Colorectal cancer Flashcards
Epidemiology
3rd most common cancer in men/women
More young individuals being diagnosed
Pathophysiology
Malignant polyps grow from the inner basement membrane of the bowel wall outward into the muscosa, submucosa, muscularis, and serosa
History of disease
Metastasis: bone, lungs, liver, lymph nodes
Risk factors
Age
Family hx
Familial Adenomatous Polyposis (FAP)
Hereditary Nonpolyposis colorectal cancer (HNPC)
Diet
Lifestyle
Polyps
Ulcerative colitis or Crohn’s disease
Familial Adenomatous Polyposis (FAP)
Autosomal dominant: mutation of adenomatous polyposis coli on chromosome 5
Result: 100% of adenomatous polyps
Result: 100% of developing colon cancer by age 40
Solution: colectomy
Hereditary Nonpolyposis Colorectal Cancer
Autosomal dominant
80% risk of developing colon caner + other tumors (endometrial, stomach, ovarian)
Genetics
dMMR: defective mismatch pair
MSI: micro satellite instability
MSI-L=low level micro satellite instability
MSI-H= high level micro satellite instability
If stage 2 + dMMR/MSI-H–> no chemo
If stage 3 + dMMR/MSI-H–> chemo
Signs/symptoms
Rectal bleeding, anemia, N/V, weight loss, change in bowel habits
Presentation
20-25% of patients will present with metastatic disease: jaundice, hepatomegaly, weight loss
50-60% of patients diagnosed with colorectal cancer will develop metastases
Fecal occult blood test (FOBT)
Avoid false positives: no red meat, raw vegetables for 3 days prior to testing
Avoid false negatives: no vitamin C more than 250 mg for 3 days prior to testing
Medical restrictions:
Avoid enemas, rectal meds, and digital rectal exams
Avoid ASA and NSAIDS for 7 days prior to testing
Avoid testing if hemorrhoids
3 days after menstrual bleeding ended
Fecal immunohistochemical test (FIT)
Detects hemmoglovin
FIT DNA
Detects hemoglobin + DNA biomarkers
When to start screening?
Normal: 45 yo
Annual FOBT or FIT
Colonoscopy every 10 years
Family history: 40 yo or 10 years younger than youngest age of diagnosis in family
FAP: 10-12 yo
HNPCC: 20-25 yo or 10 years younger than youngest person of diagnosis in family
Prevention
Diet: low fat, high fiber, high calcium
NSAIDS/ASPIRIN
Colectomy
Treatment options
Surgery: early stage disease
Chemotherapy
FOLFOX
Requires port (implantable access device)
2-day pump
More infusions overall
CapeOX
No port
Less infusions overall
Pearls: renal dose adjustments, drug-drug interactions
Stage I and II
Surgery
If high risk stage II–> may consider chemo
CHECK dMMR-MDI-H–> if high, no chemo
FOLFOX: 5-FU + leucovorin + oxaliplatin
CapeOX: Capecitabine + Oxaliplatin
Stage III
Surgery + chemo
FOLFOX
- 5-FU (bolus after leucovorin on day 1) + leucovorin + Oxaliplatin on day 1–> 5-FU continuous infusion x 2days every 14 days
Low risk: 3-6 months
High risk: 6 months
CapeOX
-Capecitabine x 14 days + Oxaliplatin on day 1 every 21 days
Low risk: 3 months
High risk: 3-6 months
Stage IV 1st line (no mutations)
FOLFOX +/- Bevacizumab
CapeOX +/- Bevacizumab
FOLFIRI +/- Bevacizumab
FOLFIRINOX +/- Bevacizumab
Stage IV 1st line KRAS wild type
FOLFOX/CapeOX + Cetuximab/Panitumumab
Stage IV 1st line dMMR/MSI-H
FOLFOX/CapeOX THEN
pembrolizumab/nivolumab/ipilimumab
Stage IV 1st line HER2+
Trastuzumab + pertuzumab/lapatinib
Trastuzumab/Deruxtecan
Stage IV 2nd line
If previously received Oxaliplatin: FOLFIRI
If previously received Irinotecan: FOLFOX OR CapeOX
Considerations in Chemo regimen for Colorectal cancer
Poor performance status
Other comorbidities:
-Neuropathy–> fewer platinum drugs
-UGT1A1 deficiency–> no irinotecan
PDL-1 status:
-dMMR/MSI-H–>pembrolizumab or nivolumab given after FOLFOX or CapeOX
KRAS: mutations predict lack of response to EGFR antibodies
-If positive–> no cetuximab or panitmumab
BRAF
