Evolution of GynecologicalBrachytherapy

Dr. Ritam JoarderR.G.Kar Medical College

1895: Discovery of X-ray by Röntgen

1896: Discovery of Radioactivity by Becquerel

1898 : Discovery of Radium & Polonium by Marie Curie and Pierre Curie

Down the memory lane……

Pierre made a rubber capsule of 0.398g of radium sulfate for Dr.Danlos of St.Luis Hospital

Dr. Henri Danlos and Paul Blotch in 1901 successfully treated lupus skin lesion with Radium

“… there is no reason why a tiny fragment of radium sealed up in a glass tube should not be inserted into the very heart of the cancer; thus acting directly upon the diseased material.

A.G. Bell Letter to Science, 1903

Margaret Abigail Cleaves

In 1903 Gynecological Brachytherapy was first introduced by…….

On 15 September 1903 she treated an inoperable cancer of the cervix uteri with 700 milligrams of radium bromide sealedin a glass tube.

Two applications of 10 minutes each were made with an interval of 3 days between.

O'Brien, F. w. (1947): Amer. J. Roentgenol., 57, 281.

And The Journey Begins Here ……

The dose prescription was entirely empirical

Due to lack of –Knowledge about the biological effects of

radiation on the normal tissues and the tumor

Understanding about the dose, dose distribution and the duration of treatment

The Concept of Dosimetric system was introduced

Dosimetric systems denotes a set of rules taking into account the source strengths ,geometry and method of application in order to obtain suitable dose distributions over the volume(s) to be treated.

Systems Brachytherapy Evolution of Gynecological

Gosta ForssellStockholm System

Claude RegaudParis System

M.C.ToddManchester

System

Edith QuimbyQuimby System

R. Paterson & H.M ParkerManchester System

B .Pierquin & A. DutreixParis System

Intracavitary systems

Interstitial systems

Stockholm system

Fractionated (2--3 applications) delivered within about a month

Each application 20--30 hours

The amount of Radium was unequal in uterus (30--90 mg, in linear tube) and in vagina (60--80 mg, in shielded silver or lead boxes)

Vaginal and uterine applicators were not fixed together

Total mg--hrs were usually 6500 to 7100 out of which 4500 mg were in vagina.

Developed by Gosta Forssell by 1913 in Radiumhemmet , Stockholm

Later perfected by James Heyman and Hans Kottmeier

Paris system

2 applicators were used a) Uterine applicator containing 13·33 + 13·33 + 6·66 mg. tubes of radium loaded in tandem fashion.

b) Vaginal colpostat and cork together containing 33·32 mg. of radium.

Single application of 120 hrs.

Vaginal and uterine applicators were not fixed together.

Total dose given to both uterus and vagina was 30 m.c.d (4000 mg-hr)

Developed by Claude Regaud by 1922 in Institute du Radium , Paris

Uterine sources in both systems were arranged in a line extending from the external os to nearly the top of the uterine cavity.

Both systems preferred the longest possible intrauterine tube to increase the dose to paracervical region and pelvic region lymph nodes.

There was a limited use of external beam therapy in Stockholm system, whereas Paris system used external beam therapy before the implant.

When compared……

Normal Tissue Tolerance :

“ paracervical triangle," ……… as roughly pyramidal in shape, with its base resting on the lateral fornix and the apex curving round with the anteverted uterus ”

Manchester system Developed by M.C.Todd & W.J.Meredith in 1938 in Holt Radium Institute ,Manchester

Later revised in 1953

“ point A is 2 cm. lateral to the central canal of the uterus and 2 cm. from the mucous membrane of the lateral fornix in the axis of the uterus”

“ a secondary point, designated B, five centimetres from the mid-line and on the same level as Point A, is either in or near enough the node to be used to give a measure of the dose received by it.”

Manchester system

Initially used radium units were 6.66mg but later changed to 2.5 mg each.

Two application 72hrs apart with 4 days in between

Dose of 8000R was delivered at pt A when radium used alone for stage I/II ds

When radium was used along with deep-X ray therapy for stage III or IV ds radium dose to pt A reduced to 6500R.

Paterson-Parker system

Dosage : 1.

because

2.

3.

Rule 1: A fraction of the total activity is placed on the periphery of the target volume with the remainder spread uniformly over the interior.

Implant Area Fraction on Periphery < 25 cm2 2/3 25 – 100 1/2

> 100 1/3Rule 2: The needles should be arranged in

parallel rows 1 cm apart with the ends crossed.

Rule 3: If the ends of the implant are uncrossed, the area should reduced by 10 % for each uncrossed end for table reading purposes.

Single Plane Implant :

1. Total amount of Ra-226 is divided into 8 parts: 4 parts in the belt, 2 parts for core, and each end 1 part.

2. Needles should be parallel, spaced uniformly and not more than 1 cm apart.

3. 7.5% is reduced from the volume for uncross end for table reading purpose.

4. The stated dose in 10% higher than min dose in the volume.

Cylindrical volume Implant :

spaced R26 needles

• The Quimby system is characterized by a uniform distribution of activity.

• Leads to higher dose in the central portion of the implant.• Designed for interstitial implants using radium needles.• Implantation Rules:

Lookup tables give number of mg-hr/1000 R in the center of the treatment plane (top or bottom of a planar implant).

Stated dose is the maximum dose in the treatment plane. Sources are spaced 1 cm apart and of same strength.Ends are crossed.

Quimby system Developed at Memorial Hospital, NYC in 1930s and 1940s by Edith Quimby for Ra sources

• Kwan System ( Kwan et al. 1983)

• Tufts System ( Zwicker et al. 1985)

• Memorial System ( Anderson et al. 1986)

• Saw System ( Saw et al. 1988)

Quimby based systems using Ir-192 seeds in ribbon

Evolution of Gynecological Brachytherapy Sources

What is an Ideal Radionuclide?

• Easily available & Cost effective

• Gamma ray energy high enough to avoid increased energydeposition in bone by PEE & low enough to minimise radiationprotection requirements

• Preferably monoenergetic: Optimum 300 KeV to 400 KeV (max=600 kev)

• Absence of charged particle emission or it should be easilyscreened (Beta energy as low as possible: filtration)

• Half life such that correction for decay during treatment is minimal

• Moderate gamma ray constant (determines activity & output) &also determine shielding required. Godden ,1988

What is an Ideal Radionuclide?

• No radioactive daughter product; No gaseous disintegration product to prevent physical damage to source and to avoid source contamination

• High Specific Activity (Ci/gm) to allow fabrication of smaller sources & to achieve higher output (adequate photon yield)

• Material available is insoluble & non-toxic form• Sources can be made in different shapes & sizes

• Disposable without radiation hazard to environment

• Isotropic: same magnitude in all directions around the source

• No self attenuationGodden ,1988

Radium• Earliest & once the most commonly used isotope• Naturally occuring ,extracted from Pitchblend ore• T ½ =1622 yrs• Disintegrates very slowly to hazardous radioactive gas Radon (Rn222)• Energy- ranging from 0.184 MeV - 2.45 MeV (avg.0.83Mev)• Some high energy β rays (max.3.26 Mev)• β filtration : 0.5 mm of platinum• Has been widely used for intracavitary,interstitial & mould applications• Radium sulfate/Ra chloride mixed with inert filler & loaded in cell(1cm

long &1mm in dia.made of 0.1-0.2 mm thick Gold foil).

• Exposure rate constant : 8.25 R cm² /mg-h

Uranium Ra Rn RaA RaB RaC Pbα α α βγ βγ

T1/2 1620Yrs 3.83days 3.05min 26.8min 19.7min Stable

0.66mg/cm

0.66mg/cmo.33mg/cm

0.33mg/cm 0.66mg/cm

Uniform

Indian Club

Dumb bell

Tube

TYPES OF RADIUM SOURCESShapes :

Physical characters :Wall thickness: 0.5mm of Pt+Ir alloy

Gold foil : 0.1 mm thick Cells : used for loading Eyelet hole

cells

Outer case(Pt+10%Ir)

Space for Ra+filler mixture

Why Radium is not used now?

• Spectrum has > 8 photon energies ranging from 0.047- 2.45 MeV : gives heterogeneous beam & non uniform dose distribution

• Low specific activity : 1 Ci/gm : requiring large diameter needles

• High gamma ray constant: requires more protection

• High energy: High radiation shielding will be required

• Rn 222 being the gaseous daughter product - threat of leaks from long bent needles

• Storage & disposal of leaked sources a big problem

• Costly Ra source

CESIUM 137: ( Cs137)

• Recovered from fission products of U-235 made in Nuclear Reactor• T1/2 : 30 yrs• Relatively cheaper, extraction simple,• Decay system :

55137 Cs 137

56Ba + 0-1e + γ

• No gaseous decay product, safer than Ra• γ ray energy = 0.662 MeV• β filtration – 0.5 mm stainless steel• Available in tubes, needles, pellets.• Replaced Ra in t/t of gynecologic cancers.• Exposure rate constant : 3.26 Rcm² /mCi-h

5mmActive bead(1.1mm dia.)

Stainless steel

1.8

Miniature cylindrical source

Spacer beads

Retaining spring

Min.cyl.sources

Spiral spring

Screw thread

Source train

Manual afterloading system of Cs

Source train consist of flexible stainless steel holder containing miniature source separated by spherical steel spacers 1.8 mm in diameter. Sources and spacers retained by a steel spring.

IRIDIUM 192 (192Ir)

T1/2 =73.8 days

Decays through β emission and electron capture to 192Pt and 192Osmium

Decay scheme: 192Ir 192 Pt+ 0-1e+ γ

Emits γ rays of energies ranging from 0.136 to 0.613 MeV (avg. 0.380 MeV)

Emits β particles max energy 0.670 MeV

β filtration =0.1mm of platinum(Eliminated by stainless steel capsule)

HVT- 4.5mm of Lead (Pb)

Available in nylon strands or as platinum cladded wire.

PHYSICAL PROPERTIES OF 192Ir seed• Seeds are 3mm long & 0.5 mm in dia.

spaced with their centre 1cm apart.• Internal core of 30%Ir +70%Pt

surrounded by 0.2 mm thick stainless wall

192 Ir wire( coil form)

Single Pin Hair Pin

Core diam: 0.1mm- 0.4mmSheath thickness : 0.1mm-0.4mmOverall thickness: 0.3mm- 0.6mm

COBALT 60 (60Co) Produced by neutron activation of stable isotope 59Co

Decay scheme: 6027Co 60

28Ni+ -1 0e + y T1/2 = 5.26 yrs

Each disintegration produces 2 y rays of energy 1.33 & 1.17 MeV (avg energy 1.25 MeV)

β energy= 0.318 MeV ; HVL in Lead = 11 mm

High specific activity , miniaturized source can be made and used in brachytherapy.

Reasons for re-emergence of 60Co as brachytherapy source

Modern techniques → Sources of higher Sp Activity → Decreased source size compatible with remote afterloading stepping source machines for HDR.

No need for frequent replacements

Cost effective

Low operating cost.

Ir-192 : A near ideal radioisotope

Compatible with after loading techniquesIdeal energy (0.3-0.4 MeV) – monoenergetic – more

radiobiological effectFlexible & malleable – can be used in form of wires of any sizeEnergy is low – thinner shields required for radiation safetyβ-energy is low – so lesser filtration requiredProduct (Pt192) not radioactiveEasily available , less costly

x Limitation Short half life (73.8 days) so source has to be replaced every 3 months

Element

Energy(MeV)

Halflife

HVL- Lead(mm)

Exposure rateConstantRcm2mCi-1h-1

Sourceform

Clinicalapplication

CesiumCs-137

0.662 30yrs 5.5 3.26 Tubes & Needles

LDR I/C & temporaryimplants

CobaltCo-60

1.25avg

5.26yrs

11 13.07 Encapsulated sphere

HDR I/C

IridiumIr -192

0.397avg

73.8Days

2.5 4.69 Seeds in Nylon;Metal wires ;Encapsulated source on cable

GoldAu-198

0.412 2.7 Days

2.5 2.38 Seeds or “Grains”

Permanent implants

RADIUM SUBSTITUTES

Evolution of Gynecological

BrachytherapyApplicators

Radium applicators for surface and intracavitary applications, used by Danlos and later by Wickham.

Applicators used to insert intracavitary sources in the uterus and vagina included

Rubber catheters and ovoids developed by French researchers.

Metallic tandems and plaques designed in Sweden.

Thin rubber tandems and ovoids of the Manchester system.

Fletcher (1953) designed a preloadable colpostat, which Suit et al. (1963) modified and made after loading.

Applicators

Ideal Characteristics of applicators

• Fixed and rigid to attain and hold better geometry of the insertions.

• Light weight (ideally 50- 60gm but should not be >100gm) for the pt's comfort

• Capable of easy sterilization.

• Should be of inert material that is not adversely affected by exposure to

gamma radiation.

• There should be minimal attenuation of gamma rays by the walls of the

applicators i.e. it should not produce its own characteristic radiations.

• Vaginal ovoids should be perpendicular to the long axis of vagina to avoid

more dose to rectum and bladder.

• I.U. tube should be angulated whenever required.

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 afterloading: Sources manipulated into applicator by means of forceps & hand-held tools

• Remote after loading: consists of pneumatically or motor-driven source transport system

Stockholm Applicators

Paris System Applicators

Vaginal applicators are essentially modification of corks described by Regaud , in the Paris technique.

Made of hard rubber, and bored along the axis to take 1 or more radium tubes of actual length 2.2 cm., active length 1.5 cm.

The shape of the ovoid follows the distribution in three-dimensional space of the isodose curves round a radium tube of 1 -5 cm. active length

Large ovoid : 3cm , Medium : 2.5 cm, Small : 2cm in shortest diameter

The ovoid pairs are separated at 1cm by a rubber made “Spacer” Or Kept in contact by means of a “Washer”

A thin rubber tube with a flange at the end, which is held by the spacer and packing

Manchester System ApplicatorsIntrauterine applicator :

Intravaginal applicator :

Loose preloaded system withchances of slipping of ovoids and hence disturbed geometry and creation of cold and hot spotsleading to high failure or increasedmorbidity.

Pair of cylindrical “small” ovoids (2 cm in diameter) with inter-locking handles.

Plastic jackets of two thicknesses are added to made medium (‘2.5 cm in diameter) and large (3 cm in diameter) sizes.

Photographs of original preloadable Fletcher applicators

The applicators have the same diameter as the Manchester ovoids but not the shape of an isodose

Fletcher et al. Radiology 60:77-84, 1953

Initial single channel remoteAfterloading machine 1962

Curietron prototype (1965)

Cobalt Ralston 1970

• In 1960-Ulrich K Henschke first described Manual afterloading• In 1962-Walstram first described remote afterloading (Based on ALARA principle – As Low As Reasonably Achievable)• In 1964- First developed Remote afterloading device

Fletcher afterloading colpostats

a. Fletcher-Suit rectangular-handle model

b. Round-handle, lighter model.

In 1958, Suit et al. developed the first afterloadable Fletcher colpostatIn 1978, Delclos et al. improved design of the afterloadable Fletcher colpostats

Fletcher

Suit

Delclos

MDR Selectron machineManual after loading source trains of 137Cs

MicroSelectron (Nucletron)

VariSource & GammaMed (Varian).

HDR plus(IBt Bebig)

Modern HDR Brachytherapy Machine

PDR Brachytherapy

Series of short HDRtreatments ( 10 minute pulse repeated at 1 hr intervals)replacing the Continuous LDR treatment lasting several days.

Overall time remains same as LDRSource strength : 1 Ci

ADVANTAGE:• Radiobiologically nearer to LDR• optimization possible• Nursing care possible without radiation hazards

Nucletron PDR afterloader

Thank You