This document discusses the use of external beam radiotherapy (EBRT) and chemotherapy in the treatment of cervical cancer. It outlines the indications for EBRT in definitive, adjuvant, and palliative settings. It describes various EBRT techniques including conventional, 3D-CRT, IMRT and discusses steps like simulation, planning, dose and fractionation. The role of concurrent chemoradiation using cisplatin is discussed based on evidence from large randomized trials showing improved survival. Adjuvant chemotherapy with cisplatin and mitomycin C is also addressed.

1. EBRT & CHEMOTHERAPY
IN CANCER CERVIX

2. SPECIFIC LEARNING OBJECTIVES
To learn about the various indications of using External beam
radiotherapy (EBRT) in cases of cervical cancer
To learn about the various techniques of EBRT – conventional, 3D-
CRT, IMRT
To learn about role of concurrent chemoradiation in treatment of
cervical cancer
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3. INDICATIONS OF EBRT
IN A DEFINITIVE SETTING:
CIS & Ia1-
 If pt prefers RT/deemed inoperable/ unfit for surgery
 Brachytherapy ± EBRT
Stages Ib- IIa2
EBRT + Brachytherapy
 May be taken up surgery but often need adjuvant RT
Stages IIb to IVa
EBRT + Brachytherapy
1. Grigsby et al. IJROBP
1991
2. Landoni et al. Lancet
1997
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4. IN ADJUVANT SETTING
Adjuvant RT alone1: (any 2/3
needed)
 >/ 1/3rd Stromal invasion
 LV space invasion
 Large ( >/ 4cm) tumor
Adjuvant CTRT2
 Positive Pelvic Nodes
 Positive / Close ( <3mm margins)
 Parametrial involvement
3Monk et al subgroup analysis showed
that benefit was less in pts with ≤2cm
tumors & only 1 positive node.
1
2
3
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5. INDICATIONS OF PALLIATIVE
RADIATION
In Stage IVb:
Vaginal bleeding (Hemostatic RT)
Pain
Urethral Obstruction
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6. TECHNIQUES OF EBRT
Conventional
3D CRT
IMRT/ IGRT
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7. STEPS OF PLANNING EBRT
•Positioning & Immobilisation
Simulation
•Field Design
Beam energy
•Dose & fractionation
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8. POSITIONING
Patients may be positioned in
Supine position or Prone position
with belly board
Supine position preferred
because: most comfortable,
reproducible, stabilizes pelvis,
can be combined with
immobilisation devices
Knee rest : Relaxes lower back
making pt more comfortable,
Minimises rotation of pelvis
Prone position on a belly board:
Belly board is used to allow the
intestinal tract to drop out of t/t
field.
Foam material – low beam abs
Preferred in Post- hysterectomy
pts, obese pts
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9. IMMOBILIZATION
Can be achieved by using
Thermoplastics
 Use difficult due to lack of bony points
for fixation
 Continuing abdominal movements with
respiration
 Presence of Fat pads & folds
Simple supine positioning with
skin markings:
 Cheap
 Reproducible
 Ease of use & comfortable for pt
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10. SIMULATION
X ray based simulation:
CT Simulation:
 Vaginal maker placed at the lower extent of disease when disease extends into
vagina to determine length of vagina involved
 Or marker placed at the external os and lower extent of disease determined
individually based on findings of clinical examinations
 IV contrast can be used to outline pelvic vessels (surrogate for nodes)
 Oral and Rectal contrast for delineation of OARs (optional)
 CT Scan Obtained from T10-T11 interspace to upper 1/3rd of Femur
 Slice thickness: 3-5mm
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11. BLADDER PROTOCOL
No ideal bladder protocol. Varies from institutions to institutions.
Bladder filling - matter of debate
George et al (1) & Pinkawa et al ( 2) recommended a full bladder for
t/t of gynecological malignancies, as the Dose-vol-load to bladder &
cranially displaced sigmoid colon/small bowel loops can be reduced
significantly.
However, Pinkawa in another stodu (3), found that bladder wall
displacements are reduced significantly ( P< 0.01) at superior &
anterior border while treating empty bladder compared to full
bladder. Less variability in size of empty bladder.
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12. Bladder filling had less impact on cervix motion than uterine motion,
with a 5.5 mm inferior and 3.9 mm anterior shift in cervical position
shown from empty to full bladder
So it is very important to establish a reproducible bladder filling
protocol for implementation of newer radiation techniques in cervical
cancers with intact uterus and cervix.
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EVIDENCE BASED MANAGEMENT OF CANCERS IN INDIA, U MAHANTSHETTY

13. CONVENTIONAL PLANNING- 2 FIELD
TECHNIQUE
Although the AP-PA field technique
provides good coverage to the target
volume, its main disadvantages are inferior
dose distribution in the region of
parametrium and increased dose to
bladder, rectum, and subcutaneous tissue
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14. 4 FIELD BOX TECHNIQUE
The conventional four field box technique with parallel opposed
AP-PA fields and two lateral opposed fields achieves better dose
distribution than the parallel opposed AP-PA field technique in terms
of tumor coverage and a relatively reduced dose to the normal
tissues.
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20. PARA-AORTIC LN IRRIDIATION
Indications:
• Def: In radiologically or Histogically positive Para-aortic LN
• Proph: In pts with high risk of para-aortic LN involvement, pt with positive pelvic
nodal ds and not receiving CTRT1
Types:
• Extended Field RT: Pelvis & para-aortic LN t/ted as contiguous extended field
portal
• Separate Field RT- gap calculation b/w pelvic & para-aortic portals to avoid
overlap & excessive dose to small intestines
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22. PARA-AORTIC: 2 FIELD VS 4 FIELD
AP – PA treatments to the para-aortic Nodal chain may overdose the
kidneys, SC & Small bowel
The SC dose ( T12 – L2-3) should be kept to Dmax < 45 Gy
This can be done by midline shielding after 40 Gy tumor dose or
using lateral ports and limiting kidney dose to Dmax < 18 Gy.
Use of 4 fields, included AP –PA & 2 lateral fields  ↓ dose to ant
small bowel, kidney & SC
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23. MIDLINE SHIELDING IN AP-PA
PORTALS
Midline blocks ( 2cm thick, 5 HVL
on the post portal) – used for
Shielding in a portion of EBRT,
delivered via AP-PA fields.
Midline blocks may be
individualized, based on the
point A isodose line or a
rectangular block of
approximately 4-cm width.
Can be used to boost the
parametria or nodes for patients
with persistent disease after
approximately 45 to 50 Gy.
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25. CONFORMAL PLANNING
Involves a. Target Volume Delineation Various Guidelines for CTV
delineation are published in the literature yet consensus definition of
CTV remains variable
 Taylor et al pelvic nodal delineation (CT Based)
 Toita et al for CTV delineation in intact cervix (EBRT) (CT Based)
 Lim et al for CTV delineation in intact cervix IMRT (MRI based)
 Small et al for CTV delineation in post op IMRT (CT Based)
 PGI Literature review & Guidelines for delineation of CTV for Intact carcinoma cervix (CT Based)
 Kim et al
b. Organs at Risk Delineation
 Pelvic Normal Tissue Contouring Guidelines for Radiation Therapy : An RTOG Consensus Panel Atlas
(CT Based)
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26. I. J. RADIATION ONCOLOGY D BIOLOGY D PHYSICS VOLUME 79, NUMBER 2, 2011 26
Red – GTV, cervix - pink, vagina -
yellow, parametria - green, and
uterus- blue

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31. ISODOSE COLOUR WASHES
4 Field Box technique via 3D
CRT
IMRT
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32. BEAM ENERGY
Because of thickness of pelvis, High energy Photon beams ( 10 MV or
higher ) are especially suited for this treatment
They decrease the dose of radiation delivered to the peripheral
normal tissues (BLADDER & RECTUM).
Provide a more homogenous dose distribution in central pelvis ,avoid
subcutenous fibrosis.
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33. DOSE & FRACTIONATION
 Primary Radiotherapy:
 Stage IB2 & Iia
 45 Gy in 25 daily # of 1.8 Gy/ 5 weeks fb Intracavitary brachytherapy
 Stage Iib or above
 50.4 Gy in 28 daily # of 1.8 Gy/ 5.5 weeks fb fb Intracavitary brachytherapy
 Persistant / Bulky parametrial tumor : Boost upto 60 Gy
 Adjuvant RT
 45 Gy in 25 daily # of 1.8 Gy in 5 weeks
 50.4 Gy in 28 daily # of 1.8 Gy in 5.5 Weeks (if microscopic residual disease)
 Para-aortic node Radiotherapy
 Adjuvant RT : 45 Gy in 25 daily #s of 1.8 Gy given in 5 weeks
 Palliative RT
 Whole Pelvis / Para-aortic Nodes
 20-30 Gy in 5 -10 daily fraction given in 1-2 weeks
 8-10 Gy in SF for hemostasis
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34. Pelvic RT or chemoradiation will invariably lead to ovarian failure in
premenopausal women.
To preserve intrinsic hormonal function, ovarian transposition may be
considered before pelvic RT for select women younger than 45 years
of age with squamous cell cancers.
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35. IMRT IN CA CERVIX
Requires Inverse Planning
Modulates intensity of beam using MLCs
Computerised software used to conform the dose
to the shape of the target in 3DBrachytherapy
Rationale:
Decrease dose to normal tissues
Dose escalation in high risk pts – Node +ve, Gross
residual dis
Replacement/ Integration with brachy
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38. CHEMOTHERAPY IN CA
CERVIX
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41. CISPLATIN
Platinum Analogue
MOA:
Covalent binding with DNA (N7 of guanine & adenine)
DNA cross links (intrastrand – 95%, interstrand 5%) – DNA adducts – inhibition of DNA synth
& transcription)
Metabolism: T1/2 – 20-30mins following bolus administration
Toxicities:
 Nephorotoxicity – Dose limiting – 30-40% pts, irreversible, ↓Mg, ↓Ca, ↓K
 CINV – Acute (< 24hr)- begins within 1 hr, can last upto 8-12 hrs, Delayed (>24hrs) : 3-5 days post
administration of drug
 Myelosuppresion: 25-30% pts – Neutropenia & TCP
 Peripheral Neuropathy – glove & stocking pattern – irreversible
 Ototoxicity – High frequency HL, tinnitus
 Ocular tox – ON, papilledema
 SIADH
 Vascular Events – MI, CVA, TMA
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42. Mitomycin C acts as an alkylating agent and inhibits DNA and RNA
synthesis.
Activation of mitomycin C is increased in hypoxic conditions, and
thus, it acts as
a hypoxic radiosensitizer. Interstitial pneumonitis and pulmonary
fibrosis are
usually related to the dose of drug. Use of IV dexamethasone before
administration of the drug may prevent pulmonary toxicity
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46. RCTS – CTRT IN CERVICAL CANCER
Author Drugs No of
patient
s
Median
Follow-Up
Time (
Year )
Survival
CTRT (%) RT(%) P value
Chemoirradiation Versus radiation Alone
Eifel et al (RTOG 9001 CF 389 6.6 67 41 <0.0001
Keys et al (GOG 123) C 369 8.4 78 64 <.015
Peters et al (SWOG
8797)
CF 243 5.2 80 66 NR
Pearcey et al (NCIC) C 253 6.9 62 58 0.53
Comparitive Trials of Chemoirradiation Regimens
Whitney et al (GOG
85)
CF vs H
Rose et al (GOG 120) C Vs H,
CHF vs
H
526 8.8 5 yr – 60, 10 yr -
53
5 yr – 61, 10 yr –
53
5 yr – 40, 10 yr –
34
5 yr – 40, 10 yr -
34
0.002
0.002
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47. ROLE OF NEOADJUVANT CHEMO
Concluded that the role of neoadjuvant chemotherapy followed by
radiation and by concomitant chemotherapy or by surgery is
controversial because no significant advantages in survival or local
control have been shown
Receiving upfront chemotherapy may compromise immune status and
the patient’s ability to receive definitive treatment with radiation or
surgery.
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48. META-ANALYSIS FAVOURING
CHEMO-RT
Benefit of CRT Green, 2001 Green, 2005 Cochrane, 2010 (IPD
Meta-analysis)
No of studies 19 total – 17 + 2
(unpub)
24 total – 21 + 3
(unpub)
13
Patients 4580 Randomised
2865 – 3611 available
4921 Randomised
3578 available
3452 randomised
3000 available
Absolute PFS Benefit 16% (47 – 63%) 13% ( 50 – 63%) 8% DFS Benefit
(50 – 58%)
Absolute OS Benefit 12% ( 40 – 52%) 10 (60 – 70%) 6% (60-66%)
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49. SPECIAL SCENARIOS:
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Small cell carcinoma of the cervix - High proliferation rate
and marked propensity for regional lymph node and distant
metastases - workup should include bone marrow aspiration
biopsy of the iliac crest, metastatic work-up. –EBRT – 45 Gy fb
nodal boost (if PET-positive nodes are identified), fb
brachytherapy - most frequently prescribed chemo - cisplatin and
etoposide (VP-16) every 3 weeks
Adenocarcinoma of the cervix – asso with HPV 18 -
endocervical involvement - Adenocarcinoma predicts
worse OS on multivariate analysis -

50. THANK YOU
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