nact in ca cervix

3. FIGO Staging
• STAGE 0 – carcinoma in situ, intraepithelial carcinoma.
• STAGE I –cervix.
Stage IA – microscopic lesion
maximum depth of 5mm and not wider than7mm.
IA1 –
≤3mm in depth.
IA2 – ≥ 3mm and <5mm in depth .
Stage IB – clinical lesion & preclinical lesion >IA.
IB1 - ≤ 4cm in size.
IB2 - > 4cm in size.

4. STAGE II – beyond the cervix but not the pelvic wall,
involve vagina but not the lower third.
IIA – no obvious parametrial involvement
IIA1< 4 cm , IIA2 >4 cm in greatest diameter
IIB – obvious parametrial involvement.
STAGE III – upto the pelvic wall,
or lower third of vagina
hydronephrosis,or
non functioning of the kidney.
IIIA – no extension onto pelvic wall, but involvement of lower third of vagina.
IIIB – pelvic wall or hydronephrosis or non functioning kidney.
STAGE IV – beyond the true pelvis or
clinically involved the mucosa of the bladder or rectum.
IVA - adjacent organs.
IVB – distant organs.

6. ESMO GUIDELINE

7. ESMO GUIDELINE

9. ESMO GUIDLINE

10. Indications - adjuvant t/t

11. stages IB2 to IVA
Chemoradiation – best choice
•Results from several cooperative oncology groups demonstrated that
cisplatin based chemotherapy when given concurrently with radiation
prolongs survival in locally advanced cervical carcinoma.
•GOG 123 Keys et al
•GOG 85 Whitney et al
•GOG 120 Rose et al
•GOG 109/SWOG 87 97 Peters et al
•RTOG 90 01 Eifil et al

12. Radiotherapy is the primary local treatment for
most patients with loco regionally advanced
cervical carcinoma.
Five-year survival rates
65% to
75%,
35% to
50%
15%
to20%

14. • For these locally advanced tumors, it was 12–18% for pelvic
failure alone, 11–61% for pelvic plus distant metastases and
15–22% for distant metastases only.
• Strategies for improving outcome should, thus, be aimed at
increasing loco-regional control and eradicating occult
metastases already present at diagnosis.
• It is, therefore, logical to combine conventional RT with other
treatment modalities to increase tumor control.

15. • The addition of other modalities including surgery, hyperbaric
oxygen, hypoxic cell sensitizer , neutron therapy , or hyperthermia
has been met with limited or no success, or has been associated
with an increased morbidity.
• These unsatisfactory results have prompted investigators to
introduce other innovative therapeutic approach.
• The addition of chemotherapy is an attractive idea, and has been
extensively studied in recent 10 years.

16. Rationale
• Tumor-size reduction may facilitate subsequent local therapy, whether
radiotherapy or surgery. This reduction can transform inoperable tumors
into radically resectable ones.
• NACT, treats the micro metastatic disease, preventing a significant
proportion of relapses.
• NACT has been suggested to increase radiosensitivity and decrease the
hypoxic cell fraction.
• Giving chemotherapy prior to radiotherapy,rather than concomitantly,
increased radiotherapy toxicity may be less likely.
• Finally, response to NACT has been identified as an important prognostic
factor in several studies.

18. Neoadjuvant chemotherapy followed by radiotherapy
versus
radiotherapy alone in locally advanced carcinoma cervix: a
prospective randomized study
Study Objective:
•To compare the disease response, disease free survivaldisease free survival, overall survival and
toxicity
•profile to neoadjuvant chemotherapy followed by radiotherapy(CT-RT group)
versus radiotherapy alone(RT alone) in locally advanced carcinoma cervix.
Materials and Method:
•July 2007 and August 2008, 113 patients with squamous cell carcinoma,
adenocarcinoma and adenosquamous carcinoma cervix, FIGO stage IIB-IIIB,
• Two cycles of cisplatin and 5- flourouracil(CT) followed by radiotherapy(RT) (CT-
RT group,n=58) or RT alone (RT alone group , n=55).

19. • Inj cisplatin : 50mg/m2 on day 1 and 2 in divided doses. The drug was given in an
infusion over a period of 90minute after adequate hydration and antiemetics
followed by mannitol diuresis.
• 5fluorouracil :- It was given in a dose of 500mg/m2 over 6 hours on day 1 and
• day 2 repeatation 3 weekly, total 2 cycles .
• Radiotherapy:
• Started within one week of randomization or within 2-3 weeks of completing the
second cycle of chemotherapy. RT treatment was same in both arms. External
beam radiation therapy was administered using cobalt 60 teletherapy machine.
• A dose of 45 Gy in 20 fractions in 4 weeks was given at a dose of 225 centi gray
per fraction daily, for 5 days in a week.
• After a gap of 1 to 2 weeks patients were reassessed for response and patient
with good local response and intracavitary brachytherapy using Selectron remote
controlled LDR system, 137Cs based, giving a dose of 35 Gy to point A.

23. Background:
•Investigated the feasibility of dose-dense neoadjuvant chemotherapy (NACT)Investigated the feasibility of dose-dense neoadjuvant chemotherapy (NACT)
with paclitaxel and carboplatin before radical chemoradiation (CRT) andwith paclitaxel and carboplatin before radical chemoradiation (CRT) and
assessed the response rate to such a regimen.assessed the response rate to such a regimen.
Methods:
This is a single-arm phase II trial ofThis is a single-arm phase II trial of 46 patients46 patients, with locally, with locally
advanced cervical canceradvanced cervical cancer (stage Ib2-IVa(stage Ib2-IVa).).
Patients receivedPatients received
•dose-dense carboplatin (AUC2) and paclitaxel (80mgm-2) weeklydose-dense carboplatin (AUC2) and paclitaxel (80mgm-2) weekly
for six cycles followed by CRT (40mgm-2 of weekly cisplatin)for six cycles followed by CRT (40mgm-2 of weekly cisplatin)
•50.4 Gy, 28 fractions plus brachytherapy). The primary end point50.4 Gy, 28 fractions plus brachytherapy). The primary end point
was response rate 12 weeks post-CRT.was response rate 12 weeks post-CRT.

24. Results:
•Baseline characteristics
were:
median age at diagnosis 43 years;
 72% squamous, 22% adenocarcinoma
and 7%adenosquamous histologies;
FIGO stage IB2 (11%), II (50%), III (33%),
IV (7%).

25. • Complete or partial response rate was 70% post-NACT and
85% post-CRT.

26. • The median follow-up
was 39.1 months.
• Overall and
progression-free
survivals at 3 years
were 67% and 68%,
respectively.

27. • Grade 3/4 toxicities
were 20% during
NACT(11%
haematological, 9%
non-haematological)
and 52% during CRT
(haematological: 41%,
non-haematological:
22%).

28. Conclusion:
•A good response rate is achieved by dose-dense weekly NACT
with carboplatin and paclitaxel followed by radical CRT.
•This treatment regimen is feasible as evidenced by the
acceptable toxicity of NACT and by the high compliance to
radiotherapy (98%).

29. META – ANALYSIS
(2004): MRC (UK) group

30. Neoadjuvant chemotherapy
for locally advanced disease:
Meta-analysis (2004): MRC (UK) group
• IPD meta-analysis
• Trials had to be properly randomised and include patients with locally
advanced cervical cancer who had received neoadjuvant chemotherapy
either before radiotherapy or surgery (or both).
• Included stage IB-IV disease
• Did not include trials with concurrent chemoradiotherapy
Objectives
• Neoadjuvant chemotherapy radical radiotherapy Vs radiotherapy.
• Neoadjuvant chemotherapy surgery Vs radiotherapy.
Tierney et al. Cochrane Database

32. (2) NACT Surgery vs RT:
• 5 trials
• N=872
• A significant improvement in 5-year OS (14%)
and DFS (13%)
• No change based on age, stage, histology,
grade and nodal status

33. Conclusions

37. Take home massage