Ovarian Cancer 101 Jessica McAlpine, MD

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Ovarian Cancer 101 Jessica McAlpine, MD

Different types of ovarian cancer: Outline: Ovarian Cancer Presentation, behavior, site of origin Primary treatment: surgery, chemo, +/-radiation Role of genetics empowering decision making Screening (lack of) and PREVENTION! Surveillance: screening for other cancers, treatment effects, interplay of other health issues

Old School. Germ Cell (3%-5%) Sex Cord-Stromal (2%-3%) Secondary (Metastatic) (5%) Epithelial (EOC) (90%) Figure modified from Gartner, L.P. & Hiatt, J.L. eds. In Color Atlas of Histology. 3rd ed. (2000) Lippincott Williams & Wilkins: Philadelphia, PA.

New Era: epithelial ovarian cancer encompasses ~5 distinct diseases Serous Endometrioid Mucinous Clear cell Transitional Undifferentiated Grade 1 3.5% 10% Grade 2 4% Grade 3 70% 10% 2% NOS Grouping reflects epidemiology, germline genetics, somatic genetics, clinical presentation and response to therapy

New Era! The only true ovarian cancers=germ cell and sex cord stromal EOC=primarily non-ovarian HGS: from the FT Clear cell and EM: from endometrioisis Mucinous:? Paratubal cysts Kurman and Shih, 2011

Anatomy 101

HGS: site of origin is the fallopian tube

Does the fallopian tube make sense? Histology of the fallopian tube epithelium is serous The surface area of the fimbriated end of the tube is massive compared the ovary

Evidence: ascending inflammation Increases risk: -PID -Tubal infertility Decreases risk: -Tubal ligation -OCP -Pregnancy

Anatomy: why are symptoms vague? Symptoms frustrating as non-specific : Gastrointestinal Bladder Pelvic

Stage and Grade: what do the mean? Stage basics: I-confined to one or both ovary(ies) II-confined to pelvis III-spread to abdomen (microscopic big or nodes) IV-distant Grade: how abnormal the cells look.aggressive features like high ratio nuclei : cytoplasm, mitoses

Treatment for ovarian cancer Surgery: remove ovaries, tubes, uterus, omentum debulk + =>

Treatment for ovarian cancer Most patients will undergo 6 cycles of outpatient intravenous and/or intraperitoneal chemotherapy Chemotherapy may start before surgery (i.e., for 3-4or even 6 cycles) or after. Most common agents used: carboplatin and paclitaxel every 3-4 weeks IV~3-5 hours to administer=outpatient

Chemotherapy Treatment for ovarian cancer Intraperitoneal chemotherapy (IP) may be combined with IV. Drugs are injected into the abdominal cavity by a catheter attached to a port. Longer infusion. Theory of bathing the cells in drug, higher dose absorbed better survival in some series but weekly taxol and other regimens ~ comparable (?!) It is inserted at staging or interval debulking surgery Side effects (especially nausea) can be more severe than traditional chemotherapy

Intraperitoneal chemotherapy

Side effects of treatment First few days post Rx: fatigue, nausea, bony aches Nausea adjustment medications/options 7-12 days post treatment: more vulnerable to infection, low blood counts/anemia Loss of hair after 1 st or 2 nd cycle Tingling/paresthesias in stocking-glove distribution

Treatment for ovarian cancer Radiation sometimes used primarily for endometrioid and clear cell histologies

Communicate your symptoms! MD needs to listen!

What about family?

Lifetime risk Family history General pop lifetime risk: 1.6% If only one first-degree relative is affected by ovarian cancer: 5% BRCA 1: 40-63% by age 70 Lifetime risk breast cancer 60-80% BRCA 2: 20-27% risk by age 75 Lifetime risk breast cancer 60-80% HNPCC: 10-12% lifetime risk Lifetime risk colorectal cancer 60-80%

Considerations for family members Both HNPCC and BRCA mutations are inherited in an autosomal dominant fashion This means a child who has a parent with a mutation has a 50% chance of inheriting that mutation. A brother, sister, or parent of a person who has a mutation also has a 50% chance of having the same mutation.

Referral to Hereditary Cancer Program Local Hereditary Cancer program-when to refer, who, how.. Family history good but will miss MANY Histology based referral very effective >20% HGS cancers will have BRCA1/2 mutation ANY high grade serous ovarian cancer should be referred for BRCA testing OR ANY clear cell or endometrioid ovarian or endometrial cancer patient where pathology comments on absent MMR proteins should be tested for HNPCC **Now recommends referral on pathology form in a growing number of centers**

What about screening?

Screening 3 large randomized controlled trials have thus far shown no appreciable difference in outcomes with an unacceptable amount of unnecessary surgery (even in high risk women) We recommend to NOT order CA125 levels and/or ultrasounds in the absence of specific symptoms suggesting presence of disease

What can we do? Annual abdominal and pelvic examination (including pelvirectal) Risk reduction with oral contraceptive pill Risk reducing surgery: tubal ligation, salpingectomy, and for BRCA mutation carriers/hnpcc consider BSO at completion of childbearing

Prevention Fallopian tube in situ lesions are precursor to ovarian cancer. Remove the precursor!

Change Surgical Convention ~18% of BC s population of women with ovarian cancer had undergone hysterectomy Hysterectomy and tubal ligation are common WHY NOTE REMOVE THE FALLOPIAN TUBE? Perform salpingectomy with hysterectomy and consider in place of tubal ligation September 2010 Campaign

Projected Outcome Conservatively, up to 40% reduction in ovarian cancer deaths after 20 years Through salpingectomy at time of hysterectomy Through salpingectomy instead of tubal ligation Through risk-reducing BSO in patients with BRCA mutations

Living with ovarian cancer Goal (and truly can be) =curable disease!

Survivorship encompasses the physical, psychological, social, and spiritual domains of individuals with cancer from the time of diagnosis, through treatment, and on

Even for 1 disease the survivorship needs can vary with different QOL considerations over the course of care e.g., along the survivorship continuum Diagnosis and Primary Treatment A. Physical nausea emesis neuropathy nephropathy fatigue hair loss bone health hormonal changes sexual health infertility pain change in bladder or bowel function B. Cognitive memory loss concentration C. Psychosocial anxiety depression fear of recurrence partners/family relationships body image D. Socioeconomic cost of treatment demand of hospital visits consideration of end-oflife financial planning E. Spiritual personal strength & growth Maintenance/ Consolidation Therapy A. Physical cumulative toxicities F. Socioeconomic additional costs and visits Cancer Surveillance/ Observation A. Physical fatigue sequelae of chemotherapy or surgery (i.e., neurotoxicity) B E. as in primary therapy F. Preventive health (re-)initiation of general healthcare guidelines/screening referral to hereditary cancer program fracture risk/bone health Treatment for recurrent or refractory disease A E. as in primary therapy cumulative treatment toxicities Increase hypersensitivity reactions (platinum) End-of-Life Support/Palliation A. Physical Pain Bowel obstruction Pleural effusions Ascites C D. Psychosocial & socioeconomic Advance directives Power of attorney E. Spiritual Peace/resolution; friends/family/self/ God(s) Long-term (>5 years) Survival A. Physical sequelae of treatment - i.e., neurotoxicity -i.e., end organ disease - i.e., secondary cancers B E. as in primary therapy F. Preventive health as in surveillance period + screening for secondary cancers

Regular intervals w/ physical examinations Some reliance on symptoms/changes We DON T tend to do: Surveillance: Routine imaging radiation dose accumulation Routine CA125 no improvement in survival and risk of decreasing the amount of good QOL time

What can we do/what should we ask? What type was my cancer, what was done, what is known about this specific disease now? Family testing and follow-up with action if + Side effects; perhaps we can help? Catch up on general health recommendations! Support and empowerment: Inspire Health, OCC, OCNA, patient and family counseling. New changes/symptoms; maybe we should examine?

Recurrence: not doom and gloom! Chemical vs. Imaging vs. Symptomatic recurrence OR/Surgery for isolated recurrence or very long time since primary disease that is resistant to chemotherapy for bowel obstruction/acute event Chemotherapy for ~ all others-consider clinical trials or molecular targeted therapy? Rarely radiation. Observation or supportive care?

Questions? BCCA 604 877 6000 x 2367 jessica.mcalpine@vch.ca