Carinoma Cervix brachytherapy

BRACHYTHERAPY
KIRON G
NOV, 2018

BRACHYTHERAPY
• Brachytherapy, from its Greek derivation, refers to ‘‘short range therapy’’
• has been described as the first form of conformal radiation therapy
• takes advantage of the inverse-square law,
• radiation dose is inversely proportional to the square of the distance from the source.

ADVANTAGES
• Precise source placement enables
• small volumes of normal tissue to be irradiated,
• with extremely high doses (hyperdoses) within the cancer and
• sufficient dose at the margin between the cancer and normal tissue, to eradicate microscopic tumor foci
and provide a high control rate.
• such high doses can’t be delivered by any technique of EBRT

DISADVANTAGES
• Invasive
• Needs expertise and experience and equipment
• Time consuming
• Difficult to maintain uniformity across various centres
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MOST SUITABLE FOR BRACHYTHERAPY
• cancers with clinically and radiologically well-defined margins,
• low histologic grading categories
• low risk of regional and metastatic spread

WHY BRACHYTHERAPY IN CERVIX
• uterus and cervix have a relatively high tolerance for radiation,
• which allows for placement of the brachytherapy sources in direct contact with the tumor.
• gynecologic brachytherapy applicators remain relatively fixed within the target
despite patient or organ motion,
• allowing for dose escalation with rapid dose falloff and lower integral radiation doses
• It is accessible organ hence Brachytherapy can be practiced with ease.
• patients who receive higher doses of external beam radiotherapy (EBRT) instead of
intracavitary brachytherapy have higher rates of local failure, shorter survival
times, and increased complications

• Patients who had ICRT had a DSS of 45% at 5 years, compared with 24% for those
treated with EBRT alone
• who received > 52 Gy of EBRT to the central pelvis had DSS rates of 27–34%,
compared with 53% for patients treated with lower doses of EBRT to the central
pelvis and more intensive ICRT
• At 5 years, the risk of major complications was also greater for patients treated with
> 52 Gy of EBRT to the central pelvis (57–68%), compared with those who had 48–
52 Gy (28%) and those who had < 47 Gy of EBRT to the central pelvis (15%)
disease-specific survival (DSS)

HISTORY
• 1985 – Roentgen discovered X rays
• 1986 – Becquerel discovered phenomenon of emitted radiation from Uranium
• 1898 : 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
• 1914 – Stockholm Dosimetric System
• 1919 – Paris system
• 1930 – Manchester System

HISTORY
• 1934 – discovery of artificial radioactivity
• 1960s - After loading technique ( Helneski)
• 1985- HDR Introduces( Ir-192 & Co-60) & ICRU-38 Published

TYPES OF BRACHYTHERAPY
• According to method of source loading :
• Preloading
• Afterloading
• Manual afterloading
• Remote afterloading
• According to type of application :
• Intracavitary
• Interstitial
• Intraluminal – cylinders/ moulds

DOSE RATE DEFINITIONS
• Lowdose rate (LDR)—a range of0.4 to 2 Gy per hour.
• Medium dose rate (MDR) a range of 2 to 12 Gy per hour.
• High dose rate (HDR) -12 Gy per hour, which must be delivered by automatic
afterloading.
• Pulsed dose rate (PDR),
• Permanent implants deliver a high total dose at a very low dose rate (vLDR),
usually at <0.4 Gy per hour

PULSED DOSE RATE
• which uses a large number of small fractions in an effort to simulate the
radiobiologic advantages of LDR,
• but with the obvious advantages of a stepping source and the radioprotection
advantages of remote afterloading as in HDR.
• Generally, the same total dose and same total time as LDR are prescribed but it is
given in a large number of small fractions, generally every 1 to 4 hours

VERY LOW DOSE RATE
• Permanent brachytherapy implants
• using low energy γ-rays,
• very rapid dose reduction outside the implanted volume,
• but carry a higher relative biologic effect (RBE).
• decrease in radiation effectiveness may be compensated for by tumor shrinkage
decreasing the distance between the sources
• The effectiveness of vLDR is dependent on the rate of proliferation of the tumor cells
involved and is therefore more effective in slowly proliferating tumors, for example, well-
differentiated prostate cancer

HIGH DOSE RATE
• HDR machines use high activity sources to deliver a treatment in the course of
minutes
• Because treatment fractions are brief, the HDR allows some treatments to be
delivered as outpatient procedures and may offer advantages to the medical
management of patients
• The high activity of the radioactive source used for HDR brachytherapy necessitates
a dedicated afterloader system

HDR VS LDR
• Patnakar et al 2015
• Overall survival is similar for LDR and HDR brachytherapy.
• Ferrigno R et al 2005 retrospective analysis
• similar outcome for Stages I and II patients treated with either HDR or LDR brachytherapy.
• Lower overall and disease-free survival and marginally lower local control were observed for
Stage III patients treated with HDR brachytherapy.
• Less late rectal complications were observed in the HDR group patients. These findings were
probably the result of the relatively low HDR brachytherapy dose delivered at Point A.
• New man et al
• No significant differences were found in the local control and toxicity

6R
• ‘‘4 Rs’’ of radiobiology, normally used
with reference to fractionation effects,
can be examined with reference to
brachytherapy.
• A fifth category, radiosensitivity
(already included in the LQ model
parameters)
• sixth R, tumor regression, could also
be added

REPAIR
• If successful sublethal damage (SLD) repair has not occurred at a particular site
before further SLD is deposited in an appropriately near site, then
lethal/unrepairable damage will form
• In terms of the LQ model the conversion of sublethal to lethal injury is operative in
the β component that accounts for the two-hit probability of damage

REPAIR
• The lower the dose rate of radiation that a cell is exposed to, the more likely it is
that repair will occur, because there will be more time for SLD repair before a
second ‘‘hit’’
• Late reacting normal tissues have a higher capacity for repair than do some tumor
cells so that tumor is preferentially killed when compared with normal tissues.

REPAIR IN HDR
• Normal tissue repair could be disadvantaged by the application of HDR unless there
is compensation in terms of a reduction in total dose
• The short treatment time of HDR brachytherapy prohibits SLD repair during the
actual irradiation.
• However, if an interval between HDR fractions of say, 12 to 24 hours is maintained,
substantial SLD repair can occur, although it may remain incomplete for up to 72
hours in some tissues, which exhibit slow forms of repair.

REPAIR IN HDR
• For HDR to be radiobiologically equivalent to LDR,
• the dose per fraction should be kept as low as is practically possible,
• so that the total dose may require to be split into different fractions.
• if protracted following external radiotherapy, may result in a markedly increased
overall treatment time

REPOPULATION
• In squamous cell carcinoma, studies have shown improved tumor control and
increased survival when radiotherapy is given in the shortest overall time.14-17
• This is because shorter treatment times allow less time for substantial tumor cell
repopulation or for the phenomenon of accelerated repopulation to establish

REPOPULATION IN LDR
• continuous administration of LDR probably prevents repopulation during
treatment, at least in all normal tissues but cancers that possess mutated cell
checkpoint genes may continue to proliferate

REPOPULATION IN HDR
• Okkan et al.18 showed that the average time to complete treatment when HDR was
used was 70 days, compared with 57 days when using LDR.
• This may decrease tumor control by allowing increased repopulation

HDR
• HDR brachytherapy was delivered at weekly intervals during external beam
therapy,* thereby reducing the overall treatment times;
• a satisfactory compromise would be to give a few brachytherapy treatments after 28
days of external radiotherapy, at weekly intervals, with the remainder at twice or
three times per week frequency following cessation of external radiotherapy.
• This would allow brachytherapy to be deferred until the benefits of tumor shrinkage
had occurred and minimize the overall treatment time.

CHEN ET AL.21
• showed that when treating cervix cancer with HDR brachytherapy, if treatment was
prolonged over 63 days there was a
• signicant decrease in disease-free survival from 83% to 65% (p = 0.004) and
• in local control from 93% to 83% (p = 0.02).
• no difference in late complications was seen in the under-63 day treatment
group,suggesting that there is no morbidity benefit in extending overall treatment
time, as may be expected for late effects

ACCELERATED REPOPULATION
• most conventional method for squamous cell cancers is to assume that accelerated
repopulation is signicant after a time delay (Tdel) of around 21 to 28 days after the
initiation of radiotherapy.24
• The BED is reduced by K(TXR − Tdel).
• This is subtracted from the standard tumor BED for cell kill,
• TXR is the overall time of all radiotherapy (including EBRT and BT)
• K is the daily BED equivalent for repopulation, 0.5 and 1 Gy per day in squamous
cell cancers.

REOXYGENATION
• Owing to inappropriate development of intratumoral vasculature there are large
proportions of poorly oxygenated cells within tumors
• Owing to the length of administration of LDR, time is allowed for transient hypoxia
to correct within the tumor during treatment.28
• HDR treatments allow time between insertions for tumor shrinkage and
reoxygenation to occur.
• LDR has a lower oxygen enhancement ratio than HDR,28,29 it may be as low as 1.6
to 1.7 for LDR compared with 2 to 3 for HDR

REASSORTMENT/CELL CYCLE
• theoretic advantage of an improved effect on cell cycle reassortment using LDR
treatment as
• cells will pass out of the relatively radio-resistant phases of late S and early G2 into
the more radio-sensitive phases of G2 and M during the overall treatment time.

REGRESSION
• Because of the sharp falloff of dose with distance, tumor volume regression effects
can influence brachytherapy dose distributions
• Fast repopulation rates, as encountered in rapidly growing cancer types such as
squamous cell cancers, can effectively oppose the shrinkage benefits
• If brachytherapy catheters have to be placed eccentrically relative to a cancer, the
shrinkage effect is also reduced, as there is a limit to the benefits of regression
• These concepts, provide a rationale for brachytherapy to be deferred until around 28
days to gain from tumor shrinkage in terms of brachytherapy dose distributions

DOSIMETRIC SYSTEM
• historical dosimetric systems were developed when computer treatment planning
and dose computations were not available
• A dosimetry system essentially consists of three parts:
• a set of rules to distribute the sources inside a defined volume to achieve a clinically
acceptable dose distribution,
• a method to calculate patient dose, and
• a system for dose prescription

STOCKHOLM SYSTEM
• fractionated course of radiotherapy delivery using 226-Ra sources over a period of 1
month
• two to three applications were used for each patient,
• each application lasting a time period of 20–30 h.
• Separated by 1-3wks
• applicators consisted of
• intravaginal applicators, which were made of lead or gold, and
• an intrauterine tube, which was made of flexible rubber
• not fixed together
(Heymann 1935; Kottmeier 1964; Ryberg et al. 1990)

STOCKHOLM SYSTEM
• unequal loading for the uterine and vaginal radium sources.
• 30–90 mg of radium (1 mg of 226Ra is equivalent to an activity of 1 mCi, 37 MBq) was
placed inside the uterus,
• 60–80 mg sources were placed inside the vagina
• prescription of the treatment
• the product of the amount of source loading in terms of the milligram of radium content
and the number of hours of treatment duration
• (i.e., the milligram-hours concept of prescription)
(Heymann 1935; Kottmeier 1964; Ryberg et al. 1990)

PARIS SYSTEM
• Single application of Radium for 120hrs (5-6days) at a dose of 7000 - 8000 mg hrs
• 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.
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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 and specification.
• Source arrangement
• Position of tandem relative to the ovoids
• Packing of the applicators
• Tumour size, and
• Patient anatomy
• Ignored the importance of tolerance of different critical organs to radiation.

MANCHESTER SYSTEM
• developed by Tod and Meredith (Tod and Meredith 1938, 1953; Meredith 1967)
• first system to attempt to define dosimetry to particular reference points.
• points were based on a geometrical arrangement in order to standardize
dosimetry from patient to patient.

MANCHESTER SYSTEM
• prescription of dose to a point, known as Point A.
• Selection of this point enabled the investigators to perform the following:
• Standardize the treatment of one patient with another.
• This point was located in a relatively low dose gradient area.
• Therefore, dose to this point was not very sensitive to small alteration in applicator position.
• Correlate the dose to point A with the clinical results.

MANCHESTER
SYSTEM
• Point A corresponds to the
paracervical triangle at the medial
edge of the broad ligament where
the uterine vessels cross the ureter
• point was revised to
• 2 cm above the external cervical os
and 2 cm lateral to midline, or
• 2 cm above the distal end of the
lowest source in the tandem and 2
cm lateral to the tandem.

MANCHESTER
SYSTEM
• In addition to Point A, the
Manchester system uses another
point (Point B), representing the
pelvic nodes.
• This point was originally defined as
5 cm lateral from the midline at the
same level of point A

POINT A
• can’t be visualized on a radiograph.
• The central tendem is placed at the external os.
• 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 A
• Chosen initially because
• Believed to be a good index of normal tissue tolerance which is the dose limiting factor
• “High dose in the paracervical tissues, where the uterine vessels are crossed by the
ureter, produces dangerous extrinsic reactions”
• And comparable from case to case, not too variable with application

POINT B
• 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.

APPICATOR IN MANCHESTER
SYSTEM
pair of ovoids & an intrauterine tube

INTRAUTERINE TUBE
• tubes were available in three separate lengths
• 2cm
• 4cm
• 6cm

OVOIDS
• Used in pairs, one in each lateral fornix
• 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
• used
• To maintain the distance between the
ovoids
• To help in their fixation
• maintained a distance of 1cm between
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,
• 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.

ICRU SYSTEM – ICRU 38
• Recommends a common terminology for prescribing recording and reporting I/C
Brachytherapy applications.
• 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 the treatment technique (source, applicator)
• Total reference air-kerma rate
• Time dose pattern
• Description of the reference volume
• Dose at reference points (bladder, rectum, lymphatic trapezoid, pelvic wall)

BLADDER
• 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
• 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

REFERENCE VOLUME
• Volume encompassed by the reference
isodose, selected and specified to
compare treatments performed in
different centres using different
techniques
• recommends reference volume be
taken as the 60-Gy isodose surface,

TREATED VOLUME
• pear shape volume that received (at least) the dose selected and specified by the
radiation oncologist to achieve the purpose of the treatment

IRRADIATED VOLUME
• 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.

DRAWBACK OF ICRU 38
• Lack of information about correlation between
• Applicator and tumour
• Applicator and OAR
• Tumour and OAR
• OAR anatomic boundaries not very clear, estimated based on contrast
• Dose to target and OARs is not reliable
• All doses reported are a point dose which do not depict the actual dose delivered to
entire structure
• Points do not correlate with local control or toxicity
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DRAWBACK OF POINT A AND B
• It relates to position of sources and not to specific anatomic structure.
• It is very sensitive to position of ovoid sources relative to tandem sources which
should not be determining factor in deciding on implant duration.
• Depending on size of cervix point A may be inside or outside of tumor.
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FLETCHER WILLIAMSON APPLICATOR

• Clinical examination documents the
tumor anatomy and spread.
• This examination is recorded before
the initiation of therapy, and at the
time of each brachytherapy insertion,
in order to determine regression and
clinically determine sites at risk.

MRI
• in addition to a thorough gynecologic
examination,
• cross-sectional imaging is
recommended at the time of diagnosis,
immediately before brachytherapy, and
• ideally at the time of each insertion, in
order to assist in brachytherapy
planning and delivery

• Anticoagulativemedications must be stopped,and the international normalized ratio
(INR) normalized before insertion.
• Warfarin(Coumadin) andaspirin are usually held 1 week before the procedure.
• Patients on Coumadin may switch to enoxaparin (Lovenox); enoxaparin is held 24 hours
before the procedure.
• The patient is instructed to have a clear liquid diet 24 hours before the procedure, and to
take nothing by mouth after midnight the night before the procedure
• Brachytherapy is usually held should the absolute neutrophil count fall below 500
cells/μl and concurrent brachytherapy on the same day as chemotherapy is avoided to
minimize increasing the risk of normal tissue complications.

• A standard dilatation and curettage (D&C)
kit that includes
• uterine sound,
• a set of uterine dilators,
• two different-sized speculum,
• two right-angle retractors, two short
retractors,
• long DeBakey forceps without teeth,
• short forceps, suture needle holder,
tenaculum, clamps, and suture should be
present

SEDATION
• Adequate sedation of brachytherapy patients is a critical component in successful
treatment delivery.
• Potential options for anesthesia include general, spinal, or IV conscious sedation.
• If the patient is not adequately relaxed with IV conscious sedation, the levator
muscles tighten, which makes the insertion very difficult to perform.

SEDATION
• A good test of whether a patient can tolerate manipulation of the uterine canal
under conscious sedation is how she undergoes a pelvic examination during her
initial assessment.
• If a patient is intolerant of a pelvic examination, she most likely will not tolerate the
procedure unless regional or general anesthesia is given.
• Conscious sedation with IV fentanyl and midazolam

STEPS
• the patient’s skin is prepped with betadine (Betadine) and draped.
• A Foley catheter is inserted with radiopaque contrast inside the Foley balloon.
• For fluoroscopic simulation, 7 mL of contrast is placed in the Foley balloon per
International Commission on Radiation Units and Measurements (ICRU)
recommendations.63
• In a CT simulation, the 7 mL may be diluted to 2 mL of contrast and 5 mL of sterile
saline. A rectal tube is inserted into the rectosigmoid with 20 to 30 mL of barium
contrast

SOUNDING/DILATION
• To sound the uterus, the anterior lip of the cervix is grasped with a single-toothed
tenaculum.
• If the anterior lip is extremely friable because of tumor involvement or is effaced, a
suture through a healthy portion of the cervix instead of a tenaculum can provide
enough traction.
• To straighten and facilitate sounding of the uterine canal, the cervix is gently pulled
2 to 3 cm down the vagina

• First all debris is swabbed,
• a careful attempt is made to probe the
area with the sound in the area where
the os should be located.
• The most common location for a
perforation is in the posterior
endocervix or the lower uterine
segment, behind the cervical tumor.

• Once the sound sits in the fundus, the depth of the uterus is recorded by grasping
the exposed portion of the sound with a clamp at the cervix, and withdrawing the
sound.
• The sound is measured from its tip to the clamp with a ruler.

• Once the cervical canal is dilated, the tandem is
inserted at the predetermined distance;
• In the event of a retroverted uterus, the tandem
is placed to follow the cavity of the uterus and is
then gently rotated into the anterior position so
as to antevert the uterus.

• The largest ovoid is placed into the
vaginal fornices to increase tumor
coverage
• Smaller ovoids or mini ovoids have no
shielding and were designed to
accommodate narrow vaginal vaults
with minimal forniceal space

INTERSTITIAL IMPLANT
• Asuture is placed at the top of the vagina to retract the vaginal apex during needle
insertion.
• The vaginal obturator is inserted with the suture threaded through the center.
• A customized disposable gynecology template is positioned over the vaginal
obturator.
• Oncetheobturator lies at the correct angle, the template is secured by suturing the
four corners to the patient’s perineal skin.

• Interstitial flexible sharp catheters
and rigid obturators are inserted 1-cm
apart through the modified-disposable
gynecologic template into the
perineum
• The catheters are numbered for
identification and glued to the
template to minimize movement
during treatment

PACKING
• Packing is a critical portion of the
insertion, as it pushes the bladder and
rectum away from the highest-dose
regions.
• Packing is carried out using 1-in. wide
gauze and the long DeBakey forceps or
manual f inger insertion.

• The goal is to aim for the floor and the ceiling, but not cephalad to the ovoids, in
order not to displace the cervix away from the ovoids.
• As the packing is placed, the retractors are gradually withdrawn.
• The amount of anterior and posterior packing must be balanced in order to ensure
midline placement.
• The posterior packing is placed first because the tolerance of the rectum is slightly
lower than the tolerance of the bladder

• The placement of an external
stabilization device such as a perineal
bar or base plate and clamp is then
performed
• Or T bandage

IMAGING
• Applicator placement geometry can be confirmed
on fluoroscopy or orthogonal films or CT or MR
scout films after the patient is returned to a
more neutral supine position with thighs together,

3D VS 2D PLANNING
• Three-dimensional image-based
planning offers a number of distinct
clinical advantages over traditional
two-dimensional point-based planning:
• confirmation of applicator placement
including recognition of inadvertent
perforation
• improved tumor coverage, and
• decreased dose to critical organs

FRENCH PROSPECTIVE MULTI-
INSTITUTIONAL TRIAL
• enrolling >700 cervical cancer patients across 20 centers, which compared 2-
dimensional LDR or PDR brachytherapy to modern 3-dimensional (mainly CT-
based) image-based PDR brachytherapy
• Three-dimensional image-based brachytherapy significantly
• improved local control across subgroups (79–100 % versus 74–92 %, p = 0.003)
• improved disease-free survival (60–90 % versus 55–87 %, p = 0.086)
• more than halving the risk of toxicity (3–9 % versus 13–23 %, p = 0.002) as compared
to conventional 2-dimensional lm-based brachytherapy

CT PLANNING
• Plain CT scan is obtained after applicator insertion with 3-5mm cuts
• Advantages:
• verifies proper placement of applicator
• reasonable estimate of the location of uterus
• fairly good for visualizing bladder and rectum.
• analyses 3D Brachytherapy dose distribution
• depicts changes in the OAR related to tumor shrinkage & filling status.
• readily available in radiotherapy departments

CT PLANNING - DISADVANTAGE
• produce artifact with metallic applicators
• overestimate tumor contours compared to MRI (although additional width contoured
on CT may not be of detriment)
• fails to provide differentiation between the uterus, cervix, pariuterine tissues
• gross tumor volume (GTV) may not be adequately delineated on CT due to difficulty
in identifying the tumor consistently even with IV contrast.
• the superior border of the cervix is not well visualized on CT, but rather the entire
tandem length is activated and the top dwell is optimized to reduce sigmoid and
small bowel dose

MRI VS CT PLANNING
• MRI-based planning offers superior soft tissue contrast and remains the standard
for GTV and CTV definition
• benefits of MRI over CT-based planning were highlighted by a prospective
international comparison between CT- and MRI-based brachytherapy which showed
that CT-based brachytherapy significantly overestimates the tumor width especially
in the context of disease extending to the parametria 22

MRI VS CT PLANNING
• for patients with a good treatment response and no parametrial involvement, CT-
and MRI-based contouring were similar;
• however there was greater variation for cases with parametrial or sidewall
extension especially those with a good response favoring MRI-based planning

MRI - DISADVANTAGE
• requires special applicators like non-ferromagnetic, metal or plastic/graphite
• very expensive
• can produce motion artifact

6 STEPS IN IGBT
1.Applicat
or
insertion
1.3D
imaging
1.Contourin
g
1.Applicator
Reconstruction
1.3d dose
planning
1.Dose
delivery

GTV – GROSS TUMOR VOLUME
• includes macroscopic tumor extension at time of Brachytherapy as detected by
clinical examination and as visualized on MRI
• may not be adequately delineated on CT

CTV – CLINICAL TARGET VOLUME
• HR CTV – Macroscopic disease
• whole cervix and the presumed extracervical tumour extension at time of BT.
• Pathologic residual tissue(s) as defined by palpable indurations and/or residual grey
zones in parametria, uterine corpus, vagina or rectum and bladder on MRI are included
in HR CTV.
• No safety margins are added.

CTV – CLINICAL TARGET VOLUME
• IR CTV - significant microscopic ds
• HR-CTV +different safety margins are added (minimal 5 to 15 mm)

IR-CTV: FOR LIMITED DISEASE
(TUMOUR SIZE<4CM)
• In AP direction, a safety margin of up to 5 mm is taken, limited by the natural
anatomical borders of the rectal and bladder wall.
• A safety margin of 10 mm cranially into the uterine corpus
• Margin of 10mm caudally into the vagina.
• In lateral direction, a 10 mm safety margin is applied into both parametria, usually
representing the internal third of the parametrium.
• In case of endocervical or lateral macroscopic tumour growth
• an additional margin of 5 mm is applied, into the direction of potential spread.

IR-CTV: FOR EXTENSIVE DISEASE
• based on macroscopic tumour extension at diagnosis (GTVD) which is superimposed
on the HR CTV taking original anatomical tumour spread as reference
• Different safety margins are used depending on the extent of disease at diagnosis
and on the regression at time of BT.

IR-CTV: FOR EXTENSIVE DISEASE : MARGIN

PLANNING – DIGITIZATION
• process, referred to as digitization or
reconstruction, requires the
identification in the image of the
implanted sources or of the available
path to an HDR/PDR source inside the
patient
• Two techniques are widely available
for the reconstruction of an applicator:
• manual digitization and
• model-based digitization.

MANUAL DIGITIZATION
• Manual digitization consists of manually identifying the central lumen of the
applicator by clicking on its location on a computer screen.
• Manual digitization can be performed when the applicator central lumen can be
unambiguously identified.
• Visibility of the applicator central lumen is generally good on CT

MODEL-BASED DIGITIZATION
• Model-based digitization consists of the overlay of a model of the applicator provided
by the vendor on the image, with registration between the model and the applicator
• use of model-based digitization is advisable in situations in which the central
channel is not clearly visible

FIDELITY
• Three factors affect the fidelity of the digitization to the physical location of the
sources:
• variability of source location inside the applicator compared to commissioning data;
• changes in implant position between imaging and treatment; and
• uncertainty in digitization due to image resolution (eg, slice thickness) and observer
uncertainty

Sample Footer Text 12/5/2018 104

OPTIMIZATION
• In general, manual optimization begins at the tip of the tandem by incremental
adjustment of dwell times while evaluating the volumetric parameters for dose
reporting.
• By adjusting the dwell times at the tip of the tandem, the dose to overlying sigmoid
or bowel can be reduced without significantly reducing target coverage.
• The tandem dwell positions located within the HR-CTV may subsequently be
adjusted, as well as those within the ring or ovoids, to improve target coverage or
reduce dose to the adjacent bladder or rectum.

OPTIMIZATION
• starting point for optimization in cervical
cancer brachytherapy is a standard loading
pattern prescribed to point A that aims at
providing a pear-shaped dose distribution
akin to the Manchester system
• Point A was first defined as a dose limiting
point 2 cm superior along the tandem and 2
cm lateral in relation to the cervical os, and
then later used for prescription.

D100, D90 FIR GTV, HR-CTV, IR-CTV

D100 VS D90
• minimum dose delivered to 100% & 90% of target
• can easily be calculated from DVH and converted to EQD2 doses which makes them
suitable for plan comparison of all dose rate techniques.

D100 - LIMITATION
• extremely sensitive to inaccuracies in contouring & dose calculation
• Due to the steep dose gradient, small spikes in the contour cause large deviations in
D100

D90 - PREFERRED
• D90 is less sensitive to these influences and is therefore considered to be a more
stable parameter

OAR
• D2 cc - useful during dose planning and for evaluating toxicities
• D0.1 cc - indicative of the maximum dose

RECOMMENDED DOSE PRESCRIPTION
• Dwell positions and times are manually optimized for each fraction aiming for
• HR-CTV dose - D 90 %≥85–90 Gy (EQD 2 Gy )
• IRCTV dose – D90% > 60Gy of 60Gy
• D 2 cc of the rectum/sigmoid < ≤70-75 Gy EQD2
• D2cc bladder < 80 Gy EQD2
• Based on prospective studies from Korea and Vienna, if these organ-at-risk
constraints are met, the risk of grade 2+ late toxicities should be <5 % [ 35 – 37 ]

GOOD VS POOR RESPONSE
• For patients with a good response, the target HR-CTV D 90 % EQD 2 Gy is 80–85
Gy,
• while for patients with a poor response, bulky tumors, or a histology of
adenocarcinoma, dose escalation to an aimed EQD 2 Gy of 85–90 Gy may improve
outcomes based on published dose response data [ 38 , 39 ]

INTRACAVITARY
TECHNIQUE
• with either a tandem-and-ring or tandem-and-
ovoid applicator and tandem and multi channel.
• A tandem-and-ring applicator has the advantages
of easier placement and fixed reproducible
geometry.
• However, in comparison to tandem and ovoids, it
can increase dose to the vaginal surface, has less
lateral throw-off of dose, and is sometimes not
suitable for patients with a narrow vagina

HYBRID INTRACAVITARY-INTERSTITIAL
APPLICATOR

HYBRID INTRACAVITARY-INTERSTITIAL
APPLICATOR
• increase lateral coverage in patients with residual bulky central or medial
parametrial disease,
• increase dose to asymmetric cervical tumors,
• decrease dose to critical organs while
• maintaining adequate coverage of the target volume
• treatment of choice for patients with residual disease extending to the lateral
parametria and distal half of the vagina, bladder, or rectum or for patients where
the endocervical canal cannot be located because of distorted anatomy

• performed under general or spinal anesthesia,
• with an epidural anesthesia catheter placed preoperatively in order to augment
postoperative pain control.
• A tandem should be placed whenever feasible, as tandem placement is critical to
maintaining adequate HR-CTV dose and central dose inhomogeneity

• Ideally needles should be placed with 1 cm
spacing aiming to cover the gross disease plus an
additional 1 cm margin;
• the spacing and geometry are often best
maintained through the use of a perineal
template.
Martinez Universal Perineal
Interstitial Template (MUPIT)
Syed-Neblett template

INDICATIONS OF INTERSTITIAL
BRACHYTHERAPY
• Extensive residual disease(not likely to be taken care of by intracavitary
application)
• Extensive parametrial +/- sidewall invasion
• Vaginal extension
• Os not negotiable
• Fistulae
• Adjacent organ invasion
• Recurrent disease (post RT/post surgery)
• Narrow vagina
• Prior supracervical hysterectomyhttps://www.slideshare.net/upasnasaxena73?utm_campaign=profiletracking&utm_medium=sssite&utm_sourc
e=ssslideview

EVIDENCE
• Syed , Puthawala et al- IJROBP Sep 2002 LDR
• No=185
• EBRT – 50.40 Gy  Template LDR 40-50 Gy in 2 applications
• 5year DFS - IB-65%, II-67%, III-49%, IV-17 %
• Grade 3,4 late complications- 10%
• Demanes et al- IJROBP Aug 1999 HDR
• NO=62 ,locally advanced , early with abn anatomy
• EBRT – 50 Gy  Template 5.5 - 6 Gy X 6 #
• 5Year DFS - I-81%, II-47% III-39%, IV-0%
• LC rate- I-100% (12/12), II- 93% (25/27) III- 95% (18/19) IV- 75% (3/4)
• Grade 3-4 late complications -6.5 %
e=ssslideview

FISTULA
• The most severe complication is rectovaginal or vesicovaginal fistulae formation,
• causes significant physical, social, and psychological distress due to persistent
leakage of atus, stool, or urine and associated bleeding, pain, and increased risk of
infection.
• Management typically includes imaging (with contrast-enhanced pelvic MRI with
water-based vaginal gel representing the preferred modality) and exam under
anesthesia to con firm the presence of a fistula and rule out recurrent disease

FISTULA
• While it is important to confirm disease recurrence in the setting of fistulae as this
often directs management, it must be recognized that mucosal changes are common
following chemoradiation therapy and indiscriminate biopsies are a significant
precipitant of fistula formation and are often low yield .
• Once a fistula is confirmed, fecal or urinary diversion is warranted More commonly
patients may experience chronic rectal bleeding (daily or episodic, not uncommonly
associated with incontinence or diarrhea) as a result of radiation proctopathy

TREATMENT FOR FISTULA
• Once a fistula is confirmed, fecal or urinary diversion is warranted

BLEEDING PR
• More commonly patients may experience chronic rectal bleeding (daily or episodic,
not uncommonly associated with incontinence or diarrhea) as a result of radiation
proctopathy
• For patients experiencing mild to moderate bleeding, conservative management
with corticosteroid, sucralfate, or mesalamine enemas is effective in >70–80 % of
patients
• endoscopic evaluation with intrarectal thermal or photocoagulation is the most
effective means of reducing moderate to severe bleeding [ 79 , 80 ].

VAGINAL STENOSIS
• Vaginal stenosis remains a signficant source of morbidity with most patients
(upwards of 90 %) experiencing mild to moderate vaginal morbidity most commonly
manifested as vaginal stenosis or dryness [ 81 ].
• Dilator use remains an important part of mitigating risks of vaginal stenosis.

IRIDIUM-192
• half-life of 73.83 days.
• It decays by β– emission
• emits, on average,
• 29 γ-rays [mean energy = 372.2 keV, yield = 2.2/(Bq s)];
• 122 x-rays [3.6 keV, 2.7/ (Bq s)];
• 174 IC electrons [266.9 keV, 0.16/(Bq s)]; and
• 29 Auger electrons [844 eV, 2.3/(Bq s)]
• Radiation Protection – The HVL thickness for this radionuclide is 2.5 mm of lead.

FOLLOW-UP CARE
• Patients should be counselled that vaginal discharge is quite common following gynecologic brachytherapy
and may last for months after applicator removal.
• Douching and sexual intercourse may resume approximately 2 weeks after treatment completion.
• The standard follow-up schedule involves a clinical and pelvic examination
• every 3 months for 2 years, alternating between the gynecologist and the radiation oncologist,
• then every 6 months for 3 years, and
• annually thereafter

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