Biomarkers in Cancer Diagnosis

Question 1

What are the 3 main approaches to treatment of cancer?

Answer 1

1. Surgical excision
2. Radiotherapy
3. Chemotherapy

Question 2

Describe how personalised medicine has evolved to what it is now.

Answer 2

• Traditionally, doctors used:
  
  • Family Hx
  • Socioeconomic circumstances
  • Environment factors
• Now:
  
  • Genomic / genetic testing
  • Proteomic profiling
  • Metabolomic analysis (study metabolites)

Question 3

What is a biomarker?

Answer 3

• A tumour marker is anything present in or produced by cancer cells or other cells of the body in response to cancer that provides information about a cancer.
• For example:
  
  • How aggressive it is
  • Whether it can be treated with a targeted therapy
  • Whether it is responding to treatment
• Tumour markers can be found in the blood, urine, stool, tumours or other tissues or bodily fluids of some patients with cancer.
• Increasingly, however, genomic markers such as tumour gene mutations, patterns of tumour gene expression and nongenetic changes in tumour DNA are being used as tumour markers.

Question 4

State the difference between sensitivity and specificity.

Answer 4

• Sensitive - able to correctly identify people who have the disease.
• Specific - able to correctly identify people who do not have the disease.
  *

Question 5

What are the 2 main types of tumour markers which have different uses in cancer care?

Answer 5

1. Circulating tumour markers
2. Tumour tissue markers

Question 6

Describe the use of circulating tumour markers.

Answer 6

• Circulating tumour markers can be found in the blood, urine, stool or other bodily fluids of some patients with cancer.
• Circulating tumour markers are used to:
  
  • Estimate prognosis
  • Detect cancer that remains after treatment (residual disease) or that has returned after treatment
  • Assess the response to treatment
  • Monitor whether a cancer has become resistant to treatment.

Question 7

Describe the use of tumour tissue markers.

Answer 7

• Tumour tissue markers are found in the actual tumours themselves, typically in a sample of the tumour that is removed during a biopsy.
• Tumour tissue markers are used to:
  
  • Stage and / or classify cancer
  • Estimate prognosis
  • Select an appropriate treatment (e.g treatment with a targeted therapy)

Question 8

State the difference between prognostic and predictive.

Answer 8

• Prognostic - used to estimate the course and severity of the disease (population level).
• Predictive - used to predict whether a particular treatment will be effective (individual level).

Question 9

What is a companion diagnostic?

Answer 9

• A companion diagnostic is a medical device which provides information on a corresponding drug or biological product.
• Companion diagnostics can:
  
  • Identify patients who are most likely to benefit from a particular therapeutic product.
  • Identify patients likely to be at increased risk for serious side effects as a result of treatment with particular therapeutic product.
  • Monitor response to treatment with a particular therapeutic product for the purpose of adjusting treatment to achieve improved safety or effectiveness.

Question 10

Which biomarker is used in colorectal cancer?

Answer 10

• CEA - carcinoembryonic antigen.
  
  • Levels used to monitor response to treatment.
• Elevated preoperative CEA levels in resectable colorectal cancer is associated with poor prognosis.

Question 11

Describe the therapy used in patients with colorectal cancer who have RAS gene mutations.

Answer 11

• Cetuximab - anti-EGFR monoclonal antibody therapy.
• KRAS/NRAS mutation analysis - no mutations - cetuximab plus chemotherapy.
• The presence of a RAS mutation predicts the lack of response to therapy.

Question 12

What are the gene mutations in lung cancer (NSCLC) and which drugs are used for those specific mutations?

Answer 12

• EGFR mutation analysis - activating mutations - erlotinib.
• KRAS mutation analysis - activating mutations - no drug.
• ALK rearrangement analysis - (4%) fusion - crizotinib.
  
  • ​ALK rearrangements are mutually exclusive with EGFR or KRAS mutations.
• ROS1 positive mutation (fusion) - crizotinib.

Question 13

Describe the correlation between PD-L1 levels and treatment for NSCLC.

Answer 13

• Squamous NSCLC:
  
  • PD-L1 <50% - anti-PD-1, carboplatin and paclitaxel.
  • PD-L1 >50% - anti PD-1.
• Non-squamous NSCLC:
  
  • PD-L1 <50% - anti-PD-L1 or anti-PD-1 and pemetrexed, platinum chemo.
  • PD-L1 >50% - anti-PD1, pemetrexed, platinum chemo.

Question 14

What are the treatment options for renal cancer?

Answer 14

• Laparoscopic cryotherapy
• Percutaneous cryotherapy
• Percutaneous radiofrequency ablation
• Laparoscopic partial nephrectomy
• Laparoscopic nephrectomy (including nephroureterectomy)
• There are multiple options for targeted therapy with no one preferred drug at present.