Principles of

Radiotherapy

Salim B. CHAMMAS BSC, MD, MSc, FRCP(Canada)

Radiation Oncologist
UMC-RH Nov 2016

Radiation Therapy is the

use of ionizing radiation
to destroy malignant
tissue.

Types of ionizing Radiation

Radiation
Electromagnetic
X-Rays
-Rays

Charge
None

None

Particles
Electrons or -rays
-ve
Protons
+ve
Neutrons
none
-Particle (He Nucleus)
+ve
Negative mesons
-ve
Heavy charged ions (C, Ne, Ar)
+ve

X-Ray production
Electrons
Anode

X-rays

Electron Accelerators

First Radiotherapy Treatment

Emil Herman Grubb
29

January 1896

woman
18

(50) with breast cancer

daily 1-hour irradiation

condition
died

was relieved

shortly afterwards from

metastases.

Historical
Perspective
Interstitial Radium
Brachytherapy for
Breast Cancer, 1917

Radiotherapy for Breast

Cancer, London Hospital,
1917

Biological Effects of RT
1.

RT causes ionization in tissue

2.

This forms free radicals

3.

Free radicals - interact and damage DNA

4.

During mitosis, abnormal DNA unable to

replicate, causing cell death

Multidisciplinary Cancer Management Course

Mechanism of Action
X-rays and gamma-rays
production of fast
electrons most of
the energy absorbed
by H2O free radicals
Mechanisms of
radiation therapyrelated cell death
Prevention of mitosis
Apoptosis

Multidisciplinary Cancer Management Course

Mechanism of Action (cont.)

DNA is a critical target
for radiation therapyinduced damage in the
cell
DNA is the target for
mitotic death
Double-stranded
break
Cells have systems to
repair radiation therapyinduced damage

Types of cellular damage

Altered metabolism
and function

repair

Cell death

Reproductive Mutation
cell death

Why treatment
takes
so long ?

Multidisciplinary Cancer Management Course

Aims of Radiation Oncology

Deliver a precise dose of radiation to a
defined tumor volume with as minimal
damage as possible to surrounding
normal tissues
Eradication of the tumor
Improvement of quality of life
Prolongation of survival

Treatment
Radiotherapy

is commonly given
as a series of equal sized doses.

Usually

5 fractions / week for

several weeks.

This

is FRACTIONATION

Fractionation: A Basic
Radiobiologic Principle

Fractionation, or dividing the total dose

into small daily fractions over several
weeks, takes advantage of differential
repair abilities of normal and malignant
tissues

Fractionation spares normal tissue

through repair and repopulation while
increasing damage to tumor cells
through redistribution and
reoxygenation

Therapeutic ratio

The aim of radiotherapy is to deliver enough

radiation to the tumour to destroy it without
irradiating normal tissue to a dose that will
lead to serious complications (morbidity).

The therapeutic ratio generally refers to the

ratio of Tumor control and Normal tissue
complications at a specified dose level;
however, it is also often defined as the ratio of
doses at a specified level of response (usually
0.05) for normal tissue.

Therapeutic Ratio

Effect

Tumor control

Tumor Dose

Late normal tissue damage

Fractionation
Fractionation

amplifies the therapeutic

ratio between normal and neoplastic
tissues for several reasons:
Repair
Repopulation
Redistribution
Re-oxygenation
Radiosensitivity

Repair
Repair

of DNA is completed over a

few hours but the extent of repair is
not equal in all tissues.
Slowly responding tissues are
capable of greater repair.
Differences are amplified
exponentially and thus allow for
tumor sterilization without harm to
normal tissues.

Repopulation
Repopulation

in proliferative tissues
takes place as a homeostatic response
to injury

Repopulation

allows acutely responding

tissues (mucosa) to tolerate increased
doses to the tumor

The

rate of repopulation in tumors is less

than that of normal tissues and this

Redistribution

Cells show large changes in radiosensitivity

as they progress through the cell cycle
===> synchronized cell population

This self sensitization is not a feature of

normal tissue that show only late effects
whose cells are essentially static

The redistribution that takes place between

successive fractions enhances the differential
effects between the critical late responding
normal tissues and tumors.

Effect of radiation on cell Cell

kinetics

Radiosensitivity of cell in
cell cycle
Relative
Survivability

G1

G2

G1

Relative survivability of cells irradiated in different phases of

the cell cycle. Synchronised cells in late G2 and in mitosis (M)
showed greatest sensitivity to cell killing.

Re-Oxygenation
Tumors

outstrip
their blood supply
==> Hypoxic cells

Hypoxic

cells are
2-3 times more
radio resistant

Fractionation

kills
oxygenated cells
and hence
increases blood

Dosage
The

dosage: The term used to

measure in units the amount of
radiation received is the Gray.
1 Gray = 100 cGY

Multidisciplinary Cancer Management Course

Radiation Oncology Modalities

External

beam
Cobalt-60
Linear accelerator
hotons
Electrons

Neutron beam therapy

Proton beam therapy

Brachytherapy
Intracavitary (Cesium137, Iridium-192)
Low-dose rate
High-dose rate

Interstitial
Temporary (Iridium-192)
Permanent (Iodine-125,
Palladium-103, Gold198)

CLINICAL ASPECT OF XRT

Role of XRT

50 - 60% of all Ca will require RT

2/3 of these for curative intent

Clinical Uses for Radiation

Therapy

Therapeutic radiation serves

two major functions

To cure cancer

External beam
radiation treatments
are usually scheduled
five days a week and
continue for one to
ten weeks

Destroy tumors that have not

spread
Kill residual microscopic disease
left after surgery or
chemotherapy

To reduce or palliate
symptoms

Shrink tumors affecting quality of

life, e.g., a lung tumor causing
shortness of breath
Alleviate pain or neurologic

Curative Role :

Head and Neck Ca

Ca Cervix
Anal and skin Ca
Prostate Ca
Bladder Ca
Early Lung Ca
Early Ca Esophagus
Seminoma
Hodgkins disease and NHL
Medulloblastoma and some brain
tumors

Palliative Modality

Pain

bleeding

compression of vital organs

brain metastases

large masses

The clinical side: workflow in Radiation Oncology

Multidisciplinary decision:
Treatment protocol

Treatment Preparation:
- Contact MD-patient
- Simulation (imaging)
- Tumour delineation*
- 3D Planning

Treatment:

Prostaat AP
(1-1-2002 tot 1-1-2003)
60

- Irradiation
- QA set-up (Imaging)

40
Aantal

- QA dose

50

30

meetresultaat

20

10

0
Afwijking (% )

Follow-up

Types of External Beam

Radiation Therapy

Two-dimensional radiation therapy

Three-dimensional conformal radiation
therapy (3-D CRT)
Intensity modulated radiation therapy
(IMRT)
Image Guided Radiation Therapy
(IGRT)
Intraoperative Radiation Therapy
(IORT)
Stereotactic Radiotherapy (SRS/SBRT)
Particle Beam Therapy

Three-Dimensional
Conformal Radiation
Therapy (3-D CRT)

Uses CT, PET or MRI

scans to create a 3-D
picture of the tumor and
surrounding anatomy

Improved precision,
decreased normal tissue
damage

Role of imaging for target

definition

CT:

MRI:

Extra cervical spread

Design of lateral
portals

PET:

Treatment planning
Nodal assessment

Lymph node
involvement

US/TRUS

Multidisciplinary Cancer Management Course

Three-Dimensional Reconstruction of
Gross Tumor Volume and Adjacent
Surrounding Organs: Cervical Cancer

Multidisciplinary Cancer Management Course

Three-Dimensional Treatment
Planning in pancreatic cancer

Multidisciplinary Cancer Management Course

3-D

2-D

IMRT

Intensity Modulated
Radiation Therapy (IMRT)

A highly sophisticated form

of 3-D CRT allowing
radiation to be shaped more
exactly to fit the tumor

Radiation is broken into many

beamlets, the intensity of
each can be adjusted
individually

IMRT allows higher doses of

radition to be delivered to
the tumor while sparing
more healthy surrounding
tissue

Multidisciplinary Cancer Management Course

Intensity-Modulated Radiation Therapy

Evolved from three-dimensional conformal
radiation therapy
Allows tightly conformal dose distribution in
complex treatment situation

Irregularly shaped
Near critical structures
Good immobilization and repositioning possible
Higher than conventional doses indicated

Multidisciplinary Cancer Management Course

Therapeutic Window: Effect

of Reducing Volume of Normal Tissue
PROBABILITY (%)

tumor control

toxicity

90

50

V1

V2

V2 < V1
DOSE OF RADIATION

Image Guidance

For patients treated with 3-D

or IMRT

Physicians use frequent

imaging of the tumor, bony
anatomy or implanted fiducial
markers for daily set-up
accuracy

Fiducial markers in prostate

visualized and aligned

Imaging performed using

CT scans, high quality Xrays, MRI or ultrasound
Motion of tumors can be
tracked to maximize tumor
coverage and minimize
dose to normal tissues

Stereotactic Radiosurgery
(SRS)

SRS is a specialized type of

external beam radiation
that uses focused radiation
beams targeting a welldefined tumor

SRS relies on detailed

imaging, 3-D treatment
planning and complex
immobilization for precise
treatment set-up to deliver
the dose with extreme
accuracy
Used on the brain or spine
Typically delivered in a single
treatment or fraction

Stereotactic Body
Radiotherapy (SBRT)

SBRT refers to stereotactic

radiation treatments in 1-5
fractions on specialized
linear accelerators

Uses sophisticated imaging,

treatment planning and
immobilization techniques

Respiratory gating may be

necessary for motions
management, e.g., lung tumors

SBRT is used for a number of

sites: spine, lung, liver, brain,
adrenals, pancreas
Data maturing for sites such
as prostate

Multidisciplinary Cancer Management Course

Stereotactic Body Radiation Therapy

in Non-Small Cell Lung Cancer

Multidisciplinary Cancer Management Course

Liver Metastasis from Colon Cancer

Script 1,200 cGy per fraction to 80%

dose: isodose for 3 fractions (total = 3,600 cGy)

Brachytherapy

Radium Needles Implants

Multidisciplinary Cancer Management Course

High-Dose-Rate Intracavitary
Brachytherapy: Uterine Cancer

Endocavitary Brachytherapy:
EsophagealCancer

Multidisciplinary Cancer Management Course

Endocavitary Brachytherapy:
Bile Duct Cancer

Multidisciplinary Cancer Management Course

Vaginal Cancer: Treatment Approach

Multidisciplinary Cancer Management Course

Permanent Interstitial Implant

Prostate Cancer

High-Dose-Rate Interstitial Brachytherapy:

Prostate Cancer

Brachytherapy catheters
hook-up and treatment.

Oral brachytherapy

Complications
Acute Tissue Reactions
Late Tissue Reactions

Radiation Therapy Basics

The delivery of external beam

radiation treatments is painless
and usually scheduled five
days a week for one to ten
weeks

The effects of radiation therapy

are cumulative with most
significant side effects
occurring near the end of the
treatment course.

Side effects usually resolve over

the course of a few weeks
There is a slight risk that radiation
may cause a secondary cancer
many years after treatment, but
the risk is outweighed by the
potential for curative treatment

{Sabin Motwani
will send us
image of mild
skin redness after
RT in a treatment
field}.
Example of erythroderma
after several weeks of
radiotherapy with moist
desquamation
Source:
sarahscancerjourney.blogsp
ot.com

Acute Toxicity
Time

onset depends on cell cycling

time
Mucosal reactions 2nd week of XRT
Skin reactions 5th week
Generally subside several weeks after
completion of treatment
Epithelial surfaces generally heal
within 20 to 40 days from stoppage of
treatment)

Common Radiation Side

Effects
Side effects during the treatment vary
depending on site of the treatment and
affect the tissues in radiation field:

Unlike the systemic side effects

from chemotherapy, radiation
therapy usually only impacts the
area that received radiation

Breast swelling, skin redness

Abdomen nausea, vomiting, diarrhea
Chest cough, shortness of breath,
esophogeal irritation
Head and neck taste alterations, dry
mouth, mucositis, skin redness
Brain hair loss, scalp redness
Pelvis diarrhea, cramping, urinary
frequency, vaginal irritation
Prostate impotence, urinary symptoms,
diarrhea
Fatigue is often seen when large areas are
irradiated

Modern radiation therapy techniques have

Common Radiation Side

Effects
Side effects during the treatment vary
depending on site of the treatment and
affect the tissues in radiation field:

Unlike the systemic side effects from

chemotherapy, radiation therapy
usually only impacts the area that
received radiation

Breast swelling, skin redness

Abdomen nausea, vomiting, diarrhea
Chest cough, shortness of breath,
esophogeal irritation
Head and neck taste alterations, dry
mouth, mucositis, skin redness
Brain hair loss, scalp redness
Pelvis diarrhea, cramping, urinary
frequency, vaginal irritation
Prostate impotence, urinary symptoms,
diarrhea
Fatigue is often seen when large areas are
irradiated

Modern radiation therapy techniques have

During RT

Module III

- 63

2 Weeks post RT

1 Month Post RT

scar

2 months Post RT

scar

Acute Toxicity
Mucositis

intensity-limiting side
effect for aggressive schedules
Radiation enteritis: cramps, diarrhea

Complications

Acute mucositis 5th week

after radiation for base of
the tongue squamous cell
carcinoma

Oral candidiasis in a patient

with marked xerostomia

Late Toxicity
Injury

tends to be permanent
Develop within months to years
Xerostomia, dental caries, fibrosis,
soft-tissue necrosis, nerve tissue
damage
Most common xerostomia in H&N
cancers

Oral Complications

Xerostomia radiotherapy
Damage to the
salivary glands
Complications
anorexia, weight
loss, dental caries,
sub mucosal fibrosis,
osteo-radionecrosis
Dental caries

Osteoradionecrosis
Radiation

induced
osteonecrosis
of the mandible

Osteonecrosis: Floor of Mouth

Tumor

Two years after radiotherapy

Three years after

radiotherapy

Late Toxicity

Fibrosis

Serious problem, total

dose limiting factor
Woody skin texture
most severe
Large daily fractions
increase risk

Ocular cataracts,
optic neuropathy,
retinopathy

Otologic serous otitis

media, nasopharynx,

Late Toxicity
Central

Devastating to patients
Myelopathy (30 Gy in 25 fractions)

Electric shock from cervical spine flexion

(Lhermitte sign)

Transverse myelitis (50 to 60 Gy)

Somnolence syndrome (months after
therapy)

Nervous System

Lethargy, nausea, headache, CN palsies, ataxia

Self-limiting, transient

Brain necrosis (65 to 70 Gy) permanent

Radiation Necrosis

Transverse Myelitis

Late Toxicity
GI

Radiation enteritis (45 Gy in 25

fractions)

Diarrhea, bleeding cramps, fibrosis, strictures,

perforations

Radiation Proctitis (50 to 60 Gy)

GU Tract

Bleeding, mucus discharge, pain ulceration

Radiation cystitis (70 Gy)

Hematuria, diminished bladder capacity, dribbling

Results of RT
At Diagnosis

At end of 6 weeks RT

Radiation Therapy Results

Squamous cell carcinoma

One month postradiotherapy

Radiation Therapy Results

Results of Treatment
Pre-RT

Post-RT

Brain Mets
Before RT

After RT

Summary
Radiation

therapy is a well
established modality for the
treatment of numerous
malignancies
Radiation oncologists are
specialists trained to treat cancer
with a variety of forms of radiation
Treatment delivery is safe, quick
and painless

Radiotherapy

Thank you