Dr. Ankit Patel provides a detailed 3 page document summarizing cervical cancer including: - Cervical cancer is the 4th most common cancer in women and most cases occur in developing countries. - Persistent HPV infection is the main cause, and vaccination can prevent infection and thus cancer. - Screening protocols in the US recommend Pap smears every 3 years from ages 21-65 or co-testing with HPV every 5 years from 30-65. - FIGO staging criteria are discussed and concurrent chemoradiation is the standard of care for locally advanced stages to improve survival rates. - Intensity modulated radiation therapy can help reduce toxicity compared to conventional radiation.

1. Dr ANKITA SINGH PATEL
MBBS,MD(KGMU)
CONSULTANT
Apex Hospital Cancer Institute
TRAINING AND FELLOWSHIP
Fortis Research Institute ,New Delhi
Tata Memorial Hospital,MUMBAI
Mob. 8765845035,9305421547
Email: dr.ankitapatel.onco@gmail.com
WEBSITE: www.apexhospitalvaranasi.com

2. 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

3. Estimated Cervical Cancer
Incidence Worldwide in 2012

4. Estimated Cervical Cancer
Mortality Worldwide in 2012

5. 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

6. 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 screen
Women>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)

7. PATHOLOGY
WHO 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)

8. SYMPTOMS
SYMPTOMS 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 )

10. 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 dimension
IB2 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

11. REGIONAL LYMPH NODES(
N) AND DISTANT
METASTASIS
FIGO DESCRIPTION
IIIB Regional lymph node metastasis
IVB Distant metastasis (peritoneal spread , SCF ,
mediastinal LN, Paraaortic LN, Lung , Liver , Bone )

17. 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

18. 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

20. PREINVASIVE
 Conization
 Loop electrosurgical excisional procedure(LEEP)
 Laser or cryotherapy ablation
 Simple hysterectomy

21. 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)

22. IA1 (with LVSI ) and stage
IA2
 Modified radical hysterectomy+ PLND
 Or
 Pelvic RT + Brachytherapy (total point A dose :70-80 GY)

23. IB1 and IIA1
 Radical Hysterectomy +PLND +- paraaortic lymph node sampling
 Or
 Pelvic RT + Brachytherapy (total dose to point A :80-85 Gy)

24. 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

26. IIb -IVA
Pelvic RT
+
Concurrent cisplatin containing chemotherapy
+
Brachytherapy

27. FIGO GUIDELINE IN
2000
 For Advanced Cervical cancer (Stage IIb , III, IVA)
Benedet et al Int J of Gynecol Oncol 2000

28. NATIONAL CANCER
INSTITUTE CLINICAL
ANNOUNCEMENT
 Concurrent chemoradiation for cervical
cancer
- FEBRUARY 1999

29. 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)

30. POST OP RT /CHEMO-RT
POST OP PELVIC RT • LVSI
• >1/3 STROMAL INVASION
• >4 cm TUMOR
POST OP CHEMO RT • +ve MARGIN
• +LN
• PARAMETRIAL OR GREATER
EXTENSION

32. WHAT IS THE NEED OF
CHEMORADIATION IN
CARCINOMA CERVIX???

33. 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

34.  Therefore, there is need to use some
additional modality of treatment with
radiation to improve results of locally
advanced carcinoma cervix.

35. 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)

36. 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.

37. OVERALL SURVIVAL BY
STAGE
SURVIVA
L(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

40. 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

41. IMRT STUDIES IN CA
CERVIX(CLINICAL STUDIES)

42. 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 IMRT
GI 28% 14%
GU 10% 3%
NEUTROPENIA 10% 3%

43. DOSE DELIVERY
EBRT (Extenal Beam Radiation Therapy)
Brachytherapy

44. STEPS of EBRT by LA
 Immobilization by thermoplastic cast
 RTP Scan(Radiotherapy Planning Scan)
 Treatment planning and Optimisation.
 Plan Evaluation.
 Treatment Delivery.
 Daily Verification.

45. Immobilization by thermoplastic
cast

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

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

48. Planning and
Dosimetry As per
RTOG guidelines

49. EXECUTION

50. Verification by CBCT( cone
beam CT)

51. INTRACAVITARY RADIOTHERAPY (ICRT)

52. ICBT (INTRACAVITARY
BRACHYTHERAPY)
 Fletcher Suit Afterloading Applicator
placement under GA
 Developed by Nucleotron Netherland ,
Europe

53. INTERSTITIAL BRACHYTHERAPY

55. 3D Planning on Oncentra Planning System (As per American
Brachytherapy Society Guidelines )

56. Treatment delivery by Remote Afterloading HDR
Brachytherapy.

59. 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

60. Physical examination
GENERAL
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

61. 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.

62. Confirmation of
diagnosis
4 Quadrant Punch biopsy

63. PET CT

64. 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

65. 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

66. Follow up
Pre treatment Post treatment