Colon Cancer Flashcards

1
Q

What are risk factors for colon cancer?

A
Age >50
Polyps (adenomatous)
Genetic predisposition
FH of colorectal cancer
T2DM, metabolic syndrome
Personal history
Lifestyle factors
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2
Q

What are the genetic risk factors for colon cancer?

A

Familial adenomatous polyposis (FAP)

Hereditary nonpolyposis colorectal cancer (HNPCC)

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3
Q

What is FAP?

A

Mutations in the adenomatous polyposis coli (APC) gene

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4
Q

How does FAP present?

A

Large # of polyps in colon/rectum between ages 5-40

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5
Q

What will happen if FAP is left untreated?

A

100% risk for cancer

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6
Q

What is HNPCC?

A

Mutation in DNA mismatch-repair (MMR) genes

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7
Q

What are the most common mutations responsible for HNPCC?

A

MLH1
MSH2
PMS2

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8
Q

What lifestyles are RFs for colorectal cancer?

A
Obesity
Physical inactivity
Moderate-heavy EtOH
Long-term smoking
High consumption of red/processed meat
Low intake of fiber/fruits and vegetables
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9
Q

What are some possible protective factors?

A

Diet (high fiber/fruit and vegetables)
Calcium and Vitamin D
NSAIDs, low dose ASA
Surgical resection in extremely high risk patients

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10
Q

What is considered Average risk for colorectal cancer?

A

Age > 50

No h/o adenoma, colorectal cancer, or IBD

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11
Q

What are methods for colorectal cancer screening?

A

FOBT/FIT
Endoscopy
Radiology-based techniques
Stool DNA test

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12
Q

What are the types endoscopic imaging?

A

Sigmoidoscopy

Colonoscopy

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13
Q

What are the types of radiology-based techniques?

A

CT

Double contrast basrium enema

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14
Q

What is the FDA approved stool DNA test?

A

Cologuard

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15
Q

Which methods of colorectal cancer screening find polyps and cancer?

A

Flexible sigmoidoscopy
Colonoscopy
Double contrast barium enema
CT colonography

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16
Q

What methods of colorectal cancer screening find cancer only?

A

FOBT
FIT
Stool DNA test

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17
Q

What is the tier 1 recommendation for average risk?

A

Colonoscopy every 10 years

Annual fecal immunochemical test

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18
Q

What is the tier 2 recommendation for average risk?

A

CT colonography every 5 years
FIT-fecal DNA every 3 years
Flexible sigmoidoscopy every 5-10 years

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19
Q

What is the tier 3 recommendation for average risk?

A

Capsule colonoscopy every 5 years

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20
Q

What is the clinical presentation of colorectal cancer?

A
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
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21
Q

How do we work up a patient with suspected colon cancer?

A
Hx and PE
Baseline labs
Radiography
PET
Biopsy
Monitoring therapy
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22
Q

Why is a PET used for when working up a patient?

A

Can confirm metastatic disease

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23
Q

When is a PET scan used?

A

If standard imaging studies are inconclusive

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24
Q

What mutations are we looking for during a biopsy?

A

RAS

BRAF

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25
Q

How do we monitor therapy in colon cancer?

A

Carcinoembryonic antigen (CEA)

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26
Q

What is CEA?

A

an ‘oncofetal’ protein

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27
Q

When is CEA expressed?

A

In embryos and in many carcinomas, particularly GI cancers

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28
Q

Can CEA be used for diagnosis?

A

No

Insensitive and nonspecific

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29
Q

What does a positive CEA correlate to?

A
Amount of tumor
Differentiation of tumor
Residual disease
Recurrence
Poor survival
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30
Q

What is CEA good for?

A

Monitoring response to therapy and progression of disease

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31
Q

How does the TNM system correlate to Duke’s stage A?

A

T1-2, N0, M0

32
Q

How does the TNM system correlate to Duke’s stage B?

A

T3-4, N0, M0

33
Q

How does the TNM system correlate to Duke’s stage C?

A

T1-4, N1-2, M0

34
Q

How does cancer staging compare to Duke’s stage A?

A

Stage I

35
Q

How does cancer staging compare to Duke’s stage B?

A

Stage II

36
Q

How does cancer staging compare to Duke’s stage C?

A

Stage III

37
Q

What is the approximate 5 year survival for Stage I?

A

> 90%

38
Q

What is the approximate 5 year survival for Stage II?

A

63-87%

39
Q

What is the approximate 5 year survival for Stage III?

A

53-89%

40
Q

What is the approximate 5 year survival for stage IV?

A

11-13%

41
Q

What is the description of a patient with Stage I colon cancer?

A

No invasion of muscular mucosa

42
Q

What is the description of a patient with Stage II colon cancer?

A

Invasion of muscular mucosa, no extracolonic spread

43
Q

What is the description of a patient with Stage III colon cancer?

A

Lymph node involvement

44
Q

What is the description of a patient with Stage IV colon cancer?

A

Metastatic

45
Q

What are the prognostic factors for colon cancer?

A

Stage at diagnosis**
Degree of lymphatic invasion
Clinical factors
High proliferation indices

46
Q

What are clinical factors for prognosis?

A

Performance status
Bowel obstruction or perforation at presentation may worsen risk
Location of tumors

47
Q

When is adjuvant chemotherapy recommended in colon cancer?

A

Stage II if very high risk

Stage III - standard of care

48
Q

What are the regimen options for colon cancer?

A

FOLFOX/FLOX
CapeOx
C
FL/LV

49
Q

What is FOLFOX/FLOX?

A

5-FU
Leucovorin
Oxaliplatin

50
Q

What is CapeOx?

A

Capecitabine

Oxaliplatin

51
Q

What is FL/LV?

A

5-FU

Leucovorin

52
Q

What are the options for Stage I colon cancer?

A

Surgery

Observation

53
Q

What are the options for Stage II colon cancer?

A

Surgery
Consider C or FL/LV
Observation

54
Q

What are the options for Stage II high risk colon cancer?

A
Surgery
FOLFOX/FLOX
CapeOx
C
FL/LV
Observation
55
Q

What are the options for Stage III colon cancer?

A

Surgery
FOLFOX/CapeOx preferred
Observation

56
Q

How do we confirm diagnosis of stage IV or advanced colon cancer?

A

Biopsy

57
Q

What is the most common site for metastases to present in colon cancer?

A

Liver

58
Q

What is a possible option in select circumstances but is not standard of care?

A

Surgery
Neoadjuvant therapy +/- colectomy +/- synchronous or staged liver or lung resection
May extend DFS (disease free survival) or produce a cure in some patients

59
Q

What are chemotherapy options for advanced/ metastatic diseases?

A
FOLFOX
CapeOx
FOLFIRI
5-FU/Leucovorin or Capecitabine
FOLFOXIRI
60
Q

What is FOLFIRI?

A

Irinotecan
5-FU
Leucovorin

61
Q

What is FOLFOXIRI?

A

5-FU
Leucovorin
Oxaliplatin
Irinotecan

62
Q

What agents may be added to chemotherapy regimens for advanced/ metastatic disease?

A

Bevacizumab
Cetuximab
Paniumumab

63
Q

When V-Ki-Ras2 Kirsten Rat Sarcoma Viral Oncogene Homolog (KRAS) is turned on what does it do?

A

Conveys proliferative, growth, and survival signals

64
Q

In a normal setting what happens after KRAS turns on?

A

Turns off after conveying the activation signal

65
Q

Which type of agents are more likely to respond to wildtype KRAS?

A

EGFR inhibitors

66
Q

What mutations should also be tested for with KRAS?

A

NRAS

67
Q

How does KRAS work?

A

Plays an important role in signal transduction

Signal in the EGFR pathway

68
Q

What is BRAF V600E?

A

Protein involved with signals that trigger cell growth

69
Q

What is TS/TYMS?

A

Thymidylate synthase
Involved in DNA synthesis
Inhibited by 5-FU

70
Q

What may happen if there is an overexpression of TS?

A

Drug resistance

71
Q

What is DPD/DPYD?

A

Dihydropyrimidine dehydrogenase

Responsible for degrading pyrimidines

72
Q

What happens when there is a deficiency of DPD?

A

5-FU/capecitabine toxicity

73
Q

What is UGT1A1?

A

Codes for UDP-glucuronosyltranserase

Part of a series of drug metabolism enzymes

74
Q

What is UGT1A1 involved in the metabolism of?

A

Bilirubin
Estrogens
Thyroid hormone
Chemotherapy agents (etoposide, irinotecan)

75
Q

Which UGT1A1 variants result in drug toxicity?

A
  • 28

* 6

76
Q

What is dMMR/MSI-H?

A

dMMR - defective mismatch repair

MSI-H - high level microsatellite instability

77
Q

Which drugs is dMMR/MSI-H a predictor of benefit of?

A

Pembrolizumab
Nivolumab
(in metastatic disease)