Post on 14-Apr-2017
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 ..