1. IGRT for Gyn Cancer?
Akila N. Viswanathan, MD MPH
Brigham and Women’s/Dana-Farber
Cancer Center
Harvard Medical School

2. Why use IGRT in Gyne?
• Decrease toxicity
• Dose escalation
• Most important area for IGRT is in
image guided brachytherapy

3. Major Issues with IMRT/IGRT
• Need for continual replanning given
rapid regression of tumor
• High margin for error with tight
margins
• Increase in integral dose
• Longer treatment times

4. Indications for IMRT/IGRT
Cervix
• Nodal involvement (pelvic or PAN)
– Maximize boost dose
• Para-aortic node treatment
– Reduce small bowel dose
• Boost sidewall in region inaccessible to
brachytherapy
• Recurrence in radiated area (re-irradiation)
• NOT for routine treatment
• NOT a replacement for brachytherapy

5. Mobile uterus, Cervix, Normal
Tissues

6. Decrease tumor size @1cm/week

7. Uterus Contouring
• ? Include whole uterus
−Account for motion?
−Varies with bladder filling
−Hard to know where cervix ends
and uterus begins

8. Movement of cervix on CT
Beadle et al IJROBP 2009;73:235-41
• Center of the cervix:
– 2.1 cm superior-inferior
– 1.6 cm anterior-posterior
– 0.82 right-left lateral
Mean maximum changes in the perimeter of
the cervix:
2.3 cm and 1.3 cm in the superior and
inferior
1.7 cm in the anterior, 1.8 cm in the posterior
0.76 and 0.94 cm in the right and left lateral

9. Movement on CT
• Haripotepornkul NH, Nath SK, Scanderbeg D, Saenz C, Yashar CM.
Evaluation of intra- and inter-fraction movement of the cervix during
intensity modulated radiation therapy. Radiother Oncol 2011;98:347-51
• Tyagi N, Lewis JH, Yashar CM, et al. Daily online cone beam computed
tomography to assess interfractional motion in patients with intact
cervical cancer. Int J Radiat Oncol Biol Phys 2011;80:273-80
• Within and between radiation treatments, cervical motion
averaged approximately 3mm in any given direction with
maximal movement of the cervix up to 18 mm from
baseline

10. In addition to movement, must
account for errors in
contouring

11. RTOG consensus on contouring the
CTV for intact cervix patients

12. Background & Aim
• More conformal radiotherapy  accurate target definition
important
– Cervix Cancer Clinical Target Volume (CTV) definitions
variable
• Aim: Evaluate the variability in CTV delineation in
preparation for a Phase 2 clinical trial being planned
by the Radiation Therapy Oncology Group (RTOG).
4F pelvis
RT IMRT
(12/10)

13. Methods & Materials
• Clinical Case:
– 35yo G4P3
– clinical stage 1B poorly differentiated
adenocarcinoma of cervix.
– No adenopathy or metastatic disease seen on
staging investigations.
– MRI report confirms no parametrial, uterosacral
ligament or myometrial invasion.
• MR & CT data sets made available
• Participants asked to contour:
– GTV
– Cervix (if seen)
– Uterus
– Upper vagina (3cm)
– Parametria
• Online (ITC RRT; Washington U) or on
participant’s treatment planning software.
Fig 1. Sample images (sagittal & axial) from clinical case.
Figure 1
(13/10)

14. Results
• 19 participants contoured on axial MR images
•Sagittal MR & axial CT images available for reference
Sensitivity Specificity Kappa
Structure
(Avg±SD) (Avg±SD) measure*
GTV 0.84±0.14 0.96±0.04 0.68§
Cervix 0.55±0.24 0.98±0.03 0.42§
Uterus 0.68±0.22 0.97±0.03 0.57§
Vagina 0.58±0.13 0.99±0.01 0.53§
Parametria 0.48±0.27 0.99±0.02 0.42§
*corrected for chance §p-value <0.0001
(14/10)

15. Results
Parametria
Vagina
Uterus
Cervix
GTV
Kappa ==0.53
Kappa = 0.42
Kappa 0.68
0.57
0.42
Kappa
Level of Agreement
measure
0.81 - 1.00 Almost perfect
0.61 - 0.80 Substantial
0.41 - 0.60 Moderate
0.21 - 0.40 Fair
0.01 - 0.20 Slight
No agreement
0.00
above chance
Complete
-1.00
disagreement
(Landis JR, Koch GG. 1977)
(15/10)

16. Results – 95% agreement
GTV
Cervix
Vagina
Uterus
Parametria
CTV
CTV
consensus
consensus
(16/10)

17. • Specificity was high
– Greater certainty about what should NOT
be included in CTV
• Sensitivity was moderate
– Greater difficulty determining the
interface between various CTV
components
• Challenging case:
– Extreme ante-version of uterus
– Ability to view sagittal images
• Substantial organ motion, deformation and
tumor regression for this site is not
addressed in this work.

18. Parametria &
change depending
on volume of
bladder
Courtesy of Karen Lim, Princess Margaret Hospital

19. Assessment of location
• Ultrasound: imprecise
• kV imaging: rough estimate
• Cone beam CT: Intensive resource
utilization

20. IMRT/IGRT
• No clear outcome benefit in cervix ca
or postop endometrial cancer
• Greatest potential benefit in nodal
recurrence

21. Rectal Sparing
• May be dangerous due to need to
include presacral nodes
(mesorectal), uterosacral
ligaments, and internal iliac nodes
• Rectal filling may vary
• NOT recommended

22. Definitive Contouring
• Consider a CTV that includes the
uterus/cervix, parametrial tissues, vagina,
and pelvic nodes, (common, internal &
external, obturator, and iliacs, presacral
nodes) with exclusion only of small bowel
and some bladder and sigmoid
• Need @3cm margin on CTV for uterine PTV;
1.5 cm on CTV cervix for PTV
• No sparing of rectum or posterior bladder;
potential sparing of small bowel with para-
aortic nodal field

23. Is IMRT/IGRT Ready for Prime
Time in the Therapy of Cervical
Cancer?
• For post-operative therapy – maybe
– Still need prospective verification of targets
(RTOG 0418)
– Rectal movement remains a concern
• For definitive therapy in cervical cancer – No
• Organ motion and volume changes during therapy
remain a significant issue
• For para-aortic nodes, spare small bowel
• Re-irradiation – unknown sequelae

24. PET/CT Fusion Nodal Contour
IMRT for Nodal boost 54-65 Gy

25. Post-operative PAN positive
no residual LN (45 Gy)

35. Vaginal recurrence
• Pelvic LN+
• 45 Gy region
• 65 Gy pelvic mass
and LN+

40. SBRT as a boost
• Node recurrence, sidewall recurrence
• Higher normal tissue dose
• Long term complication rate
HDR SBRT

41. SBRT for Recurrent Cervix Ca
Dose Failure
Deodato et al. 30 Gy/6 fractions 7/11 FAIL
Oncol Repo 22:415-419 2 Grade 4 fistulae
1 pt w vaginal recurrence 1 Grade 4 ileus
Guckenberger et al. 50 Gy + 5 Gy x 3 Fx 7/10 FAIL
Rad onc 94:53-59
7 central recurrences

42. HDR SBRT
HDR SBRT
Images courtesy of A. Damato

43. Post-operative IMRT: RTOG Atlas
www.rtog.org

44. Image-Based Brachytherapy for
Gynecologic Cancers

45. Can IMRT replace
brachytherapy? NO
After 45 Gy EBRT
• Complex internal organ
motion
– Brachy fixed to target
• Tumor response
• The proximity of
critical structures
leaves little room for
error in EBRT planning

46. Volume Based Treatment
Brachytherapy IMRT
Moves with patient Does not move with patient
Difficult to adjust with response

47. Brachytherapy is Necessary
• Tumor control probability correlated
with RT dose and cervix ca volume
Fletcher, Shukovsky J Radiol Electrol 56:383-400, 1975
External beam only External Beam +
brachytherapy
4 y PC 45% 67%
4 y Survival 19% 46%
Lanciano JROBP 20:95, 1991
Local Control 40% 52%
Montana Cancer 57:148, 1986

48. Ultrasound
• Suspected uterine
preforation
• Retroverted uterus
• Absence of
endocervical canal
• Extreme
anteversion of
uterus

49. What might appear acceptable on Xray,
may not be acceptable in 3D
Posterior placement
Proper placement
Viswanathan ASTRO 9/25/08

50. CT-Based Brachytherapy
• CT-simulators
available in most
radiation
oncology
departments
• Easy transition
from film-based
dosimetry to CT-
based dosimetry

51. MRI/CT Compatible Applicators
•MRI/CT compatible applicators inserted brachytherapy suite
Secure fixation of applicator within pt
(vaginal packing and perineal bar)

52. CT-Based Brachytherapy
• Rule out uterine perforation

53. CT-Based Brachytherapy
• Assess location and position of
applicator relative to the uterus

54. Use of Contrast
Drain bladder
bladder
Clamp foley
60 cc of 10%
hypaque contrast
into bladder
50 cc barium rectum
rectum

55. Organs at Risk:
Bladder, Rectum, Sigmoid, Small
Bowel
Rectum Bladder

56. CT based targets vs. MR-
imaging
• GTV – T2 bright areas
• HR-CTV – cervix +
visible/palpable disease at
brachy
IR CTV
• IR-CTV – 1 cm margin
around HR-CTV + initial
sites of involvement
GTV
HR CTV
• CT definitions:
• CT-CTV – 3cm above
applicator
• CE (Clinical exam)-CTV –
includes vaginal extension
GYN GEC ESTRO Recommendations (I) Radioth.Oncol. 2005, 74:235-245

57. CT Gyne Brachy Improves Outcomes:
Prospective French STIC trial
Median Overall
Imaging Local Disease Survival (%)
Mode of Follow Grade 3-4
# St During control specific
treatment up Toxicity
BT (%) Survival (%)
(years)
IB-
705 2
IIIB
76 BT and Sx Xray 92 87 95 14.6
89 BT and Sx CT 100 90 96 8.9
ChRT/BT
142 Xray 85 73 85 12.5
and SX
ChRT/BT
163 CT 93 77 86 8.8
and SX
118 ChRT/BT Xray 74 55 65 22.7
117 ChRT/BT CT 78.5* 60 74 2.6

58. External beam response
Diagnosis
MRI 1st fraction
Viswanathan ASTRO 9/25/08

59. Similar OAR contours
no significant differences
Viswanathan et al. Int J Radiat Oncol Biol, 2005
• Width larger on CT
– Good for covering
parametrium Bladder
– No issues with toxicity
• Height not determined on MR
CT unless referring to an CT
HR-CTV
MRI
– Estimate 3 cm on average
– Always treat entire length
Rectum
of tandem

60. Brachytherapy exemplifies…
• Point versus volume
Viswanathan ASTRO 11/3/09

61. 3D Brachytherapy Outcomes
• 145 patients
• Historical
comparison
• Significant ↑
– OS 53 to 64%
– CSS 62 to 74%
– Tumors > 5cm
• OS 28 to 58%
Viswanathan ASTRO 11/3/09
Pötter et al. Rad Oncol 2007

62. Physical-Biological Documentation
of Gynecologic HDR BT
EQD2: BED/1.2
BED= nd(1+d/alpha-beta ratio)
BED:
5.5Gy x 5 (1 + 5.5/10)=42.625 Gy
EQD2: 42.625/1.2 = 35.5 Gy

63. Plan for each HDR fraction
required
Radioth Oncol 81:269, 2006
Viswanathan ASTRO 9/25/08

64. HDR/PDR Treatment
Planning:
Dose Optimization
Standard plan Optimized plan
Viswanathan ASTRO 11/3/09

65. Practical implementation
• Standard plan mimics LDR loadings
• Optimization superiorly – sigmoid/small bowel
– Treat entire tandem length +/- 1cm
• Optimization posteriorly - rectum
– Watch dwell weight changes carefully
• Set to local rather than global
• Change individual positions rather than regions
• Optimization anteriorly – bladder
– Very high doses; no risk to tumor coverage
• “Over-coverage” versus “underdosage”
Viswanathan ASTRO 11/3/09

66. Summary
• IMRT – CAUTION
– OK for nodal boost, PAN treatment,
recurrence
– Not standard for primary cervical ca
– NOT a substitute for brachytherapy
– Use image guidance with brachytherapy to
reduce toxicity and maximize tumor
coverage