Colorectal Cancer

Front 1

What is the expected 5 year survival of colorectal cancer stage I, II, III and IV?

Back 1

I - 90%
II - 80%
III - 50%
IV - <10%

Front 2

Epidermal growth factor receptor blockers are used in the treatment of CRC. When are they indicated? What agents are used and how do they work?

Back 2

Inhibit cell growth by blocking the epidermal growth factor receptor.

Cetuximab, Panitumumab

These agents are used in patients that do not have the KRAS mutation

Front 3

i) What % of CRC is positive for the KRAS gene mutation?
ii) How do we test for the KRAS mutation?
iii) If the KRAS gene mutation is present how does this effect treatment?

Back 3

i) 40% of CRC is positive for the KRAS gene mutation
ii) Tissue sample of the cancer is needed -> PCR to amplify the DNA and test for the KRAS mutation
iii) If the KRAS gene mutation is identified the patient will not be eligible for EGFR blockers because the KRAS protein is activated without stimulation of the EGFR.

Front 4

i) How to vascular endothelial growth factor inhibitors work?
ii) Which VEGF inhibitors are used in CRC?

Back 4

i) Prevent angiogenesis, ultimately preventing growth of the vascular dependent tumor
ii) Bevacizumab

Front 5

What investigations are requested after identifying a CRC?

Back 5

CT chest, abdo, pelvis
KRAS mutation
CEA levels

Front 6

Conceptually how is CRC treated?

Back 6

Surgery for local disease
Adjuvant treatment - chemotherapy, biologic agents, RTx

Front 7

Which patients benefit from adjuvant therapy?

Back 7

Stage III disease (node positive)
The role of adjuvant therapy in stage II disease is controversial. Factors that may influence Tx include T4, tumor grade, life expectancy and comorbidities.

Young patients with stage II disease usually receive adjuvant chemo

Front 8

What are the most common chemotherapy regimens used in the Tx of CRC?

Back 8

FOLFOX - folinic acid and 5FU, oxaliplatin

or

XELOX - Xeloda = capecitabine and oxaliplatin

Front 9

What is the feared side effect of oxaliplatin?

Back 9

Irreversible peripheral neuropathy

Front 10

When is neoadjuvant therapy considered in CRC and what is involved?

Back 10

Rectal cancer - transmural and node positive

T3/T4 & N+ tumors

Front 11

Is metastatic CRC incurable?

Back 11

No. If metastatic disease is limited it can be curable. For example localised metastases in the liver or lung can be resected.

Front 12

What are the most common familial colorectal syndromes?

Back 12

FAP - 90% risk of CRC by age 45
Lynch Syndrome (HNPCC) - 25-75% lifetime risk of CRC

Together the above account for 5% of cases
Autosomal dominant

Front 13

What is the underlying pathology of Lynch syndrome?

Back 13

Defect in mismatch repair genes leading to microsatellite instability (detected by PCR).
90% of cases of Lynch syndrome demonstrate MSI but 15% of sporadic CRC have MSI. Thus MSI does not = Lynch syndrome but identifies pts that require additional testing -> immunohistochemistry for MMR proteins (which are absent when a disease causing defect is present)

Front 14

What criteria help to determine who should have MSI testing?

Back 14

Bethesda criteria

Front 15

Extracolonic cancers are very common in Lynch syndrome. What are sites are commonly involved?

Back 15

Endometrial cancer most common
Other sites include; ovaries, stomach, small bowel

Front 16

How should a pt with FAP be followed?

Back 16

Sigmoidoscopy from 12-15

Duodenal screening from age 25 or at time of colectomy

Front 17

How should a pt with HNPCC be followed?

Back 17

colonoscopy every 1-2 years from 25, or % years younger than familial case

Front 18

What are the current recommendations for CRC screening

Back 18

average risk - FOBT every 2 years from age 50, ? sigmoidoscopy every 5 years

moderate risk = 1st degree rel with CRC <55 or 2 1st or second degree rel with CRC at any age

- colonoscopy from every 5 years from age 50 or 10 years younger than age of diagnosis of bowel CRC in family

High risk

- suspected familial CRC

- >3 first or second degree rel with CRC

- CRC <50 and 1 rel with endometrial ca (HNPCC)

- recommend genetic testing and manage as per FAP/ HNPCC

Front 19

How is metastatic CRC treated?

Back 19

FOLFOX or FOLFIRI + Bevacizumab + Cetuximab/ Panitumumab (if KRAS wild type) - increase OS and PFS

If isolate liver or lung lesion, there is potential for cure. These patients should receive induction chemo followed by resection. Note unresectable lesions should be re-evaluated post chemotherapy to assess for resectability.

Front 20

What are the side effects of bevacizumab?

Back 20

Impaired wound healing

HTN

2 fold increase in arterial thromboembolic events

Front 21

What is the desired side effect of EGFRI?

Back 21

Rash - severity correlates with response