incidence and epidemiology -3
VIDEO**
2nd leading cause of death in men AND women
5 yr OS 64%
median dx age 70 (63% >65)
risk factors -8
age
hereditary nonpolyposis colon CA (HNPCC) or
Lynch Syndrome (5-10%, age 30 on)
familial adenomatosis polyposis (FAP) (0.5%, total colectomy when polyps appear after age 10-12 on)
IBDz (UC or crohn’s)
Polyps
Diet (high fat, low fiber, EtOH, high BMI)
FH
Prevention -3
diet (high fiber, low fat, fruits, veg, Ca++, vit D)
NSAIDs and Cox-2 inhibitors (>equal 2 tabs/wk RR 0.79)
colectomy
Screening -6
fecal occult blood testing (FOBT) - high false neg, use in combo
fecal immunochemical test (FIT)
DRE
endoscopy - flex sigmoidoscopy (lower 60% of bowel), colonoscopy (entire bowel, remove pre-malignant lesions)
barium enema
tumor markers (CEA) - inc in many GI tumors and pancreatitis, hepatitis, renal failure, smoking->use to watch chemo response
ACS screening guidelines - average risk -5
annual DRE AND FOBT or FIT after 50 + one of the following:
sigmoidoscopy q5y
colonoscopy q10y
barium enema q5y
CT colonoscopy q5y
ACS screening guidelines - family hx -1
start at age 35-40
ACS screening guidelines - HNPCC -1
start at age 30
ACS screening guidelines - FAP -1
start at age 10-12
staging - TNM -4
FAIRLY SIMPLISTIC COMPARED TO OTHER CANCERS
HUGE DIFFERENCE IN OS BY STAGING
I: local dz, no muscular mucosa invasion 5yr OS 90.1%
II: muscular mucosa invasion, no extracolonic
III: lymph node involvement (any N) 5yr 69% OS
IV: mets (liver, lung, bone) 5yr OS 11.7%
signs and symptoms 4
changes in bowel habits
blood in stool
anorexia, abd pain
weakness, wt loss
surgery - stage I or II -2
curative intent, 50% cure rate overall for all stages
partial or total colectomy +resection of primary and regional LN
surgery - stage III or IV -2
palliation/debulking (mostly)
decrease bleeding, relieve obstruction, inc QOL
surgery - isolated mets to lung or liver -1
20-25% cure rate if all mets can be resected
treatment - XRT -2
controvesial in colon CA, well established in rectal CA
OFTEN AN INCORRECT TEST ANSWER
chemotherapy - stage II -3
NOTE stage I - NO ADJ CHEMO
controversy - NOT on test
oxaliplatin OS benefit unproven
PROBABLY STRATEGY IS HIGH RISK VS STD RISK - MAY THINK IF NOT ENOUGH NODES SAMPLED THEN MAY BENEFIT FROM CHEMO - NEED 12 NODES - IF SURGERY DOES NOT EXAMINE 12 NODES OFFER CHEMO
chemotherapy- adjuvant - stage III (LYMPH NODE (+))- locally advanced dz - TOC - MOSAIC trial AND NO16968 trial -3
NOTE CHEMO DIFFERENT FOR STAGE IV
PAY ATTENTION TO AGE RESTRICTION OF BENEFIT
1 FOLFOX4 (cat 1) vs 5fu/lv is SOC:
==surgery + adjuvant 5-FU based chemo/leucovorin==
5yr DFS 73 vs 67%, subset of age 70-75yr did not benefit
OS ADVANTAGE ONLY IN STAGE 3
3yr DFS 70.9 vs 66.5%,
No OS benefit,
ADR: HFS, PN (cape-ox) vs neutropenia/NF)
chemotherapy- adjuvant - stage III - locally advanced dz: FLOX vs bolus 5FU -2
NOT PREFERRED
PAY ATTENTION TO AGE RESTRICTION OF BENEFIT
FLOX (=bolus 5FU +ox)
higher tox than FOLFOX (D and neurotox) - REASON NOT USED
inc 5yr DFS,
possible inc OS if <70yr
chemotherapy - stage III - locally advanced dz: X-ACT trial -3
PAY ATTENTION TO AGE RESTRICTION OF BENEFIT
Cape vs bolus 5FU, trend towards inc DFS and OS
chemotherapy- adjuvant - stage III - intra-arterial (portal) hepatic regional chemo -2
FUDR (floxuridine) peri-op
chemotherapy- adjuvant - stage III - mFOLFOX6 vs mFOLFOX6 +bev -3
ADRs significantly inc in BEV arm (HTN, pain, proteinuria, wound complications)
DO NOT USE
chemotherapy- adjuvant - stage III - targeted therapies and irinotecan -1
At this time cetuximab, bevacizumab or irinotecan are NOT approved for adjuvant use
chemotherapy - stage IV - resectable synchronous liver only AND/OR lung only== 3 CHOICES
ALL METASTATIC DRUGS STILL COME IN TO PLAY
1 FOLFOX or CapeOx
chemotherapy- stage IV - unresectable liver only AND/OR lung only==
start neoadjuvant, assess resectability q2mo->if CAN resect THEN adj chemo to complete 6mo peri-op chemo, if NO resection then met dz chemo -3 tx choices -2 comments
RESECTION INCREASES OS
1 FOLFIRI, FOLFOX, or CapeOX +/- bev
chemotherapy- stage IV -advanced/met dz - 1st line -4
==5FU or Cape based==
#5FU+LV >5FU alone (often use 3rd agent) #IFL(irino+bolus 5FU/LV) vs 5FU/LV: inc OS 14.8 vs 12.6mo, inc diarrhea, not effective as adjuvant (not rec'd anymore->use FOLFIRI) #FOLFOX inc OS vs IFL #FOLFIRI=FOLFOX (OS=20.4 vs 21.5mo) (modified IFL to be irino q2wk +5FU CI has replaced IFL, choice based on pt-specific characteristics #CapeOx =FOLFOX #CapeIri < FOLFIRI (dec PFS), don't use
add bev to all of above unless contraindx
EGFR inhibitors (cetuximab, panitumumab) may be used (not in addition to bev) (EXCEPTION no cetux if FOLFOX regimen)