Cervical Cancer

Front 1

Epidemiology
-Age
-Socioeconomic class
-Geography

Back 1

Epidemiology
-Age
--47% < 35 years old at dx
--10% > 65 years old at dx
-Socioeconomic class
--Affects lower class women
--Poor access to healthcare
-Geography
--Relatively uncommon in US
--Most common cancer in middle-aged women
--Also leading cause of death

Front 2

List risk factors

Back 2

HPV exposure (50% HPV-16)
Age of onset sexual activity
Multiple sexual partners
History of genital warts
Cigarette smoking
Oral contraceptives
Immunocompromise

Front 3

Etiology - HPV
-Principal cause of what two diseases
-HPV types and infection rate
-HPV-16 presence

Back 3

Etiology - HPV
-Principal cause
--Invasive cervical cancer
--Cervical intraepithelial neoplasia (CIN)
-More than 80 HPV types
-40 infect genital tract
HPV-16 present in
-50% cervical cancers
-50% high-grade CINs

Front 4

Age of onset of sexual activity

Back 4

During menarche, transformation zone is more susceptible to oncogenic agents
Higher risk of cancer
-Onset sexual activity < 16 years
-Onset sexual activity within one year of menarche

Front 5

Relative risk of cervical carcinoma:

Age at coitarche
Years from menarche to coitarche

Back 5

Age at coitarche
< 16 -- RR 16
16-19 -- 3
> 19 -- 1
Years from menarche to coitarche
< 1 -- RR 26
1-5 -- 7
6-10 -- 3
> 10 -- 1

Front 6

Relative risk of cervical carcinoma:

Total number of sexual partners
Number of partners before age 20
Genital warts
Smoked > 5 cigarettes daily

Back 6

Total number of partners
> 4 vs no/1 parnter RR 3.6
Number of partners before age 20
> 1 partners vs no partner RR 7
Genital warts (any) RR 3.2
Smoked > 5 cigarettes/day > 20 years -- RR 4

Front 7

Cigarette smoking-cancer connection

Back 7

1 Diminished immune function secondary to system effects
2 Local effect of tobacco-specific carcinogens found in cervical mucus
3 Independent risk factor for invasive and preinvasive disease

Front 8

Oral contraceptive connection

Back 8

Possible confounding factor
-Most women who use OCPs are more sexually active
-Exception may be for adenocarcinoma

Front 9

Immunocompromise

Back 9

Women with HIV have increased rates
Same for immunosuppressive rx
Due to suppression of normal immune response to HPV
88% recurrence rate in women with HIV (Maiman Obstet Gyn 1997)

Front 10

Common Symptoms

Back 10

Intermentrual bleeding in premenopausal patient
Menorrhagia
Metrorrhagia

Front 11

Staging: Clinical or Surgical?

Back 11

Clinical -- FIGO staging
-Based on histology for earlier stage I cancers and tumor sizes
-Based on extension of disease to pelvis for more advanced tumors

Front 12

Imaging allowed under FIGO for cervical cancer?

Back 12

CXR
Barium enema
IVP

Front 13

Recent FIGO modification?

Back 13

Original 1929 by League of Nations Health Organization
1950: preinvasive lesions moved from stage I to new stage 0
1976: hydronephrosis added as stage III
1994
- Current definitions of microinvasion (IA1 and IA2) added
- Subdivided IB according to cervical diameter

Better differentiation between stage IA1 and IA2
Stages patients with lesions that are clinically confined to the cervix based on size of the primary tumor

Front 14

Surgical staging better than clinical?

Back 14

Controversial
Clinical staging frequently inaccurate in predicting locoregional spread
FIGO and AJCC suggest method for using TNM categories for staging
Causes confusion when clinicall staged patients are mixed with others who have been classified based on pathologic stage

Front 15

Most common surgical staging method

Back 15

Sampling of pelvic and aortic lymph nodes

Front 16

Advantages of surgical staging

Back 16

Minimizes risk of subsequent radiation injury to small bowel due to surgical adhesions
-Allows for individualized treatment planning

Front 17

Work-up for advanced disease in non-surgical candidate

Back 17

CT abdomen and pelvis with renal and GI contrast
If aortic LN mets
--> FNA of nodes
If positive nodes
--> consider extended-field XRT

Front 18

Scalene lymph node impact

Back 18

1 Negative on clinical exam and positive aortic LN
--> scalene LN biopsy
2 If positive
--> chemotherapy indicated
3 If negative or no aortic LN involvement on CT
--> consider surgical staging

Front 19

Laparoscopic staging?

Back 19

Still investigational

Front 20

Work-up for early stage cancer

Back 20

CXR PA & lat
Stage IA - no CT prior TAH
Stage IB1 - no CT abd/pelvis

Front 21

Prognostic factors

Back 21

Clinical stage
General medical status
Nutritional status
Immune status

Front 22

Effect of anemia

Back 22

605 patients in Canada
Treated with XRT for cervical cancer
Average weekly hgb nadir was significant prognostic factor
Second only to stage
Hgb >= 12 mg/dL improved
1 XRT success
2 Disease-free survival
(1986 Bush Int J Rad Onc Bio Phys)

Front 23

List six important studies

Back 23

GOG 85
GOG 120 Cisplatin
GOG 120 Cis/5FU/H
GOG 123
SWOG 8797
RTOG 9001

Front 24

Laparoscopic staging study

Back 24

98 patients
Lap extraperitoneal approach
Mean nodes 18
23 pts with positive LN
5 required 2nd procedure
2 with complications
Identified patients who might benefit from extended-field XRT with minimal adhesion-related toxicities

Front 25

Explain the genomic iimpact of oncogenic HPV.

Back 25

HPV DNA causes persistent transcription of E6 and E7 genes
-Disrupts the cell cycle control mechanisms
-Through functional inactivation of the tumor suppressor genes
-E6 --> p53
-E7 --> Rb

Front 26

HPV strains
1 Cervical cancer
2 Gential warts

Back 26

1: 16, 18, 31, 33
2: 6 and 11

Front 27

Is cervical cancer an AIDS-defining illness?

Back 27

Yes. Added in 1993.

Front 28

Define parametrium.

Back 28

A layer of visceral pelvic fascia exterior to the smooth muscle of the uterine body and cervix that surrounds the corpus

Front 29

What ligaments support the uterus and how are they formed?

Back 29

Cardinal or transverse
-Bands of dense fibroconnective tissue at the base of the broad ligaments
-Connect the fascia of the lateral cervix and upper vagina with the fibrous tissue that surrounds the lateral pelvic vessels
Uterosacral
-Lie within rectouterine peritoneal folds
-Extend posteriorly from the supravaginal cervix around either side of the rectum
Pubocervical

Front 30

Where does cervical cancer metastasize?

Back 30

Primarily: lung
Secondarily
1 Para-aortic nodes
2 Liver
3 Bone

Front 31

Histology of cervical cancer

Back 31

Squamous carcinoma - 75%
Adenocarcinoma
-Mucinous (endocervical)
-Adenosquamous
Undiff small cell
-Aggressive, poorly diff
-Neuroendocrine features
-Similar to anaplastic small cell of the lung
-Freq widespread mets to bone, liver, skin, and brain

Front 32

The risk of lymph node mets increases with increasing depth of invasion:
1 FIGO Stage IA1
2 FIGO Stage IA2

Back 32

1 FIGO Stage IA1: 0.6%
2 FIGO Stage IA2: 7%

Front 33

The risk of paraaortic nodal involvement increases as the local disease extent increases:
1 FIGO stage IB
2 FIGO stage IIA
3 FIGO stage IIB
4 FIGO stage IIIA
5 FIGO stage IIIB
6 FIGO stage IVA

Back 33

1 FIGO stage IB: 8%
2 FIGO stage IIA: 12%
3 FIBO stage IIB: 29%
4 FIGO stage IIIA: 17%
5 FIGO stage IIIB: 27%
6 FIGO stage IVA: 47%

Front 34

Most common sites for hematogenous spread:
1
2
3

Back 34

1 Lungs
2 Liver
3 Bone

Less common: bowel, adrenals, spleen, and brain

Rare: ovarian

Front 35

In a woman being further evaluated or treated with conization, which modality is preferred?

Back 35

Cold knife cone because there is no thermal artifact to obscure interpretation of the margins.

This may be adequate treatment of stage IA1 disease.

Front 36

Differential diagnosis of cervical lesion.

Back 36

1 Nabothian cysts
2 Glandular hyperplasia
3 Mesoephric remnants or hyperplasia
4 Reactive glandular changes from inflammation
5 Endometriosis

Front 37

Define Point A based on RTOG 0116.

Back 37

Measure 2 cm along the intrauterine tandem from the cervical os or flange of the tandem and 2 cm laterally in the plane of the intracavitary system.
Point where ureter crosses uterine vessels

Front 38

Define Point B based on RTOG 0116.

Back 38

Measure 5 cm lateral from a point 2 cm vertically superior to the cervical os or flange of the central tandem along the patients’ midline.
Point of lateral parametrium.

Front 39

Point for calculation of bladder dose.

Back 39

Calculated at the center (in the superior-inferior plane) of a contrast-filled balloon of a Foley catheter and closest to the applicator system on a lateral view, as defined by ICRU 38.

Front 40

Point for calculation of rectal dose.

Back 40

Calculate the dose at a point 0.5 cm posterior to the vaginal ovoid or vaginal packing in the lateral projection, defined by ICRU 38.

Front 41

Point for calculation of vaginal surface dose.

Back 41

Calculated at the vaginal surface lateral to the midpoint at the surface of the ovoid

Front 42

Per RTOG 0116 what are the max doses for the following normal structures:
1 Spinal cord
2 Bladder
3 Rectum

Back 42

1 Spinal cord: 45 Gy
2 Bladder: 80 Gy
3 Rectum: 75 Gy

Front 43

Per RTOG 0116 what are the max doses for the following normal structures:
4 Vaginal surface
5 Kidney
6 Small bowel
7 10 x 10 area

Back 43

4 Vaginal surface: 135 Gy
5 Kidney: 18 Gy
6 Small bowel: 60 Gy
7 10 x 10 area: 45 Gy

Front 44

Cervical cancer T staging

Back 44

Cervical cancer T staging
T1/I - Confined to uterus
T2/II
- Invades beyond uterus
- Not to pelvic wall or lower 1/3 of vagina
T3/III
- Extend to pelvis wall +/- lower 1/3 vagina
- Causes hydronephrosis
T4/IV
- Invades bladder or rectal mucosa
- Extends beyond true pelvis

Front 45

Cervical cancer FIGO IA

Back 45

Cervical cancer FIGO IA

Confined to the uterus

IA1 - Stromal ≤ 3mm; horiz ≤ 7mm
IA2 - Stromal 3-5mm; horiz ≤ 7mm

Front 46

Cervical cancer FIGO IB

Back 46

Cervical cancer FIGO IB

Visible lesion continued to cervix or lesion > IA2

IB1 Lesion ≤ 4cm

IB2 Lesion > 4 cm

Front 47

Cervical cancer FIGO II

Back 47

Cervical cancer FIGO II

Invades beyond uterus but not pelvic wall or lower 1/3 vagina

IIA No parametrial invasion

IIB Parametrial invasion

Front 48

Cervical cancer FIGO III

Back 48

Cervical cancer FIGO III

Extends to pelvic wall or lower 1/3 vagin or hydro

IIIA Involves lower 1/3 vagina

IIIB Pelvic wall +/- hyddro

Front 49

Cervical cancer FIGO IV

Back 49

Cervical cancer FIGO IV

IVA
- Invades rectal or bladder
mucosa
- Extends beyond true pelvis
IVB
- Distant metastasis

Front 50

In early-stage cervical cancer, which risk factors indicate adj RT after rad hyst and lymphadenectomy?

What are the risk factors?

Back 50

GOG 92 - Sedlis & Rotman

Adj RT for stage IB1 if 2 or more risk factors
- LVSI
- > 1/3 stroma invasion
- Tumor >= 4cm

Front 51

In early-stage cervical cancer, which risk factors indicate adj CRRT after rad hyst and lymphadenectomy?

What are the risk factors?

Back 51

Intergroup 0107 - Peters

Adj CCRT if any feature
1 Positive nodes
2 Positive margins
3 Parametrial involvement

Front 52

What did the Landoni study show?

Back 52

For stage IB and IIA cervial cancer, either surgery or RT was effective.
No difference in PFS, LRR, or OS
More morbidity with surgery +RT (28 v 12%)

Front 53

Does adjuvant hysterectomy after EBRT and brachytherapy for patients with cervical tumors > 4 cm improve PFS and OS?

Back 53

GOG 71 - Keys

No difference in OS
Trend toward decrease LR
No difference in toxicity

Front 54

Does prophylactic extended field RT improve LRC or OS in patients with IIB cervical cancer with no clinical or radiographic evidence of PAN involvement?

Back 54

RTOG 79-20 - Rotman

WPRT 45 or EFRT 45

Improved 10yr OS (55 v 44%)
No difference in LRC or DM
Increased toxicity with EFRT (8 v 4%)

Front 55

Cervical cancer - Tx by stage IA

Back 55

Cervical cancer - Tx by stage IA

IA1
- Simple hysterectomy
- Cone biopsy with negative margins for fertility preservation
IA2: Rad hyst
Brachy alone (7 Gy x 5-6 Fx)
If high-risk features, treat like IB

Front 56

Cervical cancer - Tx by stage IB1

Back 56

Cervical cancer - Tx by stage IB1

Rad hyst with pelvic LND
Def RT
- EBRT WP 45
- Brachy (6Gy x 5 Fx)

Front 57

Cervical cancer - Tx by stage IB2-IIA

Back 57

Cervical cancer - Tx by stage IB2-IIA

CCRT with cisplatin
- EBRT WP 45
- ICBT HDR 6 Gy x 5 Fx

Front 58

Cervical cancer - Tx by stage IIB

Back 58

Cervical cancer - Tx by stage IIB

CCRT with cisplatin
- EBRT WP 45-50.4
- ICBT HDR 6 Gy x 5 Fx

Front 59

Cervical cancer - Tx by stage IIIA

Back 59

Cervical cancer - Tx by stage IIIA

CCRT with cisplatin
- EBRT WP, vagina, and inguinal nodes 50-54
- ICBT 6 Gy x 5 Fx
- If node+, add PAN IMRT (45-60 Gy)

Front 60

Cervical cancer tx by stage: IIIB-IVA

Back 60

Cervical cancer tx by stage: IIIB-IVA

CCRT with cisplatin
- EBRT WP 50-54 Gy
- ICBT 6 Gy x 5 Fx
- If LN+, add PAN IMRT (45-60 Gy)

Front 61

For IIB-IVa, IB-IIA >= 5cm, OR LN+ cervical cancer, is EFRT + ICBT better than WP RT with ICBT and cisplatin/5FU?

Back 61

RTOG 90-01 - Morris & Eifel

CCRT
- Improved OS (67 v 41%)
- DFS (61 v 46%)
- LRF (18 v 35%)

Front 62

For IIB-IVA surgically staged/node-negative cervical cancer, is WP + ICBT with
1 weekly cisplatin
2 cis/5FU/hydroxyurea
3 hydroxyurea alone
better?

Back 62

GOG 120 - Rose

Cisplatin arms
- Improved 4yr OS (65 v 47%)
- Decreased recurrence (34 v 54%)
- Less toxicity with single agents.

Front 63

For IA, IIA > 5cm, and IIB cervical cancers, is WP + ICBT better than WP + ICBT with cisplatin?

Back 63

NCIC - Pearcey

No differences in 3/5yr OS.

Criticized because required only CT staging of nodes and small sample size (353).

Front 64

For IB2 cervical cancer, is WP + ICBT followed by adj simple hysterectomy better than WP + ICBT with weekly cisplatin?

Back 64

GOG 123 - Keys

CCRT
- Improved 3 yr OS (83 v 74%)
- Decreased LR (21 v 37%)
- Increased pCR (52 v 41%)

Felt that improved LC led to increased OS due to cisplatin and adding hysterectomy did not improve OS.

Front 65

According to the Intergroup 0107 trial, patients with IA2, IB, or IIA cervix ca did NOT show benefit after adj pelvic RT and 5FU/cisplatin chemo if they had which of the following pathologic findings?
A Positive parametria
B Positive surgical margin
C Positive pelvic nodes
D Positive LVSI

Back 65

According to the Intergroup 0107 trial, patients with IA2, IB, or IIA cervix ca did NOT show benefit after adj pelvic RT and 5FU/cisplatin chemo if they had which of the following pathologic findings?

D Positive LVSI

Front 66

RTOG 90-01 studied CCRT versus EFRT in high-risk cervical patients. What percentage overall reduction in risk of recurrence was associated with CCRT at median f/u 6.6 years?
A 15%
B 25%
C 50%
D 80%

Back 66

RTOG 90-01 studied CCRT versus EFRT in high-risk cervical patients. What percentage overall reduction in risk of recurrence was associated with CCRT at median f/u 6.6 years?

C 50% (18 v 35% LRF)

Front 67

Which is FALSE about survival with regard to hemoglobin levels in patients with cervical ca treated with CCRT?
A Pretx hgb predicts survival.
B End-of-tx hgb is most predictive of survival.
C Mean hgb during tx is predictive of dz progression.
D Hgb in last 1/3 of tx are most predictve of progression.

Back 67

Which is FALSE about survival with regard to hemoglobin levels in patients with cervical ca treated with CCRT?

Not scored (GOG 0191)

Front 68

Which is true based on Landoni?
A Both arms had identical OS.
B Surgery arm did not receive RT if postive margins.
C Surgical arm pts received adj 5FU if positive nodes.
D Morbidity from urologic cx was identical for both arms.

Back 68

Which is true based on Landoni?

A Both arms had identical OS.

Front 69

GOG 123: Optimal mgt of bulky IB cervical cancer?
A Rad hyst and opstop pelvic RT
B Rad hyst and postop CCRT pelvic
C CCRT + ICBT
D CCRT + ICBT with adj hyst

Back 69

GOG 123: Optimal mgt of bulky IB cervical cancer?

D CCRT + ICBT with adj hyst (in-service answer!)

Front 70

GOG 92: Which is FALSE?
A Addition of pelvic RT improved OS by 20%
B Addition of pelvic RT resulted in more grade 3 and 4 adverse events
C Addition of pelvic RT reduced risk of local recurrences by 47%
D Eligible patients had at least two risk factors (>1/3 stroma, large tumors, LVSI)

Back 70

GOG 92: Which is FALSE?

A Addition of pelvic RT improved OS by 20%

Front 71

42yo s/p rad hyst/PLND for IB2 sqcca cervix: 5cm tumor, deep stromal invasion, +LVSI, all nodes neg. GOG 92: next tx?
A No further therapy
B Pelvic RT alone
C Pelvic RT plus vaginal brachy
D CCRT

Back 71

42yo s/p rad hyst/PLND for IB2 sqcca cervix: 5cm tumor, deep stromal invasion, +LVSI, all nodes neg. GOG 92: next tx?

D CCRT

Front 72

ICRU 38 rectal dose point is how many cm posterior to the vaginal wall on lateral radiograph?
A 0.1 cm
B 0.5 cm
C 1.0 cm
D 1.5 cm

Back 72

ICRU 38 rectal dose point is how many cm posterior to the vaginal wall on lateral radiograph?

B 0.5 cm

Front 73

RTOG 79-20 (Rotman): which at 10 years is most likely with prophylactic EFRT with IIB and bulky IB and IIA cervix ca?
A Diff in OS but not DFS
B Survival after first failure was higher in pelvic RT only arm
C Higher % of local failures were salvaged long-term in pelvic RT alone arm
D Cumulative incidence of death due to cervix ca was higher in EFRT arm

Back 73

RTOG 79-20 (Rotman): which at 10 years is most likely with prophylactic EFRT with IIB and bulky IB and IIA cervix ca?

A Diff in OS but not DFS

Front 74

GOG 92 (Sedlis): Which is true about adding adj RT in patients with poor px features?
A No benefit in pts with adenoca
B No improvement in PFS
C Benefits if deep third of stroma or LVSI
D Reduced risk of recurrence by 80%

Back 74

GOG 92 (Sedlis): Which is true about adding adj RT in patients with poor px features?

C Benefits if deep third of stroma or LVSI

Front 75

GOG 85/SWOG 8695 Intergroup (Whitney): RT with various CT
A Severe leukopenia more common 5FU/Cis group
B 5FU/Cis group with better OS and PFS
C +PAN had best OS rates
D Hydroxyurea arm had fewer pelvic recurrences

Back 75

GOG 85/SWOG 8695 Intergroup (Whitney): RT with various CT

B 5FU/Cis group with better OS and PFS

Front 76

GOG 120 (Rose): RT with 3 different chemo regimens
A IB1 treated with Cis/5FU/HU had better local control
B Three-drug regimen had lowest grade 3 and 4 side effects
C Cisplatin-based CT improved OS and PRS rates
D OS was highest with HU only arm

Back 76

GOG 120 (Rose): RT with 3 different chemo regimens

C Cisplatin-based CT improved OS and PRS rates

Front 77

GOG surg-path (Delgado): 3-yr DF interval after rad hyst in pIB sqcca cx with deep third stromal invasion?
A 94%
B 85%
C 74%
D 53%

Back 77

GOG surg-path (Delgado): 3-yr DF interval after rad hyst in pIB sqcca cx with deep third stromal invasion?

C 74%

Front 78

GOG 123 (Keys): relative risk of progression with preop CCRT versus preop RT alone for bulky IB cervix ca?
A 0.26
B 0.35
C 0.51
D 0.99

Back 78

GOG 123 (Keys): relative risk of progression with preop CCRT versus preop RT alone for bulky IB cervix ca?

C 0.51

Front 79

GOG 8797 (Peters): which path finding after rad hys/PLND is indication for adj CCRT?
A Tumor > 5 cm
B LVSI
C Deep third stroma invasion
D Microscopic parametrial involvement

Back 79

GOG 8797 (Peters): which path finding after rad hys/PLND is indication for adj CCRT?

D Microscopic parametrial involvement

Front 80

Which molecular mechanism is implicationed in cervical cancer with prior HPV infection?
A E7 inactivates p53
B E7 inhibits Rb
C E6 suppresses G2-M cell cycle arrest
D E6 activates c-myc

Back 80

Which molecular mechanism is implicationed in cervical cancer with prior HPV infection?

B E7 inhibits Rb