Colon Flashcards

1
Q

incidence and epidemiology -3

VIDEO**

A

2nd leading cause of death in men AND women

5 yr OS 64%

median dx age 70 (63% >65)

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2
Q

risk factors -8

A

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

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3
Q

Prevention -3

A

diet (high fiber, low fat, fruits, veg, Ca++, vit D)

NSAIDs and Cox-2 inhibitors (>equal 2 tabs/wk RR 0.79)

colectomy

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4
Q

Screening -6

A

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

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5
Q

ACS screening guidelines - average risk -5

A

annual DRE AND FOBT or FIT after 50 + one of the following:

sigmoidoscopy q5y

colonoscopy q10y

barium enema q5y

CT colonoscopy q5y

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6
Q

ACS screening guidelines - family hx -1

A

start at age 35-40

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7
Q

ACS screening guidelines - HNPCC -1

A

start at age 30

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8
Q

ACS screening guidelines - FAP -1

A

start at age 10-12

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9
Q

staging - TNM -4

FAIRLY SIMPLISTIC COMPARED TO OTHER CANCERS

HUGE DIFFERENCE IN OS BY STAGING

A

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%

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10
Q

signs and symptoms 4

A

changes in bowel habits

blood in stool

anorexia, abd pain

weakness, wt loss

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11
Q

surgery - stage I or II -2

A

curative intent, 50% cure rate overall for all stages

partial or total colectomy +resection of primary and regional LN

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12
Q

surgery - stage III or IV -2

A

palliation/debulking (mostly)

decrease bleeding, relieve obstruction, inc QOL

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13
Q

surgery - isolated mets to lung or liver -1

A

20-25% cure rate if all mets can be resected

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14
Q

treatment - XRT -2

A

controvesial in colon CA, well established in rectal CA

OFTEN AN INCORRECT TEST ANSWER

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15
Q

chemotherapy - stage II -3

NOTE stage I - NO ADJ CHEMO

A

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

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16
Q

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

A

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)

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17
Q

chemotherapy- adjuvant - stage III - locally advanced dz: FLOX vs bolus 5FU -2

NOT PREFERRED

PAY ATTENTION TO AGE RESTRICTION OF BENEFIT

A

FLOX (=bolus 5FU +ox)

higher tox than FOLFOX (D and neurotox) - REASON NOT USED
inc 5yr DFS,
possible inc OS if <70yr

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18
Q

chemotherapy - stage III - locally advanced dz: X-ACT trial -3

PAY ATTENTION TO AGE RESTRICTION OF BENEFIT

A

Cape vs bolus 5FU, trend towards inc DFS and OS

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19
Q

chemotherapy- adjuvant - stage III - intra-arterial (portal) hepatic regional chemo -2

A

FUDR (floxuridine) peri-op

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20
Q

chemotherapy- adjuvant - stage III - mFOLFOX6 vs mFOLFOX6 +bev -3

A

ADRs significantly inc in BEV arm (HTN, pain, proteinuria, wound complications)

DO NOT USE

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21
Q

chemotherapy- adjuvant - stage III - targeted therapies and irinotecan -1

A

At this time cetuximab, bevacizumab or irinotecan are NOT approved for adjuvant use

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22
Q

chemotherapy - stage IV - resectable synchronous liver only AND/OR lung only== 3 CHOICES

  1. colectomy+resection->adj ???,
  2. neoadj ???->colecotomy+resection->adj???,
  3. colectomy->mix neoadj/adj chemo???->resection->adj??? -7

ALL METASTATIC DRUGS STILL COME IN TO PLAY

A

1 FOLFOX or CapeOx

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23
Q

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

A

1 FOLFIRI, FOLFOX, or CapeOX +/- bev

24
Q

chemotherapy- stage IV -advanced/met dz - 1st line -4

A

==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)

25
Q

chemotherapy- stage IV - unresectable abdominal periotoneal mets -2

A

1 nonobstruction->met chemo 1st line

26
Q

chemotherapy- stage IV -advanced or metastatic dz - 1st line - NCCN if can tolerate intensive chemo
-4

DO NOT USE DUAL (OR COMBINED) BIOLOGIC TX IN COLON CA

A

1 FOLFOX +/-bev or +/-panit (NO CETUX)

27
Q

chemotherapy- stage IV -advanced / met dz - 1st line - NCCN if CANNOT tolerate intensive chemo

-3

A

1 5FU/LV or cape +/- bev

28
Q

chemotherapy- stage IV -advanced dz - isolated hepatic mets -2

A

1 surgical resection with FUDR intra-arterial hepatic infusion (high hepatic extraction + drug conc, little systemic exposure), inc ORR, no consistent inc in OS, tox=biliary stenosis, chemical hepatitis, catheter thrombosis, duodenal ulceration

29
Q

chemotherapy- stage IV -advanced dz - 2nd line - CONCEPTS -2

A

important to give all active traditional chemo (5FU, irino, oxal)!!!!

inc OS and is independent of drug order

30
Q

chemotherapy- stage IV -advanced dz - 2nd line - ROLE OF bev -2

A

1 if not given 1st line add to FOLFOX (inc OS 2.1mo)

31
Q

chemotherapy- stage IV -advanced dz - 2nd line - if FOLFOX or CapeOx 1st -4

FYI MOST PTS END UP GETTING FOLFOX 1ST (80-85%)

GIVE WHAT THEY DID NOT GET

A

1 FOLFIRI +/- bev OR +/-panit (inc PFS 5.9 vs 3.9mo) OR +/- ziv-aflibercept vs FOLFIRI (OS 13.5 vs 12.1 mo) OR +/- cetux

#3 single agent cetux (RASH ASSOCIATED WITH INC OS) in kras wt vs BSC (9.5 vs 4.8mo) OR single agent panit vs BSC (no OS, RR8%, included non-kras wt pts) 
USE IF CANT tolerate chemo
32
Q

chemotherapy- stage IV -advanced dz - 2nd line - if FOLFIRI 1st -4

GIVE WHAT THEY DID NOT GET

NOT AS MUCH DATA FOR TARGETED TX

A

1 FOLFOX or CapeOx +/- bev or egfr (do no use egfr if used in 1st line)

33
Q

chemotherapy- stage IV -advanced dz - 3rd or 4th line -2

A

1 regorafenib: OS 6.4 vs 5.0 mo,

(if kras wt also need to fail EGFR tx prior to using)

In patients previously treated with fluoropyrimidine-, oxaliplatin-, and irinotecan-containing chemotherapy, and anti-VEGF therapy, and if KRAS wild type, an anti-EGFR therapy:

34
Q

irinotecan -3

A

ADR: severe diarrhea, neutropenia

dose adjustments: with caution or reduced with Gilbert’s dz or elevated serum bilirubin

genetic test: UGT1A1*28 allele (SN-38 -> SN-38 glucuronide, poor metabolizers =inc tox

35
Q

oxaliplatin -2

A

ADR: neuropathies are cummulative-> “stop and go” may dec tox without effecting OS.

Recent phase III trial showed dec in >= grade 2 chronic neuropathies with Ca++/Mg++ infusions however data insufficient

36
Q

ASCO and NCCN kras testing -1

A

test ALL colon CA pt prior to start of EGFR tx - only work in kras wt

37
Q

braf testing -3

A

1 V600E braf mutation pts appear to have poorer prognosis

38
Q

increasing cetuximab dose to rash - EVEREST trial -2

A

may increase RR

RASH MANAGEMENT - doxycycline px

39
Q

continuation of bev after dz progression -1

A

inc OS compared to no further tx OR additional tx without bev

40
Q

surveillance - ASCO guidelines -4

A

1 annual CT c/a for 3yr for pts at higher risk of recurrence or who could be candidates for curative intent surgery

41
Q

RECTAL - general concepts -4

XRT IS GOOD!!

5FU OR CAPE +XRT (KEY!!)

OXAL DOES NOT HELP!! ONLY ADDS TOX

A

1 same as colon EXCEPT use concurrent XRT either neoadj, adj, or both in early stage dz (stage II or III) due to relatively high risk of locoregional recurrence.

#2 fluoropyrimidines are TOC with XRT. 
NCCN does NOT recommend irino, bev, cetux, panit, or oxal with XRT (inc diarrhea with Ox)
42
Q

RECTAL - staging -4

A

I: T1-2

II: T3-4

III: N1-2

IV: M1

43
Q

FOLFOX4 AND ADR -2

A

Day 1: oxal 85 over 2h +LV 200 over 2h, followed by 5FU 400 bolus then 600 over 22h
Day 2: LV 200 over 2h, followed by 5FU 400 bolus then 600 over 22h q2wks

neutrop, D, neuropathies INC OVER 5FU

44
Q

FOLFOX6

A

oxal 100 over 2h +LV 200 over 2h, followed by 5FU 400 bolus then 2400 over 46h q2wks

45
Q

mFOLFOX6

A

oxal 85 over 2h +LV 200 over 2h, followed by 5FU 400 bolus then 2400 over 46h q2wks

46
Q

FOLFIRI

A

irino 180 + LV 200, followed by 5FU 400-500 bolus, then 2400-3000 over 46h q2wks

47
Q

CapeOx +/-bev

A

cape 1000 bid po d1-14, oxal 130 D1 q3wks +/- bev 7.5 D1

48
Q

CapeIri

A

cape 1000 bid po D1-14, irino 100 D1 and D8 q22days

NOT USED

49
Q

regorafenib regimen

A

160mg po daily D1-21 q28d

50
Q

irinotecan regimen

A

350 over 90min D1 q3wks

51
Q

bev ADR -2

A

inc risk of stroke and other arterial events in those >65yr

reduced wound healing

52
Q

Which patients do not benefit from 5-FU/LV? -2

A

high microsatellite instability OR defective DNA mismatch repair

can test MMR protein for stage II to see if chemo a good option (rec for all pts <50 or stage II)

53
Q

Are any monoclonal Ab’s OR irinotecan approved for adjuvant use? -1

A

NO

WILL SEE THESE INCORRECT ANSWERS ON TEST QUESTIONS

54
Q

WHY DO KRAS MUTANT PTS NOT RESPOND TO EGFR TX? -1

A

KRAS is downstream of receptor

55
Q

DOES ANYTHING PREDICT bev RESPONSE? -1

A

NO

56
Q

egfr testing -1

A

THIS DOES NOT MATTER - DOES NOT EFFECT OUTCOME