robert e. bristow, md, mba professor and director division of gynecologic oncology university of...

Robert E. Bristow, MD, MBAProfessor and Director

Division of Gynecologic OncologyUniversity of California, Irvine – Medical Center

Update on Ovarian Cancer

Ovarian Cancer Center

Mission:•To provide exemplary and holistic clinical care to patients with ovarian cancer.•To enhance community awareness of ovarian cancer regarding the importance of early diagnosis and the benefits of centralized expert care.•To advance the science of the prevention and treatment of ovarian cancer in a meaningful way.

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Gynecologic OncologyFaculty

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Ovarian Cancer Center• Clinical Services - coordination of multidisciplinary care - prevention, early detection, cancer survivorship - surgery and regional therapeutics - chemotherapy and clinical trials - ancillary services• Community Outreach and Education - web-based platform - virtual support group survivor network - conferences - international visiting scholar program• Research and Discovery - molecular biology and translational science - healthcare outcomes

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Ann’s Clinic

High-risk patients

- genetic counseling & testing

- surveillance programs

- cancer prophylaxis

Cancer survivors

- programmatic plan

- psycho-social wellness

- management of treatment toxicities

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Screening, Early Detection, Cancer Survivorship

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Peritoneal Surface Malignancies

Disease confined to peritoneal cavity for

much of natural history

Generally amenable to surgical resection

Positive survival impact of chemotherapy

- varies by disease site

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Sigmoid Tumor

Left Ovary

Right OvaryUterus

Bladder Tumor

Radical Surgery for Ovarian Cancer

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Culdesac Tumor

Distal SigmoidCervix

Uterus

Bladder Tumor

Radical Surgery for Ovarian Cancer

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RectosigmoidColon

Vaginal Cuff

Radical Surgery for Ovarian Cancer

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Development of Intra-Peritoneal (IP) Chemotherapy

• 1950’s: First use of intraperitoneal chemotherapy for malignant ascites

• 1968: Long-term peritoneal access device• 1978: Demonstration of slow peritoneal

clearance of some drugs• 1984: Feasibility of intermittent large volume

intraperitoneal therapy• 1996: First report of a survival benefit for IP

vs. IV chemotherapy in advanced ovarian cancer

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Armstrong DK et al. NEJM 2006; 354:34.

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Armstrong DK et al. NEJM 2006; 354: 34.

PFS: 18.3 vs 23.8 months OS: 49.7 vs 66.9 months

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12 14

24

37

52

57.466.9

0

20

40

60

80

Mo

nth

s

1975 1983 1986 1996 1998 2003 2006

IP Rx IP RxAlkeranAlkeran CisplatinCisplatin PaclitaxelPaclitaxel

(Optimal)(Optimal)

The ‘Evolution’ of Treatment forAdvanced Ovarian Cancer and Effect on Survival

Surgical & Chemotherapy Improvements

(Suboptimal)

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IP Therapy

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IP Therapy

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IP Therapy

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IP Therapy

Study Chemotherapy Residual Median Survival

GOG152 IV-CDDP/IV-Taxol >1cm 36 months

GOG172 IV-CDDP/IV-Taxol <1cm 50 months

IP-CDDP/IV+IP-Taxol <1cm 67 months

Primary Cytoreductive Surgery

Contemporary Survival Outcomes

0.1–1.0cm 39 monthsno gross 78 months

0.1–1.0cm 53 monthsno gross 127 months

Rose PG et al. N Eng J Med 2004; 351: 2489.Armstrong DK et al. N Eng J Med 2006; 354: 34.

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Hyperthermia and Neoplasia

Directly cytotoxic to cancer cells

- disrupts microtubule system

- induces primary protein damage

- promotes vascular stasis

Synergistic with some chemotherapy agents

Heat is…

Knox 1991, Stellar 1998

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HIPEC Schematic

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HIPEC Techniques

Open (colisuem)

Closed

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Role of HIPEC in Ovarian Cancer

Melis A et al. Bull Cancer 2011, doi 21659062.

Retrospective study design (1995-2005)

Advanced ovarian cancer (n=43)

Up-front HIPEC cisplatin + IV chemotherapy

Morbidity – 13.9%; mortality – 2.3%

Median OS = 53 months

- complete initial resection = 131 months

Median PFS = 39 months

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Burger RA et al. NEJM 2011; 365: 2473.

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PFS: +3.8 month maintenance Rx OS: no significant effect

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Burger RA et al. NEJM 2011; 365: 2473.

Fertility Preservation• Ovarian cancer - conservative surgery - young patients - early stage disease, atypical tumor types - chemotherapy with ovarian suppression

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Robotic Surgery

● daVinci surgical platform - patient-side robot

- vision cart

- robotic master console

AdvantagesImproved visualization

Finer instrument control and dexterityErgonomic design

Autonomous surgical environment

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da Vinci® – Robotic Surgery Technology

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Clinical Trials

• Ovarian cancer

- intraperitoneal chemotherapy / HIPEC

- molecular profiling

- quality of life / cancer survivorship

- developmental therapeutics / biologic agents

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Research and Discovery

Research and Discovery

• PhD recruitment underway

• Collaborative effort

• Genetic screening and early detection

• Molecular basis of disease

- characteristics of long-term survivors

- circumventing chemo-resistance

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QOH Ovarian Cancer Research Laboratory

Research and Discovery

• Surgical techniques

• Advanced imaging techniques / onco-imaging

• Clinical trials of new chemotherapeutic agents

• Biological therapies

• Public health applications

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Modern Approach to Cancer Therapeutics

Patient Metabolism

Pathways Analysis

Mutations

Genes Upregulated

Genes Downregulated

Research and Discovery

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OVA1 Qualitative serum test – 5 immunoassays - Apolipoprotein A - Transthyretin

- 2 Microglobulin - Transferrin

- CA125 II

Single numerical result: 0 - 10 FDA approved September 2009 Ovarian mass, > 18y/o, planned surgery Triage tool for surgical decision-making Not a screening or independent diagnostic test

Category Low Risk High RiskPremenopausal <5.0 ≥5.0Postmenopausal <4.4 ≥4.4

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Performance Preoperative Assessment

Assessment + OVA1

Sensitivity % 75 96

Specificity % 79 35

NPV % 87 95

PPV % 62 40

Subjects OVA1 CA125-II

All cancers (n=161) 92.5% 68.9%

All epithelial ovarian cancers (n=96) 99.0% 82.3%

Early stage EOC (n=41) 97.6% 65.9%

Premenopausal women w/ early stage EOC (n=14)

92.9% 35.7%

OVA1

Ueland F. et al. Int Gyn Cancer Soc Annual Meeting, 2010, Prague.

Sensitivity vs CA125

Overall Performance

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Disparities in Epithelial Ovarian CancerQuality of Care and Survival According to

Race and Socioeconomic Status:a Study of 47,160 Patients fromthe National Cancer Data Base

Robert E. Bristowa, Matthew A. Powellb, Noor Al-Hammadic, Ling Chenc,J. Phillip Millerc, Phillip Y. Rolandd, David G. Mutchb, William A. Clibye

aDivision of Gynecologic Oncology, Department of Obstetrics and GynecologyUniversity of California, Irvine School of Medicine

bDivision of Gynecologic Oncology, Department of Obstetrics and GynecologycDepartment of Biostatistics

Washington University in St. Louis School of MedicinedGynecologic Oncology, Department of Gynecology and Obstetrics

Saint Francis Francis Hospital and Medical CentereDivision of Gynecologic Surgery, Department of Obstetrics and Gynecology

Mayo Clinic

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Adherence to NCCN GuidelinesRace

35.6%

43.9%

51.3%

61.5%56.4%

65.6%

*p<0.0001* * *

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Adherence to NCCN GuidelinesPayer

* *p<0.0001**

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5-year Overall SurvivalAdherent White 41.4%Non-adherent White 37.8%Adherent African-American 33.3%Non-adherent African-American 22.5%p<0.0001

N=47,160

Adherent/Non-Adherent Care by Race

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Outreach and EducationPublic Community

- Education and Awareness

- Virtual support network

Resource for Professionals

- Education and Awareness

- Expedited referral system

- Partnering in patient care

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Thank you!