S10) Incidence, Prognosis & Treatment of Neoplasms Flashcards
Outline the incidence of different malignant neoplasms in the UK
Breast, lung, prostate and bowel carcinomas accounted for over half of all new cancers in the UK (53%)
Outline the incidence of malignant neoplasms in terms of age
- The great majority is diagnosed in people aged over 65 but only a small proportion in people up to age 24
- In children younger than 14, leukaemias, CNS tumours and lymphomas are most common
What is the significance of understanding survival rates and mortality for cancer?
Survival rates and mortality rates indicate how aggressive a cancer is
The survival rates for different malignant neoplasms in the UK is variable.
State the 5 year survival rates for the following:
- Testicular cancer
- Melanoma
- Breast cancer
- Pancreatic cancer
- Lung cancer
- Oesophageal cancer
- Testicular cancer (98%)
- Melanoma (90%)
- Breast cancer (87%)
- Pancreatic (3%)
- Lung (10%)
- Oesophageal cancers (15%)
What is the biggest cause of cancer-related deaths in the UK?
Lung cancer
Which 7 factors should one consider to predict the outcome from malignant neoplasms?
- Age
- General health status
- Tumour site
- Tumour type
- Tumour grade (i.e. differentiation)
- Tumour stage
- Availability of effective treatments
Describe the use of tumour stage
Tumour stage is a measure of the malignant neoplasm’s overall burden
The commonest method for assessing the extent of tumour is the TNM staging system that is standardised across the world.
Outline TNM staging
- T refers to the size of the primary tumour (T1 –T4)
- N refers to the extent of regional node metastasis (N0 to N3)
- M refers to the extent of distant metastatic spread (M0 or M1)
For a given cancer the T, N and M status are then converted into a stage from I to IV.
Outline how cancers are staged from I - IV using TMN staging
- Stage I is early local disease
- Stage II is advanced local disease (i.e. N0, M0)
- Stage III is regional metastasis (i.e. any T, N1/more, M0)
- Stage IV is advanced disease with distant metastasis (i.e. any T, any N and M1)
Lymphoma has its own special system called Ann Arbor staging.
Outline this form of tumour staging
- Stage I indicates lymphoma in a single node region
- Stage II indicates two separate regions on one side of the diaphragm
- Stage III indicates spread to both sides of the diaphragm
- Stage IV indicates diffuse or disseminated involvement of one or more extra-lymphatic organs e.g. bone marrow or lung
Dukes staging has been used to determine survival rates for colorectal carcinoma.
Outline this form of tumour staging
- Dukes’ A: invasion into but not through the bowel
- Dukes’ B: invasion through the bowel wall
- Dukes’ C: involvement of lymph nodes
- Dukes’ D: distant metastases but TNM staging is the preferred system worldwide
Describe the use of tumour grade
- Tumour grade describes the degree of differentiation of a neoplasm
- It is more important for planning treatment and estimating prognosis in certain types of malignancy e.g. soft tissue sarcoma, primary brain tumours, lymphomas, breast and prostate cancer
Outline the tumour grading system used for squamous cell carcinoma and colorectal carcinoma
- G1 is well-differentiated
- G2 is moderately differentiated
- G3 is poorly differentiated
- G4 is undifferentiated or anaplastic
Some cancers use an internationally recognised formal grading system.
Identify and describe the grading system used for breast carcinoma
Bloom-Richardson system – assesses tubule formation, nuclear variation and number of mitoses
How can cancer be treated?
Cancer can be treated by surgery, radiotherapy, chemotherapy, hormone therapy and treatment targeted to specific molecular alterations
Surgery is the mainstay of treatment for most cancers but the precise role for each type of treatment varies for each cancer and also depends on the cancer’s stage.
Describe the surgical treatment of cancer in terms of adjuvant and neoadjvant treatment
- Adjuvant treatment is given after surgical removal of a primary tumour to eliminate subclinical disease
- Neoadjuvant treatment is given to reduce the size of a primary tumour prior to surgical excision
Explain how radiation therapy kills proliferating cells by triggering apoptosis or interfering with mitosis
X-rays, etc kill rapidly dividing cells (especially in G2 phase):
- High dosage causes either direct or free-radical induced DNA damage that is detected by the cell cycle check-points, triggering apoptosis
- Double-stranded DNA breakages cause damaged chromosomes that prevent M phase from completing correctly
How is normal tissue damage minimised in the radiotherapy treatment of cancer?
- Radiotherapy is focused on the tumour with shielding of surrounding healthy tissue
- It is given in fractionated doses to minimise normal tissue damage
Several classes of chemotherapy agents exist.
Identify them
- Antimetabolites
- Alkylating and platinum-based drugs
- Antibiotics
- Plant-derived drugs
Chemotherapy drugs affect proliferating cells in different ways.
Explain the action of antimetabolites
Antimetabolites mimic normal substrates involved in DNA replication e.g. Fluorouracil
Chemotherapy drugs affect proliferating cells in different ways.
Explain the action of alkylating and platinum-based drugs
Alkylating and platinum-based drugs cross-link the two strands of the DNA helix e.g. cyclophosphamide and cisplatin
Chemotherapy drugs affect proliferating cells in different ways.
Explain the action of antibiotics
Antibiotics act in several different ways e.g. doxorubicin inhibits DNA topoisomerase, which is needed for DNA synthesis, while bleomycin causes double-stranded DNA breaks
Chemotherapy drugs affect proliferating cells in different ways.
Explain the action of plant-derived drugs
Plant-derived drugs block microtubule assembly and interferes with mitotic spindle formation e.g. vincristine
Hormone therapy is relatively non-toxic treatment for certain malignant tumours.
Explain the use of selective oestrogen receptor modulators to treat breast cancer
- Selective oestrogen receptor modulators bind to oestrogen receptors, preventing oestrogen from binding e.g. tamoxifen
- They are used to treat hormone receptor-positive breast cancer
Hormone therapy is relatively non-toxic treatment for certain malignant tumours.
Explain the use of hormone therapy to treat prostate cancer
Androgen blockade is used for prostate cancer
Oncogenes can be targeted by cancer therapy.
Explain the use of Hercepetin in breast cancer
- ¼ of breast cancers have gross over-expression of the HER-2 gene
- Herceptin can block Her-2 signalling
Oncogenes can be targeted by cancer therapy.
Explain the use of Imatinib in chronic myeloid leukaemia
- CML shows a chromosomal rearrangement creating an abnormal ‘Philadelphia’ chromosome in which an oncogenic fusion protein (BCR-ABL) is encoded
- Imatinib inhibits the fusion protein
Explain how tumour markers allow for the monitoring of the cancer burden
- Various substances are released by cancer cells into the circulation
- Although some have a role in diagnosis, in general they are most useful for monitoring tumour burden during treatment and follow up
Identify four types of tumour markers and provide examples of each
- Hormones e.g. human chorionic gonadotrophin released by testicular tumours
- Oncofetal antigens e.g. alpha fetoprotein released by hepatocellar carcinoma
- Specific proteins e.g. prostate-specific antigen released by prostate carcinoma
- Mucins/glycoproteins e.g. CA-125 released by ovarian cancer
What does cancer screening involve?
Cancer screening involves looking for early signs of disease in healthy people
What are the aims of cancer screening?
Cancer screening attempts to detect cancers as early as possible when the chance of cure is highest
Identify some issues with cancer screening
- Lead time bias
- Length bias
- Over diagnosis
Identify three established national screening programmes in the UK
- Cervical cancer
- Breast cancer
- Bowel cancer
Cervical carcinoma is quite a common malignancy in women in the UK.
What is known about its aetiology?
- Cervical carcinoma is associated with infection with high-risk HPV
- HPV disrupts the normal cell cycle and extends the life-span of genital epithelial cells
- Vaccination against HPV can prevent carcinoma
Identify 6 predisposing factors to cervical carcinoma
- Early age at first intercourse
- Multiple sexual partners
- Increased parity
- Lower social class
- Oral contraceptives and nicotine
- Genital infection
Describe the sequence of events which occur in cervical epithelium which result in the development of invasive cervical carcinoma
- Sequence: normal cervical epithelium → viral infection → CIN I →CIN II → CIN III → invasion
- Involves a progressive loss of differentiation and increasing atypia in more layers of the epithelium
What is the value of cervical screening?
It picks up CIN (pre-cancerous lesions) and treatment can be given before invasion occurs (therefore curative)
Which women are invited for cervical cancer screening and at what intervals?
- 25-49 years – every three years
- 50-64 years – every five years
- 65+ years – only those not screened since age 50 years or those with recent abnormal tests
Identify the relevant tumours to match these descriptions:
- A rare type of cancer that usually affects the bones of children and adolescents
- Often produces CEA
- Commonest cause of cancer death in the UK
- Ewing’s sarcoma: rare type of cancer that usually affects the bones of children and adolescents
- Colon cancer: often produces CEA
- Lung cancer: commonest cause of cancer death in the UK
Identify the relevant tumours to match these descriptions:
- Has a known association with Aspergillus flavus
- Tumour that can produce 5HT (well differentiated neuroendocrine tumour)
- Associated with EBV
- Hepatocellular carcinoma: has a known association with Aspergillus flavus
- Carcinoid tumour: tumour that can produce 5HT (well differentiated neuroendocrine tumour)
- Burkitt’s lymphoma: associated with EBV
Identify the relevant tumours to match these descriptions:
- A cancer of the skin that rarely metastasises
- Produces vanillyl mandelic acid
- Another name for nephroblastoma
- Basal cell carcinoma: a cancer of the skin that rarely metastasises
- Phaeochromocytoma: produces vanillyl mandelic acid
- Wilm’s tumour: another name for nephroblastoma
Identify the relevant tumours to match these descriptions:
- A tumour often within the skin and frequently associated with HIV infection
- A tumour of the thyroid gland that can produce calcitonin
- Kaposi’s sarcoma: a tumour, often within the skin and frequently associated with HIV infection
- Medullary carcinoma: a tumour of the thyroid gland that can produce calcitonin
Identify the relevant tumours to match these descriptions:
- Associated with asbestos exposure
- A type of lung tumour most often associated with ectopic production of ADH
- Malignant mesothelioma: associated with asbestos exposure
- Small cell carcinoma: type of lung tumour most often associated with ectopic production of ADH
