Non surgical management of Ca Cevix

1. Non surgical management
of Carcinoma Cervix
Dr Naresh Jakhotia
Radiation Oncologist
BMCHRC

4. FIGO staging - 2009
 Evaluation procedures –
 Colposcopy
 Biopsy
 Conization of cervix - invasiveness
 Cystoscopy
 Proctosigmoidoscopy
 CXR-PA view
 Intravenous Pyelography
 Barium enema
 Complex radiologic and surgical staging – not addressed.

5.  Directly aligns with AJCC staging
 No Stage 0 in FIGO
 Regional LN mets not included
 Not altered by LVSI
 FIGO Staging –
 intended for comparison purposes only
 Not as a guide for therapy
FIGO staging - 2009

6. • In United States, modalities used to guide treatment
options and design –
 CT
 MRI
 PET-CT
 Surgical staging

7. WORK-UP
 History
 Physical Examination
 CBC
 RFT/LFT
 CXR-PA view
 CT
 PET-CT
 MRI
 Imaging – optional for stage ≤ IB 1
 Cystoscopy & Proctoscopy – if bladder or rectal extension
is suspected
 May aid in treatment
planning
 Not accepted for formal
staging purposes

8.  NCCN panel
 Uses FIGO definitions as stratification system for
guidelines
 Imaging studies (CT & MRI) - used to guide treatment
options and design
 MRI –
 To rule out disease high in endocervix
 To guide b/w fertility-sparing v/s non-fertility-sparing
treatment approaches.
 To determine soft tissue and Parametrial involvement in
advanced tumors

9. Management
 Surgery –
 Early stage disease
 Smaller lesion – stage IA, IB1, selected IIA1
 Concurrent Chemoradiation –
 Stage IB2 to IVA
 Not medically fit for hysterectomy
 Invariably lead to ovarian failure in premenopausal
women
 Ovarian transposition
 Before pelvic RT
 Select F < 45 yr, with Sq. cell cancer

10. Stage Fertility Sparing Non- Fertility sparing
I A1
(No LVSI)
Cone biopsy
( Negative margin)
Extrafascial / Modified
radical Hysterectomy ±
Pelvic LN dissection
( SLN mapping)
I A1 ( with LVSI)
& IA2
•Cone Biopsy with
Negative margin + Pelvic
LN dissection ± Para-
aortic LN sampling
•Radical trachelectomy +
Pelvic LN dissection ±
Para- aortic LN sampling
( SLN mapping)
•Modified Radical
Hysterectomy + Pelvic LN
dissection ± Para- aortic
LN sampling
( SLN mapping)
• Pelvic RT +
Brachytherapy
(70-80 Gy • A)
I B1 & II A 1
(selected)
•Radical Trachelectomy
+Pelvic LN dissection ±
Para- aortic LN sampling
( SLN mapping)
(< 2cm)
• Radical Hysterectomy +
Pelvic LN dissection ±
Para- aortic LN sampling
( SLN mapping)
• Pelvic RT + BT ± CCT
(80-85 Gy • A)

11.  Stage IB2 & II A2 -
 Definitive Pelvic RT + CCT + BT ( Total dose • A ≥ 85 Gy)
– (Category 1)
 Radical Hysterectomy + Pelvic LN dissection ± Para-
aortic LN sampling ( category 2B)
 Stage IIB, IIIA, IIIB, IV A –
 Definitive Pelvic RT + CCT + BT
 Para-aortic LN +ve –
 Extended-field RT

13. Randomized study of radical surgery v/s
radiotherapy for stage Ib-IIa cervical cancer:
Lancet 1997
 Only prospective trial comparing radical surgery with
radiotherapy
 Design
Surgery
EBRT+ICR
pT2b , <3
mm
margins,
positive
margins,
positive
pelvic
node,
parametria
l extn.
Post op RT
IB and
IIA
343

14. Results
Median follow-up of 87 months
Worse morbidity seen in combined modality
Treatment
modality
5-year
overall
and
disease-
free
survival
Toxicity
Surgery 83% & 74
%
25% 28%
Radiotherap
y
83 % &
74%
26% 12%
Local
recurren
ce
P=0.004

15. Non randomized comparative studies
study Stage of ca
cervix
Outcome Results
Kielbinska et al STAGE 1
n=792
survival, general
health, incidence of
recurrent
carcinoma
Equivalent results
Piver et al Stage IB
N=103
5-year disease-free
survival
92.3% for the
surgical group and
91.1% for the
radiation therapy
group
Perez et al 118 patients with
stage IB or IIA
5-year tumor-free
survival
Stage IB=80% and
82%
stage IIA= 56%
and 79%
Perez et al 415 patients with
stage IB or limited
stage IIB
10-year cause-
specific survival
rate
61% and 68% for
non bulky tumors

17.  N = 10,933 - Largest patterns-of-care analysis to
date evaluating patients with local EOD IB-IIB
cervical cancer
 Use of different treatment modalities over a 26-year
time period - from 1983 to 2009
 AIM - To reduce treatment related morbidity without
compromising outcomes.

18.  For Stage IB-IIA cancers, definitive radiation has 5-year
overall & disease specific-survival rates equivalent to
surgery with radiation given for risk factors, with a
reduction in grade 2 or 3 morbidity of greater than 50%
for patients undergoing RT alone.
 Careful selection of patients for radical hysterectomy
should be done to prevent increased toxicity of multiple
therapies.
 Improved imaging technology –better pretreatment
evaluation.

19.  Preoperative nodal assessment - most challenging
pretreatment evaluation.
 High sensitivity and specificity of PET for pelvic LN
detection compared to other imaging modalities.
 Algorithm for LN positivity –
 Age < 50 yrs
 Tumor size
 Grade 2 and 3 disease
 Local extent of disease IB2, IIA, and IIB
 Depth of invasion
 LVI
 Parametrial extension

20. Decision tree for pretreatment
evaluation of cervical cancer

21. GOG -92 Protocol - stage IB – Adjuvant T/t

22. Intergroup Gynecologic Oncology
Group (GOG) Trial 109
( Adj. RT v/s Adj. CTRT)

23. American Brachytherapy Society –
 Recommends
 primary therapy should avoid routine use of
both Radical surgery and RT
 to minimize morbidity related to multimodality
therapy.
 Overall treatment time should be ≤ 8 weeks.

24. Treatment of Stage IIB–IVA Cervical
Cancer

26.  CTRT results in 30-50 % decrease in risk of death
compared with RT alone.
 These trials established role for con. Cisplatin-based
chemoradiation.
 Long term follow-up of 3 of these trials confirmed
that concurrent cisplatin-based chemoradiation
improves progression-free survival (PFS) and overall
survival, compared with RT with (or without)
hydroxyurea.

32. NCI - ALERT
 Strong consideration should be given for using
concurrent chemoradiation instead of RT alone in
cervical cancer

33.  Chemoradiotherapy leads to 6% improvement in 5-
year survival
 Hazard ratio – 0.81
 P<0.001

34.  N= 4069
 Confirmed that chemoradiotherapy improved
outcomes when compared with RT alone

35. Radiation Treatment Planning
 CT-based treatment planning with conformal
blocking and dosimetry – standard of care for EBRT
 CBCT – helpful in defining daily internal soft tissue
positioning.
 Extending overall treatment time beyond 6 to 8
weeks can result in approximately 0.5 – 1 %
decrease in pelvic control and cause specific survival
for each extra day of overall treatment time.
 Entire RT course – should be completed within 8
weeks.

36. Brachytherapy
 Critical component of definitive / adjuvant therapy
 Special shape of zone to be treated –
 Not symmetrical around the sources
 Considerable variation in size & shape of organs concerned
 Typically combined with EBRT in an integrated
treatment plan

37.  Approach –
 A) Intracavitary – intrauterine tandem and vaginal
colpostats
 B) Interstitial – anatomy / tumor geometry
 C) Vaginal cylinder – selected post-hysterectomy
cases.
 SBRT – not routine alternate to brachytherapy.
 Image-based volumetric brachytherapy
 Improve precision and quality of treatment

39. Paracervical triangle
 Aim of treatment : to raise to as high dose as can be
tolerated to this thin triangle of tissue
 Important uterine arteries and ureter run through this
 Initial lesion of radiation necrosis due to high dose
effects in the medial edge of broad ligament
 Radiation tolerance – limiting factor in treatment of ca
cervix

40. Point A
 Represent paracervical reference point
 At or near to point where uterine artery crosses
ureter
 Most widely used, validated, and reproducible
dosing parameter
 Point 2cm lateral to centre of uterine canal and 2
cm from mucous membrane of lateral fornix of
vagina in plane of uterus

41.  Recommended total dose to point A-
 Small tumors – at least 80 Gy
 Larger tumors - ≥ 85 Gy
 Limitation – it does not take into account -
 3-D shape of tumors,
 Individual tumor to normal tissue structure correlations.

42. Point B
 Dose – indicate rate of
fall-off of dosage
laterally
 Located at same level
as Point A but 5 cm
from midline
 Chosen because of
proximity to obturator
gland.

44. EBRT volume
 Gross disease
 Parametria
 Uterosacral ligaments
 Sufficient vaginal margins from gross disease (3 cm)
 Presacral LN
 Other LN at risk
 Neg LN on surgical/radiologic staging –
 Obturator, Ext. & Int. iliac LN
 Higher risk of LN involvement ( bulky tumor,
suspected/confirmed LN confined to true pelvis)
 Volume increased to cover common iliac LN also

45.  For lower one third vaginal lesion –
 Inguinal LN – must be treated
 Para-aortic LN (occult or macroscopic) –
 45 Gy
 Bowel, spinal cord, renal tolerances
 Gross disease in parametria or unresected LN –
boosted to 60-65 Gy
 SBRT – not considered routine alternate to
brachytherapy

47. RADIOLOGICAL MARKINGS
 Superior border –
 At the L4-5 inter space to include external &
internal iliac L.N.
 This margin must be extended to the L3-4 inter
space if common iliac nodal coverage is
indicated.
 Inferior border - at the inferior border of the
obturator foramen.
 For vaginal involvement, lower border is 2-3cm
below the lower most extent of disease
 tumours that involve lower third of vagina,
inguinal nodes should be included in the fields
 Lateral borders - 1.5 - 2cm margin on the widest
portion of pelvic brim

48. RADIOLOGICAL MARKINGS
 Anterior margin - at the pubic
symphysis
 Posterior margin – at S2 – S3
junction and it should extend to the
sacral hollow in patients with
advanced tumours
 Superior & inferior margins -
same as that for AP/PA Fields

50. Composite of 6MV beam
6MV color wash
Composite of 15MV beam
15MV color wash

51.  Documented common iliac and/or para-aortic LN –
 Extended –field pelvic or para-aortic RT, upto level of
renal vessels.
 EBRT dose to LN –
 Microscopic – 45 Gy
 Gross unresected – 10-15 Gy (Boost)

52. IMRT
 Minimize dose to bowel and other critical structures in
 post-op cases
 PALN
 Useful when high doses are required to treat gross
disease in regional LN
 Not alternative to brachytherapy for treatment of central
disease in intact cervix
 Very careful attention to detail and reproducibility
required

54. Intraoperative Radiation Therapy
 Single, highly focused dose of radiation to –
 Tumor bed at risk
 Isolated unresectable residual disease, during surgery
 Esp. useful – recurrent disease within previously
radiated volume
 Overlying normal tissue are displaced
 Delivered with pre-formed applicators – variable
sizes.

55. Dose prescription points for BT in cervical cancer

62. CONCLUSION
 These are sq. cell ca. that are moderately sensitive to
radn. Radiation plays an important role in management
of carcinoma cervix.
 Predictable pattern of spread helps in designing radn
portals.
 Since tolerance of Cx is very high hence high dose can
be delivered.
 Aim is to deliver curative dose of around
 Early stage - 80 - 85Gy to point A
 Advanced stage - 85-90Gy to point A

63.  But this dose can’t be delivered by EBRT alone
because of presence of dose limiting structures
like bladder & rectum in the beam path.
 To achieve tumor control – radiation is delivered
by combined technique of EBRT &
Brachytherapy.

64.  The cervical cancer has two components
 Central component - Disease confined to cervix , vagina
& medial parametria- best treated by brachytherapy
 Peripheral component - Disease involving lateral
parametria & lymph nodes-best treated by EBRT&
brachytherapy as boost
CONCLUSION

65.  Patients with stage IA ca cx are managed by radical
hysterectomy alone.
 If inoperable, then dose of approx.80 Gy is delivered by
brachytherapy alone
 Patients with stage IB may be managed by a
radical hysterectomy alone if the tumor is <4 cm in
size with no other adverse features.
 Stage IB with tumor > 4 cm, and all patients with
stage IIA, IIB, IIIA, IIIB, and IVA are managed with
EBRT with concurrent chemotherapy and
Brachytherapy.
CONCLUSION

66. Thank you