Colon Cancer Flashcards
What are risk factors for colon cancer?
Age >50 Polyps (adenomatous) Genetic predisposition FH of colorectal cancer T2DM, metabolic syndrome Personal history Lifestyle factors
What are the genetic risk factors for colon cancer?
Familial adenomatous polyposis (FAP)
Hereditary nonpolyposis colorectal cancer (HNPCC)
What is FAP?
Mutations in the adenomatous polyposis coli (APC) gene
How does FAP present?
Large # of polyps in colon/rectum between ages 5-40
What will happen if FAP is left untreated?
100% risk for cancer
What is HNPCC?
Mutation in DNA mismatch-repair (MMR) genes
What are the most common mutations responsible for HNPCC?
MLH1
MSH2
PMS2
What lifestyles are RFs for colorectal cancer?
Obesity Physical inactivity Moderate-heavy EtOH Long-term smoking High consumption of red/processed meat Low intake of fiber/fruits and vegetables
What are some possible protective factors?
Diet (high fiber/fruit and vegetables)
Calcium and Vitamin D
NSAIDs, low dose ASA
Surgical resection in extremely high risk patients
What is considered Average risk for colorectal cancer?
Age > 50
No h/o adenoma, colorectal cancer, or IBD
What are methods for colorectal cancer screening?
FOBT/FIT
Endoscopy
Radiology-based techniques
Stool DNA test
What are the types endoscopic imaging?
Sigmoidoscopy
Colonoscopy
What are the types of radiology-based techniques?
CT
Double contrast basrium enema
What is the FDA approved stool DNA test?
Cologuard
Which methods of colorectal cancer screening find polyps and cancer?
Flexible sigmoidoscopy
Colonoscopy
Double contrast barium enema
CT colonography
What methods of colorectal cancer screening find cancer only?
FOBT
FIT
Stool DNA test
What is the tier 1 recommendation for average risk?
Colonoscopy every 10 years
Annual fecal immunochemical test
What is the tier 2 recommendation for average risk?
CT colonography every 5 years
FIT-fecal DNA every 3 years
Flexible sigmoidoscopy every 5-10 years
What is the tier 3 recommendation for average risk?
Capsule colonoscopy every 5 years
What is the clinical presentation of colorectal cancer?
Changes in bowel habits GI (N/V, discomfort, bloating, fullness, cramps, ab pain, ascites) Rectal bleeding/blood in stool Fatigue Wt loss Leg edema/pain Back pain w/lymph node involvement Hepatomegaly, jaundice, possibly LFTs with metastatic disease
How do we work up a patient with suspected colon cancer?
Hx and PE Baseline labs Radiography PET Biopsy Monitoring therapy
Why is a PET used for when working up a patient?
Can confirm metastatic disease
When is a PET scan used?
If standard imaging studies are inconclusive
What mutations are we looking for during a biopsy?
RAS
BRAF
How do we monitor therapy in colon cancer?
Carcinoembryonic antigen (CEA)
What is CEA?
an ‘oncofetal’ protein
When is CEA expressed?
In embryos and in many carcinomas, particularly GI cancers
Can CEA be used for diagnosis?
No
Insensitive and nonspecific
What does a positive CEA correlate to?
Amount of tumor Differentiation of tumor Residual disease Recurrence Poor survival
What is CEA good for?
Monitoring response to therapy and progression of disease
How does the TNM system correlate to Duke’s stage A?
T1-2, N0, M0
How does the TNM system correlate to Duke’s stage B?
T3-4, N0, M0
How does the TNM system correlate to Duke’s stage C?
T1-4, N1-2, M0
How does cancer staging compare to Duke’s stage A?
Stage I
How does cancer staging compare to Duke’s stage B?
Stage II
How does cancer staging compare to Duke’s stage C?
Stage III
What is the approximate 5 year survival for Stage I?
> 90%
What is the approximate 5 year survival for Stage II?
63-87%
What is the approximate 5 year survival for Stage III?
53-89%
What is the approximate 5 year survival for stage IV?
11-13%
What is the description of a patient with Stage I colon cancer?
No invasion of muscular mucosa
What is the description of a patient with Stage II colon cancer?
Invasion of muscular mucosa, no extracolonic spread
What is the description of a patient with Stage III colon cancer?
Lymph node involvement
What is the description of a patient with Stage IV colon cancer?
Metastatic
What are the prognostic factors for colon cancer?
Stage at diagnosis**
Degree of lymphatic invasion
Clinical factors
High proliferation indices
What are clinical factors for prognosis?
Performance status
Bowel obstruction or perforation at presentation may worsen risk
Location of tumors
When is adjuvant chemotherapy recommended in colon cancer?
Stage II if very high risk
Stage III - standard of care
What are the regimen options for colon cancer?
FOLFOX/FLOX
CapeOx
C
FL/LV
What is FOLFOX/FLOX?
5-FU
Leucovorin
Oxaliplatin
What is CapeOx?
Capecitabine
Oxaliplatin
What is FL/LV?
5-FU
Leucovorin
What are the options for Stage I colon cancer?
Surgery
Observation
What are the options for Stage II colon cancer?
Surgery
Consider C or FL/LV
Observation
What are the options for Stage II high risk colon cancer?
Surgery FOLFOX/FLOX CapeOx C FL/LV Observation
What are the options for Stage III colon cancer?
Surgery
FOLFOX/CapeOx preferred
Observation
How do we confirm diagnosis of stage IV or advanced colon cancer?
Biopsy
What is the most common site for metastases to present in colon cancer?
Liver
What is a possible option in select circumstances but is not standard of care?
Surgery
Neoadjuvant therapy +/- colectomy +/- synchronous or staged liver or lung resection
May extend DFS (disease free survival) or produce a cure in some patients
What are chemotherapy options for advanced/ metastatic diseases?
FOLFOX CapeOx FOLFIRI 5-FU/Leucovorin or Capecitabine FOLFOXIRI
What is FOLFIRI?
Irinotecan
5-FU
Leucovorin
What is FOLFOXIRI?
5-FU
Leucovorin
Oxaliplatin
Irinotecan
What agents may be added to chemotherapy regimens for advanced/ metastatic disease?
Bevacizumab
Cetuximab
Paniumumab
When V-Ki-Ras2 Kirsten Rat Sarcoma Viral Oncogene Homolog (KRAS) is turned on what does it do?
Conveys proliferative, growth, and survival signals
In a normal setting what happens after KRAS turns on?
Turns off after conveying the activation signal
Which type of agents are more likely to respond to wildtype KRAS?
EGFR inhibitors
What mutations should also be tested for with KRAS?
NRAS
How does KRAS work?
Plays an important role in signal transduction
Signal in the EGFR pathway
What is BRAF V600E?
Protein involved with signals that trigger cell growth
What is TS/TYMS?
Thymidylate synthase
Involved in DNA synthesis
Inhibited by 5-FU
What may happen if there is an overexpression of TS?
Drug resistance
What is DPD/DPYD?
Dihydropyrimidine dehydrogenase
Responsible for degrading pyrimidines
What happens when there is a deficiency of DPD?
5-FU/capecitabine toxicity
What is UGT1A1?
Codes for UDP-glucuronosyltranserase
Part of a series of drug metabolism enzymes
What is UGT1A1 involved in the metabolism of?
Bilirubin
Estrogens
Thyroid hormone
Chemotherapy agents (etoposide, irinotecan)
Which UGT1A1 variants result in drug toxicity?
- 28
* 6
What is dMMR/MSI-H?
dMMR - defective mismatch repair
MSI-H - high level microsatellite instability
Which drugs is dMMR/MSI-H a predictor of benefit of?
Pembrolizumab
Nivolumab
(in metastatic disease)