Colorectal Cancer Flashcards
What is key about colorectal cancers?
These malignancies do not tend to present early
Which cancers are upper GI cancers?
oesophageal, gastric cancer, liver cancer, pancreatic cancer, gall bladder, small intestine
Which cancers are lower GI cancers?
Colorectal, anus
Which symptoms are associated with upper GI cancers?
Anorexia, dysphagia, weight loss, epigastric mass, recent onset of dyspepsia, over 55 years old, persistent vomitting, anaemia
What are common symptoms of lower GI cancers?
abdomen pain, change in bowel habit, passing of mucus, blood in the stool/rectal bleed, anaemia, intestinal obstruction, palpable mass in the abdomen
Which symptom is commonly associated with both upper and lower GI cancers?
Anaemia - as it is associated with bleeds
What are the risk factors for colorectal cancer?
Family history, modifiable risk factors
Which modifiable factors increase the risk of colorectal cancer?
Smoking, eating processed meat, alcohol intake, red meat, low fruit and veg intake, body fat/obesity
Which modifiable factors decrease the risk of colorectal cancer?
Increased physical activity, eating whole grains, increasing dietary fibre, fish intake, tree nuts, vitamins, calcium supplements
How is colorectal cancer screened for?
Screening programmes use the faecal immunochemical test, which aims to detect very small amounts of blood in the faeces and antibodies specific to human haemoglobin
Which investigations can be done for colorectal cancer?
Clinical history and examination, symptoms can be vague and varied. Colonoscopy, scans. There is a 2 week rule from presentation to the GP with suspected colorectal cancer
What are the T stages for colorectal cancer?
T1 - tumour is only in the inner layer of the bowel
T2 - tumour is in the muscle layer of the bowel wall
T3- tumour in the outer lining of the bowel wall
T4 - tumour has grown through outer lining of the outer bowel wall
What are the N stages for colorectal cancer?
N0 - no nodal involvement
N1 - 1-3 lymph nodes close to the bowel wall contain cancer cells
N2 - cancer cells present in 4 or more lymph nodes
What are the M stages for colorectal cancer?
M0 - no spread
M1 - Spread to other parts of the body
Why is tumour location important?
For overall prognosis, as different areas require different targeted treatment. Right sided colorectal cancer is associated with mutations in checkpoints and has a worse prognosis
What is right sided colorectal cancer associated with?
Mutations in checkpoints, has a worse prognosis
What are the treatment strategies for colorectal cancer?
Surgery, radiotherapy, chemotherapy
How is surgery used for colorectal cancer?
Removal of section of the bowel that contains the tumour. Some patients require a STOMA to allow faeces to pass, rest the bowel and improve recovery. Colorectal surgery is associated with better overall outcomes
What are short term complications are associated with colorectal cancer surgery?
Leakage of stoma, infection, DVT, haemorrhage
What are long term complications associated with colorectal cancer surgery?
urinary incontinence, sexual dyfunction, bowel dysfunction,
How are patients prepared for bowel cancer surgery?
With enhanced recovery after surgery techniques, which involves early management of feeding and analgesia, use modern surgical techniques, provide prophylaxis antibiotics, analgesia, oral osmotic laxatives to clear the bowel and reduce chances of infection
When is systemic treatment initiated for colorectal cancer patients?
If the tumour is large with nodal involvement, there is a potential for relapse, so systemic treatment is initiated post surgery as an adjuvant. In Dukes class B and C
What are the DUKE classifications relating to colorectal cancer?
Percentage survival
What is DUKES A for colorectal cancer?
T1-T3 - confined to bowel wall, has more than 83% survival
What is DUKES b for colorectal cancer?
T4, N0 - tumour involves bowel wall. 45% survival rate
What is DUKES c for colorectal cancer?
N1, N2, Mo - involving nodes has a 38% survival
What is DUKES d for colorectal cancer?
M1 - metastases - less than 5% chance of survival
Which drugs are typically used for systemic treatment of colorectal cancer?
Platinum derivative - oxaliplatin and an antimetabolite - capceitabine or 5 fluorouracil
What is capecitabine?
An oral 5 fluorouracil pro-drug, which mimics continuous infusion of 5 fluorouracil, whilst having higher efficacy. Thymidine phosphorylase converts capecitabine to 5 FU which has a high concentration in colon tissue, therefore it has a more selective action
What is significant about patients with a DPd deficiency if they are taking capecitabine or 5-FU?
Dihydropyrimidine dehydrogenase metabolises 5FU and capecitabine, so patients that are deficient in this enzyme are at a risk of severe side effects
Discuss 5fu with relation to colorectal cancer
5-fluorouracil is the most widley used drug in colorectal cancer treatment. It works on the S phase of the cell cycle and inhibits DNA synthesis. It is time dependent and increased exposure ensures that the majority of cells are in the S phase. It inhibits the synthesis of thymidine monophosphate.
What are common side effects with capecitabine and why does it not happen in 5 fu?
PDE - hand/foot syndrome, which is red/sore dry skin and patients can lose their finger prints. Common with antimetabolites. Capecitabine has to be converted by thymidine phosphorylase to 5FU, and there is high levels of thymidine phosphorylase in the hands/feet, so capecitabine accumulates here and has toxic effects
What is oxaliplatin?
A platinum derivative which targets the S phase of the cell cycle, cross links DNA strands and inhibits DNA synthesis and function
What are the main side effects of platinum derivatives?
- infusion related
- bone marrow suppression (sore throat)
- numbness in larynx
- progressive neuropathy
- GI toxicity
How is metastatic disease treated in colorectal cancer?
- palliative colon surgery to reduce tumour burden
- resection of liver/lung metastases
- palliative chemotherapy
- targetted therapies, such as EGFR/VEGF inhibitors but these are expensive
How can response to treatment be monitored in colorectal cancer?
- radiological findings, tumour markers, clinical examination
Which targeted therapies can be used for colorectal cancer?
Panitumab/cetuximab
What are panitumumab/cetuximab and how do they work?
- monoclonal antibodies targetting the epidermal growth factor receptor (EGFR)
- Bind to the extracellular domain of EGFR, competitive antagonist. Promote internalization of EGFR, block EGFR signalling
Leads to reduced angiogenesis and reduced tumour invasiveness
How can colorectal cancer be prevented?
- lifestyle modification to reduce modifiable risk factors
- screening programmes
- exercise
- smoking
- support patients towards modifications that are what they want
How is refractory metastatic disease in colorectal cancer treated?
LONSURF (trifluridine/tipiracil)
What is LONSURF and how does it work?
Composed of Trifluridine and tipiracil. Trifluridine is a thyimidine based nucleoside analogue. Tipiracil is a thymidine phosphorylase inhibitor. Tipiracil increases trifluridine exposure by inhibiting its metabolism by TP. Trifluridine is incorporated into cancer cell DNA, interferes with DNA synthesis and inhibits cell proliferation. It is an oral therapy that can cause myelosuppression
