Colorectal Cancer

Question 1

How common is colorectal?

Answer 1

2nd most common in men and women

9% of cancer dx

Question 2

What is the medium age of dx?

Answer 2

68 men, 72 women

Question 3

In which age group is incidence increasing?

Answer 3

Those <50

Question 4

What is the percentage 5 year survival of stage 1 vs 4

Answer 4

98.6 vs 13.4

Question 5

When is FOBT given?

Answer 5

Second yearly for those 50-74

Question 6

What is the percentage of positive FOBT have cancer?

Answer 6

1:29

Question 7

What are risk factors?

Answer 7

IBD
Previous abdominopelvic radiation 
Obesity
Diabetes and insulin resistance
Meat consumption 
Family history

Question 8

Which IBD subgroup is highest risk?

Answer 8

USC with PSC

Question 9

When should screening begin post abdopelvic radiation?

Answer 9

5 years after or at aged 30

Question 10

What are the molecular subtypes?

Answer 10

CMS1 - MSI-immune
CMS2 - canonical
CMS3 - metabolic
CMS4 - Mesenchymal

Question 11

What percentage of CRC are from genetic syndromes?

Answer 11

5%

Question 12

What are the main genetic syndrome and what are the genes?

Answer 12

Polyposis syndrome inc FAP. APC gene

Lynch syndrome (Hereditary non-polyposis coli HNPCC). Loss of MLH1, MSH2, PMS2 or MSH6 - microsatellite instability

Question 13

How do you differentiate familiar and sporadic lynch

Answer 13

Loss at normal tissue for loss of MLH1

Question 14

What does deficiency in mismatch repair mean for outcomes

Answer 14

Better outcomes with deficient over proficient

Question 15

Why are liver mets common in colon ca?

Answer 15

Colon is drained by portal vein

Cf to rectal cancer where lung mets are more common

Question 16

How many LNs should be resected?

Answer 16

14

Question 17

What is the rectum?

Answer 17

Below the peritoneal reflection

Question 18

When do you get chemoradiotherapy in rectal?

Answer 18

Neoadjuvant

Question 19

In which stages do you give adjuvant therapy in CRC?

Answer 19

Stage three and high risk stage 2

Question 20

What is high risk stage 2 disease?

Answer 20

T4 (extending into peritoneum)
Presenting with obstruction or perforation
Inadequate node sampling
Presence of lymhovascular or perineural invasion

Question 21

What are the T types?

Answer 21

Tx - cannot be assessed
T0 - no primary
Tis - carcinoma in situ, intraepithelial or invasion of lamina propria
T1 - invasion of submucosa
T2 - invasion of muscular propria
T3 - through muscularis propria into pericolorectal tissues
T4a - penetrates surface of visceral peritoneum
T4b - in invades or adherent to other organs or structures

Question 22

What are the N classes?

Answer 22

Nx - cannot be assessed
N0 - no LN mets 
N1 - Mets in 1-3 regional LNs 
N1a - mets in one regional LN
N1b - mets in 2-3 regional LN
N1c - tumour deposit in subserosa, mesentery, or nonperitonealised pericolic or perirectal tissues without region LN mets 
N2 - mets in 4 or more regional LNs 
N2a - mets in 4-6 regional LNs 
N2b - mets in 7 or more regional LNs

Question 23

What are the M classes?

Answer 23

M0 - no distant mets
M1 - distant mets
M1a - mets confined to one organ site (eg liver, lung, nonregional LN)
M1b - mets in more than one organ/site or the peritoneam

Question 24

What are the stages in relation to TNM?

Answer 24

0 - Tis 
I - T1/2
IIA/IIB/IIC - T3/T4a/T4b
III - T1-4 + N1-2b
IV - Any T, any N with M1a or 1b

Question 25

What is the aim of adjuvant chemo?

Answer 25

Cure - mop up micro-metastasis

Question 26

What adjuvant chemo is used?

Answer 26

Fluoropyrimidine (either 5FU or capecitabine) and oxaliplatin ie FOLFOX or CAPOX

Question 27

How long do you give adjuvant chemo?

Answer 27

3 in lower risk (T1-3, N1), 6 in higher (T4 and/or N2)

Question 28

What does the presence of post-op circulating tumour DNA mean?

Answer 28

Recurrence is inevitable

Question 29

What percentage of CRC express CEA?

Answer 29

70%

Question 30

How do you surveil post curative treatment?

Answer 30

No Australia guidelines - follow US: Full colonoscopy if not already had one then at 3 years then 5 yearly Exam w CEA 3monthly for three years then 6 monthly CT CAP annually for three years

Question 31

What percentage of CRC presents with metastatic disease?

Answer 31

25%

Question 32

When is mutational status important?

Answer 32

Metastatic disease

Question 33

What are the implications of the different mutations?

Answer 33

RAS/RAF - predictive of response to EGFR directed therapy BRAF - poor responders, rapid development of chemotherapy resistance and nodal spread MMR status - MSI-H do poorly

Question 34

Which agents are used with EGFR positive?

Answer 34

Cetuximab | Panitumimab

Question 35

How is stage 4b managed?

Answer 35

Metastatic chemotherapy - FOLFOX and FOLIFIRI No surgery

Question 36

Which vascular endothelial growth factor inhibitor is used?

Answer 36

Bevacizumab

Question 37

When are targeted therapies used?

Answer 37

Metastatic disease | Not in adjuvant therapy

Question 38

What is the 5 year survival of M1a disease?

Answer 38

as high as 40%

Question 39

How long is neoadjuvant therapy given in M1a?

Answer 39

3 months

Question 40

What side CRC is poorer prognosis?

Answer 40

Right

Question 41

What met CRC benefits from anti-EGFR therapy?

Answer 41

Left-sided RAS wildtype | cetuximab & panitumimab

Question 42

Which mutations are more common on which side?

Answer 42

BRAF - right side | RAS/RAF - left side

Question 43

What is hte mechanism of fluoropyrimidines (5FU)

Answer 43

Inhibit thymidine synthesis - metaabolites incorportted into DNA - apoptosis

Question 44

What is FOLFIRI?

Answer 44

5FU w irinotecan

Question 45

What is FOLFOX?

Answer 45

5FU w oxaliplatin

Question 46

What are the toxicities of fluoropyridines?

Answer 46

Mucocitis - oral to anus N/V Coronary artery vasospasm Myelosuppression

Question 47

What is the variation in fluoropyrimidine metabolism?

Answer 47

Deficiency in enzyme dihydropyrimidine dehydrogenase Present in 2-8% of population Presents with early myelosuppression and bad mucositis Antedote present

Question 48

What is the toxicity of irinotecan?

Answer 48

Diarrhoea, myelosuppression and fatigue UAT181 enzyme metabolises SN-38 - deficiency in this (also in Gilbert's syndrome) can lead to fatal toxicity with myelosuppresion

Question 49

What is the toxicity of oxaliplatin?

Answer 49

Peripheral neuropathy - cumulative effect, irreversible Cold dysaesthesia Fatigue Infusion reactions

Question 50

What are the EGFR inhibitors?

Answer 50

Cetuximab and panitumimab

Question 51

What are the the VEG-F inhibitors?

Answer 51

Bevacizumab only one available in Aus

Question 52

When is bevacizumab used?

Answer 52

R sided RAS/RAF mCRC

Question 53

What are some side effects of bevacizumab?

Answer 53

HTN, proteinuria, thromboembolism, wound breakdown