Ovarian Cancer

Question 1

Ovarian Cancer

• Leading cause of death in the US from gynecologic malignancies
• Peak incidence is ~ __ years of age
  – Lifetime risk is 1 in ___

Answer 1

• 65
• 72

Question 2

Etiology and Pathogenesis

exact cause unknown

The “incessant ___ ” theory
– A women’s risk of developing ovarian cancer is related to her ___ of ovulatory cycles
– Ovulation results in disruption and repair of the epithelial lining of the ovaries
– The ___ of the lining is proposed as one origin of sporadic ovarian cancer

Answer 2

• ovulation
• number
• repair

Question 3

Etiology

• Germ line mutations are responsible for ~ 5 - 10% of all ovarian cancers
• Lifetime risk of ovarian cancer in a patient with a ___ mutation is 25 - 45%
• Lifetime risk of ovarian cancer in a patient with a ___ mutation is up to 30%
• 5 to 10% of patients have hereditary non- polyposis colorectal cancer (HNPCC) or other rare genetic syndromes

Answer 3

• BRCA1
• BRCA2

Question 4

Risk Factors

• Early menarche, late menopause
• (increased number and/or duration of ___ cycles)
  – Increased ___
  – Nulliparity
  – ___ fertilization (Use of ovulatory stimulating agent can ↑ the
  number of ovulatory cycles)
  – Two or more first degree relatives with ovarian cancer
• Genetic factors: ___, ___have ↑’d risk for development of ovarian cancer
• Lynch II syndrome (Hereditary nonpolyposis colorectal cancer (HNPCC)

Answer 4

• ovulatory
• age
• in-vitro p53
• BRCA,

Question 5

Decreased Risk

• Multiple ___
• Prolonged use of ___ - > 50% ↓ after 5 years of use
• Prophylactic ___

Answer 5

• pregnancies
• oral
• oophoretomy

Question 6

Clinical Presentation: “Silent Killer”

• Most patients with Stage I and II disease are asymptomatic
• Leads to the unfortunate result of most patients presenting with ___ disease (stage III and IV) - 70%

Answer 6

advanced
- In advanced disease symptoms could include: ascites, pleural effusion, constipation, small bowel obstruction, nausea or vomiting

Question 7

Initial Treatment

Most patients will achieve a clinical
complete remission to initial treatment
* However, 70-90% of patients will recur in the first 3 years

Initial treatment approach:
– Goal is ___
– Surgery + adjuvant chemotherapy is standard approach first line (neoadjuvant?)
– With relapse any therapy is ___

Should have genetic risk evaluation, germline and somatic testing in all patients to help decide ___ therapy; in absence of BRCA mutations, ___ ___ ___ (HRD) may help determine therapy

Answer 7

• cure
• palliative
• maintenance
• homologous recombination deficiency

Question 8

Homologous Recombination Deficiency (HRD)

50% high-grade serous ovarian carcinomas are homologous recombination deficient

• Defect in one or more genes involved in homologous ___ pathway
• Includes germline and somatic ___ pathogenic variants

Answer 8

• repair
• BRCA

Question 9

Treatment Overview

0) ± neoadjuvant platinum-based
chemotherapy
1) Surgical staging and debulking
2) Adjuvant platinum-based chemotherapy
3) Frontline maintenance therapy
4) Relapse
5) Recurrence therapy
6) Maintenance therapy of recurrence

Answer 9

Question 10

Surgery

“Debulking” Surgery generally entails:
* Total abdominal hysterectomy (TAH)
* Bilateral salpingo-oophrectomy (BSO)
* Omentectomy
* Pelvic and para-aortic lymph node sampling
* Peritoneal biopsies
* Peritoneal washings

Answer 10

Question 12

Surgical Outcomes

• Optimally debulked: < 1 cm of disease
• Sub-optimally debulked: > 1 cm of disease remaining

Answer 12

Patients that have a sub-optimally debulked surgery have a poorer prognosis

Question 13

Adjuvant Chemotherapy

Stage IA or IB grade 1 disease
* Observation and follow up every 3 months

All other stages should receive adjuvant chemotherapy. Standard of care:
- ___ and ___

Answer 13

• Paclitaxel
• Carboplatin

Question 15

Adjuvant Chemotherapy

Most patients will receive 6 cycles of
chemotherapy

Carboplatin dosing:
– Elimination of carboplatin closely mirrors GFR

Calvert equation:
* Carboplatin dose = AUC x (GFR + 25)
The AUC is usually __ - __ if given every 3 weeks

Answer 15

5 -7.5

Question 16

Hypersensitivity Reactions

• Agents commonly used are paclitaxel, docetaxel, carboplatin, and cisplatin
• All agents are known culprits to causing hypersensitivity reactions
• Exposure to multiple cycles of chemotherapy (i.e., > 7) ___ risk of carboplatin hypersensitivity reactions

Answer 16

increases

Question 17

Type I Hypersensitivity

___ contact with agent
* Mechanism: Cross linking to mast cells and basophils which trigger release of histamine and other inflammatory mediators
* Symptoms: ___ , itching, rash, chest tightness

Answer 17

• initial
• Anaphylaxis

Question 18

Type IV Hypersensitivity

With ___ exposure to agent
- Mechanism: T-cells recognize antigens (MHC, APC)
* Symptoms: ___ , induration

Answer 18

• repeated
• Erythema

Question 19

Common Chemotherapy Culprits

Allergic to the drug itself
- Carboplatin
- Cisplatin
- Docetaxel
- Paclitaxel
- Rare: Etoposide, topotecan
- NEED ___
- Symptoms ___ after
stopping infusion

Often Infusion Related Reactions
- Paclitaxel – ___ EL
- Doxil - liposome
- Decreasing ___ ___typically resolves symptoms
- Symptoms ___ quickly after
stopping infusion

Answer 19

• DESENSITIZATION
• persist
• cremophor
• infusion rate
• resolve

Question 20

Paclitaxel

• Most manifest as a Type __ reaction
• Most reactions occur within the first few ___ of the infusion with the first or second dose
• Believed to be due to the ___ diluent as opposed to the chemotherapy

Answer 20

• Type I
• minutes
• Cremophor EL

Question 21

Taxane Infusion Reactions

• Likely a result of direct effects on immune cells
• Usually occurs during ___ or ___ exposure

Most common reactions to paclitaxel
- Facial flushing
- Back pain
- Chest or throat tightness

The risk of having a recurrent reaction ___ with repeated exposures

Answer 21

• 1st, 2nd
• decreases

Question 22

Paclitaxel: Ways to Avoid Problems

Standard pre-medications
- ___ , ___ , and ___ 30 minutes prior
- ___ infusion may resolve
symptoms
- Always when administering, should have an ___ kit at bedside

Answer 22

• dexamethasone, diphenhydramine, famotidine
• prolonging
• anaphylactic

Question 23

Carboplatin Hypersensitivity

Hypersensitivity to platinum agents generally develops after ___ cycles of treatment
- Peak incidence of hypersensitivity reactions to carboplatin occurs at a median of __ cycles

Most common symptoms
– Cutaneous symptoms
– Vomiting
– Hypotension

Answer 23

• multiple
• 7

Question 24

Carboplatin

Mechanism could be 2-fold
- Type I: Drug/antigen specific IgE’s that have high binding affinity to receptors on mast cells and basophil
- Type IV: Delayed hypersensitivity reaction occurring when antigen sensitized cells release cytokines after subsequent contact
- ___ exposures (≥ __ cycles of carboplatin) increased risk of hypersensitivity reactions

Answer 24

repeated, 8

Question 25

Maintenance Bevacizumab?

• Bevacizumab recommended in those that received bevacizumab with chemotherapy upfront prior to surgery to continue as monotherapy
• Not recommended in those with ___ mutations

Answer 25

BRCA

Question 26

PARP Inhibitors

MOA: prevents the
PARP protein from repairing damaged DNA in cancer cells

Three agents approved in ovarian cancer:

Answer 26

– Olaparib (Lynparza)
– Rucaparib (Rubraca)
– Niraparib (Zejula)

Question 27

PARP inhibitors

monitoring parameters
- Olaparib: CBC, ___ function
- Niraparib: CBC, __, HR
- Rucaparib: CBC, ___ (if warfarin cant be avoided)

AE
- N/V, fatigue, anemia, neutropenia, thrombocytopenia

Answer 27

• renal
• BP
• INR

Question 28

Metastatic Disease

• Ultimately, 60 - 80% of pts will relapse
• The goal is no longer ___
• Decisions about therapy should include toxicity, regimen, and convenience of administration, and quality of life
• No standard therapy for recurrent disease

Answer 28

• cure

Question 29

Recurrence Definitions

if the pt relapses > 6 months following completion of their initial platinum containing regimen, the patient is “Platinum ___ ”
- May be treated with the ___ chemotherapy regimen again

If the patient relapses < 6 months after
receiving a platinum containing regimen, the patient is considered “Platinum ___ ”
- a ___ regimen is generally chosen

Platinum ___ : (Platinum refractory)
- No response or progression of disease during primary therapy with ___ / ___

Answer 29

• sensitive
• initial
• resistant, salvage
• progressive
• paclitaxel/carboplatin

Question 30

Recurrence Definitions

If the patient is platinum sensitive, re-use ___ / ___ combination

Answer 30

paclitaxel/carboplatin

Question 31

Treatment Regimens

Single agent non-
platinum based if
platinum resistant:

Answer 31