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.

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.

ESMO GUIDELINE

ESMO GUIDELINE

ESMO GUIDLINE

Indications - adjuvant t/t

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

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%

• 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.

• 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.

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.

Neoadjuvant chemotherapy followed by radiotherapy versus

radiotherapy alone in locally advanced carcinoma cervix: aprospective 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).

• 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.

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) and with 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 of This is a single-arm phase II trial of 46 patients46 patients, with locally , with locally advanced cervical cancer advanced cervical cancer (stage Ib2-IVa(stage Ib2-IVa). ). Patients receivedPatients received•dose-dense carboplatin (AUC2) and paclitaxel (80mgm-2) weekly dose-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 point 50.4 Gy, 28 fractions plus brachytherapy). The primary end point was response rate 12 weeks post-CRT.was response rate 12 weeks post-CRT.

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%).

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

• The median follow-up was 39.1 months.

• Overall and progression-free survivals at 3 years were 67% and 68%, respectively.

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

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%).

META – ANALYSIS(2004): MRC (UK) group

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

(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

Conclusions

Take home massage