Term
| etiology of colorectal cancer |
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Definition
environment (80%):
primarily related to diet high in animal fats and red meat
diet low in fiber
pyrolysis products (benzopyrenes) - from BBQ, charcoal
insufficient micronutrients including vitamins C and E, selenium, folic acid, and beta-carotene
genetics (20%):
risk is 2-4 x greater if primary relative with colorectal cancer
K-RAS mutations
deleted in colon cancer (DCC gene)
loss of p53
other genetic mutations also included |
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Term
| pathology of colorectal cancer |
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Definition
90-95% of tumors are adenocarcinomas
poor prognosis if:
tumor adheres/fixated to adjacent structures
bowel perforation
bowel obstruction
aneuploidy (abnormal # of chromosomes)
deletion of 18q (DCC)
% of cells in S phase |
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Term
| colorectal cancer risk factors |
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Definition
AGE > 50
POLYPS
FAMILY HISTORY: INCLUDING COLORECTAL CANCER SYNDROMES; INCLUDING FH OF POLYPS
geography
diet
inflammatory bowel disease
previous colorectal cancer or pelvic irradiation
obesity
smoking
ETOH
previous non-cancer surgery |
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Term
| colorectal cancer risk by age/gender |
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Definition
| for both males and females the risk from birth to death is 1 in 17 |
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Term
|
Definition
most colon cancers come from adenomatous polyps
few polyps progress to cancer
all colorectal cancers come from a polyp, but not every polyp turns into colorectal cancer
FH of polyps is risk factor for colon CA |
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Term
|
Definition
Familial Adenomatous Polyposis (FAP, 1%):
100s-1000s of tiny adenomatous polyps, evident by age 25
3x more common in women
autosomal dominant
Adenomatous Polyposis Coli (APC) gene on chromosome 5
total colectomy recommended
the chance of one of the polyps turning into cancer is very high; have to remove the colon
Hereditary Nonpolyposis Colorectal Cancer (5%):
also called Lynch syndrome
Type 1 = no extracolonic involvement
Type 2 = extracolonic malignancies including ovary, breast, uterus, stomach, or bile duct
autosomal dominant - mismatch repair gene mutations
right sided cancers
early age of onset (median onset = 46 years)
should be screened for other malignancies (ovarian, breast) |
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Term
| colorectal cancer negative risk factors |
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Definition
aspirin/NSAID use?
decreased risk of colorectal cancer in patients who are at extremely high risk; should NOT take aspirin for primary prophylaxis b/c or risk of bleed
HRT in women?
MVI with folic acid?
not proven
Ca supplementation?
not proven
high fiber diet?
not proven |
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Term
| colorectal cancer presentation |
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Definition
early tumors may be asymptomatic
general signs: rectal bleeding, abdominal pain, change in bowel habits, abdominal distension
locational signs:
right colon - less sympomatic, ulcerative lesions can result in blood loss; anemia
transverse, left colon - obstructive symptoms
rectum, sigmoid colon - hematochezia (bright red blood in stool), sense of incomplete evacuation, painful defecation, narrowing of stool shape |
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Term
| diagnosis of colorectal cancer |
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Definition
complete history and physical exam
endoscopy, barium enema
CBC
blood chemistry
LFTs - most common site of metastasis for colorectal caner is the liver
CEA (cancer embrionic antigen) - tumor marker; nl < 2.5 ng/mL; not a screening tool but used to monitor patient's response to therapy
chest X-ray
abdominal CT scan |
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Term
| spread of colorectal cancer |
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Definition
direct extension
lymphatic spread
hematogenous metastasis |
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Term
| screening of colorectal cancer |
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Definition
beginning at age 50, both men and women should follow one of the following options:
sigmoidoscopy every 5 years
double contrast barium enema every 5 years
CT colonography (virtual colonoscopy) every 5 years
COLONOSCOPY EVERY 10 YEARS = GOLD STANDARD
yearly fecal occult blood tests (does not find polyps) |
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Term
| high risk colorectal cancer screening |
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Definition
FH of colorectal cancer in first degree relative < 60 yo or 2 or more first degree relatives any age:
colonoscopy every 10 years starting at 40
FAP: should have colectomy (no screening)
HNPCC: colonoscopy every 1-2 years from 21-40, then annually thereafter
IBCs (including UC and Chron's): colonoscopy yearly |
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Term
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Definition
if a polyp was found (and was not cancerous), repeat screening is more stringent
colonoscopy in 3-6 years, if normal go back to regular schedule
colon cancer survivors:
one year after treatment, repeat in 3 years, then every 5 year schedule |
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Term
| fecal occult blood test (FOBT) |
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Definition
to avoid false positives:
for 3 days before test avoid red meat, turnips, broccoli, cauliflower, and radishes (high in iron), iron supplementations, rectal penetration (drugs, DRE, other)
to avoid false negatives:
avoid vitamin C for 3 days prior to test
avoid testing dehydrated samples (DO NOT REHYDRATE SAMPLES) |
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Term
| colorectal cancer prevention |
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Definition
diet:
< 30% FAT, < 5 servings of red meat per week, 5 servings of fruits or vegetables daily (high fiber intake)
NSAIDs:
4-6 aspirin per week can decrease incidence by 30-50% in patients at extremely high risk (FAP patients that didn't get colectomy)
COX-2 inhibitors may also confer benefit
other:
don't smoke, limit alcohol intake, be physically active, vitamin C and E, folic acid may lower risk
estrogen may be protective |
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Term
| treatment of colorectal cancer |
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Definition
treated based on stage
colon and rectal cancers: treatment varies
surgery is mainstay of therapy
most recurrences in first 4-5 years
radiation:
colon - seldom used (more difficult to pinpoint the radiation; more collateral damage without much benefit)
rectal - adjuvant therapy AND palliation |
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Term
| treatment of Stage I (A) colorectal cancer |
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Definition
SURGERY
resection of primary tumor and regional mesenteric lymph nodes
surgery results in a partial colectomy
patients frequently will require colostomy bag
can later be reversed after patient heals |
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Term
| treatment of stage II (B) colorectal cancer |
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Definition
SURGERY
THEN
ADJUVANT CHEMOTHERAPY
5FU/leucovorin |
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Term
| 5FU/leucovorin major counseling points |
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Definition
ADRs
QUICK:
hypersensitivity
SHORT TERM:
N/V
myelosuppression
alopecia
HAND FOOD SYNDROME
stomatitis
diarrhea |
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Term
| treatment of stage III (C) colorectal cancer |
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Definition
locally advanced disease
SURGERY
THEN
ADJUVANT CHEMOTHERAPY:
FOLFOX-4 = 5FU, leucovorin, and oxaliplatin |
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Term
| FOLFOX - 4 (5FU, leucovorin, oxaliplatin) major counseling points |
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Definition
ADRs
QUICK:
hypersensitivity
SHORT TERM:
N/V
myelosuppression
alopecia
hand foot syndrome
stomatitis
diarrhea
NEUROPATHIES - oxaliplatin; intolerance to heat and cold |
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Term
| treatment of stage IV (D) colorectal cancer |
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Definition
NOT CURATIVE
surgery is JUST for palliation
CHEMOTHERAPY + BEVACIZUMAB
FOLFOX-4 (5FU, leucovorin, oxaliplatin) + bevacizumab
OR
FOLFIRI (5FU, leucovorin, irinotecan) + bevacizumab
liver mets:
systemic chemo + hepatic artery infusion of floxuridine (derivative of 5FU) |
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Term
| FOLFOX (5FU, leucovorin, oxaliplatin) + bevacizumab major counseling points |
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Definition
ADRs
QUICK:
hypersensitivity
SHORT TERM:
N/V
myelosuppression
alopecia
hand-food syndrome
stomatitis
diarrhea
neuropathies
VTEs - bevacizumab
bowel perforation - bevacizumab
proteinuria - bevacizumab |
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Term
| FOLFIRI (5FU, leucovorin, irinotecan) + bevacizumab major counseling points |
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Definition
ADRs
QUICK:
hypersensitivity
SHORT TERM:
N/V
myelosuppression
alopecia
hand food syndrome
stomatitis
DIARRHEA - irinotecan
VTEs
bowel performation
proteinuria |
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Term
| treatment of stage I rectal cancer |
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Definition
SURGERY
resection of primary tumor and regional mesenteric lymph nodes
surgery results in a partial colectomy
patients frequently will require colostomy bag
can later be reversed after patient heals |
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Term
| treatment of stage II rectal cancer |
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Definition
SURGERY
THEN
adjuvant RATIATION with continuous infusion of 5FU
THEN
CHEMOTHERAPY with 5FU/leucovorin
same regimen as colon cancer but add radiation
radiation is most effective when the cells are in the S phase; 5FU keeps the cells in the S phase so is given at the same time as the radiation |
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Term
| treatment of stage III rectal cancer |
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Definition
neoadjuvant RADIATION with 5FU
THEN
SURGERY
THEN
adjuvant CHEMO with FOLFOX-4 (5FU, leucovorin, oxaliplatin) |
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Term
| treatment of stage IV rectal cancer |
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Definition
same as colon cancer except radiation
NOT CURATIVE
surgery is for palliation
radiation is for palliation
CHEMOTHERAPY + BEVACIZUMAB:
FOLFOX-4 (5FU, leucovorin, oxaliplatin) + bevacizumab
OR
FOLFIRI (5FU, leucovorin, irinotecan) + bevacizumab
liver mets: surgery + systemic chemo + hepatic artery infusion of floxuridine |
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Term
|
Definition
H and P every 3 months for 2 years, then every 6 months for total of 5 years
CEA every 3 months for 2 years then every 6 months for 2-5 years
colonoscopy one year after treatment, repeat in 3 years, then every 5 year schedule (assuming everything normal) |
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Term
|
Definition
salvage regimens:
combination therapy (for good performance status):
FOLFOX or FOLFIRI with bevacizumab (if not previously used)
CAPOX (oxaliplatin + capecitabine)
IROX (irinotecan + oxaliplatin)
cetuximab + irinotecan
single agent (for poor performance status):
capecitabine
irinotecan
cetuximab/panitumumab
CLINICAL TRIALS |
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Term
| capecitabine (prodrug of 5FU) |
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Definition
role of capecitabine is highly controversial
some data says it can be used to replace 5FU/leucovorin
can also be used single agent in recurrent disease in patients who cannot tolerate combination therapy |
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Term
| chemotherapy with cetuximab and panitumumab |
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Definition
monoclonal antibody that blocks EGFR
only used in relapsed disease
primary toxicity - infusion reaction
CANNOT BE USED IF K-RAS MUTATION
if the patient has a mutation in K-RAS they will NOT respond to these drugs; confers resistance to cetuximab and pannitumumab
other common ADRs: rash, dry skin, fever, weakness, constipation |
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