Colorectal Cancer

Question 1

How is FOBT done?

Answer 1

second yearly test for 50-74 year olds

Question 2

What does the FOBT measure?

Answer 2

human globin in stool

Question 3

What is the most common cause of positive FOBT?

Answer 3

haemorrhoids, diverticular disease

Question 4

What are the risk factors for colorectal cancer?

Answer 4

FHx, inflammatory bowel disease, previous abdominopelvic radiation, obesity, diabetes, meat consumption

Question 5

What percentage of colorectal cancer is due to genetic syndromes?

Answer 5

5%

Question 6

What are the polyposis syndromes?

Answer 6

FAP and MUTYH-associated polyposis

Question 7

What is the pathogenesis of FAP?

Answer 7

loss of APC gene on chromosome 5 (autosomal dominant)

Question 8

What is the pathogenesis of lynch syndrome?

Answer 8

loss of MLH1, MSH2, PMS2 or MSH6 leading to microsatellite instability - can be sporadic or hereditary

Question 9

What is the risk of developing colorectal cancer in FAP?

Answer 9

90%

Question 10

What is the risk of developing colorectal gene if MLH1 deficient?

Answer 10

50%

Question 11

Which type of colorectal cancer can use immunotherapy?

Answer 11

mismatch repair deficient colorectal cancer because of the development of neoantigens

Question 12

What is the management for T3 and above rectal cancer?

Answer 12

neoadjuvant therapy - either radiotherapy or chemoradiotherapy, to prevent local spread and improve chance of an R0 resection or to achieve complete pathological response

Question 13

How is colorectal cancer staged?

Answer 13

T - tumour - where it is in relation to the bowel wall
N - regional lymph nodes
M - metastases

Question 14

What is the role of adjuvant chemotherapy/

Answer 14

to ‘mop up’ micro-metastatic disease before it establishes as metastatic disease

Question 15

What is the recommended treatment for stage 3 CRC?

Answer 15

adjuvant chemotherapy with a fluoropyrimidine (5FU or capecitabine) and oxaliplatin

Question 16

What is ctDNA?

Answer 16

a blood test which assess the presence of circulating tumour DNA in those who’ve had a curative procedure -> maybe will be used to escalate or de-escalate therapy in locally advanced rectal cancer

Question 17

What is the follow up for colorectal cancer?

Answer 17

colonoscopy at conclusion of treatment, 3 years, then 5 yearly
physical exam and CEA 3 monthly for 3 years then 6 monthly
CTCAP annually for 3 years

Question 18

What percentage of colorectal cancer presents as denovo metastatic disease?

Answer 18

25%

Question 19

What precentage of patients with local disease will relapse with metastatic disease?

Answer 19

50%

Question 20

What is predictive of response to EGFR directed therapy in metastatic CRC?

Answer 20

absence of RAS/RAF mutations

Question 21

What is the prognosis for BRAF positive patients with CRC?

Answer 21

poor - rapidly develop chemotherapy resistance

Question 22

Is MMR deficient status a good or bad prognostic sign?

Answer 22

good prognosis in stage 1-3 but bad prognosis in stage 4

Question 23

What is the management in stage 4b CRC?

Answer 23

palliative intent chemotherapy
often no role for surgery
combined with a targeted agent - a vascular endothelial growth factor inhibitor or endothelial growth factor receptor

Question 24

Is there any role for targeted agents in adjuvant treatment?

Answer 24

no

Question 25

What are the most common sites of metastases in CRC?

Answer 25

liver, lung, peritoneum

Question 26

What is oligometastatic disease?

Answer 26

metastases to one visceral organ

Question 27

What is the difference between management for M1a (oligometastatic) and M1b disease?

Answer 27

can use neoadjuvant therapy and aggressive surgical therapy for oligometastatic

Question 28

Is right sided disease or left sided disease more aggressive?

Answer 28

R sided

Question 29

What mutation is more common in right sided disease?

Answer 29

BRAF

Question 30

What mutation is more common in left sided disease?

Answer 30

RAS/RAF

Question 31

What are the common toxicities with fluoropyrimidine chemotherapy?

Answer 31

mucositis, diarrhoea, nausea, vomiting, coronary artery vasospasm, myelosuppression

Question 32

How is fluoropyrimidine metabolised?

Answer 32

by dihydropyrimidine dehydrogenase - deficient in 8% of the population - potential for fatal toxicity, manifests as early myelosuppression and bad mucositis - can lead to perforation and death

Question 33

What are the fluoropyrimidines?

Answer 33

5FU and capecitabine

Question 34

What is in FOLFIRINOX?

Answer 34

5FU and oxaliplatin plus irinotecan

Question 35

What is the mechanism of action of fluoropyrimidines?

Answer 35

thymidine synthetase inhibition

Question 36

What is the mechanism of action of irinotecan?

Answer 36

inhibits topoisomerase-1

Question 37

How is irinotecan metabolised?

Answer 37

the active metabolite SN-38 is metabolised by UAT181 - if deficient then irinotecan can cause fatal toxicity

Question 38

What are the toxicities of oxaliplatin?

Answer 38

peripheral neuropathy, cold dysaesthesia, fatigue, infusion reactions

Question 39

What mutations confer resistance to EGFR inhibitors?

Answer 39

RAS/RAF/HER2

Question 40

What are the toxicities of EGFR inhibitors?

Answer 40

hypomagnesia and cutaneous acneform rash

Question 41

What are the toxicities of VEG-F inhibitor?

Answer 41

hypertension, wound breakdown/impaired healing, GI perforation, proteinuria, thromboembolic events