Colorectal Cancer Flashcards
How common is colorectal?
2nd most common in men and women
9% of cancer dx
What is the medium age of dx?
68 men, 72 women
In which age group is incidence increasing?
Those <50
What is the percentage 5 year survival of stage 1 vs 4
98.6 vs 13.4
When is FOBT given?
Second yearly for those 50-74
What is the percentage of positive FOBT have cancer?
1:29
What are risk factors?
IBD Previous abdominopelvic radiation Obesity Diabetes and insulin resistance Meat consumption Family history
Which IBD subgroup is highest risk?
USC with PSC
When should screening begin post abdopelvic radiation?
5 years after or at aged 30
What are the molecular subtypes?
CMS1 - MSI-immune
CMS2 - canonical
CMS3 - metabolic
CMS4 - Mesenchymal
What percentage of CRC are from genetic syndromes?
5%
What are the main genetic syndrome and what are the genes?
Polyposis syndrome inc FAP. APC gene
Lynch syndrome (Hereditary non-polyposis coli HNPCC). Loss of MLH1, MSH2, PMS2 or MSH6 - microsatellite instability
How do you differentiate familiar and sporadic lynch
Loss at normal tissue for loss of MLH1
What does deficiency in mismatch repair mean for outcomes
Better outcomes with deficient over proficient
Why are liver mets common in colon ca?
Colon is drained by portal vein
Cf to rectal cancer where lung mets are more common
How many LNs should be resected?
14
What is the rectum?
Below the peritoneal reflection
When do you get chemoradiotherapy in rectal?
Neoadjuvant
In which stages do you give adjuvant therapy in CRC?
Stage three and high risk stage 2
What is high risk stage 2 disease?
T4 (extending into peritoneum)
Presenting with obstruction or perforation
Inadequate node sampling
Presence of lymhovascular or perineural invasion
What are the T types?
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
What are the N classes?
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
What are the M classes?
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
What are the stages in relation to TNM?
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
What is the aim of adjuvant chemo?
Cure - mop up micro-metastasis
What adjuvant chemo is used?
Fluoropyrimidine (either 5FU or capecitabine) and oxaliplatin
ie FOLFOX or CAPOX
How long do you give adjuvant chemo?
3 in lower risk (T1-3, N1), 6 in higher (T4 and/or N2)
What does the presence of post-op circulating tumour DNA mean?
Recurrence is inevitable
What percentage of CRC express CEA?
70%
How do you surveil post curative treatment?
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
What percentage of CRC presents with metastatic disease?
25%
When is mutational status important?
Metastatic disease
What are the implications of the different mutations?
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
Which agents are used with EGFR positive?
Cetuximab
Panitumimab
How is stage 4b managed?
Metastatic chemotherapy - FOLFOX and FOLIFIRI
No surgery
Which vascular endothelial growth factor inhibitor is used?
Bevacizumab
When are targeted therapies used?
Metastatic disease
Not in adjuvant therapy
What is the 5 year survival of M1a disease?
as high as 40%
How long is neoadjuvant therapy given in M1a?
3 months
What side CRC is poorer prognosis?
Right
What met CRC benefits from anti-EGFR therapy?
Left-sided RAS wildtype
cetuximab & panitumimab
Which mutations are more common on which side?
BRAF - right side
RAS/RAF - left side
What is hte mechanism of fluoropyrimidines (5FU)
Inhibit thymidine synthesis - metaabolites incorportted into DNA - apoptosis
What is FOLFIRI?
5FU w irinotecan
What is FOLFOX?
5FU w oxaliplatin
What are the toxicities of fluoropyridines?
Mucocitis - oral to anus
N/V
Coronary artery vasospasm
Myelosuppression
What is the variation in fluoropyrimidine metabolism?
Deficiency in enzyme dihydropyrimidine dehydrogenase
Present in 2-8% of population
Presents with early myelosuppression and bad mucositis
Antedote present
What is the toxicity of irinotecan?
Diarrhoea, myelosuppression and fatigue
UAT181 enzyme metabolises SN-38 - deficiency in this (also in Gilbert’s syndrome) can lead to fatal toxicity with myelosuppresion
What is the toxicity of oxaliplatin?
Peripheral neuropathy - cumulative effect, irreversible
Cold dysaesthesia
Fatigue
Infusion reactions
What are the EGFR inhibitors?
Cetuximab and panitumimab
What are the the VEG-F inhibitors?
Bevacizumab only one available in Aus
When is bevacizumab used?
R sided RAS/RAF mCRC
What are some side effects of bevacizumab?
HTN, proteinuria, thromboembolism, wound breakdown
