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Dr ANKITA SINGH PATEL
MBBS,MD(KGMU)
CONSULTANT
Apex Hospital Cancer Institute
TRAINING AND FELLOWSHIP
Fortis Research Inst...
INTRODUCTION
 Cervical cancer is the fourth most common cancer in women.
Parkin DM,Bray F.Global cancer statistics,2002.c...
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 o...
CERVICAL SCREENING
PROTOCOL
(Release Date: March 2012 by
United States Preventive Services Task Force (USPSTF) and the Ame...
PATHOLOGY
WHO recognizes 3 categories:
 Squamous cell ca(70-80%)
 Adenocarcinoma(10-15%)
 Other Epithelial tumors( Neur...
SYMPTOMS
SYMPTOMS DESCRIPTION
Abnormal vaginal bleeding>80%
GENERAL Vaginal discharge
Symptoms of pelvic organ compression...
FIGO INTERNATIONAL FEDERATION OF GYNECOLOGY AND OBSTETRICS) STAGING 2010
I Cervical carcinoma confined to uterus
IA Invasi...
REGIONAL LYMPH NODES(
N) AND DISTANT
METASTASIS
FIGO DESCRIPTION
IIIB Regional lymph node metastasis
IVB Distant metastasi...
LYMPH NODE METASTASIS
Perez CA,dIsAIA pj,Knapp RC,et al.Gynecologic tumors.In:Devita VT Jr,Hellman S,Rosenberg SA,eds.Canc...
DIAGNOSTIC AND METASTATIC
WORK UP
HISTORY AND
PHYSICAL
EXAMINATION:
• Pelvic and
rectovaginal
examination:
• Cervical port...
PREINVASIVE
 Conization
 Loop electrosurgical excisional procedure(LEEP)
 Laser or cryotherapy ablation
 Simple hyster...
IA1 ( no LVSI )
 CONE BIOPSY
 1)Negative Margin and inoperable– Observe
 2) Negative Margins and operable – extrafascia...
IA1 (with LVSI ) and stage
IA2
 Modified radical hysterectomy+ PLND
 Or
 Pelvic RT + Brachytherapy (total point A dose ...
IB1 and IIA1
 Radical Hysterectomy +PLND +- paraaortic lymph node sampling
 Or
 Pelvic RT + Brachytherapy (total dose t...
IB2 and IIA2
 Definitive pelvic RT +Concurrent cisplatin containing
chemotherapy + Brachytherapy
 Or
 Radical hysterect...
IIb -IVA
Pelvic 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)...
POST OP RT /CHEMO-RT
POST OP PELVIC RT • LVSI
• >1/3 STROMAL INVASION
• >4 cm TUMOR
POST OP CHEMO RT • +ve MARGIN
• +LN
• ...
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...
 Therefore, there is need to use some
additional modality of treatment with
radiation to improve results of locally
advan...
Aim of concurrent
chemotherapy with
Radiotherapy
 To Improve survival by
1. Increasing control of the primary cervical tu...
SURVEILLANCE(NCCN Guidelines
2015)
Interval H& P 3-6 monthly 2yrs
6-12 monthly 3-5 yrs
>5 yrs annually
Cervical and vagina...
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%...
RATIONALE OF USING PRECISION
RADIOTHERAPY
IN CA CERVIX
CONVENTIONAL RT --Toxicities due to inclusion of cconsiderable volu...
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 c...
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...
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)
INTRACAVITARY RADIOTHERAPY (ICRT)
ICBT (INTRACAVITARY
BRACHYTHERAPY)
 Fletcher Suit Afterloading Applicator
placement under GA
 Developed by Nucleotron Ne...
INTERSTITIAL BRACHYTHERAPY
3D Planning on Oncentra Planning System (As per American
Brachytherapy Society Guidelines )
Treatment delivery by Remote Afterloading HDR
Brachytherapy.
Clinical History
 40 Yr female from Sasaram presented in our OPD with C/O
 Intermenstrual bleeding P/V for 3 months
 Fo...
Physical examination
GENERAL
EXAMINATION
 GC
 PALLOR
 ICTERUS
 GENERALISED LYMPHADENOPATHY
 OEDEMA
SYSTEMIC EXAMINATI...
Local Examination
P/S cervix replaced by ulceroproliferative
growth
Lesion not involving vagina
P/V cervix replaced by fra...
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...
Dose Priscription (as per
RTOG GUIDELINES)
 Concurrent Chemoradiation (EBRT)
Weekly Chemotherapy ( Cisplatin 40mg/m2 )(Mo...
Follow up
Pre treatment Post treatment
Ca cervix—standards of care
Ca cervix—standards of care
Ca cervix—standards of care
Ca cervix—standards of care
Ca cervix—standards of care
Ca cervix—standards of care
Ca cervix—standards of care
Ca cervix—standards of care
Ca cervix—standards of care
Ca cervix—standards of care
Ca cervix—standards of care
Ca cervix—standards of care
Ca cervix—standards of care
Ca cervix—standards of care
Ca cervix—standards of care
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Ca cervix—standards of care

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CA CERVIX, DR ANKITA PATEL , APEX HOSPITAL ,SYMPTOMS, DIAGNOSIS,STAGING, NCCN GUIDELINES FOR THE MANAGEMENT, SURVIVAL , MULTIMODALITY APPROACH , CHEMOTHERAPY , RADIOTHERAPY , SURGERY

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Ca cervix—standards of care

  1. 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. 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. 3. Estimated Cervical Cancer Incidence Worldwide in 2012
  4. 4. Estimated Cervical Cancer Mortality Worldwide in 2012
  5. 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. 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. 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. 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 )
  9. 9. 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
  10. 10. 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 )
  11. 11. 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
  12. 12. 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
  13. 13. PREINVASIVE  Conization  Loop electrosurgical excisional procedure(LEEP)  Laser or cryotherapy ablation  Simple hysterectomy
  14. 14. 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)
  15. 15. IA1 (with LVSI ) and stage IA2  Modified radical hysterectomy+ PLND  Or  Pelvic RT + Brachytherapy (total point A dose :70-80 GY)
  16. 16. IB1 and IIA1  Radical Hysterectomy +PLND +- paraaortic lymph node sampling  Or  Pelvic RT + Brachytherapy (total dose to point A :80-85 Gy)
  17. 17. 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
  18. 18. IIb -IVA Pelvic RT + Concurrent cisplatin containing chemotherapy + Brachytherapy
  19. 19. FIGO GUIDELINE IN 2000  For Advanced Cervical cancer (Stage IIb , III, IVA) Benedet et al Int J of Gynecol Oncol 2000
  20. 20. NATIONAL CANCER INSTITUTE CLINICAL ANNOUNCEMENT  Concurrent chemoradiation for cervical cancer - FEBRUARY 1999
  21. 21. 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)
  22. 22. 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
  23. 23. WHAT IS THE NEED OF CHEMORADIATION IN CARCINOMA CERVIX???
  24. 24. 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
  25. 25.  Therefore, there is need to use some additional modality of treatment with radiation to improve results of locally advanced carcinoma cervix.
  26. 26. 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)
  27. 27. 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.
  28. 28. 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
  29. 29. 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
  30. 30. IMRT STUDIES IN CA CERVIX(CLINICAL STUDIES)
  31. 31. 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%
  32. 32. DOSE DELIVERY EBRT (Extenal Beam Radiation Therapy) Brachytherapy
  33. 33. STEPS of EBRT by LA  Immobilization by thermoplastic cast  RTP Scan(Radiotherapy Planning Scan)  Treatment planning and Optimisation.  Plan Evaluation.  Treatment Delivery.  Daily Verification.
  34. 34. Immobilization by thermoplastic cast
  35. 35. RTP (Radiotherapy Treatment Planning)SCAN by laser – CT System and lead pellets and fiducials
  36. 36. TPS (Teletherapy Planning system) (Xio , Monte Carlo Based Planning System as approved by US FDA and AERB)
  37. 37. Planning and Dosimetry As per RTOG guidelines
  38. 38. EXECUTION
  39. 39. Verification by CBCT( cone beam CT)
  40. 40. INTRACAVITARY RADIOTHERAPY (ICRT)
  41. 41. ICBT (INTRACAVITARY BRACHYTHERAPY)  Fletcher Suit Afterloading Applicator placement under GA  Developed by Nucleotron Netherland , Europe
  42. 42. INTERSTITIAL BRACHYTHERAPY
  43. 43. 3D Planning on Oncentra Planning System (As per American Brachytherapy Society Guidelines )
  44. 44. Treatment delivery by Remote Afterloading HDR Brachytherapy.
  45. 45. 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
  46. 46. 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
  47. 47. 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.
  48. 48. Confirmation of diagnosis 4 Quadrant Punch biopsy
  49. 49. PET CT
  50. 50. 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
  51. 51. 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
  52. 52. Follow up Pre treatment Post treatment
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CA CERVIX, DR ANKITA PATEL , APEX HOSPITAL ,SYMPTOMS, DIAGNOSIS,STAGING, NCCN GUIDELINES FOR THE MANAGEMENT, SURVIVAL , MULTIMODALITY APPROACH , CHEMOTHERAPY , RADIOTHERAPY , SURGERY

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