pancreatic Flashcards
pancreatic cancer mutations
p16 80%; p53 70%; SMAD4 55%; K-RAS 90%; the more the worse
risk factor pancreatic cancer
A-A, male, tobacco (RR 2.5), obesity, fat/alcohol, chronic pancreatitis, diabetes, chronic hep B/C, cirrhosis
familial pancreatic cancer
10% of patients; BRCA, peutz-jegher, HNPCC (MLH1,MSH2), ataxia telangiectasia
resectable pancreatic cancer treatment
2 options: up front surgery versus NACT +/- chemorad
borderline resectable pancreatic treatment
favor neoadjuvant with chemoradiation (one of only situations where chemorad is used)
pancreaticoduodenectomy
mortality 2-4% morbidity 30%, high volume center maximizes outcome
post-op chemo for pancreatic
CONKO-001: gem v. observation–> doubling of OS; 10yr OS 12.2 v 7.7%; ESPAC-3: compare to 5-FU: no difference, gemcitabine better because of improved toxicity
gemcitabine complications
HUS, pneumonitis
adjuvant chemoradiation in addition to adjuvant therapy?
NO, inferior
adjuvant 2 versus one chemo?
all pending trials
adjuvant S1 v. gem?
70 v 53% 2yr OS in favor of S1! but was non-inferiority endpoint
pancreatic adeno thromboembolic events
20-50% rate
metastatic: gem v. 5-FU
gem 18% 1yr OS v. 2%
chemo metastatic setting
addition to 5-FU or platinum to gem might be better
Prodige 4-ACCORD 11
ECOG0-1, FOLFIRINOX v. gemcitabine–> 11.1 v 6.8mo, delays worsening quality of life; ORR rate 31 v 9.4%,
FOLFIRINOX tox
neuropathy, febrile neurtopenia 5%, thrombocytopenia, neuropathy, diarrhea 13%, vomiting 14%
MPACT
KPS 70-100; Nab-pac + gem v. gem; OS 8.5 v 6.7mo, worsening neuropenia,fatigue,neuropathy
erlotinib data in pancreatic
PA.3–> 6.24mo v 5.9mo median OS but significant. FDA APPROVED WITH GEMZAR!
GERCOR phase III trial- locally advanced
gem +/- erlotinib, then +/-chemoRT–> adding erlotinib worse; chemoradiation not clearly better
well-diff neuroendocrine tumor
mostly aerodigestive tract (carcinoid)
PNET
pancreatic neuroendocrine; only <20% functional
behavior of NE tumors
look at differentiation and Ki67 and grade (high grade >20mit/HPF and 20%ki67
PROMID study
octreotide v. placebo: 14.3mo time to tumor progression v 6mo
genetic mutations in pancreatic
KRas, P16, p53, SMAD4, BRCA1/2 (5%), MMR, STK11(Peutz-Jeghers), FANCC/FANCG (fanconi)
Whipple surgery for pancreas
mortality <.5% in major institutions, median survival 2years. complicated by leaks, fistula
borderline resectable pancrease cancer
significant venous involvement, but not arterial. favor neoadjuvant therapy and re-staging. may require vascular resection
adjuvant chemo for pancreas
CONKO-001 trial- gem v. observation, doubling of DFS, 2.6month improved OS. doubling of 5yr survival (20v.10), 12% 10-year survival. if gem not tolerated (pneumonitis), can complete adjuvant therapy with bolus 5-FU which has same survival.
pancreatic cancer sequelae
50% thrombolic,
prognosis pancreatic
ECOG2 2.8mo OS, 0 OS 8mo
first line metastatic pancreas
gem>5, 1yr OS 18% v. 2%
FOLFIRINOX for pancreatic ca
FOLFIRINOX v. gem- PS0-1, improved OS 11.1 v. 6.8mo, delays worsening of QOL,
FOLFIRINOX toxicities
myelosuppression, GI tox, need for GMCSF, LFTs, 9% neuropathy. age limit 70, only ECOG 0-1
nab-taxol + gem v. gem for pancreatic
improved OS 8.5 v. 6.7mo, significant,
locally advanced pancreatic
if no progression after chemo, may consider switching to chemoRT with 5-FU based regimen but no data to support
second line chemo for pancreatic
FOLFOX, what you didn’t get
well-diff PNET when to tx
treat if uncontrolled Sx, or progression under observation
when to resect a PNET
can debulk if a lot of symptoms with some benefit. if resectable, can resect
treatment of PNET options
octreotide v. placebo- time to progression 14.3 v. 6mo; lanreotide is subQ monthly, improved PFS.
other tx for PNET
temozolamide, strep/dox, 5-FU, regional approaches, pancreas-sunitinib, everolimus, maybe somatostatin analogues
Peutz-Jehgers
STK11/LKB1 gene mutation. mucocutaneous lesions, hamartomas of GI tract, pancreatic cancer, breast, lung, ovarian
adjuvant radiation for pancreas
no definitive data, can give adj chemo+5-U +/- gemcitabine (pre and post)
unresectable pancreatic cancer
standard is infusional 5-FU/RT –> gem alone. Alternative is gem alone (no RT). no data yet on nab/gem or FOLFIRINOX
MENI
pancreatic neuroendocrine tumors, pituitary tumors, parathyroid tumors (men 1)
MENII
RET gene- parathyroid tumors, pheo, and medullary thyroid [2 is worse]
carcinoid tumor prognossi
great if resected and LN-negative. latent mets frequent if LN-positive
appendix carcinoid management
appendectomy if
intestinal carcinoids
only have systemic symptoms if liver mets (due to liver first pass clearance)
carcinoid evlauation
if long disease course, need echo to look for R side of heart. PET is bad. get octreotide scan or CT/MRI
carcinoid/PNET resections
can be complete, or palliative for debulking
therapies for carcinoid
octreotide, interferon alpha (superior to streptozocin/5-FU)
standardtherapy for non-carcinoid PNET tumor
streptozosin + doxorubicin
poorly differentiated gut neuroendocine tumors therapy
small cell regimens: etoposide/cisplatin
PNET alternative therapies
sunitib, everolimus. NOT effective for carcinoids
high grade neuroendocrine/carcinoid
TREATED AS SMALL CELL/LARGE CELL– chemo
