Pancreatic Cancer - Adjuvant

Question 1

Familial Syndromes a/w pancreatic cancer

Answer 1

Hereditary pancreatitis
HNPCC
Hereditary Breast and Ovarian cancers
Peutz-Jeghers syndrome
Ataxia Telangiectasia
Familial atypical multiple mole melanoma syndrome
Li-Fraumeni Syndrome

Question 2

How many percent of pancreatic cancers are due to genetic alteration?

Answer 2

5-10%

Question 3

What are the main risk factors of pancreatic cancer?

Answer 3

Tobacco
Dietary habits (BMI, red meat intake, low fruit & Veg intake, DM, alcohol)

Question 4

What is the breakdown of pancreatic occurrence in each anatomical location?

Answer 4

Head: 60-70%

Body and tail: 20-25%

Question 5

Most common Pancreatic cancer type:

Answer 5

Ductal Adenocarcioma (80%) of all pancreatic cancers.

Morphological variants include:

• Colloid carcinoma
• Medulary carcinoma

Other variants (poorer px):

• Adenosquamous carcinoma
• undifferentiated carcinomas with osteoclasts-like giant cells

Other variants (slightly better px):
- Acinar cell pancreatic cancers

Neuroendocrine tumors are second most common pancreatic cancers

Question 6

What are the cystic neoplasms of the pancreas?

Answer 6

10-15% of cystic lesions of pancreas

Most common:

• serous cystadenoma
• intraductal papillary mucinous neoplasm (IPMN)
• Mucinous cystic neoplasm (Cystadenoma OR Cystadenocarcinoma)

Non-mucinous lesions have no malignant potential

Question 7

What are the combinations of genetic mutations in pancreatic cancers?

Answer 7

1) Mutational activation of oncogenes
- Commonly KRAS found in >90% of pancreatic cancers
2) Inactivation of tumor suppressor genes
- TP53
- p16/CDKN2A
- SMAD4
3) Inactivation of genome maintenance genes
- hMLH1
- MSH2
* most are somatic aberrations

Question 8

What about CA 19-9?

Answer 8

• Not useful for primary Dx of pancreatic CA
• Increased in ~80% of advanced disease
• Those with no functional Lewis enzyme (10% of population), levels of CA19-9 are typically undetectable or below 1.0U/ml
• Correlated to level of bilirubin
• Significant value as a prognostic factor
• can be used to measure disease burden and potentially guide tx options

Question 9

Function of EUS in staging of adenoCA

Answer 9

• Limited value in detection of all metastatic LN (Sen 70%, Spec 80%)
• Valuable in detection of vascular invasion
• Predicts resectability

Question 10

How many lymph nodes is considered adequate in resection of pancreatic cancer?

Answer 10

15

Question 11

T staging in TNM for pancreatic Cancer

Answer 11

T0: No evidence of primary tumor
Tis: Carcinoma-in-situ

T1: Tumor limited to pancreas, 2cm or less
T2: Tumor limited to pancreas, >2cm

T3: Extends beyond pancreas, no involvement of celiac axis/SMA
T4: Involves Celiac axis/SMA (= Unresectable primary tumor)

Question 12

What is the Whipple’s surgery

Answer 12

1) HOP
2) Duodenectomy
3) 1st 15 cm of jejune my
4) GB
5) CBD
6) Partial gastric tony

Question 13

What is considered R1?

Answer 13

Margin

Question 14

Surgical Outcomes Analsis and Research (SOAR) pancreatectomy score

Answer 14

Calculated based on pre-op factors

Question 15

ESPAC-1

Answer 15

RCT, n=300, 2x2 factorial design

S/p curative resection randomized into:

1) Adjuvant chemo [Bolus 5FU/Folinic acid]
2) ChemoRT only [split course 40Gy + 5FU]
3) ChemoRT–> Chemo
4) Surveillance alone

S/p chemo:
- longer median survival 20m vs 15.5m

Question 16

CONKO-001 Trial

Answer 16

Gemcitabine vs Observation

Confirmed benefit of adjuvant chemotherapy.

Improved DFS (13m vs 7m) 
Improved OS (23m vs 20m)

Question 17

ESPAC-3

Answer 17

Comparing adjuvant chemo:
(I) 6# FU/Folinic acid
(II) Gemictabine

No difference in OS/Recurrence-free QoL nor survival

Question 18

Why should adjuvant ChemoRT NOT be given to patients except in clinical trials?

Answer 18

3 RCTs comparing adjuvant ChemoRT against surveillance alone:
(I) GITSG
- ChemoRT arm: 40Gy+5FU
- stopped prematurely after 40 pts. INterim analysis showed low rate of inclusion and significant difference in favor of ChemoRT arm
(II) EORTC trial
- ChemoRT vs surveillance
- survival benefit for adjuvant ChemoRT not significant
(III) ESPAC-1
- suggested deleterious effect of adjuvant ChemoRT
- RFS 11m (ChemoRT) vs 15m (Surveillance)

Even in R1 patients, no benefit

Question 19

Management of Locally advanced Pancreatic Cancer

Answer 19

Highly controversial
OS ~1 year
Standard of care: 6 months of gemcitabine

LAP07 trial
Meta-analysis
ChemoRT>chemo or RT alone

2 trials NOT showing benefit of ChemoRT over chemo or RT:

1) French trial
- obsolete regimen of ChemoRT (50Gy +5FU CDDP)
- survival better in gemcitabine mono therapy arm [13m vs 9m]

Question 20

Name the Adjuvant Pancreatic CA trials

Answer 20

1985 - GITSG
1989 - EORTC
2004 - ESPAC-1
2007 - CONKO-1
2008 - RTOG 9704
2009 - ESPAC-3
2013 - JASPAC 01

Question 21

ESPAC-1
NEJM 2004
Neoptolemus

Answer 21

2x2, n=290
Respected pancreatic ducal adenoCA.
4 arms:
- CRT alone (20Gy, 2week period+5FU)
- Chemo alone (FU)
- CRT and Chemo
- Observation

5-yr survival :

• 10% in CRT, 20% with no CRT
• 20% with chemo, 10% with no chemo