizing radiations
in the treatment of patients with malignant, occasionally
benign diseases.
 Aim is to deliver a precisely measured dose of irradiation to a
defined tumor volume with as minimal damage as possible to
surrounding healthy tissue, resulting in:
 eradication of the tumor,
 high quality of life
 prolongation of survival.

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 How Does Radiation Make
Changes In Tissues?

i. Physical phase

ii. Chemical phase

iii. Biological phase

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H2O

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 General Forms of DNA Damage
DNA-protein
crosslinks

DNA
Single strand break protein

Base-damage

DNA-DNA link on
DNA double the same strand
strand breaks

DNA-DNA
crosslinks

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What Happens When DNA is
Affected by Irradiation ?

Repair Recovery

Cell death
Prevent cell division
Misrepair Point mutations
Deletions
and translocations DNA
abberations

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POSSIBLE OUTCOME OF
IRRADIATION CONT’D
 Possible outcomes of cell irradiation:
• No effect.
• Division delay: The cell is delayed in going through division.
• Apoptosis: The cell dies before it can divide.
• Reproductive failure: The cell dies when attempting the mitosis.
• Genomic instability: There is a delay in reproductive failure.
• Mutation: The cell survives but contains a mutation.
• Transformation: The mutation leads to a transformed
phenotype and possibly carcinogenesis.
• Bystander effects: An irradiated cell may send signals to
neighboring unirradiated cells and induce genetic damage in
them.
• Adaptive responses: The irradiated cell becomes more radio-
resistant.

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POSSIBLE OUTCOME OF
IRRADIATION CONT’D
Cell remains the same after irradiation

Cell affected by irradiation but repairs itself

Cell becomes deformed after irradiation

Cell dies after irradiation

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INDIRECT ACTION IN CELL KILL BY
RADIATION (CONT’D)
In indirect action the radiation interacts with other
molecules and atoms (mainly water, since about 80% of a
cell is composed of water) within the cell to produce free
radicals, which can, through diffusion in the cell, damage
the critical target within the cell.

Indirect action can be modified by chemical sensitizers or

radiation protectors.

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 INDIRECT ACTION IN CELL KILL
BY RADIATION (CONT’D)

The basic radiochemical reactions that may occur in water

molecules disrupted by passage of an ionizing particle
are as follows:

(1)

(2)

(3)

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 INDIRECT ACTION IN CELL KILL
BY RADIATION CONT’D

The highly reactive species produced in water through

-
the radiochemical reactions are: e aq, OH. and H.

These reactive species bring about the indirect radiation

damage to biological system by reacting and damaging
the molecules in cells.

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 INDIRECT ACTION IN CELL KILL
BY RADIATION CONT’D

The free radicals, such as H2O+ (water ion) and OH.

(hydroxyl radical), that break the chemical bonds and
produce the chemical changes that lead to biological
damage are highly reactive molecules because they have
an unpaired valence electron.

About two thirds of the biological damage by low LET

radiations (sparsely ionizing radiations), such as x rays
and electrons, is due to indirect action and one third is
due to direct action.

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 Indirect action in cell kill by
radiation cont’d
The series of events of the incident photon to the final biological damage
is as follows:
Typical time scale involved in these 5 steps:

– (1) The physics of the process

takes of the order of 10-15 s.
– (2) The ion radicals have a
lifetime of the order of 10-10 s.
– (3) The free radicals have a
lifetime of the order of 10-5 s.
– (4) The step between the
breakage of bonds and the
biological effect may take hours,
days or years. 7/24/21 13
 INDIRECT ACTION IN CELL KILL
BY RADIATION CONT’D
The steps involved in producing biological damage by
the indirect action of x rays are as follows:
(1) Primary photon interaction (photoelectric effect, Compton
effect, pair production) produces a high energy electron or
positron.

(2) The high energy light charged particle in moving through

tissue produces free radicals in water.

(3) The free radicals may produce chemical changes in DNA

from the breakage of chemical bonds.

(4) The changes in chemical bonds result in biological effects.

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 INDIRECT ACTION IN CELL KILL
BY RADIATION CONT’D

Time scale
 The timescale involved between the breakage of
chemical bonds and the biological effect may be hours to
years, depending on the type of damage.

 If cell kill is the result, it may happen in hours to days,

when the damaged cell attempts to divide (early effect of
radiation).
 This can result in early tissue reactions (deterministic
effects) if many cells are killed.

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FRACTIONATION IN
RADIOTHERAPY
 Administration of total radiation dose in small bits . Example:

• 50Gy in 25 fractions

• 20Gy in 10 fractions

• 15Gy in 5 fractions

• 10Gy in 2 fractions

• 9Gy in 3 fractions

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FRACTIONATION IN RADIOTHERAPY
CONT’D

 Fractionation of radiation treatment so that it is given over

a period of weeks rather than in a single session results in
a better therapeutic ratio.

 To achieve the desired level of biological damage the

total dose in a fractionated treatment must be much larger
than that in a single treatment.

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TYPES OF RADIOTHERAPY
FRACTIONATION
a. Standard/conventional
fractionation……2Gy/day 5x
a week for 5 weeks, e.g
50Gy in 25 fraction
b. Altered fractionation
i. Hypo (Split course)
ii. Hyperaccelarated
iii. Accelerated

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FRACTIONATION IN RADIOTHERAPY
CONT’D

 Other forms of fractionation include:

o Hyperfractionation

o Accelerated hyperfractionation

o Hypofractionation

o Split dose fractionation

o Continuous hyperfractionated accelerated radiation therapy
(CHART) is an experimental program used with three fractions per
day for 12 continuous days.

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FRACTIONATION IN RADIOTHERAPY
CONT’D

The basis of fractionation is rooted in 5 primary biological

factors called the five Rs of radiotherapy:
Radiosensitivity. Mammalian cells have different radio-
sensitivities.
Repair. Mammalian cells can repair radiation damage.
Repopulation. Cells repopulate while receiving fractionated
doses of radiation.
Redistribution in proliferating cell population throughout the
cell cycle phases increases the cell killing from a
fractionated treatment.
Reoxygenation of hypoxic cells occurs during a fractionated
course of treatment, making them more radiosensitive to
subsequent doses of radiation.

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Increase in
total dose
(%10-15)

Short overall
treat. time
(%20-50)

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ADVANTAGES OF
FRACTİONATİON
 Reduction in the number of hypoxic cells through cell killing
and reoxygenation

 Radiation induced redistribution of cells within cell cycle

tends to sensitize rapidly proliferating cells.

 Acute normal tissue toxicity of single dose can be decreased

with fractionation.

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Comparison of Various Fractionation Schedules
Indication Conventional Split course Accelerated Hyper
Tumors growth Average Average or slow Rapid Average / Slow
rate

Normal tissue
effects,
Acute Standard Stand/Greater Greater Stand/Greater
Late Standard Greater Standard/Great. Lower
Advantages -- Shorter actual Destroys more Lower OER
treatment time tumor cells; with small
(Fewer fractions) Prevents tumor doses,
repop., Spares late
Less OTT damage; allows
reoxyg., allows
stem cell repop.
Disadvantages -- May permit -- More 7/24/21
fractions
23
tumor
 DOSE –TIME FACTORS: 5
‘R’S OF RADIOBIOLOGY
 Complex relationship between
total dose, time and number of
fractions in the production of a
biologic effect within a given tissue
volume.
 This is closely related to the 5 ‘R’s
of ionizing radiation. 7/24/21 24
CONT’D
i. Repair of sublethal damage

ii. Repopulation of cells between fractions

iii. Redistribution of cells throughout the cell cycle

iv. Reoxygenation

v. Radiosensitivity

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CELL CYCLE-Redistrubition

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Oxygen

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 Reoxygenation

As the tumour size is decreased by irradiation,

vascular supply is increased. Necrotic area is decreased
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Where do the biological changes
occur ?
1. TUMOUR
TUMOUR KILL
LOCAL-REGIONAL CONTROL
SURVIVAL BENEFIT
2. HEALTHY TISSUES ADJACENT TO
TUMOUR
• SIDE EFFECTS

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Radiosensitivity – Acute Effects

Rapidly
proliferating tissues

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 Radiosensitivity –
Late Effects

Mesenchimal tissues

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 Explanations for Different
Radiosensitivities of Tumors
• Degree of Repair
• Hypoxia
• Proportion of clonogenic cells
• Inherent radiosensitivity of tumor
cells
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 SIDE EFFECTS OF
RADIOTHERAPY
1. Time related onset 2. Systemic
a. Acute – Fatigue
– Decrease in blood
(During treatment/ first 3 cell count
months )
– Skin reactions
b. Subacute ( 3 - 6 – Decreased appetite
months ) – etc, etc
c. Late ( > 6 months ) 3. Organ specific

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 TOXICITIES OF RADIOTHERAPY
CONT’D
 In-field toxicities
– Mucositis: painful inflammatory changes and ulcerations
– Radiation dermatitis, moist desquamation

 Systemic toxicities
– Nausea, vomiting, diarrhea
– Neurotoxicity, nephrotoxicity, ototoxicity
– Hematologic toxicity

 Chronic toxicities
– Soft-tissue fibrosis: neck, trismus
– Osteoradionecrosis
– Small bowel obstruction and perforation

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LATE RADIOTHERAPY EFFECTS:
LYMPHOEDEMA COMPLICATING
AXILLARY CLEARANCE

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GOOD COSMESIS POST EBRT FOR
RIGHT BREAST MALIGNANCY

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AN ADVANCED INOPERABLE LEFT
BREAST CANCER

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LEFT CHEST WALL, AXILLA AND
SUPRACLAVICULAR IRRADIATION FIELDS
WITH A PARASTERNAL FIELD FOR POST
MASTECTOMY LEFT BREAST CANCER.

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TYPICAL PRESENTATION - YOUNG TO MIDDLE AGED
WOMAN WITH ADVANCED BREAST CANCER. NOTE
NIPPLE RETRACTION AND DEVIATION, EDEMA AND
PEAU D’ORANGE OF OVERLYING SKIN.

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PAGET’S DISEASE ASSOCIATED WITH BREAST
MASS

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OLD WOMAN WITH PROMINENT AXILLARY
INVOLVEMENT AS WELL AS RIGHT BREAST SWELLING.
THERE IS INCREASE IN SIZE OF THE AREOLA AND
EDEMA OF THE NIPPLE AREOLA COMPLEX

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 Thorax

Acute Late

• Cough • Fibrosis
• Dyspnoea • Coronary artery disease
• Pneumonia • Cardiomyopathy
• Dysphagia • Pericarditis

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 Abdominopelvic

Acute Late

• Emesis • Adhesions
• Diarrhoea • Stricture
• Dysurea • Proctitis
• Tenesmus • Decrease in the bladder
• Amenorrhea / capacity
azospermia 7/24/21 45
Types of Radiotherapy According
to Aim

• Curative (radical, primary, definitive)

- Combined CT (concomitant, sequential)
• Adjuvant / neoadjuvant (preop, postop,
intraoperative)
• Palliative (metastatic, local tumour site)

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 Clinical Aspects

– Does local tumor control have an impact on

survival ?

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 Clinical Aspects

– YES

– Breast
– Prostate
– Lung
– Head and Neck

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 Application of Radiobiologic
Concepts to Radiation Therapy
Process Potential Manipulation Examples of Therapy

DNA damage Increase damage in tumor cells Hypoxic cell sensitizers,

Thymidine analogues
DNA Repair Decrease repair in tumor cells Fluoroprymidines, Hydroxyurea,
Cisplatin

Signal Transduction Inhibit protective signaling Protein kinase inhibitors

cascades in tumor cells

Radiation induced gene Use gene therapy Tumor necrosis factor linked to
expression radiation responsive promoter
Growth factor expression Increase expression of protective Il-2, GCSF,GMCSF, Fibroblast GF
factors TGF-Beta, antibodies against
Block exp.of factors producing EGF
long term toxicity
Apoptosis Force tumor to undergo Transfection of wild type p53
apoptosis
Cell cycle Synchronise in sensitive (S,M) Antimetabolites, paclitaxel phase,
Prevent G2 arrest cyclin inhibitors
Cyclin inhibitors 7/24/21 49
7/24/21 50
SOME COMMON CANCERS IN OUR
ENVIRONMENT
General Considerations in management of malignancies:
1.History taking including personal data: name, age, sex,
address, occupation, marital status, next of kin, etc
2.Presenting complaints

3.History of presenting complaints

4.Past medical history

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 SOME COMMON CANCERS IN OUR
ENVIRONMENT CONT’D
5. Family and social history
6. Gynecologic history
7. General physical examination
8. Specific examination
9. Working diagnosis
10. Investigations: FBC + Differentials, Urea, Electrolytes,
Creatinine, serum proteins, urinalysis, RBS, RVS test and system
specific tests as necessary etc.

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SOME COMMON CANCERS IN OUR
ENVIRONMENT CONT’D
11. Radiologic examinations such as:
 chest x-ray

 ultrasound abdomen and pelvis

 CT

 MRI

 Bone scan

 PET scan when indicated.

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SOME COMMON CANCERS IN OUR
ENVIRONMENT CONT’D
1. Breast cancer
 Most common female malignancy in our environment and
the world over.
 Affects about 1% of the male population
 Late presentation is common with fungating ulcers
 Some present with distant metastases to sites like brain,
lungs, liver and bones

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 SOME COMMON CANCERS IN OUR
ENVIRONMENT CONT’D
 Genetic predisposition plays a significant role in its aetiology

 Commonly presents as a breast lump discovered surreptitiously

 Ulceration of breast

 Swollen lymph nodes in axilla and supraclavicular region

 Symptoms of distant metastases to lungs, liver, brain and bones

etc.

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SOME COMMON CANCERS IN OUR
ENVIRONMENT CONT’D
 Treatment options available for breast cancer include:

 Surgery

 Chemotherapy

 Radiotherapy

 Hormonal manipulation

 Targeted therapy

 Palliative and supportive care.

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SOME COMMON CANCERS IN OUR
ENVIRONMENT CONT’D
 Available screening methods are:

 Breast Self Examination

 Clinical Breast Examination

 Breast ultrasonography

 Mammography

 MRI/mammography

 Fine needle aspiration cytotology

 Fine needle aspiration biopsy etc, etc

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SOME COMMON CANCERS IN OUR
ENVIRONMENT CONT’D
2. Cervical Cancer
 Commonest gynecologic malignancy in our environment

 Human papilloma virus types 16 and 18 implicated in its

aetiology
 Promiscuity

 Grand multiparity

 Alcohol and tobacco use

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 SOME COMMON CANCERS IN OUR
ENVIRONMENT CONT’D
Symptoms include:
 Vaginal discharge

 Vaginal bleeding….post coital, intermenstrual, menorrhagia,

polymenorrhoea, contact bleeding
 Back and waist pain

 Symptoms of distant metastases

 Renal failure

 PAP smear useful for screening

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SOME COMMON CANCERS IN OUR
ENVIRONMENT CONT’D
 Treatment options available for cervical cancer:

 Surgery in form of hysterectomy for early cases

 Chemotherapy

 External beam radiotherapy

 Brachytherapy

 Targeted therapy

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 SOME COMMON CANCERS IN OUR
ENVIRONMENT CONT’D
3. Prostate Cancer.
 Commonest male malignancy in our environment

 Strong genetic predisposition in families

 Exposure to cadmium and other chemical elements

 Age

 Race/ethnicity

 Alcohol and tobacco use etc etc

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 SOME COMMON CANCERS IN OUR
ENVIRONMENT CONT’D
 Some symptoms of presentation include:
 Urinary: urgency, hesitancy, incomplete
bladder emptying
 Straining at micturition
 Urinary retention
 Heamaturia
 Bone pains
 Pathological fractures
 Symptoms related to distant metastases
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 SOME COMMON CANCERS IN OUR
ENVIRONMENT CONT’D
 Treatment options available:
 Surgery, i.e prostatectomy
 Hormonal manipulation including
orchidectomy
 Chemotherapy
 Targeted therapy
 Radiotherapy (EBRT & Brachytherapy)
 Screening by DRE (digital rectal
examination), PSA
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 SOME COMMON CANCERS IN OUR
ENVIRONMENT CONT’D
4. Colorectal Cancer
 Commonest GIT malignancy in our
environment
 Risk factors include:
 Low fibre high fat diet
 Sedentary lifestyle
 Familial predisposition
 History of cancer or polyps
 Ano-receptive sex
 Inherited syndromes, e.g Lynch, FAP, Peutz-
jehgers syndrome 7/24/21 64
SOME COMMON CANCERS IN OUR
ENVIRONMENT CONT’D
 Symptoms include:

 Change in bowel habits, including diarrhea, constipation,

change in consistency of stool for ≥ 4 wks.
 Rectal bleeding or blood in the stool.

 Persistent abdominal discomfort, such as cramps, gas or pain.

 Symptoms of metastases

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SOME COMMON CANCERS IN OUR
ENVIRONMENT CONT’D
 Treatment options available include:
 Surgery
 Radiotherapy for select patients
 Chemotherapy
 Targeted therapy
 Screening methods include:
 DRE
 CEA
 Colonoscopy
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ROLE OF THERAPY RADIOGRAPHER
IN THE MANAGEMENT OF BREAST
CANCER
1. Handles the radiotherapy equipment
2. Implementation of radiotherapy dose
prescription
3. Pre-treatment patient counselling
4. Enforcing radiation protection
5. Looks out for early signs of radiation
toxicity
6. Serves as check and balance for radiation
prescription
7. Keeping patients radiotherapy treatment records
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ROLE OF THERAPY RADIOGRAPHER IN THE
MANAGEMENT OF BREAST CANCER
CONT’D
8. Informs and monitors on the state of the radiotherapy
equipment
9. Participation in clinical trials/research
10.

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