1. Evolution of intracavitary brachytherapy in Carcinoma
Cervix
DR AJEET KUMAR GANDHI
MD (AIIMS), DNB, UICCF (MSKCC,USA)
ASSISTANT PROFESSOR, RADIATION
ONCOLOGY
DR RMLIMS, LUCKNOW

2. Overview of presentation
 Role of brachytherapy in carcinoma cervix
 History of Brachytherapy in carcinoma cervix
 Evolution :
 Radiation physics
 Radiobiology
 Treatment delivery techniques
 Imaging
 Current standard of ICBT practices
 Clinical results and future research
 Conclusion

3. Role of brachytherapy in carcinoma cervix
 Integral component of radical treatment for all stages
 Several methods: Intracavitary, Intravaginal, Interstitial or a combination of
these
 Use of brachytherapy is associated with increased overall survival as well as
increased local control rates* (5 year survival 65% versus 50%)
 Advantages:
 Organ preservation, less normal tissue damage, less radiation morbidities
*Han K et al. IJROBP 2013;87:111-119

4. History of brachytherapy in carcinoma cervix

5. Margaret Abigail Cleaves (1848-1917)
 September 16, 1903: Treated a case of carcinoma cervix initially
treated with Intracavitary X-rays: Radium vials applied to fornices 10
min Day 1 and 5 min Day 2 [Intracavitary radium for gynecological
malignancies Med Rec 1903;64:601-606]
 Albert Doderlein (Germany; 1903) and William J Morton (New York;
1903): treated carcinoma cervix with radium

6. Early history: 1903-1913
 1908, 1910, 1912: ICBT started in Vienna, Stockholm,
Paris
 1912: Gosta Forssell (Stockholm) reported 24 cases
of carcinoma cervix treated with radium therapy
 1913: Robert Abbe (New York) reported long term
control of carcinoma cervix-8 years

7. Early applicators: 1903-1913
Figure 1 : Wickham and Degrais; St. Louis hospital, Paris
Figure 2&3: Carl Josef Gauss (‘Inter-cervical tubes’ and Portio plates): Mostly used in
Germany

8. 1903-1913
 Sporadic reports of ICBT from different parts of world
 Most reports: “Enthusiastic or magical” reporting rather than
scientific
 There was little knowledge of the biological effects of treatment on
the normal and tumor tissues
 Uterine tandem was used alone without vaginal colpostats
 Non-durable responses in these patients or overwhelming
toxicities
 No definite consensus on dose prescription and reporting and
mostly were empirical and personal opinion based

9. Dawn of a new era: 1910-1930
 Stockholm System: Gosta
Forssell (1910)
 Paris System: Claude Regaud
(1912)
 Manchester System : Todd and
Meredith (1930)

10. STOCKHOLM METHOD
 Intra-vaginal boxes Silver or gold ; Intrauterine tube: flexible rubber
 Applicator not fixed together
 Unequal loading
 30 - 90 mg (50 mg) of radium in uterus
 60 - 80 mg in vagina
 Three insertions each of 22 hours separated by 1-3 weeks
 Total prescribed dose: 6500-7100 mg Ra
 4500 mg Ra contributed by the vaginal box
 Dose rate-110R/hr or 2500mg/hr/#
Limited use of EBRT.

11. PARIS METHOD
 Single application of radium for 120 hours
 Two cork colpostats (cylinder) with 13.33 mg radium in each and an
intrauterine tube of silk rubber containing 33.3 mg of radium
 3 radioactive sources, with source strength ratio of 1:1:0.5 in
uterus
 Delivers a dose of 5500 mg-hrs of radium over a period of five
days at dose rate of 45R/h
 Equal loading of sources in uterus and vagina
 Combined with EXTRT.

12. DRAWBACKS OF PARIS AND STOCKHOLM
SYSTEMS
 Long treatment time, discomfort to the patient, no specific dose
prescription
 Uterine sources arranged in a line from the external os to nearly the top
of the uterine cavity
 Both systems preferred the longest possible intrauterine tube to
increase the dose to paracervical region and pelvic region lymph
nodes.

13. MANCHESTER
SYSTEM
Developed by Todd & Meredith in 1930 and pioneered by Patterson &
Parker
 Unique dosage system necessary for pelvis
 roentgen unit in favor of mg/hrs
 Dose to a point
 Constant dose rate
 Reproducible technique

14. Point A & B
 Classic definition : fixed point 2cm
lateral to the center of uterine canal and
2 cm above from the mucosa of the
lateral fornix
 Revised definition #1: 2 cm above the
external cervical os and 2 cm lateral to
midline
 Revised definition #2 (1953, Tod &
Meredith): 2 cm above the distal end of
the lowest source in the tandem and 2
cm lateral to the tandem
 Common variation: use flange at cervical
os

15.  Initially used radium units were 6.66mg but later
changed to 2.5 mg each.
 Two application 72hrs apart with 4 days in between
 Dose of 8000R was delivered at pt A when radium used
alone for stage I/II ds
 When radium was used along with deep-X ray therapy
for stage III or IV ds radium dose to pt A reduced to 6500R.

17. MANCHESTER SYSTEM : PRELOADED
APPLICATORS
AP & Lateral radiographs were taken to
verify appropriate applicator position
not for dosimetry

18. Manchester System
Advantages: Well studied, reproducible, better control rates and morbidity
Dis-advantages:
 Loose system
 Based on ideal cervical and para-cervical anatomy
 Radiation hazard : being a preloaded system.
Need for fixed preloaded systems and afterloading systems!!!

20. Pair of cylindrical “small” ovoids (2 cm in
diameter) with inter-locking handles.
Plastic jackets of two thicknesses are
added to made medium (‘2.5 cm in
diameter) and large (3 cm in diameter)
sizes.
Fletcher preloadable applicators
Fletcher et al. Radiology 60:77-84, 1953

21. •In 1960-Ulrich K Henschke first described Manual
afterloading
•In 1962-Walstram first described remote afterloading
•In 1964- First developed Remote afterloading device

22. Fletcher afterloading colpostats
a. Fletcher-Suit
rectangular-handle model
b. Round-handle,
lighter model.
In 1958, Suit et al. developed the first afterloadable Fletcher colpostat
In 1978, Delclos et al. improved design of the afterloadable Fletcher colpostats
Fletcher
Suit
Delclos

23. IDEAL APPLICATION
 Tandem
 1/3 of the way between S1 –S2 and the
symphysis pubis
 Midway between the bladder and S1 -S2
 Bisect the ovoids
 Ovoids
 Largest
 Separated by 0.5-1.0 cm
 Axis of the tandem-central
 Bladder and rectum -should be packed
away from the implant

24. Evolution of radiation source

25. Radium: The pitfalls
•Heterogeneous beam & non uniform dose distribution
• Low specific activity : 1 Ci/gm
• High energy (0.047-2.45 MeV)
• Rn 222 being the gaseous daughter product - threat of leaks from long bent
needles
• Storage & disposal of leaked sources

26. CESIUM 137: ( Cs137)
 T1/2 : 30 yrs
 Relatively cheaper, extraction simple
 No gaseous decay product, safer than
Ra
 γ ray energy = 0.662 MeV
 β filtration – 0.5 mm stainless steel
 Available in tubes, needles, pellets
 Replaced Ra in t/t of gynecologic
cancers
COBALT 60 (60Co)
 T1/2 = 5.26 yrs
 Each disintegration produces 2 y rays of
energy 1.33 & 1.17 MeV (avg energy 1.25
MeV)
 High specific activity , miniaturized source
can be made and used in brachytherapy.

27. ICBT: 1960s-1980s
 Cesium-137/Co-60 had almost replaced Radium at most centres
 Low dose rate brachytherapy most commonly used
 Manchester method became the standard of practice
 Remote after loaders were rapidly phasing out all the manual after loaders
 Tandem and Ovoid standard Fletcher-suit applicators were commonly
used
 X-rays were used for verification but not for dosimetry

28. Ir-192 : A near ideal radioisotope
Compatible with after loading techniques
Ideal energy (0.3-0.4 MeV) – monoenergetic – more radiobiological effect
Flexible & malleable – can be used in form of wires of any size
Energy is low – thinner shields required for radiation safety
β-energy is low – so lesser filtration required
Product (Pt192) not radioactive
Easily available , less costly
x Limitation
Short half life (73.8 days) so source has to be replaced every 3 months

29. Intracavitary Brachytherapy :Changing
Dose Rates
1968 : HDR brachytherapy was introduced
with cathetrone containing Co-60 sources.
1982 : MDR brachytherapy was introduced
with Selectron MDR using Cs-137 pallet
sources.

30. Why HDR??

31. Why HDR??

32. MicroSelectron
(Nucletron)
VariSource & GammaMed
(Varian).
HDR plus
(IBt Bebig)
Modern HDR Brachytherapy Machine

33. PDR Brachytherapy
Series of short HDR
treatments ( 10 minute
pulse repeated at 1 hr
intervals)replacing the
Continuous LDR treatment
lasting several days.
Overall time remains same as LDR
Source strength : 1 Ci
ADVANTAGE:
•Radiobiologically nearer to LDR
•optimization possible
•Nursing care possible without radiation hazards
Nucletron
PDR
After loader

34. ICRU-38: Dose-Volume specification for reporting intracavitary
Therapy in Gynecology [1985]
• Definition of terms and concepts for ICBT
• Treatment techniques
• Absorbed dose pattern and volumes
• Specification of radioactive sources
• Recommendations for reporting absorbed doses and volumes in ICBT
• TRAK
• Reference volume
• Absorbed dose at reference points
• Calculation of dose distributions
• Time-Dose pattern
• Radiobiological considerations
• Recommendations for reporting time-dose pattern

35. ICRU-38:Dose specification

37. Time to move from points to
profiles
 Point A &B are not anatomical sites. The variation in position and distribution of
sources significantly changes the anatomic structures in which points A & B are
located.
 No one point is representative even of a small volume.
 It is viewed as a treatment reference point.

38. Image based brachytherapy
 Newer imaging modalities are used to define target
volumes
 USG, CT, MRI (preferred), PET
 Prescribed dose - related to the target
 Shape the spatial dose to conform to the target volume
 Reduce dose to normal tissues & hence reduce the normal tissue
toxicity.
 Escalate dose to the tumor to produce greater rates of local
control

40.  GTV
 Includes macroscopic tumor extension - clinical examination & as visualized on MRI
 At diagnosis GTVD
 At brachytherapy GTVB
 CTV
 High risk CTV (HR CTV)
 Major risk of recurrence because of residual macroscopic tumor
 whole cervix + presumed extra-cervical tumour extension at time of BT
 Intent is to deliver a total dose as high as possible to eradicate all residual
macroscopic tumor ( 80-90 Gy)
 Intermediate risk CTV (IR CTV)
 Major risk of recurrence in areas that initially had macroscopic extent of disease with
residual microscopic disease at time of BT
 Intent is to deliver dose appropriate to cure microscopic disease in cervix cancer,
(60Gy)

42. Dose prescription
 The prescribed dose is always related to the target.
 The prescription dose is the planned dose to cover this target as completely as
possible.
 HR-CTV Dose
 Small tumor – 80-85 Gy
 Large tumor, good response – 85-90 Gy
 Large tumor, poor response - 90+ Gy
 IR-CTV ~ 60 Gy
 For comparison, dose reporting should refer to the prescribed dose to the image-
based target & to the traditional system - point A

43. Modern day applicators: I

44. Modern day applicators: II

45. Clinical results

46. HDR Brachytherapy In Carcinoma Cervix –Summary Of
Retrospective Analysis
Author Stage Pt No. EBRT
(GY)
HDR GY*# LC Survival Late
Complic
ations
Lorvidhya et al I-III 1992 30-50 7-7.5 *4
5.5-6 *6
75.2% 68.2%(5y) 4.8%b
3.5%u
Potter et al I-IV 189 48-50 7 * 3-6 77.6%(3Y) 58.2%
Toita et al I-III 88 50 6*3 82%(3Y) 77% 6%r
4%b
2.9%u
Sood et al I-III 49 45+9 9-9.4*2 77%
88% cct
78% 4.1%
Patel et al I-III 121 40-46 9*5
9*2
87.5% 1.7%u
Ferringo et al I-III 118 40-50 6*4 65% 55% 6%r
6%b
1.7%u
Souhami et al I-IVA 282 45 8*3 75%(15y) 57% 6.3%b
3.5%u

47. HDR V/S LDR BT IN CA CX – RCTS
Pt. No. Local Control 5 YR Survival
Author Stage EBRT
(GY)
LDR HDR LDR% HDR% LDR% HDR%
Shigema
tsu et al
IIB-III 40 106 143 77 90 55 55
Teshima
etal
I
II
III
40 171 259 73 76 89
73
45
66
61
47
Patel et
al
I-III 35-45 246 236 80 76 58 58
Hareyam
a et al
II
III
50 71 61 87
60
69
51
Lertsang
ua et al
I-III 40-54 109 112 89 86 71 68

48. Outcomes of Image based Brachytherapy

50. Xray Ct scan MRI 2D/3D
ABS (USA) 43% 56% 1% 77%/21%/3%
Canada 50% 45% 5% 50*%/44%
Australia
NZ
30% 65% 15% 65%/35%
Results of Survey for 3D Brachytherapy

51. Current standard of practice
 Remote afterloaders (HDR) with Ir-192 most commonly used
 LDR, PDR limited to some Institutions
 Fletcher suit (tandem-ovoids) and Ring applicators (Vienna) in common
practice
 X-ray based dosimetry still common followed by CT and MRI
 Point-A based prescription mostly, less widespread use of ICRU-38;
GEC-ESTRO

52. Evolution and Experience: AIIMS

53. 1984: LDR brachytherapy [Cesium-137; Remote after loading; X-ray
based treatment; NPS; Point A based prescription]
2003: HDR V2 (microselectron); PLATO TPS; PDR
2004: CT based planning (Use of bladder & rectal points)
2006: HDR V3 (microselectron); Oncentra TPS
2007: Inverse planning simulated annealing
2007-2008: Sedation instead of general anesthesia
2013: MRI based volumetric brachytherapy

54. Rath GK et al. Clin Oncol (R Coll Radiol).1994
Results of radical radiotherapy in carcinoma of
the uterine cervix stage I-III
• 271 patients
• Dose
• Early cases (34 Gy X2 f/b 36 Gy external radiotherapy )
• Late stage disease 50 Gy of external radiotherapy f/b 30 Gy to point A
• Late Grade III bladder and bowel complications were 2.5% and 4.7%
respectively.
• The actuarial 5-year survivals were 65%, 63% and 35% for Stages I, II and
III disease, respectively

55.  48 patients (2003-2005)
 Follow-up period 3 to 50 months (median: 15 months)
 Overall grades III to IV late toxicity rate at 50 months was 6%
 The actuarial recurrence-free survival in stages I to II was
82% and stages III to IV was 78%

58. Future directions!!

59. Re-emergence of 60Co as brachytherapy source
 Modern techniques → Sources of higher Sp
Activity → Decreased source size compatible
with remote afterloading stepping source
machines for HDR.
 No need for frequent replacements
 Cost effective
 Low operating cost.

62. CT based volumetric planning

64. IJROBP 2015; 92 (5): 1093-1100
 111 patients (2003-2009); 57% stage III-IV and 26% stage II
 Median follow up: 42 months
 Late grade toxicities: 8%
 4 year local, loco-regional, distant control: 94%, 91.9% and
69.1%

66. Phase II Randomized Study of brachytherapy versus
chemobrachytherapy in locally advanced cervical
cancer
Eligibility
Stage IIB to IVA SCC of carcinoma
cervix in patients aged 20 – 65 years
Patients treated with radical EBRT 50.4
Gray / 28 # / 5.5 weeks with concurrent
weekly cisplatin ( 40 mg / m2 )
R
HDR INTRACAVITARY
RADIOTHERAPY 7 GRAY FOR THREE
WEEKLY SESSIONS
HDR INTRACAVITARY RADIOTHERAPY 7
GRAY FOR THREE SESSIONS WITH
CONCURRENT CHEMOTHERAPY
Computer
generated
randomization
1:1
ASSESSMENT OF
TOXICITY,
LOCOREGIONAL
CONTROL AT 1, 3 AND 6
MONTHS

67. Phase II Randomized Study of brachytherapy versus
chemobrachytherapy in locally advanced cervical
cancer

69. Conclusion
 ICBT in carcinoma cervix has evolved over the last century in many
spheres:
 Remote after loading system, Radiation source
 Dose rates, Applicator
 Points to Volumes
 X-rays to MRI/CT/PET
 Overall it has made us more:
 Safe, accurate, reproducible
 Decreased morbidities
 Improved outcomes

70. Conclusion
 Future research should focus on:
 More accessible and cost effective (USG & CT vs. MRI)
 Precise definition of the tumor volume (MRI, PET-CT)
 Adapt to the weekly changes in the treatment volume (adaptive
planning)
 Improving local control further (integration of systemic therapy)
 Optimum dose and dose per fraction (resource constrained setting!!)
 Research in to a competitive or better source than Ir-192

71. Thanks for your kind attention!!