OQ: Uterine Cancer

Question 1

Picture of uterine serous carcinoma, how do you manage this?

Answer 1

This answer really is no different between USC, CCC, UC, CS. -Preop CA-125 (elevation correlates with advanced disease for UPSC; may or may not predict recurrence) -Preop C/A/P CT to evaluate for metastatic disease “Staging (hyst, BSO, PPALND, omental biopsy) vs. maximal cytoreduction followed by systemic treatment first as it’s an aggressive histology then radiation to decrease risk of locoregional recurrence.” IA: no residual, observation. Residual C/T x 6 with VCB. IB-IIIC1: C/T x 6, pelvic RT IIIC2: C/T x 6, EFRT IV: C/T x 6, +/- RT +/- Herceptin for advanced stage USC depending on IHC/FISH.’

Question 2

Patient on pembrolizumab now with diarrhea, how do you work-up and manage?

Answer 2

If grade 1 then no workup needed (<4 stools over baseline) G2: 4-6 over baseline G3: 7+ over baseline with hospitalization or affects ADL G4: life threatening G2-4 - CBC, CMP, ESR, c. diff, stool O&P, CMV, GI consult,+- lactoferrin consider CT AP consider endoscopy to determine ulcerations (indicates refractory to steroid) requiring infliximab if infliximab, then HIV, Hep A/B, and TB Quantiferon testing

Question 3

Describe GTV/CTV/PTV

Answer 3

GTV: visible tumor on imaging CTV: areas with high risk for microscopic disease PTV: all areas getting radiated with adjustment for changes in organ position and patient position between treatment days

Question 4

Max tolerate doses of stomach, small bowel, colon, rectum, bladder, liver, kidneys, ovary, vagina upper/middle/lower, bone marrow, femoral head?

Answer 4

GIT stomach: 45gy small bowel: 45gy colon: 60gy rectum: 75gy bladder : 75Gy Small portions of liver: 70-90Gy whole liver: 30Gy Kidneys: 18Gy Ovary: 5-15Gy (older = lower tolerance before ovarian failure) Vagina: upper/middle/lower 120/85/65 Gy Bone marrow 40Gy Femoral head: 50Gy

Question 5

How would you manage stage I leiomyosarcoma?

Answer 5

Surgical staging: Hyst, BSO, +/- omental sampling -No LND if frozen LMS; if in doubt, do LND -Okay to leave ovaries in situ if premenopausal -When to take back if final path is LMS? –cx stump – post-myomectomy –morcellated –mets on postop imaging –ER+/PR+ and has ov and >40 Observation

Question 6

How do you manage stage III leiomyosarcoma?

Answer 6

-Gem/tax OR adria -GeDDIS trial - do adria first, then gem/tax second -Max dose adriamycin 400mg - no cardiotoxicity, 450 mg - 5% risk cardiotoxicity, 550mg max lifetime dose -Pretreatment MUGA /echo -Other chemo options?

Question 7

How do you treat uterine carcinosarcoma? What are all your chemotherapy options?

Answer 7

Similar answer to USC card. Here you can quote GOG 261 showing carbo/taxol was not inferior to ifos/taxol for OS with longer PFS and similar QOL and neurotoxicity. Similar trends for ovarian carcinosarcomas, as well.

Question 8

“Lynch syndrome: List MMR mutations. MLH1 histology slides. What’s next? Hypermethylation study. How do you do this? What if PMS2 also absent. Hypermethylation negative. Genetic testing. Who gets genetic counseling? Do you know Amsterdam criteria? What other cancers, what prophylactic surveillance can you offer family members? How does ovarian cancer risk change by each Lynch mutation?

Answer 8

TBD

Question 9

Endometrioid path slide.

Answer 9

TBD

Question 10

What is CT’s sensitivity for detecting affected LNs in endometrial cancer?

Answer 10

High false negative rates, PET/CT and CT AP ~50% sensitive for nodal dz, ~30% sensitive for peritoneal disease (soliman 2019 Cancer).

Question 11

Who are candidates for fertility sparing endometrial cancer? How do you treat, how do you follow?

Answer 11

TBD

Question 12

You are doing high paraaortics. Patient develops fluid collection up there. It is drained and continues to drain. What is causing it? What are the treatments?

Answer 12

TBD

Question 13

How do you treat CCC of the uterus?

Answer 13

Same as USPC, go through this, may need a “CCC” study.”

Question 14

Tell me about TCGA and grade 3 endometrial cancer.

Answer 14

TBD

Question 15

Tell me about TCGA and grade 3 endometrial cancer.

Answer 15

5-year overall survival of 89%, 75%, 69% and 47% for POLE-ultramutated, MMRd, NSMP (no specific molecular profile) and p53abn group, respectively. Some data from PORTEC-3 suggesting the high-risk groups benefit from CT-RT more than the lowest risk group, where all patients did very well.

Question 16

How high do you do paraaortic lymph nodes, why?

Answer 16

Per Mayo prospective study, with positive Mayo criteria, high rate of lymphatic metastasis above the IMA indicates need for pelvic and para-aortic lymphadenectomy (not just sampling) up to renal vessels. 77% of patients with positive para-aortic mets had them above IMA.

Question 17

How does PDL1 inhibitor work?

Answer 17

TBD

Question 18

Why do we give carbo/taxol for endometrial cancer, tell me how we got here?

Answer 18

Prior to the availability of taxanes, anthracyclines and platinum compounds represented the most active cytotoxic agents, each producing single-agent responses in the range of 20–30%. In 1990s, the GOG reported 45% of patients responding to doxorubicin plus cisplatin in advanced or recurrent endometrial carcinoma. This was significantly superior in a randomized trial to the 27% response obtained from doxorubicin alone. Overall survival (OS), however, was not significantly better in the combination arm, with a median of ∼9 months [1.]. A EORTC trial had the same result. Finally, GOG 177 showed TAP better than AP, but this combination was very toxic and hard to administer and it was felt would combined poorly with targeted therapies.

Question 19

What’s the data for treatment of stage IA uterine serous?

Answer 19

Fader 2009 retrospective, USC IA patients much better PFS and CSS with CT+/-RT over just RT or obs. Addition of RT to CT didn’t seem to make a difference in this subgroup for PFS, but did improve local control.

Question 20

Why do we give carbo/taxol for endometrial cancer, tell me how we got here?

Answer 20

Prior to the availability of taxanes, anthracyclines and platinum compounds represented the most active cytotoxic agents, each producing single-agent responses in the range of 20–30%. In 1990s, the GOG reported 45% of patients responding to doxorubicin plus cisplatin in advanced or recurrent endometrial carcinoma. This was significantly superior in a randomized trial to the 27% response obtained from doxorubicin alone. Overall survival (OS), however, was not significantly better in the combination arm, with a median of ∼9 months [1.]. A EORTC trial had the same result. Finally, GOG 177 showed TAP better than AP, but this combination was very toxic and hard to administer and it was felt would combined poorly with targeted therapies. 209 finally came along, noninferiority trial of CT vs. TAP, no significant difference between them.

Question 21

What’s the data for treatment of stage IA and IB uterine serous?

Answer 21

Fader 2009 retrospective, Stage I USC patients much better PFS and CSS with CT+/-RT over just RT or obs. Addition of RT to CT didn’t seem to make a difference in this subgroup for PFS, but did improve local control. IB no recurrences in 12 patients receiving CT/RT vs. 2/7 recurrences for CT alone.

Question 22

What is the accuracy of your institutional frozen section?

Answer 22

I wouldn’t dig too deep, just say some internal reviews by hospitals suggested high degree of concordance between frozen and final for tumor grade and invasion.

Question 23

How do you decide upon the sequencing of your adjuvant therapy for endometrial cancer, what data do you have to support this?

Answer 23

Fuck need to think about this one.

Question 24

Who gets brachytherapy in endometrial cancer and what is this based on what? What do you quote as the risk of vaginal recurrence in a HIR patient with and without brachytherapy?

Answer 24

HIR, based on GOG-99 and PORTEC 2.

Question 25

General OBGYN does TVH for grade 1 endometrial cancer. Leaves tubes/ovaries in a young woman. Low-risk disease, would I take out ovaries/tubes?

Answer 25

TBD

Question 26

What are the big takeaways in terms of risk of LN metastasis with the data from GOG 33.

Answer 26

TBD