Uterine

Question 1

Gene alterations (4 categories) associated with endometrial cancer

(Clear cell not included in the TCGA analysis, only serous & endometrioid)

Answer 1

1. POLE ultramutated
   - younger age
   - best PFS
2. MIcrosatellite instability hypermutarrd
   - RAS/b-care in pathway mutations
   - PI3CA/PTEN pathway mutations
3. Copy # low
4. Copy # high
   - 97% serous found here
   - high p53 mutatations
   - worse prognosis
   - worst PFS

Question 2

Role of trastuzumab in uterine ca tx

Answer 2

Survival benefit with adding trastuzumab to platinum/taxane in advanced/recurrent HER2+ uterine serous

Question 3

Studies looking at adjuvant chemo & chemoRT in advanced dz

Answer 3

GOG 258: no OS or relapse free survival to combined tx in stage 3 & 4a

PORTEC-3: OS benefit w/ high-risk features (G3, LVSI, outer half DOI) if treated w/ chemoRT vs RT alone

Question 4

Importance of sequencing chemo & RT in advanced dz

Answer 4

Importance most pronounced in stage III dz and 5 year OS: RT followed by chemo (vs CCRT or CT-RT) based on review of NCDB

Question 5

What chemotherapy agents are ineffective in endometrial cancer?

Answer 5

Liposomal doxorubicin
Oral Etoposode
Topotecan
Docetaxel
Pemetrexed
Gemcitabine

Question 6

Prior to carbo/taxol in adjuvant treatment for advanced/recurrent endometrial cancer, TAP (cis/doxorubicin/taxol) was used. GOG209 compared carbo/taxol to TAP

Answer 6

GOG209 compared regimens every 21 days for 7 cycles

• non-inferiority study
• carbo/taxol was not inferior to TAP (OS 32 vs 38 mos, PFS 14 vs 4 mos)
• TAP had more G3 thrombocytopenia, vomiting & diarrhea
• neutropenia more common in carbo/taxol

-carbo/taxol became first line standard for advanced endometrial cancer based on this trial

Question 7

What is the indication for use of Keytruda (pembrolizumab) in unresectable or recurrent rumors progressing after 1st line therapy?

Answer 7

MMR deficient (MSI- high)

• this was the first FDA drug approval to include e some trial cancer in over 40 years
• studies ongoing looking at carbo/taxol +/- pembro followed by maintenance pembro

Question 8

What did GOG99 (by Keys et al) establish?

Answer 8

The role of pelvic radiation in intermediate risk, early stage dz

HIR defined as: 1) moderate:poorly differentiated tumor 2) LVSI+ 3) outer 1/3 DOI [if 70+yo need 1 risk factor, if <50yo. need 3 risk factors]

OS rates - no sig difference

Question 9

When is the addition of chemotherapy to RT associated with improved OS?

Answer 9

Stage III disease

-this was demonstrated in PORTEC3 where RT vs RT+chemo was evaluated in high-risk patients

Question 10

When is radical Hyst indicated for uterine cancer?

Answer 10

Historically for stage II

• recent retrospective studies & systematic review didn’t show OS benefit to rad hyst vs simple hyst
• study published this year w/ 7500 patients did not show survival benefit compared to simple hyst & subanalysis of Rad hyst without adjuvant RT had worse OS compared to simple hyst with adjuvant RT

Question 11

Do you perform sLND or full LND for uterine serous carcinomas?

Answer 11

Full LND has been shown to have no different survival outcomes vs sLND with lower morbidity with sLND

Question 12

FIRES Trial

Answer 12

The first prospective cohort study to examine the use of SLN mapping an early stage endometrial cancer. Included all histologic subtypes. Multi institution.

Confirmed accuracy and benefit of SLN mapping

Question 13

Significance of ITCs

Answer 13

Insufficient evidence to support clear adjuvant treatment recommendations in ITC positive patients

-appear to have higher recurrence rates compared to no negative patients but lower recurrence rates compared to micro or macro metastatic disease.