Update on Ovarian Cancer
Robert E. Bristow, MD, MBA
Professor and Director
Division of Gynecologic Oncology
University of California, Irvine – Medical Center
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.
Discover ▪ Teach ▪ Heal
Gynecologic Oncology
Faculty
Discover ▪ Teach ▪ Heal
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
Discover ▪ Teach ▪ Heal
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
Discover ▪ Teach ▪ Heal
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
Discover ▪ Teach ▪ Heal
Radical Surgery for Ovarian Cancer
Uterus
Bladder Tumor
Right Ovary
Sigmoid
Tumor
Left Ovary
Discover ▪ Teach ▪ Heal
Radical Surgery for Ovarian Cancer
Uterus
Bladder Tumor
Distal Sigmoid
Cervix
Culdesac Tumor
Discover ▪ Teach ▪ Heal
Radical Surgery for Ovarian Cancer
Vaginal
Cuff
Rectosigmoid
Colon
Discover ▪ Teach ▪ Heal
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
Discover ▪ Teach ▪ Heal
Armstrong DK et al. NEJM 2006; 354:34.
Discover ▪ Teach ▪ Heal
PFS: 18.3 vs 23.8 months
OS: 49.7 vs 66.9 months
Armstrong DK et al. NEJM 2006; 354: 34.
Discover ▪ Teach ▪ Heal
The ‘Evolution’ of Treatment for
Advanced Ovarian Cancer and Effect on Survival
Surgical & Chemotherapy Improvements
66.9
57.4
80
52
(Optimal)
(Optimal)
Months
60
37
24
40
12
(Suboptimal)
14
20
0
1975
Alkeran
1983
1986
Cisplatin
1996
1998
Paclitaxel
2003
2006
IP Rx
Discover ▪ Teach ▪ Heal
Discover ▪ Teach ▪ Heal
IP Therapy
Discover ▪ Teach ▪ Heal
IP Therapy
Discover ▪ Teach ▪ Heal
IP Therapy
Discover ▪ Teach ▪ Heal
IP Therapy
Discover ▪ Teach ▪ Heal
Primary Cytoreductive Surgery
Contemporary Survival Outcomes
Study
Chemotherapy
Residual Median Survival
GOG152
IV-CDDP/IV-Taxol
GOG172
IV-CDDP/IV-Taxol
0.1–1.0cm
<1cm
no gross
39 months
50 months
78 months
IP-CDDP/IV+IP-Taxol
0.1–1.0cm
<1cm
no gross
53 months
67 months
127 months
>1cm
36 months
Rose PG et al. N Eng J Med 2004; 351: 2489.
Armstrong DK et al. N Eng J Med 2006; 354: 34.
Discover ▪ Teach ▪ Heal
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
Discover ▪ Teach ▪ Heal
HIPEC Schematic
Discover ▪ Teach ▪ Heal
HIPEC Techniques
 Open (colisuem)
 Closed
Discover ▪ Teach ▪ Heal
Role of HIPEC in Ovarian Cancer
 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
Melis A et al. Bull Cancer 2011, doi 21659062.
Discover ▪ Teach ▪ Heal
Burger RA et al. NEJM 2011; 365: 2473.
Discover ▪ Teach ▪ Heal
PFS: +3.8 month maintenance Rx
OS: no significant effect
Burger RA et al. NEJM 2011; 365: 2473.
Discover ▪ Teach ▪ Heal
Fertility Preservation
• Ovarian cancer
- conservative surgery
- young patients
- early stage disease, atypical tumor types
- chemotherapy with ovarian suppression
Discover ▪ Teach ▪ Heal
Robotic Surgery
● daVinci surgical platform
- patient-side robot
- vision cart
- robotic master console
Advantages
Improved visualization
Finer instrument control and dexterity
Ergonomic design
Autonomous surgical environment
Discover ▪ Teach ▪ Heal
da Vinci® – Robotic Surgery Technology
Discover ▪ Teach ▪ Heal
Research and Discovery
Clinical Trials
• Ovarian cancer
- intraperitoneal chemotherapy / HIPEC
- molecular profiling
- quality of life / cancer survivorship
- developmental therapeutics / biologic agents
Discover ▪ Teach ▪ Heal
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
Discover ▪ Teach ▪ Heal
Research and Discovery
• Surgical techniques
• Advanced imaging techniques / onco-imaging
• Clinical trials of new chemotherapeutic agents
• Biological therapies
• Public health applications
Discover ▪ Teach ▪ Heal
Research and Discovery
Modern Approach to Cancer Therapeutics
Pathways
Analysis
Patient
Metabolism
Genes
Downregulated
Mutations
Genes
Upregulated
Discover ▪ Teach ▪ Heal
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
Premenopausal
Postmenopausal
Low Risk
<5.0
<4.4
High Risk
≥5.0
≥4.4
Discover ▪ Teach ▪ Heal
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.
Discover ▪ Teach ▪ Heal
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
Discover ▪ Teach ▪ Heal
Adherence to NCCN Guidelines
Race
65.6%
61.5%
56.4%
51.3%
43.9%
35.6%
*
*
*
*p<0.0001
Discover ▪ Teach ▪ Heal
Adherence to NCCN Guidelines
Payer
*
*
*
*p<0.0001
Discover ▪ Teach ▪ Heal
Adherent/Non-Adherent Care by Race
5-year Overall Survival
N=47,160
Adherent White
Non-adherent White
Adherent African-American
Non-adherent African-American
p<0.0001
41.4%
37.8%
33.3%
22.5%
Discover ▪ Teach ▪ Heal
Outreach and Education
Public Community
- Education and Awareness
- Virtual support network
Resource for Professionals
- Education and Awareness
- Expedited referral system
- Partnering in patient care
Discover ▪ Teach ▪ Heal
Thank you!
Discover ▪ Teach ▪ Heal