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A New Test for Assessing the Risk of Ovarian Cancer in Women with Adnexal Mass

A New Test for Assessing the Risk of Ovarian Cancer in Women with Adnexal Mass. Presenter Place Date. Ovarian Cancer is a Major Women's Health Problem. High morbidity and mortality Appropriate treatment improves survival 1 Oncology specialists High volume centers

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A New Test for Assessing the Risk of Ovarian Cancer in Women with Adnexal Mass

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  1. A New Test for Assessing the Risk of Ovarian Cancer in Women with Adnexal Mass Presenter Place Date

  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 1ACOG Practice Bulletin. Obstet Gynecol. 2007;110:201-213.

  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 1FDI-03 Clinical Study Report.

  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. ROMA™ Will Improve Treatment of Women with Adnexal Mass

  6. Agenda • Ovarian Cancer Risk Assessment • ROMA™ Development • Multicenter Validation Trial • Conclusion and Summary

  7. Ovarian Cancer Risk Assessment

  8. Need New Tools to Better Assess Ovarian Cancer Risk

  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. 1 in 5 Women will havea 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 1Curtin JP. Gynecol Oncol. 1994;55:S42-S46. 2NIH Consensus Development Conference Statement. Gynecol Oncol. 1994;55:S4-S14.

  11. Survival Rates for Ovarian Cancer Need to be Improved 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. How can we Affect Ovarian Cancer Survival? • Prevention • Screening • Early detection • Surgery • Chemotherapeutic agents

  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 1McGuire WP et al. NEJM. 1996;334(1):1-6. 2Armstrong DK et al. NEJM. 2006;354(1):34-43. 3Engelen MJA et al. Cancer. 2006;106(3):589-598. 4Bristow RE et al. J Clin Oncol. 2002;20(5):1248-1259

  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. 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. 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. Oncology Specialist Most Likely to Perform Comprehensive Surgery * South Carolina admissions Goff BA et al. Cancer. 2007;109(10):2031-2042.

  18. High Volume Surgeons Most Likely to Perform Comprehensive Surgery Goff BA et al. Cancer. 2007;109(10):2031-2042.

  19. Less than Half of Ovarian Cancer Surgery is at High Volume Hospital Goff BA et al. Cancer. 2007;109(10):2031-2042.

  20. Significantly Higher Survival Rates with Oncology Specialists Type of Surgeon Impacts Survival Rates Type of Hospital Impacts Survival Rates TH: Teaching hospital NTH: Nonteaching hospital Paulsen T et al. Int J Gynecol Cancer. 2006;16(Suppl 1):11-17.

  21. Significantly Higher Survival Rates with Oncology Specialists 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. 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. 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 1Goff BA et al. Cancer. 2007;109(10):2031-2042. 2ACOG Practice Bulletin. Obstet Gynecol. 2007;110:201-213.

  24. Current Clinical Tools to Assess Risk of Ovarian Cancer • History • Physical exam • Imaging (US, CT and MRI) • Tumor markers (CA 125)

  25. We can Improve the Care for Ovarian Cancer Patients • Better risk assessment • Improved patient care and management

  26. Validation of ROMA™ as a Risk Assessment Tool and Patient Benefit

  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. 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. 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. 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. Pivotal Trial Enrollment • 566 patients enrolled • 530 evaluable patients • 246 premenopausal • 284 postmenopausal • 94% of patients were evaluable FDI-03 Clinical Study Report.

  32. Study Cohort Disease Distribution: Enriched for EOC FDI-03 Clinical Study Report.

  33. Spectrum of Benign Disease as Expected Data on file, FDI.

  34. Stage Distribution forEOC as Expected Data on file, FDI.

  35. Most Ovarian Cancers Correctly Classified FDI-03 Clinical Study Report.

  36. Most Ovarian Cancers Correctly Classified FDI-03 Clinical Study Report.

  37. Most Early Stage EOC Correctly Classified *All EOC including unstaged EOC FDI-03 Clinical Study Report.

  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. 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. ROMA™ has Increased Sensitivity Compared with RMI Benign and EOC: All Stages *Two Sample Test of Equality of Proportions p=0.0129 CI: Confidence Interval Data on file, FDI.

  41. ROMA™ has Increased Sensitivity vs RMI for Early Stage Cancer Benign and EOC: Stage I & II *Two Sample Test of Equality of Proportions p=0.0510 CI: Confidence Interval Data on file, FDI.

  42. ROMA™ DemonstratesSuperior 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. Additional Slides

  44. Ovarian Cancer Epidemiology Age adjusted incidence is 2 to 15 cases per 100,000 women Incidence ratesare stable orslowly increasing

  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 cancerwill have an adequate staging or cytoreductive surgery1,2. Gynecologic Oncologists are trained in staging of ovarian cancer. 1Carney ME et al. Gynecol Oncol. 2002;84:36-42. 2McGowan L et al.Obstet Gynecol. 1985;65(4):568-572.

  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. 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. Biomarkers for Ovarian Cancer • 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 1NIH Consensus Development Conference Statement. Gynecol Oncol. 1994;55:S4-S14. 2ACOG Practice Bulletin. Obstet Gynecol. 2007;110:201-213.

  49. 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. 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.

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