Ovarian Cancer 101: Breakout session for recently diagnosed ovarian cancer patients

1. Ovarian Cancer 101: Breakout session for recently diagnosed ovarian cancer patients Christopher Morse, MD Fellow, Gynecologic oncology UW MEDICINE CONFIDENTIAL – DO NOT DISTRIBUTE

2. Overview • Introduction to ovarian cancer • Diagnosis and treatment • Surgery and chemotherapy • Surveillance • Genetic testing • Quality of life and managing effects of treatment • Open Q&A CONFIDENTIAL – DO NOT DISTRIBUTE

3. Ovarian Cancer - Introduction • In 2019 there will be an estimated 22,530 new cases of ovarian cancer diagnosed.  • Ovary, fallopian tube, primary peritoneal • Second most common GYN cancer (uterine more common) • Most common cause of GYN cancer related death and ovarian cancer is the 5th leading cause of cancer related death among females American Cancer Society 2019 CONFIDENTIAL – DO NOT DISTRIBUTE

4. Ovarian cancer - Survivorship • While many patients (75%) be diagnosed with an advanced stage (III or IV), after surgery and chemotherapy most (80%) will enter remission.  • In 2016, there were an estimated 230,000 ovarian cancer survivors living in the US • Patients with ovarian cancer are unique: • Undergo major abdominal surgery • Chemotherapy • Maintenace therapy • Many unique issues that ovarian cancer survivors face that impact QOL CONFIDENTIAL – DO NOT DISTRIBUTE

5. Ovarian cancer - Risk factors • The lifetime risk of developing ovarian cancer is 1.3% • 1:80 women will be diagnosed with ovarian cancer • The average age of diagnosis is 63, younger in women with hereditary cancers • Risk factors:  • Age, family history, PCOS, infertility, PID, endometriosis, cigarette smoking, environment and location • Protective factors: • Prior pregnancy, history of breastfeeding, OCP use, tubal ligation CONFIDENTIAL – DO NOT DISTRIBUTE

6. Ovarian Cancer – diagnosis • Presenting symptoms are common and can be overlooked • Women with ovarian cancer experience frequent symptoms – 20 to 30x month • Bloating (7.4x) • Increased abdominal size (3.6x) • Urinary symptoms (2.5x) • Ultrasound and/or CT scan • Pelvic mass • Ascites • Blood work • CA-125, HE4 Goff 2004 CONFIDENTIAL – DO NOT DISTRIBUTE

7. Ovarian Cancer – subtypes • The majority (95%) of ovarian cancers originate from the surface epithelium of the ovary or from the fallopian tube  • Serous histology ~75% • Other types are less common • Sex cord stromal tumors • Germ cell tumors • Rare subtypes Image from UpToDate 2019.  CONFIDENTIAL – DO NOT DISTRIBUTE

8. Ovarian Cancer – FIGO staging CONFIDENTIAL – DO NOT DISTRIBUTE

9. Ovarian Cancer – initial treatment • Evaluation by a Gynecologic Oncologist • Approach 1: surgery -> chemotherapy • Traditional approach to ovarian cancer treatment • For patients who are surgical candidates with resectable disease • Approach 2: neoadjuvant chemotherapy -> surgery -> chemotherapy • For patients that are not surgical candidates (medical comorbidities) • For patients with disease distribution that is not resectable • Surgery: removal of uterus, cervix, fallopian tubes, ovaries, staging, debulking • Several large randomized trials have compared these approaches and demonstrated that neoadjuvant chemotherapy is not worse than doing surgery first Vergote 2010; Kehoe 2015 CONFIDENTIAL – DO NOT DISTRIBUTE

10. Ovarian Cancer – chemotherapy • Chemotherapy – every 21 days for six cycles • Carboplatin – inhibits DNA synthesis • Side effects: low counts (esp platelets), cleared by kidneys • Paclitaxel – derived from the bark of the Pacific yew tree, prevents cancers cells from dividing • Side effects: low counts (esp WBC), neuropathy, hair loss, cleared by liver • Both: nausea/vomiting, fatigue • Alternative delivery/dosing strategies  • Dose-dense paclitaxel • Weekly low-dose carbo/paclitaxel • Intraperitoneal chemotherapy Pacific Yew Tree CONFIDENTIAL – DO NOT DISTRIBUTE

11. Surveillance and monitoring - overview • Following aggressive surgery and chemotherapy most patients (80%) will enter remission.  • Recommended to have close follow up with Gynecologic Oncologist. SGO Post-treatment surveillance guidelines 2017. CONFIDENTIAL – DO NOT DISTRIBUTE

12. Surveillance and monitoring – tumor markers • CA-125 – a protein in the blood that is commonly elevated in ovarian cancer • Most commonly followed tumor marker • Approximately 1 of 4 patients will have normal CA-125 at diagnosis • Non-specific – many things can elevate • HE4 – an alternative biomarker, may be elevated in patients with normal CA-125 • May be elevated in endometrioid subtype Structure of CA-125 CONFIDENTIAL – DO NOT DISTRIBUTE

13. Surveillance and monitoring – tumor markers • Do you have to follow CA-125?  • 529 women with ovarian cancer randomized to exam and CA-125 every 3 months • Patients and investigators blinded to CA-125 results • Once CA-125 >2x upper limit of normal: • Early treatment – chemotherapy started with CA-125 elevation • Delayed treatment - chemotherapy started with symptoms • There was no difference in overall survival between the two groups • 2nd line chemotherapy was started on average 5 months earlier in early treatment arm • To follow (or not) is an individual decision to make with your Gynecologic Oncologist.  Rustin 2011, EORTC 55955 CONFIDENTIAL – DO NOT DISTRIBUTE

14. Surveillance and monitoring – imaging • Do I need a CT scan on a regular basis?  • There is no role for routine imaging in ovarian cancer surveillance • Most providers do not routinely perform imaging studies in asymptomatic ovarian cancer patients in surveillance • However, with onset of new symptoms or elevated tumor markers • CT or PET CT is recommended CT scan of a patient with ovary cancer CONFIDENTIAL – DO NOT DISTRIBUTE

15. Genetic testing • All patients diagnosed with ovarian cancer should undergo genetic testing for hereditary breast and ovarian cancer (HBOC) genes • 15-20% of patients will have a mutation • germline (in all the cells) • somatic (in the tumor) • It is important to undergo testing for many reasons:  • Counseling and genetic testing of other family members • Maintenance strategies after primary chemotherapy (PARP inhibitors) • Clinical trial eligibility • Future treatment options • Don’t wait, ask your provider for a referral to a genetic counselor CONFIDENTIAL – DO NOT DISTRIBUTE

16. Quality of life – during and after treatment • How does treatment affect my quality of life (QOL)?  • Patients on two GOG protocols (#152 and 172) completed QOL surveys during and after treatment.  • Functional Assessment of Cancer Therapy – Ovarian (FACT-O) • Physical, functional, social, emotional well being • Scores lower in physical, functional and emotional well being • Higher scores in social well being • May be reflective of increased social support during/after diagnosis and treatment • Baseline physical well-being may be associated with improved overall survival CONFIDENTIAL – DO NOT DISTRIBUTE Wenzel 2005, von Gruenigen 2010, von Gruenigen 2012

17. Managing the effects of treatment • Neurologic and cognitive • Fatigue and energy • Gastrointestinal toxicity • Loss of fertility and sexual dysfunction • Menopause and hormone therapy • Psychiatric/psychosocial issues • Living a healthy life style CONFIDENTIAL – DO NOT DISTRIBUTE

18. Neurologic and cognitive effects • Chemotherapy-induced peripheral neuropathy (CIPN) can affect to 50% of patients • Numbness/tingling, sensitive to touch, burning, decreased hot/cold sensation • During treatment • Modify dosing and chemotherapy agent • Gabapentin – decrease in patient reported CIPN • Cold mitts and socks – limited data but intriguing • Other – multivitamins, glutamic acid, glutathione • More limited and mixed outcomes • After treatment • Physical therapy • Gabapentin, duloxetine, glutamine • Acupuncture CONFIDENTIAL – DO NOT DISTRIBUTE

19. Neurologic and cognitive effects • Cognitive changes • GOG prospectively studied 231 women with ovarian cancer undergoing primary treatment, assessed cognitive impairment • After 4th cycle chemo – 25.2%  • After 6th cycle chemo – 21.1% • 6 month follow up – 17.8% • A subset of patients had evidence of cognitive decline during chemotherapy but was limited to no more than one domain • Hard to separate the effects of treatment from the underlying effects of the disease itself Hess 2015 CONFIDENTIAL – DO NOT DISTRIBUTE

20. Fatigue • Some fatigue is almost universal during treatment • Fatigue may persist for 6-12 months after chemotherapy • Among survivors of ovarian cancer, 22% experience chronic fatigue. • Fatigue can have a negative impact of emotional functioning and QOL • Small studies support a benefit of physical activity behavioral interventions to combat fatigue Liavaag 2007, Donnelly 2011 CONFIDENTIAL – DO NOT DISTRIBUTE

21. Gastrointestinal effects • Many women had gastrointestinal (GI) symptoms at time of diagnosis • Persistent worry that new GI symptoms related to recurrence • GI symptoms may be a result of complications from surgery (adhesions), related to disease recurrence, or from unrelated medical conditions (IBS) • Should always be reported to treatment team and investigated • Pain and abdominal symptoms associated with lower QOL, emotional status, and more fear of recurrence in ovarian cancer survivors Mirabeau-Beale 2009 CONFIDENTIAL – DO NOT DISTRIBUTE

22. Gynecologic effects • Fertility – 15% of ovarian cancer pts will be <40 yo at diagnosis.  • Fertility loss is an important part of counseling at diagnosis and should be addressed with referral to fertility specialist as soon as possible.  • Sexual dysfunction - 60% of ovarian cancer survivors report that cancer has affected their sexual life in a negative way • Decrease interest in sex and decreased sexual activity • Treatment: vulvovaginal atrophy, addressing dyspareunia, loss of libido, partner and relationship factors  - sexual health programs for cancer survivors • Session 4, Saturday afternoon breakout session • Sexual Health after Cancer (SakethGuntupalli, Colorado) CONFIDENTIAL – DO NOT DISTRIBUTE

23. Gynecologic effects • Menopause • Average age of ovarian cancer diagnosis – early 60s.  • Many patients are postmenopausal will not experience significant side effects • Symptoms: hot flushes, mood changes, sleep disturbances, vaginal atrophy • Hormone replacement therapy (HRT) • Vulvovaginal atrophy – topical estrogen, low systemic absorption • May consider systemic treatment with estrogen in select women • No conclusive data that HRT negatively affects survival or recurrence CONFIDENTIAL – DO NOT DISTRIBUTE

24. Psychiatric effects • Depression • Up to 15% of ovarian cancer survivors meet criteria for depression • Symptoms of depression are associated with sleep disorders • Anxiety - may have an even greater impact on QOL than depression • Fear of recurrence – affects more than half of survivors • Preoccupation with CA-125 value  - anxiety about CA-125 is common • Guilt and cancer-related distress • Delay in diagnosis, familial guilt (HBOC), survivors' guilt CONFIDENTIAL – DO NOT DISTRIBUTE

25. Living a healthy lifestyle • Living healthy • Obesity is a risk factor for cancer (breast, endometrial, colon) • American Cancer Society Recommendations • Maintain a healthy weight, attempt weight loss if overweight/obese • Engage in 30 minute of moderate activity 5x weekly • Consume a healthy diet with 5 or more servings of fruits or vegetables daily • Limit alcohol intake • No more than 1 drink/day for women, 2/day for men • Clinical trial opportunity • Currently enrolling patients in a study of Moderate Exercise in Ovarian Cancer Survivors (University of Washington, PI: Pennington) CONFIDENTIAL – DO NOT DISTRIBUTE

26. Patient Resources • SGO.org • Survivorship toolkit for gynecologic cancers • OCRAhope.org • Patient resources: general information, support groups, financial assistance, end of life, advocacy • American Cancer Society • Nat'l Cancer Survivorship Resource Center • Survivorship support groups through your local cancer center CONFIDENTIAL – DO NOT DISTRIBUTE

27. CONFIDENTIAL – DO NOT DISTRIBUTE

28. Questions • What side effects from treatment (surgery or chemotherapy) did you find most difficult?  • What did you find most effective to treat or cope with these side effects?  • When during your treatment did you discuss the role of genetic testing?  • How has ovarian cancer affected your well-being?  • Physical, functional, emotional, and social CONFIDENTIAL – DO NOT DISTRIBUTE

29. Thank you! CONFIDENTIAL – DO NOT DISTRIBUTE