Dr ANKITA SINGH PATELMBBS,MD(KGMU)

CONSULTANT

Apex Hospital Cancer Institute

TRAINING AND FELLOWSHIPFortis Research Institute ,New Delhi

Tata Memorial Hospital,MUMBAI

Mob. 8765845035,9305421547Email: dr.ankitapatel.onco@gmail.com

WEBSITE: www.apexhospitalvaranasi.com

CARCINOMA CERVIX

INTRODUCTION

Cervical cancer is the fourth most common cancer in women. Parkin DM,Bray F.Global cancer statistics,2002.ca Cancer J Clin 2005;55:74-7108

More than 85% of Global burden occurs in developing countries,

where cervical cancer is the leading cause of death in women. International agency for Reasearch on Cancer.globocon.iarc.fr.factsheet cancer.aspx

Jemel A, Bray F,Center MM,et al.CA CancerJ Clin 2011;61:69-90

Estimated Cervical Cancer Incidence Worldwide in 2012

Estimated Cervical Cancer Mortality Worldwide in 2012

HPV and Ca Cervix Persistent HPV infection - most important cause.

Incidence of Cervical Ca is related to prevelance of HPV in population.

In countries with high incidence of Ca Cervix, prevlence of HPV is 10-20%.

In countries with low incidence of Ca Cervix ,prevlence of HPV is 5-10%.

Immunization against HPV will prevent persistent infection with HPV and thus

carcinoma.

In developed countries , the substantial decline in incidence and mortality of

Squamous cell carcinoma is presumed due to result of effective screening.

Lancet Oncol2005;6:271-278

N Engl J Med 2007;369:1861-1868

J Clin Virol2007;38:189-197

CERVICAL SCREENING PROTOCOL (Release Date: March 2012 by United States Preventive Services Task Force (USPSTF) and the American Cancer Society (ACS)

Women ages 21-65 Screen with cytology every 3 years

Women Ages 30-65 Screen with cytology every 3 years or cotesting with HPV every 5 years.

Women<21 Do not screenWomen>65, had adequate prior screening and are not at high risk

Do not screen

Women after hysterectomy with removal of cervix ,no h/o high grade precancer or cervical cancer

Do not screen

Women<30yrs Do not screen with HPV testing(alone or with cytology)

PATHOLOGYWHO recognizes 3 categories:

Squamous cell ca(70-80%)

Adenocarcinoma(10-15%)

Other Epithelial tumors( Neuroendocrine tumors , undifferentiated Ca)

Carcinoma can be

EXOPHYTIC(growing out of surface)

ENDOPHYTIC (stromal infiltration with minimal

surface growth)

SYMPTOMSSYMPTOMS DESCRIPTION

Abnormal vaginal bleeding>80%

GENERAL Vaginal discharge

Symptoms of pelvic organ compression or extension /invasion

EARLY DISEASE SYMPTOMS Abnormal vaginal bleeding

Dyspareunia,Pelvic pain

LATE DISEASE SYMPTOMS

Triad 1) Sciatic pain(from lumbosacral plexus

involvement /compression by tumor)2) Lower extremity edema (from extensive pelvic

lymph node involvement / lymphatic obstruction)3) Hydronephrosis ( ureteral obstruction)

Pelvic pain , urinary , rectal symptoms ( e.g. bowel and/or urinary obstruction , vesicovaginal /rectovaginal fistula )

FIGO (International Federation of Gynecology And Obstetrics) STAGING

FIGO INTERNATIONAL FEDERATION OF GYNECOLOGY AND OBSTETRICS) STAGING 2010

I Cervical carcinoma confined to uterus

IA Invasive carcinoma diagnosed only by microscopy.

IA1 Measured stromal invasion 3 mm or less in depth and 7mm or less in horizontal spread.

IA2 Measured stromal invasion more than 3 mm and <5mm, and 7mm in horizontal spread.

IB Clinically visible lesion confined to cervix or microscopic disease greater than IA1,2

IB1 Clinically visible lesion <= 4cm in greatest dimensionIB2 Clinically visible lesion > 4cm in greatest dimension

IIA Cervical lesion w/o parametrial involvement

IIA1 Clinically visible lesion <= 4cm in greatest dimension

IIA2 Clinically visible lesion > 4cm in greatest dimension

IIB Cervical lesion with parametrial involvment but not upto LPW

IIIA Tumor involving lower third of vagina,no extension to LPW

IIIB Tumor extending to LPW and/or causing hydronephrosis or nonfunctioning kidney

IVA Tumor invades mucosa of bladder or rectum and or extend beyond true pelvis(bullous edema is not sufficient to classify a tumor as IVA)

IVB Disant mets(peritoneal spread ,SCF ,Mediastinal LN, lung,liver or bone

REGIONAL LYMPH NODES( N) AND DISTANT METASTASISFIGO DESCRIPTION

IIIB Regional lymph node metastasis

IVB Distant metastasis (peritoneal spread , SCF , mediastinal LN, Paraaortic LN, Lung , Liver , Bone )

LYMPH NODE METASTASIS

Perez CA,dIsAIA pj,Knapp RC,et al.Gynecologic tumors.In:Devita VT Jr,Hellman S,Rosenberg SA,eds.Cancer:Principles and Practice

of Oncology,2nd edition Philadelphia:jb Lippincott,1985;1013-1041.

STAGE PELVIC LN(%) PARA-AORTIC LN(%)

IA1 0.5 0

IA2 4.8 <1

IB 15.9 2.2

IIA 24.5 11

IIB 31.4 19

III 44.8 30

IVA 55 40

DIAGNOSTIC AND METASTATIC WORK UP

HISTORY AND PHYSICAL

EXAMINATION:

• Pelvic and rectovaginal

examination:• Cervical portio,os• Tumor extension• SCF LN

PROCEDURES:

• Colposcopy• Pap smear if no

bleeding• 4 Quadrant punch

biopsy• Cold knife conization if

no gross lesion visible

or microscopic

carcinoma suspected

LAB• Cbc• Blood

chemistries• Urinalalysis

RADIOLOGY• Chest xray• CT or MRI of

abdomen

and pelvis• PET/PET-CT

PREINVASIVE Conization

Loop electrosurgical excisional procedure(LEEP)

Laser or cryotherapy ablation

Simple hysterectomy

IA1 ( no LVSI ) CONE BIOPSY

1)Negative Margin and inoperable– Observe

2) Negative Margins and operable – extrafascial hysterectomy

3)Positive Margin for dysplasia or carcinoma – Extrafacial or modified Hysterectomy+PLND(if margins positive for carcinoma)

IA1 (with LVSI ) and stage IA2 Modified radical hysterectomy+ PLND

Or

Pelvic RT + Brachytherapy (total point A dose :70-80 GY)

IB1 and IIA1 Radical Hysterectomy +PLND +- paraaortic lymph node sampling

Or

Pelvic RT + Brachytherapy (total dose to point A :80-85 Gy)

IB2 and IIA2 Definitive pelvic RT +Concurrent cisplatin containing

chemotherapy + Brachytherapy

Or

Radical hysterectomy +PLND +- Paraaortic lymph node sampling

Or

Pelvic RT +Concurrent cisplatin containing chemotherapy + Brachytherapy + Adjuvant hysterectomy

IIb -IVAPelvic RT +Concurrent cisplatin containing chemotherapy+Brachytherapy

FIGO GUIDELINE IN 2000

For Advanced Cervical cancer (Stage IIb , III, IVA)

Benedet et al Int J of Gynecol Oncol 2000

NATIONAL CANCER INSTITUTE CLINICAL ANNOUNCEMENT Concurrent chemoradiation for cervical

cancer- FEBRUARY 1999

Advanced /Metastatic disease Usually symptomatic.

Role of chemotherapy is palliative(relieve symptoms and

improve QOL)

Cisplatin is single most cytotoxic agent.

Phase III trial comparing 4 cisplatin combination

regimen(Cis-pacli , Cis-topotecan, Cis-Gem,Cis –

vinorelbine) –No difference in overall survival.(J Clin Oncol

2009; 27:4649-4655)

POST OP RT /CHEMO-RTPOST OP PELVIC RT • LVSI

• >1/3 STROMAL INVASION• >4 cm TUMOR

POST OP CHEMO RT • +ve MARGIN• +LN• PARAMETRIAL OR GREATER

EXTENSION

WHAT IS THE NEED OF CHEMORADIATION IN CARCINOMA CERVIX???

FAILURE RATE FOLLOWING RADICAL RADIATION IN CARCINOMA CERVIX

STAGE PELVIC FAILURE

DISTANT METS

IB 10% 16%

IIA 17% 30%

II B 23% 28%

III 42% 45%

IVA 74% 65%Mallinckrotd Institute of Radiology, 1959-89

Therefore, there is need to use some

additional modality of treatment with

radiation to improve results of locally

advanced carcinoma cervix.

Aim of concurrent chemotherapy with Radiotherapy To Improve survival by

1. Increasing control of the primary cervical tumor

(Radiosensitization)

2. Decrease the rate of distant metastasis (Direct anti tumor effect for

micro-metastasis and indirect effect on future metastasis by

preventing cervical tumor recurrence)

SURVEILLANCE(NCCN Guidelines 2015)

Interval H& P 3-6 monthly 2yrs

6-12 monthly 3-5 yrs

>5 yrs annually

Cervical and vaginal cytology as indicated for lower genital tract neoplasia

Annual

Imaging as indicated CT, PET ,MRI

Lab Assessment as indicated CBC ,BUN, Creatinine

Patient education Symptoms of potential recurrence

Lifestyle

Obesity

Exercise

Nutrition

Sexual health and vaginal dilator use.

OVERALL SURVIVAL BY STAGESURVIVAL(5YR)

Last Revised: 02/26/2015

IA 93%

IB1 83%

IB2 80%

IIA 63%

IIB 38%

IIIA 35%

IIIB 32%

IVA 16%

IVB 15%

The rates below were published in 2010 in the 7th edition of the AJCC staging manual.

They are based on data collected by the National Cancer Data Base from people diagnosed between 2000 and 2002.

These are the most recent statistics available for survival by the current staging system

PRECISION RADIOTHERAPY IN CARCINOMA CERVIX

RATIONALE OF USING PRECISION RADIOTHERAPY IN CA CERVIX

CONVENTIONAL RT --Toxicities due to inclusion of cconsiderable volumes of normal structures

PRECISION RADIOTHERAPY

1)Reduce dose to normal structure,hence sequelae 2)Allow simultaneous boost of involved lymph node.

SMALL BOWEL Diarrhea,SBO,enteritis,malabsoption

RECTUM Diarrea,proctitis ,rectal bleeding

BLADDER Urgency,dysuria,haematuria,contracture

BONE MARROW Reduced WBC, Platelet , anemia

PELVIC BONES Insufficiency fracture,necrosis

IMRT STUDIES IN CA CERVIX(CLINICAL STUDIES)

IMRT STUDIES IN CA CERVIX(CLINICAL STUDIES – INDIAN DATA )

14 month median follow up:No difference in response or tumor control

TATA MEMORIAL HOSPITAL. PHASE III randomised trial Convention RT vs IMRT 58 cervical cancer patients (as of jan 2009)

GRADE >=2 CONVENTIONAL IMRTGI 28% 14%

GU 10% 3%

NEUTROPENIA 10% 3%

DOSE DELIVERY

EBRT (Extenal Beam Radiation Therapy)

Brachytherapy

STEPS of EBRT by LA Immobilization by thermoplastic cast

RTP Scan(Radiotherapy Planning Scan)

Treatment planning and Optimisation.

Plan Evaluation.

Treatment Delivery.

Daily Verification.

Immobilization by thermoplastic cast

RTP (Radiotherapy Treatment Planning)SCAN by laser – CT System and lead pellets and fiducials

TPS (Teletherapy Planning system)(Xio , Monte Carlo Based Planning System as approved by US FDA and AERB)

Planning and Dosimetry As per RTOG guidelines

EXECUTION

Verification by CBCT( cone beam CT)

BRACHYTHERAPY

INTRACAVITARY RADIOTHERAPY (ICRT)

ICBT (INTRACAVITARY BRACHYTHERAPY)

Fletcher Suit Afterloading Applicator placement under GA

Developed by Nucleotron Netherland , Europe

INTERSTITIAL BRACHYTHERAPY

3D Planning on Oncentra Planning System (As per American Brachytherapy Society Guidelines )

Treatment delivery by Remote Afterloading HDR Brachytherapy.

CASE:

Clinical History 40 Yr female from Sasaram presented in our OPD with C/O

Intermenstrual bleeding P/V for 3 months Foul smelling discharge P/V for 4 months Post coital bleeding P/V for 4 months Lower abdomen pain for 1 month Generalised weakness for 1 month

Physical examinationGENERAL EXAMINATION GC PALLOR ICTERUS GENERALISED LYMPHADENOPATHY OEDEMA

SYSTEMIC EXAMINATION

CNS No neurological deficit CVS S1,S2 normal,no murmur RESPIRATION B/L Breath sound nrmal,no

added sound P/A No organomegaly No Supraclavicular Lymphnode

FAIR NO NO NO NO

NAD

Local Examination P/S cervix replaced by ulceroproliferative growth

Lesion not involving vagina

P/V cervix replaced by fragile growth which bleeds on touch, b/l fornices partially obliterated.

P/R rectal mucosa free, b/l para involved but not upto LPW.

Confirmation of diagnosis

4 Quadrant Punch biopsy

PET CT

Discussed in Apex Tumor Board

TREATMENT PLAN

In view of locally advanced (Stage IIb) , patient was planned as per NCCN Guidelines

EXTERNAL BEAM RADIOTHERAPY(EBRT)

Followed by

Remote Afterloading HDR BRACHYTHERAPY

Dose Priscription (as per RTOG GUIDELINES)

Concurrent Chemoradiation (EBRT)Weekly Chemotherapy ( Cisplatin 40mg/m2 )(Monday)

50 Gy in 25# @200cGy/# , 5#/week (Monday to Friday) by Highly Conformal radiotherapy by Linear Accelerator

HDR Brachytherapy 7Gy per fraction ,3 fractions,1 fraction per week

Follow up

Pre treatment Post treatment

THANKS ..