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Screenforovca.9saudia1 (1)

  1. 1. SCREENING FOR OVARIAN CANCER DANIEL  H.  SMITH,  MD   DIRECTOR,  GYNECOLOGIC  ONCOLOGY  AND  MINIMALLY   INVASIVE  GYNECOLOGY   HOLY  NAME  MEDICAL  CENTER   TEANECK,  NEW  JERSEY,  USA     MAY  14,  2013  
  2. 2. FIRST   DOCUMENTED   CANCER  CASE  
  3. 3. OVARIAN CANCER EVOLUTION OF THOUGHT, HISTORICALLY •  TRADITIONALLY  CALLED  ‘STOMACH  CANCER’   –  FEW  LIVED  FOR  VERY  LONG   –  TREATMENTS   •  SURGERY  –  IF  DIDN’T  DIE  FROM  OPERATION   •  CHEMOTHERAPY     –  LIFE  COULD  BE  SUSTAINED   –  …WITH  COSTS!   •  THE  CURE   •  CHEMOTHERAPY     –  LIFE  COULD  BE  SUSTAINED   –  …WITH  COSTS!   –  ADVANCED  DISEASE  DAUNTING   •  NEW  DRUGS,  TRIALS,  PROCEDURES   •  EFFECTIVE?   –  EARLY  DISEASE  –  PATIENTS  DO  MUCH  BETTER   •  ?EARLIER  DETECTION   –  SCREENING   –  FINDING  SMALLER  CANCERS  
  4. 4. OVARIAN CANCER SCREENING GENERAL IMPRESSION
  5. 5. OVARIAN CANCER SCREENING REALITY
  6. 6. WORLD HEALTH ORGANIZATION 1968 1.  The  condi,on  should  be  an  important  health  problem.   2.  There  should  be  a  treatment  for  the  condi,on.   3.  Facili,es  for  diagnosis  and  treatment  should  be  available.   4.  There  should  be  a  latent  stage  of  the  disease.   5.  There  should  be  a  test  or  examina,on  for  the  condi,on.   6.  The  test  should  be  acceptable  to  the  popula,on.   7.  The  natural  history  of  the  disease  should  be  adequately  understood.   8.  There  should  be  an  agreed  policy  on  whom  to  treat.   9.  The  total  cost  of  finding  a  case  should  be  economically  balanced  in  rela,on  to   medical  expenditure  as  a  whole.   10.  Case-­‐finding  should  be  a  con,nuous  process,  not  just  a  "once  and  for  all"  project.  
  7. 7.                             WHAT DIFFERENCE CAN SCREENING MAKE????
  8. 8. SCREENING FOR EARLY DISEASE OVARIAN CANCER •  METHODOLOGY   –  PHYSICAL  EXAMINATION   –  SYMPTOMS  and/  or    SIGNS   –  TESTING   •  IMAGING   •  BLOOD  TESTS   •  GENETIC  TESTS  
  9. 9. •  PHYSICAL  EXAMINATION-­‐  PELVIC  EXAM!   –  RARELY  DONE  (ABSOLUTE  NUMBER  STILL  HIGH)   –  FINDING  EARLY  DISEASE  ???   –  SIGNS  OF  ADVANCED  DISEASE  (ASCITES,  MASSES)   •  RED  HERRING  –   –  NEW  YORK  TIMES,  APRIL  30,  2013   •  ADVOCATING  AGAINST  PELVIC  EXAMINATION   •  NO  EVIDENCE  THAT  RELEVANT  CONDITIONS  ARE  FOUND   •  EVIDENCE  THAT  EXAMINATIONS  CAUSE  UNNECESSARY   SURGEY   SCREENING FOR EARLY DISEASE OVARIAN CANCER
  10. 10. SCREENING FOR EARLY DISEASE PELVIC EXAMINATION •  AN  EXAM  WITH  POOR  RESULTS   –  ROUTINE  PELVIC  CHECKUPS  CAN  CAUSE  MORE  PROBLEMS  THAN  THEY   UNEARTH,  EXPERTS  SAY   –  DISCOVERY  OF  BENIGN  CONDITIONS  CAN  LEAD  TO  UNNECESSARY  FOLLOW-­‐UP   •  63.4  MILLION  ANNUAL  PELVIC  EXAMINATION  –  USA   •  PURPORTED  REASONS  OF  PERFORMING  THE  EXAMINATION  -­‐      ALL  OF  WHICH  CAN  BE  PERFORMED  WITHOUT  A  PELVIC  EXAM   –  PAP  SMEAR  –  NEW  GUIDELINES   •  LONGER  INTERVALS  WITH  NORMAL  HISTORY   •  NOT  RECOMMENDED  FOR  MANY  –  OLDER,  YOUNGER,  THOSE  WITH  NEGATIVE  PAP  AND   CO-­‐TESTING   –  DETECTION  OF  SEXUALLY  TRANSMITTED  DISEASE   –  DETECTION  OF    ASYMPTOMATIC  PELVIC  MASSES   –  ASSEDSSMENT  FOR  HORMONAL  CONTRACEPTION   NEW  YORK  TIMES,  TUESDAY,  APRIL  30,  2013  -­‐  JANE  E.  BRODY  
  11. 11. SCREENING FOR EARLY DISEASE PELVIC EXAMINATION •  FOR  WOMEN  WHO  ARE  APPARENTLY  HEALTHY   –  ROUTINE  BIMANUAL  EXAMINATION  IS  NOT  SUPPORTED  BY  MEDICAL  EVIDENCE   –  INCREASES  COSTS  OF  MEDICAL  CARE   –  DISCOURAGES  SOME  WOMEN,  PARTICULARLY  ADOLESCENTS,  FROM  SEEING  DOCTORS   •  ROUTINE  EXAMS  IN  USA     –  TWICE  THE  INCIDENCE  OF  CERTAIN  SURGERIES   •  OVARIAN  CYSTECTOMY   •  HYSTERECTOMY   –  NATIONAL  CANCER  INSTITUTE  STUDY  –  NO  OVARIAN  CANCERS  FOUND   –  ENDORSED  BY  AMERICAN  COLLEGE  OF  OBSTETRICIANS  AND  GYNECOLOGISTS   •  ACKNOWLEDGES  THAT  MEDICAL  EVIDENCE  TO  JUSTIFY  IS  LACKING   NEW  YORK  TIMES,  TUESDAY,  APRIL  30,  2013  -­‐  JANE  E.  BRODY  
  12. 12. SCREENING FOR EARLY DISEASE PELVIC EXAMINATION •  CURRENTLY  A  TRADITION  FOR  ALL  WOMEN                                      …  EVEN  WITHOUT  SYMPTOMS   •  FOR  SYMPTOMATIC  WOMEN   –  INDICATED   –  OFTEN  NOT  DONE  
  13. 13. SCREENING FOR EARLY DISEASE OVARIAN CANCER •  SYMPTOMS   –  BLOATING   –  CHANGE  OF  BOWEL  HABITS   –  CLOTHES  DO  NOT  FIT   –  INDIGESTION   •  SIGNS   –  ABDOMINAL  SWELLING   –  LOSS  OF  WEIGHT,  INITIALLY   –  NAUSEA  OR  VOMITING   •  ALL  OF  THE  ABOVE  ARE  SIGNS  AND  SYMPTOMS   OF  ADVANCED  DISEASE  
  14. 14. SCREENING FOR EARLY DISEASE OVARIAN CANCER •  TESTING  CURRENTLY  AVAILABLE   –  IMAGING   •  U/S   •  CT   •  MRI   •  PET   •  RADIONUCLEOTIDE  TAGGING   –  BLOOD  TESTS   •  TUMOR  MARKERS   –  CA125   –  OVA  CHECK   –  OVA  1   –  H4   –  GENETIC  TESTS   •  LIMITED  APPLICABILITY   •  LIMITLESS  POSSIBILITIES   NOT  PROVED  EFFECTIVE    IN  SCREENING  
  15. 15. SCREENING FOR EARLY DISEASE OVARIAN CANCER •  COMBINE  TESTS   – IMAGING   •  U/S   – BLOOD  TESTS   •  TUMOR  MARKERS   –  CA125   –  OVA  CHECK   –  OVA  1   –  H4   •  DEFINE  AND  TEST  HIGH  RISK  POPULATIONS  
  16. 16. SCREENING FOR EARLY DISEASE ULTRASOUND +/- CA125 •  GOALS  OF  SCREENING–   –  ACHIEVE  EARLIER  DIAGNOSIS   –  DECREASE  MORTALITY  
  17. 17. SCREENING FOR EARLY DISEASE ULTRASOUND +/- CA125 •  USA  (BUYS  et.  al.  –  JAMA  2011;  305-­‐2295)   –  Prostate,  Lung,  Colon,  Ovary  (PLCO)    TRIAL-­‐  2011   •  ANNUAL  SCREENING   –  FOUR  YEARS  TRANS  VAGINAL  ULTRASOUND   –  SIX  YEARS  CA125  TESTING   •  NO  CHANGE  IN  STAGE  OR  MORTALITY   •  UK    (MENON  et.  al.-­‐EVID  BASED  MED  2012:17:47-­‐48)   –  PLCO  ANALYSIS   •  RR  FOR  SCREENED  RELATIVE  TO  CONTROL  WAS  1.18   •  1080/68,557  (~2%)  HAD  SURGERY  FOR  FALSE  POSTIVE  FINDINGS   –  15%    OF  THESE  WOMEN  HAD  SERIOUS  COMPLICATIONS   –  UNDERTAKING  MODIFICATIONS  OF  STUDY   •  RESULTS  DUE  2015   •  JAPAN  (KOBAYASHI  et.  al.-­‐INT  J  GYNECOL  CANCER,  2008,MAY-­‐JUN;  18 (3):414-­‐20.)   –  41,688  SCREENED  WITH  ANNUAL  U/S  +  CA125            =            27  CANCERS                    %  STAGE  I   LARGER  (P  >  0.05)   –  40,779  CONTROLS                                                                                                                =          31  CANCERS   –  MORTALITY  NOT  DISCLOSED    
  18. 18. SCREENING FOR EARLY DISEASE BLOOD MARKER TESTS •  CA125   –  TUMOR  ASSOCIATED  ANTIGEN   –  LEVELS  OF  SIGNIFICANCE   •  ?  BASE-­‐LINE   •  ?  CHNAGES  IN  LEVEL   –  POSITIVITY   •  90  %  OF  WOMEN  WITH  OVARIAN  CANCER   •  ONLY  50%  OF  WOMEN  WITH  STAGE  I  DISEASE   •  FALSE  POSITIVES   –  FIBROIDS,  ENDOMETRIOSIS   –  OTHER  CANCERS   –  BEST  USE  IS  MONITORING  TREAMENT  PROGRESS   •  HE-­‐4     –  HUMAN  EPIDYDIMIS  4  –  A  GENE  WHICH  MAKES  A  PROTEIN  HE-­‐4   –  USED  WITH  WOMEN  WITH  NORMAL  CA125   –  ELEVATED  WITH  BENIGN  PROCESSES  AND  OTHER  CANCERS   •  OVA1   –  FIVE  PROTEIN  SIGNATURE  IN  BLOOD   –  FOR  PRE-­‐OPERATIVE  ASSESSMENT  OF  PELVIC  MASS  
  19. 19. SCREENING FOR EARLY DISEASE BLOOD MARKER TESTS •  CA125   •  HE-­‐4     •  OVA1   •  OVACHECK    -­‐    WITHDRAWN,  RESULTS  NOT                                          REPRODUCIBLE  
  20. 20. •  COMBINE  TESTS   –  IMAGING   •  U/S   •  CT   •  MRI   •  PET   •  RADIONUCLEOTIDE  TAGGING   –  BLOOD  TESTS   •  TUMOR  MARKERS   –  CA125   –  OVA  CHECK   –  OVA  1   –  H4   –  GENETIC  TESTS   •  LIMITED  APPLICABILITY   •  LIMITLESS  POSSIBILITIES   SCREENING FOR EARLY DISEASE OVARIAN CANCER
  21. 21. USING  GENETICS   SCREENING  FOR  EARLY  DISEASE   PREVENTION  OF  ANY  DISEASE   OVARIAN  CANCER  
  22. 22. UNIVERSAL  TRUTH:        GENETIC  MUTATIONS  CAUSE  CANCER  
  23. 23. ALL CANCER IS GENETIC, BUT NOT ALL CANCER IS HEREDITARY SPORADIC HEREDITARY FAMILIAL? SPORADIC HEREDITARY FAMILIAL?
  24. 24. ALL CANCER IS GENETIC, BUT NOT ALL CANCER IS HEREDITARY SPORADIC HEREDITARY FAMILIAL? SPORADIC HEREDITARY FAMILIAL?
  25. 25. SCREENING FOR EARLY DISEASE OVARIAN CANCER????? •  PAP  TEST   – UNIVERSALLY  DONE   – ?  OTHER  MATERIAL  THERE   •  DNA  FROM  UPPER  TRACT   –  UTERUS   –  OVARY/FALLOPIAN  TUBE   –  CELOEMIC  CAVITY   – APPLICABILITY   – LIMITS   – POSSIBILITIES    
  26. 26. SCREENING FOR EARLY DISEASE PAP SMEAR! •  APPLICABILITY   –  ANY  WOMAN,  ANY  AGE,  MULTIPLE  DISEASES   –  MUST  HAVE   •  UTERUS  AND  CERVIX  PRESENT   •  FALLOPIAN  TUBES  PRESENT   •  CANAL  PATENT   •  LIMITS   –  SENSITIVITY   –  SPECIFICITY   –  AGE   –  ANATOMIC  BARRIERS   •  POSSIBILITIES     –  LIMITLESS  
  27. 27. SCREENING FOR EARLY DISEASE OVARIAN AND UTERINE CANCER •  LOOKED  AT  PATIENTS  WITH  UTERINE  AND  OVARIAN   CANCER   –  RECOGNIZED  A  PANEL  OF  GENES  THAT  ARE  COMMONLY   MUTATED  IN  ENDOMETRIAL  AND  OVARIAN  CANCERS   •  CONFIRMED  BY  TESTING    TISSUE  FROM  24  ENDOMETRIAL   CANCERS  AND  22  OVARIAN  CANCERS   •  EXAMINED  DNA  FROM  LIQUID  PAP  SMEAR  SPECIMENS   –  IDENTIFIED  TUMOR  PROTEIN  IN  100%  (24  OF  24)   PATIENTS  WITH  ENDOMETRIAL  CANCER   –  IDENTIFIED  TUMOR  PROTIEN  IN  41%  (9  OF  20)  PATIENTS   WITH  OVARIAN  CANCER   KINDE  et  al.  SCIENCE  TRANSLATIONAL  MEDICINE.  5:  JAN  9,  2013;  167  
  28. 28. SCREENING FOR EARLY DISEASE COLON CANCER AND POLYPS •  COLOGARD   •  STUDIED  DNA  IN  STOOL  SPECIMENS     –  +  IN  92%  OF  PATIENTS  WITH  COLON  CANCER   –  +  IN  42%  PRECANCEROUS  POLYPS   –  FALSE  +  13%   •  Epi  proColon   –  BLOOD  TEST    FOR  GENETIC  VARIANT   –  DETECTED  71%  OF  CANCERS  (NOT  FOR  POLYPS)   –  19%  FALSE  POSITIVES   •  HEMOCCULT  (BLOOD  IN  STOOL)   –  DETECTS  ~80  CANCERS   –  DETECTS  20-­‐40%  POLYPS   –  COSTS  $25   •  COLONOSCOPY  STILL  THE  GOLD  STANDARD   –  ONLY  50%  OF  PEOPLE  OVER  50  YEARS  OF  AGE  ARE  SCREENED   KINDE  et  al.  SCIENCE  TRANSITIONAL  MEDICINE.  5:  JAN  9,  2013,  167.  
  29. 29. MEDICAL ONCOLOGY CENTRAL REGIS
  30. 30. PREVENTION OVARIAN CANCER •  PREVENT  GENE  MUTATIONS   •  MEDICATIONS  TO  BLOCK  CANCER  FORMATION   •  SURGICAL  PROCEDURES  TO  LOWER  CANCER   RISK   •  IDENTIFY  HEREDITY  FACTOR  
  31. 31. PREVENTION OVARIAN CANCER •  PREVENT  GENE  MUTATIONS   – ENVIRONMENT-­‐  WHERE  YOU  LIVE   – CHEMICALS  –    TO  WHAT  YOU  ARE  EXPOSED   – VIRUSES  –  EXPOSURE  TO  INFECTIOUS  AGENTS   – LIFESTYLE  –  SMOKING,  EATING,  CLOTHING  
  32. 32. PREVENTION OVARIAN CANCER •  PREVENT  GENE  MUTATIONS   –  ENVIRONMENT-­‐  LIVE  IN  SCANDANAVIA  (USE  SUNBLOCK!)   –  CHEMICALS  –    LIVE  FAR  FROM  URBAN  AREAS  (UP  WIND)   –  VIRUSES  –  GET  VACCINATED/BE  A  HERMIT  (FOREGO  FAMILY)   –  LIFESTYLE  –  HOPE  FOR  BETTER  THINGS?  ?  
  33. 33. SIMILARITIES  IN  GENETICS   OF  MULTIPLE  CANCERS   •  BREAST  CANCER   •  COLON  CANCER   •  ENDOMETRIAL  CANCER   •  OVARIAN  CANCER   •  ACUTE  MYELOID  LEUKEMIA   •  LUNG  CANCER   NEW  YORK  TIMES,  THURSDAY,  MAY  1,  2013  
  34. 34. SIMILARITIES  IN  GENETICS   OF  MULTIPLE  CANCERS   •  ABILITY  TO  STRATIFY  FOR    RISK   •  ENDOMETRIAL  CANCER   •  ACUTE  MYELOID  LEUKEMIA   •  SUSCEPTIBILITY  TO  DRUGS  USED  FOR  OTHER  CANCERS   •  LUNG  CANCER   NEW  YORK  TIMES,  THURSDAY,  MAY  1,  2013  
  35. 35. SIMILARITIES  IN  GENETICS   OF  MULTIPLE  CANCERS   NEW  YORK  TIMES,  THURSDAY,  MAY  1,  2013   LUNG   CANCER  ENDOMETRIA L  CANCER   OVARIAN   CANCER   COLON   CANCER   ACUTE   MYEOLID   LEUKEMIA   BREAST   CANCER  
  36. 36. GENETIC  STUDIES  AND  CORRELATIONS   • CANCER  DETECTION   • CANCER  TREATMENT   • CANCER  PREVENTION  
  37. 37. •  FACTORS  MODIFYING  MUTATION  BEHAVIOR   –  MEDICATIONS   •  HORMONE  RECEPTOR  BLOCKING  –  TAMOXIFEN   •  HORMONAL  MODIFICATION  OF  PRECUSORS  –  PROGESTERONE   •  PREVENTION  OF  PHYSICAL  INJURY  –  ORAL  CONTRACEPTIVES   •  SUPPLEMENT  DEFICIENCIES  CAUSED  BY  GENETIC  MALFUNCTION  -­‐    VITAMIN  C   –  SURGICAL  PROCEDURES   •  REMOVE  TARGET  ORGAN   •  REMOVE  ORGAN  INCITING  OR  PROMOTING  EFFECTS  OF  GENETIC  MALFUNCTION   PREVENTION OVARIAN CANCER
  38. 38. PREVENTION •  HEREDITY  
  39. 39. HEREDITARY SYNDROMES …IN WOMEN?   • BREAST OVARIAN CANCERS (BrCa 1 or 2) – BREAST – OVARIAN – BOTH • HEREDITARY NON-POLYPOSIS COLON CANCER SYNDROME (HNPCC or LYNCH II) • LI FRAUMENI • RETINOBLASTOMA  
  40. 40. MECHANISM OF ACTION LOSS OF HETEROZYGOSITY ON CHROMOSOME 17 SUPPRESSOR ACTION BRCA1 MUTATION BRCA1 MUTATION NORMAL BRCA1 NEW MUTATION TIME MUTATION EVENT N Y N N
  41. 41. 0% 10% 20% 30% 40% 50% 60% 70% 80% 90% 100% BRCA MUTATION GEN POP BREAST CA OVARIAN CA MALE CA BR 2'ry CA BR OV CA AFTER BR CA CANCER  RISKS   FOR  BRCA  MUTATION  CARRIERS  
  42. 42. BRCA1-ASSOCIATED CANCERS: LIFETIME RISKS BREAST CANCER – 50-80% SECOND PRIMARY BREAST CANCER – 40-60% OVARIAN CANCER – 30-40% NO  CLEAR  EVIDENCE  FOR  INCREASED  RISK  AT  OTHER  SITES  
  43. 43. BREAST CANCER – 40-80% MALE BREAST CANCER – 6% OVARIAN CANCER – 15-25% INCREASED RISK OF PROSTATE, PANCREATIC, GALLBLADDER/BILE DUCT, GASTRIC, HEAD AND NECK CANCERS AND MELANOMA BRCA2-ASSOCIATED CANCERS: LIFETIME RISKS
  44. 44. HPNCC-ASSOCIATED CANCERS: LIFETIME RISKS COLON CANCER – 80% ENDOMETRIAL CANCER – 40-60% OVARIAN CANCER – 12%
  45. 45. FOUNDER EFFECT A HIGH FREQUENCY OF A SPECIFIC GENE MUTATION IN A POPULATION FOUNDED BY A SMALL ANCESTRAL GROUP ORIGINAL POPULATION MARKED POPULATION DECREASE, MIGRATION, OR ISOLATION GENERATIONS LATER
  46. 46. FOUNDER EFFECT
  47. 47. SURGICAL PROCEDURES TO MODIFY RESULTS OF GENE MALFUNCTION
  48. 48. RISK REDUCTION BSO • CAN BE DELAYED TO ALLOW COMPLETION OF CHILDBEARING • LAPAROSCOPIC APPROACH MINIMIZES HOSPITAL STAY/RECOVERY • ?ROLE OF HRT • DECREASES OVARIAN/FALLOPIAN TUBE CANCERS AND MAY PROTECT AGAINST BREAST CANCER
  49. 49. PROACTIVE CANCER MANAGEMENT REDUCES THE RISKS (BRCA1/2 Patients) 0% 10% 20% 30% 40% 50% 60% 70% 80% 90% 100% BREAST CANCER OVARIAN CANCER TAMOXIFEN MASTECTOMY OOPHORECTOMY ORAL CONTRACEPTIVES
  50. 50. ALL CANCER IS GENETIC, BUT NOT ALL CANCER IS HEREDITARY SPORADIC HEREDITARY FAMILIAL? SPORADIC HEREDITARY FAMILIAL?
  51. 51. MEDICAL ONCOLOGY CENTRAL REGIS RISK REDUCTION BSO • CAN BE DELAYED TO ALLOW COMPLETION OF CHILDBEARING • LAPAROSCOPIC APPROACH MINIMIZES HOSPITAL STAY/RECOVERY • ?ROLE OF HRT • DECREASES OVARIAN/FALLOPIAN TUBE CANCERS AND MAY PROTECT AGAINST BREAST CANCER
  52. 52. SCREENING GOAL WORKED!   WORKED!   WORKED!   WORKED!   FAILED!  
  53. 53. WORLD HEALTH ORGANIZATION 1968 1.  The  condi,on  should  be  an  important  health  problem.   2.  There  should  be  a  treatment  for  the  condi,on.   3.  Facili,es  for  diagnosis  and  treatment  should  be  available.   4.  There  should  be  a  latent  stage  of  the  disease.   5.  There  should  be  a  test  or  examina,on  for  the  condi,on.   6.  The  test  should  be  acceptable  to  the  popula,on.   7.  The  natural  history  of  the  disease  should  be  adequately  understood.   8.  There  should  be  an  agreed  policy  on  whom  to  treat.   9.  The  total  cost  of  finding  a  case  should  be  economically  balanced  in  rela,on  to   medical  expenditure  as  a  whole.   10.  Case-­‐finding  should  be  a  con,nuous  process,  not  just  a  "once  and  for  all"  project.  

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