Neoplasms 4 Flashcards
What accounts for over half of all new cancers in the UK?
Breast, lung, bowel and prostate carcinomas
What % of malignant neoplasms are diagnosed in those over the age of 65?
More than 60%
What % of malignant neoplasms are diagnosed in those under the age of 24?
1%
What type of malignant neoplasms are most common in children younger than 14?
Leukaemias, central nervous system tumours and lymphomas
What is the survival rate for different cancer types?
Very variable
What cancers have the best outcomes in women, and what are there 5 year survival rates?
Melenoma (90%)
Hodgkin’s lymphoma (83%)
Breast cancer (79%)
What cancers have the worst outcomes in women, and what are there 5 year survival rates?
Pancreatic (2%)
Lung (6%)
Oesophageal (8%)
What cancers have the best outcomes in men, and what are there 5 year survival rates?
Testicular (95%)
Hodgkin’s lymphoma (84%)
Melanoma (78%)
Overall, what cancers account for the greatest proportion of cancer deaths, and what % of deaths do they account for?
Lung (22%), colorectal (10%), breast (7%) and prostate cancer (7%)
What factors should be considered when determining which individuals will have a favourable outcome for malignant neoplasms?
Age General health status Tumour site Tumour type Grade (i.e. differentiation) Tumour stage Availability of effective treatments
What is the most common method for assessing the extent of a tumour?
The TNM staging system
Why is the TNM method the most common?
It is standardised across the world
What does the T in TNM refer to?
The size of the primary tumour
How is T in TNM typically expressed?
T1 through to T4
What does the N in TNM describe?
The extend of regional node metastasis
How is N in TNM expressed?
N0 to N3
What does the M in TNM denote?
The extent of distant metastatic spread
How is M in TNM expressed?
M0 or M1
What happens to the TNM for a given cancer?
It is converted into a stage, from I to IV
What to the stages of cancer mean?
The details vary for each cancer, but broadly speaking-
Stage I is early local disease
Stage II is advanced local disease
Stage III is regional metastasis
Stage IV is advanced disease with distant metastasis
What would the TNM be for stage I and II cancers?
N0, M0
What would the TNM be for stage III cancers?
Any T, N1 or more, and M0
What would the TNM be for stage IV cancers?
Any T, any N, M1
What cancer has its own special staging system?
Lymphoma
What is the lymphoma staging system called?
Ann Arbor staging
Describe the Ann Arbor staging system
Stage I indicates a 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, such as bone marrow or lungs
Why is cancer staging useful?
It is a powerful predictor of survival
What staging system has been used for colorectal carcinoma?
Dukes staging
Describe Dukes 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
What does tumour grade describe?
The degree of differentiation of a neoplasm
How does tumour grading differ from tumour staging?
It is not as standardised
Describe the tumour grading system
Typically- G1 well-differentiated G2 moderately differentiated G3 poorly differentiated G4 undifferentiated or anaplastic
What is the tumour grading system used for?
Squamous cell carcinoma and colorectal carcinoma
What is used to grade some cancers?
An internationally recognised formal grading system
What is used to grade breast carcinomas?
The Bloom-Richardson system
What does the Bloom-Richardson system assess?
Tubule formation
Nuclear variation
Number of mitoses
Where is tumour grading used?
In planning treatment and estimating prognosis
What malignancies is tumour grading more important in?
Soft tissue sarcomas Primary brain tumours Lymphomas Breast cancer Prostate cancer
How can cancer be treated?
Surgery Radiotherapy Chemotherapy Hormone therapy Treatment targeted to specific molecular alterations
How does cancer treatment vary between different cancers?
Surgery is the mainstay of treatment for most cancers, but the precise role of each treatment varies for each cancer, and also depends on the cancers stage
What is adjuvant treatment?
Treatment given after surgical removal of a primary tumour to eliminate subclinical disease
What is neoadjuvant treatment?
Treatment given to reduce the size of a primary tumour primary to surgical excision
What does radiation therapy do?
Kills proliferating cells by triggering apoptosis or interfering with mitosis
How is normal tissue protected in radiotherapy?
Radiotherapy focused on the tumour, with shielding of the surrounding healthy tissue
Given in fractionated doses to minimise damage to normal tissues
What is given in radiotherapy?
X-rays or other type of ionising radiation
How does radiotherapy work?
It kills rapidly dividing cells, especially in G2 of the cell cycle. This is because high dosage causes either direct of 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
What classes of chemotherapy agents exist?
Antimetabolites
Alkylating and platinum-based drugs
Antibiotics
Plant-derived drugs
What do antimetabolites do?
Mimic normal substrates involved in DNA replication
Give an example of an antimetabolite
Fluorouracil
What do alkylating and platinum-based drugs do?
Cross-link the two strands of the DNA helix
Give two examples of alkylating and platinum-based drugs
Cyclophosphamide and cisplatin
Give 2 examples of antibiotics that can act as chemotherapy agents
Doxorubicin
Bleomycin
What does doxorubicin do?
Inhibits DNA topoisomerase, which is needed for DNA synthesis
What does bleomycin do?
Causes double-stranded DNA breaks
Give an example of a plant-derived drug
Vincristine
What does vincristine do?
Blocks microtubule assembly and interferes with mitotic spindle formation
What is the advantage of hormone therapy?
It is a relatively non-toxic treatment for certain malignant tumours
What do selective oestrogen receptor modulators (SERMs) do?
Bind to oestrogen receptors, preventing oestrogen from binding
Give an example of a SERM?
Tamoxifen
What are SERMs used to treat?
Hormone receptor-positive breast cancer
What is used to treat prostate cancer?
Androgen blockade
Give an example of a cancer-specific alteration?
Oncogene mutations
What can identifying cancer-specific alterations provide?
An opportunity to target drugs specifically at cancer cells
Give two early examples of drugs targeted specifically at cancer cells
Trastuzumab (Herceptin)
Imatinib (Gleevec)
What is herceptin used to treat?
Some breast cancers
How does herceptin treat breast cancer?
Up to a quarter of breast cancers have gross over-expression of the HER-2 genes, and herceptin can block Her-2 signalling
What does imatinib treat?
Chromic myeloid leukaemia
How does imatinib treat chronic myeloid leukaemia?
Chronic myeloid leukaemia (CML) shows a chromosomal rearrangement (t9:22), creating at abnormal ‘Philadelphia’ chromosome in which an ontogenic fusion protein (BCR-ABL) is encoded. Imatinib inhibits the fusion protein
What do cancer cells release?
Various substances into the circulation
What are the substances released by cancer cells used for/
Some have a role in diagnosis
Most useful for monitoring tumour burden during treatment and follow up
What kind of molecules are tumour markers?
Hormones
‘Oncofetal’ antigens
Specific proteins
Mucins/glycoproteins
Give an example of a hormone tumour marker
Human chorionic gonadotropin released by testicular tumours
Give an example of an ‘oncofetal’ antigen tumour marker
Alpha fetoprotein released from heptocellular carcinoma
Give an example of a specific protein tumour marker
Prostate-specific antigen released by prostate carcinoma
Give an example of a mucin/glycoprotein tumour marker
CA-125 released by ovarian cancer
What does cancer screening attempt to do?
Detect cancers as early as possible when a cure is still possible
What problems can screenings have?
Lead time bias
Length bias
Over diagnosis
