A new test for assessing the risk of ovarian cancer in women with adnexal mass
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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 l.jpg

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 l.jpg
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.


Roma a novel ovarian cancer risk assessment tool l.jpg
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.


Roma a novel ovarian cancer risk assessment tool4 l.jpg
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


Roma will improve treatment of women with adnexal mass l.jpg

ROMA™ Will Improve Treatment of Women with Adnexal Mass


Agenda l.jpg
Agenda

  • Ovarian Cancer Risk Assessment

  • ROMA™ Development

  • Multicenter Validation Trial

  • Conclusion and Summary



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Need New Tools to Better Assess Ovarian Cancer Risk


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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/


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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.


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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.


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How can we Affect Ovarian Cancer Survival?

  • Prevention

  • Screening

  • Early detection

  • Surgery

  • Chemotherapeutic agents


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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


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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


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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


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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


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Oncology Specialist Most Likely to Perform Comprehensive Surgery

* South Carolina admissions

Goff BA et al. Cancer. 2007;109(10):2031-2042.


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High Volume Surgeons Most Likely to Perform Comprehensive Surgery

Goff BA et al. Cancer. 2007;109(10):2031-2042.


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Less than Half of Ovarian Cancer Surgery is at High Volume Hospital

Goff BA et al. Cancer. 2007;109(10):2031-2042.


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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.


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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.


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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.


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Current Practice is Sub-Optimal for Ovarian Cancer Patients 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.


Current clinical tools to assess risk of ovarian cancer l.jpg
Current Clinical Tools to PatientsAssess Risk of Ovarian Cancer

  • History

  • Physical exam

  • Imaging (US, CT and MRI)

  • Tumor markers (CA 125)


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We can Improve the Care for Ovarian Cancer Patients Patients

  • Better risk assessment

  • Improved patient care and management


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Validation of ROMA™ as a PatientsRisk Assessment Tool and Patient Benefit


Development and validation of roma l.jpg
Development and Validation Patientsof 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


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Primary Objective of PatientsPivotal 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.


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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.


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Pivotal Trial Methods Population

  • 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.


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Pivotal Trial Enrollment Population

  • 566 patients enrolled

  • 530 evaluable patients

    • 246 premenopausal

    • 284 postmenopausal

  • 94% of patients were evaluable

FDI-03 Clinical Study Report.


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Study Cohort Disease Distribution: Enriched for EOC Population

FDI-03 Clinical Study Report.


Spectrum of benign disease as expected l.jpg
Spectrum of Benign Disease Populationas Expected

Data on file, FDI.


Stage distribution for eoc as expected l.jpg
Stage Distribution for PopulationEOC as Expected

Data on file, FDI.


Most ovarian cancers correctly classified l.jpg
Most Ovarian Cancers PopulationCorrectly Classified

FDI-03 Clinical Study Report.


Slide36 l.jpg

Most Ovarian Cancers PopulationCorrectly Classified

FDI-03 Clinical Study Report.


Most early stage eoc correctly classified l.jpg
Most Early Stage PopulationEOC Correctly Classified

*All EOC including unstaged EOC

FDI-03 Clinical Study Report.


Roma vs rmi l.jpg
ROMA™ vs RMI Population

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.


Secondary analysis of roma vs rmi l.jpg
Secondary Analysis of PopulationROMA™ vs RMI

  • Able to calculate an RMI for 80% of patients

  • Utilized US, CT scans and MRI results for RMI imaging scores


Roma has increased sensitivity compared with rmi l.jpg
ROMA™ has Increased Sensitivity Compared with RMI Population

Benign and EOC: All Stages

*Two Sample Test of Equality of Proportions p=0.0129

CI: Confidence Interval

Data on file, FDI.


Roma has increased sensitivity vs rmi for early stage cancer l.jpg
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.


Roma demonstrates superior performance l.jpg
ROMA™ Demonstrates CancerSuperior 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.



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Ovarian Cancer Epidemiology Cancer

Age adjusted incidence is 2 to 15 cases per 100,000 women

Incidence ratesare stable orslowly increasing


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Surgical Staging Cancer

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.


Ovarian cancer l.jpg
Ovarian Cancer 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


Edrn top ten biomarkers for detection of ovarian cancer l.jpg
EDRN “Top Ten” Biomarkers for CancerDetection 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)


Biomarkers for ovarian cancer l.jpg
Biomarkers for Ovarian Cancer 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.


    Genetic risk factors for ovarian cancer l.jpg
    Genetic Risk Factors for CancerOvarian 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


    Ultrasound assessment of pelvic mass l.jpg
    Ultrasound Assessment of Pelvic Mass Cancer

    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.


    Preoperative differentiation of benign and malignant pelvic masses l.jpg
    Preoperative Differentiation of Benign and Malignant CancerPelvic 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


    Epidemiologic risk factors for ovarian cancer l.jpg
    Epidemiologic Risk Factors for Ovarian Cancer 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.


    Surgical staging53 l.jpg
    Surgical Staging Cancer

    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.


    Ultrasound and ca125 l.jpg
    Ultrasound and CA125 Cancer

    Jacobs I et al. Br J Obstet Gynecol.1990; 97:992-929.


    Adequacy of surgical staging l.jpg
    Adequacy of Surgical Staging Cancer

    Young RC et al. JAMA.1983;250(22):3072-3076.


    Ultrasound evaluation of a pelvic mass l.jpg
    Ultrasound Evaluation of a Pelvic Mass Cancer

    Ferrazzi E et al. Ultrasound Obstet Gynecol.1997;10:192-197.


    Pivotal trial referral patterns l.jpg
    Pivotal Trial Referral Patterns Cancer

    N=524 of the 566 trial population

    Data on File, FDI.


    Acog referral guidelines l.jpg
    ACOG Referral Guidelines Cancer

    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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