1. Update on Ovarian Cancer
Robert E. Bristow, MD, MBA
Professor and Director
Division of Gynecologic Oncology
University of California, Irvine – Medical Center

2. 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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3. Gynecologic Oncology
Faculty
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4. 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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5. Screening, Early Detection, Cancer Survivorship
Ann’s Clinic
Screening, Early Detection, Cancer Survivorship
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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6. 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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7. Radical Surgery for Ovarian Cancer
Sigmoid Tumor
Left Ovary
Right Ovary
Uterus
Bladder Tumor
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8. Radical Surgery for Ovarian Cancer
Uterus
Bladder Tumor
Cervix
Distal Sigmoid
Culdesac Tumor
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9. Radical Surgery for Ovarian Cancer
Rectosigmoid
Colon
Vaginal Cuff
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10. 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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11. Armstrong DK et al. NEJM 2006; 354:34.
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12. PFS: 18.3 vs 23.8 months OS: 49.7 vs 66.9 months
Armstrong DK et al. NEJM 2006; 354: 34.
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13. The ‘Evolution’ of Treatment for
Advanced Ovarian Cancer and Effect on Survival
IP Rx
Alkeran
Cisplatin
Paclitaxel
(Optimal)
Surgical & Chemotherapy Improvements
(Suboptimal)
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14. Discover ▪ Teach ▪ Heal

15. IP Therapy
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16. IP Therapy
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17. IP Therapy
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18. IP Therapy
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19. Primary Cytoreductive Surgery Contemporary Survival Outcomes
Study Chemotherapy Residual Median Survival
GOG152 IV-CDDP/IV-Taxol >1cm months
GOG172 IV-CDDP/IV-Taxol <1cm months
IP-CDDP/IV+IP-Taxol <1cm months
0.1–1.0cm months
no gross months
0.1–1.0cm months
no gross 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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20. Hyperthermia and Neoplasia
Heat is…
 Directly cytotoxic to cancer cells
- disrupts microtubule system
- induces primary protein damage
- promotes vascular stasis
 Synergistic with some chemotherapy agents
Knox 1991, Stellar 1998
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21. HIPEC Schematic
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22. HIPEC Techniques  Open (colisuem)  Closed Discover ▪ Teach ▪ Heal

23. Role of HIPEC in Ovarian Cancer
 Retrospective study design ( )
 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
Melis A et al. Bull Cancer 2011, doi
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24. Burger RA et al. NEJM 2011; 365: 2473.
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25. PFS: +3.8 month maintenance Rx OS: no significant effect
Burger RA et al. NEJM 2011; 365: 2473.
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26. Fertility Preservation
• Ovarian cancer
- conservative surgery
- young patients
- early stage disease, atypical tumor types
- chemotherapy with ovarian suppression
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27. Robotic Surgery ● daVinci surgical platform Advantages
- patient-side robot
- vision cart
- robotic master console
Advantages
Improved visualization
Finer instrument control and dexterity
Ergonomic design
Autonomous surgical environment
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28. da Vinci® – Robotic Surgery Technology
Script:
“So what makes da Vinci Surgery different from conventional open surgery and laparoscopy?
The da Vinci System’s seamless integration of …Intuitive motion, 3D high definition (HD) visualization and fully articulating instruments (called EndoWrist Instruments)…
provides surgeons with unparalleled precision, dexterity and control formerly achievable only in open surgery. These enabling features allow surgeons to perform complex surgery using a minimally invasive approach, with even more precision, dexterity and control than with an open approach -- thus improving patient outcomes and satisfaction.
Comparison of lap vs. da Vinci:
“Conventional laparoscopy has had limited adoption for complex procedures due to its technological limitations, not a deficiency in surgeon capabilities: Here is how da Vinci addresses and overcomes these limitations:
Intuitive® Motion: “With laparoscopic surgery, the surgeon had to learn to overcome the fulcrum effect, where if the surgeon moved his/her hand to the right, the instrument went to the left. da Vinci maintains a corresponding eye-hand instrument tip alignment, allowing for intuitive instrument control, which helps to replicate the experience of open surgery. The surgeon’s hand movements are scaled, filtered and seamlessly translated to the robotic arms and instruments at the patient’s side.”
3D HD Vision: “With conventional laparoscopic visualization on a standard video monitor, there was no depth perception available, which made complex suturing and dissection difficult. The da Vinci System’s three-dimensional, high definition vision with up to 10x magnification offers surgeons an immersive view of the operative field superior to any other surgical approach, including traditional open surgery and laparoscopy.
EndoWrist® Instrumentation: “With conventional laparoscopy, the surgeon lost the natural dexterity of his/her hand and wrist because it was replaced by straight, rigid instruments. EndoWrist Instruments are designed to provide surgeons with natural dexterity and a range of motion far greater than even the human hand. EndoWrist instruments come in a wide array of tips designed to facilitate procedures ranging from mitral valve repair to hysterectomy. These multi-use instruments are available in 8mm and 5mm diameters.”
Dual Console Capability: “An optional second console with the da Vinci® Si™ system allows an additional surgeon to provide an assist, and facilitates teaching and proctoring. By emulating the teaching environment of open surgery, dual console functionality maximizes the efficiency and effectiveness of da Vinci training for new surgeons.”
“Bottom line: patients can now benefit from a minimally invasive option for many complex procedures. Now, let me show you some features of the new da Vinci Si system that distinguish it from our previous two generations of da Vinci systems: The Standard and the S.”
*Note: Magnification varies as a function of distance of scope from tissue.
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29. Research and Discovery
Clinical Trials
• Ovarian cancer
- intraperitoneal chemotherapy / HIPEC
- molecular profiling
- quality of life / cancer survivorship
- developmental therapeutics / biologic agents
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30. Research and Discovery QOH Ovarian Cancer Research Laboratory
• 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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31. 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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32. Modern Approach to Cancer Therapeutics
Research and Discovery
Modern Approach to Cancer Therapeutics
Pathways Analysis
Patient Metabolism
Mutations
The contemporary approach to guiding the choice of therapeutics, and even drug development, is based largely on molecular targeting. Comprehensive pathway analysis, mutational status, up and down gene regulation, and patient metabolism are all critical components of personalized medicine. Designing therapeutics with these molecular targets in mind will ultimately increase drug efficacy in select patient populations as well as reduce the cost of drug development.
Genes Downregulated
Genes Upregulated
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33. OVA1  Qualitative serum test – 5 immunoassays
- Apolipoprotein A - Transthyretin
- 2 Microglobulin - Transferrin
- CA125 II
 Single numerical result:
 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 Risk
Premenopausal < ≥5.0
Postmenopausal < ≥4.4
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34. Preoperative Assessment
OVA1
Sensitivity vs CA125
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%
Overall Performance
Performance
Preoperative Assessment
Assessment + OVA1
Sensitivity % 75 96
Specificity % 79 35
NPV % 87 95
PPV % 62 40
Ueland F. et al. Int Gyn Cancer Soc Annual Meeting, 2010, Prague.
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35. Disparities in Epithelial Ovarian Cancer
Quality of Care and Survival According to
Race and Socioeconomic Status:
a Study of 47,160 Patients from
the 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 Gynecology
University of California, Irvine School of Medicine
bDivision of Gynecologic Oncology, Department of Obstetrics and Gynecology
cDepartment of Biostatistics
Washington University in St. Louis School of Medicine
dGynecologic Oncology, Department of Gynecology and Obstetrics
Saint Francis Francis Hospital and Medical Center
eDivision of Gynecologic Surgery, Department of Obstetrics and Gynecology
Mayo Clinic
Good morning, on behalf of my co-authors and the SGO Quality and Outcomes Committee, I would like to thank you Dr, McMeekin, Dr. Curtin, members of the program committee, and members and guests of the Society for the opportunity to present our research on disparities in ovarian cancer care and survival according to race and socioeconomic status.
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36. Adherence to NCCN Guidelines
Race
65.6%
61.5%
56.4%
51.3%
43.9%
The distribution of subjects according to the different components of care revealed that African American ovarian cancer patients were significantly less likely to receive proper surgery and chemotherapy compared to White patients. Overall, African American patients received NCCN guideline therapy in just 36% of cases, compared to 44% of White patients.
35.6% *
*p<0.0001 * *
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37. Adherence to NCCN Guidelines
Payer
Unadjusted for other factors, the distribution of subjects by elements of care stratified by payer status revealed that patients with Medicare payer status were less likely to receive guideline care due to the higher proportion of elderly patients in this subset. These data also show that patients with Medicaid and those who were Not Insured were significantly less likely to receive proper surgery and overall care compared to patients with Private insurance or Managed Care. * * *
*p<0.0001
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38. Adherent/Non-Adherent Care by Race
5-year Overall Survival
Adherent White %
Non-adherent White 37.8%
Adherent African-American 33.3%
Non-adherent African-American 22.5%
p<0.0001
N=47,160
A significant difference was observed in 5-year overall survival stratified by race and NCCN guideline adherent care. As you can see, the 5-year survival for White patients receiving both adherent and non-adherent care were significantly better compared to African American patients in either category. White patients receiving NCCN guideline adherent care survived almost twice as long as African American patients receiving substandard care. The directionality and significance of these trends in survival were unaffected by either facility type or annual ovarian cancer case volume.
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39. Outreach and Education
Public Community
- Education and Awareness
- Virtual support network
Resource for Professionals
- Expedited referral system
- Partnering in patient care
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40. Thank you!
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