[ROQs] GYN, Cervical/Endometrial Flashcards
1
Q
What is the ASTRO cervical cancer tx algorithm?
A
Chino J, et al. Radiation Therapy for Cervical Cancer: Executive Summary of an ASTRO Clinical Practice Guideline. Pract Radiat Oncol. 2020 Jul-Aug;10(4):220-234.
2
Q
What is the ASTRO endometrial cancer TX algorithm for early-stage endometroid histologies?
A
Harkenrider, et al. Radiation Therapy for Endometrial Cancer: An American Society for Radiation Oncology Clinical Practice Guideline. Pract Radiat Oncol. 2023 Jan-Feb;13(1):41-65.
3
Q
What is the ASTRO endometrial cancer TX algorithm for early-stage high-risk histologies?
A
Harkenrider, et al. Radiation Therapy for Endometrial Cancer: An American Society for Radiation Oncology Clinical Practice Guideline. Pract Radiat Oncol. 2023 Jan-Feb;13(1):41-65.
4
Q
What is the ASTRO endometrial cancer TX algorithm for advanced-stage all histologies?
A
Harkenrider, et al. Radiation Therapy for Endometrial Cancer: An American Society for Radiation Oncology Clinical Practice Guideline. Pract Radiat Oncol. 2023 Jan-Feb;13(1):41-65.
5
Q
What is the staging for cervical cancer?
A
6
Q
What is the general tx paradigm for FIGO IA1 cervical cancer?
A
CKC: Cold Knife Conization
7
Q
What is the general tx paradigm for FIGO IA2 cervical cancer?
A
CKC: Cold Knife Conization
8
Q
What is the defining feature of FIGO Stage IIIB cervical cancer?
A
- Hydronephrosis
9
Q
What is the general tx paradigm for FIGO IB1-2 cervical cancer?
A
10
Q
What is the general tx paradigm for locally advanced cervical cancer?
A
11
Q
How do you manage superficial vein (non-varicose) thrombosis for a pt undergoing RT or Brachytherapy for cervical cancer?
A
- Conservative management
- no anti-coagulation
- should not delay tx
12
Q
How do you manage acute deep vein thrombosis (DVT) for a pt undergoing RT or Brachytherapy for cervical cancer?
A
- Start AC
– Lovenox BID - Hold med the night before and the morning of RT
- Do not use SCDs 2/2 risk of dislodging DVT → PE
13
Q
Where is the superior border of the RT field when treating up to common iliac LNs for pt’s receiving RT for gynecologic cancers?
A
L1-L2 interspace
14
Q
Where is the superior border of the RT field when treating up to para-aortic LNs for pt’s receiving RT for gynecologic cancers?
A
T11/T12 interspace
15
Q
Which vertebral level corresponds to the bifurcation of common iliacs into external and internal iliacs?
A
L4-L5
16
Q
What is the risk of pelvic and PA LN involvement according to the stages of cervical cancer?
A
- Pelvic: ROT, Stage x 15%
– Stage I: 15%
– Stage II: 30%
– Stage III: 45% - Para-aortic: ROT, 1/2 x risk of pelvic
17
Q
What is the recommended overall treatment time for definitive EBRT + Brachytherapy of cervical cancer?
A
- ≤ 8 wks (56 days) (Song et al., U Chicago, 2013)
- Each day beyond this resulks in:
– If pt is receiving RT alone, 0.5-1% decrease in local control and survival
– If pt is receiving concurrent CHT, 0.5-1% decrease in local control ONLY
18
Q
What are the most common histologies for cervical cancer?
A
- SqCC: 80%
– > 95% Related to HPV! - ACA: 10-20%
– Endometrioid, mucinous, serous, clear cell - Rare: Neuroendocrine, small cell, RMS, lymphoma
19
Q
How does bladder filling factor into a patient being simulated for definitive or adjuvant IMRT for cervical cancer?
A
- Perform full & empty bladder scans → ITV
- Tx planning is done on the full scan
20
Q
What is the rate of G3/4 tox w/ concurrent and adjuvant cisplatin/gemcitabine w/ RT for cervical cancer?
A
- 85%!
21
Q
What are the indications for adjuvant CRT (as opposed to RT only) for cervical cancer?
A
-
Peter’s criteria (GOG109 aka RTOG 9112)
– Positive margins
– Positive LNs
– Parametrial involvement
22
Q
What was the pt population, randomization, and end point of Peters et al. (GOG 109 aka RTOG 9112) for cervical cancer?
A
- Stage IA2, IB, IIA s/p radical hysterectomy + PLND who met the Peter’s criteria:
– ≥1 of node positive
– Positive margin
– Parametrial involvement - Randomization:
– WPRT 49.3 Gy/ 29 fx
– 🏆 WPRT + x2 cycles concurrent cis/5-FU and x2 adjuvant cis/5FU x4
– If common iliac LN+, 45 Gy/ 1.5 Gy daily to PA nodes given - Endpoint: OS, PFS
23
Q
What were the results of the Peters et al. (GOG 109 aka RTOG 9112) for cervical cancer?
A
- RT vs. CRT
– 4-yr OS 71% vs. 81%
– 4-yr PFS 63% vs. 80% - Other takeaways
– No difference in recurrence patterns
– 60% completed all 4 cycles of chemo
– Gr4 toxicity in 4% vs. 17%
– Gr5 in n=1 in CRT arm but this patient declined chemo
24
Q
How was chemo delivered in the CRT arm of Peters et al. (GOG 109 aka RTOG 9112) for cervical cancer?
A
- Cisplatin (70 mg/2) and 5FU (1000 mg/m2) q3 wks x 4C
- 2C concurrent, 2C adjuvant
25
Upon reanalysis (Monk et al), what subgroup did not show an OS benefit from the addition of chemotherapy to RT in Peters et al. (GOG 109 aka RTOG 9112) for cervical cancer?
No OS benefit for:
- Tumor size < 2 cm
- Only 1 LN+
26
Pre-sacral LNs are at the risk of involvement from what primary cancers?
- Cervical
- Rectal
27
Why is the pre-sacral space at risk for spread from cervical primaries?
- Uterosacral ligaments
-- Posterior from cervix to sacrum, inserting into S1-S3
-- Cervical cancer can track along the ligaments
28
What was the pt population, randomization, and end point of GOG 71 for cervical cancer?
- Bulky IB disease (tumor or cervix ≥ 4cm)
- Randomization:
-- 🏆 40 Gy EBRT + 40 Gy LDR
-- 45 Gy EBRT + 30 Gy LDR + extrafascial hysterectomy
- Mnemonic: 71 → before defintive CRT was the norm
29
What were the results of GOG 71 for cervical cancer?
- Def RT, vs. RT f/b hyst
-- No OS difference
-- 5-yr LR 27% vs. 14%, p=0.08
-- 5-yr PFS 53% vs. 62%, p=0.09
-- Disease progression 46% vs. 37%, p=0.07
-- Gr 3-4 toxicity not different
30
How do you mark the extent of the disease for a stage IIIA cervical cancer during simulation?
- By placing a fiducial marker in the tumor
- CTV extends 3 cm inferior to this marker
- Can also help w/ brachytherapy planning should tumor regress during EBRT
31
What is a special consideration prior to simulation/treatment planning for a stage IIIB cervical cancer during simulation?
Ureteral stent placement to relieve hydronephrosis
32
What is the classic inferior border of the AP/PA field for def RT for cervical cancer?
Whichever is lower:
- 3-4 cm below the inferior extent of the tumor
- lowest extent of obturator foramen
33
What are the classic superior and lateral borders of the AP/PA field for def RT for cervical cancer?
- Superior: L4-L5
- 1.5-2 cm lateral to the pelvic brim
34
What are the classic borders of the Lateral field for def RT for cervical cancer?
- Sup: L4-5
- Inf:
-- 3-4 cm below the inferior extent of the tumor
-- lowest extent of obturator foramen
- Ant: 1 cm anterior to the pubic symphysis
- Post: Entire Sacrum
35
What was the pt population, randomization, and primary endpoint of GOG 120 for cervical cancer?
- IIB-IVA disease, surgically staged, PA LN-
- Randomization:
-- Cisplatin alone (40 mg/m2 weekly x 6C)
-- Cisplatin (50 mg/m2 on days 1, 29) with 5-FU (4 g/m2 on days 1, 29) and hydroxyurea (2 g/m2 twice weekly x 6 weeks), or
-- Hydroxyurea(3 g/m2 twice weekly x 6 weeks)
- all received EBRT (40.8/24 or 51/30) f/b BT
- Endpoints: OS, PFS
36
What were the main results of GOG 120 for cervical cancer?
- Cis alone, combo, vs. hydroxyurea alone
-- 2 yr PFS 67%, 64%, 47%
-- 10 yr PFS 46%, 43%, 26%
-- 10 yr OS 53%, 53%, 34%
- Current SOC is weekly cisplatin (40 mg/m2)
-- Acute tox less for cisplatin alone vs. combo.
37
What are the most commonly involved LN chains for invasive cervical cancer?
- External iliac (35%)
- Obturators (43%)
- Parametrial (22%)
38
What was the pt population, randomization, and notable endpoints of GOG 92 (Sedlis et al.) for cervical cancer?
- Stage IB, N0 s/p radical hysterectomy meeting **S**E**DL**IS Criteria**, ≥2 risk factors of:
-- **S**ize ≥4 cm
-- **D**eep invasion (>1/3)
-- **L**VI
-Randomization:
-- 🏆 WPRT 46 Gy or 50.4 Gy
-- obs
- Endpoints: PFS
-- Not powered for OS
39
What were the main results of the GOG 92 (Sedlis et al.) for cervical cancer?
- Adj RT vs. Obs
-- 10-yr LR 14% vs. 21%
-- 10-yr PFS 78% vs. 65%
-- 10-yr OS 80% vs. 71%, p=0.07
-- 12-yr recurrence adenocarcinoma or adenosquamous 8.8% vs. 44%
-- Acute gr 3 & 4 toxicity 7% vs. 2%
40
What is the usual dose for an LDR boost following EBRT for def RT for cervical cancer?
35-45 Gy
41
What is the usual dose **rate** to point A for an LDR boost following EBRT for def RT for cervical cancer?
0.4-0.6 Gy/hr
42
What is the usual dose **rate** to point A for an HDR boost following EBRT for def RT for cervical cancer?
0.8-1.2 Gy/hr
43
What type of hysterectomy is recommended for stage IA1 w/o LVSI cervical cancers?
**Extrafascial** hysterectomy
44
What type of hysterectomy is recommended for stage IA1 w/ LVSI and IA2 cervical cancers?
***Modified*** radical hysterectomy
45
What type of hysterectomy is recommended for stage IB... cervical cancers?
radical hysterectomy
46
What is the usual dose for a boost to unresected LNs during EBRT for def RT for cervical cancer?
10-15 Gy (55 Gy total)
47
What is the usual dose for the boost to the parametria during EBRT for def RT for cervical cancer?
- 5.4-9 Gy (50.4 or 54 Gy total)
48
What is the usual dose for the pelvis during EBRT for def RT for cervical cancer?
- 45 Gy in 25 fx
49
What are the standard CHT regimens used for adjuvant/definitive CRT for cervical cancer?
- Cisplatin
-- Prefered 2/2 lower tox profile
- Cisplatin/5-FU
-- Higher tox, including NVD, mouth sores, depressed blood counts
50
What are the A and B Rx points for T&O brachytherapy?
51
Which tumors are most appropriate for an interstitial brachytherapy boost?
- Apical Tumors
- > 0.5 cm thick
- Well-defined
- Mobile
52
What are the appropriate doses and fractionation for HDR boost after pelvic RT for definitive RT of cervical cancer?
- ≤ 4 cm of residual disease post CRT → EQD2 ≥ 80
-- 5.5 Gy x 5 fx
- > 4 cm of residual disease post CRT → EQD2 ≥ 85-90
-- 6 Gy x 5 fx
- 5 Gy x 6 fx
- 7 Gy x 4 fx
53
For medically inoperable endometrial cancer (stage IA) being tx w/ brachytherapy alone, what application and dose regimen/fx can be used?
- The applicator used must treat the entire uterine cavity
-- Tandem & avoids
-- Tandem & ring
-- Tandem and cylinder applicators
-- Rotte "Y" applicator
- Doses: totals range b/w 34-45
-- 8.5 Gy x 4 fx
-- 7.3 Gy x 5 fx
-- 6.4 Gy x 6 fx
-- 6.0 Gy x 6 fx
-- 5.7 Gy x 7 fx
-- 5.0 Gy x 9-10 fx
54
What vertebral levels corresponds to the top of the PA field?
L1-L2
55
What vertebral levels corresponds to the kidneys?
- T12-L3
- Mnemonic: Kidneys begin under the ribs!
56
What is the sensitivity of a PET vs. CT scan for identifying invovled abdominal LNs in locally advanced cervical cancer pts?
- PET: 50%
- CT: 42%
57
What is the specificity of PET vs. CT scan for identifying invovled abdominal LNs in locally advanced cervical cancer pts?
- PET: 85%
- CT: 89%
58
What is the NCCN recommended tx paradigm for recurrent cervical cancer after surgery?
RT ± CHT
59
What % of HPV infections are cleared w/i 2 yrs w/o any intervention?
90%
60
When is the rate of recurrence the highest for cervical cancers post definitive tx?
Within 2-3 yrs → 75% recurrences
61
What is the NCCN recommended strategy for surveillance for cervical cancer pts psot definitive therapy and a -ve 6-12 wk PET?
- H&P q3-6 mos for 2 yrs
- Then q6-12 mos for 3-5 yrs
- Then annually
- NB: Imaging in not recommended, unless pt is at a high risk for recurrence!
62
What is the recommended total dose (EBRT + Brachy boost) recommended for cervical cancer?
- 45 Gy EBRT + 35-45 Gy LDR/HDR
- Total: 80-90 Gy
63
What are the current USPTF PAP smear recommendations for cervical cancer in the USA?
- < 30 yrs: Pap q3 yrs
- ≥ 30 yrs: One of
-- Pap q3 yrs
-- Pap + HPV co-testing q5 yrs
- ≥ 65 yrs: No testing
64
How does the 5-yr cervical cancer OS depend on the stage?
- IA1 - 97.5%
- IA2 - 94.8%
- IB1 - 89.1%
- IB2-75.7%
- IIA - 73.4%
- IIB - 65.8%
- IIIA - 39.7%
- IIIB - 41.5%
- IVA - 22.0%
- IVB - 9.3%
- Note sharp drop in OS w/ stage III
65
What is the defining feature of stage III**B** cervical cancer?
Extension to pelvic side wall OR tumor causing **hydronephrosis or non-functioning kidney**
66
How should a pap smear that shows Atypical SqC of Unknown Significance (ASCUS) be managed?
ASCUS:
- 70% resolve spontaneously
- <1% progress to invasive carcinoma
Management:
- 21-24yrs (lowest risk for cancer) → repeat Pap smear in 12 mos
- > 25 yrs → HPV testing
-- HPV- → repeat Pap smear and HPV testing in 3 yrs
-- HPV+ → immediate colposcopy
67
How should a pap smear that shows Low Grade Intraepithelial lesion (LGSIL) be managed?
LGSIL:
- 50% resolves spontaneously
< 5% progress to invasive disease
Management:
- 21-24 yrs (lowest risk for cancer) → repeat Pap smear in 6-12 mos
- 25-29 yrs → colposcopy
- > 30 yrs
-- If HPV- → repeat Pap smear and HPV testing in 6-12 mos
-- If HPV+ → immediate colposcopy
68
How should a pap smear that shows High Grade Intraepithelial lesion (LGSIL) be managed?
HGSIL:
- Represents moderate to severe dysplasia, or CIN2/3
- 20% will progress to invasive disease
Mangement:
- 21-24 yrs (lowest risk for cancer) → repeat Pap smear in 6 mos
- >25 years → immediate colposcopy with biopsy
69
What is the treatment paradigm for bulky or locally adavanced cervical cancers?
Bulky (>4 cm, IB3, IIA2) or locally advanced → CRT w/ brachy boost
70
What is defined as a bulky tumor in cervical cancer?
- Size > 4 cm
- Main tx paradigms are based on this size cut off, and it is also prognostic
71
When can a hysterectomy be considered following definitive CRT for cervical cancer?
- Inability to deliver a definitive brachy dose
- PET evidence of residual local disease w/o distant metastases 3 mos after completion of EBRT + brachytherapy.
- Bx-proven local disease persistence 8+ weeks EBRT + Brachy
72
How much of the vagina does class I (total abdominal) remove?
Small rim of the cuff
73
How much of the vagina does class II (modified-radical) remove?
Upper 1-2 cm
74
How much of the vagina does class III (radical) hysterectomy remove?
- Upper 1/3
- Most commonly performed
75
How much of the vagina does class IV (extended radical) hysterectomy remove?
Upper 2/3
76
How far down do you cover pre-sacral nodes for cervical cancer?
Down to S3
77
How do you assess parametrial extension of cervical cancer on physical examination?
During the rectal portion of the examination, parametrial extension can be felt as nodularities resulting in a loss of the normal barell shaped contour of the cervix.
78
Which MRI sequence best shows the parametrial extension from a cervical cancer tumor?
T2
79
How do cervical tumors appear on T1 and T2 MRIs?
- T1: low intensity signal
- T2: high intensity signal
80
What was the pt population, randomization, and primary end point of the Italian trial for cervical cancer?
- Stage IB + IIA cervical cancer
- Randomization
-- 47 Gy EBRT + LDR to 70-90 Gy (median 76)
-- Radical hyst + LND + adjuvant RT as indicated
--- Adjuvant EBRT to 50.4 Gy for ≥pT2b, ≤3 mm cervical stroma margin, cut-through, or N+ (given in 64%)
81
What were the main results of the Italian trial for cervical cancer?
RT vs. Surgery
- 5-yr OS: ~83%
-- 20-yr OS: ~75%
- 5-yr DFS: ~74%
- 5-yr LRR: ~ 25%
- Time to relapse 13.5 vs. 11.5 mos (p=0.10)
- Gr 2-3 tox: 12% vs 28%
- 20-yr late complications: 23% vs. 32%
- 64% in surgery arm had adjuvant RT
82
What LN region is added to the nodal CTV for cervical cancer that extends to the lower 1/3rd of the vagina?
Inguinal
83
When are paraaortic LNs included in the CTV for cervical cancer?
- ≥ 1 Common iliac LN+
- ≥ 3 Multiple pelvic LN+
84
What was the pt population, randomization, and primary endpoint of GOG 123 for cervical cancer?
- IB2 cervical cancer
- Randomization:
-- 🏆 neoadjuvant definitive WPRT+brachy+weekly cisplatin → hysterectomy
-- neoadjuvant definitive WPRT+brachy → simple hysterectomy
85
What were the main results of GOG 123 for cervical cancer?
- neoadj. CRT vs. neoadj. RT alone
-- 3-yr OS 83% vs. 74%
-- 3-yr LR 21% vs. 37%
-- 5-yr PFS 71% vs. 60%
-- 5-yr OS 78% vs. 64%
-- pCR 52% vs. 41%
86
What bowel constraint should be used for post-op cervical cancer cases?
V40 < 30%
87
What are the normal tissue constraints per RTOG 0724 for post-op cervix?
- Kidney: 2/3 of each kidney < 18 Gy
- Spinal cord: 0.03 cc should receive > 45 Gy
- Bowel ("bowel space" includes small bowel, colon, and sigmoid out to the edge of the peritoneum)
-- V40 Gy < 30%
- Rectum: V45 Gy < 60%
- Bladder: V45 Gy < 35%
88
What is the probability of PA nodal involvement for a cervical cancer pt w/ -ve PET outside the pelvis?
~10%
89
During brachytherapy boost planning for cervical cancer, what does the HR-CTV include?
- Entire cervix
- Uterine, parametrial, vaginal extent of the disease
90
What are the recommended normal tissue dose constraints for OARs for brachytherapy?
- ICRU bladder point, ICRU rectal point: ≤ 3.7 Gy x 5 fractions
- D2cc bladder: ≤ 90 Gy EQD2
- D2cc rectum: ≤ 75 Gy EQD2
- D2cc sigmoid: ≤ 75 Gy EQD2
91
What was the pt population, randomization, and primary endpoint of PORTEC 1 for endometrial cancer?
- Inclusion:
-- < 50% MMI and G 2-3
-- ≥ 50% MMI and G 1-2
-- all histologies allowed, but the vast majority were endometrial
-- Sampling of suspicious LN only. Routine LN dissection not done
- Specifically excluded:
-- No MMI
-- < 50% MMI and G1
-- ≥ 50% MMI and G3
- Randomization:
-- Obs
-- 🏆 WPRT 46 Gy / 23 fx
- Mnemonic: 1→ unimodality vs. 1 adj. tx
92
What were the main results of the PORTEC 1 for endometrial cancer?
WPRT vs. Obs
- 15-yr LRR 6% vs. 16% (p<0.0001)
-- ~75% in vaginal vault
-- 5 yr LRR 4% vs. 14% (p<0.001)
- 15 yr OS: 52% vs. 60% (NS)
- 15 yr DM: 9% vs. 7% (NS)
The greatest benefit in HIR disease (established post-hoc, requires 2 of 3):
-- Age > 60
-- MMI ≥ 50%
-- Grade 3
Sx, WPRT vs. Obs
- Physical fx: 50.5% vs. 61.6% (p=0.004)
- Urinary, Bowel sx: 23.6%, 14.1% vs. 28.1%, 19.5% (p<0.001)
93
What is the primary interpretation of the PORTEC 1 for endometrial cancer?
- WPRT reduces LR. OS is unchanged.
- At 15-year f/u, WPRT has long-term GI and GU toxicity and worse physical function.
-- WPRT should be limited to HIR patients
94
What is the FIGO 2009 staging for endometrial cancer?
- I: Confined to the uterine corpus
-- IA (T1a): Invades < 50% of the myometrium
-- IB (T1b): Invades ≥ 50% of the myometrium
- II (2): Invades cervix, but no extension beyond the uterus
- III (3): Local and/or regional spread
-- IIIA (T3a): Involves the serosa and/or adnexa
-- IIIB (T3b): Involves the vagina and/or parametrium
-- IIIC1 (N1): Pelvic lymph node metastasis
-- IIIC2 (N2): Para-aortic lymph node metastasis
- V: Metastasis
-- IVA (4): Invades bladder and/or bowel mucosa
-- IVB (M1): Distant metastasis, including inguinal lymph node involvement
95
What is the stage cut-off for endometrial cancer when pelvic RT is favored over VCB post-TAH/BSO?
- Up to IB Gr II → VCB
- > IB Gr II → Pelvic RT
96
What are the standard VCB-alone regimens for postop tx of endometrial cancer?
- LDR: 60 Gy to the vaginal mucosa
- HDR:
-- 7 Gy x 3 fx, Rx to 5 mm
-- 5.5 Gy x 4 fx, Rx to 5 mm
-- 6 Gy x 5 fx, Rx to vaginal mucosa
97
What are the standard VCB-boost regimens for postop tx of endometrial cancer?
- LDR: ~70 Gy to the vaginal mucosa
- HDR:
-- 6 Gy x 3 fx, Rx to the vaginal mucosa
-- 6 Gy x 2 fx, Rx to the vaginal mucosa
98
What are the standard post-WPRT VCB regimens for postop tx of endometrial cancer?
- 45 Gy WPRT → VCB 6 Gy x 3 fx to the vaginal mucose (RTOG 0921)
- 50.4 Gy WPRT → 6 Gy x 2 fx to the vaginal mucosa (RTOG 0418)
99
What are type I histologies for endometrial cancers?
- Type 1:
-- ~80% of endometrial carcinomas.
-- Endometrioid histology, Gr 1-2
-- Estrogen-driven w/ a favorable prognosis.
- Type 2:
-- Less common and more aggressive.
-- Endometrioid histology, Gr 3
-- Non-endometrioid histologies; Clear cell, undifferentiated, squamous, and serous adenocarcinoma
-- Not estrogen-responsive
-- More aggressive w/ a worse prognosis
100
What is the typical CHT regiment for endometrial ca post TAH/BSO?
- conc. cisplatin x2
- adjuvant carbo/taxol x4
101
What was the pt population, randomization, and primary endpoint of PORTEC 3 for endometrial cancer?
- High-risk endometrial cancers
-- Any FIGO I G3 w/ deep MMI and/or LVSI
-- Endometroid: FIGO II-III
-- Serous or clear cell: FIGO I-III
- Randomization:
-- 🏆 WPRT + conc. cisplatin x2 and adjuvant carbo/taxol x4
-- WPRT 48.6 Gy + VCB for cervical invasion
- Mnemonic: 3→trimodality treatment (Surgery + CRT)
102
What are the results of PORTEC 3 for endometrial cancer?
- CRT vs. RT: Overall
--**5-yr OS 81% vs. 76% (p=0.03)**
-- **5-yr FFS 77% vs. 69% (p=0.016)**
-- **5-yr isolated DM 21% vs. 29%**
- The greatest benefits were seen in **Stage III** and **Serous** histology
-- Stage I-II OS ~83%, FFS ~80% (NS)
-- Stage III 5-yr OS 79% vs. 69%
-- Stage III 5-yr FFS 71% vs. 58%
-- *Serous:*
--- 5-yr OS 71% vs. 53%
--- 5-yr FFS 60% vs. 48%
103
What are the main interpretation of PORTEC 3 for endometrial cancer?
- OS and FFS benefit from CRT
-- Limited to Stage III.
-- On histologic analysis, most sig. in serous histology
-- On molecular analysis, the benefit is only in p53abn (a/w serous hist)
-- There was no benefit in Stage I-II, POLEmut, MMRd, or NSMP.
- IMRT had less toxicity than 3DCRT
104
Which molecular profiles impact survival in high-risk endometrial cancer patients?
- The associated recurrence-free survivals (primary endpoint) were:
-- p53abn: 48%
-- MMRd: 72%
-- NSMP: 74%
-- POLEmut: 98%
- The 5-year RFS for EBRT alone vs CRT + adjuvant CHT were:
-- p53abn: 36% --> 59% (p=0.02)
-- MMRd: 76% -> 68% (p=0.43)
-- NSMP: 68% --> 80% (p=0.24)
-- **POLEmut: 97% --> 100% (p=0.64)**
105
In high-risk endometrial cancers, which histology and terminology are usually a/w p53abn?
- Serous
- Copy number high
106
What are the findings of QOL data for PORTEC 3 for endometrial cancer?
- Gr 2 or 3 AEs were more common in patients receiving CRT *during treatment* but not *12 and 24 mos post-treatment*
-- Notable exception: Neuropathy is more common in those who received CRT
107
What is the patient population, randomization, and primary endpoint of PORTEC 2 for endometrial cancer?
- Pt population
-- HIR (2 of 3): age > 60, > 50% MMI, Gr 3
-- Stage IIA (endocervical gland involvement) and any age
-- Grade 3 w/ >1/2 MMI excluded
-- Adenocarcinoma only
-- Nodes: Suspicious pelvic or PA lymph nodes removed. Routine LN dissection not allowed
- Randomization:
-- WPRT 46 Gy
-- 🏆 VCB to *proximal 1/2 of vagina*, HDR 21 Gy in 3 fx, or LDR 30 Gy Rx to 5mm depth
- Mnemonic: 2→ choice b/w 2 RT options (WPRT vs. VCB)
108
What are the main results of PORTEC 2 for endometrial cancer?
WPRT vs. VCB:
- 5-yr VR 1.6% vs. 1.8% (NS)
-- 10-yr VR 2.4 vs. 3.4% (NS)
- **5-yr pelvic recurrence 0.5% vs. 3.8%**
-- **10-yr pelvic recurrence 1% vs. 6%**
- 5-yr OS ~84%
- 10-yr OS ~68%
- 10-yr CSS ~90%
- 10-yr DM ~10%
- Gr 1-2 tox
-- **54% vs. 13%**
109
When is CHT indicated for serous endometrial cancer?
- Stage IB-IV
-- consider multi-modal therapy including CHT ± WPRT ± VCB
- Serous is considered high-grade histology
110
What was the pt population, randomization, and primary endpoint of GOG 122 for endometrial cancer?
- Stage III or IV with ≤2cm residual post-op disease
- Randomization:
-- Cisplatin/Doxorubicin x 7C f/b Cisplatin x1C
-- Whole abdomen RT (30 Gy/ 20 fx with 15 Gy boost)
111
What were the results of GOG 122 for endometrial cancer?
- WART vs. CHT, unadjusted (p values not provided)
-- 5-yr PFS 38% vs. 42%
-- 5-yr OS 42% vs. 53%
- After adjusting for the stage, since arms were unbalanced:
-- 5-yr PFS 38% vs. 50% (p < 0.01)
-- 5-yr OS 42% vs. 52% (p < 0.01)
- With chemo, more grade 3-4 heme and GI toxicity
112
What are the main criticisms of GOG 122 for endometrial cancer?
- Stat sig. came only after adjustment for stage imbalance in the arms
- As residual disease was included, the RT dose is NOT sufficient
- VCB was NOT used
- RT volumes were large
- Relapse rates were high in both arms
- Only 63% completed CHT
113
What are the features of high vs. low-risk endometrial cancer?
114
What were the pt population, randomization, and primary endpoint of GOG 99 for endometrial cancer?
- HIR Endometrial Cancer:
-- Age ≥70 with 1 risk factor
-- ≥50 with 2 risk factors
-- or any age with 3 risk factors
- Factors are Gr 2-3, LVSI, or outer 1/3rd invasion
- Randomization:
-- 🏆 WPRT 50.4 Gy
-- Observation
115
What were the main results of GOG 99 for endometrial cancer?
WPRT vs. Obs:
- 2-yr LR 3% vs. 12%
- LR in vagina 2% vs. 13%
- LR in pelvis only 0% vs. 4%
- 4-yr OS 92% vs. 86% (NS)
- In HIR subgroup
-- 2-yr LR 6% vs. 26%
116
What is the primary interpretation of GOG 99 for endometrial cancer?
- WPRT reduced LR, especially in the HIR group
117
Per GOG 99 for endometrial cancer, what % of recurrences occur in the vagina?
~75%
118
What features comprise the LR risk group per GOG 99 for endometrial cancer??
- Low-Risk **(LR)**, Per GOG 99
-- Stage IA, Gr 1, LVSI-
119
What features comprise the LIR risk group per GOG 99 for endometrial cancer??
- Per **GOG 99**, path risk factors (GOLs)
-- **G**r 2 or 3
-- **O**uter 1/3rd MMI
-- +**L**VSI
- Low-Intermediate Risk **(LIR)**:
-- Stages IB, IC, II
-- ≤50 yr and ≤2 risk factors
-- 50–69 yrs and ≤1 risk factor
-- ≥70 yr and no risk factors
120
What features comprise the HIR risk group per GOG 99 for endometrial cancer??
- Per **GOG 99**, path risk factors (GOLs)
-- **G**r 2 or 3
-- **O**uter 1/3rd MMI
-- +**L**VSI
- High-Intermediate Risk **(HIR)**:
-- Stages IB, IC, II
-- ≤50 yr and 3 risk factors
-- 50–69 yrs and ≥ 2 risk factors
-- ≥70 yr and ≥ 1 risk factors
121
What features comprise the HIR risk group per post-hoc analysis of PORTEC 1 for endometrial cancer??
- 2 of 3:
-- > 60 y
-- G 2/3
-- MMI >50%
122
What features comprise the HR risk group per GOG 99 for endometrial cancer??
- High-Risk **(HR)**, Per GOG 99
-- Stage III
-- Stage IVA
123
Which endometrial cancer pts benefit from adjuvant **RT** post-TAH/BSO?
- Per GOG 99, **adjuvant RT** vs. Obs
-- **2 yr LR (all): 3% vs. 12% (p=0.007)**
-- **2yr LR (HIR): 6% vs. 26% (p=0.007)**
-- 4 yr OS: 92% vs. 86% (p=0.557)
- High-Intermediate Risk **(HIR)**:
-- Stages IB, IC, II
-- ≤50 yr and 3 risk factors
-- 50–69 yrs and ≥ 2 risk factors
-- ≥70 yr and ≥ 1 risk factors
- Per **GOG 99**, path risk factors (GOLs)
-- **G**r 2 or 3
-- **O**uter 1/3rd MMI
-- +**L**VSI
124
What is the strongest pathologic risk factor for local and distant recurrence?
+LVSI
125
Which endometrial cancer pts benefit from adjuvant **CRT** post-TAH/BSO?
**PORTEC 3 Eligibility Criteria** for CRT:
- Any FIGO I G3 w/ deep MMI and/or LVSI
- Endometroid: FIGO II-III
- Serous or clear cell: FIGO I-III
PORTEC 3 results
- CRT vs. RT: Overall
- **5-yr OS 81% vs. 76% (p=0.03)**
- **5-yr FFS 77% vs. 69% (p=0.016)**
- **5-yr isolated DM 21% vs. 29%**
- The greatest benefits were seen in **Stage III** and **Serous** histology
-- Stage I-II OS ~83%, FFS ~80% (NS)
-- Stage III 5-yr OS 79% vs. 69%
-- Stage III 5-yr FFS 71% vs. 58%
-- *Serous:*
--- 5-yr OS 71% vs. 53%
--- 5-yr FFS 60% vs. 48%
126
Which endometrial cancer patients are at the lowest risk for LN metastases?
- MMI < 50%
- Size < 2 cm
- well- or moderately- differentiated
127
What medication may be used for an attempt at fertility preservation for pts w/ stage IA, G1 endometrial cancer pts?
- Megestrol acetate (Megace): Continous progesterone-based agent
-- PR+ tumors respond best, but a durable response is achieved in ~50% of the pts
-- Close observation w/ endometrial sampling q3-6 mos
128
What is the most common site of failure for endometrial ca pts post TAH/BSO and VCB?
Abdomino-Pelvic (Sub-Diaphragmatic)
129
In patients w/ advanced or recurrent endometrial cancer, which IO drug added to standard CHT improves PFS?
Pembrolizumab (NRG-GY018)
130
What were the pt population, randomization, and primary endpoint of RTOG 1203 (TIME-C) for endometrial cancer?
- Pt
-- Endometrial ± cis
-- Cervix ± cis
- Randomization:
-- 3DCRT
-- 🏆 IMRT
131
What were the results of RTOG 1203 (TIME-C) for endometrial cancer?
- 7.8% of IMRT pts had to take antidiarrheal medications 4+ times daily compared to 20.4% 3D CRT pts
- 33.7% of IMRT pts had frequent or almost constant diarrhea compared to 51.9% of 3D CRT pts
- Overall, IMRT pts reported less diarrhea, frequency of incontinence, and interference of incontinence with IMRT
132
What does a properly positioned T&O implant look like?
