Pancreatic Flashcards
Pathogenesis -4
VIDEO**
90% ductal adenocarcinoma.
2/3’s head.
1/3 body and tail.
70% over 65 yrs old.
K –ras >85%.
p16 tumor suppressor gene inactive in 95%.
BRCA-2 mutations contribute.
Risk factors -5
Cigarette smoking,
High fat diet,
processed meat diet
obesity,
diabetes,
chronic pancreatitis (alcoholics)
occupational exposure(gasoline, DDT).
Familial 5– 10% of cases.
Screening
CA19-9 is Normal in early stages!!
No screening recommendations.
Signs and symptoms -9
Jaundice,
pain (typically felt in upper abdomen that wraps around waist and radiates to the back),
weight-loss,
anorexia,
early satiety,
diarrhea, steatorrhea,
Trousseau’s sx (VTE, hypercoag, crops of clots),
Virchow’s node (“the seat of the devil”, L supraclavicular LN)
Natural history of disease -4
Spreads early to regional lymph nodes,
subclinical liver mets present in the majority of patients at dx.
Tumor can cause obstruction of biliary and G.I. tracts.
Local invasion equals pain and inability to perform curative surgery
Hx of metastasis -3
At dx 85% of tumors extended beyond pancreas to liver, peritoneum, or lung (most frequent extra abdominal.
Local recurrence in 85% after surgery alone.
Liver mets after surgery+adj chemo-xrt in 50-70%
CA 19-9 -4
- Not specific for pancreatic cancer
- Levels are high in other GI cancers
- Useful in follow-up during and after treatment
- Elevated in jaundice, wait until after jaundice resolved
Diagnosis -3
- Helical, thin–section CT c/a/p with contrast is preferred. -> Avoids unnecessary surgery for unresectable lesions
- Endoscopic ultrasound (EUS) -Describe local extent of disease, guide FNA regional lymph nodes
- ERCP -symptomatic stenting, failed EUS FNAs
Staging categories -3
potentially resectable (5yr survival 20%, median 15-19 mo),
locally advanced unresectable (median 8-13 mo),
metastatic (median 3-6 mo)
Surgery -4
- Criteria for unresectability (extrahep mets, superior mesenteric vein occlusion/encasement, crucial artery involvement)
- 15-20% eligible for total resection NOT MANY
- Radical resection. Head= whipple (pancreaticoduodenectomy). Body or tail = distal pancreatectomy
- Palliative - biliary stent, bypass biliary obstruction
Radiation -3
- Postsurgery radiation alone does not improve OS
- Neoadj RT+ 5-fu improve resectability but not OS (not really done)
- Palliative RT controls pain
Chemotherapy concepts -3
- 5-fu and gemcit most successful single agents. RR low. Non-curative in advanced dz.
- Encourage clinical trial
- Combo chemo = better RR but minimal inc OS
Treatment by clinical stage – resectable OR potentially resectable that leads to surgery -4
TWO CHOICES OF CHEMO
SEQUENCING OF XRT-CHEMO DOES NOT MATTER
gem OR 5fu/lv alone BEFORE OR AFTER chemoXRT (gem or 5fu/lv based) (cat 2A)
gem or 5fu/lv alone (cat 1)
capecitabine (cat 2b)
CLINICAL TRIAL
Treatment by clinical stage – locally advanced (unresectable) key concepts -5
NOT SUPER CLEAR
- Chemo-xrt > xrt alone 10.5 vs 5 mo
- Chemo-xrt > chemo alone 1 yr os 41 vs 19%
- Gem-xrt = 5-fu-xrt, OS 11.4 mo
- Combo chemo gaining favor and many centers use over chemo-xrt KEY!!!
- Little evidence to support neoadjuvant
Treatment by clinical stage – locally advanced (unresectable)
NCCN -9
QUESTION:
1. WHAT IS PS?
Good PS: Clinical trial (preferred),
FOLFIRINOX 2A,
gemcitabine 2A,
gemcitabine-based combo (platinum or taxane) 2A,
gemcitabine plus erlotinib (cat 1)***
capecitabine (cat 2b)
ALL–followed by chemo-xrt consolidation in select pts (THOSE WITHOUT SYSTEMIC METS)
Poor PS:
Gemcitabine (cat 1)***
Best supportive care
Treatment by clinical stage – metastatic - key chemo concepts - gem vs 5FU/lv -5
Clinical benefit response =improvement in pain, lean body mass, and performance status.
CBR: Gem 23.8% vs 5-fu 4.8%. OS 5.65 vs 4.41mo.
ADR: more anemia, more neutropenia
FDA gemcitabine approval based on this
Combo better RR but not better OS
Fixed – dose rate infusion of gemcitabine cat 2b -5
Longer infusion time =pk benefit??
Intracellular activation of gemcitabine to active drug is saturated at infusion rate of 10mg/min/m2.
Dose 1500 mg/m2 over 150 min vs 2200 over 30 min.
Phase 2 data showed promising results. This has not been confirmed in phase 3.
NCCN cat 2b
Treatment by clinical stage – metastatic -Folfirinox in metastatic dz and ADR – cat 1 -3
PS 0 or 1
Infusional and bolus 5– fluorouracil, leucovorin, irinotecan and oxaliplatin vs gem 1000 7/8 wks then 3/4 wks
OS 11 vs 6.8mo
ADR: neutrop, FN, thromboc, diarrhea, PN, inc LFTs
Treatment by clinical stage – metastatic - nccn first line -10
KNOW CAT 1 RECS
Mono FOR POOR PS
Gem std cat 1***
Gem fixed dose rate cat 2b
Cape cat 2b
Combo For those with good PS
Gem+erlotinib cat 1***
Folfirinox cat 1***
Gem+ cape 2A
Gem+ cis 2A
Gem+ docet, cape (GTX) cat 2b
Gem+ nab-paclitaxel cat 2b
Folfox, xelox cat 2b
Treatment by clinical stage – metastatic - nab-paclitaxel +gem vs gem cat 2b
OS 8.5 vs 6.7 mo
Treatment by clinical stage – metastatic - gem + erlotinib cat 1 -4
more diarrhea with erlotinib
Gem 1000 wkly x7/8wks then x3/4wks + placebo/erlotinib
OS 5.9 vs 6.4mo (sig)
Grade 2 rash = OS 10.5 vs 5.2 mo
No correlation with EGFR expression
Treatment by clinical stage – metastatic - nccn second line
No standard of care for those failed gemcitabine
generally use what you did not use.
Supportive care symptoms and treatment -6
Pain,
obstructive jaundice (biliary decompression->stent, bypass surg),
gastric outlet obstruction-> (stent, g-j ostomy surg, PEG tube),
diarrhea (steatorrhea and malabsorption-> creon: inc if stool greasy malodorous or floats, dec if constipation
nutrition,
depression
