Ovarian Cancer FRCR CO2A Flashcards
what’s the most common cause of death from gynecological malignancy in western world ?
Ovarian Cancer
Which cancers share similar characteristics and behaviour with ovarian Cancer?
- Epithelial ovarian cancer
- Fallopian tube cancer
- Peritoneal cancer
Where does ovarian cancer arise from
Epithelium 90%
when does the patients usually present with ovarian cancer?
Late, 2/3rd in stage III or IV
What are different types of tumor affecting ovary? WHO classification
Surface epithelial stromal tumors
Sex cord stromal tumors
Germ cell Tumors
Tumors of rete ovaraii
Lymphomas and hematopoietic tumors
secondary tumors
Misc
what are different types of surface epithelial stroma tumors
- Benign
- Borderline
- malignant
subtypes are serous, mucinous, endometroid, malignant mixed mullerial tumor (carcinosarcoma), clear cell, transitional cell, squamous cell, mixed and undifferentiated
what are different sex cord stromal tumors?
- Granulosa Cell tumor: GCT and theca fibroma tumors, sertoli cell tumors , sex cord tumors of mixed or unclassified cell types, gynandroblastoma and steroid cell tumors
What are different Germ cell Tumors ?
Primitive GCT (Dysgerminoma, Yolk Sac tumor, embryonal carcinoma)
Biphasic or triphasic (immature and mature teratoma) and monodermal teratoma
what’s the common age affected by Ovarian epithelial cancers?
> 80% are above 50 years of age
which type of ovarian cancers occur at younger age?
Borderline tumors or hereditary cancers particularly a/w BRCA1
How does Family History of cancer affect risk of ovarian Cancer?
- 1st degree relative with breast or ovarian cancer doubles the risk
- relative with Ca Stomach, intestine or lung or lyphoma increases the risk of ovarian cancer
What Genetic mutations are a/w ovarian cancer?
BRCA1 or BRCA2, inherited in AD form
BRCA1 carrier :breast cancer risk: 56 - 68% and ovarian cancer risk: 16 - 39%
BRCA2 carrier BReast cancer: 45 - 54% and ovarian cancer: 11 - 16%
what other cancers are a/w BRCA mutation?
FAllopian tube and peritoneal carcinoma, distal fallopian tube
What cancers are a/w HNPCRC?
40 to 60 % of Colon cancer
40 to 60 % endometrial cancer and 12% ovarian cancer
What are protective factors for ovarian cancer?
- Pregnancy
- Breast Feeding
- USE of OCPs, tubal ligation and hysterectomy
what are possible protective factors for Ovarian Cancer?
- Late Menarche
- Early Menopause
- Exercise and outdorr lifestyle, ? Vit D
- diet rich in fruit and veg
what RFs are a/w ovarian cancer?
Infertility and HIgh SE status.
POssible RFs: long term HRT, obesity, occupational hazards, organic dusts and asbestos
What is difference between Type 1 and Type II Malignant epithelial stromal tumors?
Type I tend to be low grade and less aggressive whereas
Type II are more common and high grade and aggressive
How does type I Malignant epithelial stromal tumors develop?
through adenoma carcinoma sequence
What mutations are a/w type I Malignant epithelial stromal tumors?
KRAS
BRAF
ERBB2
PTEN
PIK3CA
What mutations are a/w type II. Malignant epithelial stromal tumors?
TP53
Most are high grade serous caricnomas
What is the mode of spread of Ovarian Cancer?
Mainly Local and peritoneal
Local to the local structures
Peritoneal to omentum, paracolic gutters, bowel mesentry and undersurface of diaphragm
spread to pleural cavity and pericardium
what LNs are affected by Ovarian Cancer?
Pelvic and PA
about 9% of pts with st I ovarian cancer have nodal spread
How common is hematogenous spread and where?
Rare, liver, bone and lung (very rare)
How is screening done for women at high risk (family hx or + BRCA mutation)
TVS and CA 125 levels, frequently then annually
what has UKCTOCS result about screeening shown?
Screening with CA 125 and TVS sensitivity of around 85 to 90%
what strategy can be applied for prevention of ovarian cancer for high risk women?
- prophylactic salpingo-oophorectomy, dramatically reduces the risk
why is ovarian cancer known as Silent Killer?
No symptoms in early stage or vague symptoms
what are common S/S of ovarian cancer?
- increased abdominal girth
- persistent bloating
- pelvic and abdl pain
- early satiety,
- Nausea n anorexia
- increased urinary urgency or frequency
what are initial tests for pelvic mass?
TVS and Serum CA 125, with AFP and Beta HCG if pt is < 40 years of age
what is Relative Malignancy Index (RMI)
Its for patient with pelvic mass to predict the chances of malignancy
How is RMI calculated?
product of serum CA 125 (IU/mL), the ultrasound score (U) and menopausal status (M)
How is Ultrasound scoring for RMI done
- multilocular cyst
- solid areas
- b/l lesions
- ascites and
- intraabdominal metastases
U=0, if no above feature, U=1, 2, 3 or 4 depending on above
How is M scoring done for RMI?
premenopausal : 1
Postmenopausal: 3
when is RMI considered significant
score > 250, should be refered to specialist gynae oncology team
when is tissue diagnosis necessary?
in advanced disease, if pt is to receive NACT
Percutaneous image guided omental biopsy is gold standard, cytology is ok , if biopsy not possible
what are the aims of surgery in ovarian cancer?
- obtain histology
- accurately stage the tumor
- achieve maximal cytoreduction
what is optimal cytoreduction?
residual disease < 1 cm
now changing to no visible disease
How is optimal debulking useful?
- increased response to chemo
- less platinum resistance and
- improved survival
what surgical procedure is advised for ovarian cancer?
Optimal Surgical Staging:
1. midline laparotomy
2. TAH and BSO
3. Infracolic omentectomy
4. biopsies of any peritoneal deposits; random biopsies of pelvic and abdominal peritoneum
5. RP LN assessment
when is fertility sparing option available with surgery for ovarian cancer?
Good prognosis tumors (borderline tumors, GCTs, stage IA epithelial cancers)
when can post op chemotherapy avoided in ovarian cancer/
Low risk patients
1. stage IA/B with Grade 1/2 disease provided adequate surgical staging has been done
whats the standard Adj Chemo for Stage II- IV ovarian cancer?
for serous/clear cell/carcinosarcoma
Paclitaxel/carboplatin q3weeks
* Paclitaxel/carboplatin/bevacizumab + maintenance bevacizumab (ICON 7, GOG 218)
for mucinous
1. FOLFOX and/or Bevacizumab
2. CAPEOX and/or Bevacizumab or
Paclitaxel/carboplatin q3weeks
* Paclitaxel/carboplatin/bevacizumab + maintenance bevacizumab (ICON 7, GOG 218)
What drugs are used as premedication for paclitaxel and Carboplatin?
Dexamethasone
Chlorpheniramine
Ranitidine
What are common S/Es of Pacli CArbo?
Alopecia
Peripheral neuropathy
muscle and joint pain
How is alopecia dealth with?
offer use of scalp cooling, wigh, head scarf
How is Platinum sensitive ovarian caner defined?
Relapse > 12 months after response to platinum
How is Platinum resitant defined?
relapse < 6 month after response to platinum
How is partially platinum sensitive defined?
Relapse in between 6 to 12 months after response to platinum
How is platinum refractory ovarian cancer defined?
when it does not response to platinum based treatment
What are Chemo options for platinum sensitive pts in recurrent setting?
- CALYPSO trial: PLD and Carboplatin
- GCIG study : Gem and Carboplatin
- OCEANS : BEvacizumab added to Gem CArb
for BRCA mutated pts, how is maintenance therapy
Olaparib
what are chemo options for platinum refractory disease
- PLD and Paclitaxel
- topotecan
what can be done for allergy to carboplatin?
mild grade 1 and 2: rechallenge with increased prophylaxis
Grade 3 or 4: carboplatin should be stopped , may be replaced with cisplatin
How is acites in ovarian cancer treated?
Paracentesis (daycare)
indwelling peritoneal catheter placement
How is pleural effusion treated?
Daycare: aspiration or pleurodesis
what’s the role of RT in ovarian cancer?
palliative RT for vaginal bleeding (20 to 30 Gy in 5 to 10 fractions) when disease is confined to pelvis
How are hormones therpay in ovarian cancer?
Tamoxifen response rate 10%, but may be beneficial in patients with long history
what are borderline ovarian tumors
lack of stromal invasion in the ovary
who are affected by borderline ovarian tumors
younger people
what are most of the borderline ovarian tumors
mucinous or serous, 1/2 are serous and 1/3 are mucinous
what’s is the treatment of borderline ovarian tumors
Surgery with maximal cytoreduction
how should women be followed up post conservative surgery? borderline ovarian tumors
close follow up coz the c/l ovary may become affected
is there role of adjuvant treatment in borderline ovarian tumors?
not yet defined
when is platinum based chemo used in borderline ovarian tumors?
recurrent setting
what is pseudomyxoma peritonei?
abundant mucinous ascites in the pelvis and abdominal cavity, surrounded by fibrous tissue
it usually indicates metastatic disease from appendix or elsewhere in GI tract rather than primary ovary
what’s Rx for pseudomyxoma perionei?
removal of the tumor and complex peritonectomy with intraperitoneal chemotherapy,
long term prognosis is poor
what are granulosa cell tumor of ovary?
< 5% of all ovarian tumor
two types
- juvenile <5% (<30 yrs)
- Adult 95% (middle to old age)h
what’s the presentation of granulosa cell tumor?
present in stage I disease commonly
- non specific abdominal or pelvic symptoms
- vaginal bleeding to to endometrial hyperplasia or adenocarcinomas a/w increased estrogen production by tumor cells
- acute tumor rupture and hemoperitoneum
what’s Rx for younger people of Granulosa cell tumor?
Conservative fertility sparing surgery (U/L SO)
What’s Rx for older pts with Granulosa cell tumor?
TAH and bso and Infracolic omentectomy
any role of adjuvant Rx in granulosa cell tumor
Mostly no until relapse
when is adjuvant Rx with chemo done for granulosa cell tumor?
- stage IC disease
- high mitotic index
- st II-IV
What adjuvant Rx is for Granulosa cell tumor?
BEP
what are prognostic factors for granulosa cell tumor ovary?
- stage of disease
- age
- tumor rupture
- amount of residual disease
what are ovarian Germ cell tumor?
Primitive GCTs: Dysgerminoma n yolk sac tumor
Biphasic or triphasic : immature teratoma and mature teratoma
Monodermal teratoma including struma ovarii
what’s peculiar about struma ovarii?
composed of thyroid tissue
when is the peak incidence of malignant germ cell tumors of ovary?
< 5%
women under the age of 20 , peak around 18, majority are u/l
How does pts of malignant germ cell tumors of ovary present?
pelvic mass and pain
what investigations should be included in malignant germ cell tumors of ovary patients?
AFP and Beta HCG
how is surgery done for malignant germ cell tumors of ovary?
U/L oophorectomy
more radical avoided, to preserve fertility, it doesnot compromise cure
what’s Rx for malignant germ cell tumors of ovary relapse and what is the cure rate?
BEP
90%
What % of pts on EMACO develop recurrence and what 2nd L is used?
20%
EP-EMA
How is EMACO regimen modified for choriocarcinoma with brain mets?
higher dose of methotrexate for CNS penetration
for how long Rx is continued for Pts with CNS metastasis?
8 weeks
How is the prognosis of pts with choriocarcinoma with liver metastasis and how to treat them?
poor prognosis, 50% cure rate, EMA-EP regimen
How are pts of choriocarcinoma with lung mets treated?
initial moderate dose of ChT to avoid bleeding risk
to start with Etoposide and cisplatin D1, D2 followed by BEP regimen as in Germ cell tumor
How to treat placental site trophoblast tumor?
Hysterectomy is often curative, with mets: EP-EMA, continue for 8 weeks after normalisation of HCG levels failing to normal values
what’s the risk of relapse for low risk and high risk diz treated with EMA CO?
2.5% for low risk
8% for high risk
how long does it take for menstrual cycle to come back post chemo ?
6 months
