Gyn.apkg Flashcards
1
Q
what does FIGO stand for
A
International Federation of Gynecologists and Obstetricians
2
Q
what is sentinel lymph node for cervical dissemination va lateral pelvic route
A
obturator node - spreads from there to ext iliacs
3
Q
what lymph node allows spread fo deep inguinals for vulvar cancer
A
“saphenofemoral junction lymph node<div><img></img><br></br></div>”
4
Q
what stages of cervical cancer are amenable to cryo, laser cone, CN cone, LEEP, or radical trachelectomy, or simple hysterectomy
A
stage IA, no LVSI
5
Q
what stage cervical cancer is best managed via modified rad hysterectomy
A
stage Ia, +LVSI
6
Q
which stages of cervical cancer are treated with radical hysterectomy
A
selected IB, IIA
7
Q
what stage cervical cancer is treated definitively with RT without concurrent chemo?
A
stage IB1
8
Q
what stages of vulvar cancer are treated surgically vs definitely not surgically
A
IA,IB,II<div><br></br></div><div>vs</div><div><br></br></div><div>IVA,IVB</div>
9
Q
what is the rule of 15s for cervical cancer
A
stage 1: 5yr OS 85%, 15% +pelvic LN<div>stage 2: 5yr OS 70%, 30% +pelvic LN<br></br></div><div>stage 3: 5yr OS 55%, 45% +pelvic LN<br></br></div>
10
Q
What imaging contributes to FIGO stage for uterine cancer
A
Just CXR<div>Nothing else contributes to clinical stage</div><div>So someone can be staged as 1B but practically will be treated as 3C</div>
11
Q
what aspect of uterine staging was dropped in most recent FIGO update
A
dropped cervical gland involvement from stage IIA - just cervical stomal invasion matters
12
Q
GOG99 Keys 2004 high risk factors
A
grade 2-3<div>LVSI</div><div>outer 1/3 myometrial invasion</div>
13
Q
what paper supports use of IMRT over 3DCRT four field for postop endometrial cancer
A
RTOG 1203 / TIME-C<div><br></br></div><div>worse GI,GU side effects and poorer measures of QOL</div>
14
Q
what are the aggressive uterine cancers (other than sarcoma)
A
papillary serous<div>clear cell</div>
15
Q
GOG-33 Creasman et al 1987: describe study, pt selection, one-liner results
A
prospective surgical path study of 621 stage I endometrial cancer (excluded occult stage II via endocervical curettage)<div><br></br></div><div><br></br></div>
16
Q
what are the differences between FIGO 2014 vs 2018 staging for cervical cancer
A
eliminated width criteria in IA dz<div><br></br></div><div>added >5mm depth to stage IB</div><div>redefined IB1 (previously =4cm, now <2cm) and IB2 (previously >4cm, now 2-4cm), added IB3 (now >4cm)</div><div><br></br></div><div>added IIIC1/2 for pelvic vs para-aortic LAD</div><div><br></br></div><div>can use MRI, PET, ultrasound as part of staging</div>
17
Q
what are you covering if you extend WPRT field to T11
A
psoitive common iliac nodes or paraaortic nodes
18
Q
Why was point A chosen? Historical significance?
A
People used to get bladder and bowel necrosis, thought to be due to damage to uterine artery which provides some vasculature to these organs as well <div><br></br></div><div>Idea wasn’t to get dose to point A, but to avoid exceeding 85 Gy to point A</div>
19
Q
Where is point B in T&O brachy? Meant to represent what? Goal dose at pelvic sidewall?
A
Up 2cm and over 5cm from patient midline<div>Proxy for pelvic sidewall/obturator nodes</div><div>61 Gy prescription dose for Ir129</div>
20
Q
What is indication for interstitial needles for cervical cancer
A
Dz extension not covered by standard intracavitary brachy<div><br></br></div><div>Difficult to reach if >0.5cm from mucosa</div><div>Significant Palpable parametrial dz on rectovaginal exam</div>
21
Q
When after surgery to perform VBT for endometrial cancer
A
Bring pt back 4wks after surgery to examine healing<div>If good, proceed</div><div><br></br></div><div>Decline in control if not done within 9wks after surgery</div>
22
Q
What to Eval on plain film for T&O?
A
Is there packing above ovoids?<div>Is tandem bisecting space between ovoids?</div><div>Is tandem roughly midline in patient?</div><div>Are ovoids and tandem marker flush w fiducials?</div><div>Are ovoids rotated or level with each other? (Know rotated if see more than one dumbbell)</div><div>Is there packing on ant and post vaginal wall?</div><div><br></br></div>
23
Q
How to differentiate grade 1/2/3 endometrial cancer
A
<5% nonsquamous, nonglandular cells<div>5-50% nonsquamous, nonglandular cells</div><div>>50% nonsquamous, nonglandular cells</div>
24
Q
Does parametrium require sampling with either uterine or cervical cancer?
A
Required w cervical
25
what describes the rate of rapid dose falloff in brachytherapy?
inverse square law
26
what is most common isotope used for gyn brachy?
Irridium-192
27
what 2 trials support whole pelvic PORT for endometrial cancer in high risk pts?
PORTEC-1, GOG-99
28
what trial supports substitution of VBT for WPRT in select patients for PORT for endometrial cancer?
PORTEC-2
29
where are 75% of recurrences in PORTEC-1 trial?
vaginal cuff
30
what is the effect of vaginal cylinder diameter on dose to 5mm depth?
"thicker vaginal cylinder (3cm) can slightly underdose at 5mm depth
![]()
"
31
which cylinder position reduces dose to rectum: neutral vs parallel vs angled?
"parallel looks best to me![]()
![]()
"
32
what was the question in GOG-99? pt population? regimen?
"
PRT 392 pts with “intermediate risk” endometrial CA evaluating TAH/BSO with pelvic and PA nodal sampling and cytology randomized to no adjuvant therapy or WPRT (50.4 Gy/28 fx)
"
33
what were revised inclusion criteria for GOG-99?
"high intermediate risk as defined by GOG-33
"
•Age >70 with 1 risk factor
•Age >50 with 2 risk factors
•Any age with 3 risk factors
Risk factors include grade 2-3, LVSI or outer 1/3 myometrial invasion
34
what were results from GOG-99?
"Reduction in 2-yr recurrence rates for all patients (12% vs 3%) with biggest benefit in HIR pts (26% vs 6%), no difference in OS (was not powered for OS)
Reduction for low intermediate risk 6 vs 2%
"
35
what was the patient population/eligibility/regimen for PORTEC-1?
"
-PRT 714 pts w/ stage I endometrial cancer evaluating TAH/BSO + cytology +/- pelvic RT (no IVRT or PLND)
-Eligibility: <1/2 MI and G2-3 or >=1/2 MI and G1-2
-RT given as 46 Gy/23 fx in 2-4 fields within 8 weeks post-op
"
36
what were LRR results from PORTEC-1? Who obtained most benefit?
"
Reduction in 15-yr LRR (16% vs 6%), greatest benefit observed in pts with 2-3 risk factors (age ≥60, >50% MI and Grade 3), no difference in OS or DM
"
37
what were the tested regimens in PORTEC-2?
"
PRT of 427 HIR pts s/p TAH/BSO (no PLND) randomized to EBRT (46 Gy/23 fx) vs VBT (21 Gy/3 fx) HDR or 30 Gy LDR
"
38
what were differences in vaginal recurrence in PORTEC-2?
1.6% EBRT, 1.8% VBT
39
what were differences in local regional recurrence in PORTEC-2?
2.1% EBRT, 5.1% VBT
40
what were differences in pelvis only recurrence in PORTEC-2?
1.5% EBRT vs 0.5% VBT
41
was there a difference in OS or DFS in PORTEC-2?
no
no recurrences differences were statistically significant, either
42
what toxicity improvements were observed with VBT vs EBRT in PORTEC-2?
"53.8% vs 12.6% grade 1-2 GI toxicity
2% vs 0% late grade 3 GI toxicity
better QoL scores w brachy
"
43
what two prospective randomized trials examined the question of the utility of VBT +/- WPRT in postop endometrial cancer?
Aalders, Norway 1980
Sorbe, Swedish intermediate risk 2012
44
what was pt population in Aalders Norway trial?
"
PRT 540 pts with stage I endometrial CA evaluating TAH/BSO (no PLND) followed by VBT then randomized to no further treatment vs pelvic EBRT
"
45
what were differences in local recurrence vs distant mets on Aalders Norway trial?
"
•Pelvic RT arm had decreased 9-yr LR (6.9% vs 1.9%), but non-statistically more distant mets (5.4% vs. 9.9%)
"
46
what was difference in OS for all-comers vs important subset on Aalders Norway trial?
"
No difference in 5 or 9-yr OS (90% vs 87%)
on subset analysis pelvic RT did improve survival for patients with G3 and >50% MI or LVSI (72% vs 82%)
*recall that all pts on this trial were stage 1
"
47
what was the pt population and tested regimen in the Sorbe Swedish intermediate risk trial?
"
"
PRT 527 pts randomized to TAH/BSO+VBT +/- WPRT
•Stage I endometrioid with 1 RF (G3, IB or DNA aneuoploidy)
•EBRT 46 Gy + VBT or VBT alone (3 Gy x 6, 5.9 Gy x 3 or 20 Gy x 1 to 5 mm)
48
what was difference in pelvic recurrences and OS in Sorbe Swedish Int Risk trial?
"
Reduced pelvic recurrences with combined VBT+WPRT (5% vs 1.5% at 5 yrs)
no difference in survival
"
49
what trial shows no need for postop VBT in low risk endometrial cancer?
Sorbe Swedish Low Risk Trial 2009
50
what was difference in vaginal recurrence rates in Sorbe Swedish Low Risk trial?
"
No significant difference in vaginal recurrenc (3.1% w/o vs 1.2% w/, p = 0.114)
"
51
what was difference in toxicity in Sorbe Swedish low risk trial?
"
Toxicity slightly higher with VBT (2.8% vs 0.6%)
"
52
what is difference in recommended dosing per ABS for T&O for cervical cancer if pt has <4cm residual dz vs nonresponder or >4cm residual disease? What is dose per fraction?
EQD2 >80 Gy = 5.5 Gy / 5 fx
vs
EQD2 85-90 Gy = 6 Gy / 5 fx
53
what is are the pros/cons of tandem and ring vs tandem and ovoid?
Ring is better for shallow fornices, higher vaginal wall dose however
Ovoids have better lateral displacement
54
what and where is point P in Manchester system?
"2cm superior to ovoids and 6cm lateral
![]()
"
corresponds to pelvic sidewall
55
what is dose-limiting structure in T&O brachy plan in Manchester system?
rectal point
56
what % of local failures for cervical cancer occur in HR-CTV or IR-CTV as defined by GEC-ESTRO?
"98%
EMBRACE I (prospective study of MRI adaptive brachytherapy)
"
57
what is data to guide GEC-ESTRO guidelines for EQD2 >85Gy to HR-CTV?
"
"
RetroEMBRACE: retrospective multi-center report of clinical and dosimetric outcomes using image-guided brachytherapy for locally advanced cervical cancer
•Excellent LC (81%), PC (87%), OS (74%), CSS (79%) with limited morbidity
•Significant correlation between local control and dose to target volumes (D90 >=85 Gy to HR-CTV resulted in >94% control for small targets, >93% for medium targets and >86% for large targets) à used of combined intracavitary-interstitial in necessary cases increased LC
58
what influence does poor placement of ovoids or packing have on disease control?
"![]()
-Patients with unacceptable symmetry of ovoids to the tandem had higher risk of LR compared to acceptable group (HR = 2.67)
-Displacement of ovoids relative to cervical os increased risk of LR (HR = 2.50) and DFS (HR = 2.28)
-Inappropriate placement of packing resulted in lower DFS rate (HR = 2.06)
"
59
what is time period (range) between initial HPV infection and development of cervical caner?
5-20 years
60
which HPV viruses are assoc w highest risk of cervical cancer?
HPV 16 and HPV 18
61
what is AJCC 8th edition nodal staging for cervical cancer?
"![]()
"
62
what study established WPRT+brachy for standard of care for stage IB-IIA cervical cancer?
Milan study
aka Landoni et al 1997, update in 2017
63
what is the clinical relevance of the Milan study for cervical cancer?
Surgery and RT have similar efficacy. RT preferable for larger tumors >4cm vs surgery preferable for adenocarcinoma.
Tumor diameter, histology, age, and comorbidities should be considered.
64
what was the pt population studied in the Milan / Landoni cervical cancer trial?
343 patients with stage IB-IIA cervical cancer
65
what was the regimen studied in the Milan / Landoni cervical cancer trial?
radical hysterectomy + LND + adj RT if indicated vs 47 Gy EBRT + LDR to 70-90 Gy (median 76)
indicated for adj RT after surgery = pT2b, =3mm cervical stroma margin, tumor cut-through, N+. 65% got adj RT
66
what was 5 vs 20yr OS rates in Milan / Landoni cervical cancer trial
5yr OS 83%
20yr OS 75%
no differences between surg vs RT
67
what was recurrence rate in Milan / Landoni cervical cancer trial
25%
68
what was median time to relapse in Milan / Landoni cervical cancer trial
13.5 mos for surgery
11.5mos for RT
p=0.10
69
what additional morbidites were seen with adjuvant RT in Milan / Landoni cervical cancer trial
hydronephrosis, cystitis, LE edema, bowel obstruction
70
what is the clinical relevance of GOG 71 (Keys 2003)?
showed no overall benefit to hysterectomy after definitive RT
Though on subanalysis, hysterectomy seemed to be favored in larger tumors size 4-6cm
71
what was patient population studied in GOG 71 (Keys 2003)?
256 patients with bulky IB cervical cancer (tumor/cervix 4cm or larger)
72
what was the regimen studied in GOG 71 (Keys 2003)
40 Gy EBRT + 40 Gy LDR
vs
45 Gy EBRT + 30 Gy LDR + extrafascial hysterectomy
73
what was differences in 5yr local recurrence, PFS, and disease progression in GOG 71 (Keys 2003)
5yr LR 27 vs 14%
5yr PFS 53 vs 62% p=0.09
5 yr disease progression 46 vs 37% p =0.07
all slightly favoring hysterectomy over RT alone
74
was grade 3-4 toxicity different in GOG 71 (Keys 2003)
no
75
what was the clinical relevance of the Tata Memorial Centre trial (Gupta 2018) in cervical cancer?
Induction chemotherapy (carbo/taxol) prior to hysterectomy provided no benefit compared to definitive chemoRT, and DFS was worsened.
76
what was the patient population studied in Tata Memorial Centre trial (Gupta 2018) for cervical cancer
635 patients with cervical SCC stage IB2, IIA, IIB
77
what were the regimens compared in Tata Memorial Centre trial (Gupta 2018) for cervical cancer
neoadjuvant carbo/taxol, radical hysterectomy, and postop RT or chemo as indicated
vs
definitive RT + cisplatin
78
what was 5yr OS vs DFS in Tata Memorial Centre trial (Gupta 2018) for cervical cancer
5yr DFS 69% vs 78%, p<0.05
5yr OS 75% both arms
79
what was differences in toxicity in Tata Memorial Centre trial (Gupta 2018) for cervical cancer
late toxicities generally worse w RT.
rectal 2.2 vs 3.5%
bladder 1.6 vs 3.5%
vaginal 12 vs 26%
80
what 2 studies are considered most important for establishing definitive chemoRT for management of cervical cancer
Univ of Liverpool meta-analysis (Green, Lancet 2012)
GOG 123 (Keys 1999, Stehman 2007)
81
what was the patient population and regimen studied in the Liverpool metaanalysis (green et al, Lancet 2001)?
19 trials of patients with cervical cancer randomized to RT vs RT with concurrent chemo
82
what was the differences in PFS and OS in Liverpool metaanalysis (green et al, Lancet 2001) for cervical cancer?
PFS 47 vs 63%
OS 40 vs 52%
favoring chemoRT
83
was there difference in toxicities for RT vs chemoRT in Liverpool metaanalysis (green et al, Lancet 2001) for cervical cancer?
no
84
what was the patient population in GOG 123 (Keys NEJM 1999, Stehman 2007)
369 patients with IB2 cervical cancer
85
what were the tested regimens in GOG 123 (Keys NEJM 1999, Stehman 2007)
WPRT + brachy followed by adj simple hysterectomy
vs
WPRT + brachy + weekly cisplatin followed by adj simple hysterectomy
86
what was rates of pCR at hysterectomy in GOG 123 (Keys NEJM 1999, Stehman 2007)?
52% vs 41% favoring chemoRT
87
what was 5yr PFS and OS in GOG 123 (Keys NEJM 1999, Stehman 2007)
5yr PFS 71 vs 60%
5yr OS 78 vs 64%
(for reference only)
3yr LR 21 vs 37%
3yr OS 83 vs 74%
all favoring chemoRT over RT
88
what is the clinical relevance of GOG 33 (Creasman 1987)
surgical studying demonstrating Increased grade and invasion correlates with probability of nodal mets in 621 patients with clinical stage 1 endometrial cancer who underwent TAH/BSO, PLND, and peritoneal histology
89
what defined low/medium/high risk categories from results of GOG 33?
low: grade 1, invasion of endometrium only
moderate: grade 2-3 or up to invasion of middle third of myometrium (33-66% DOI)
high: intraperitoneal disease or outer 1/3 myometrial invasion
90
what two factors corresponded most strongly with extrauterine disease in GOG 33?
grade and depth of myometrial invasion
91
what is risk of pelvic node involvement based on grade and DOI in GOG 33?
Risk of pelvic nodes
Grade 1 2 3
inner 1/3 | <5% | 5% | 10%
middle 1/3 | 5% | 10% | 10%
outer 1/3 | 10% | 20% | 35%
92
what is rough risk of PA node involvement based on grade and DOI in GOG 33?
"Risk of PA nodes
Grade 1 2 3
inner 1/3 |<5% | 5% | 5%
middle 1/3 | 5% | 5% | 5%
outer 1/3 | 5% | 15% | 25%
"
93
what was clinical relevance of GOG 99?
This trial showed that HIR patients w endometrial cancer s/p TAH benefit from adjuvant WPRT. The later PORTEC 2 showed that VC brachy is as effective as WPRT and with less adverse effects.
94
does undergoing LND affect pelvic recurrences following TAH/BSO+PLND for FIGO 1 endometrial cancer based on data from GOG 99 and PORTEC-1?
"pelvic recurrence in GOG 99 (which used LND) with no RT is 4%, same as PORTEC-1 (no LND allowed), which is 3.6% (Creutzberg 2000).
"
"
95
what was patient population in GOG 99?
IB, IC, occult IIA,B s/p TAH/BSO
Excluded: pap serous/clear cell, cytology
Originally included intermediate risk, then amended to include HIR
96
how was high intermediate risk defined on GOG 99?
based off of data from GOG 33
age ≥70 with 1 risk factor, ≥50 with 2 risk factors, or any age with 3 risk factors. Factors are grade 2-3, LVI, or outer 1/3 myometrial invasion
97
what were treatment regimens tested in GOG 99?
TAH/BSO with selective LND of pelvis and paraaortic nodes, then randomized to WPRT to 50.4 Gy versus observation
98
how many months after TAH/BSO do most pelvic recurrences occur in endometrial cancer (based on GOG 99)?
18 months
99
what were local recurrence rates in total patient population vs HIR in gog 99?
"whole population: 2-yr LR 3% WPRT vs. 12% obs
HIR: 2-yr LR 6% vs. 26%
"
100
where do majority of endometrial cancers occur following TAH/BSO?
"at the cuff, as demonstrated on GOG 99:
![]()
73% of first recurrences were at cuff on PORTEC-1
"
101
Was there increase in secondary malignancies following RT in PORTEC-1 (WPRT) or PORTEC-2 (cuff brachy)?
no (Witlink 2014)
102
what was patient population of PORTEC-1?
715 patients with Stage I (no IC Gr 3 or IB Gr 1) who underwent TAH/BSO (any histo allowed, but vast majority endo) without routine LND (performed if lymph nodes appeared suspicious)
103
what was high intermediate risk defined in PORTEC-1?
need 2/3 factors of:
age >60
invasion >50%
grade 3
104
what were differences in high intermediate risk groups as defined by GOG 99 versus PORTEC-1?
"risk factors for GOG 99: grade 2-3, LVI, or 66% invasion. then add age as additional risk factor. if >70, treat with only one factor, if >50, treated with two risk factors, treated any age with all 3 risk factors
risk factors for PORTEC-1: need 2/3 factors of age >60, invasion >50%, or grade 3
"
105
what was tested treatment regimen in PORTEC-1?
WPRT 46 Gy versus observation following TAH/BSO
106
were rates of distant mets or overall survival different in PORTEC-1?
no. 5yr DM rate 7%, 5 yr OS ~82% in both arms
107
what was rate of 5 yr LRR in total population versus HIR in PORTEC-1?
4% WPRT vs 14% obs for total population
HIR: 4% vs 23%
108
what is salvage rate following vaginal recurrence for patients on PORTEC-1?
Nomogram in Creutzberg et al, IJROBP, 2015
If vaginal recurrence, long term control 68% (most treated with radiation and brachy), with 2-yr OS 79% (worse compared to 5yr OS 82% in rest of trial population)
109
what is risk of late complications (15 years) following PORTEC-1 regimen?
"
Late complications 26% WPRT vs. 4% obs
At 15 years, WPRT group had more urinary incontinence, diarrhea, fecal leakage, and limits on daily activities
Late grade 3-4 toxicity 3% vs. 0% (all GI)
"
110
what was clinical relevance of PORTEC-2?
This trial set a standard of VC brachytherapy for HIR patients instead of WPRT (tested on GOG 99, GOG 249, and PORTEC-1).
111
what was patient population in PORTEC-2?
427 patients with HIR stage 1 endometrical cancer or stage IIA
excluded: rare histologies, stage IIA with concurrent grade 3 or deep MI)
112
how was HIR defined on PORTEC-2?
1) age >60 and 66% MI with grade 1-2, or 0-66% MI with grade 3
2) any age with stage IIA (no grade 3 or MI >50% in this group)
113
what was tested regimen in PORTEC-2?
noninferiority design of WPRT 46 Gy vs VCB to proximal 1/2 of vagina
114
what was brachy cuff dosing in PORTEC-2?
proximal 1/2 of vagina
HDR 7 Gy x 3 versus LDR 30 Gy
to 5mm depth
115
what were rates of vaginal recurrence in PORTEC-2?
5-yr VR 1.6% WPRT vs. 1.8% VCB, noninferior
10-yr VR 2.4-3.4%, not different
116
what was pelvic recurrence rates in PORTEC-2?
"5-yr pelvic recurrence 0.5% vs. 3.8% 10-yr pelvic recurrence 1% vs. 6% 10-yr pelvic recurrence first failure 0.5% vs. 2.5%, p=0.10"
117
why did PORTEC-2 conclude that cuff brachy is optimal choice for HIR patients with endometrial cancer despite reduced pelvic recurrences in WPRT group?
recurrence rates at cuff were identical, and majority of all recurrences occur at cuff.
most pelvic recurrences occur with simultaneous distant metastases.
QoL significantly better with cuff brachy.
118
what was patient population studied in Aalders 1980 (Norwegian Radium Hospital)?
540 patients with FIGO 1 adenocarcinoma of uterus s/p TAH/BSO
119
what were tested regimens in Aalders Norwegian trial (endometrial cancer)?
60 Gy cuff brachy +/- WPRT 40 Gy to pelvic lymph nodes
120
what were differences in local control between VCB +/- WPRT in Aalders trial? how did it change in select higher risk patients?
9yr LR 2% WPRT vs 7% VCB
In FIGO IC grade 3 tumors: LC 5% WPRT vs 20%
with LVSI: 0% without versus 20% with LVSI
121
why was overall survival reduced in VCB+WPRT arm in Aalders Norwegian trial?
After 20-yr followup, OS not changed, except decreased in patients age <60 due to 2nd cancer, HR 1.3. Risk of 2nd cancer increased HR 2.0. Most common 2nd malignancy was skin cancer.
Aalders used betatron and Cobalt brachy sources, which are associated with increased scatter. Subsequent analyses of PORTEC 1, PORTEC 2, and TME study in rectal cancer showed no increase in secondary malignancies.
122
what is a significant criticism of PORTEC 1?
Many patients who were reported as having grade 2 disease actually had grade 1 disease. The trial studies a lower risk population than what was anticipated to be enrolled.
123
why do PORTEC trials use age cutoff of 60 as a risk factor instead of age 70, as in GOG trials?
"![]()
Age 60-70 recurrence rates are more similar to patients over age 70.
Recurrence rates for age >60 were ~3x higher compared to <60.
"
124
what was clinical significance of GOG 249?
cuff brachy followed by 3 cycles of outback chemo was not superior to WPRT for stage 1 (HIR), stage 2 endometrial cancer. Acute toxicity (from chemo) was significantly worse, late toxicity was similar.
125
what was patient population in GOG 249?
601 patients with
Stage I endometrial HIR
Stage II endometrial adenocarcinoma
Stage I-II serous (15% total pop) or clear cell (5%) with negative peritoneal cytology
126
what was tested regimen in GOG 249?
TAH/BSO (89% with PLND) followed by
WPRT 45-50 Gy + optional VC for serous, pap or Stage II
vs
VC brachy then carbo/paclitaxel x3
127
what were differences in pelvis or PA nodal recurrences in GOG 249 with WPRT versus VCB+chemo?
4% WPRT vs 9%
other endpoints not different:
5 yr OS ~86%
RFS 76%
VCR 2.5%
DM 18%
128
"what is significance of McGill retrospective study (Niazi 2005) in treating endometrical caner?"
supports treating stage 1 endometrial cancer with single modality HDR in patients who are poor operative candidates
129
what was patient population in retrospective McGill (Niazi 2005) analysis?
38 patients with Clinical (not pathologic) Stage I-II endometrial adenocarcinoma, high operative risk
130
what % of patients received HDR alone in the McGill (Niazi 2005) study for intact endometrial cancer? what was regimen?
79% treated with HDR alone, 21% treated with EBRT + HDR
median EBRT 42 Gy, median HDR 24 Gy in 3 fractions
131
what were disease-specific survival rates in McGill study (Niazi 2005) for endometrical cancer treated with definitive RT?
15-yr DSS 78% for all stages
stage I DSS 90% and stage II DSS 42%
If Stage I by MRI and at least 30 Gy HDR, then 10-yr DSS 100%
132
what clinical factors may indicate need for WPRT instead of cuff brachy, in contrast to initial PORTEC-2 findings?
from 15 year update of PORTEC-2 with molecular analysis:
substantial LVSI
p53 mutation
L1CAM mutation
assocaited with reduction in pelvic recurrences with EBRT compared to cuff brachy
133
What was the clinical relevance of RTOG 9001 (Eifel JCO 2004) for cervical cancer?
trial demonstrating addition of chemo to definitive RT improves OS, LR, and DM
concurrent chemoRT is superior to extended field RT for these metrics in cervical cancer.
134
What was the patient population studied in RTOG 9001 (Eifel JCO 2004) for cervical cancer?
386 patients with stage IIB-IVA, or IB-IIA wih tumor >5cm or +pelvic LN
135
What was the regimen studied in RTOG 9001 (Eifel JCO 2004) for cervical cancer?
→45 Gy EFRT + LDR to 85 Gy
vs.
→WPRT + LDR to 85 Gy + cisplatin/5-FU
136
What were the results of RTOG 9001 (Eifel JCO 2004) for cervical cancer?
8-yr OS 41% in EFRT vs. 67% chemoRT
DFS 46% vs. 61%
LRF 35% vs. 18%
DM 35% vs. 20%
Late effects unchanged.
137
What RTOG trial supports use of EFRT for cervical cancer?
RTOG 7920 (Rotman, JAMA 1995)
138
What was clinical relevance of RTOG 7920 (Rotman, JAMA 1995) for cervical cancer?
EFRT has improved OS over WPRT with less DM and salvage. DFS and LRF are unchanged.
139
What was patient population in RTOG 7920 (Rotman, JAMA 1995) for cervical cancer?
367 patients with IB-IIA ≥ 4cm, or IIB cervical cancer
140
What were the tested regimens in RTOG 7920 (Rotman, JAMA 1995) ?
→WPRT 40-50 Gy
vs.
→EFRT 44-45 Gy
both → 30-40 Gy intracavitary brachytherapy to point A
141
What were the results of RTOG 7920 (Rotman, JAMA 1995)?
Benefit in OS and DM with EFRT
10-yr OS 44% vs. 55% EFRT
DM 23% vs. 16%
DFS ~42%, not different
LRF 31-35%, not different
Local salvage 8% vs. 25%
142
What was difference in toxicity with EFRT for cervical cancer in RTOG 7920?
Grade 4-5 toxicity 4% vs. 8% (p=0.06)
caveat: not IMRT
143
Does outback chemo improve PFS in stage IIB-IVA cervical cancer?
yes, per México City trial (Duenas-Gonzales, JCO 2011)
BUT at the cost of grade 3/4 toxicity 87% vs 46%
and more hospitalizations 30% vs 11%
and no OS benefit
so not standard of care, but currently tested with RTOG 274 without gemcitabine in regimen
144
What was patient population in México City trial (Duenas-Gonzales, JCO 2011) for cervical cancer?
515 patients with stage IIB-IVA cervical cancer
145
What was tested regimen in México City trial (Duenas-Gonzales, JCO 2011) for cervical cancer?
"→EBRT 50.4 Gy + brachy 30-35 Gy with weekly cisplatin
vs.
→Same RT + concurrent cis/gem + ""outback"" cis/gem
"
146
what was PFS benefit with outback chemo in México City trial (Duenas-Gonzales, JCO 2011) for cervical cancer?
3yr PFS 74% outback chemo vs 65% without
BUT with no OS benefit and at significant cost of grade 3/4 toxicity 87 vs 46%
147
what was clinical relevance of Sedlis trial (GOG 92) for cervical cancer?
established adjuvant RT improves PFS and LR in int risk IB cervical cancer.
defines indications for postop RT for cervical cancer
148
what was patient population in Sedlis trial (GOG 92) for cervical cancer?
277 patients with Stage IB cervical cancer, N0 s/p radical hysterectomy.
Simplified criteria: at least two of >1/3 stromal invasion, LVI, ≥4cm tumor (see paper for more detailed criteria)
149
what was the regimen investigated in Sedlis trial (GOG 92) for cervical cancer?
radical hysterectomy showing IB N0 disease, then
→WPRT 46 Gy or 50.4 Gy
vs.
→obs
150
what were LR, PFS, OS results in Sedlis trial (GOG 92) for cervical cancer?
10-yr LR 14% vs. 21%
10-yr PFS 78% vs. 65%
10-yr OS 80% vs. 71%, p=0.07
Update: recurrence 8.8% (adenocarcinoma or adenosquamous) vs. 44% in obs
151
"what was patient population in ""Peters trial"" GOG 109/SWOG 8797/RTOG 9112/INT 0107?"
"243 patients with IA2, IB, IIA cervical cancer and LN+, +margin or +parametria s/p radical hysterectomy"
152
"what was clinical relevance of IA2, IB, IIA and ""Peters trial"" GOG 109/SWOG 8797/RTOG 9112/INT 0107 for cervical cancer?"
established indications for postop chemoRT for cervical cancer
153
"what was tested regimen in ""Peters trial"" GOG 109/SWOG 8797/RTOG 9112/INT 0107?"
radical hysterectomy, then either
WPRT 49.3 Gy/ 29 fx
vs.
WPRT + concurrent cis/5-FU and 2x adjuvant cis/5FU
154
"what were results of ""Peters trial"" GOG 109/SWOG 8797/RTOG 9112/INT 0107 for OS and PFS for cervical cancer?"
favor chemoRT
4-yr OS 81% vs. 71%
4-yr PFS 80% vs. 63%
155
What was clinical relevance of EMBRACE and retroEMBRACE for cervical cancer?
Demonstrated outcomes and practice patterns of image guided BT to the HRCTV. Dose constraints are recommended.
156
what was patient population studied in EMBRACE?
1416 patients with locally advanced cervical cancer who underwent MRI-guided brachytherapy
157
According to EMBRACE, does tandem and ring or tandem and ovoid provide better coverage?
tandem and ring
158
According to EMBRACE, what incremental dose is required to compensate for each 1wk break in treatment delivery?
5 Gy
159
According to EMBRACE, interstitial brachytherapy has better LC than tandems in size over...?
30cc
160
what were local control rates for stage IB, IIB, IIIB cervical cancers in EMBRACE study?
5-yr LC 98% Stage IB
91% IIB
75% IIIB
this compares favorably to historical controls. most failures are systemic.
161
what was OS rates in EMBRACE study?
overall 3-yr OS 74%, 5-yr OS 65%
162
why is D2cc to rectum <65 Gy based on EMBRACE data?
2x less proctitis if <65 Gy
but this is difficult to meet frequently
163
what is rate of fistula if rectum D2cc > 75 Gy on EMBRACE study?
12.5%
vs 0% if <75 Gy
164
According to EMBRACE, keeping rectal dose under what dose keeps grade 2+ toxicity to <10%?
D2cc<69.5 Gy
165
what are vaginal stenosis rates at 65 Gy, 75 Gy, and 85 Gy to rectovaginal point on EMBRACE study?
20%
27%
34%
166
what RTOG trial established IMRT for postop cervical or endometrial cases?
TIME-C (NRG RTOG 1203, Yeung JCO 2020)
167
what was patient population in TIME-C (NRG RTOG 1203, Yeung JCO 2020)?
289 patients with either:
•Endometrial + cis: <50% inv G3 or >50% inv G1-2
•Endometrial ± cis: >50% inv, G3, USC, CCC, any stage II or IIIC1
•Cervix ± cis: Sedlis criteria
•Cervix + cis: pelvic or parametrial node+
168
what were results of TIME-C (NRG RTOG 1203, Yeung JCO 2020)?
patients reported less diarrhea, frequency of incontinence, and interference of incontinence with IMRT
no difference in clinician reported adverse events
169
what is bowel space constraint on TIME-C (NRG RTOG 1203, Yeung JCO 2020)?
V40 < 30%
170
what is rectum constraint on TIME-C (NRG RTOG 1203, Yeung JCO 2020)?
V40 < 80%
171
what is bladder constraint on TIME-C (NRG RTOG 1203, Yeung JCO 2020)?
V45 < 35%
172
what is bone marrow constraint on TIME-C (NRG RTOG 1203, Yeung JCO 2020)?
V40 < 37%
V10 < 90%
173
What was patient population in ASTEC trial (not ASTEC/EN.5) for endometrial cancer?
1408 patients with endometrial cancer limited to uterus body
174
what was tested regimen in in ASTEC trial (not ASTEC/EN.5) for endometrial cancer?
→pelvic LND vs.
→no PLND
Patients int/high risk (33%) further randomized to ASTEC/EN.5 RT trial, regardless of node status
175
what were results of ASTEC trial for endometrial cancer?
No change in RFS or OS with lymphadenectomy
9% positive nodes detected
5% crude rate of lymphedema
On subanalysis, no difference with depth, histology, grade, age, or performance status
176
why would someone still consider LND in patients with endometrial cancer despite negative results of ASTEC trial?
If LND resulted in positive nodes, no adjuvant therapy was required.
N dissection does provide staging information and guides therapy that could result in increased OS.
177
what was patient population in ASTEC/EN.5 trial for endometrial cancer?
905 patients with Stage IA to IIB endometrial cancer, Grade 1-3 (int/high risk).
Pap serous and clear cell allowed.
Positive pelvic nodes allowed in ASTEC, but not in EN.5. Total 4%
PA nodes are excluded
~30% had PLND (from ASTEC randomization)
178
what was tested regimen in in ASTEC/EN.5 trial for endometrial cancer?
pts randomized to PLND in ASTEC, then to ASTEC/EN.5 if they had int/high risk features (33%).
then
→WPRT (median 45 Gy)
vs.
→obs
~50% brachy given in both arms
→WPRT (median 45 Gy)
vs.
→obs
~50% brachy given in both arms
179
what was effect of WPRT on pelvic or vaginal recurrences, OS, and DSS in ASTEC/EN.5 trial for postop endometrial cancer?
Isolated pelvic or vaginal recurrence improved: 3.2% WPRT vs. 6.1%
No change in OS or DSS
180
What was differences in toxicity with WPRT in ASTEC/EN.5 trial for endometrial cancer?
Toxicity worse with EBRT:
57% WPRT vs. 27% observation,
moderate toxicity 22% vs. 8%
late tox 8% vs. 3%
181
what was patient population of FIRES trial (Rossi, Lancet 2017)?
385 patients with Clinical Stage I endometrial cancer of all histologies and grades undergoing robotic staging.
predominantly lower lower grade and postop lower stage cancers
182
what was purpose of FIRES trial (Rossi, Lancet 2017)?
validate SLN approach in endometrial cancer:
evaluate prospective cohort.
→SLN mapping with cervical injection of indocyanine green, plus
→ pelvic LND ± PA LND
Negative SLNs were ultrastaged with immunohistochemistry for cytokeratin
183
what was sensitivity and NPV of SLN mapping on FIRES trial for endometrial cancer?
SLN detected nodal mets in 97% of LNDs (in 12% with positive nodes on dissection)
Sensitivity 97%, NPV 99.6%
184
what was pt population in PORTEC 3?
686 patients with
stage IA endometrial cancer with invasion, G3, and LVSI
or IB G3
or II
or IIIA, IIIC, IIIB if parametrial
or IA with invasion, IB, II, or III with serous or clear cell histology
185
what was tested regimen in PORTEC-3?
hysterectomy, then
→WPRT 48.6 Gy + VCB for cervical invasion
vs.
→WPRT + conc cisplatin x2 and adjuvant carbo/taxol x4
186
what were OS, FFS results of PORTEC-3 after longer followup and adjustment for misbalanced arms from randomization?
5-yr OS 81% vs. 76%, p=0.034
5-yr FFS 77% vs. 69%, p=0.016
These OS and FFS benefits were only in Stage III.
Stage I-II OS ~83%, FFS ~80%, not different
187
what were rates of distant metastases and isolated pelvic/vaginal recurrences on PORTEC-3?
5-yr isolated DM 21% vs. 29%
isolated pelvic (0.3%) and vaginal recurrence (0.9%) not different
188
what was results of PORTEC 3 regimen for papillary serous carcinoma?
5-yr OS 71% RT vs. 53% chemoRT + chemo
5-yr FFS 60% vs. 48%
serous had highest risk of recurrence
189
what was patient population in GOG 258 (Matei, NEJM 2019) for endometrial cancer?
736 patients with
-advanced endometrial carcinoma
-Stage III-IVA, serous papillary and undifferentiated carcinomas allowed
-Stage I-II clear cell or serous carcinoma
-Lymph node dissection optional
-advanced endometrial carcinoma
-Stage III-IVA, serous papillary and undifferentiated carcinomas allowed
-Stage I-II clear cell or serous carcinoma
-Lymph node dissection optional
190
what was tested regimen in GOG 258 (Matei, NEJM 2019) for endometrial cancer?
→WPRT 45 Gy + cisplatin + VCB (for cervix or vaginal involvement) then carbo/paclitaxel x4
vs.
→carbo/taxol x6 alone
191
what was clinical interpretation of GOG 258, which tested chemoRT with 4 cycles adj chemo vs 6 cycles chemo alone in advanced stage III-IVA or serous/undifferentiated endometrical cancer?
RT with concurrent and adjuvant chemo did not significantly improve RFS compared to chemo alone. OS results still maturing.
ChemoRT had less VR, LN recurrence, and toxicity.
Chemo alone had less DM.
OS results are maturing.
192
what were 5yr rates of distant met on GOG 258?
27% chemoRT + chemo vs 21% chemo alone
193
what is common criticisms of GOG 258?
85% finished chemo cycles vs 75% finished chemo in chemoRT arm
4 cycles of carbo/taxol adjuvantly in chemoRT arm vs 6 cycles in chemo arm
194
what study is used for modern planning techniques for vaginal cancer?
ABS guidelines from Beriwal 2012
195
what study provides evidence for favorable outcomes with definitive RT in vaginal cancer?
retrospective study of <200 pts
MDACC Frank et al, IJROBP 2005
196
what was 5yr disease-specific survival for vaginal cancer in Frank MDACC study by stage?
85% stage I
78% stage II
58% stage III-IVA
197
what was 5yr DSS for vaginal tumors <4cm vs >4cm in MDACC Frank study?
82% <4cm
60% >4cm
198
what was relapse rate for early vs late stage vaginal cancer in MDACC Frank study?
68% early
83% late
199
what was vaginal vs pelvic control for vaginal cancer treated w definitive RT in MDACC Frank study?
Vaginal control:
I-II 91%, III-IVA 83%
Pelvic control:
I 86%, II 84%, II-IVA 71%
200
what study established indications for postop RT for vulvar cancer?
"previously called ""heaps"" criteria, which we are trying to rename because the Dr. Heaps in question is convicted of sexual battery of his patients.
now called the UCLA criteria, published 1990
"
201
what were risk factors assoc w recurrence following resection of vulvar cancer in UCLA study?
in order of significance:
stage, margin, depth, growth pattern, vascular invasion, keratin amount, mitotic activity
202
what 3 factors were NOT associated with local recurrence of vulvar cancer following surgery in UCLA study?
tumor size, nucleoli, grade
203
what were recurrence rates with margin <8mm vs <5mm on UCLA postop vulvar study?
8mm: 48%
5mm: 57%
204
what was pt population in GOG 37 (vulvar cancer)?
114 pts with +groin nodes after vulvectomy and lymphadenectomy
205
what was tested regimen in GOG 37?
RT 45-50 Gy to bilateral pelvic and inguinal nodes (excludes primary)
vs.
pelvic node resection
206
what was 6yr groin recurrence for RT vs pelvic LND in GOG 37?
5% vs 24%
207
what was 2 vs 6yr OS rates from GOG 37 (vulvar cancer)?
2yr: 68% vs 54%, favoring surgery
6yr: 51% vs 41%
on subanalysis, benefit in palpable N+, +ECE, ulcerated LN, or 2+ nodes
208
what trial established adjuvant RT for resected vulvar cancer with palpable N+, ECE, ulcerated, or 2+ nodes?
GOG 37
randomized to pelvic and inguinal RT vs pelvic LND
209
what was patient populatin in GOG 88 (Stehman, IJROBP 1992)?
58 pts with clinically N0 vulvar cancer
210
what was tested regimen in GOG 88 (Stehman, IJROBP 1992)?
Radical vulvectomy →
→50 Gy inguinal RT to 3 cm depth
vs.
→groin dissection + pelvic dissection if positive
211
what trial showed superior OS and LC with inguinal LND vs RT for clinically N0 vulvar patients? what is important caveat to this result?
GOG 88
Nodes were treated to depth 3cm, which led to significant underdosage. LF of 18% comparable to historical GOG failure of 24% without RT.
212
what were relapse and OS rates in GOG 88?
trial terminated early due to:
19% relapse in RT vs 0 in surgery
OS 63% vs 88%
but bear in mind, their RT was designed poorly to 3cm depth, resulting in underdosage
213
what trial established SLNbx as a reasonable approach for vulvar cancer?
GOG 173 (Levenback, JCO 2012)
214
what was pt population in GOG 173 (Levenback, JCO 2012)?
452 pts with vulvar cancer with ≥1 mm invasion, size ≥2 cm to <6 cm, clinically node negative
215
what regimen was studied in GOG 173 (Levenback, JCO 2012)?
Phase II
SLN → inguinal dissection to all (regardless of SLN status)
SLN → inguinal dissection to all (regardless of SLN status)
216
what was false negative node rate versus flase negative predictive value in GOG 173?
8.3% with false negative nodes
FN predictive value 3.7%
side note: For tumors <4 cm, FNPV 2.0%
217
what was tested in GROINSS-V? what was general result?
inguinal LND for vulvar cancer if SLN positive
Inguinal LND guided by SNLB leads to low groin failure (5yr recurrence 2.5% with SLN neg, 8% with SLN positive)
218
what was 10 yr DSS for vulvar cancer in GROINSS-V if LR occurred?
reduced from 90% to 69%
note that this provides rationale for postopRT, since local recurrences without RT result in substantially reduced OS
219
what is the question of GROINSS-VII (GOG 270)? what were general results?
can RT replace LND if SLNbx was positive?
yes, if SLNbx only shows micromet
otherwise, require LND due to high failure rate
220
what was purpose of GOG 205?
determine if neoadjuvant chemoRT in unresectable vulvar cancer would improve patient outcomes compared to historical control (phase 2)
221
what was pt population in GOG 205?
58 patients with T3-4, N+ vulvar cancer, deemed unresectable
222
what was tested regimen in GOG 205 for vulvar cancer?
Phase II:
→RT 57.6 Gy/ 32 fx + weekly cis
→ resection
cCR defined by biopsy, pCR defined by surgical resection
223
what was clinical complete response and pCR rates in GOG 205 following neoadj chemoRT for vulvar cancer?
cCR 64%
pCR 50%
