Radiotherapyfundamental principles and

methods
Dr. Tatiana Hadjieva, MD, PhD
Professor ,
University Radiotherapy Clinic
Medical University Sofia

Radiotherapy
=

Radiation
Oncology

First X-rays photo,

demonstrated at the
Roenten lecture at the
Society of medical physics
Wurzburg,
22 .12.1895

History
Publication facsimile A new beam
type preliminary report 28.12.1895

Boom of letters with over 1000

financial announcements after the
first week

First X ray treatment in Oncology

29.1.1896 .
Dr. Emil Groube,
Chicago,
I radiation for
breast cancer
18 days 1
hour
treatment

History of Radiotherapy

Before
treatment

40 years later

4 1899 Tom Stenbeck, Stockholm

I radical irradiation course for skin cancer-
basocellulare nasi 99 fractions

Radiotherapy fundamentals

Clinical ad scientific discipline

Mainly treatment of neoplasms ( and nonmalignant disease) using

Ionizing radiation alone or in combination

with other modalities

Exploration
of
radiobiological
physical basis of RT

Education of medical and stomatological

students and post-graduated fellows

and

Types of radiotherapy
According to

Radiotherapy aim
Curative
Palliative
Place of the radioactive
source toward body
External beam RT
Curietherapy
( Brachitherapy)

Special categories
RT

Brachitherapy sealed
sources

Intersitial

Intracavitary

Non sealed
radionucleids
metabolic BT

Radiotherapy goal
Curative radiotherapy
Goal

Organ at risk

To achieve
Total tumour control
Quality of life

Radiation
beams

Target
tumour

Probability of long-term control with

undesirable but acceptable side effects
Application of precisely defined and

measured dose
in the
Accurately determined tumour volume

with

Minimum normal tissue morbidity

Patient

Palliative radiotherapy
Aim
No hope of survival for
extended period
Provides

Effective palliation or
prevention of symptoms
related to tumour ( pain,
impaired function or bone
integrity )

The dose applied are 75%

lower

Quality of life minimal

radiation morbidity

Types of radiotherapy
According to

Radiotherapy aim
Currative
Palliative
Place of the radioactive
source toward human
body

External beam RT

Curietherapy

( Brachitherapy)

Special categories
RT

Kind of radioactive source

Brachitherapy sealed
sources

Intersitial

Intracavitary

Non sealed radionucleds

metabolic BT

Prototype of external beam therapy

X- ray tube

Prototype of the first gamma ray facility external beam therapy

226- Ra

Modern radiotherapy

1952 -1970 USA high energy X ray generators

circular and linear accelerators LINACS
End of 60-s teleradiotherapy wide distribution
with a leading role USA, England and France

Kilovoltage X ray therapy machine

Cobalt 60 tellegammatherapy

Linac + electrons cone

Electron
applicator

Radiotherapy initial hopes

and disappointments

Anri Becquerel Pierre

Curie radium produced
skin erythema
Pierre Curie first
volunteer examining
skin reactions: from
skin erythema
proceeding to moist
desquamation of the
skin and recover
process.

Massive one-time
treatment

Tumour control

Recurrence

Radiation necrosis Radiation death

Fractionation in radiotherapy

Massive one-time

French school XX century 20-s

treatment

Claude Regaud , Henri Coutard

Tumour control

Recurrence

Same anti-tumour effect

Radiation necrosis -

Normal tissue preservation

Radiation death

Smaller daily doses

Types of radiotherapy
According to

Radiotherapy aim
Currative
Palliative
Place of the radioactive
source toward human
body

External beam RT

Curietherapy

( Brachitherapy)

Special categories
RT

Kind of radioactive source

Brachitherapy sealed
sources

Intersitial

Intracavitary

Non sealed radionucleds

metabolic BT

History of Curietherapy

26 december 1898
- 226 Radium - Maria
Sclodowska & Pierre Curie Curietherapy on the
animals

1903. Nobel price for natural radioactivity

Becquerel & Curie

Interstitial Curie therapy 1901 Danlos & Bloch,

Paris, radium tubes into the tumour ;- Treatment
duration -hours and days

Intracavitary Curietherapy - 1903 Doederlein,

Tubingen; Clieves, New York for Ca of uteribe
cervix.

Skin moulds - 1901

Types of radiotherapy
According to

Radiotherapy aim
Currative
Palliative
Place of the
radioactive source
toward body
External beam RT
Curietherapy
( Brachitherapy)

Brachitherapy
sealed sources

Intersitial

Intracavitary

Non sealed
radionucleids
metabolic BT

Special
categories RT

Curietherapy
Brachytherapy

Brachy Short distanceplacing sealed RA source

close to or in the contact
with target tissue
Different techniques for
RAS implantation
Surgical methods (
interstitial,
intracavitary,
intraluminal,mould
CTH
)
Temporary or permanent
implant
High dose rate HDR ; Low
dose rate LDR for short
or for long time

Interstitial Curietherapy
Stevenson V, Dublin, British Med. Journal, 1914
226 Ra; 7 weeks, out-patient clinic

Radioactive sources
External beam RT

History
of XX c

Natural radioactivity
226 Ra

20-s

Artificial radioactivity
137 Cs ; 60 Co

50-s

Curietherapy
Ra
needles
60

Co

Non
sealed RA
Nuclear
Medicine

131J

Modern
NM

182

Ra
tubes

Ra
mould

137Cs

192 Ir

198Au

90Yt

32 P

252

Cf

183 Pal
145 Sa

HDR Afterloading Machine

Iridium-19

High dose rate BRTH of floor of

the mouth

Interstitial curiethetapy

192-Ir wire
Breast Ca

Cervix cancer

Interstitial curiethetapy for

prostate cancer
with permanent implant
125 I,103 Pd , doses 120-140 Gy

Avangard techniques
Interstitial curiethetapy for prostate cancer
with permanent implant
125 I,103 Pd

PC planning programme base on sonograpgy image

PC planning programme base on CT image

Interstitial curiethetapy for prostate

cancer
with permanent implant 125 I

120
Volume (%)

100
80
60
40
20
0
0

20

40
Dose (Gy)

60

80

Types of radiotherapy
According to

Radiotherapy aim
Currative
Palliative
Place of the
radioactive source
toward body
External beam RT
Curietherapy
( Brachitherapy)

Brachitherapy
sealed sources

Intersitial

Intracavitary

Non sealed
radionucleds
metabolic BT

Special categories RT

Intra-operative RT
with accelerated electrons from LINAC
radioresistant and relatively RR tumours

Pancreatic cancer
Stomach cancer
Rectal cancer
Retro-peritoneal
sarcomas
Gynecological
malignancies

Intra-operative RT

Radiotherapy essence
Local treatment method 90% of the cases
having
similar to the surgery results,but
avoids mutilating action of the surgery

Radiotherapy essence
In 10% - alternative to the systemic drug
treatment
131I

Metabolic
curietherapy
for
dissiminated
thyroid
cancer

Radiotherapy essence
In 10% - alternative to the systemic pain
medication in disseminated malignomas

89

Sr,

222Re,
145

Sa

Radiotherapy essence
In 10% - alternative to the systemic drug
treatment
Whole body and half
body irradiation

Lymphomas and
Leucosis

Bone marrow
transplantation

Time -scale of RT acting with the

biological matter

DNA -target

Biological stage

Target - DNA molecule single and double

hit lesions
Reparation of sublethal damages
Tumour cell death lost of reproduction
capability
Mitotic cell death death during mitosis
Interface cell death rare process
Normal tissue cell damage death of stem
cells, endothelial cell death of the vessel
into the connective tissue

Repair

sublethal damages , one break and doubled

break of DNA

Rules of the game RT

Narrow therapeutic ratio ( Gain) requires precise
planning !!!

Maximal Probability of tumour contol

with minimal
(acceptable) frequency of
complications
Type of the tumour and normal
tissue
Dose effect curve 2Gy/fraction

Tumour radiosensitivity

High

radiosensitive

tumours

malignant

lymphomas,

seminoma,

dissgerminomas

Moderately radiosensitive tumours epithelial neoplasmas carcinomas

SCC (G1-G3 Ca cutis, colli uteri, ORL; adenocarcinomas

Radioresitant

tumours- mesenhymomas- bone and soft tissue sarcomas,

some epithelial blastomas (adenosquamous or mucoepidermoid type)

Reality

Normal tissue radiosensitivity

Early effects during and up to 3 m after RT. Reversible

symptoms, do not limit the dose
Late effects
Intrinsic radiosensitivity of the tissue

Tissue with low tolerance to radiation hemopoetic

sys\tem, reproductive organs, lens, spinal cord, liver, lung
Tissue with high tolerance to radiation- bones, muscles,
nerves

Volume of the irradiated normal tissue : whole, parts

dose-volume histograms
Tumour response modifiers chemotherapy (Cisplatin
nephrotoxicity, Adriablastin-cardiotoxicity

Early reactions

Reversible, temporary

1 slight function
changes 10%;
2- moderate 25%
3- strong 50%
4- severe life
treatening75%
5- fatal 100%

Late reactions

After 6 m to 5 years

Non reversible

Higher in hypofractionation

Lower in hyperfractionation

Late radiation side effects in RT

of breast

Extension of therapeutic window

Physical and technical approach

Extension of the therapeutic window

1. Physical and technical approach
Implementation of radiations with different energy therefore
with different tissue penetration

Extension of the therapeutic window

1. Physical and technological approach
Radiation with different LET- different RBE

RBE

Innovations

56

3 D Conformal

IMRT

Flat dose profile

Intensity Modulated
Dose

Extension of the therapeutic window

2. Radiobiological approach
Modifiers of the tumour
response

RADIOSENSITISERS

Hypoxic cells inhibitors

Hyperfractionated RT

Accelerated RT

Chemo-radiation

Hyperthermia and RT
Augmentation of the normal tissue tolerance to
radiation

Normal tissue radioprotectors

Extension of the therapeutic window

2. Radiobiological approach
Modifiers of the tumour
response

Hyperfractionated RT

Chemo-radiation

Hyperthermia and RT

Augmentation of the normal tissue tolerance to

radiation

Normal tissue radioprotectors

Hypoxic cells sensitization

Extension of the therapeutic window

2. Radiobiological approach
Modifiers of the tumour
response

Hyperfractionated RT

Chemo-radiation

Augmentation of the normal tissue tolerance to

radiation

Normal tissue radioprotectors

Fractionation effect

Large fractions
palliation

Small fractions
hyperfractonation
bigger effect

Extension of the therapeutic window

2. Radiobiological approach
Modifiers of the tumour
response

Chemo-radiation

Augmentation of the normal tissue tolerance to

radiation

Normal tissue radioprotectors

Mechanism of action
DNA damage Increasing
Preventing radiation repair
Overcoming hypoxia-mediated
radioresistance - Reoxygenation after
tumor shrinkage
Preventing repopulation
Cytokinetic cooperation and
synchronization

Cervix cancer

GBM

ERBITUX + RT
Locally advanced H&N tumours

Overall survival (%)

100
80
60
40
20

29.3

49.0

0
0

10

20

30

40

50

Months

Bonner et al. N Engl J Med 2006; 354:567-78.

60

70

Questions ???