Ovarian Flashcards
LGSC vas HGSC- histologic criteriag
LGSC: G1, minimal atypia <12 motives/10hpf Mutations - KRAS++, BRAF+, ER/PR +++, PAX2 Precursor- SBT
HGSC: G2/3 & marked nuclear atypia >12 mits/10hpf Mutations- P53++++ Precursor- tubal intraepithelia neoplasia
Clinical trials on LGSOC
No upfront trial data on LGSOC
- -often hormonal treatment due to robust ER/PR+ expression - - multiple studies show AIs are more effective than tamoxifen
GOG281: 14% patients responded to letrozol (SD rate in this cohort was 70%), none responded to tamoxifen
NCDB study- stage III/IV
–no OS diff between chemo after primary surgery vs those who didn’t get chemo
LGSOC Tx by institution
MD Anderson: 203 pts w/ stage II-IV, surgery followed by carbo/taxol +/- hormonal tx. PFS 26mos in no HT vs 64.9mos in HT (p<0.001)
Johns Hopkins: tx all with HT alone after surgery (>50pts). No PFS or OS data available
NCCN (2017): advanced stage- chemo followed by HT vs HT alone (AI, tamoxifen, lupron)
Response rates to chemo range from 5-60% & less than 5% in recurrent setting
What type of ovarian cancers are DICER1 & FOXL2 mutations?
DICER1- sertoli leydig
FOXL2- granulosa cell
How often have STIC lesions been found in sporadic serous ovarian cancers
50-60% & studies show that p53 mutations match precursor lesion in tube with the ovary, suggesting a clinal origin
Ovarian cancer lifestyle risks
High BMI has been shown to increase risk w/ type I (low grade serous/endometriosis/clear cell) ovarian cancers but not type II
-reported by Ov ca association consortium
Other lifestyle factors such as Exercise and fat intake have not been clearly associated with ovarian cancer
What is the lifetime reduction risk with OCP use?
- 40 to 50% In women with average risk of ovarian cancer
- A meta-analysis of women with BRCA1 and BRCA2 mutations identified a significant reduction with OCP use
- unclear benefit of OCP use after salpingectomy for BRCA
- risk reduction w/ BTL comparable to OCP use in BRC1, not confirmed for BRCA2
What are the subtypes of mucinous ovarian cancers
- Expansive
- stage 1= radical or fertility sparing surg = USO, peritoneal staging, NO LND
- lower metastatic potential
- obs recommended for stage IA/B after surgery
- unclear on need for adjuvant treatment for stage IC
- Infiltrative
- stage 1= radical or fertility sparing surg = USO, peritoneal staging AND LND
- more aggressive (25% present w/ advanced stage dz), worse prognosis
- adjuvant chemo recommended for stage I
Which PARPi is approved in combination w/ Avastin for HRD positive advanced ovarian cancer, following CR or PR to 1st line platinum chemo?
Lynparza (Olap)
37mos PFS vs 17.7 mos with Avastin alone
Role of secondary cytoreductive surgery
DESKTOP III: OS benefit if had complete resection (60 vs 46 months) but worse outcomes if no complete resection
Phase 2 study with/without carbo HIPEC in recurrent plat sens dz–> preliminary OS & PFS no different
Ongoing trial if HIPEC
OVIHIPEC-2:
Stage III EOC
Primary cytoreductive surg +/- HIPEC
Does Avastin have a role in ovarian ca tax with BRCAmt?
No PFS or OS benefit with Avastin maintenance in BRCAmt but improved PFS with BRCAwt
PAOLA1
Stage III & IV - addition of maintenance olap & Avastin following carbo/taxol/Bev resulted in 6 month PFS vs Avastin alone
-FDA approved this combo for advanced ov ca as a maintenance option if BRCAmt or HRD
Would you offer HRT to a young patient with serous BOT?
Although there are no large prospective studies demonstrating the safety of HRT in this situation, the preponderance of evidence favors the benefits of HRT and outweigh the small theoretical risks.
In general, there is no evidence that HRT is contraindicated in patients with EOC and the overall consensus is that HRT should be considered in ovarian cancer patients with menopausal symptoms
