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Management of Carcinoma Cervix
Carcinoma cervix is the most common cancer in Indian women.
The incidence rates range from 19-44 per 1 lakh women in various
Cancer registries.
The diagnostic workup includes a Thorough Clinical History
with special emphasis on age at marriage, age at first pregnancy,
parity, multiple sexual partners, sexually transmitted diseases and
H/o smoking which is associated with increase in risk.
Physical Examination consists of general examination as well as
bimanual pelvic and rectal examinations. Examination under
anesthesia can be done if required.
Lab studies include a complete blood count, levels of blood urea
and serum creatinine to assess the renal function, liver function
tests , blood sugar analysis and analysis of urine.
These are followed by Pap smears and Colposcopy with
directed biopsies in women with abnormal pap test.
Endocervical Curettage is indicated in women with abnormal
Pap smear but having negative colposcopic findings or when the
entire squamocolumnar junction is not visualized.
Conization is indicated in patients who have inadequate
colposcopic findings but where the endocervical curettage shows a
high grade lesion or when the biopsy suggests microinvasion.
Punch biopsies are taken from the edges of any gross visible
tumor.
Cystoscopy and Rectosigmoidoscopy are indicated in cases of
suspicion of bladder and bowel involvement.
Radiologic studies include chest X-ray and IVP.
Barium enema is done from stage III onwards, and earlier stages if
symptoms are referable to colon or rectum.
Various complimentary procedures that are of help in diagnosis
and treatment planning are

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Ultrasonography of abdomen and pelvis, CT or MRI scans,
Recently PET scans have also been included and also the surgical
staging.
These procedures aid in treatment planning but cannot be used to
determine or alter the FIGO stage.
The FIGO Staging includes stages from stage 0 to stage IV.
Stage 0 is preinvasive carcinoma or carcinoma in Situ.
Stage I tumors are confined to cervix
stage IA is microinvasive cancer.
It has again been divided into stages IA1 and IA2 based on
the depth of invasion.
Stage IA1 is stromal invasion less than 3 mm and
IA2 is invasion between 3 to 5 millimeters.
In both these stages, the horizontal spread should not be more than
7 millimeters.
Stage IB is any clinically visible lesion confined to cervix or
microscopic disease greater than IA2.
On the basis of size, it has again been divided into stages IB1 and
IB2.
Stage IB1 is a lesion 4cm or less in diameter.
Stage IB2 is tumor more than 4 cm in size.
Stage II:
When the tumor spreads beyond uterus, but not upto the lateral
pelvic wall or lower 1/3rd of vagina, it is classified as stage II
tumor.
Tumor with no parametrial invasion is IIA and if it invades the
parametrium, it is classified as IIB.

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Stage III is the tumor extending up to the lateral pelvic wall or
lower 1/3rd of the vagina.
Tumors associated with hydronephrosis or non-functioning kidney
are also classified as stage III.
IIIA lesions are tumors invading the lower 1/3rd of vagina.
IIIB tumors extend up to the lateral pelvic wall or are associated
with hydronephrosis or nonfunctioning kidney.
Stage IV tumors have been classified as either stage IV A or B.
IV A tumors have invaded the mucosa of the bladder or rectum or
extended beyond the true pelvis.
IV B: Patients with distant metastases are classified as IV B.
In FIGO 2008 system, Stage IIA is subdivided
into stage IIA1 and IIA2 based on size (≤4 vs.
>4 cm).
Pathology:
Squamous cell carcinoma is the most common histological
subtype of carcinoma cervix and is diagnosed in over 90% of
cases.
7 to 10% are adenocarcinomas.
Stage wise management of carcinoma cervix:
1.) Management of STAGE 0 or carcinoma in situ depends
on whether the patient desires to preserve her fertility.
In patients who desire fertility preservation,
Ectocervical lesions can be managed with either of the following
procedures ie., LEEP, laser therapy, cryotherapy or conization.

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Patients with Endocervical canal involvement can be treated
with conization if they wish to preserve their fertility.
For Post Menopausal women,
The treatment of choice is either total abdominal or vaginal
hysterectomy.
Medically inoperable patients are treated with Intracavitary
irradiation alone up to a dose of 45 to 50 Gy to Point A.
2.) I A 1 ( No LV Invasion)
Conization for those who wish to preserve fertility.
Or,
Total hysterectomy in other patients (also indicated in patients
in whom cone margins are positive).
Patients unfit for surgery:
Intracavitary Brachytherapy alone is an option for patients
who are unfit for surgery.
Doses to Point A range from 60 to 70 Gy.
Patients with LVS invasion are treated in a manner similar
to stages I A2 and IB1

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3.) IA2:
Radical Hysterectomy with pelvic lymph node dissection.
Women not fit for surgery are treated with Brachytherapy
+ EBRT to pelvis to a total dose of 75 to 80 Gy to point A.
4.) STAGE IB1 and IIA (<4 cm)
Patients with Stage IB1 tumors and non bulky IIA lesions can
be treated with either Radical Hysterectomy plus pelvic
node dissection
Or
Pelvic RT plus Brachytherapy to a total dose up to 80 Gy to
Point A.
The results of either modality are equivalent.
The ABS recommends that:
Primary therapy should avoid the routine use of both radical
surgery and radiotherapy to minimize the morbidity related to
multimodality treatment.
5.) STAGE IB2 and Bulky IIA(>4cm):
Radical Radiotherapy + concurrent cisplatin based chemotherapy
with a total Point A dose of 85 Gy or more.
There is a lower level of evidence supporting radical surgery alone
as a treatment modality in this group of patients

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INDICATIONS OF ADJUVANT RADIOTHERAPY
(Post Operative)
In Node Negative Patients:
i.) Any two of the following features:
> 1/3rd Stromal Invasion
LV space Invasion
Large (>4 cm) tumor
ii.) Positive surgical margin & iii.) Positive parametrium
(Tx of choice for options (ii.) & (iii.) is pelvic radiotherapy with
concurrent cisplatin based chemotherapy and vaginal
brachytherapy if vaginal margins are positive).
In Pelvic Node Positive Patients:
Pelvic radiotherapy with concurrent cisplatin based chemotherapy
and vaginal brachytherapy if vaginal margins are positive.
6). STAGES IIB/IIIA/IIIB:
Pelvic RT + concurrent Cisplatin based chemotherapy

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followed by Brachytherapy
7.) STAGE IVA:
The treatment of Stage IV A needs to be individualized based on
the extent of bladder or rectal involvement, Renal function,
Parametrial involvement and performance status of the patient.
Surgical exenteration can be tried in patients with no or minimal
parametrial invasion and in patients with good performance status,
in the form of anterior, posterior or total exenteration, based on the
extent of bladder or rectal invasion.
Concurrent RT/CT is an option in selected patients with good
general and renal status who are not suitable for surgical
exenteration.
But majority of patients in this stage have poor general condition
and have extensive disease and are best treated with palliative RT
alone.
A short regime of 30 Gy in 10 fractions for two weeks can be tried
in these patients and those responding well can be followed up
with intracavitary application.
8.) Stage IV B:
Stage IV B patients are treated with palliative intent.
Radiotherapy can be used for palliation of distant metastases in
brain and painful bony metastases.

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Symptoms due to extensive central disease like pain, bleeding and
tenesmus can be effectively palliated with radiotherapy.
There is no standard chemotherapy regimen for palliative treatment
But combinations like cisplatin/paclitaxel, cisplatin/topotecan, and
cisplatin/ifosfamide have been used with varying response rates.
The ABS and NCI recommend the addition of ciplatin based
chemotherapy during the course of definitive irradiation from stage
IB2 onwards.
5 randomized trials have shown significant improvement in local
control as well as survival in these patients.
Most of these trials were performed in affluent countries, in
women with better nutritional and performance status, and better
renal parameters.
But patients in India are usually from lower socioeconomic status
and have more advanced disease with poor renal parameters and
there is a problem of doubtful compliance to treatment.
Therefore radical RT alone can still be considered as an acceptable
treatment approach in our patients.
INVASIVE CANCER FOUND AFTER SIMPLE
HYSTERECTOMY
Two Treatment Options:
1. Immediate Resurgery- Radical Parametrectomy and
Pelvic LND.
2. Post op RT:
Another option is post op. radiotherapy in the form of whole
pelvis radiotherapy 45-50 Gy, for patients with no disease or

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Pelvic RT with Concurrent Cisplatin based Chemotherapy for
patients with microscopic disease at margins followed by ICRT to
boost the dose at vaginal apex to 60-65 Gy(total dose).
For patients with gross residual disease in vault, whole pelvis dose
of 40 Gy is followed by additional 20 Gy to parametrium with
Concurrent Cisplatin based Chemotherapy and subsequent ICRT
up to 65 Gy mucosal dose.
RECURRENT DISEASE:
The treatment of recurrent disease depends on whether it is a post
RT recurrence or recurrence after surgery:
Post RT:
For small central recurrences after radiotherapy, either radical
hysterectomy or brachytherapy alone can be considered.
For larger central lesions in patients with good performance status,
pelvic exenteration is an option.
For pelvic side wall recurrences, only treatment options include
palliative chemotherapy or symptomatic or supportive care.
Post Surgery:
Post surgical recurrences can be treated with definitive pelvic RT
along with cisplatin based chemotherapy.
Extrapelvic/Distant Mets:

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Extrapelvic or distant metastases are treated with palliative intent.
RADIOTHERAPY
Radiotherapy for carcinoma cervix is delivered both as external
beam treatment and Brachytherapy.
EBRT treats the whole pelvis and parametria and intracavitary
brachytherapy primarily treats the central disease ie., cervix,
vagina and medial parametria.
EBRT is delivered before ICRT in the following circumstances:
1. In case of bulky cervical lesions to improve the geometry.
2. In exophytic easily bleeding tumors
3. In tumors with necrosis and infection
4. In cases with parametrial involvement.
EBRT Portals for AP/PA fields are:
Superior border is taken at L4-5 interspace in order to include the
common iliac nodes.
Inferior border is at lower border of obturator foramen. In case of
vaginal involvement, entire length down to introitus is included in
the portal.
The lateral border is taken 2 cm lateral to the bony pelvis on either
sides. In cases of involvement of lower 1/3 rd vagina, inguinal nodes
are covered.
Lateral Portal:

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Anterior margin of the lateral portal is taken at cortex of the
symphysis pubis in order to adequately cover the external iliac
nodes.
Posterior margin covers at least 50% of the rectum in stage IB, and
extends to sacral hollow in more advanced tumors.
Lateral fields allow a decrease in dose to small bowel and a portion
of the low rectum but care must be taken to include the all
structures of interest.
Midline Shielding
Midline shielding may be used for part of pelvic RT to shield
bladder and rectum to allow a higher dose to be given by
brachytherapy.
These can be made by simple rectangular blocks 4 cm wide at
midplane.
Customized blocks can also be made based on radiographs.
When inserted before 40 Gy, these should not extend to the top of
the pelvic field otherwise the common iliac and presacral nodes do
not receive adequate doses.
BRACHYTHERAPY:
 ABS strongly recommends that:
1) Definitive Irradiation for cervical carcinoma must
include brachytherapy as a component.
2) Precise applicator placement is essential for improved
local control and reduced morbidity.
3) Interstitial brachytherapy should be considered for
patients with disease that can’t be optimally encompassed

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by intracavitary brachytherapy.
4) Total treatment duration be less than 8 weeks when possible
(exceeding beyond 8 wks can reduce local control and survival
by about 1% per day of prolongation.
 Treatments Classified with respect to Source
loading:
1) Preloading: The applicator is preloaded and
contains radioactive sources at the time of placement into
the patient.
2) Afterloading: The applicator is placed first into the
target position and the radioactive sources are loaded
later, either by hand (MANUAL) or by a machine
( REMOTE AFTERLOADING).
 Treatments Classified with respect to Dose
Rate:
LDR: 0.4 – 2 Gy/hr
MDR: 2- 12 Gy/hr
HDR: > 12 Gy/hr ( practically much higher
dose rate used)
 Evolution Of Brachytherapy In Carcinoma Cervix:
First application of Radium in treatment of
uterine cancer- 1908
Three Basic Systems evolved:

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The Stockholm System
The Paris System
The Manchester System
Most systems used throughout the world are
derived from these three basic systems
Stockholm/Paris System- Applications reported in
terms of “mg.h”( milligram hours)- product of total
mass of Radium contained in the sources (in mg) and
duration of the application (in hours).
Manchester System: Designed to deliver a constant dose
rate to defined points near cervix, irrespective of variation
in size and shape of uterus/vagina.
Application specified in terms of “dose” in Roentgens delivered
at specific points ( Point A, Point B, Bladder Point, Rectal Point).
Duration of implant based on the dose rate calculated at Point A.
Optimal dose taken as 8000 R (72.8 Gy) in two sessions of 72 hrs.
each, 4-7 days interval.
POINT A: Originally defined as 2 cm superior to
the lateral vaginal fornix and 2 cm lateral to the
cervical canal( later redefined as 2 cm superior to
the ext cervical os/cervical end of the tandem,
and 2 cm lateral to the cervical canal).
POINT B: Defined 3 cm lateral to Point A( intended
to quantify the dose delivered to the Obturator L.Ns.)
Receives ~1/3–1/4 of dose to point A.
Dose to Bladder and Rectum: Localization of

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bladder and rectum can be performed using radiographs
taken with contrast media in bladder/rectum.
Maximum dose to bladder/rectum: 80% or less than
the dose to point A.
MANCHESTER SYSTEM APPLICATORS:
 Two vaginal Ovoids- made of hard rubber
Locked in position by spacer or a washer
Ovoid Sizes: 2.0/2.5/3.0 cm
 Intrauterine Tubes- made of thin rubber
Three different lengths for 1/2/3 radium
tubes each about 2 cm long.
Each tube is closed at one end and has a flange at the
other.
 Manchester ovoid dimensions and applicator
loadings were designed to ensure a dose rate of
about 0.52 Gy/hr , which remained constant for
all allowed applicator loadings and combinations.
Vaginal contribution to point A was limited to
40% of the total dose.
 Current Practice- Point A dose is used to
denote the average or minimum dose to the
tumor.

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Manchester System: Definition of Points “A” and “B”

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Modern Fletcher-Suit Applicator Systems
 Adhered to the basic Manchester design.
 After loading capability was added to the
Fletcher applicator by Suit and co-workers.
 Because of the similarity of Fletcher loadings
to the Manchester loadings, Point A dose rates
are nearly independent of the applicator
dimensions.
 Use of Cs-137 instead of radium.
Vaginal Cylinder
 Used in conjunction with an Intrauterine tandem
to irradiate the vagina when the disease extends
from the uterine cervix along the vaginal walls.
 Cylinder can be used alone after a radical
hysterectomy if there is a close or positive
vaginal margin.

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 Also useful for a patient with a very narrow vagina.
 Available in various diameters(1-5 cm) and lengths to
fit any vaginal width or length.
CESIUM- 137
 Most LDR intracavitary systems use Cesium as
as the implanted radioisotope.
 Similar in size and shape and have an output
similar to radium sources.
 Elimination of Radon gas leakage.
 Less required shielding for radiation protection
(lower energy, 0.662 Mev)
Characteristics of good insertion in brachytherapy
A-P View:
1) Tandem midline, unrotated
2) Tandem midway between colpostats
3) Colpostats high in the fornices along cervix
(approx 1/3rd of the ovoid should be superior
to the cervical collar and two-thirds should be
inferior).
Lateral View:
1) Tandem bisects the colpostats
2) Sufficient anterior and posterior packing
3) Foley baloon firmly tugged down

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SIMULATION:
After insertion of the applicator, dummy sources
are loaded into the afterloading applicators and
an orthogonal pair of radiographs are taken.
The isocenter is set at the centre of the collar for
Fletcher-Suit tandem and ovoid applications.
ICRU BLADDER and RECTAL REF POINTS:
Bladder Point- Foley balloon is filled with 7 cc of
radiopaque fluid( Hypaque) and pulled down towards
the bladder neck.
On Lat radiograph, obtained by drawing a
line through the center of the balloon and the posterior surface
of the balloon is used as the reference point.
On the anterior radiograph, the ref. point is taken at centre
of the balloon.
Rectal Ref Point:
Lat radiograph- An AP line drawn from the lower end of
the IU sources( or from the middle of the IV sources).
The Rectal point is taken at a depth of 0.5 cm, posterior
to the point where this line traverses the posterior
vaginal wall( identified by intravaginal radiopaque gauge.
AP radiograph- the Rectal point is at the lower end of the
IU source or at the middle of thr IV sources at the midline.
Dose Limitation:

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LDR: limit rectal point <70 Gy and bladder point
<75 Gy.

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Advantages of HDR versus LDR :
Presently there is a move towards HDR brachytherapy from
traditional Low dose rate systems:
1. Eliminates radiation exposure hazard for caregivers
and visitors.
2. Allows shorter treatment times.
3. Less risk of applicator movement during therapy.
4. Allows greater displacement of nearby normal tissues.
5. Possible to treat larger no. of patients.
6. Allows use of smaller diameter sources than are used in LDR
7. Reduces the need for dilatation of cervix and
therefore, reduces the need for heavy sedation or GA
every time.
8. Physically easier to insert applicator into the cervix.
9. Makes treatment-dose-distribution optimization possible.
HDR Equipment:
 Source most commonly used: Ir-192
 Half life- 74 days
 The encapsulated Ir-192 source is attached to
the end of a cable, which can be advanced or retracted
in precise increments using stepper motors ( stepping
source)
 The ability to control the locations and dwell times
permits greater flexibility modifying the dose distributions.
The HDR dose to Point A is approximately about 60 % of the LDR
dose.

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Dose Limitation:
HDR: limit bladder and rectal points to <70% of point
A dose
with HDR.
The Ring Applicator:
 Particularly useful when the vaginal fornices are asymmetric
or absent.
 It is popular because it has a reproducible geometry and is
easy to insert.
 It is important that the plastic cap of the ring applicator be in
place with each insertion, because excessive vagina mucosal
doses would be delivered without them.
 Also important not to activate the entire ring circumference;
usually the lateral 4 – 6 dwell positions are activated on each
side of the ring, dependent on the ring diameter.
SEQUELAE OF RADIATION THERAPY
Acute:
 Nausea, diarrhea, abdominal cramping, rectal discomfort,
Occasionally, rectal bleeding.
 Dysuria, frequency, nocturia, rarely hematuria;
UTIs .
 Pruritus, erythema, pigmentation, dry/moist desquamation in
perineum or intergluteal fold.

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 Radiation vaginitis/superficial ulceration of vagina/
vaginal stenosis
HDR and LDR morbidity are equivalent:
uterine perforation (<3%), vaginal laceration
(<1%),
DVT (<1%).
Late:
 Rectovaginal/vesicovaginal fistula- 1to2%
 Proctitis/cystitis(3-5% stage I-IIA, 10-15%
for stage IIB-III).
 ureteral stricture (1–3%)
 Intestinal obstruction or perforation(<5%)
 Vaginal stenosis,
 Anal Incontinence
 Femoral neck fractures/ lumbosacral plexopathy
(extremely rare)
FOLLOW UP:
Every month- For first 3 months.
Every 3 months- For remaining of the first year.
Every 4 months- The 2nd year.
Every 6 months- During the 3rd through 5th year.
And yearly thereafter.
Patients undergo Complete physical+ pelvic/rectal examination
with Pap smear taken from 3 months onwards. Follow-up Pap
smears controversial due to post-RT change.

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(+ chest X-ray annually for 5 years; CBC, Urea/creat. 6
monthly)
Other investigations( USG/CT) as clinically indicated.

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