MoD Session 11 Flashcards
Which 6 cancers have the best survival rates?
Testicular Malignant melanoma Breast Hodgkin lymphoma Prostate Uterine
Which 5 cancers have the worst survival rate?
Stomach Brain Oesophagus Lung Pancreas
Why does pancreatic cancer have a disproportionate number of deaths considering it is a rare cancer?
Presents late so there is deceased survival
What factors affect the mean 5-year survival rates of cancers?
Age of patient General health status Tumour site and type Intrinsic aggressiveness Treatment available Stage Amount of differentiation
Which three cancers are specific to children
Leukaemias
CNS
Lymphomas
What does tumour staging indicate?
How much tumour is present in the body
What is T1-4 in the TNM classification of tumour staging?
Size of primary tumour
What is N0-3 in the TNM classification of tumour staging?
Extent of regional node metastasis
What is M0/1 in the TNM classification of tumour staging?
Is distant metastasis present?
What is done before classifying a tumour as stage I-IV?
TNM tumour staging
What sort of treatments are used generally to treat stage IV tumours?
Chemotherapy/radiotherapy
Palliative care
What TNM stages indicate a stage I tumour in a theoretical cancer?
T = 1/2 N = 0 M = 0
What TNM stages indicate a stage II tumour in a theoretical cancer?
T = 3/4 N = 0 M = 0
What TNM stages indicate a stage III tumour in a theoretical cancer?
T = any N = 1 or more M = 0
What TNM stages indicate a stage IV tumour in a theoretical cancer?
T = any N = any M = 1
What type of cancer is Ann Arbor staging used for?
Lymphoma
Describe the four stages of Ann Arbor tumour staging.
I = single node region II = two or more nodes on the same side of the diaphragm III = two or more nodes in either side of diaphragm IV = involvement of one or more extra-lymphatic organs
Which type of staging is used clinically in the UK instead of the worldwide preferred TNM staging for colorectal carcinoma?
Duke’s
What type of cancer is Duke’s staging used for?
Colorectal carcinoma
Describe stages A-D in Duke’s staging.
A = invasion into muscularis propria B = invasion through muscularis propria C = involvement of lymph nodes D = distant metastases
Which stage of Duke’s do most colorectal carcinomas present as?
B-D
How does the 5 year survival rate of colorectal carcinoma compare at Duke’s stage A to stage D?
A = 93% D = 6%
What does tumour grade measure?
Degree of differentiation
Why is tumour grading a more subjective way of classifying tumours than staging?
Grading criteria less defined
Describe the four tumour grades used in squamous cell/colorectal carcinoma.
G1 = well differentiated G2 = moderately differentiated G3 = poorly differentiated G4 = undifferentiated/anaplastic
What grading system is used internationally for breast carcinoma?
Bloom Richardson
What does the Bloom Richardson grading system score?
Presence of tubules
Mitoses
Nuclear pleomorphism
What is the percentage survival difference between G1 and G3 on the Bloom Richardson scale?
~40
Which types of cancer is tumour grading important for both planning treatment and estimating prognosis?
Soft tissue sarcoma Primary brain tumours Lymphomas Breast cancer Prostate cancer
What two things are usually more important for planning treatment and estimating prognosis in cancers where tumour grading is less important?
Age of patient
Stage of cancer
What is mainstay treatment for cancer?
Surgery
How does the intent of surgery performed for stage I tumours differ to that for stage III tumours?
Stage I is curative but III is palliative e.g. removal of an ulcer
What is adjuvant treatment of cancer?
Given after surgical removal of primary tumour to reduce the chance of recurrence (assumed metastasis is present)
What is neoadjuvant treatment of cancer?
Given before surgery to reduce primary tumour size so surgical excision is possible
How does radiation therapy treat cancer?
Triggers apoptosis
Interferes w/mitosis
What type of cells does radiation therapy target?
Rapidly proliferating
Why is a fractionated dose of radiation therapy used to treat cancer?
Allows damaged healthy cells to recover between doses
What type of radiation is used in radiation therapy?
X-Rays
Ionising
What DNA damage can be caused by radiation therapy?
Direct
Free-radical induced
Which stage of there’ll cycle is particularly affected in radiation therapy?
G2
What implications does a double strand DNA break have on cell proliferation?
Damaged chromosomes cannot complete M phase correctly
Why does chemotherapy cause hair loss, bone marrow suppression and nausea?
Non-specific targeting of rapidly proliferating areas
How do anti metabolites work in chemotherapy treatment?
Mimic normal DNA replication substrates
How do alkylating/plantinum-based agents work in chemotherapy?
Cross link DNA double helix
How does Doxorubicin carry out its chemotherapy action?
Inhibits DNA to poisoners thus inhibiting DNA synthesis
Other than inhibiting DNA synthesis, how else can antibiotics be used for chemotherapy?
Cause double strand breaks
How do plant-derived drugs such as vincristine act as chemotherapy agents?
Block microtubule and mitotic spindle formation
What are SERMs?
Selective oestrogen receptor modulators e.g. Tamoxifen
When is tamoxifen used in breast carcinoma?
If the tumour has oestrogen receptors
What hormone therapy is used to treat prostate cancer?
Androgen blockade
Which oncogenes are identified in melanoma?
BRAF
When is herceptin used to treat breast cancers?
To inhibit HER-2 signalling in tumours which have HER-2 receptor over expression
How does gleevec treat chronic myeloid leukaemia?
Inhibits the fusion protein BCR-ABL coded for by the Philadelphia chromosome formed by (t9:22)
Why are tumour markers more useful for monitoring tumour burden and follow up after treatment than diagnosis?
Most do not have a clear boundary between healthy and cancerous levels
Which hormone can be used as a biomarker for testicular tumours?
hCG
Which oncofetal antigen can be used as a biomarker for hepatocellular and testicular tumours?
Alpha-fetoprotein
Which specific protein can be used as a biomarker for prostate carcinoma?
Prostate specific antigen
What is CA-125 used as a biomarker for?
Ovarian cancer
Which class of biomarkers does CA-125 belong to?
Mucins/glycoproteins
What is lead time bias?
Screening leads to earlier detection and treatment but the point of death is not changed from if the cancer was detected later and treated
What is length time bias?
More likely to detect slow-growing tumours and miss fast growing, potentially lethal tumours
How can length-time bias be used to dispute the effectiveness of prostate cancer screening?
Can be argued it doesn’t detect the tumours it is screening for
Why is over-diagnosis a problem with cancer screening?
Identify and treat tumours which would never have progressed and led to pathology/death
Who is screened for breast cancer?
47-73 y.o. females
How often is an individual screened for breast cancer assuming there are no other indications?
Every 3 years
Under what circumstances are women more frequently screened for breast cancer?
First degree relative w/ +ve Hx
Presence of BRCA1/BRCA2/Tp53
How is a breast cancer screen conducted?
X-Ray from above and X-ray into axilla
Who is screened for cervical cancer?
25-64 y.o. females
How frequently are women screened for cervical cancer?
25-49 y.o. every 3 years
50-64 y.o. every 5 years
How is cervical cancer screening carried out?
Pap smear test using liquid based cytology for analysis
Who is screened for colorectal cancer?
60-74 y.o. females and males
How often are people screened for colorectal cancer?
Every 2 years
How is colorectal cancer screening conducted?
FOB test - test still sample for presence of blood which is not normally seen
When is measurement of biomarkers in the blood more useful than biomarkers from tissue biopsy?
Inaccessible primary tumour e.g. brain
Metastases that do not resemble primary tumour
Which four cancer make up ~54% of all new diagnoses?
Breast
Lung
Prostate
Bowel
Why does the risk of cancer increase with age?
Co-morbidities
Lag time
More time for genetic mutation
What are the three groups of anti tumour defences?
Genes that correct genetic errors or eliminate cells that have them
Immune system
Non-specific responses, primarily inflammation
What is the normal action of p53 on G1?
Prolong it to allow extra time for correcting defects in DNA
What is the normal activity of p53 on genes in differentiation?
Stimulates transcription so the cell is set on a path opposite to carcinogenesis
Why does p53 have so many effects?
Binds to multiple sites in the DNA chain so controls a variety of genes
In normal conditions, how much p53 can be detected in the cell?
Very little
What is p53 turned on by which is prevalent in malignant tumours?
Hypoxia
How antigenic are tumours in general?
Poorly
Which types of tumours are the most antigenic?
Those induced by viruses
How can tumours evade the immune system?
Produce cells that are less antigenic
What is a malignant effusion?
Essentially inflammatory exudates that contain tumour cells and many leucocytes formed when a malignant tumour spreads over a serosal surface
What are the 5 reasons why leucocytes can congregate in a tumour?
Chemotaxins secreted by tumour cells
Chemotaxins secreted by inflammatory cells
Chemotaxins released by necrotic tumour cells
Bacterial chemotaxins in ulcerated and infected tumours
Adhesion molecules expressed by the endothelium of the tumour’s vessels
Does the presence of inflammation in a tumour indicate better prognosis?
No but they appear to be performing some defensive functions
What are intravesical injections of BCG (attenuated strain of mycobacterium tuberculosis) used in the treatment of?
Superficial bladder cancer
Describe the timeline of haemangioma in infants.
Grows very fast appearing within 2-4 weeks after birth
Begins to regress
Gone by age of 10 usually leaving a scar
What is the mechanism of regression of a haemangioma in infants?
Not understood - not thrombosis or infarction, endothelial channels fade away
Can the primary tumour in melanoma regress?
Yes, partially or even completely
What explains the occasional finding of metastatic melanoma in the absence of primary melanoma?
Regression - primary tumour went unnoticed and the disappeared
How does regression of melanoma probably occur?
Immunologic mechanism
Why can the epidemiology of cancer be described as a ‘spotty’ problem?
Genes, parasites, chemicals, lifestyle and age affect incidence
What factors does cancer of the colon tend to parallel?
Degree of economic development
Consumption of red meat and animal fat
Which group of the population has more cancer?
Males
Males have a larger proportion of which kind of cancers?
Self-inflicted e.g. Skin, mouth, lungs
Which two types of cancer are increasing in prevalence?
Cancer of the lung
Melanoma of the skin
Which types of cancer are decreasing in prevalence?
Stomach (better food processing and refrigeration so less nitrates)
Uterus
How has the mortality rate of breast cancer changed?
Steadily increased
Name a carcinogen found in tobacco smoke.
Benzopyrene
What dietary actions can be correlated with the development of cancer?
Salted fish and nasopharyngeal carcinoma Broiling Smoking Frying in fats that have been used over and over again Nitrites Over nutrition
What types of cancer does obesity in women predispose them to?
Endometrium
Gall bladder
Why is the level of oestrogens in the blood directly proportional to the degree of adiposity after the menopause?
Fat cells synthesise it from adrenal hormones
What can cause large exposure to hormonal stimulation which can increase the risk of breast cancer?
Early menarche
Delayed first pregnancy
Induced abortion
Late menopause
Why is cervical cancer a venerable disease?
It correlated with early sex and multiple partners
What does an undescended testicle have a greater risk of?
Developing cancer
Which HPV types are a risk factor for cervical cancer?
16 and 18
Which type of cancer has a correlation with genital warts?
Anal
What is the Bence-Jones protein?
Found in the urine and indicates the presence of multiple myeloma
What is prostate-specific antigen?
Glycoprotein specific for prostatic epithelium whose level in the blood doubles if the prostate is massaged - marker for prostatic cancer and its response to therapy
Is PSA seen in the normal adult?
Yes, increased by hypertrophy of prostate which can be benign or malignant
What is CEA?
Carcinoembryonic antigen, an oncofoetal protein not significantly expressed in the adult but becomes depressed in some tumours
Where is the gene for CEA mainly active?
Normal foetus
What type of protein is CEA?
Glycoprotein
Which types of cancer is CEA seen in?
Colon
Pancreatic
Lung
Rectal
When is alpha-fetoprotein seen in cancer?
Liver carcinoma
Germ cell tumours (except seminomas)
Pancreatic
Stomach
What naturally synthesises AFP?
Liver
Yolk sac
GI epithelium
Which histiological features does grading evaluate the aggressiveness of a tumour from?
Cellular atypia Architectural atypia Number of mitoses Degree of differentiation Degree of invasiveness
Which system is used to grade the adenocarcinoma of the prostate gland?
Gleason
In grading, what is poor prognosis generally correlated with?
Aneuploidy
Which type of cancer therapy is appropriate for systemic disease?
Chemotherapy
What hampers chemotherapy?
Safety margin b/w toxicity for tumour and patient is narrow
Metastatic cells hide behind endothelial barriers that are impassable to drugs e.g. Blood-brain barrier
Tumour cells, particularly in metastases can become insensitive to drugs
How can tumour cells survive cytotoxic drugs?
Adapt their metabolism to inactivate a drug or reduce its action
What methods of metabolism alteration can tumour cells carry out to become drug resistant?
Modify, reduce or overproduce target proteins
Alter transport mechanisms
Improve DNA repair
Why does infection remain a major complication of advanced cancer?
Bodily defences are depressed by many factors, including chemotherapy
