ovarian

Question 1

what is the lifetime risk of developing ovarian cancer with a BRCA1 or BRCA2 mutation

Answer 1

BRCA1 - 40-60%
BRCA2 - 10-30%

Question 2

What is the histological classification of ovarian cancer

What is the commonest histological type

Answer 2

Epithelial (90%)
Low grade serous papillary, endometrioid, clear cell, mucinous & transitional cell
High grade serous , endometrioid, carcinosarcoma, undifferentiated, mixed epithelial

Non-epithelial (10%) - sex cord stromal tumour (Granulosa cell tumours) & malignant germ cell tumour

High grade serous commonest

Question 3

What is typically the nature of ovarian mucinous cystadenomas

Answer 3

Typically they are metastases from the GI tract
Primary ovarian mucinous carcinomas do not present with gross pseudomyxoma peritonei

Question 4

What mutation is commonly present in ovarian mucinous tumours

Answer 4

K-ras in 75%

Question 5

What mutation is most commonly present in high grade serous ovarian carcinoma

Answer 5

p53, and 15% have germline mutations in BRCA1-2

Question 6

What is screened for in all high grade ovarian cancers

Answer 6

BRCA1, BRCA2 & HNPCC

Question 7

How should a new ovarian cancer be investigated

Answer 7

Bloods - Ca125, CEA, HCG & LDH - consider germ cell tumour
Imaging - USS, CT staging
Biopsy - germline and somatic genetics - p53, BRCA, MMR

Question 8

how is the Relative Malignancy Index calculated

Answer 8

Ca125 x menopausal status x USS score

Where pre-MP = 1 and post-MP = 3

0 features on USS = score 0
1 feature on USS = score 1
≥2 features on USS = score 3

Features on USS (5):
Solid components
Multilocular cysts
Bilateral lesions
Ascites
Intra-abdominal lesions

> 250 - 80% chance of ovarian malignancy - refer
25-250 - 20% risk
<25 - <3% risk

Question 9

how is a stage 1 ovarian cancer defined

Answer 9

disease confined to the ovary
1A - one ovary
1B - bilateral ovaries
1C - one or both ovaries with either disease on the surface or ruptured capsule or tumour cells in ascites or peritoneal washings

Question 10

How is a stage 2 ovarian cancer defined

Answer 10

Disease confined to pelvis
2A - extension to uterus or fallopian tubes
2B - extension to other pelvic organs

Question 11

How is stage 3 ovarian cancer defined

Answer 11

Abdominal extension or lymph node involvement
3A1 - retroperitoneal nodes
3A2 - microscopic peritoneal met

3B - macroscopic peritoneal met <2cm, including extension to capsule of the liver or spleen

3C - peritoneal met >2cm, including parenchymal (non capsule) extension to the liver or spleen

Question 12

How is a stage 4 ovarian cancer defined and classified

Answer 12

Distant mets

4A - pleural effusion with positive cytology

4B - liver or spleen parenchymal mets, inguinal or extra-abdominal nodes

Question 13

What is the aim of initial debulking surgery for ovarian cancer

Answer 13

Surgical staging
No residual macroscopic disease

Question 14

When is adjuvant chemotherapy indicated for ovarian cancer

What adjuvant treatment regimen is advised

Answer 14

All stage 2 and above (disease on uterus /tubes, or other pelvic organs)
Any stage of high grade serous or high grade endometrioid
Clear cell carcinoma ≥stage 1C2 (capsule rupture before surgery or disease on ovarian surface)
Mucinous ≥stage 1B (bilateral ovaries / tubes affected)

Advise carboplatin & paclitaxel x6 (or carboplatin x6), but can accept x3 unless HGSOC or HG-EC or stage ≥1C

Question 15

When is adjuvant treatment after surgery for ovarian cancer not indicated

Answer 15

stage 1A LGSOC or Low grade endometrioid
Stage 1A-B mucinous

more than this, consider adjuvant treatment

Question 16

What is the response rate to first line carbo/taxol for ovarian cancer, and outcome
What is the benefit

Answer 16

70-80% RR
50% will achieve complete remission

7% survival benefit to adjuvant ChT
ICON1 and Action trials - 9% survival benefit to 6x single agent carboplatin in adjuvant setting

Question 17

What is the adjuvant treatment regimen for ovarian cancer

Answer 17

Carboplatin (AUC5-6) +/- Paclitaxel (175mg/m2) (or carbo/caelyx or docetaxel)
+ 18x Bevacizumab 7.5mg/kg if Stage III (sub-optimally debulked) or Stage IV (dependent on paclitaxel)

stage III-IV - 6 cycles
stage I-II - 3 cycles minimum, with 6 for HGSOC / HG epithelioid

Question 18

When is neoadjuvant chemotherapy indicated for ovarian cancer

Answer 18

Primary surgery preferred if complete resection can be achieved

But if not fit or unresectable tumour, give 3 cycles of carboplatin/paclitaxel Neo-adjuvantly, and 3 cycles adjuvantly

Bevacizumab can be added if stage 3B or above prior to NA treatment

Question 19

When is bevacizumab indicated in adjuvant setting in ovarian cancer
What was the benefit

Answer 19

stage III with residual disease (>1cm), or stage 4
x18 cycles
Given with carboplatin and paclitaxel (must include paclitaxel), and for up to 18 cycles as monotherapy

ICON 7 trial - for stage 4, inoperable or stage 3 with residual disease - 5mth increase in OS

Question 20

What maintenance treatment is given for ovarian cancer following adjuvant chemotherapy

Answer 20

PARP inhibitor

Niraparib - as monotherapy for stage 3 or 4 ovarian cancer, independent of BRCA mutation and who have responded to first line Pt-based chemotherapy
Given for 3yrs or until disease progression
Prima trial - longer PFS - 13.8mths vs 8.2mths, but better response in HR deficient population - 21.9mths vs 10.4mths

Olaparib - BRCA mut only, stage 3-4 ovarian cancer that has responded to first line Pt-based ChT
Given for 2yrs or until disease progression
PFS 56mths vs 13.8mths - SOLO1 trial

Question 21

When is bevacizumab contraindicated
What are the SE

Answer 21

Serosal disease or those not receiving paclitaxel
SE: htn, GI bleed, perforation, poor wound healing, proteinuria

Question 22

How is proteinuria on bevacizumab managed

Answer 22

G1 = 1-2+ or <1g in 24 hr -> continue bev & urine dip monitoring
G2 = 3+ -> continue bev & 24hr collection before each cycle
If <2g – continue bev;
If >2g – withhold bev until rpt 24hr <2g

Question 23

What is the indication for olaparib and bevacizumab given in combination
What was the benefit and based on what trial

Answer 23

Stage 3 or 4 high grade ovarian cancer, in response to first line Pt-based chemotherapy and with HR-deficiency (BRCA mut or genomic instability)
Paola-1 trial - ITT population, PFS 22mths vs 16.6mths

Question 24

When are olaparib, bevacizumab and niraparib indicated

Answer 24

Olaparib is approved for us in BRCA1/2 mutated tumours, olaparib/bev in HRD-positive tumours and niraparib regardless of biomarker status of the tumour.

Question 25

What must be monitored when starting niraparib
What is the long term risk

Answer 25

Thrombocytopenia (weekly monitoring for niraparib for 4wks)
Htn (weekly monitoring for niraparib for 8wks)

Risk of myelodysplasia or AML - 1-2%

Question 26

What mutation is required to give olaparib as maintenance monotherapy for ovarian cancer

Answer 26

BRCA mut, and following response to first line Pt-based ChT

Question 27

What is the relapse rate for ovarian cancer with stage 3-4 disease
What guides future management
What is the threshold to treat

Answer 27

70%
Mx guided by disease free interval

Progression on treatment or within 1mth - Pt-refractory disease
Progression within 6mths - Pt-resistant disease
Progression >6mths - Pt-sensitive disease

Start treatment when pt symptomatic of disease or large volume relapse

Question 28

How is a recurrence of ovarian cancer best treated (Pt-sensitive)

Answer 28

Surgical resection if amenable
Systemic treatment - Pt based or not based on disease free interval (carboplatin / liposomal doxorubicin)

Maintenance treatment:
- PARP-inhibitor if not used previously. Niraparib can be used independent of BRCA/HRD status
- bevacizumab for Pt-sensitive recurrent disease with carboplatin/paclotaxel or gemcitabine, or with paclitaxel / caelyx / topotecan if no more than 2 previous lines of therapy

Letrozole if ER+

Question 29

What is the advantage of carbo/caelyx over paclitaxel in the relapse setting

Answer 29

non-inferior to carbo/taxol. Less hypersensitivity, alopecia, neuropathy & arthralgia

Question 30

How is a recurrence of ovarian cancer best treated (Pt-resistant)

Answer 30

weekly or 3wkly paclitaxel
caelyx
topotecan
gemcitabine

tamoxifen - 10% response rate

overall response rate approx 15% with PFS 3-4mths
Survival typically <12mths

Question 31

How is small cell carcinoma of the ovary hypercalcaemic type treated

Answer 31

Stage I-II - surgery and adjuvant chemotherapy and radiotherapy
Stage III-IV - NACT if debulking not feasible, surgery and adjuvant chemotherapy and radiotherapy

Question 32

What tumour marker is not expressed by dygerminomas

Answer 32

Equivalent of seminoma in males - does not express AFP

Question 33

How is a dysgerminoma or yolk sac ovarian tumour treated adjuvantly

Answer 33

Dysgerminoma or yolk sac tumour
Stage 1A-1C - no adjuvant tx
Stage II-IV - BEP or EP 3-4 cycles

Question 34

How is a immature teratoma ovarian tumour treated adjuvantly

Answer 34

Immature teratoma
Stage 1A Grade 1 - no adjuvant tx
Stage >1A Grade 2-3 - 3-4 cycles adjuvant BEP

Question 35

What tumor marker is used for sex cord stromal ovarian tumours
What is the adjuvant treatment

Answer 35

serum inhibin
If stage 1c or above - BEP, EP if >40yrs or lung disease, or carboplatin, paclitaxel, or Pt-agent alone

Question 36

What is the risk of ovarian cancer in someone with Lynch syndrome

Answer 36

3-14%