ovarian Flashcards
what is the lifetime risk of developing ovarian cancer with a BRCA1 or BRCA2 mutation
BRCA1 - 40-60%
BRCA2 - 10-30%
What is the histological classification of ovarian cancer
What is the commonest histological type
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
What is typically the nature of ovarian mucinous cystadenomas
Typically they are metastases from the GI tract
Primary ovarian mucinous carcinomas do not present with gross pseudomyxoma peritonei
What mutation is commonly present in ovarian mucinous tumours
K-ras in 75%
What mutation is most commonly present in high grade serous ovarian carcinoma
p53, and 15% have germline mutations in BRCA1-2
What is screened for in all high grade ovarian cancers
BRCA1, BRCA2 & HNPCC
How should a new ovarian cancer be investigated
Bloods - Ca125, CEA, HCG & LDH - consider germ cell tumour
Imaging - USS, CT staging
Biopsy - germline and somatic genetics - p53, BRCA, MMR
how is the Relative Malignancy Index calculated
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
how is a stage 1 ovarian cancer defined
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
How is a stage 2 ovarian cancer defined
Disease confined to pelvis
2A - extension to uterus or fallopian tubes
2B - extension to other pelvic organs
How is stage 3 ovarian cancer defined
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
How is a stage 4 ovarian cancer defined and classified
Distant mets
4A - pleural effusion with positive cytology
4B - liver or spleen parenchymal mets, inguinal or extra-abdominal nodes
What is the aim of initial debulking surgery for ovarian cancer
Surgical staging
No residual macroscopic disease
When is adjuvant chemotherapy indicated for ovarian cancer
What adjuvant treatment regimen is advised
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
When is adjuvant treatment after surgery for ovarian cancer not indicated
stage 1A LGSOC or Low grade endometrioid
Stage 1A-B mucinous
more than this, consider adjuvant treatment
What is the response rate to first line carbo/taxol for ovarian cancer, and outcome
What is the benefit
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
What is the adjuvant treatment regimen for ovarian cancer
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
When is neoadjuvant chemotherapy indicated for ovarian cancer
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
When is bevacizumab indicated in adjuvant setting in ovarian cancer
What was the benefit
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
What maintenance treatment is given for ovarian cancer following adjuvant chemotherapy
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
When is bevacizumab contraindicated
What are the SE
Serosal disease or those not receiving paclitaxel
SE: htn, GI bleed, perforation, poor wound healing, proteinuria
How is proteinuria on bevacizumab managed
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
What is the indication for olaparib and bevacizumab given in combination
What was the benefit and based on what trial
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
When are olaparib, bevacizumab and niraparib indicated
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.
What must be monitored when starting niraparib
What is the long term risk
Thrombocytopenia (weekly monitoring for niraparib for 4wks)
Htn (weekly monitoring for niraparib for 8wks)
Risk of myelodysplasia or AML - 1-2%
What mutation is required to give olaparib as maintenance monotherapy for ovarian cancer
BRCA mut, and following response to first line Pt-based ChT
What is the relapse rate for ovarian cancer with stage 3-4 disease
What guides future management
What is the threshold to treat
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
How is a recurrence of ovarian cancer best treated (Pt-sensitive)
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+
What is the advantage of carbo/caelyx over paclitaxel in the relapse setting
non-inferior to carbo/taxol. Less hypersensitivity, alopecia, neuropathy & arthralgia
How is a recurrence of ovarian cancer best treated (Pt-resistant)
weekly or 3wkly paclitaxel
caelyx
topotecan
gemcitabine
tamoxifen - 10% response rate
overall response rate approx 15% with PFS 3-4mths
Survival typically <12mths
How is small cell carcinoma of the ovary hypercalcaemic type treated
Stage I-II - surgery and adjuvant chemotherapy and radiotherapy
Stage III-IV - NACT if debulking not feasible, surgery and adjuvant chemotherapy and radiotherapy
What tumour marker is not expressed by dygerminomas
Equivalent of seminoma in males - does not express AFP
How is a dysgerminoma or yolk sac ovarian tumour treated adjuvantly
Dysgerminoma or yolk sac tumour
Stage 1A-1C - no adjuvant tx
Stage II-IV - BEP or EP 3-4 cycles
How is a immature teratoma ovarian tumour treated adjuvantly
Immature teratoma
Stage 1A Grade 1 - no adjuvant tx
Stage >1A Grade 2-3 - 3-4 cycles adjuvant BEP
What tumor marker is used for sex cord stromal ovarian tumours
What is the adjuvant treatment
serum inhibin
If stage 1c or above - BEP, EP if >40yrs or lung disease, or carboplatin, paclitaxel, or Pt-agent alone
What is the risk of ovarian cancer in someone with Lynch syndrome
3-14%
What is the management of a granulosa cell tumour
Young women & stage 1: unilateral salpingo-oopherectomy
Older women: total hysterectomy, BSO and infra-colic omentectomy
Stage ≥1c - consider adjuvant chemotherapy
BEP or EP if >40yrs or lung disease
Carboplatin & paclitaxel
