Pancreatic Cancer - Adjuvant Flashcards
Familial Syndromes a/w pancreatic cancer
Hereditary pancreatitis HNPCC Hereditary Breast and Ovarian cancers Peutz-Jeghers syndrome Ataxia Telangiectasia Familial atypical multiple mole melanoma syndrome Li-Fraumeni Syndrome
How many percent of pancreatic cancers are due to genetic alteration?
5-10%
What are the main risk factors of pancreatic cancer?
Tobacco Dietary habits (BMI, red meat intake, low fruit & Veg intake, DM, alcohol)
What is the breakdown of pancreatic occurrence in each anatomical location?
Head: 60-70%
Body and tail: 20-25%
Most common Pancreatic cancer type:
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
What are the cystic neoplasms of the pancreas?
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
What are the combinations of genetic mutations in pancreatic cancers?
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
What about CA 19-9?
- 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
Function of EUS in staging of adenoCA
- Limited value in detection of all metastatic LN (Sen 70%, Spec 80%)
- Valuable in detection of vascular invasion
- Predicts resectability
How many lymph nodes is considered adequate in resection of pancreatic cancer?
15
T staging in TNM for pancreatic Cancer
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)
What is the Whipple’s surgery
1) HOP
2) Duodenectomy
3) 1st 15 cm of jejune my
4) GB
5) CBD
6) Partial gastric tony
What is considered R1?
Margin
Surgical Outcomes Analsis and Research (SOAR) pancreatectomy score
Calculated based on pre-op factors
ESPAC-1
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
CONKO-001 Trial
Gemcitabine vs Observation
Confirmed benefit of adjuvant chemotherapy.
Improved DFS (13m vs 7m) Improved OS (23m vs 20m)
ESPAC-3
Comparing adjuvant chemo:
(I) 6# FU/Folinic acid
(II) Gemictabine
No difference in OS/Recurrence-free QoL nor survival
Why should adjuvant ChemoRT NOT be given to patients except in clinical trials?
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
Management of Locally advanced Pancreatic Cancer
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]
Name the Adjuvant Pancreatic CA trials
1985 - GITSG 1989 - EORTC 2004 - ESPAC-1 2007 - CONKO-1 2008 - RTOG 9704 2009 - ESPAC-3 2013 - JASPAC 01
ESPAC-1
NEJM 2004
Neoptolemus
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
