Management of cacrinoma cervix: Techniques of radiotherapy (2D conventional, 3D Conformal radiotherapy (3DCRT) and IMRT with a review of various contouring guidelines.

1. Radiotherapy Techniques
In Carcinoma Cervix
Dr Animesh Agrawal
Dr Ram Manohar Lohia Institute of Medical Sciences, Lucknow

2. • Cervical cancer has two components:
• Central
• Disease in the cervix, vagina & medial parametria
• Peripheral
• Disease involving lateral parametria & regional lymph nodes

3. Intent of using EBRT
• Definitive
• Adjuvant (post operative)
• Palliative

4. Indications of definitive RT
CIS and IA1
• If patient prefers RT /deemed inoperable / unfit for surgery
• Brachytherapy + External beam radiotherapy
Stages IB-IIA2
• EBRT + brachytherapy
- May be taken up for surgery but often need adjuvant RT
Stages IIB to IVA
• EBRT + Brachytherapy
1. Grigsby et al. IJROBP 1991
2. Landoni et al. Lancet 1997

5. • Adjuvant RT alone (no chemotherapy)1:
• > 1/3rd Stromal Invasion
• LV space Invasion
• Large (> 4 cm) tumor
• Concurrent chemotherapy with EBRT2,3:
• Positive Pelvic Nodes
• Positive/close (<3 mm) margins
• Parametrial involvement
Indications of Adjuvant RT
1. Rotman et al. IJROBP 2006
2. Peters et al. JCO 2000
3. Monk et al. Gynecol Oncol 2005

6. EBRT: treat the whole pelvis (WPRT)
Target volume includes:
• Uterus and cervix
• Tumor bed (in postoperative cases)
• Vagina: Depending on extent of involvement
• Parametrial tissue
• Lymph nodes: Paracervical, parametrial, obturator, presacral,
internal iliac, external iliac, common iliac.
• Para-aortic nodes – Clinician’s discretion

7. EBRT techniques
• Conventional
• 3DCRT
• IMRT/IGRT
Planning technique
• Positioning & Immobilization
• Simulation
• Field design
• Beam energy
• Dose & fractionation

8. Positioning & Immobilization
Patients may be positioned in
• Supine position
• Prone position with belly board
Supine position is preferred
• Most comfortable
• Reproducible position
• Stabilizes pelvis
• Can be combined with immobilization devices
Knee rest can be used
• Relaxes lower back; may be more comfortable
• Minimizes rotation of pelvis
• Knee rest with indexing limits superior-inferior and lateral motion
Belly Board

9. Prone position on a belly board
• Used to allow the intestinal tract to drop out of treatment field1.
• Esp. in hysterectomy pts, small bowel may drop into the pelvic area so
prone position may be beneficial
• Made of foam material has a low absorption of the beam.
• For patients with an intact cervix, the small bowel often lies
superior to the uterus and above the pelvic brim, creating less need
to shift the bowel out of the pelvis.
Wiesendanger-Wittmer et al. Radiother Oncol 2012

10. Immobilization options
• Thermoplastics difficult to use in the pelvis:
- Lack of bony points for fixation
- Continuing abdominal movements with respiration
- Presence of fat pads and folds
• Simple supine positioning with skin markings:
- Inexpensive
- Reproducible
- Ease of use and comfortable for patient.

11. Need of contrast during simulation
• Primary target and OAR structures can be contoured even without
contrast on CT.
• May be helpful in conventional simulation to enhance soft-tissue
detail
• Contrast may be placed at following sites
• iv contrast to localize the pelvic vessels and assist nodal delineation
• Oral contrast to delineates small bowel.
• Foley’s catheter with bladder contrast
• Barium in the rectum,
• Vaginal tube in the vagina

12. X-Ray Simulation
• Conventional simulator can be used to acquire patient data
• Patient position:
• Supine with arms on the chest/by the side
• Knee and lower leg immobilisation may be used to minimize pelvic rotation
• Orthogonal laser beams aligned with anterior and lateral tattoos marked with
radio-opaque material.
• For obese patients, a prone belly board may be used.
• Lower extent of disease marked with radio-opaque material (intravaginally or at
perineum)
• Bladder and rectal protocol may used.
• AP and lateral simulator films are then taken.

13. Field borders: AP-PA
Superior border
• At the L4-5 space to include common iliac
nodes.
• Extended to T11-12 to treat paraaortic nodes
Inferior border
• At inferior margin of the obturator foramen
OR 2-3cm below the lower most extent of
disease
(Whichever is lower.)
Lateral borders
• 1.5 - 2cm margin on the widest portion of
pelvic brim.
• For tumours that involve lower third of
vagina, inguinal nodes should be included.

14. Anterior margin
• Vertical line at the anterior edge of pubic
symphysis to cover external iliac lymph
nodes.
Posterior margin
• S2 – S3 junction (covers the presacral nodes)
• Extend to sacral hollow in patients with
advanced tumours to cover uterosacral
ligaments & cardinal ligaments.
Superior & inferior margins
• Same as that for AP/PA Fields
Field borders: Lateral

15. Shielding of A-P fields
•Red: cervix;
•Blue: uterus;
•Green: bladder;
•Brown: rectum
•Orange: common illiac LNs;
•Yellow: external illiac LNs;
•Light Green: obturator LNs;
•Purple: internal illiac LNs;
•Dark Green: presacral LNs
Superior
corners, for
bowel loops
Inferior
corners, for
femoral heads

16. Shielding of Lateral fields
• Lateral beams: for
sacral nerve roots
posteriorly.
• For simulation of para-
aortic nodal beams,
intravenous contrast is
required to localise
kidneys for shielding
•Red: cervix;
•Blue: uterus;
•Khaki: bladder;
•Brown: rectum
•Orange: common illiac LNs;
•Yellow: external illiac LNs;
•Light Green: obturator LNs;
•Purple: internal illiac LNs;
•Dark Green: presacral LN

17. Schematic diagram depicting nodal coverage with the 4-field
box in the (A) AP-PA fields and (B) lateral fields.

18. Midline shielding
• Midline shielding with rectangular or
specially designed blocks have been used
for a portion of EBRT dose delivered with
the AP-PA ports.1
• Allows higher paracentral doses, boosting
the central disease with brachytherapy.
1. Perez & Brady's Princ1iples and Practice of Radiation Oncology, 6th edition
2. McIntyre et al. Cancer 1995
• Midline blocks may be individualized, based on the point A
isodose line or a rectangular block of approximately 4-cm width.
• However a midline block has been questioned because it may
result in tumor underdosing (eg. Uterosacral ligaments) while still
contributing significant dose to the ureter, sigmoid, and rectum2.

19. Para-arotic nodal irradiation
• Extended field (EFRT)
• Pelvis & para-aortic L.N. should be treated as contiguous
extended field portal
• Separate field
• Para-aortic L.N. and the pelvis are irradiated through separate
portals
• Patient position: Arms above the head

20. Para-aortic LN field borders: AP-PA
Superior Border: T11-T12 or T12-L1 junction
Inferior Border: L5-S1 junction
Lateral borders: as per
imaging
Typically 8-10 cms (4-5cm
either side of midline)

21. Para-aortic field: 2 field vs. 4 field
• AP-PA treatments to the para-aortic nodal chain may overdose the
kidneys, spinal cord, and small bowel.
• This can be done by:
• Interposing a 2cm wide shield on the posterior portal (usually
after 40Gy) OR
• Using lateral ports and limiting the (mean) kidney dose to ~
18 Gy.
• The use of four fields, including AP-PA and two lateral fields, is
implemented as an alternative to AP-PA alone as a way to reduce
some of the dose to the anterior small bowel, kidney and cord.

22. Para-aortic L.N field borders
2cm

23. TWO FIELD
• Heterogeneous dose
distribution
• Parametrium under dosed
• More skin reaction
• Useful when lower part of
vagina involved
FOUR FIELD
• Homogeneous box shaped
dose distribution
• Whole target volume
including parametrium gets
adequate dose
• Skin reaction are decreased
• Treatment time more

24. Dose distribution -2 field vs. 4 field

25. Beam Energy
• Depends on the thickness of the patient.
• Because of the thickness of the pelvis, in general high-energy
photon beams (10 MV or higher) are typically useful.
• Provide a more homogeneous dose distribution in the central
pelvis.
• Decrease the dose of radiation delivered to the peripheral
normal tissues (particularly bladder and rectum)
• Lesser chances of subcutaneous fibrosis (as the Dmax is deeper).

26. Dose & Fractionation
Definitive radiotherapy
• 45 – 50.4 Gy in 25-28 daily fractions of 1.8 – 2 Gy over 5-5.5
weeks followed by Intracavitary brachytherapy.
Persistent /bulky parametrial tumor: May boost upto 60 Gy
Adjuvant radiotherapy
• 45 – 50.4 Gy in 25-28 fractions of 1.8 – 2 Gy over 5-5.5 weeks
followed by vaginal brachytherapy.
Practical Radiotherapy Planning; Jane Dobbs

27. Limitations of the 4-Field Box
• Several authors have suggested that there are chances
geographic miss of disease.1-4
• Beadle et al in a retrospective review of 197 patients with
recurrent disease found that most failures were marginal.5
• This suggests a deficiency in target volume coverage by
this field arrangement.
1. Bonin et al. IJROBP 1996
2. Zunino et al. IJROBP 1999
3. Knocke et al. Strahlenther Onkol 1999
4. Finlay et al. IJROBP 2006
5. Beadle et al. IJROBP 2010

28. N = 197
Beadle et al. IJROBP 2010

29. A Shift to Conformal Techniques
• With the advent of planning based on CT and MRI, target
volumes can be more accurately defined.
• 3D imaging based planning allows a better approximation of
the location of nodes and gross disease.
• Combined with findings from the clinical examination,
forms the current standard of delivering pelvic RT.

30. • Comparisons between the conventional and 3D-conformal
planning techniques have shown better coverage of target
volumes with the latter without a significant increase in
toxicity.1-4
• Hsieh et al demonstrated a survival benefit for patients treated
with 3D-CRT vs 2D-RT (82.3% vs 73.0% at 5 years, p = 0.007)5.
1. Gulia et al. South Asian J Cancer, 2013
2. Mahanshetty et al. South Asian J Cancer, 2013.
3. Goswami et al. South Asian J Cancer, 2013.
4. Van de Bunt et al. Int J Radiat Oncol
Biol Phys, 2006.
5. Hsieh et al, ISRN Oncol, 2013

31. • 50 patients of locally advanced cervix cancer (stage II - III)
- 32 patients (64%) belonged to Stage IIB and 18 (36%) to
Stage IIIB.
• Nodal CTV was contoured as per Taylor’s guidelines, and
primary CTV included the uterine corpus, cervix, upper third of
the vagina, and parametrium.
• 4 field plan was made (superior border at L4-L5) and coverage
of the PTV by was analysed.
Four field vs CT based treatment planning
for CA Cervix: A Dosimetric Study
Gulia et al. South Asian J Cancer, 2013

32. • The target volume delineated was then projected onto the digitally
reconstructed radiograph (DRR) and the distance of the target
volume from the edges of the field was measured.
• V95 was subtracted from the total target volume to calculate the
volume that would have been missed in conventional planning
based on bony landmarks
Gulia et al. South Asian J Cancer, 2013

33. Results:
• In 48 out of 50 patients, the conventional four field box failed
to encompass the whole of target volume.
• Areas of miss were at the superior and lateral borders of the
anterior-posterior fields, and the anterior border of the lateral
fields.
Gulia et al. South Asian J Cancer, 2013

34. • There was a statistically significant increase in volume of tissue
irradiated while using CT-based 3-D plans.
• In addition, the mean dose to the bowel and bone marrow was
increased significantly in the CT-based plan when compared with
four field plan
Conclusion: Study shows inadequate target volume coverage
with conventional four field box technique.

35. 3D Conformal Planning
• Patient position and immobilization
• Volumetric data acquisition
• Image transfer to the TPS
• Target volume delineation
• Planning
• Dose distribution analysis
• Treatment QA & delivery

36. CT Simulation
• CT based planning is recommended.
• Patients are usually scanned in supine position, arms overhead ,
knees immobilised with knee rest
• For obese patients: Prone belly board may be used
• Lower extent of disease marked by a marker:
• Intravaginally, OR
• At the introitus; border set according to clinical examination findings
• Iv contrast may be used to facilitate target delineation.
• Oral and rectal contrast may be given for delineation of critical
structures.
• Slice thickness may vary from 3-5 mm depending upon
institutional protocol.

37. • In pelvic malignancies bladder filling status has largely been the
matter of debate.
• A full bladder pushes the GI loops outside the pelvis thereby
reducing dose. However there is considerable variability in
bladder filling and the resulting bladder positions1-3.
• The ideal bladder filling status is yet to be determined; a
“comfortably full” bladder protocol is sometimes advocated4.
Bladder Protocol for Simulation
1. Georg P et al. Radiother Oncol 2006
2. Pinakawa et al. Radiother Oncol 2003
3. Pinakawa et al. Radiother Oncol 2007
4. Perez and Brady’s Principles and
Practice of Radiation Oncology, 6th ed.

38. Target Volume delineation
• For definitive treatment of carcinoma cervix with conformal
radiation techniques, accurate target delineation is vitally
important,
• Various guidelines for CTV delineation are published in the
literature yet a consensus definition of clinical target volume
(CTV) remains variable
• Clinical judgement remains the most important aspect of
determining the target volumes

39. Delineation of Target Volumes
Guidelines for organs at risk (OARs)
• Pelvic Normal Tissue Contouring Guidelines for Radiation
Therapy: A Radiation Therapy Oncology Group Consensus Panel
Atlas (CT based, by the RTOG)
Based on Author
CT
Taylor Pelvic nodal delineation
Small CTV delineation in post-op gynecological IMRT
Bansal
PGI literature review & guidelines for delineation
of CTV in carcinoma of the intact cervix
MRI Lim CTV delineation in intact cervix IMRT

40. Mapping pelvic lymph nodes: Guidelines for
delineation in intensity-modulated radiotherapy
Taylor et al. IJROBP 2005
• MRI images pre and post contrast (USPIO, Ultrasmall Particles
of Iron Oxide) were used to delineate nodes.
• Five Nodal CTVs were contoured as 3mm, 5mm, 7mm, 10mm
and 15mm margins to the blood vessels and the nodal coverage
thus obtained was analysed.
• Apart from presacral and lateral external iliac group, > 95% of all
other nodes were covered by a 7mm margin.
• The lateral external iliac group was covered by expanding the
margin by another 10mm, i.e. a total of 17mm.
• As there are no major vessels in the pre-sacral region, a 10mm
wide strip was suggested for coverage.

41. Nodal group Recommended margins
Common Iliac 7-mm margin around vessels; extend posterior and
lateral borders to psoas and vertebral body
External Iliac 7-mm margin around vessels; extend anterior border
by additional 10-mm anterolaterally along iliopsoas
muscle to include lateral external iliac nodes
Obturator Join external and internal iliac regions with 18-mm-
wide strip along pelvic sidewall
Internal Ilian 7-mm margin around vessels; extend lateral borders
to pelvic sidewall
Pre-sacral 10-mm strip over anterior sacrum
Taylor et al. IJROBP 2005
Recommend margins for delineation of Nodal CTV

42. Taylor et al. IJROBP 2005
Common Iliac: 7-mm margin around vessels; extend posterior and lateral
borders to psoas and vertebral body

43. External iliac: 7
mm margin around
vessels.
Extend border by a
further 10 mm
anterolaterally along
the iliopsoas muscle
to include the
lateral external
iliac nodes
Internal iliac: 7 mm
margin around
vessels. Extend
lateral borders to
pelvic side wall.
Taylor et al. IJROBP 2005

44. Obturator Join external and internal iliac regions with 18-mm-wide strip along
pelvic sidewall
Taylor et al. IJROBP 2005

45. Pre-sacral 10-mm strip over anterior sacrum
Taylor et al. IJROBP 2005

46. • CTV definition for the post-operative therapy of endometrial and
cervical cancer should include the common, external, and internal
iliac lymph node regions.
• The upper 3.0 cm of vagina and paravaginal soft tissue lateral to
the vagina should also be included.
• For patients with cervical cancer, or endometrial cancer with
cervical stromal invasion, it is also recommended that the CTV
include the presacral lymph node-region.
Guidelines For The Delineation Of The Clinical
Target Volume In The Postoperative Treatment Of
Endometrial And Cervical Cancer
Small et al, IJROBP 2008

47. Volume Recommended margins
Upper Vagina Vaginal cuff and 3 cm of vagina inferior to cuff
Parametrium/
Paravaginal
From vaginal cuff to medial edge of internal obturator
muscle/ischial ramus on each side
Common Iliac
Nodes
From 7 mm below L4–L5 interspace to level of
bifurcation of common iliac arteries into external and
internal iliac arteries
External Iliac
Nodes
From level of bifurcation of common iliac artery into
external artery to level of superior aspect of femoral head
where it becomes femoral artery
Internal Iliac
Nodes
From level of bifurcation of common iliac artery into
internal artery, along its branches (obturator, hypogastric)
terminating in paravaginal tissues at level of vaginal cuff
Pre-sacral node Nodal region anterior to S1 and S2
Consensus clinical target volume for adjuvant (postoperative)
radiotherapy for cervical and endometrial cancer
Small et al, IJROBP 2008

48. Upper Common Iliac Mid Common Iliac and Pre-sacral
Lower Common Iliac and Pre-sacralUpper External and Internal Iliac, Pre Sacral
Small et al, IJROBP 2008

49. Parametrial/Vaginal (green) CTV
Vaginal CTV
Small et al, IJROBP 2008

50. Consensus guidelines for delineation of clinical target
volume for intensity-modulated pelvic radiotherapy for the
definitive treatment of cervix cancer
Lim et al. IJROBP 2011
The group consensus was that entire uterus should be
included in the CTV because:
• Uterus & cervix are embryologically one unit with
interconnected lymphatics and no clear separating fascial plane.
• Determination of myometrial invasion can be difficult.
• Uterine recurrences have been reported (2%) though the exact
location of these recurrences (fundal vs. corpus) have not been
stated.

51. Components of CTV
Lim et al. IJROBP 2011

52. Parametrial contouring guidelines
Lim et al. IJROBP 2011

53. Superior boundaries of parametria are at the top of the fallopian tube, and
contours should stop once loops of bowel are seen next to the uterus as this is
clearly above the broad ligament. For the very anteverted uterus, particularly where
the fundus lies below the cervix, the parametrial volume should stop once the
cervix is seen.
Inferiorly, the parametrial tissue finish at the muscles of the pelvic floor.
Lim et al. IJROBP 2011

54. Anteriorly boundary lies at the posterior wall
of the bladder or in patients with a very small
bladder (which lies deep in the pelvis),
posterior border of the external iliac vessel
Posteriorly: bounded by the mesorectal fascia
and uterosacral ligaments. Parametrial
volumes would extend up to the rectal
contour in advances stages.
Laterally, the parametrial volume should
extend to the pelvic sidewall (excluding
bone and muscle).
Some overlap of this volume with nodal
CTV, particularly along the obturator strip

55. Lim et al. IJROBP 2011

56. • CTV nodal consists of common iliac, external iliac, internal
iliac, pre-sacral and obturator nodes.
• CTV primary consists of the gross tumor volume (GTV),
uterine cervix, uterine corpus, parametrium, upper third of
vagina and uterosacral ligaments.
• Pelvic LN CTV is contoured in accordance with the Taylor’s
guidelines with some modifications.
• This was the first report to provide guidelines for delineating
both the primary and nodal CTV.
PGI guidelines for delineation of clinical target
volume for intact carcinoma cervix
Bansal A et al. JCRT, 2013

57. • Organs at risk to be contoured as per RTOG guidelines.
CTV1
• Nodal CTV; to include common iliac, internal and external iliac,
obturator and presacral nodes.
• Delineation is as per Taylor’s guidelines, except:
- 10 mm added margin for lateral external iliac nodes is not given.
- Obturator nodal strip to be 17mm wide.
- 10mm margin to all grossly visible nodes.
CTV2 and 3: Primary CTV
• CTV2 includes gross tumor volume of the primary tumor (GTV),
uterine cervix, corpus, vagina and ovaries.
• CTV3 includes the parametrium; extent similar to Lim’s.
ITV margin to the uterus: 15mm AP and CC, 7mm laterally.
Bansal A et al. JCRT, 2013

58. Problems with contouring for gynecological cancers
On CT images
• The GTV itself may not be well seen
• Parametrial disease is difficult to appreciate
On MR images
• Expensive to do routine MR-based planning
• Problems with the availability of MR-based TPS
• Though pelvic nodal contouring is systematic, we still tend to end
up replicating the traditional cranio-caudal boundaries of a 4-field
box.

59. IMRT in CA Cervix
• Involves inverse planning.
• Modulates the intensity of the beam using the motion of
multileaf collimators.
• Computerized software used to conform the dose to the shape
of the target in 3 dimensions.
• Allows better coverage of the PTV with rapid dose fall off
outside it, lowering the dose to OAR but increasing the risk of
geographical miss.

60. Rationale
• Improved delivery of conventional doses
• Reduced dose to normal tissues: bowel and rectum1,2; bladder2,
marrow3, femoral heads.
• Dose escalation in high risk patients: Node positive/gross
residual disease
• Replacement or integration with Brachytherapy

61. • Studies have shown that IMRT can reduce bowel, rectal, bladder,
and bone marrow doses and toxicity with definitive RT.
Clinical studies that found benefit with definitive IMRT
Brixey et al, 2002 Single arm, n = 36
(cervix 24)
Significantly lower hematological
toxicity
Mundt et al, 2003 Single arm, n = 40 Significantly lower GI toxicity
Haselle et al, 2011 Single arm, n=81/111 Significantly lower Grade 3 toxicity
Gandhi et al, 2013 WP-IMRT (22) vs
WP-CRT (22)
Significantly lower GI toxicity
Naik et al, 2016 3D-CRT (20) vs
IMRT (20)
Significantly lower GI and GU toxicity
Similar haematological toxicity
• These studies are not without limitations:
• Single institution experiences
• Heterogenous populations studied
• Small numbers of patients
• Short follow up
• Variability in margins and dose prescription

62. Conventional 4-field plan: Bladder and Rectum within the TV

63. VMAT plan: Better conformity with sparing of bladder and rectum

64. IMRT vs Conventional Pelvic RT for LACC
IIB - IIIB CA Cervix
50.4Gy/28#
n = 44
Conventional RT
IMRT
N = 22
N = 22
• Bladder protocol: 1 Litre water 30-45 mins before simulation and
treatments.
• Intra-vaginal marker for lowermost extent of disease.
• Target volume delineation according to Taylor guidelines.
• All patients received weekly concurrent cisplatin.
• Brachytherapy: 3 applications of 7 Gy once a week.
• Primary end point: Acute GI toxicity (CTCAE v3.0)
• Secondary end point: Disease free survival
Gandhi et al. IJROBP 2013

65. • Median OTT was 9.1
weeks in both arms.
• Median no. of
chemotherapy cycles
was 5.
• The median follow-up
in the WP-CRT arm
was 21.7 months and
21.6 months in the
IMRT arm.
• There was significantly lower grade ≥2 (31.8% vs 63.6%, p=.034) and grade ≥3
gastrointestinal toxicity (4.5% vs 27.3%, P=.047) with IMRT than with CRT.
• DFS was 79.4% in the WP-CRT arm versus 60% in the WP-IMRT arm (p=.651).
• OS was 76% in the WP-CRT arm versus 85.7% in the WP-IMRT arm (P=.645).
Gandhi et al. IJROBP 2013

66. Conclusion
• WP-IMRT is associated with significantly less toxicity
compared with WP-CRT and has a comparable clinical
outcome.
Limitation
• Small sample sizes and short follow-up times no use of image
guidance.
Gandhi et al. IJROBP 2013

67. IMRT in the postoperative patient:
Need for small bowel dose reduction
• Conventional 4 field technique exposes most of the true pelvis
to the prescribed dose (45-50.4 Gy in 25-28 fractions).
• In post-op patients, small bowel tends to fall into the vacated
space in the true pelvis, increasing the amount of bowel treated,
increasing the risk of small bowel complications.
• The major (potential) advantage of IMRT in the postoperative
setting is the ability to deliver a lower dose to intraperitoneal
pelvic contents (i.e., small and large bowel) than to the
surrounding pelvic lymph nodes.
• This should make it possible to reduce the acute and late side
effects of treatment.

68. • Several studies have shown that IMRT in the adjuvant setting
can help reduce toxicity while providing favourable outcomes.
Clinical studies that found benefit with Post-op IMRT
Haselle et al, 2011 Single arm,
n=30/111
Significantly lower Grade 3
toxicity
Vandecasteele et al, 2012 N = 65 IMAT has low acute and late
toxicity
Klopp et al, 2012
(RTOG 0418)
N = 83 IMRT has low rates of HT and
high rates of weekly cisplatin
dose.
Barillot et al, 2014 N = 46 Low rates of GI toxicity (<
30% Grade 2)
Lan et al, 2016
(retrospective comparison)
3D CRT (89)
VMAT (26)
Lower GI and GU toxicity
with similar DFS.
• No head on comparisons; trials underway.
HT: Hemtological toxicity, GI: Gastrointestinal, GU: Genitourinary

69. IMRT in CA Cervix: Problems
• Adequate margin in the intact cervix setting is debatable given
significant motion of target (uterus, cervix) and OARs (bladder,
rectum) during treatment.
• The combined effect of setup errors and internal organ motion necessitates
frequent image verification during treatment.
• NCCN and FIGO suggest daily verification with replanning where possible.
• Uncertainties in the definition of target volumes arise using 3D
techniques.
• OAR dose constraints still evolving with the understanding of
PTV margins.
• Logistic issues: Time and manpower

70. Can IMRT replace brachytherapy?
• Complex internal organ motion
• Brachytherapy source (applicator) fixed to target

71. Sharma et al. Brachytherapy 2013
• To compare the dosimetry achieved by IBT and IMRT in patients
not suitable for ICRT.
• CT imaging data previously used for IBT planning of 12 patients
with cervical carcinoma was used to generate IMRT plans.
• Prescribed dose to the PTV:
• 20 Gy in 2-weekly HDR fractions of 10 Gy each with IBT
(biologically equivalent dose [BED10] 40 Gy)
• 33 Gy/13 fractions/2.5 wk with IMRT (BED10 41 Gy)
Interstitial brachytherapy vs IMRT for cervical
carcinoma not suitable for ICRT

72. Results
• For PTV, the mean D95 was better with IBT (57.16 Gy vs.
41.47 Gy, p50.003).
• The mean conformity index was 0.94 and 0.90 with IBT and
IMRT, respectively ( p = 0.034).
• IBT delivered significantly reduced doses to bladder and
rectal volume as compared with IMRT.
Conclusion
• IBT has superior dosimetry as compared with IMRT;
therefore, IBT remains the standard treatment for patients
with cervical carcinoma who are not suitable for ICRT.
Sharma et al. Brachytherapy 2013

73. • Encouraging results, with minimal late toxicity and local
control rates from 78%1 to 100%2,3
• Acute toxicity rates comparable to those of Brachytherapy
series’.
• Data difficult to interpret due to short follow up and limited
sample sizes.
• Remains investigational at present.
SBRT Boost following Pelvic RT
1. Marnitz et al. Radiat Oncol 201
2. Hsieh et al. Onco Targets Ther 201
3. Haas et al. Front Oncol 2012

74. Paraaortic nodal irradiation
• In radiologically/histologically positive paraaortic nodes OR in patients with
high risk of paraaortic involvement; positive pelvic nodal not receiving CTRT.
Studies evaluating prophylactic Para-aortic nodal irradiation
Haie et al, for
EORTC (1988)
RCT, n = 441 Conventional Better locoregional control
but similar survival.
RTOG 79-20 (1995) RCT, n = 337 Conventional Para-aortic RT improves OS
RTOG 90-01 (2004) RCT, n = 390 Conventional Pelvic CCRT better OS and
DFS than Pelvic + Para-
aortic RT alone
Park et al (2014) Retrospective
n = 203
Conventional,
CCRT 133/201
No survival benefit with EF-
CCRT
Zhang et al (2014) Retrospective
n = 45
IMRT
(CCRT)
Acceptable acute and late
toxicity
Liu et al (2016) Phase II
n = 48
IMRT-SIB
(CCRT)
Grade 3 GI toxicity < 5%

75. RTOG 79-20: Pelvic RT only vs Pelvic +
Para Aortic RT – 10 year results
IB-IIB CA Cervix
n = 367
Pelvic RT
40-50 Gy @ 1.6-.18 Gy/#
Pelvic + Para aortic RT
44-45 Gy @ 1.6-1.8 Gy/#
• 73% IIB disease
• No concurrent chemotherapy (1979-1986)
• Brahytherapy boost of 4000 to 5000 mg/h radium equivalent or 30
to 40 Gy to point A.
• Exclusion:
• Prior curative surgery (Radical or total hysterectomy)
• Positive Para-aortic nodes (Radiological or Surgical; 63% patients evaluated)
N = 167
N = 170
RTOG 79-20. Rotman et al. JAMA, 1995
30 excluded

76. Results
• 152/337 patients had died, and 95/185 remaining had been
followed for at least 8 years.
• Mortality due to radiotherapy complications was higher in the
pelvic plus para-aortic arm (2%) compared with the pelvic only
arm (1%) (p = .38).
• Distant failure as a first event trended lower with Pelvic + para-
aortic RT than with pelvic RT only (16% vs 23%, p = 0.053).
Pelvic RT only Para-aortic RT p
10 yr OS 44 % 55% 0.02
10 yr DFS 40% 42% NS
LRF 35% 31% 0.44
Grade 4 & 5
toxicities
8% 4% 0.06
RTOG 79-20. Rotman et al. JAMA, 1995

77. Conclusions
• Para-aortic irradiation can improve survival in CA cervix.
• The statistically significant difference in OS at 10 years without
a difference in DFS, can be explained by the following:
• Lower incidence of distant failure in complete responders
• Better salvage in the complete responders who later failed locally;
higher percentage of local failures were salvaged long-term on the
pelvic plus para-aortic arm (25% vs 8%).
RTOG 79-20. Rotman et al. JAMA, 1995

78. • N=403, 13 excluded; EFRT arm was the control, established on the basis
of the RTOG 79-20.
• Primary end point: Overall Survival
• Secondary end points: DFS, LRR, Para-aortic recurrence, Distant mets,
cause-specific failure, time to late side effects grade 3 or higher, and time
to late side effects grade 4 or higher.
IB-IVA CA Cervix
• IB / IIA had to be > 5cm
• Biopsy proven Pelvic
Node +ve
Pelvic RT + Chemotherapy
45 Gy @ 1.8 Gy/#
Pelvic + Para aortic RT
45 Gy @ 1.8 Gy/#
N = 195
N = 195
RTOG 90-01: Pelvic Chemoradiation vs
Pelvic + Para Aortic RT
n = 403
Eifel et al. JCO 2004

79. Results
* All except risk of para-aortic failure favoured the test arm, i.e. CT-RT arm
Median FU:
4.6 years
Benefit greater
for early stage
disease
Rate of serious
complications
similar
73% vs 52%
63% vs 41%
68% vs 43%
61% vs 36%
18% vs 34%
18% vs 35%
7% vs 4%
9% vs 4%
18% vs 31%
20% vs 35%
24% vs 41%
26% vs 47%

80. Conclusion:
• Mature analysis confirms that the addition of fluorouracil and
cisplatin to RT significantly improved the survival rate of women
with locally advanced cervical cancer without increasing the rate of
late treatment-related side effects.
Drawback
Control arm weak due to lack of concurrent chemotherapy.

81. Para-Aortic Nodal Irradiation: Thereputic
Author Year n
RT dose
(Gy)
5 year
survival (%)
Misc
RT alone
Piver 1981 21 60 9.6
Potish 1995 81 43.5-50.75 2.4
Lovecchio 1985 36 45 50 IB-IIA
Podczaski 1990 35 42.5-51 29
Kodaira 1999 97 50-70 -
ChemoRT
Podczaski 1990 33 42-51 31
Malfetano 1997 13 45 0
Varia 1998 95 45 14
Grigsby 1998 29 54-58 bid At 2 years: 47
31.4% Gr 4
toxicity
Grigsby 2001 43 30.6-55 32
Kim 2003 12 - At 2 years: 50
Small 2007 26 45-64.8 -
87% Gr ¾
toxicity
Kim 2009 33 59.4 42
Rajsooriyar 2011 39 50.4-54 19.4

82. EF-IMRT Plan: Dose Distribution

83. Para-aortic Nodal Irradiation: Summary
• No evidence of survival benefit in patients with grossly
enlarged para-aortic nodes.
• Investigational in the prophylactic setting, especially given
the associated morbidity.
• IMRT offers the possibility of dose escalation to these nodes.
• Management to be individualized; systemic therapy may be
considered.

84. Radiation Adverse Effects
Acute Effects
• Acute gastrointestinal side effects
- Upper GI: anorexia, abdominal discomfort, nausea + vomiting, hematemesis or
malena, ileus, distention, perforation
- Lower GI: Abdominal cramping, rectal discomfort, mucus discharge, diarrhea,
and occasionally, rectal bleeding, obstruction, perforation.
• Genitourinary symptoms: Secondary to cystourethritis; dysuria, frequency, and
nocturia, pelvic pain (bladder spasms) microscopic or gross hematuria + clots.
• Skin reactions: Erythema and dry or moist desquamation may develop in the
perineum or intergluteal fold(s).
• Hematological toxicity: Anemia is frequent; leukocytes and platelets may also
be supressed.
• Acute radiation vaginitis: Erythema, superficial ulceration of the vagina, and
vaginal stenosis.

85. Radiation Adverse Effects
Late Effects
• Gastrointestinal: Abdominal cramping, rectal discharge and/or
bleeding, diarrhea, obstruction
• Genitourinary symptoms: mucosal atrophy, telangiectasia,
dysuria, hematuria, frequency, contracted bladder
• Skin reactions: Atrophy, hair loss, telangiectasia, ulceration.
• Vaginal stenosis

86. Thank you