Lecture 16 - Ovarian Cancer Flashcards
Epidemiology
leading cause of death in US from gynecologic malignancies
minimal improvement over the past 7 decades
Etiology and pathogenesis
exact cause is unknown
“incessant ovulation” theory - women’s risk of developing ovarian cancer is related to # of ovulatory cycles, ovulation results in disruption and repair of epithelial lining of ovaries, repair of lining proposed as one origin of sporadic ovarian cancer
Etiology
germ line mutations responsible for ~5-10% of all ovarian cancers: BRCA1 and 2
5-10% of pts have hereditary non-polyposis colorectal cancer (HNPCC) or other rare genetic syndromes
Risk factors: increased risk
early menarche, late menopause (increased # and/or duration of ovulatory cycles)
increased age, nulliparity, in-vitro fertilization, 2 or more 1st degree relatives with ovarian cancer
genetic factors: BRCA-1, BRCA-2, p53 have increased risk for development of ovarian cancer
lynch II syndrome (HNPCC) - familial predisposition
Risk factors: decreased risk
multiple pregnancies, prolonged use of oral contraceptives, prophylactic oophorectomy (especially if BRCA mutation)
Clinical presentation: “silent killer”
most pts with stage I and II are asymptomatic
advanced disease: ascites, pleural effusion, constipation, small bowel obstruction, N/V - if experienced these sx for 12 or more days out of a month for 2 consecutive months, seek medical attention
Disease progression
disease dissemination invades through the ovarian capsule and throughout the peritoneal cavity
common presenting symptoms is ascites
Initial treatment
goal is cure
surgery + adjuvant chemo is standard approach first line
with relapse any therapy is palliative
Homologous recombination deficiency
50% high-grade serous ovarian carcinomas are homologous recombination deficient
defect in one or more genes involved in homologous repair pathway - includes germline and somatic BRCA pathogenic variants
Treatment overview
+/- neoadjuvant platinum-based chemo –> surgical staging and debulking –> adjuvant platinum-based chemo –> frontline maintenance therapy –> relapse –> recurrence therapy –> maintenance therapy of recurrence
Surgery
debulking surgery generally entails: total abdominal hysterectomy, bilateral salpingo-oophrectomy, omentectomy (fat layer over abdominal organs), pelvic and para-aortic lymph node sampling, paritoneal biopsies, paritoneal washings
Surgical outcomes
after surgery, pts divided into 2 groups: optimally debulked < 1 cm of disease (goal) or sub-optimally debulked > 1 cm of disease remaining (poorer prognosis)
second surgery following chemo is called a second look (not standard of care)
Adjuvant chemotherapy
stage IA or IB grade 1 disease: observation and follow up every 3 mo
all other stages: receive adjuvant chemo
current standard of therapy: paclitaxel and carboplatin given IV every 3 weeks; most pts receive 6 cycles of chemo
cyto-reductive surgery (tumor debulking) followed by adjuvant chemo
Hypersensitivity reactions
GYN/ONC pop is susceptible to these rxns due to chemotherapeutic agents utilized as well as # of cycles of chemo they receive
agents commonly used: paclitaxel, docetaxel, carboplatin, cisplatin all of which cause hypersensitivty rxns
exposures to multiple cycles of chemo increases risk of carboplatin hypersentivity rxns
Type I hypersensitivity
initial contact with agent
MOA: cross linking to mast cells and basophils which trigger release of histamine/other inflammatory mediators
sx: anaphylaxis, itching, rash, chest tightness
