conventional brachytherapy in carcinoma cervix

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Conventional Brachytherapy In Carcinoma Cervix

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Conventional Brachytherapy In Carcinoma Cervix

BRACHYTHERAPY• Brachytherapy is a type of radiation treatment in which

small, encapsulated radioactive sources are arranged in a geometric fashion in & around tumor.

• ADV.– It delivers very high dose of radiation to tumor– Sparing normal tissue– Dose delivered in short duration as compared to External beam

RT.

BRACHYTHERAPY in Cervix• Brachytherapy plays vital role in treatment of ca cx. &

is mainly applied as an intracavitary procedure in selected cases complemented by interstitial implants.

• It consists of positioning specially designed applicators bearing sealed radioactive sources into a body cavity in close proximity to the target tissue.

• I/C applications are temporary that are left in the patient for a specified time to deliver prescribed dose.

WHY I/C BRACHYTHERAPY• Uterine cx. is ideally suited for I/C brachytherapy

because

– High tolerance of cervix ,uterus & vagina– It is accessible organ hence Brachytherapy can be practised

with ease. – The endocervical canal & vaginal vault form a suitable

vehicle to carry rigid applicators with radioactive sources.– These applicators can be used with minor modifications in

all pts.

ADV. OF I/C BRACHYTHERAPY

• High dose of radiation is delivered in shortest time.• Cervix receives 20,000 – 25000 cGys. • Uterus receives 20,000- 30000 cGys• Vagina receives 10,000 cGys.

such high doses can’t be delivered by any technique of EBRT.• Best long term control is achieved • Sharp Fall off of dose and hence less dose to the normal

structure. • Less late radiation morbidity .• Preservation of normal anatomy.• Better sexual functional life.

HISTORY1898 : Discovery of Radium by Marie Curie in Paris.

1903 : Margaret Cleaves, a New York physician

described inserting Radium into the Uterine cavity

of a patient with Ca Cervix.

1908 : I/C brachytherapy started in Vienna

1910 : I/C brachytherapy started in Stockholm

1912 : I/C brachytherapy started at Paris.

1930 : Todd & Meredith developed Manchester system

in U.K. 1960s - After loading technique ( Helneski)

1970- Paris System of dosimetry for Interstitial Brachytherapy evolved 1975- Remote Control LDR ( Cs-137)

1985- HDR Introduces( Ir-192 & Co-60) & ICRU-38 Published - Concept of Volume in place of point introduced - Joshlin Published data about the discrepancies in point A & B

1990s - Miniaturized stepping source with optimization

DOSIMETRIC SYSTEMS• The historical dosimetric systems were developed when

computer treatment planning and dose computations were not available

• Term ‘system’ specifies a set of rules for – Geometrical arrangement of a specific set of radio isotopes in a

specialised applicator

– To obtain suitable dose distributions over the volume to be treated. – It specifies treatment in terms of the dose, time and administration

– A specified set of tables to allow, reproducible and easy calculation in most of the encountered clinical scenarios.

– A system ensures safety and is based on clinical experience.

STOCKHOLM SYSTEM• Fractionated (2-3 #s) course over a period of one month.

• For a period of 22 hours each.

• Separated by 1-3wks

• This system used– Intravaginal boxes made up of silver or gold – The intrauterine tube made up of flexible rubber.– These were not fixed together

• Unequal loading of Radium– 30 to 90 mg of Radium was placed inside the uterus– While 60 - 80 mg were placed inside the vagina.

• A total dose of 6500 -7100 mg -hrs was prescribed out of which 4500 mg Ra was contributed by the vaginal box. (dose rate-110R/hr)

PARIS SYSTEM• Single application of Radium for 120hrs (5-6days)

• In this system, almost an equal amount of Radium was used in the uterus and the vagina.

• The system incorporated – Two cork colpostats (cylinder) with 13.3mg Radium

in each – An intrauterine tube of silk rubber with 33.3mg

Radium

• The intrauterine sources contained three radioactive sources, with source strengths in the ratio of 1:1:0.5.

• The colpostats contained sources with the same strength as the topmost uterine source

• Designed to deliver a dose of 7000 - 8000 mg hrs over a period of 5days (45R/hr) (5500mg/hr)

DOSE SPECIFICATION

• Done in mg-hr i.e. simple mathematical product of mg of Radium times the duration (in hours) of the implant.

• It was easy to use.

• The dose prescription was entirely empirical due to the 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.

• Only applicable when both tandem & ovoids are used & sources are loaded in a rigidly prescribed manner.

FALLACIES• Long treatment time, discomfort to the patient

• Dose prescription method was empirical. Both systems specified dose in mg-hour.

• Does not give any information about dose distribution.

• When used in conjunction with EBRT, overall radiation treatment can’t be adequately defined

• Dose specification method lacks the information on – Source arrangement– Position of tandem relative to the ovoids– Packing of the applicators– Tumour size, and – Patient anatomy.

• With the use of this dose prescription method dose to important anatomical targets could not be quantified adequately.

• Ignored the importance of tolerance of different critical organs to radiation.

MANCHESTER SYSTEM

• The Manchester system is one of the oldest & extensively used systems in the world.

• Developed by Todd & Meredith in 1930 & was in clinical use by 1932.

• This system was initially developed for radium tubes, but was easily adapted to different afterloading systems.

MANCHESTER SYSTEM• Manchester system was based on following principles:

• To define the treatment in terms of dose to a point. To be acceptable this point should have following criteria :– It should be anatomically comparable from patient to patient.– Should be in a region where the dosage is not highly sensitive to small

alteration in applicator position.– Should be in position that allows correlation of dose with clinical effects

• To design a set of applicators and their loading (with a given amount of radium), which would give the same dose rate irrespective of the combination of applicators used.

• To formulate a set of rules regarding the activity, relationship & positioning of the radium sources in the tandem & vaginal ovoids to achieve desired dose rate.

POINT A

• Todd & Meredith defined a point in paracervical triangle where the uterine vessels cross the ureter as point A.

• Point A is defined as a point 2cm. lateral to the center of the uterine canal and 2 cm. superior to the mucosa of the lateral fornix, in the plane of the uterus.

• Now point A is defined as a point 2cm above the distal end of lowest source in cervical canal & 2cm lat. to centre of tandem.

POINT A• Although point A is defined in relation to important

anatomic structures, these can’t be visualized on a radiograph.

• The keel is placed at the external os. It serves as important reference point as it can be visualized on radiograph.

• Dose at point A showed a correlation with local control and the incidence of late normal tissue toxicity in the pelvis

POINT B

• Point B is defined 2cm above external os & 5 cm laterally to midline

• Represents dose to the pelvic wall, obturator L.N.

• The dose at point B is approx. 25 -30% of the dose at point A.

• Dose to point B, depends little on the geometric distribution of radium, but on the total amount of radium used.

DOSE LIMITING STRUCTURES

• Bladder

• Rectum

• Vaginal mucosa

• Rectovaginal septum– No more than 40% of total dose at point A could be delivered safely

through the vaginal mucosa.

– The rectal dose should be 80% or less of the dose at point A; this rectal dose can usually be achieved by careful packing.

MANCHESTER SYSTEM

• In this system, the dose distributions were not calculated for individual patients.

• Applications outside the standard variations were corrected

for, but the majority of patients had applicators in place for a standard time.

• The Manchester system was a time system based on the use of standard applicators

APPICATOR IN MANCHESTER SYSTEM

• Similar to that used in Paris system• It had a pair of ovoids & an intrauterine tube

INTRAUTERINE TUBE• The intrauterine tube was made up of the thin rubber ( to prevent

excessive dilatation of the cervical canal) • These tubes were available in three separate lengths

– 2cm

– 4cm

– 6cm

• In order to accommodate 1, 2 or three Radium tubes (2 cm long) in line

I.U.tubes were closed at one end, and had a flange at the other end so that when packed into position, the uterine tube did not slip out during the treatment.

OVOIDS• Used in pairs, one in each lateral fornix

• The shape of ovoids mimics the shape of isodose curves around a Radium tube having "active length" of 1.5 cm.

• The ovoids were designed to be adaptable to the different vaginal capacity, with diameter of– 2 cm– 2.5 cm– 3 cm

• The largest ovoid are placed in the roomiest vagina in order to achieve the best lateral dose throw off

SPACERS• Apart from ovoids & I.U.tubes spacers or washers were used

– To maintain the distance between the ovoids

– To help in their fixation

• Spacer was used to give the largest possible separation b/w the ovoids so that the dose could be carried out as far laterally as possible.

• It maintained a distance of 1cm b/w the ovoids.

PACKING

• Manchester applicators do not incorporate rectal shielding.

• Hence gauze is packed firmly and carefully

– behind the ovoids,– anteriorly b/w the ovoids and the base of the bladder,– and around the applicator tubes down to the level of the

introitus

• Packing helps to – keep the applicators in position– to reduce dose to bladder and anterior rectal wall.

RULES• The point A should receive the same dose rate, irrespective of the

combination of applicators used.

• Not more than one third of the total dose to point A should be delivered by the vaginal ovoids. So that tolerance of vagina mucosa is not exceeded

• Standard or ideal loading is 60-40 i.e. 60% of the dose to point A is contributed by intrauterine sources while 40% is contributed by ovoids.

• Total Dose to point A : 8000 R– Total number of applications : 2– Total time for each application : 72 hrs– Total time : 144 hrs– Dose rate desired : 55.5 R /hour to point A

• Amount of radium to be used was defined in terms of units.

• 1 unit = 2.5 mg of radium filtered by 1 mm platinum.

• The loadings were specified in terms of integral multiples of this unit.

LOADING PATTERN• Total dose at point A using different combinations of

I.U tube & ovoids :– Large tube with large ovoid and washer : 57.5 R– Large tube with large ovoid and spacer: 56.9 R– Large tube with small ovoid and washer: 57.6 R– Medium tube with small ovoids and spacer: 57.3 R

• The variations were thus within 1.5% range.

ICRU SYSTEM

• For reliable and relevant comparison of different methods and their clinical results ICRU 38 recommends a common terminology for prescribing recording and reporting I/C Brachytherapy applications.

• The ICRU recommends a system of dose specification that relates the dose distribution to the target volume, instead of the dose to a specific point

• The dose is prescribed as the value of an isodose surface that just surrounds the target volume.

ICRU REPORTING• Description of technique

• Time dose pattern (application duration)

• Description of reference volume

• Dose at reference points

Description of the Technique

• Minimum information should include the

– orthogonal radiographs of the application.

– Source used (radionuclide, shape and size of source, and filtration)

– applicator type

– Loading pattern

– Simulation of linear source for point or moving sources

– Applicator geometry (rigidity, tandem curvature, vaginal uterine connection, source geometry, shielding material)

DOSE AT REFERENCE POINTS

• The dose to bladder and rectum depends on the distribution of sources in a given application.

• The maximum dose to bladder and rectum should be less than 80% of the dose to point A

• The localization of bladder and rectum can be performed using radiographs taken with contrast media in the bladder and rectum.

BLADDER POINT• ICRU recommends :

o Foley balloon filled with 7 cm3 radiopaque fluid and pulled down against urethra

• On a lat. radiograph reporting dose at a point at posterior surface of Foley balloon on AP line through centre of balloon.

• On AP radiograph, reference point is taken at the centre of the balloon

RECTAL POINT• The dose is calculated at a

point 5 mm posterior to (opacified) vaginal cavity along an AP line midway between vaginal sources.

• On the frontal radiograph, this reference point is taken at the intersection of (the lower end of) the intrauterine source through the plane of the vaginal sources.

LYMPHATIC TRAPEZOID• Lymphatic trapezoid represents

dose at lower Para-aortic , common and external iliac L.N.

• A line is drawn from S1-S2 junction to top of symphysis, then a line is drawn from middle of this line to middle of ant. aspect of L4

• A trapezoid is constructed in a plane passing through transverse line in pelvic brim plane and midpoint of ant. aspect of body of L4

PELVIC WALL REFERENCE POINTS• The pelvic wall reference point, represents

absorbed dose at the distal part of the parametrium and at the obturator L.N.

• Reporting dose at reference points related to well defined bony structures & L.N. areas is particularly useful when I/C BT is combined with EBRT

• On a AP radiograph, pelvic-wall reference point is located at intersection of following lines– a horizontal line tangential to the highest

point of the acetabulum,– a vertical line tangential to the inner aspect

of the acetabulum.

• On a lat. radiograph, the highest points of the right & left acetabulum, in cranio -caudal direction, are joined & lateral projection of the pelvic-wall reference point is located mid-way b/w these points.

REFERENCE VOLUME• Volume encompassed by the

reference isodose, selected and specified to compare treatments performed in different centres using different techniques.

• ICRU (43) recommends reference volume be taken as the 60-Gy isodose surface, resulting from the addition of dose contributions from any external-beam whole-pelvis irradiation and all I/C insertions. – Height h, – Width w, and– Thickness t. – and their product should be reported

separately

TREATED VOLUME

• The Treated Volume is the pear and banana shape volume that received (at least) the dose selected and specified by the radiation oncologist to achieve the purpose of the treatment e.g. tumour eradication or palliation, within the limits of acceptable complications

IRRADIATED VOLUME

• The irradiated volume is the volume, surrounding the treated volume, encompassed by a lower isodose to be specified, e.g., 90 – 50% of the dose defining the treated volume.

• Reporting irradiated volumes is useful for

interpretation of side effects outside the treated volume and for purpose of comparison.

APPLICATORS• Applicators are small-caliber tubes that are inserted into body

cavities to hold the brachytherapy sources in clinically defined configurations.

• The applicators include

– A tandem to be inserted into the uterus • with different lengths that allow for adaptation according to the

individual anatomy (with a fixed uterine flange)

• Angled at varying degrees to the line of the vaginal component (0°,15°,30°,45° )

• The deliberate angle in the tube draws the uterus, in most patients, into a

central position in the pelvis away from the pouch of Douglas, the sigmoid colon, and the anterior rectal wall.

– Two ovoids, to be positioned in the vaginal vault abutting the cervix.

APPLICATORS• 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

– It should have a fixed geometry.

– It should be made of rigid material as fixed & rigid applicators attain and hold better geometry of the insertions

– Lightweight (ideally 50- 60gm but should not be more than 100gm) for the patient's comfort

– capable of easy sterilization.

– Applicators should be of inert material that is not adversely affected by exposure .

– There should be minimal attenuation of radiation 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

FLATCHER APPICATOR• Based on Manchester System• Stainless steel • Cylindrical ovoid• Rectal shield• Preloaded but modified by Suit

for after loading• Disadvantages

– Presence of shielding lead to uncertainty in dosimetry.

– Cylindrical caps lead to non-uniform doses to vaginal mucosa.

Fletcher - Suit- Delclosapplicator for afterloading with Ir-192

HENSCHKE APPLICATOR• Ovoids are hemispherical in

shape.

• Three ovoid diameters & various tandem lengths are available

• The radioactive sources are placed parallel to the long axis of the bladder & rectum

• Thus delivering a higher dose to these organs

PGI APPLICATOR• Fixed geometry applicator

• Desired dose can be delivered around area of interest

• Easy & accurate dosimetry

• Less rectal dose because of obtuse angle.

• Perineal plate which helps to maintain fixed geometry of application

• Disadv.– Bladder complications are more as it

receives higher dose due to more angulation

MDR/HDR APPLICATOR

• Modern after loading applicator that mimics classical Manchester based applicator.

• I.U. tube with different lengths graduated in centimeters (4& 6cm)

• The vaginal ovoids are of ellipsoid shape (large, medium, small, half)

• These tubes are held together and their relative positions fixed by a clamp ensuring an ideal physical arrangement.

RING APPLICATOR• Based on Stockholm technique• Intrauterine tubes are of different

lengths & angulations• Ring is available in different

diameters (26, 30, 34mm)• Acrylic caps cover the ring tube to

reduce dose to vaginal mucosa. • The ring and the intrauterine tube

are fixed to each other with a screw. • A rectal retractor helps in pushing

rectum so that it receives less dose.• Adv. of ring applicator:

– Fixed geometry– Interrelationship b/w ovoids is

maintained.– Customized planning can be done

IDEAL APPLICATION• Use longest tandem that the

patient's anatomy can accommodate.

• Increasing the tandem length increases the point B (lateral parametrium and pelvic lymph nodes) contribution relative to the uterine cavity surface dose

• The radioactivity near the ends of the long tandem contributes little to the surface dose (because of inverse-square law), whereas each tandem segment makes roughly equal contributions to points remote from the applicator.

IDEAL APPLICATION• Colpostats /ovoids with largest clinically indicated diameter

should be used to deliver highest tumor dose at depth, for a given mucosal dose.

• As colpostat diameter increases from 2 to 3 cm, the vaginal surface dose decreases by 35% relative to the dose 2 cm from the applicator surface; This is simply a consequence of increasing the source-to-surface distance.

• The geometry of the insertion must prevent under dosing

around the cervix

• Sufficient dose must be delivered to the Para cervical areas; and

• Tolerance of vaginal mucosa, bladder and rectum must be respected.

IDEAL APPLICATION

• Tandem -1/3 of the way b/w S1 –S2 and the symphysis pubis

• The tandem -midway b/w the bladder and S1 -S2

• Marker seeds may be placed in the cervix

• Ovoids should be against the cervix (marker seeds)

• Tandem should bisect the ovoids

• The bladder and rectum should be packed away from the implant

IDEAL APPLICATION• The tandem should be in the midline or as

nearly as possible equidistant from the lateral pelvic wall

• The vaginal colpostats should be symmetrically positioned against the cervix in relation to the tandem

• The ovoids should fill the vaginal fornices, add caps to increase the size of the ovoids if necessary

.• The ovoids should be separated by 0.5 –

1.0 cm, admitting the flange on the tandem.

• The axis of the tandem should be central between the ovoids.

• Computerized dose optimization cannot make up for a poor applicator position.

PATIENT PREPARATION

• Pt is anaesthesitized.

• Patient is in lithotomy position

• Perineal area is disinfected

Anesthesia

• Potential options include general, spinal or iv conscious sedation.

• With IV conscious sedation – levator muscle tightens making application difficult.

• Conscious sedation with Iv fentanyl and midazolam is preferred in most patients.

• General or spinal anesthesia result in complete immobilization during insertion and treatment which may be 2-4 hr

APPLICATOR CHECK

• Applicator set is check for integrity and completeness

• Dilatation of the cervix with standard tooling.

Tandem placement:

• Hegar uterine dilators are used to dilate the os to 6 mm.

• Tandem length is usually 6–8 cm but its variable from patient to patient.

• For tandems >8 cm, avoid loading/active source at end to protect small bowel.

• Tandem should be located centrally between the ovoids on the AP view and bisect the ovoids on the lateral view.

PROCEDURE

• Correct length of IU-tube & ovoids are selected

• Inserted one by one and attached to fixing mechanism.

• To determine the rectal wall on CT or radiograph a radio opaque marker is inserted

• After insertion of applicator gauze packing is done behind the ovoids to push rectum and bladder away reducing the dose to these organs

• After procedure orthogonal radiographs are taken to check applicator geometry.

Brachytherapy• Stage IA (microinvasive) tumors

– Treated with Brachytherapy alone– LDR dose is approximately 60 Gy in one insertion or

75 to 80 Gy in two insertions to point A

OR– with HDR an equivalent dose, with one or two

fractions per week.

• A reasonable target is to give to Point A – 65-75 Gy for Stage IA disease– 75-85 Gy for IB - IIB– 85-90 Gy for III – IVA

LIMITATIONS OF (2 D)RADIOGRAPHIC IMAGING

For determination of target

• point based dosimetry• point A may overestimate or underestimate the tumor dose based on 3D

imaging*

• no optimization:• tumor coverage relies on tumor volume at time of BT, larger tumors requiring

greater optimization to be adequately covered by the prescribed isodose line• Kim et al** found that dose to point A was significantly lower than

the D90 for HR-CTV calculated using 3D image-based optimization

• dose escalation not possible

• *Kim RY, Pareek P. Radiography-based treatment planning compared with computed tomography (CT)-based treatment planning for intracavitary brachytherapy in cancer of the cervix: analysis of dose-volume histograms. Brachytherapy 2003;2:200–206.

• **Kim H, Beriwal S, Houser C, et al. Dosimetric analysis of 3D image-guided HDR brachytherapy planning for the treatment of cervical cancer: is point A-based dose prescription still valid in image-guided brachytherapy? Med Dosim 2011;36:166–170.

AIM

to analyze dosimetric outcome of 3D IGBT &compare dose coverage of HRCTV to traditional Point A dose.

• N=32patients (stage IA2-IIIB cervical cancer) treated with IGBT• dose: 5.0-6.0 Gy/# ×5 fractions. • delineation of CTV as per GYN GEC/ESTRO guidelines. • D90 for HRCTV was 80-85 Gy, • D2cc of bladder, rectum, and sigmoid was limited to 85 Gy, 75 Gy &75 Gy.

• RESULTS• The mean D90 for HRCTV was 83.2 ± 4.3 Gy SD significantly higher (p <0.0001)

than mean value of Point A dose (78.6 ± 4.4 Gy). • The dose levels of the OARs were within acceptable limits • Dose to Point A was found to be significantly lower than the D90 for HRCTV

• Image-based 3D brachytherapy provides adequate dose coverage to HRCTV, with acceptable dose to OARs in most patients.

• ICRU bladder point:

• Foley Bulb in the trigone of bladder with7 cc of dilute contrast is used • only report point estimates. • wide range of anatomic variations in bladder points along he length of implant• doses may be different at bladder base & neck, multiple points have to be taken

• ICRU point may underestimate maximum doses to the OAR, in particular for the bladder

• ICRU bladder volume point does not represent the hottest part of the bladder that usually falls about 2 cm superior. highest dose often is about 2-4 times the dose at the bulb

For determination of OAR

Bladder Point

Rectal point

ICRU rectal point:

• rectal markers is used which tend to lie on posterior wall of rectum while the anterior wall is at greater risk.

• Stiff markers can move rectum, flimsy ones are difficult to push deep.• ICRU rectal point doesn’t usually represent the maximum rectal does, which,

again often is 2-4 cm cephalad.• maximum does is up to 3 times the ICRU point

None of this localizes the superior bowel - an organ very much at risk.

Thank you