Radiobiology of Brachytherapy, Indications and Techniques in cervical and vaginal cancers

1. BRACHYTHERAPY IN
GYNAECOLOGICAL
CANCERS
Dr. Pradeep MCh Surg Onco PG
Tamil Nadu Govt Multi Superspecialty
Hospital, Chennai
01 Feb 2019

2. Background
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3. Overview
■ Historical Timeline
■ Introduction to Brachytherapy
■ Pros and Cons
■ Radiobiological effect
■ Sources and Applicators
■ Indications in Gynaecological cancers
■ Techniques employed
■ Treatment planning
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4. History
■ 1896 – Discovery of Radioactivity
■ Henry Becquerel
■ French Physicist
■ 1898 – Radium discovered by Madame curie
■ 1899 – First use in cancer (SCC and BCC) with
radium surface moulds in Stockholm
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5. History
■ 1901 – Pierre Curie
■ Suggested Danlos (doctor) that radioactivity can
be used to treat cancer
■ Early use by Danlos and Robert Abbe in 1905 to
treat cervix
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6. Timeline
■ 1903-1950 – Pioneers
– Margaret Cleeves – Cervical cancer
– Hugh Hampton Young – Prostate cancer
– Goeffrey Keynes – Breast cancer
■ Treatment Systems were introduced to arrange
radioactive sources
– Stockholm and Paris in 1914 and 1919
– Manchester system by 1930
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7. Timeline
■ 1934 – Discovery of artificial radioactivity Irene
Curie
■ 1963 - Ulrich Henschke the first person to
clinically explore Ir 192 effects
■ 1970 – Introduction of Afterloading machine
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8. Then and Now…
■ 1990 – Image based guidance of treatment
planning
■ 2000 – Virtual treatment planning using
computerized brachytherapy machines
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9. What is Brachytherapy?
■ “brachy” means for short distance
■ Placing sealed radioactive sources very close to or
in contact with target cancer tissue temporarily or
permanently
■ Internal radiotherapy, sealed source radiotherapy,
Endocurie therapy
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10. Classification
■ Based on Source placement
– Interstitial (directly)
– Contact (space next to it)
■ Intracavitary
■ Transluminal
■ Plesiocurie or mold therapy
■ Based on Duration of therapy
– Temporary or Permanent
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11. Classification
■ Based on Source loading technology
– Preloaded
– Manual afterloading
– Remote afterloading
■ Based on dose rate
– Low (0.4 to 2 Gy/h)
– Medium (2 to 12 Gy/h)
– High (>12 Gy/h)
– Ultralow dose rate (0.01 to 0.3 Gy/h)
– Pulsed Dose Rate
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12. Dosimetry Characteristics
■ Factors influencing dose distribution of photon
sources
– Distance (Inverse Square Law)
– Attenuation (Active core and Encapsulation)
– Attenuation (Surrounding medium)
– Scattered photon build up (Surrounding
medium)
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14. Isodose curves
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15. Pros
■ High biological efficacy
■ Rapid dose fall off
■ Higher tolerance of normal tissues
■ Decreased risk of tumor population
■ Better cosmesis
■ Minimal radiation morbidity
■ Therapeutically relevant distant range is 3 to 20
mm
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16. Cons
■ Difficult for inaccessible regions
■ Higher dose inhomogeneity
■ Limited for small tumors alone
■ Small errors in placement – can cause gross dose
variation
■ Invasive and require RA/GA
■ Radioactive hazard
■ Costly
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17. Radioactive Sources
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18. Isotopes
Element Isotope Half life Energy(MeV) HVL (mm)
Radium Ra 226 1626 yrs 0.83 16
Radon Rn 222 3.83 days 0.83 16
Caesium Cs 137 30 days 0.662 3.28
Iridium Ir 192 73.8 days 0.397 6
Cobalt Co 60 5.26
years
1.25 11
Iodine I 125 59.6 days 0.028 0.025
Palladium Pd 103 17 days 0.020 0.013
Gold Au 198 2.7 days 0.412 6
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19. Isotopes and Usage
■ Intracavitary BT
– Ra 226 and Cs 137
– HDR Sources – Ir 192 and Co 60
– Experimental – Cf 252, Yb169, Am 241
■ Temporary Interstitial BT
– Preloaded – Ra and Cs needles
– Afterloading – Ir 192 ribbons and wires
■ Permanent Interstitial BT
– Au 198 seeds, Pd 103, I 125 seeds
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20. Ideal Brachytherapy Isotope
■ Moderate half life
■ High specific activity
■ Moderate gamma ray constant
■ Versatile to implant
■ Adequate penetration to the depth desired
■ Rapid fall off to prevent surrounding OAR
■ Easily available, inexpensive materials
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21. Treatment planning & Dose
prescription
■ Historically systems
■ For intracavitary
– Manchester system
– Stockholm system
– Paris system
■ For interstitial
– Manchester or P-P system
– Paris system
– Quimby system
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22. Pros and Cons of HDR
Pros Cons
Perfect Optimization Requires two or three fractions
Immobilization and
stability
Error hazard
Dose reduction to normal
tissue
Potential for very high radiation
doses in case of technical errors
Lesser time Demand more resources
Outpatient procedure Costly
Less discomfort due to
small size
Elimination of delays
Radiation safety
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23. Carcinoma Cervix
 Stages IB2 to IVA
 Brachytherapy needed after EBRT
 Sources – HDR (Cobalt and Iridium)
 Applicators
 Intracavitary
 Hybrid Intracavitary-Interstitial
 Interstitial
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24. HDR Workflow
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25. Applicator selection
■ Tandem and Rings (Shallow vaginal fornices,
higher vaginal dose, lesser lateral throw off)
■ Tandem and Ovoids (for barrel shaped cervix,
ovoids snugly fit into lateral fornix, better lateral
dose)
■ Tandem and Cylinder (Upper vaginal stenosis,
superficial disease involving lower vagina)
■ Interstitial (poorly fitting intracavitary
applicators, lower vaginal involvement)
■ Hybrid
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26. Fletcher Suit Declos applicator
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27. Procedure
■ Anaesthesia
■ Lithotomy position
■ Bladder catheterized and filled with contrast
■ Measure Uterine length with sound (manual or
USG guided to reduce risk of perforation)
■ Cervical sleeve placement
■ Tandem inserted
■ Rectal pack f/b bladder pack
■ Then applicator connected to applicator base plate
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28. Imaging
■ CT or MRI with slice thickness 1-5mm
■ 2D
– Tandem should bisect ovoid in both AP and
lateral
– Ovoids should be symmetrical and not displace
inferiorly from flange on Lateral image
– Superior tip of tandem should be located
below sacral promontory inside pelvis
– Tandem should extend one half or one third
the distance from symphysis to promontory
– RO packing be anterior and posterior to ovoids
and not superior to it
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29. 2/1/2019

30. Dose points
■ Classical Manchester point A – 2 cm perpendicular
lateral to tandem and 2 cm cephalad along tandem
from the apices of vaginal fornices
■ Point B – 5 cm lateral to tandem, indicates dose to
pelvic nodes
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31. Revised point A & ICRU 38 Bladder
and Rectal reference points
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32. Treatment Planning System
■ Oncentra Brachy Planning Software
■ Catheter reconstruction
■ Virtual activation
■ Normalization
■ Optimization
■ Prescription
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33. Catheter Reconstruction
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34. Contouring – GEC ESTRO Group
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35. Activation and Normalization
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36. Optimization for OAR
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37. Treatment Room
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38. Dose delivery
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39. Treatment Control Station
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40. 2/1/2019

41. American Brachytherapy Society
■ Stage IB2 – IVA
– EBRT to pelvis 45 to 50Gy
– Brachytherapy with Goal of EQD2 of 80 to
90Gy to point A or HR CTV
■ 80 to 85Gy point A dose for early stage
■ 85 to 90Gy point A dose for advanced stage
■ 50 to 55Gy and 55 to 65Gy are pelvic side wall
dose for early and advanced stage diseases
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42. Dose
■ After 45Gy EBRT to pelvis with concurrent
cisplatin
■ 7-8 Gy per # for 3 # in interval of 1 week
■ Point Based dose and 1/3 rd of point A dose will
reach point B
■ Rectum should not cross 67-68 Gy, Risk is 8 to
13% and upto 12% if combined with EBRT
■ Bladder should not cross 85 Gy, Risk of cystitis is
3% in doses upto 50Gy and 18% if >80Gy, can
develop days to year after radiation
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43. Issues with HDR Brachytherapy
■ Treatment along with EBRT and BT should be
completed in less than 8 weeks
■ Interdigitation of BT with EBRT (BT to be given on
non EBRT days, In 2# per week in a total of 5#, not
start too early in case of large bulky tumors)
■ Central shielding and additional boost to
parametria or nodes on non BT days
■ Chemotherapy not administered on BT day
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44. Hybrid Brachytherapy
■ Utrecht and Vienna
applicator
■ MRI compatible
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45. Endometrial Cancer
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46. Role of Brachytherapy
■ As adjuvant in decreasing vaginal failures
following surgical staging
■ As definitive treatment along with EBRT in
medically inoperable patients
■ Treating the vaginal recurrence
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47. Vaginal cuff Brachytherapy
Stage Grade 1 or Grade 2 Grade 3
Stage IA Observation Observation vs
IVRT
Stage IB IVRT IVRT + IMRT
Stage II (<50%
Stromal invasion)
IVRT IVRT + IMRT
Stage II (>50%) IVRT + IMRT IVRT + IMRT + CT
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48. Preapplication assessment
■ Define anatomy (if any dog ear present)
■ Ensure appropriate healing
■ Vaginal cuff integrity
■ Rule out any herniation of bowel
■ Started 4 to 8 weeks postoperatively and not
beyond 12 weeks
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49. HDR Brachy Applicators
■ Cylinder
■ Usually
single channel
■ Ovoids, Rings, molds
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50. Procedure
■ Consent
■ Empty bladder
■ Dorsal lithotomy
■ Selected cylinder applicator inserted forward and
dorsally
■ Confirm it is in contact with vaginal apex
■ Fixed with perineal bar or external immobilization
devices
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51. Problems
■ Air pockets
■ Small introitus with larger apex
■ Increased dose to rectum and bladder
■ In such cases, multichannel applicators can
provide conformal dose
■ Underdosed in dog ear vaginal vaults
■ Vaginal ovoids or molds are best
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52. Assessment
■ AP and Lateral X rays with applicator in position
■ CT simulation from pelvis to ischial tuberosity
with 0.25cm slices
■ Assess Apex approximation, dog ears, air pockets
■ Assess rectovaginal septum
■ Identify Clinical target volume which is 3 to 5 cm
of upper vagina
■ Bladder and Rectal volume can be known
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53. HDR Brachytherapy
■ BT alone 7 Gy x 3# at a depth of 0.5cm
■ As boost following EBRT, 6 Gy X 2-3# given
■ Vaginitis, mild cystitis, proctitis
■ Fibrosis, Telengiectasia, dryness, shortening and
narrowing – compromise sexual QOL
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54. Where Entire Vagina treated?
■ Type II Endometrial cancer (Clear cell, papillary
serous type)
■ Extensive LVSI
■ Entire vagina treated with EBRT to pelvis, with
boost to upper vagina with brachytherapy
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55. Vaginal Cancer
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56. Vaginal Cancer
■ Role of Brachytherapy
■ Primary treatment modality in Stage I
■ Stage II to IVA, as an adjunct to EBRT to boost the
target tissues
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57. Applicator choice
Intracavitary vs Interstitial
■ Location, Extent and Thickness of disease after
EBRT
■ Proximal or mid vaginal disease
■ Superficial (<5mm thickness)
■ Single channel vs multichannel (middle or distal
vagina, single wall involvement)
■ Dose reduction to rectum and bladder
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58. 2/1/2019

59. Image based planning
■ After placing applicators
■ CT or MRI guided
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60. Dose recommendations
■ Following EBRT of 45 to 50.4Gy
■ 7Gy x 3#
■ 4 to 5.5Gy x 5# or 3Gy in 9-10#
■ EQD2 for CTV is 75Gy
■ Maintaining rectum, sigmoid dose <70Gy, Bladder
dose <80Gy, urethral maximum dose <100% of
prescribed dose
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61. Interstitial Brachytherapy
■ Thicker lesions
■ Lesions in distal vagina limited to single wall
■ Anaesthesia required
■ Apical lesions – Perineal template guided with
vaginal cylinder
■ Distal lesions – free hand or perineal template
■ Needles placed with 1cm spacing to cover disease
with additional 1 cm margin
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62. Martinez Universal Perineal
Interstitial Template (MUPIT)
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63. Syed Neblett Template
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64. Treatment
■ Delivered twice daily
■ Interaction interval 6 hours
■ Goal of 70 to 80Gy to CTV
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65. Vulval Cancer
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66. RT Indications
In adjuvant setting
■ Positive margins
■ Close margins (<8mm)
■ LVSI positive
■ DOI > 5mm
■ ECE of tumor or nodes
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67. Dose
■ EBRT given 45 to 50.4 Gy in Elective setting
■ Microscopic disease 55 Gy
■ ECE 60 Gy
■ Residual disease 65 to 70 Gy
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68. Role of BT in vulval cancer
■ Very limited
■ As a boost
■ Inoperable vulval cancers
■ Median dose 60 Gy (53 to 88 Gy)
■ High risk of necrosis
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69. Thank You
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