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C- 1
A New Test for Assessing
the Risk of Ovarian Cancer
in Women with Adnexal Mass
Presenter
Place
Date
C- 2
Ovarian Cancer is a Major
Women's Health Problem
• High morbidity and mortality
• Appropriate treatment improves surv...
C- 3
ROMA™: A Novel Ovarian
Cancer Risk Assessment Tool
• Evaluated 15 biomarkers including HE4, which is:
– Putative prot...
C- 4
ROMA™: A Novel Ovarian
Cancer Risk Assessment Tool
• Stratify risk of ovarian cancer
• Ensure treatment by right surg...
C- 5
ROMA™ Will Improve
Treatment of Women
with Adnexal Mass
C- 6
Agenda
• Ovarian Cancer Risk Assessment
• ROMA™ Development
• Multicenter Validation Trial
• Conclusion and Summary
C- 7
Ovarian Cancer Risk Assessment
C- 8
Need New Tools to Better
Assess Ovarian Cancer Risk
C- 9
Ovarian Cancer is a
Deadly Disease
• 204,499 new cases in 2008
• 124,860 deaths
• Leading cause of gynecologic cancer...
C- 10
1 in 5 Women will have
a Pelvic Mass
• 20% of women will be diagnosed with an
adnexal mass1
• 5 - 10% of women will ...
C- 11
Survival Rates for Ovarian
Cancer Need to be Improved
Ovarian Cancer 5-yr Survival Rate by Stage
Stage Distribution
...
C- 12
How can we Affect Ovarian
Cancer Survival?
• Prevention
• Screening
• Early detection
• Surgery
• Chemotherapeutic a...
C- 13
Surgery can Impact Survival
• Cytoxan to Paclitaxel
– 14 month survival advantage1
• Intravenous to Intraperitoneal
...
C- 14
The Optimal Care
for Ovarian Cancer
• Cytoreductive surgery with complete
surgical staging
• Rationale for surgical ...
C- 15
Surgical Debulking Increases
Survival for Ovarian Cancer
Optimal surgical debulking can include:
• Hysterectomy
• Re...
C- 16
Gynecologic Oncologists are
Ovarian Cancer Specialists
• Gynecologic oncologist
– Recognized sub-specialty in US
• R...
C- 17
Oncology Specialist Most Likely to
Perform Comprehensive Surgery
*Ovarian Cancer Surgery by: Surgeon
Surgeon Special...
C- 18
High Volume Surgeons Most Likely to
Perform Comprehensive Surgery
Ovarian Cancer Surgery by: Surgeon
Surgery Volume
...
C- 19
Less than Half of Ovarian Cancer
Surgery is at High Volume Hospital
Ovarian Cancer Surgery by: Hospital
Surgery Volu...
C- 20
Significantly Higher Survival
Rates with Oncology Specialists
0.0
0.2
0.4
0.6
0.8
1.0
0 200 400 600 800 1000
Surviva...
C- 21
Significantly Higher Survival
Rates with Oncology Specialists
Study
Gynecologic
Oncologists
Gynecologists/
General
S...
C- 22
Cytoreductive Surgery Increases
Survival for Ovarian Cancer Patients
Multiple studies and large meta-analyses have
s...
C- 23
Current Practice is Sub-Optimal
for Ovarian Cancer Patients
• In the US only 50% of women with ovarian
cancer are op...
C- 24
Current Clinical Tools to
Assess Risk of Ovarian Cancer
• History
• Physical exam
• Imaging (US, CT and MRI)
• Tumor...
C- 25
We can Improve the Care for
Ovarian Cancer Patients
• Better risk assessment
• Improved patient care and management
C- 26
Validation of ROMA™ as a
Risk Assessment Tool and
Patient Benefit
C- 27
Development and Validation
of ROMA™
• Two pilot studies combined to generate ROMA™
– Patients enrolled from:
• Women...
C- 28
Primary Objective of
Pivotal Trial
• To validate a predictive model utilizing a dual
marker assay of HE4 and CA 125 ...
C- 29
Pivotal Trial Study Sites Chosen to
Enrich Ovarian Cancer Population
• 14 geographically dispersed sites across the ...
C- 30
Pivotal Trial Methods
• Prospective double-blind multicenter trial
• Eligibility criteria:
– ≥18 years of age
– Ovar...
C- 31
Pivotal Trial Enrollment
• 566 patients enrolled
• 530 evaluable patients
– 246 premenopausal
– 284 postmenopausal
•...
C- 32
Study Cohort Disease
Distribution: Enriched for EOC
Pivotal Trial:
Pathology Distribution for All Cases
Pathology Pr...
C- 33
Spectrum of Benign Disease
as Expected
Pathology Pre Post All %
Serous cystadenoma/Cystadenoma 25 53 78 22.2
Endomet...
C- 34
Stage Distribution for
EOC as Expected
Invasive
EOC
Premenopausal
(N)
Postmenopausal
(N)
All Patients
(N)
Stage I 4 ...
C- 35
Most Ovarian Cancers
Correctly Classified
All Patients: Distribution of Benign vs EOC + LMP Tumors
Disease
Low
Risk
...
C- 36
Age Groups
LMP
EOC Stage
% EOC
incorrectly
classified
% EOC
correctly
classified
I II
III
&
IV
Not
Staged
Postmenopa...
C- 37
Most Early Stage
EOC Correctly Classified
Correctly
Identified
Total
Cases
Percentage
correctly
Identified
Stage I &...
C- 38
ROMA™ vs RMI
Risk of Malignancy Index (RMI)
RMI = U x M x serum CA 125 level
U = 0 for imaging score of 0
= 1 for im...
C- 39
Secondary Analysis of
ROMA™ vs RMI
• Able to calculate an RMI for 80% of patients
• Utilized US, CT scans and MRI re...
C- 40
ROMA™ has Increased Sensitivity
Compared with RMI
Pre & Post
Menopausal
Benign (n=315) vs EOC (n=124)
Sensitivity* (...
C- 41
ROMA™ has Increased Sensitivity
vs RMI for Early Stage Cancer
Pre & Post
Menopausal
Benign (n=315) vs Stage I-II EOC...
C- 42
ROMA™ Demonstrates
Superior Performance
• Correctly identifies 94% of EOC1
• Performs better than RMI
• Simple and e...
C- 43
Additional Slides
C- 44
Ovarian Cancer Epidemiology
• Age adjusted
incidence is 2 to
15 cases per
100,000 women
• Incidence rates
are stable...
C- 45
Surgical Staging
• The current standard of care for ovarian cancer is cytoreductive
surgery with complete surgical s...
C- 46
Ovarian Cancer
• Age at presentation is bimodal with
peaks at age 40 and 60 years old
• Symptoms often are nonspecif...
C- 47
EDRN “Top Ten” Biomarkers for
Detection of Ovarian Cancer
• CA 125
• HE4
• CA 15-3
• CA 72-4
• B7-H4 (Ov-
110)
• Tra...
C- 48
CA 125
• “Gold Standard” biomarker in ovarian cancer
• Elevated CA 125 in 50% of Stage I disease and 80% of epitheli...
C- 50
Genetic Risk Factors for
Ovarian Cancer
• BRCA 1 (17q21)
• BRCA 2 (13q12)
• P53 (17q13)
• PTEN (10q24)
• HNPCC
– MLH...
C- 51
Ultrasound Assessment of Pelvic Mass
• Limitations of Ultrasound
– Not all morphologic variables are commonly
report...
C- 52
Preoperative Differentiation of Benign and Malignant
Pelvic Masses
• To evaluate the risk of a malignancy
• To deter...
C- 53
Epidemiologic Risk Factors for Ovarian Cancer
• Age
• Early age at menarche
• Late age at menopause
• Nulliparity
• ...
C- 54
Surgical Staging
Surgical Staging by Specialty
Study
Gynecologic
Oncologist
Gynecologist General surgeon
Earle 2006
...
C- 55
Ultrasound and CA125
RMI
Score
Sensitivity
(%)
Specificity
(%)
Likelihood ratio for
malignancy
if result is:
Positiv...
C- 56
Adequacy of Surgical Staging
Results of repeat staging in apparent early stage ovarian cancers
Initial Stage # of Pa...
C- 57
Ultrasound Evaluation of a Pelvic MassUltrasound Evaluation of a Pelvic Mass
Study Score
Sensitivity
(%)
Specificity...
C- 58
Pivotal Trial Referral Patterns
Gastroenterologist
0%
Self-referred
1%
Other
10%
Gynecologist
69%
Family Practitione...
C- 59
ACOG Referral Guidelines
• Premenopausal
– CA125 > 200
– Ascites
– Evidence of
metastasis
– Family history of
breast...
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  1. 1. C- 1 A New Test for Assessing the Risk of Ovarian Cancer in Women with Adnexal Mass Presenter Place Date
  2. 2. C- 2 Ovarian Cancer is a Major Women's Health Problem • High morbidity and mortality • Appropriate treatment improves survival1 – Oncology specialists – High volume centers • Need better risk assessment tools 1 ACOG Practice Bulletin. Obstet Gynecol. 2007;110:201-213.
  3. 3. C- 3 ROMA™: A Novel Ovarian Cancer Risk Assessment Tool • Evaluated 15 biomarkers including HE4, which is: – Putative protease inhibitor – CE-Marked and available for clinical use • Assess Risk of ovarian cancer in patients with Pelvic Mass • Monitor patients with ovarian cancer – Expressed in reproductive, respiratory tissues – Complementary to CA 125 • Developed ROMA™ – 89% sensitive1 – 75% specific1 1 FDI-03 Clinical Study Report.
  4. 4. C- 4 ROMA™: A Novel Ovarian Cancer Risk Assessment Tool • Stratify risk of ovarian cancer • Ensure treatment by right surgeon/right facility • Used in conjunction with other Dx methods • Not intended for detection or screening
  5. 5. C- 5 ROMA™ Will Improve Treatment of Women with Adnexal Mass
  6. 6. C- 6 Agenda • Ovarian Cancer Risk Assessment • ROMA™ Development • Multicenter Validation Trial • Conclusion and Summary
  7. 7. C- 7 Ovarian Cancer Risk Assessment
  8. 8. C- 8 Need New Tools to Better Assess Ovarian Cancer Risk
  9. 9. C- 9 Ovarian Cancer is a Deadly Disease • 204,499 new cases in 2008 • 124,860 deaths • Leading cause of gynecologic cancer deaths • 5th leading cause of cancer deaths in women International Agency for Research on Cancer. Globocan 2002. http://www-dep.iarc.fr/
  10. 10. C- 10 1 in 5 Women will have a Pelvic Mass • 20% of women will be diagnosed with an adnexal mass1 • 5 - 10% of women will have surgery for an ovarian neoplasm (100,000 to 200,000)2 • 13 - 21% of these masses will be malignant2 1 Curtin JP. Gynecol Oncol. 1994;55:S42-S46. 2 NIH Consensus Development Conference Statement. Gynecol Oncol. 1994;55:S4-S14.
  11. 11. C- 11 Survival Rates for Ovarian Cancer Need to be Improved Ovarian Cancer 5-yr Survival Rate by Stage Stage Distribution at Diagnosis Survival Rate Stage I 20-27% 73-93% Stage II 5-10% 45-70% Stage III 52-58% 21-37% Stage IV 11-17% 11-25% Heintz APM, et al. FIGO Annual Report on the Results of Treatment in Gynecologic Cancers. 2000; 24 :107-138. Holschneider CH, Berek JS. Semin Surg Oncol. 2000;19:3-10.
  12. 12. C- 12 How can we Affect Ovarian Cancer Survival? • Prevention • Screening • Early detection • Surgery • Chemotherapeutic agents
  13. 13. C- 13 Surgery can Impact Survival • Cytoxan to Paclitaxel – 14 month survival advantage1 • Intravenous to Intraperitoneal – 16 month survival advantage2 • Surgery by gynecologic oncologist – 12 month survival advantage3,4 1 McGuire WP et al. NEJM. 1996;334(1):1-6. 2 Armstrong DK et al. NEJM. 2006;354(1):34-43. 3 Engelen MJA et al. Cancer. 2006;106(3):589-598. 4 Bristow RE et al. J Clin Oncol. 2002;20(5):1248-1259
  14. 14. C- 14 The Optimal Care for Ovarian Cancer • Cytoreductive surgery with complete surgical staging • Rationale for surgical staging: – Define the extent of disease – Determine the need for adjuvant treatment – Provide prognosis – Outline a plan of care
  15. 15. C- 15 Surgical Debulking Increases Survival for Ovarian Cancer Optimal surgical debulking can include: • Hysterectomy • Removal of ovaries • Bowel resection • Peritoneal stripping • Diaphragmatic stripping • Lymph node debulking
  16. 16. C- 16 Gynecologic Oncologists are Ovarian Cancer Specialists • Gynecologic oncologist – Recognized sub-specialty in US • Residency in Obstetrics and Gynecology (4 yrs) • Fellowship in Gynecologic Oncology (3-4 yrs) – Outside US Gynecologists with high oncology surgical volume • Experienced in: – Surgical care – Medical management – Chemotherapy – Natural history
  17. 17. C- 17 Oncology Specialist Most Likely to Perform Comprehensive Surgery *Ovarian Cancer Surgery by: Surgeon Surgeon Specialty Rate of Comprehensive Surgery Gynecologic oncologist 75.7% Obstetrician gynecologist 37.3% General surgeon 38.5% Goff BA et al. Cancer. 2007;109(10):2031-2042. * South Carolina admissions
  18. 18. C- 18 High Volume Surgeons Most Likely to Perform Comprehensive Surgery Ovarian Cancer Surgery by: Surgeon Surgery Volume Percentage of Cases Rate of Comprehensive Surgery Very Low 1 case/year 25.2% 55.2% Low / Medium 2-9 cases/year 22.7% 65.1% High ≥ 10 cases/year 52.1% 75.2% Goff BA et al. Cancer. 2007;109(10):2031-2042.
  19. 19. C- 19 Less than Half of Ovarian Cancer Surgery is at High Volume Hospital Ovarian Cancer Surgery by: Hospital Surgery Volume Percentage of Cases Rate of Comprehensive Surgery Low 1-9 cases/year 33.3% 57.4% Medium 10-19 cases/year 18.1% 69.5% High ≥ 20 cases/year 48.6% 73.7% Goff BA et al. Cancer. 2007;109(10):2031-2042.
  20. 20. C- 20 Significantly Higher Survival Rates with Oncology Specialists 0.0 0.2 0.4 0.6 0.8 1.0 0 200 400 600 800 1000 Survival in days CumulativeSurvival 0.0 0.2 0.4 0.6 0.8 1.0 0 200 400 600 800 1000 Survival in days CumulativeSurvival Type of Surgeon Impacts Survival Rates Type of Hospital Impacts Survival Rates Paulsen T et al. Int J Gynecol Cancer. 2006;16(Suppl 1):11-17. TH: Teaching hospital NTH: Nonteaching hospital
  21. 21. C- 21 Significantly Higher Survival Rates with Oncology Specialists Study Gynecologic Oncologists Gynecologists/ General Surgeons p value Eisenkop 1992 35 months 17 months <0.001 Junor 1999 18 months 13 months <0.005 Carney 2002 26 months 15 months <0.01 Tingulstad 2003 21 months 12 months 0.01 Eisenkop SM et al. Gynecol Oncol. 1992;47(2):203-209. Junor EJ et al. Br J Obstet Gynaecol. 1999;106(11):1130-1136. Carney ME et al. Gynecol Oncol. 2002;84:36-42. Tingulstad S et al. Obstet Gynecol. 2003;102(3):499-505.
  22. 22. C- 22 Cytoreductive Surgery Increases Survival for Ovarian Cancer Patients Multiple studies and large meta-analyses have shown residual disease following surgery is the most significant prognostic factor: 53 studies, 6,885 patients Optimal cytoreduction ↑ survival from 22.7 to 33.9 months (50% ↑) Bristow RE et al. J Clin Oncol. 2002;20(5):1248-1259.
  23. 23. C- 23 Current Practice is Sub-Optimal for Ovarian Cancer Patients • In the US only 50% of women with ovarian cancer are operated on by high volume surgeons or at high volume centers1 • Studies around the world show that survival rates are improved when patients have surgery by surgeons and at centers experienced in the management of ovarian cancer2 1 Goff BA et al. Cancer. 2007;109(10):2031-2042. 2 ACOG Practice Bulletin. Obstet Gynecol. 2007;110:201-213.
  24. 24. C- 24 Current Clinical Tools to Assess Risk of Ovarian Cancer • History • Physical exam • Imaging (US, CT and MRI) • Tumor markers (CA 125)
  25. 25. C- 25 We can Improve the Care for Ovarian Cancer Patients • Better risk assessment • Improved patient care and management
  26. 26. C- 26 Validation of ROMA™ as a Risk Assessment Tool and Patient Benefit
  27. 27. C- 27 Development and Validation of ROMA™ • Two pilot studies combined to generate ROMA™ – Patients enrolled from: • Women and Infants’ Hospital, Providence RI • Massachusetts General Hospital, Boston MA • Pivotal trial (FDI-03) to validate ROMA™ – National trial – New patient cohort for validation
  28. 28. C- 28 Primary Objective of Pivotal Trial • To validate a predictive model utilizing a dual marker assay of HE4 and CA 125 to assess the risk for epithelial ovarian cancer including borderline/low malignant potential tumors in women with a pelvic mass FDI-03 Clinical Study Report.
  29. 29. C- 29 Pivotal Trial Study Sites Chosen to Enrich Ovarian Cancer Population • 14 geographically dispersed sites across the US • Divisions of Gynecologic Oncology, within Departments of Obstetrics and Gynecology • Sites chosen to enrich study population FDI-03 Clinical Study Report.
  30. 30. C- 30 Pivotal Trial Methods • Prospective double-blind multicenter trial • Eligibility criteria: – ≥18 years of age – Ovarian cyst or a pelvic mass – Planned surgical intervention • All EOC patients to be surgically staged • All blood samples obtained preoperatively • Central pathology review FDI-03 Clinical Study Report.
  31. 31. C- 31 Pivotal Trial Enrollment • 566 patients enrolled • 530 evaluable patients – 246 premenopausal – 284 postmenopausal • 94% of patients were evaluable FDI-03 Clinical Study Report.
  32. 32. C- 32 Study Cohort Disease Distribution: Enriched for EOC Pivotal Trial: Pathology Distribution for All Cases Pathology Premenopausal (N) Postmenopausal (N) All Patients (N) Benign 200 151 351 (66%) Invasive EOC 18 111 129 (24%) LMP Tumors 16 6 22 (4%) Non EOC 6 0 6 (1%) Metastatic 5 9 14 (3%) Other Gyn 1 7 8 (2%) Total 246 284 530 FDI-03 Clinical Study Report.
  33. 33. C- 33 Spectrum of Benign Disease as Expected Pathology Pre Post All % Serous cystadenoma/Cystadenoma 25 53 78 22.2 Endometriosis 42 2 44 12.5 Simple/Paratubal 34 21 55 15.7 Teratoma 18 11 29 8.3 Adenofibroma/Cystadenofibroma 6 16 22 6.3 Mucinous Cystadenoma 9 13 22 6.3 Leiomyoma 16 3 19 5.4 Fibroma/Fibrothecoma 3 15 18 5.1 Tubo-ovarian abscess/Hydrosalpinx 8 6 14 4.0 Functional cyst/Hemorrhagic cyst 14 0 14 4.0 Normal 3 2 5 1.4 Other 22 9 31 8.8 Total 200 151 351 100 Data on file, FDI.
  34. 34. C- 34 Stage Distribution for EOC as Expected Invasive EOC Premenopausal (N) Postmenopausal (N) All Patients (N) Stage I 4 13 17 (13%) Stage II 3 15 18 (14%) Stage III 8 76 84 (65%) Stage IV 1 5 6 (5%) Unstaged 2 2 4 (3%) Total 18 111 129 Data on file, FDI.
  35. 35. C- 35 Most Ovarian Cancers Correctly Classified All Patients: Distribution of Benign vs EOC + LMP Tumors Disease Low Risk (N) High Risk (N) All (N) Sensitivity Specificity PPV NPV Benign 262 89 351 89% 75% 60% 94% EOC + LMP 17 134 151 Total 279 223 502 FDI-03 Clinical Study Report.
  36. 36. C- 36 Age Groups LMP EOC Stage % EOC incorrectly classified % EOC correctly classified I II III & IV Not Staged Postmenopausal (n=111) 3 1 3 1 1 5% 95% Premenopausal (n=18) 6 1 - - 1 11% 89% All Ages (n=129) 9 2 3 1 2 6% 94% Most Ovarian Cancers Correctly Classified FDI-03 Clinical Study Report.
  37. 37. C- 37 Most Early Stage EOC Correctly Classified Correctly Identified Total Cases Percentage correctly Identified Stage I & II 30 35 86% Stage III & IV 89 90 99% All Invasive EOC* 121 129 94% *All EOC including unstaged EOC FDI-03 Clinical Study Report.
  38. 38. C- 38 ROMA™ vs RMI Risk of Malignancy Index (RMI) RMI = U x M x serum CA 125 level U = 0 for imaging score of 0 = 1 for imaging score of 1 = 3 for imaging score of 2-5 M = 1 if premenopausal = 3 if postmenopausal Jacobs I et al. Br J Obstet Gynecol.1990; 97:992-929.
  39. 39. C- 39 Secondary Analysis of ROMA™ vs RMI • Able to calculate an RMI for 80% of patients • Utilized US, CT scans and MRI results for RMI imaging scores
  40. 40. C- 40 ROMA™ has Increased Sensitivity Compared with RMI Pre & Post Menopausal Benign (n=315) vs EOC (n=124) Sensitivity* (95% CI) Specificity (95% CI) RMI 85% (77% to 90%) 75% (70% to 80%) ROMA™ 94% (89% to 98%) 75% (70% to 80%) Benign and EOC: All Stages *Two Sample Test of Equality of Proportions p=0.0129 CI: Confidence Interval Data on file, FDI.
  41. 41. C- 41 ROMA™ has Increased Sensitivity vs RMI for Early Stage Cancer Pre & Post Menopausal Benign (n=315) vs Stage I-II EOC (n=35) Sensitivity* (95% CI) Specificity (95% CI) RMI 66% (48% to 81%) 75% (70% to 80%) ROMA™ 86% (70% to 95%) 75% (70% to 80%) Benign and EOC: Stage I & II *Two Sample Test of Equality of Proportions p=0.0510 CI: Confidence Interval Data on file, FDI.
  42. 42. C- 42 ROMA™ Demonstrates Superior Performance • Correctly identifies 94% of EOC1 • Performs better than RMI • Simple and easy to use • Quantitative test • No subjective data • Assigns a risk for malignancy Data on file, FDI.
  43. 43. C- 43 Additional Slides
  44. 44. C- 44 Ovarian Cancer Epidemiology • Age adjusted incidence is 2 to 15 cases per 100,000 women • Incidence rates are stable or slowly increasing
  45. 45. C- 45 Surgical Staging • The current standard of care for ovarian cancer is cytoreductive surgery with complete surgical staging. • Complete surgical staging includes: – Laparotomy – Hysterectomy – Bilateral salpingo-oophorectomy – Careful evaluation of all peritoneal surfaces – Multiple washings for cytology – Multiple peritoneal biopsies – Hepatic and diaphragmatic cytology – Omentectomy – Pelvic and periaortic lymphadenectomy • Less than 50% of women undergoing surgery for an ovarian cancer will have an adequate staging or cytoreductive surgery1,2 . Gynecologic Oncologists are trained in staging of ovarian cancer. 1 Carney ME et al. Gynecol Oncol. 2002;84:36-42. 2 McGowan L et al. Obstet Gynecol. 1985;65(4):568-572.
  46. 46. C- 46 Ovarian Cancer • Age at presentation is bimodal with peaks at age 40 and 60 years old • Symptoms often are nonspecific: – Abdominal bloating – Pelvic pressure – GI symptoms – Respiratory – Constitutional
  47. 47. C- 47 EDRN “Top Ten” Biomarkers for Detection of Ovarian Cancer • CA 125 • HE4 • CA 15-3 • CA 72-4 • B7-H4 (Ov- 110) • Transthyretin • IGFBP-2 • SMRP (Mesomark™) • HK6 • Cytokeratin 19 (CYFRA 21-1)
  48. 48. C- 48 CA 125 • “Gold Standard” biomarker in ovarian cancer • Elevated CA 125 in 50% of Stage I disease and 80% of epithelial ovarian cancers1 • Elevated in the pre-clinical asymptomatic phase of the disease Limitations – Elevated levels in benign gynecological disease1,2 – Low sensitivity in Stage I ovarian cancer – CA 125 alone is not a sensitive marker HE4 • A commonly up-regulated biomarker in ovarian cancer • Serum HE4 is a useful biomarker in the early diagnosis of ovarian cancer Biomarkers for Ovarian Cancer 1 NIH Consensus Development Conference Statement. Gynecol Oncol. 1994;55:S4-S14. 2 ACOG Practice Bulletin. Obstet Gynecol. 2007;110:201-213.
  49. 49. C- 50 Genetic Risk Factors for Ovarian Cancer • BRCA 1 (17q21) • BRCA 2 (13q12) • P53 (17q13) • PTEN (10q24) • HNPCC – MLH 1 (3p21) – MSH 2 (2p16) – PMS 1 (2q31) – PMS 2 (7p22) Only 10% of ovarian cancers are inherited
  50. 50. C- 51 Ultrasound Assessment of Pelvic Mass • Limitations of Ultrasound – Not all morphologic variables are commonly reported or measured – User variability (tertiary care vs community) – Ultrasound reporting is not standardized – Quality and complexity of machine (e.g. Doppler) – Complex algorithms Moore RG et al. J Clin Oncol. 2007;25:4159-4161.
  51. 51. C- 52 Preoperative Differentiation of Benign and Malignant Pelvic Masses • To evaluate the risk of a malignancy • To determine the need for surgery • To triage patients • To Improve the quality of care for patients – Allow patients to stay in their community – Appropriate patients referred to specialists • Medical-legal implications
  52. 52. C- 53 Epidemiologic Risk Factors for Ovarian Cancer • Age • Early age at menarche • Late age at menopause • Nulliparity • Infertility • Caucasian race • History of endometriosis ACOG Practice Bulletin. Obstet Gynecol. 2007;110:201-213.
  53. 53. C- 54 Surgical Staging Surgical Staging by Specialty Study Gynecologic Oncologist Gynecologist General surgeon Earle 2006 60% (nodes) 118/198 36% (nodes) 146/409 16% (nodes) 23/144 Engelen 2006 61% (nodes) 40/65 30% (nodes) 41/135 - Grossi 2002 47% (ext staging) 15% (ext staging) 0% (ext staging) Earle CC et al. J Ntl Cancer Inst. 2006;25:172-180. Engelen MJA et al. Cancer. 2006;106:589-598. Grossi M et al. MJA..2002;177:11-16.
  54. 54. C- 55 Ultrasound and CA125 RMI Score Sensitivity (%) Specificity (%) Likelihood ratio for malignancy if result is: Positive Negative 25 100 62.2 2.7 0.00 50 95.1 76.5 4.1 0.06 75 92.7 84.7 6.1 0.09 100 85.4 87.8 7.0 0.17 150 85.4 93.9 14.0 0.16 200 85.4 96.9 42.1 0.15 250 78.0 99.0 76.9 0.22 Jacobs I et al. Br J Obstet Gynecol.1990; 97:992-929.
  55. 55. C- 56 Adequacy of Surgical Staging Results of repeat staging in apparent early stage ovarian cancers Initial Stage # of Patients % Upstaged IA 37 16 IB 10 30 IC 2 0 IIA 4 100 IIB 38 39 IIC 9 33 Total 100 31 Young RC et al. JAMA.1983;250(22):3072-3076.
  56. 56. C- 57 Ultrasound Evaluation of a Pelvic MassUltrasound Evaluation of a Pelvic Mass Study Score Sensitivity (%) Specificity (%) PPV (%) NPV (%) Ferrazzi 1997 9 87 67 41 95 Granberg 1990 2 87 49 31 93 Sassone 1991 9 74 65 36 90 DePriest 1993 5 88 40 28 93 Lerner 1994 4 87 59 36 95 Ferrazzi E et al. Ultrasound Obstet Gynecol.1997;10:192-197.
  57. 57. C- 58 Pivotal Trial Referral Patterns Gastroenterologist 0% Self-referred 1% Other 10% Gynecologist 69% Family Practitioner 9% Surgeon 2% Internist 9% N=524 of the 566 trial population Data on File, FDI.
  58. 58. C- 59 ACOG Referral Guidelines • Premenopausal – CA125 > 200 – Ascites – Evidence of metastasis – Family history of breast or ovarian cancer • Postmenopausal – CA125 >35 – Ascites – Fixed or nodular mass – Evidence of metastasis – Family history of breast or ovarian cancer ACOG Practice Bulletin. Obstet Gynecol. 2007;110:201-213.

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