General Flashcards
What is the WHO score used for
To predict prognosis and chemosensitivity
What constitutes high risk
7 or greater is high risk
<7 is low risk
(double check this)
What is your high risk regimen and how do you dose it?
…
Cisplatin
MTX
Vincristine
Actinomycin D
Induction EP? When do you use this?
How do you dose single agent MTX?
Methotrexate 0.4 mg/kg IV or IM daily for 5 d, if no response increase to 0.6 mg/kg or switch to actinomycin D protocol
OR
Methotrexate Days 1/3/5/7 1 mg/kg with Folinic Acid Days 2/4/6/8 0.1mg/kg
What are risk factors to resistance to single agent MTX?
choriocarcinoma
metastatic disease
when pretreatment serum hCG levels exceeded 50,000 milli-International Unit/mL
What is considered an adequate response to MTX ? How do you respond to inadequate response?
An adequate response is defined as a fall in the hCG level by 1 log after a single course of chemotherapy.
If the response to the first course was inadequate, the dosage of MTX should be increased from 1 to 1.5 mg/kg/d for each of the 4 treatment days. If the response to two consecutive courses of MTX-FA is inadequate, the patient is considered to be resistant to MTX, and Act-D should be promptly substituted in patients with nonmetastatic and low-risk metastatic GTN.
What are components of EMA-CO
Day 1: VP-16 (etoposide), 100 mg/m2, IV infusion in 200 mL of saline over 30-min Actinomycin D, 0.5 mg, IV push, Methotrexate, 100 mg/m2, IV push, followed by a 200 mg/m2 IV infusion over 12 hr
Day 2: VP-16 (etoposide), 100 mg/m2, IV infusion in 200 mL of saline over 30-min Actinomycin D, 0.5 mg, IV push
Folinic acid, 15 mg, IM or orally every 12 hr for 4 doses beginning 24 hr after start of methotrexate
Day 8: Vincristine, 1 mg/m2, IV push
Cyclophosphamide, 600 mg/m2, IV in saline
What are components of EMA-EP
Day 1: VP-16 (etoposide), 100 mg/m2, IV infusion in 200 mL of saline over 30-min Actinomycin D, 0.5 mg, IV push, Methotrexate, 100 mg/m2, IV push, followed by a 200 mg/m2 IV infusion over 12 hr
Day 2: VP-16 (etoposide), 100 mg/m2, IV infusion in 200 mL of saline over 30-min Actinomycin D, 0.5 mg, IV push
Folinic acid, 15 mg, IM or orally every 12 hr for 4 doses beginning 24 hr after start of methotrexate
Day 8: EP, Cisplatin
What is success rate of EMA-EP
EMA-EP–induced complete remission in 12 of 18 patients (66.7%) with EMA-CO-resistance or relapse.
What are side effects of EMA-CO
Universal alopecia
Rare stomatitis and nausea and vomiting
Myelosuppression is often the acute dose-limiting acute toxicity - many have used stem cell support with granulocyte colony-stimulating factor to avoid dose reductions or treatment delays during EMA/CO therapy.
Why use induction before EMA-Co?
VERY High risk patients are at risk of early death
Bowers 1997: 4% early death due to respiratory complications
Do induction EP in patients with extensive disease in chest, liver, or brain, WHO over 12 or at risk of major bleeding
Charing Cross instituted a policy of using low-dose induction chemotherapy with cisplatin (20 mg/m 2 ) and etoposide (100 mg/m 2 ) on day 1-2 and repeat weekly for 1-2 cycles before EMA-CO to minimize the overwhelming amount of cell death that patients experience upon chemotherapy initiation - reduces early death to <1% without difference in EMACO resistance
Alifrangis JCO 2012
They successfully significantly reduced the rates of early death when patients received induction EP to 0.7% versus 7.6% when patients were treated initially with EMA/CO alone.
What is diagnostic criteria for GTN?
Plateau: 4 values over 3 weeks (0,7,14,21) <10% change
> 10% rise over 3 values over 2 weeks (0,7,14)
Choriocarcinoma on path
Persistently elevated hCG at 6 mo
What is risk of GTN after molar pregnancy
Complete: 20%
Partial: 1-5%
How to differentiate between partial and complete mole
p57 IHC: Picks up maternal tissue thus partial role
(complete moles will have extravillous staining, partial will have villous staining but not extravillous staining)
Flow cytometry for karyotyping
What imaging do you get for GTN work up?
CXR - if negative then get CT Chest
- Charring Cross did studies if small lung lesions getting multiagent chemo regimen does not have survival benefit (look this up)
CT A/P
Brian MRI if there are lung mets or non-post molar choriocarcinoma
What are the FIGO STAGES for GTN
Stage I: Confined to uterus
Stage II: Confined to pelvic organs
Stage III: Lungs without genital tract involvement
Stage IV: All other metastatic sites
Discuss role of 2nd D&C
GOG 242 - Osborne Obstet Gynecol 2016
Complete (90% of study population) or partial mole at first D&C with WHO score 0-6
No e/o mets
Treatment outcomes:
- Surgical cure: 40%, trended hCG monthly until 6mo
- Surgical response: 3% - hCG camge back up
- Surgical failure -> restaged: 48%
1/60 had perforation, 1/60 G3 uterine hemorrhage
What are chemo options for low risk GTN?
Methotrexate : 1/3/5/7 day regimen with folinic acid on 2/4/6/8 repeated every 2 weeks (74-90% remission) or 0.4mg/kg IM or IV for 5 days every 2 weeks (87-93% remission) - note the weekly 30-50mg/m2 regimen has 49-75% remission rate thus is not commonly used
Actinomycin D: 0.5mg IV for 5 days ever 2 weeks (77-94%) or “pulsed” 1.25mg/m2 IV every 2 weeks (69-90%)
Lurain GTN II Am J Obstet Gynecol 2011
Act D
-824/1000 remission
- 154/1000 Failure first line
- 462/1000 nausea
MTX
-536/1000 remission
-547/1000 failure first line
Lawrie Cochrane 2016
Can you prevent GTN by giving chemo in GTD
3 RCTs with 650 patients total - may decrease GTN transformation but increases drug resistance and toxicity thus is not reocmmended (cochrane 2012)
GOG 055: OCPs vs barrier contraception - 23% on OCPs developed GTN vs 33% with barrier contraception thus OCPs are OK to use
What are side effects of EMA-CO
100% alopecia
Nausea vomiting Stomatitis
Neutropenia
Discuss prognosis of GTN
Bower 1997 - LOOK AT THIS
5y survival :
Prior chemo: Yes 89% No 84%
Brain: Yes 69% No mets 89%
Is there a hereditary risk of mole?
Familial repetitive hydatiform mole missense mutation NLRP7 on locus chromosome 19
When do GTNs tend to recur
85-95% within first 18mo picked up by hCG
NEED effective contraception and hCG for 1 year
When do you use hysterectomy for GTN
Localized disease AND
Primary: 47% have complete remission after hysterectomy
Chemoresistance: 95% ended up going to remission!
Life threatening hemorrhage
If metastatic, remission is not achieved
Eysbout Gynecol Oncol 2017
What can patients with history of GTN expect from future fertility
95% resume menses
menopause usually 3 years earlier
2/3 will have live birth
Need to send placenta to path
Need to have a quant at their postpartum visit
Gadducci 2016
Discuss hyperglycosylated hCG
Made by extravillous trophoblasts
Can be helpful for quiescent GTN with persistent low level circulating hcG (<200) without detectable disease on scan or exam.
Normal hCG H <1% is diagnostic - these patients should NOT Get chemo as hcgH is a marker of trophoblastic invasion and is NORMAL
What is hook effect
Falsely low hCG values if testing gets oversaturated
Discuss secondary malignancy with GTN
Due to cumulative dose of etoposide (topoisomerase inhibitors) if over 2mg/m2
AML!
What are salvage regimens for high risk
MAC
VIP: etoposide, ifos, mesna
TP/TE: Taxol 135 cis 75 D1, Taxol 135 Etop 150mg/m2 D15 every 2 weeks
BEP
Discuss trials for low risk GTN
GOG 69
GOG 79
Look at Davidson lecture
