Session 11 - Neoplasia 4 Flashcards
In what age group are the majority of new diagnoses of cancer made in?
-Over 65
What are the 3 most common cancers in children younger than 14?
- Leukaemias
- Central nervous system tumours
- Lymphomas
Which 3 cancers have the highest 5 year survival rate?
- Testicular
- Melanoma
- Breast
Which 3 cancers have the poorest 5 year survival rate?
- Pancreatic
- Lung
- Oesophageal
What type of cancer is the biggest cause of cancer-related deaths in the UK?
-Lung
What factors are considered when predicting the outcome of a malignant neoplasm?
- Tumour Site
- Tumour type
- Grade
- Stage
- Age and general health
What is meant by the tumour type?
-The characteristics which a tumour possesses (eg malignant melanoma almost always invades and is agressive whereas basal cell carcinoma almost never metastasises)
What is the most common method of staging?
-TNM
What does T refer to in TNM staging?
-T is primary tumour size, typically expressed between T1 and T4
What does N describe in TNM staging?
-The extent of regional node metastases (N0 to N3)
What does M describe in TNM staging of tumours?
-M is the extent of the metastatic spread (M0 or M1)
What happens to the T, N and M scores calculated for a given cancer?
-They are converted into a stage from I to IV
Describe the levels of staging I to IV, generally
Stage I -> Early local disease
Stage II -> Advanced local disease
Stage III-> Regional metastases
Stage IV -> Advanced disease with distant metastases
Is staging the same for every type of cancer?
-No it alters depending on the specific cancer to incorporate specific characteristics (size, invasion etc)
What is the ann arbour system? Briefly describe its stages
- The staging system used in lymphoma
- Stage 1 indicates lymphoma in a single node region
- Stage 2 indicates 2 separate regions on one side of the diaphragm
- Stage 3 indicates spread to both sides of the diaphragm
- Stage 4 indicates diffuse or disseminated disease with involvement of one or more extra-lymphatic organs (BM or lungs)
What is Dukes staging? Breifly describe the stages?
-A type of staging used in colorectal cancer
A-> Invasion into but not through the bowel into muscularis propria
B-> Invasion into or through the muscularis propria
C-> Involvement of lymph nodes
(D -> distant metasteses (not original dukes))
What doe the grade of a neoplasm refer to?
-How well differentiated the tumour is
What does stage of a tumour refer to?
-Tumour burden and how much tumour is present in the body
What is the usual method of treatment to ‘cure’ cancer?
-Surgery
What are the possible grades of cancer and what do they generally mean?
G1 -> Well differentated
G2-> Moderately differentiated
G3-> Poorly differentiated
G4-> Undifferentiated or anaplastic
Is grading the same for all types of cancer?
-No some have theyre own specific grading system
What is the Bloom-Richardson system?
-The grading system used in breast cancer
What characteristics does the Bloom-Richardson grading system for breast cancer assess?
- Tubule formation of cells
- Nuclear variation
- Number of mitoses
In which malignancys is grade important for planning treatment and prognosis?
- Soft tissue sarcoma
- Primary brain tumours
- Lymphomas
- Breast and prostate cancer
What are the 5 groups of possible treatments of cancer?
- Surgery
- Radiotherapy
- Chemotherapy
- Hormone therapy
- Treatment targeted to specific molecular alterations
What is the aim of advanced cancer surgery?
-For palliative intent to ease the symptoms and pain for the patient
Are all cancers treated in the same way?
-No, whilst surgery is the mainstay of treatment for most cancers, the precise role of each type of treatment varies for each cancer and also depends on the cancer’s stage
What is adjuvant treatment?
-Treatment which is given after surgical removal of a primary tumour to eliminate subclinical disease (ie limits the possibility of relapse by attempting to erradicate any micrometastases)
What is neoadjuvant treatment?
-Treatment given before surgical excision of the tumour to try and reduce the size of the primary tumour
Briefly, how does radiotherapy treat cancer?
-X-rays or other types of ionising radiation used to kill rapidly dividing cells by triggering apoptosis or interfering with mitosis
What is important to ensure when using radiotherapy?
-That the surrounding healthy tissue is shielded as much as possible
Why is radiotherapy given in fractionated doses?
-To minimise damage to normal tissues
How does radiotherapy trigger apoptosis in cells?
-Directly damages DNA or induces free radical DNA damage which is detected by the cell cycle check points in G2 and triggers apoptosis
How does radiotherapy interfere with mitosis?
-Causes double stranded DNA breaks damage chromosomes and prevent completion of M phase
Why are cancer cells effected more that healthy cells in cancer treatments such as radiotherapy and chemotherapy?
-The treatments effect all cells but target highly proliferating cells
What are the 4 major classes of chemotherapy agents?
- Antimetabolites
- Alkylating and platinum-based drugs
- Antibiotics
- Plant-derived drugs
How do antimetabolites act as a chemotherapy agent?
-Mimic normal substrates which the cells use during DNA replication and thus interfere with the replication, preventing completion and resulting in cell death
Give an example of an antimetabolite chemotherapy agent
-Fluorouracil -> mimics thiamine
How do alkylating agents and platinum derived drugs act as chemotherapy agents?
-Crosslink the two strands of the DNA double helix which interferes with replication and induces apoptosis
Give an example of an alkylating chemotherapy agent
-Cyclophosphamide (cisplatin is platinum based)
How does the antibiotic doxorubicin act as a chemotherapy agent?
-Inhibits DNA topoisomerase which is essential for correct DNA synthesis
How does the antibiotic bleomycin act as a chemotherapy agent?
-Causes double stranded DNA breaks
Name a plant-derived drugs which acts as a chemotherapy agent? State its mechanism of action
- Vincristine
- Block microtubule assembly and interferes with mitotic spindle formation
Why does hair loss, vomiting and nausea occur with chemotherapy?
-Chemotherapy agents are not specific for cancer cells, they just target highly proiferating cells and this the epithelium is effected
Name two types of hormone therapy used for treatments of cancers
- Selective oestrogen receptor modulator (SERMS) eg tamoxifen
- Androgen blockade
When is tamoxifen used? State its mechanism of action
- Hormone-receptor positive breast cancer
- Bind to oestrogen receptors, prevents oestrogen from binding which has shown to stop progression of the cancer and sometimes reduce the size of the tumour
When are androgen blockades commonly used?
-Prostate cancer
What is the benefit of treatments which target specific molecular alterations?
-Provides an opportunity to target drugs specifically at cancer cells
What are the two common, well known examples of drugs which target specific genetic alterations?
- Herceptin
- Gleevec
When and why is Herceptin used?
- In the treatment of HER-2 positive breast cancers
- A quarter of breast cancers have gross over-expression of HER-2 gene and herceptin blocks HER2 signalling which has shown to prevent progression/reduce the tumour size
When is gleevec used and why?
- Gleevec is used in the treatment of chronic myeloid leukaemia
- In CML there is a chromosomal rearrangement (t9:22) creating an abnormal ‘Philadelphia’ chromosome in which an oncogenic fusion protein is encoded
- Gleevec inhibits the fusion protein
In which sites are tumour markers present?
-Tissues, blood, urine and faeces
What is a tumour marker?
-Various substances are released by cancer cells into the circulation which are most useful for monitoring tumour burden during treatment
What types of tumour markers are there?
- Hormones
- Oncofetal antigens
- Specific proteins
- Mucins/glycoproteins
What is a useful tumour marker released from testicular tumours?
-Human Chorionic Gonadotrophin hormone (hCG)
Name a oncofetal antigen used as a tumour marker and state the possible types of tumours related to it
- Alpha fetoprotein
- Hepatocellular carcinoma
- Yolk sac tumour
What is a tumour marker released in prostate cancer? What is this tumour marker non-specific?
- Prostate-specific antigen
- High variation in the natuarl levels, also secreted in benign hypertrophic prostate
Name a glycoprotein often used as a tumour marker for ovarian cancer
-Cancer Antigen-125
What is the purpose of screening programs?
-To detect cancer as early as possible when there is the highest chance of cure
What is length bias?
-Fast tumours will grow in between screens so are not detected where as slow growing tumours are often detected -> can lead to screening looking better than it is
Why is overdiagnosis a potential problem with screening?
-Detects things that would have never progressed to kill the patient
Describe Breast screening in the UK
- Women who have BRCA1/BRCA2 or are related to a woman who does
- Woman over 50
- Every 3 years unless risk factors are present
Which 4 cancers have the highest incidence rate in the UK?
- Breast
- Lung
- Prostate
- Bowel
