This document discusses radiation therapy for carcinoma of the cervix. It provides details on epidemiology, anatomy, staging, imaging, and treatment options. Some key points: - Carcinoma of the cervix accounts for over 4700 new cases and over 71,000 deaths worldwide each year, with over 80% of cases occurring in developing countries. - Staging is done according to the FIGO system, which classifies tumors from Stage 0 (carcinoma-in-situ) to Stage IV (distant metastases). Imaging such as CT, MRI, and PET can help determine tumor size, parametrial invasion, and lymph node involvement to guide treatment planning. - Treatment options include surgery,

1. RADIATION THERAPY
CARCINOMA CERVIX

2. CANCER CERVIX
Estimated 4,70000 new cases per year
worldwide
> 80% cases in developing countries
27% cases occur in India
1,20000 cases annually
71,000 deaths
15.2% to 50% of all female cancers
>80% of all cases present in advanced
stages

3. ANATOMY
PRIMARY SITE:
Cancer Cervix originates - vaginal surface
- cervical canal
NODAL STATIONS:
> parametrial,internal iliac(obturator-
hypogastric)
>External iliac, presacral & common iliac
METASTATIC SITES:
Paraaortic nodes
Lungs
Bone
Liver
Brain

4. PRE-TREATMENT EVALUATION
Complete physical and gynaecological
examination
CBC , Biochemistry and urine analysis
Chest X Ray
USG or CT Scan/MRI abdo & pelvis
Biopsy punch
CPE for bladder involvement
Colposcopy/ Barium Enema /
Sigmoidoscopy / IVU
PET-CT is optional

5. CERVICAL CA STAGING:
0: Carcinoma-in-situ
I: Confined to cervix
Ia: Microinvasive
Ia1: Depth </= 3mm Width </= 7mm
Ia2: “ - 3 – 5 mm “ “
Ib: Invasive – Clinically visible
Ib1: <4cm dia
Ib2: >4cm dia
II: Beyond cervix but not to pelvic wall
IIa: Upper 2/3 of vagina
IIb: Parametrial involvement (not to PSW)
III: Extension to PSW / Lower 1/3 rd Vagina / Hydronephrosis
IIIa: Lower 1/3 of vagina
IIIb: PSW or hydronephrosis
IV: Extension beyond true pelvis / bladder / rectum
IVa: Bladder or rectal mucosa
IVb: Spread outside true pelvis / Distant metastases

6. 1A
4B
</=4cm > 4cm
Upper 2/3 of vagina Parametrial involvement not to PSW
Lower 1/3 of vagina PSW or hydronephrosis
Bladder or rectal mucosa
Spread outside true pelvis / Distant metasts

7. RULES FOR CLASSIFICATION
FIGO guidelines:
Clinical-Diagnostic staging:
Staging based on clinical evaluation(EUA)
Clinical Staging must NOT be changed because of
subsequent findings
If stage doubtful EARLIER stage allocated

8. FOLLOWING EXAMINATIONS
PERMITTED
Inspection
Palpation
Colposcopy
Endocervical curettage
Hysteroscopy
Cystoscopy
Proctoscopy
IVU
X Ray Chest
Conization regarded as physical examination

9. FOLLOWING INVESTIGATIONS
OPTIONAL
Lymphangiography,Venography
Laproscopy
USG,CT Scan,MRI (planning therapy)
> Not generally available
> intepretation variable
FNAC : scan detected LN (planning therapy)

10. IMPACT OF IMAGING ON TREATMENT
DECISION AND PLANNING
The choice of treatment depends on –
- Tumor size
- Parametrial invasion
- Invasion to the ureter, bladder & rectum
- Lymph node metastases , esp above the level of true pelvis &
distant metastasis

11. METS TO PARA-
AORTIC LN
Stg IB 8%
Stg IIA 18%
Stg IIB 20-30%
Stg IIIB 33-46%
Stg IV 25 -50%

12. ROLE OF IMAGING -USG
Delineates the location ,size and extent of tumor
Hydronephrosis
Determine nodal spread
Follow up
Sensitivity for Parametrial spread – 56 %
and specificity is – 67 %

13. 24/12/05 14/03/05

14. ROLE OF IMAGING – CT
To determine extent of disease to aid in planning
treatment
Determine nodal and Parametrial spread
Sensitivity to determine parametrial spread is 67 %
and specificity is 70 %
Assessment of patients with a persistent mass after
treatment for cervical cancer to differentiate
residual or recurrent disease from benign
anatomical or post treatment changes
Bulky I B / Lower uterine segment involved or Stage
II / III B

15. ROLE OF IMAGING - MR
To determine extent of disease to aid in planning
treatment
Determine nodal and Parametrial spread
Sensitivity to determine parametrial spread is 96 % and
specificity is 92 %
Recommended for assessment of depth of tumor/
Parametrial spread / tumor volume(> 40 cc worse
prognosis)
DURING THERAPY: During first 2 weeks provides tumor
regression information especially for brachytherapy
tailoring
FOLLOW UP- Assessment of patients with a persistent
mass after treatment for cervical cancer to differentiate
residual or recurrent disease from benign anatomical or
post treatment changes

16. CORELATION OF MRI WITH SURGICAL
SPECIMEN

17. ROLE OF PET IMAGING
Grigsby et al PET vs CT
2 yr PFS based on para-aortic positive nodes :
- 64% in CT neg & PET neg
- 18% in CT neg & PET + ve
- 14% in CT + ve & PET + ve

18. ROLE OF PET – CA CERVIX
Higher incidence of para – A LN positivity
on PET when endometrial invasion present
on D&C
( Grigsby et al)
Planning for brachytherapy improving
overall dose distribution & reduction of
dose to sorrounding pelvis
During therapy: Reduction in physiologic
tumor volume of 50% within 20 days of Rx
(Lin et al)
Follow up

19. CT V/S MRI in cervical
cancer

20. PROGNOSTIC FACTORS
PATIENT:
Age < 35 yrs have decreased survival
European studies have shown the reverse
TUMOR:
Stage
Tumor volume
Vascular/ Lymphovascular Invasion

21. TREATMENT
Choice of Treatment depends upon:
1. Stage of disease
2. Age
3. General Condition
4. Desire for fertility

22. RADIATION
Radiotherapy uses megavoltage radiation
Diagnostic Radiology uses kilovoltage radiation
Radiation acts by interaction with patients
tissues + reactions causing DNA damage

23. RADIATION – CA CERVIX
EBRT :
Whole pelvis + parametria + common iliac
nodes + para- aortic LN
Brachytherapy:
Central disease for cervix , vagina, medail parametria

24. EBRT
EBRT delivered before ICRT in patients :
. Bulky cervical lesions to improve
geometry for ICRT
. Exophytic easily bleeding tumors
. Tumors with necrosis / infection
. Parametrial involvement

25. RADIOTHERAPY MODALITIES
External Radiation:
- Cobalt 60 gamma rays
- Megavoltge Radiation with Linear
Accelerator
- Conventionl Fractionation 40-50Gy/25# to
pelvis over 4 to 5 weeks
Aim: Divide total dose over time
Allows normal tissue to repair damage

26. EXTERNAL RADIOTHERAPY

27. TARGET VOLUME
Whole Pelvis
- encompassing extent of primary tumor
- Lower margins vagina involved / not invov
- Cover inguinal nodes if distal vagina
involved
- pelvic lymph nodes upto LV- 5
- precautions to keep min bowel in field
Methods:
- 2,3,4 Field 2-D RT
- 3-D CRT
- IMRT

28. TARGET VOLUME
Post Operative RT:
- extreme care for EBRT + ICRT
. Bladder & rectum very close to sources
. Vascular supply compromise by surgery

29. CONVENTIONAL TREATMENT
Pelvic RT
Paraaortic RT
Mutic S et al IJROBP 55 (2003) 28
Region 2: 45Gy (para-aortic LN)
Region 1: 45Gy + 5.4Gy EBT
+ brachytherapy boost

30. ROLE OF IMAGING FOR TARGET
DEFINITION
CT:
 Treatment planning
 Nodal assessment
MRI:
 Extra cervical spread
 Design of lateral portals
PET:
 Lymph node involvement
US/TRUS
Mutic S et al IJROBP 55 (2003) 28

31. IMRT TO PELVIS

32. ROLE OF IMRT IN CERVIX
CANCER
For pelvic treatment sparing of
normal structures (bone
marrow, intestines)
Potentially replace
brachytherapy (80Gy possible
with 0.5cm margin) -
alternatively applicator based
IMRT (Low et al 2002)
Simultaneous integrated boost
Lujan
2003

33. BRACHYTHERAPY – CA
CERVIX
LDR ( Low dose rate) 137 Cs 0.4 to 2 Gy/ hr
HDR ( High Dose rate) 192 Ir > 12 Gy/ hr

34. BRACHYTHERAPY
Intracavitary : Tandem and Ovoids
Miniovoids
Central Vaginal applicator
Interstitial : Needles Ra , Cs
Residual tumor, parametrial
involvement

35. RADIATION THERAPY
(BRACHYTHERAPY)
ICRT: ( Done under GA )
Radical
Boost ( Combined with EBRT )
Place applicators
Vaginal packing radiopaque
Radiographs using dummy sources
Actual treatment
Good application delivers high dose of RT
to cervix, upper vagina, medial parametria
without exceeding tolerance dose to
bladder & rectum

36. HDR VS LDR
LDR: 20 hrs continous application
Admission to hospital
Lesser number of applications (2)
30 Gy to pt A - 2nd week EBRT
- after completion of EBRT
HDR: Day procedure
Treatment time 10 min
5 applications recommended
7 Gy to pt A – weekly starting week 2 of EBRT
Lower toxicity (GI & GU)
Control rates comparable

37. TANDEM WITH OVOIDS

38. BRACHYTHERAPY UNDER MR

39. MR - BRACHYTHERAPY

40. AFTER LOADER, WITH 192 IR

41. RT - COMPLICATIONS
Acute – EBRT GI
GU
ICA Cx of GA
Perforation/Laceration
Late – Hematuria
Hematochesia
Fistula

42. MANAGEMENT OF CA CERVIX
Stage 0 ( Carcinoma in situ)
Ectocervical Lesions:
- Loop Electrosurgical Excision (LEEP)
- Laser
- Conisation
- Cryotherapy
Endocervical Canal Lesions:
- Laser/Cryo (Fertility preservation)
- TAH
- Radiation Therapy > Single Intracavitary insertion 80 Gy
vaginal surface dose (Grade B recommendation)

43. POST SURGICAL TREATMENT –
PATHOLOGICAL STAGING
Accurate assessment of disease extent
Does not change clinical stage
Helps decide adjuvant treatment post Sx

44. STAGE IA
Stg IA1 (not >3mm depth, no wider than 7mm) (Lymph node mets < 1%)
- Conisation
- Total Abdominal Hysterectomy
or
- Intracavitary brachytherapy (2# upto 100 Gy VSD)
if no LVI, then no EBRT
Stg IA2 (Lymph node mets < 5%)
- Radical Hysterectomy Type II with pelvic node
dissection
or
- Radiation therapy
Radical Intracavitary / EBRT + Intracavitary

45. POST OPERATIVE RISK
GROUPING
HIGH RISK:
Lymph node involvement
Parametrial invasion
Positive surgical margins
Management
Adjuvant CT + RT
Reduces local failure rate & improves PFS vs
Surgery alone

46. POST OPERATIVE RISK
GROUPING
INTERMEDIATE RISK:
Deep Stromal Invasion
Lymphovascular space invasion
Tumor size > 4 cm
Management
Adjuvant RT if 2 out of 3 on HPR
Reduces local failure rate & improves PFS vs
Surgery alone

47. POST OPERATIVE SURGICAL
RISK GROUPING
LOW RISK:
All other patients
No adjuvant therapy recommended
Observation

48. ISODOSE DISTRIBUTIONS

49. STAGEIB/IIA
Appropriate Investigations
(Lymph node mets 10-20%)
SURGERY:
Type III Radical Hysterectomy + Pelvic lymphadenectomy
Risk Grouping
Low - Observe
Intermediate- Pelvic RT
High Risk -- Concurrent CT+ RT( weekly cisplatin)
OR
RADIOTHERAPY
IB1: Radical Radiotherapy
IB2: CT+ RT
Comparable OAS for RT and Sx ( 80 to 90 %)

50. STAGE IIB TO IIIB
Appropriate Investigations + Imaging (LN inv upto 40%)
Radiotherapy is primary local treatment
Primary RT OAS –
Stage II B – 65 - 75 %(5 Yr survival)
Stage III B – 35 - 50 %(5 Yr survival)
Stage IV A – 15 -20 %(5 Yr survival)
Para-aortic LN negative:
- CT+RT
- Radical RT
Para-aortic LN positive:
- Extended field RT+CT
- Neoadj CT 2-3 cycles  Extended field RT

51. STAGE II B TO III B
Radiation dose –
II B – 40 Gy EBRT to Pelvis + MLB – 20 Gy
HDR – 7 Gy / 5 #
or LDR – 30 Gy / 2 # to Pt A
III B – 50 Gy EBRT / 25 #
HDR 7 Gy / 3#
or LDR – 25 Gy / 1 # to Pt A

52. STAGE IVA (15 -20 % 5 YR SURVIVAL)
Pelvic Exenteration
Neo adj CT or CT+RT
Palliative Radiotherapy(30 Gy / 10 #)
- Effective pain relief in symptomatic
mets.(Bone/Brain/LN’s)
- Control of bleeding

53. LOCAL RECURRENCE FOLL
SURGERY
RT (Grade C Recommendation)
CT+RT (Grade B Recommendation)
Pelvic Exenteration (Gr C recommendation)

54. LOCAL RECURRENCE POST
RT
Central Recurrence:
Pelvic exenteration
Selection of patient
- DFS > 6 months
- Recurrent tumor < 3 cm
- No pelvic sidewall fixation
Pelvic Sidewall / Extrapelvic Recurrence
Palliative Chemotherapy

55. INTERSTITIAL RT
INDICATIONS –
RECURRENCE
VAULT RECURRENCE
PARAMETRIAL RECURRENCE

56. INTERSTITIAL BRACHYTHERAPY
GYNECOLOGICAL APPLICATOR

57. NEEDLES TROUGH A TEMPLATE

58. HDR – LDR EQUIVALENTS
HDR dose LDR equivalent 6 Gy x 432 Gy 6 Gy x 540 Gy
Taiwan (1996) -— "Determination of the appropriate
fraction number and size of the HDR brachytherapy for
cervical cancer." Liu WS et al. Gynecol Oncol. 1996
Feb;60(2):295-300.
Detroit (1991) -— "Comparison of high and low dose rate
remote afterloading for cervix cancer and the importance of
fractionation." Orton CG et al. Int J Radiat Oncol Biol Phys.
1991 Nov;21(6):1425-34.
 Analysis of 17,000 cervix cancer pts in 56 institutions using HDR.
 Conversion of dose from LDR to HDR, use dose factor of 0.54.

59. BRACHYTHERAPY
Three systems:
Paris system
Stockholm system
Manchester system

60. BRACHYTHERAPY
Manchester system
Point A dose definitions:
 Allegedly, Point A corresponds to the paracervical triangle in the medial
edge of the broad ligament where the uterine vessels cross the ureter
 Original definition: draw a line connecting the superior aspects of the
vaginal ovoids and measuring 2 cm superior along the tandem and then 2 cm
perpendicular to this. (weakness: failure of localization radiographs to show
the surface of the ovoids' caps)
 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
 Point B - 5 cm lateral from the midline at the same level as Point
A

61. MANCHESTER SYSTEM
The Manchester applicators consisted of a rubber tandem and two ellipsoid
"ovoids" with diameters 2, 2.5, and 3 cm. No shielding in ovoids, so needed
generous packing anteriorly and posteriorly. Used radium. Used 17.5, 20, and
22.5 mg Ra for the small, medium, and large ovoids, respectively.
Designed such that:
Point A dose rate was approximately 0.53 Gy/hr for all allowed applicator
loadings
Vaginal contribution to Point A was limited to 40% of the total dose
The rectal dose should be 80% or less of the Point A dose
Prescribed 80 Gy to point A in two applications, total of 144 hours, in the absence
of external beam.
Weakness:
- Wide variation in Point A in respect to the ovoids.
- Point A often occurs in a high-gradient region of the isodose distribution.
Therefore, minor differences in position can result in large differences in dose.

62. ICRT - APPLICATORS
Fletcher applicator
Derives from the Manchester system. Added internal shielding in
the colpostats. Afterloading ability. Colpostat has 2 cm diameter
that can be increased to 2.5 or 3 cm by the addition of plastic caps.
Minicolpostats are 1.6 cm and have a flat inner surface and have no
shielding. Used 15, 20, and 25 mg Ra for small, medium, and large
colpostats; use 10 for the minis. Tandems are available in three
curvatures. Flange on the tandem avoids slippage past the cervical
os, and a keel helps keep it from rotating. A yoke attaches the
tandem and colpostats to maintain proper position. Loading of the
tandem is 20 - 10 - 10 mgRaEq with Cs-137.
Plastic Fletcher applicators are available to be compatible with CT
simulation or MRI.

63. BRACHYTHERAPY PLANNING
AP View
 Tandem midline, unrotated
 Tandem midway between colpostats
 Keel (flange) in close proximity to gold seed
markers
 Colpostats high in the fornices along cervix
Lateral View
 Tandem bisects the colpostat
 Sufficient anterior and posterior packing
 Foley balloon firmly tugged down

64. BRACHYTHERAPY
Good Insertion Characteristics
American Brachytherapy Society (ABS)
Recommend prescribing to Point H - Draw
a line connecting the mid-dwell positions of
the ovoids and find the point this line
intersects the tandem. Follow 2 cm superior
(along the tandem) plus the radius of the
ovoids, then 2 cm perpendicular to the
tandem. Note: This is basically 2 cm above
the top of the ovoids.

65. BRACHYTHERAPY
 Specification of image-guided GTV and CTV
Osaka (Japan)(1983-1989) -- HDR fractional dose 7.5 Gy/fx
vs. 6.0 Gy/fx
 Randomized. 165 patients with cervix adenoCA, Stage IA-IV.
Treated with 2 separated dose schedules depending on stage.
Arm 1) EBRT + BT using 7.5 Gy/fx (either 37.5/5 or 30/4 or
22.5/3) vs. Arm 2) EBRT + BT using 6.0 Gy/fx (either 36/6 or
30/5 or 18/3).
 5-years; 1994 -- "A prospective randomized study concerning
the point A dose in high-dose rate intracavitary therapy for
carcinoma of the uterine cervix. The final results." (Chatani M,
Strahlenther Onkol. 1994 Nov;170(11):636-42.)
 Outcome: 5-year CSS: Stage I 100% vs. 100%, Stage II 82% vs. 85%, Stage
III 62% vs. 52%, Stage IV 22% vs. 31% (all NS). No difference in LRF or DM
 Toxicity: No difference
 Conclusion: No difference between the two treatment schedules; small
number of fractions at 7.5 Gy/fx may be advantageous due to short
duration

66. DOSE CALCULATIONS -
BRACHYTHERAPY
ABS,
Problem: What dose/fraction of HDR delivered in six
fractions will be equivalent in terms of tumor control to 60
Gy delivered to Point A at 0.55 Gy h−1?
Solution: Assume α/β (tumor) = 10 Gy, μ (tumor) = 0.46
h−1.
Then: BED (LDR) = 60[1 + (2 × 0.55)/(0.46 × 10)] = 74.3
Equating this to the BED for 6 HDR fractions with
dose/fraction d gives:
74.3 = 6d(1 + d/10)
Solving this quadratic equation for d gives: d = 7.20 Gy.
Conclusion: 6 fractions of 7.20 Gy with HDR is
equivalent in terms of tumor control to 60 Gy delivered at
0.55 Gy h−1.

67. HDR dose LDR equivalent
6 Gy x 4 = 32 Gy
6 Gy x 5 = 40 Gy

68. Bladder point - on the surface of a Foley balloon filled with 7 cc of contrast;
located at center of balloon on AP film, posterior surface of the balloon on a
line through midballoon on lateral film
Rectum point - 0.5 cm posterior to the posterior vaginal wall at the level of
the bisection of the T&O. May also use barium + air contrast in rectum
Vaginal mucosa - at surface of ovoids
Pelvic sidewall, and external, common, and para-aortic LN points should be
reported according to ICRU defintions
Keep dose to rectum and bladder points below 80% of dose to Point H (ABS
recommendation). Or, maximum dose to rectum, 75 Gy (avg dose 68 Gy);
bladder, 80 Gy (avg 70 Gy); vagina, 120-140 (avg 125 Gy).

69. BRACHYTHERAPY -
COMPLICATIONS
Acute complications
(1960-1992) - "Perioperative and
postoperative complications of
intracavitary radiation for FIGO stage I-
III carcinoma of the cervix." Jhingran A et
al. Int J Radiat Oncol Biol Phys. 2000; 46
(5):1177-83
 Retrospective. 7662 intracavitary procedures
in 4043 patients for FIGO I-III cervical CA
 2.8% uterine perforation rate, 14% have fever
>101 C during at least 1 admission, 0.1% fatal
thromboembolism rate. Perforation did not
affect DSS in stage I, II, but did lead to worse
prognosis in stage III.

70. Late complications
1995 (1960-89) — "Time course and incidence of late
complications in patients treated with radiation therapy for
FIGO stage IB carcinoma of the uterine cervix." Eifel PJ et al.
Int J Radiat Oncol Biol Phys. 1995 Jul 30;32(5):1289-300.
 Retrospective. 1784 pts, FIGO stage IB. Grade 3 or higher
complications occurred in 7.7% at 3 yrs and 9.3% at 10 yrs. After
10 yrs, 0.34% per year, so at 20 yrs, 14.4% risk.
 Risk of rectal complications was the greatest, more than urinary
complications.
 Conclusion: low risk of major complications using brachytherapy.

71. BRACHYTHERAPY
Guidelines
Keep total duration (of EBRT + implants) to < 8
weeks. For HDR, this necessitates beginning
brachytherapy while EBRT is ongoing. Usually give
an HDR treatment once per week, not giving EBRT
on that day.
ABS recommendations
LDR (2002) — "The American Brachytherapy Society
recommendations for low-dose-rate brachytherapy
for carcinoma of the cervix." Nag S et al. Int J Radiat
Oncol Biol Phys. 2002 Jan 1;52(1):33-48.
HDR (2000) — "The American Brachytherapy Society
recommendations for high-dose-rate
brachytherapy for carcinoma of the cervix." Nag S et
al. Int J Radiat Oncol Biol Phys. 2000 Aug
1;48(1):201-11.

72. SCREENING FOR CANCER
CERVIX
NCCP – Priority for early detection & treatment
No current screening programme- technical,
financial, manpower constraints
Aim: Reduce morbidity & mortality
Detection of precancerous lesions
HPV Vaccine – Primary prevention . It is a
bivalent virus like particle against subtypes 16 &
18.Three doses at 0 , 1 & 6 mths.
Efficacy – 100 % in preventing new and persistent
infection of genital tract.
Duration of protection – Not known

73. UNITS OF RADIATION
Roentgen : Unit of exposure
Absorbed Dose: Energy deposited by
radiation as it passes thru tissue to create
biological effects
RAD: Represents absorption of 0.01J/Kg
of
absorbing material
GRAY: Dose associated with absorption
of 1J of energy / kg of absorbing
material
1 RAD = 10 mGY

74. RADIATION UNITS
Equivalent Dose(E): Diff
types of radiation
produce diff degree of
biological damage
SIEVERT = Measures dose
equivalent
Absorbed Dose (Gy) X
Radiation weighting factor
For this
procedure:
Your effective
radiation
dose is:
Comparable
to natural
background
radiation for:
(CT)-
Abdomen
10 mSv 3 years
(IVP) 1.6 mSv 6 months
(CT)-Head 2 mSv 8 months
(CT)-Chest 8 mSv 3 years
Radiography-
Chest
0.1 mSv 10 days