Radioisotopes and dose rates used for brachytherapy

Moderator : Dr. A. S.Oinam
Presented By : Dr. Subhash Thakur
3rd year JR, Department of Radiotherapy
PGIMER, Chandigarh, India
Presented On : 18/08/2018a
Radioisotopes and Dose Rates
Used For Brachytherapy

RADIOISOTOPES
 An unstable form of element that emit radiation to
transform into stable form
 These are mostly artificially produced in research
reactor or accelerators by exposing the target material
to particles such as neutron or protons.eg.
 Co59 + neutron = Co60

Brachytherapy
 Definition:
It is a method of treatment in which sealed
radioactive source are used to deliver
radiation at a short distance by various
methods.
 Brachytherapy developed largely through the use
of sealed radium and radon sources.
 In the 1950s, alternative artificially produced
nuclides became available.
 Gradually radium and radon were replaced with
137Cs, 192Ir, 60Co, 198Au, and 125I sources

Properties of brachytherapy
sources and radionucleides
 Clinical utility of any radionuclide depends on
 Half life
 Radiation output per unit activity
 Specific activity (Ci/gm)
 Photon energy
 Whereas
 Methods of producing radionuclide, its physical
and chemical properties determine its cost
effectiveness and toxicity

Some Terms which will be used
frequently :
 Radioisotopes
 Brachytherapy
 Activity
 Half life
 Specific activity
 Air Kerma
 Reference air Kerma rate
 Exposure rate
 Exposure rate constant

IMPORTANT DEFINITIONS
Radioactivity:
No. of disintegrations per unit time (sec ,min,hrs.)
expressed in curies
• 1 curie (ci)=3.7x1010 disintegration /sec
• 1 Bequerel (Bq) =1 disintegration / sec.
(S.I.unit)
Half life(T1/2):
“The time required for a radioactive isotope to
lose half of its original activity .”
Half Value layer (HVL):
The thickness of the specified substance that
when introduced into the path of radiation
coming from source, reduces the exposure rate

 Kerma (dEtr/dm)
 Where dEtr is the sum of initial kinetic energy
of all the charged ionizing particles released by
uncharged particles in a material of mass dm.
 Unit : J/Kg
 Air Kerma Strength
 Air kerma strength is defined the product of air
kerma rate in free space and the square of
distance of the calibration point for the source
center along the perpendicular bisector.
 Unit : J m2/kg-hr

 REFERENCE AIR KERMA RATE (RAKR)
“the kerma rate to air, in air, at a reference distance of 1
m,corrected for air attenuation and scattering”.
µGy/ h at 1 m LDR
µGy /s at 1 m and mGy /h at 1 m HDR

TOTAL REFERENCE AIR KERMA
 There are steep dose gradients in the region of the
sources, so that specifying a treatment in terms of
the dose at a point is not recommended.
 TRAK IS THE SUM OF THE PRODUCTS OF RAKR
AND THE DURATION OF THE APPLICATION FOR
EACH SOURCE
 independent of the source geometry and
proportional to the integral dose to the patient.
 compare treatments within one centre or between
different centres and to explain possible differences
in the delivered dose or in the treatment volume
dimensions.
 useful index for radiation protection of personnel

Types of Brachytherapy
Brachytherapy
Types of implant
1. Interstitial
2. Intracavitary
3. Intraluminal
4. Intravascular
5. Surface Mould
Dose rate of irradiation
1. LOW DOSE RATE (LDR): 0.4-2 Gy/hr
2. MEDIUM DOSE RATE (MDR): 2-12
Gy/hr
3. HIGH DOSE RATE (HDR): > 12 Gy/hr
Treatment Duration
1. TEMPORARY
2. PERMANENT
Source Loading
1. Preloading
2. Afterloading

Radioisotopes in
Brachytherapy
Radium
1. Discovered by Madam
Curie in 1898
2. Naturally occuring
radionucleide
3. Complex decay
scheme
4. 1st used in 1906 in
clinics, led to Radiation
Necrosis due to
intense beta ray dose
from the Radium
5. 1920 : successful
filtration of the beta
rays was achieved

Radium
 Cascade of transformation of one daughter product
to another ending with stable isotope of Lead206

RADIUM-226
88Ra226 →
86Rn222 + 4He2
H
1. Gamma Energy 0.184 -2.54 MeV (avg. energy -0.83
MeV)
2. Beta Energy 0.07 - 3.25 MeV
3. Half life 1600 years
4. Specific activity 0.97 Ci /gm
5. HVL 12mm of Pb.
6. Exposure Rate Const. 8.25 Rcm2/mg-hr
7. Spectrum wide range of 49 gamma rays
8. Encapsulation 0.5 mm Platinum.
9. Physical form Tubes, Needles

 Radium sources are
specified by (a) active
length, the distance
between the ends of the
radioactive material;
 (b) physical length, the
distance between the
actual ends of the source;
 (c)activity or strength of
source, milligrams of
radium content;
 (d) filtration, transverse
thickness of the capsule
wall, usually expressed in
terms of millimeters of
platinum.

WHY RADIUM IS NOT USED NOW A
DAYS
 Daughter products, RADON is an alpha emitter.
 It is a Gas which is soluble in tissue.
 Not easily detected by a visual check
 can escape through hairline crack in the radium
capsule
 Radium and its daughter products may become
deposited more or less permanently in the bone if
ruptured within patients body
 Radiation protection for these sources requires large
thicknesses of lead, which can cause problems when it
comes to:
 Transporting sources in heavy containers.
 Using very heavy protective screens around the
patient.
 The need for a heavy rectal shield in applicators used
for gynecological treatment.
 Sources of higher activity are bulky and not suitable for

Properties of the Ideal
Brachytherapy Source.
 Ideal radionuclide should produce a single gamma ray
spectrum with energy of around 0.5 MeV.
 acceptable half life
 Cheap and easily produced
 Preferably solid
 Stable solid decay products
 High specific activity
 Closest to the ideal radionuclide for LDR at present time is
Cesium 137

Radium Substitutes
 The first sources to be used as alternatives to
radium were
 Cobalt-60,
 Gold-198,
 Cesium-137 and
 Iridium-192.

Cesium
 discovered in the late 1930s by Glenn Seaborg and
Margaret Melhase
Product of nuclear fission
• Gamma Energy - 0.662 MeV.
• Beta Energy - 0.5-1.17 MeV
• Half life - 30 yrs
• Specific activity - 10 Ci/gm.
• HVL - 5.5 mm of Pb
• Exposure Rate Const - 3.26 R cm 2/mCi-hr.
• Spectrum- Single Gamma ray with beta rays
• Encapsulation - 0.5 mm of Pt.
• Physical form- Needles, microspheres, powder
• 2% annual reduction in source activity occurs

Source specification
 insoluble powders or ceramic microspheres,
labeled with 137Cs, and doubly encapsulated in
stainless steel needles and tubes.

Cobalt 60
Properties of Cobalt 60
 Production : by neutron activation of the stable
isotope cobalt-59
 Half Life : 5.27 years
 Decay Scheme : 27Co60
28 Ni60 + -1 β + γ
 Beta energies : 0.318 MeV
 Photon energies : 1.17 MeV and 1.33 MeV
 Beta filtration : typical source wall thickness
 Half value layer in lead : 10 mm

Form of source Co60
 Cobalt brachytherapy sources are usually
fabricated in the form of needle
 An alloy wire composed of 45% cobalt & 55%
nickel, so called cobanic
 Encapsulated in a sheath of platinum of stainless
steel
 Because cobalt tends to be corrosive, it is usually
nickel plated;
 encapsulation with 0.1 mm to 0.2 mm platinum-
equivalent is necessary to filter the b-particles.

Iridium192
 Used for HDR brachytherapy
Properties of Iridium192
 Production : by neutron activation of the stable
isotope Iridium191
 Half Life : 73.83 days
 Decay Scheme : 77Ir192
78Pt192 + -1e0
+ γ
 Beta energies : 0.079-0.672 MeV
 Photon energies : 0.2 – 1.06 MeV
 Beta filtration : 0.1 Platinum
 Half value layer in lead : 4.5 mm

 Most common form of source : wire in 1 m length
coils, wire consists of an active iridio platinum
core, 0.1 mm thick, encased in a sheath of
platinum, 0.1 mm thick

 iridium seeds
 seeds are 3 mm long and
0.5 mm in diameter
 Made up of 30% Ir + 70%
Pt surrounded by 0.2 mm
thick stainless wall
 pure iridium is very hard
and brittle, and is difficult
to fabricate.

GOLD198
Au 197 + 0
1n → Au198 +Υ
• Gamma Energy: 0.412 MeV
• Beta Energy 0.69 MeV.
• Half Life 2.7 days
• HVL : 2.5 mm Pb
• Exposure rate const. : 2.38 Rcm2/mCi–
hr
• Physical form: seed
• Used for permanent implant
• Gold seeds of size 2.5 mm long & 0.8 mm
diameter

Advantages of Gold over
others
 The average photon energy of gold is 0.406 Mev,
making the radiation protection requirements
much easier and cheaper to implant than those of
Ra226 , Rn, Co or Cs
 Very short half life so useful for permanent
implants

IODINE125
• Xe124 +
0n1 → Xe125 → I 125
• Allen Reid and Albert keston discovered I125 in 1946
• Gamma Energy - 0.028 MeV (avg).
• Beta Energy- None
• Half life - 59.4days
• Specific activity - 1739 Ci/gm
• HVL - 0.025 mm OF Pb
• Spectrum - Three gamma rays
• Exposure rate const. - 1.46 Rcm2/mCi–hr
• Encapsulation - 0.5 mm titanium
• Physical form- seed
• Used for permanent interstitial implants.

125I decays by electron capture to an excited state of
125Te which decays to ground state releasing
35.5keV .
 IODINE FROM FM KHAN

 The high specific activity of I125 enables the
production of miniature sources sufficient activity
for use in both permanent and temporary
implants
 The main current application field of I125 is
permanent interstitial implant for prostate
cancer

Palladium103
46Pd102 + 0n1 →
46Pd103
• Gamma Energy : 0.021 MeV (avg)
• Beta Energy: None
• Half life : 17days
• Specific activity 7448 Ci/gm
• HVL : 0.008 mm of Pb
• Encapsulation : Titanium
• Exposure rate constant: 1.48 Rcm2/mCi–hr.
• 103Pd decays by electron capture (20-23 keV x
rays)

 Pd103 has been introduced as replacement for
I125 sources for permanent implant
 Its short half life of 17 days makes Pd103 only
appropriate for permanent implants
 Its short half life and high specific activity enables
dose delivery at initial dose rate higher than that
of I125
 This feature is beneficial when used for rapidly
proliferating tumors

Advantages of one over
another
 Cs over Radium
 Reduced amout of shielding is required and absence of
gaseous daughter product
 Cs over Cobalt
 Longer half life of 30.07 years compared with 5.27 years
of Co, which enables the clinical use of Cs source over a
long period of time
 Low production cost
 Smaller amount of shielding required
 Disadvantages of Cs
 Lowest specific activity, doesnot allow the production of
miniature sources of very high activity for HDR remote
controlled loading BT
 Thus appropriate only for LDR

 Cobalt over Cs
 Due to high specific activity, Co is appropriate for
fabrication of small high activity source
 Cobalt over Radium
 Cobalt wires can be bent to conform to the shape of
tumor
 No danger of leakages or breakages
 cobalt over iridium
 Half life of cobalt is much more than of iridium, hence it
need not to be replaced as frequently as iridium
 25 source exchanges are required for 192Ir for one
exchange of a 60Co source
 THOUGH INTEGRAL DOSE IS HIGHER IN CO60

Types of Brachytherapy……
 Depending on source loading pattern:
 Preloaded: inserting needles/tubes containing
radioactive material directly into the tumor
 After loaded: first, the non-radioactive tubes
inserted into tumor
 Manual: Ir192 wires, sources manipulated into applicator by
means of forceps & hand-held tools
 Computerized remote controlled after loaded: consists of
pneumatically or motor-driven source transport system

Preloading pattern
 Advantage:
 Loose & flexible system(can be inserted even
in distorted cervix)
 Excellent clinical result
 Cheap
 Long term results with least morbidity (due to
LDR)
 Disadvantages:
 Hasty application -Improper geometry in dose
distribution
 Loose system – high chance of slipping of
applicators – improper geometry
 Application needed special instruments to
maintain distance.
 Radiation hazard

After loading pattern
MANUAL AFTERLOADING
Advantages
1. Circumvents radiation protection problems of preloading
2. Allows better applicator placement and verification prior
to source placement.
3. Radiation hazard can be minimized in the OT / bystanders
as patient loaded in ward.
4. Advantages of preloading remain.
Disadvantages:
specialized applicators are required.

REMOTE AFTERLOADING
Advantages :
1. No radiation hazard
2. Accurate applicator placement
-ideal geometry maintained
-dose homogeneity achieved
-better dose distribution
3. Information on source positions available
4. Individualization & optimization of treatment possible
5. Higher precision , better control
6. Decreased treatment time- opd treatment possible
7. Chances of source loss nil .
Disadvantages :
1. costly

Different dose rates used for
brachytherapy
 treatment dose rates fall into these categories:
 Ultra LDR : 001 to 0.3 Gy/hr : dose rate used in
permanent implants with I125 and Pd103
 LDR : 0.4 to 2 Gy/hr, compatible with conventional
manual or automatic after loading technique
 MDR : 2 – 12 Gy/hr, can also be delivered by manual or
automatic afterloading, although the latter is far more
frequent
 HDR : >12 Gy/hr and only automatic afterloading can
be used because of the high source activity
 PDR : pulses of 1 to 3 Gy/hr, delivers the dose in a
large number of small fractions with short intervals
 Permanent Implants : deliver a high total dose (eg.

Sources for LDR intracavitary
brachytherapy
 Active length should be 1.3 to 1.5 cm
 Half Life should be 5 to 10 years working life
without variation in prescription dose rates
 Average photon energy : 60 to 100 keV
 Sources : Radium226 and Cesium137

Sources for permanent Interstitial
Brachytherapy
2 Basic approach
1. Classical LDR permanent brachytherapy
 Radon 222
 Au 198 seeds
 HALF LIFE : FEW DAYS
 High energy photons
 Patient must be confined to the hospital until the
source strength decays to safe level (10 days)

2. ULDR brachytherapy
 Larger lives but low energy emitters – Pd103 and I125
 Patients tissue or thin lead foils are sufficient to
limit exposure to negligible levels
 No need to hospitalize patients solely for radiation
protection
 During the implant procedure, decreased radiation
exposure to O.T. persons

Sources for HDR brachytherapy
 Uses high intensity source to deliver discrete
fractions ranging from 3 to 10 Gy
 A remote after loading device must be used
 Radio-nuclide with high specific activity (Ci/gm) is
needed so that treatment dose rates of at least 12
Gy/hr can be achieved.
 A miniature source no longer than 1 mm
diameter and 4 mm length with an exposure rate
of 1 R/sec at 1cm is required.

The radiobiology of
brachytherapy
 Brachy : not only short treatment distance but
also short treatment time
 Short overall treatment time, compared to EBRT
minimizes tumor repopulation in rapidly growing
tumors
 Short overall treatment time in brachytherapy are
likely to contribute significantly to clinical efficacy
for tumor sites like cervix, head and neck and
lung where long overall treatment time is
associated with reduced local control.

Radiobiology of the brachytherapy
and Dose Rate Effect
 The biological effects of radiotherapy depends on
 Dose distribution
 Treated volume
 Dose rate
 Fractionation and
 Treatment duration
 However these are of different importance in
determining the outcome of EBRT and of
brachytherapy

Radiobiological difference between
EBRT and brachytherapy
Factors EBRT Brachytherapy
Volume treated Large Very small
Dose homogenity -5 to +7% acceptable Very inhomogenous
Volume effect
relationship
>tolerance dose, not
well toleraable
Very high doses
tolerated well
Time dose factors Small daily fractions of
few seconds/minutes
Continuous deliver and
short treatment

Radiobiological Mechanisms
 The bilogical damage inflicted by irradiation of
human cells can be divided into three consecutive
steps :
 Physical phase : short initial phase, excitation of
electrons and ionisation, energy deposition phase
 Chemical Phase : ionized and excited atoms
interact directly or indirectly through the formation of
free radicals to the breakage of chemical bonds.
 Biological Phase : Longer phase, seconds to years,
cells reaction to inflicted chemical damage, specific
repair enzymes successfully repair the majority of
DNA lesions, however few may not repair and lead
to cell death.
 Early reactions
 Late reactions

Radiobiology – LDR Vs HDR
In terms of 4Rs
 Repair :
 LDR : allows time for sublethal damage repair in
normal tisues
 HDR : short treatment time prohibits this repair
 Reassortment :
 LDR : theoretic advantage of an improved result
 HDR : ---
 Only shown in vitro, but in vivo the effect of
reassortment has not been shown to give a true
advantage, possibly due to disruption of the
mechanism of cell cycle in cancer cells

 Repopulation
 LDR & PDR : probably prevents repopulation during
treatment
 HDR : short treatment time, so no issue of
repopulation
 Reoxygenation :
 2 types of hypoxia : chromic and transient
 LDR : transient hypoxia may correct during
treatment time
 HDR : not possible
 If brachytherapy is fractionated, tumor shrinkage
and re-oxygenation of areas of chroni hypoxia may
occur between insertions

Biophysical Modeling of
Brachytherapy
 In 1970s, before the diffrential response of early
and late responding tissues was understood, the
most widespread approach for designing
alternative fractionation schedule was Nominal
Standard dose equation (NSD)
 This equation was based on data from early
responding tissues and it didn’t account for
diffrential response to fraction size/dose rate of
early Vs Late effects

Linear Quadratic Model
 Distinguishes between early and late response
 Based on mechanistic notion and how cells are
killed by radiation
 After several decades of investigation and use,
LQ model have been well supported by clinical
experience and outcome date

Mechanistic basis of LQ model
 In this approach radiotherapeutic response is
primarily related to cell survival
 Cell killing is the dominant determinant of
radiotherapeutic response both for early and late
responding end points
 S(D)=e-αD-βD2

The Linear Quadratic Model
 Type A damages:
 Two Critical Target within a cell are
simultaneously damaged (hit) in a
single radiation interaction event
leading to cell death
 Type B damages:
 Two critical Target are damaged in
separate events, after which the
damaged sites interacts to produce
cell death
 Sub Lethal damages:
 The damages which are not so
effective for lethality of cell

Linear component related to single
track events,
Quadratic component related to
interaction of multi-track events
low dose radiation
 single track events predominate and
are far apart in time to produce any
significant double track events. The
curve is straight with no shoulder.
high dose radiation
 Multiple track events predominate.
Survival curve bends and becomes
curved.
dose
E
f
f
e
c
t
e-
e-
e-
Linear
EαD
Quadratic
EαD2
Basis of LQ model

The Linear Quadratic Model
Sparsely
ionizing
particles
Densely
ionizing
particles
βD2
αD
α/β
4 8 12
The expression for cell survival curve by this model
P (survival) or SF = exp (-αd -βd2)
2 components of cell killing:
Type A damages –
Cell Killing proportional to dose D
i.e E, effect proportional to D
Type B damages –
Cell Killing proportional to the
square of the dose D2.
i.e E, effect proportional to D2
Fowler (1989)

Low Dose Rate continuous
Brachytherapy
BED = D [1+g. R /(α/β)]
Where
Total dose = D = Dose Rate x Time = R.T
g = incomplete repair factor
g = (2/µT).[1-(1/µT).{1-exp(-µT)}]
and µ = 0.693/t1/2

Use of LQ model in Brachytherapy
quantifing the rationale for LDR
 Lowering the dose rate generally reduces
radiobilogical damage.
 For high dose rates, the dose reduction needed
to match the late effects is larger than the dose
reduction needed to match tumor control
 For any selected dose, increasing the dose rate
will increase late effects much more than it will
increase tumor control
 Conversly
 Decreasing dose rate will decrease late effects
much more than it will decrease tumor control
 Thus the therapeutic ratio increases as the dose
rate decreases

Use of LQ model in Brachytherapy
quantifing the rationale for LDR

High Dose Rate Brachytherapy
BED = D [1+d/(α/β)]
Where
D = n.d
n = no. of fractions
d = dose per fraction
DNA Repairs doesn’t occurred in a short period of time
of 10 min.
DNA repairs occurs between two successive fractions
only
Bur for well spaced fraction >>12 hrs, Correction for
incomplete Repairs is not required

Radiobiological principles involved in
moving from LDR to HDR
 This is the
case for
cervical
brachythera
py because
bladder and
rectum are
generally
some
significant
distance
from
implant

Brachytherapy for prostate cancer
Optimized dose protraction for
prostate cancer Brachytherapy
 Prostate tumors contain unusually small fractions
of cycling cells
Low α/β ratio
So they behave like late responding
normal tissues

Ca prostate : Brachytherapy
Radiobiological Basis
 α/β value for prostate cancer is similar to that for
surrounding late responding normal tissue, HDR could be
employed to match conventional fractionated regimen with
respect to tumor control and late sequalae while reducing
early urinary sequalae
 The α/β value for grade 2 or higher late rectal toxicity is
4.8 and this value is larger than of the prostate tumor α/β
ratio
 This suggests that HDR prostate Brachytherapy might
actually improve the therapeutic outcomes of prostate cancr
Brachytheapy

Advantages of HDR Over LDR
 Radiation Protection
 After loading
 No source preparation and transportation
 Only one source, there is no risk of losing a radioactive
source
 Short treatment times
 Less discomfort to patient
 Low risk of applicator movement during therapy
 Treat large no of patients
 Smaller diameter
 Reduced dilation of cetvix
 After loading
 Treatement dose optimization Possible

Disadvantages of HDR over LDR
 Radiobilogic
 Short treatment times : no sublethal damage repair,
no reassortment , redistribution and reoxygenation
 Limited experience
 The economic disadvantages
 Costly remote after loaders
 Required shielded room and more labor intensive
 Greater potential Risk
 High specific activity source used, if machine
malfunctions or there is calculation error, there is
very short time to detect and correct errors

Difference between LDR & HDR
brachytherapy treatment Planning
 HDR BT differs from LDR BT in 3 Ways :-
 1st difference : time Course
 The patient waits in the treatment position during the treatment
plan generation in HDR while
 Treatment plan generation performed with the patient
elsewhere in LDR
 2nd difference : quantities involved with dose calculation
 HDR : one source strength and many different dwell times
 LDR : input – source strength input by user, many sources
 In both case, dose calculation algorithm uses the
product of source strength and time at a given location
 3rd difference : role of quantities as input or output
 LDR : input : source strength and treatment duration
 HDR : reverse process start with dose pattern disingned and
working backward to the dwell time distributing necessary to
achieve that dose

Conversion from Low to High Dose
rate Brachytherapy
 Biggest questions : How many fractions to use
???
What dose/fraction ????
 Increasing the number of fractions increases
therapeutic ratio but each additional fraction
brings
 Costs for departmental resources and
 Inconvenience to patient
 So Most regimens use 5 or 6 #s if applicator
insertions involved and 8 -12 #s if applicators can
be left in place

Dose/# ????
 BEDHDR = BEDLDR
 calculate dose/#
 α/β : comes into play again
 If normal tissue toxicity is kept constant, α/β = 3
 If tumor cure is kept constant then α/β = 10 (or value
of particular type of tumor)
 If late complications are to be kept constant then α/β=2
 For intracavitary applications, normal tissue can be
kept away from the applicator, which allow us to
calculate dose based on equivalent tumor control

Experimental Results
 In vitro studies in sixties have shown that there is an
effect of dose rate on cell survival
 This effect differs with cell type
 The dose needed for 1% survival is roughly 1.5-3
times higher at 1 Gy/hr than it is at 1 Gy/min

Pulse Dose Rate (PDR)
 Combined physical advantage of HDR BT and
radiobiological advantage of LDR BT
 PDR BT was proposed and introduced as a
method to replace continuous LDR
 advantages of PDR brachytherapy compared with
LDR
 full radiation protection for caregivers
 no source preparation necessary
 no extensive source inventory, that is, only one
iridium-192 source per afterloader to be replaced
every 2 or 3 months

Compared with HDR
brachytherapy,
 PDR offers similar quality of dose distribution, and
similar treatment procedure and technical
verification, both being stepping source
technologies
Clinical results : Ca Cervix
source

 Most Studies
 Local control : 80-90%
 Overall survival : 4 yrs for 55% Patients
 Low incidence of gr II GI and GU late toxicity
 Disadvantage of PDR
 PDR delivered by stepping source might
behave more like HDR than LDR,
 Especially for tissues with a substantial
component of repair of very short T1/2

 1990-1992, 180 patients, St IIB-III
 All patients received EBRT@ 45 Gy/25#/4.5 weeks
 Divided into two arms
 Dose reduction arm (30%) – 2450 cGy to Pt A
 Dose reduction arm (12.5%) – 3060 cGy to Pt A
Vs
Previously treated IIB and III patients with LDR
(55-65 cGy/hr)

 MDR – 30 : results were comparable to LDR group, so
this group was retained
 MDR – 12.5 : discontinued due to increased morbidity
 So, decided to evaluate dose reduction between LDR
and MDR 30
 20% dose reduction was decided upon
 1st : MDR –30 2nd : MDR – 20

 Summary
 No statistical difference in local control between
LDR, MDR – 30, MDR -20 and MDR – 12.5
 However significant increase in late complications
with MDR -12.5 and higher trend seen with MDR -
20
 So its important to know the absolute dose received
by critical organs _ rectum and bladder

Clinical Results : LDR, MDR and
HDR brachytherapy
 Many clinical data have been accumulated over
the years in brachytherapy, but very few
randomized trials.
 These retrospective studies help to better
understand the biological background of
brachytherapy and devise the rules that can be
followed in clinical practise.

Results of HDR Vs LDR
Cervical Cancer
 LDR brachytherapy : experience > 100 years
 It is very important to critically analyze how the
results obtained with HDR Brachytherapy which
has a much shorter history to be compared with
LDR
 Meta Analysis By Orton et al, 56 institutes
 HDR : 17068 patients
 LDR : 5666 patients
 5 year survival date was available for 6639 HDR
patients and 3365 LDR patientsStage HDR LDR
I 82.7% 82.4%
II 66.6% 66.8%
III 47.2% 42.6%

 1999, Pertreit and Peracy, Literature review
 5619 patients with HDR treatment
 5 year pelvic control rates were 91% for stage I, 82% for
stage II and 71% for Stage III Patients
 5 years OS was similar to previous metaanalysis
 4 Randomised Studies by
 Shigematu et al
 Hareyama et al
 Patel et al and recently
 Teshima et al (2004) from thailand
 Which all of them have showed no difference in OS,
RFS or Pelvic Control and
 No statistical difference in complication rates for rectum,
bladder or small Bowel

 Total no of patients = 423, EBRT @ 45 Gy/20# f/b
 Two groups
 LDR group : 220 pts, dose rate @ 55cGy/hr to 90
cGy/hr, dose 35 Gy in single inserrtion with Cs137
 HDR group : 203 patients, radionucleide Co60 , dose
8.5 to 9.5 Gy to point A, 2 sessions

Results
 Patients with complete response after completion
of treatment : 90 % LDR Vs 89 % HDR
 Recurrence cervical : 9 % LDR Vs 10 % HDR
 Parametrial : 12% LDR Vs 11% HDR, at last f/u,
end of 5 yrs
 Overall control of disease : 72% with LDR and
72% with HDR

Ca Prostate
 Permanent implantation of I125 or Pd103 is the
most common type of prostate Brachytherapy
 However several centers have used HDR
Brachytherapy as a boost to EBRT with
encouraging results
 Potential advantage of HDR Brachytherapy in
prostate cancer is the theoretical consideration
that prostate cancer cells behave more like late
reacting tissues with low α/β , they should therefore
respond more favourably to HDR fractions rather than
LDR Brachytherapy

 Galalae et al, 611 patients treated at 3 institutes
with EBRT followed by Brachytherapy for
localized prostate cancer
 Five year biochemical control :
Low risk 96%
Intermediate risk 88%
High Risk 69%

Carcinoma Breast
 EBRT is standard radiation modality after
Lumpectomy
 Over the past decade, increasing use of
Brachytherapy as the sole modality of treatment
to decrease the treatment time from 6 weeks to
about 5 days
 ABS recommends : 34 Gy/10# to CTV when HDR
Brachytherapy is used as the sole modality
 Data on use of HDR as boost is very limited

 Polgar et al, 207 patients with stage I and stage II
patients
 All patients underwent BCS f/b WBRT
 Two arms :
 No further treatment
 Radiation boost by either 16 Gy of electrons or HDR
BT12 to 14 Gy
 52 patients with HDR Boost
 5 year local tumor control was 91.4%
 And excellent to good cosmesis : 88.5%
 Same results were obtained with electron
irradiation

Esophageal Carcinoma
 Brachytherapy is relatively simple to perform
because a single catheter is used for treatment
 Largest diameter applicator should be used to
minimize the mucosal dose relative to dose at
depth
 ABS recommends : HDR dose of 10 Gy in 2 #,
prescribed at 1cm from source to boost 50Gy of
EBRT

 Sur et al, 1992, 50 patients with squamous cell
carcinoma
 One arm : EBRT alone
 Another arm : EBRT + HDBT
(12Gy/2#)
 12 month survival 44% Vs
78%
 Relief of dysphagia at 6 months 53.5% Vs
90.5%

 For medically inoperable patients with submucosal
esophageal cancer, EBRT with ILBT is an attractive
approach
 Ishikawa et al, 5 year cause specific survival to be
86% with EBRT and ILBT and 62% with EBRT alone
 In pallilative setting to relieve dysphagia HDBT is
more defined
 Sur et al, 50 Patients, EBRT @ 35 Gy/15#,
 1st arm : kept on f/u
 2nd arm : 12 Gy/2# HDR
 6 month relief of dysphagia : 84% Vs 13%
 1 year survival : 69% Vs 16%

Head and Neck Cancers
 Head and Neck area doesnot tolerate high dose
per fraction
 Nasopharynx : Easily accessed by intracavitary
HDR applicator
 Lovenderg et al, have shown patients most suitable
for HDR BT boost are tghose with T1 and T2 lesion
following 60 to 70 Gy of EBRT
 HDR of 18 Gy/6 # are delivered by special
nasopharynx applicator
 T3, T4 : better suited to be boosted by IMRT

HDR Brachytherapy as salvage in
H&N Cancer
 Loco-regional recurrence is the primary pattern of
failure in H&N caners despite of advancement in
surgery, concurrent CCT and EBRT
 Surgical Treatment is the preferred treatment,
however it is not possible in all cases
 EBRT is as effective as salvage treatment but
with high toxicity
 HDR BT has been used in previously irradiated
patients, initial results appear to be comparable to
other modalities

Conclusion
 Beginning of brachytherapy started with the
discovery of Radium.
 With the improvement in specific activity of
sources the era of HDR came along with the
decreased radiation exposure to the persons
involved .
 Though theoritically , LDR is radio biologically
better than HDR , clinical trials have shown the
result of HDR as good as LDR .

Radioisotopes and dose rates used for brachytherapy

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