Colorectal Cancer Flashcards
How is FOBT done?
second yearly test for 50-74 year olds
What does the FOBT measure?
human globin in stool
What is the most common cause of positive FOBT?
haemorrhoids, diverticular disease
What are the risk factors for colorectal cancer?
FHx, inflammatory bowel disease, previous abdominopelvic radiation, obesity, diabetes, meat consumption
What percentage of colorectal cancer is due to genetic syndromes?
5%
What are the polyposis syndromes?
FAP and MUTYH-associated polyposis
What is the pathogenesis of FAP?
loss of APC gene on chromosome 5 (autosomal dominant)
What is the pathogenesis of lynch syndrome?
loss of MLH1, MSH2, PMS2 or MSH6 leading to microsatellite instability - can be sporadic or hereditary
What is the risk of developing colorectal cancer in FAP?
90%
What is the risk of developing colorectal gene if MLH1 deficient?
50%
Which type of colorectal cancer can use immunotherapy?
mismatch repair deficient colorectal cancer because of the development of neoantigens
What is the management for T3 and above rectal cancer?
neoadjuvant therapy - either radiotherapy or chemoradiotherapy, to prevent local spread and improve chance of an R0 resection or to achieve complete pathological response
How is colorectal cancer staged?
T - tumour - where it is in relation to the bowel wall
N - regional lymph nodes
M - metastases
What is the role of adjuvant chemotherapy/
to ‘mop up’ micro-metastatic disease before it establishes as metastatic disease
What is the recommended treatment for stage 3 CRC?
adjuvant chemotherapy with a fluoropyrimidine (5FU or capecitabine) and oxaliplatin
What is ctDNA?
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
What is the follow up for colorectal cancer?
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
What percentage of colorectal cancer presents as denovo metastatic disease?
25%
What precentage of patients with local disease will relapse with metastatic disease?
50%
What is predictive of response to EGFR directed therapy in metastatic CRC?
absence of RAS/RAF mutations
What is the prognosis for BRAF positive patients with CRC?
poor - rapidly develop chemotherapy resistance
Is MMR deficient status a good or bad prognostic sign?
good prognosis in stage 1-3 but bad prognosis in stage 4
What is the management in stage 4b CRC?
palliative intent chemotherapy
often no role for surgery
combined with a targeted agent - a vascular endothelial growth factor inhibitor or endothelial growth factor receptor
Is there any role for targeted agents in adjuvant treatment?
no
What are the most common sites of metastases in CRC?
liver, lung, peritoneum
What is oligometastatic disease?
metastases to one visceral organ
What is the difference between management for M1a (oligometastatic) and M1b disease?
can use neoadjuvant therapy and aggressive surgical therapy for oligometastatic
Is right sided disease or left sided disease more aggressive?
R sided
What mutation is more common in right sided disease?
BRAF
What mutation is more common in left sided disease?
RAS/RAF
What are the common toxicities with fluoropyrimidine chemotherapy?
mucositis, diarrhoea, nausea, vomiting, coronary artery vasospasm, myelosuppression
How is fluoropyrimidine metabolised?
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
What are the fluoropyrimidines?
5FU and capecitabine
What is in FOLFIRINOX?
5FU and oxaliplatin plus irinotecan
What is the mechanism of action of fluoropyrimidines?
thymidine synthetase inhibition
What is the mechanism of action of irinotecan?
inhibits topoisomerase-1
How is irinotecan metabolised?
the active metabolite SN-38 is metabolised by UAT181 - if deficient then irinotecan can cause fatal toxicity
What are the toxicities of oxaliplatin?
peripheral neuropathy, cold dysaesthesia, fatigue, infusion reactions
What mutations confer resistance to EGFR inhibitors?
RAS/RAF/HER2
What are the toxicities of EGFR inhibitors?
hypomagnesia and cutaneous acneform rash
What are the toxicities of VEG-F inhibitor?
hypertension, wound breakdown/impaired healing, GI perforation, proteinuria, thromboembolic events
