MoD session 11: incidence, prognosis and treatment of malignant neoplasms Flashcards
The 4 most common types of cancer make up 54% of all cancers in the UK. What are they (in order from most common)?
Breast
Lung
Prostate
Bowel
What are the most common cancers in children younger than 13?
Leukaemia, CNS tumours and lymphomas
Describe the variation in 5 year survival rates
Testicular (98%), melanoma (90% if early stage) and breast (87%) are much better than pancreatic (3%), lung (10%) and oesophageal (15%). Lung is biggest cause of cancer-related deaths in UK
What factors are considered when predicting outcome of cancer?
Age General health status Tumour type Grade (differentiation) Stage Availability of effective treatments
What is tumour stage and how is it usually measured?
A measure of the malignant neoplasm’s overall burden, which gives a strong indication of survival. E.g. melanoma survival is very high at stage I but by stage IV is very low
Usually measured using the TNM staging system:
- T refers to size of tumour, typically T1 to T4 (small to large)
- N: extent of regional node metastasis, e.g. N0 to N3
- M: extent of distant metastatic spread, e.g. M0 or M1
- each cancer has its own specific TMN criteria
T, N and M status then converted into a stage from I to IV. Details vary but in general stage I=early local disease, stage II=advanced local disease (i.e. N0, M0), stage III=regional metastasis (i.e. any T, N1 or more, M0) and stage IV is advanced disease with distant metastasis (i.e. any T, any N and M1)
Describe the staging system for lymphoma
Ann Arbor
Stage I: lymphoma in a single node region
Stage II: two separate regions on one side of the diaphragm
Stage III: spread on both sides of diaphragm
Stage IV: diffuse/disseminated involvement of one or more extra-lymphatic organs such as bone marrow or lungs
Describe Dukes staging for colonic carcinoma with the % 5 year survival
Dukes’ A: invasion into but not through the bowel. 93%
Dukes’ B: invasion through the bowel wall. 77%
Dukes’ C: involvement of lymph nodes. 48%
Dukes’ D: distant metastases. 6%
What is tumour grade?
Describes the degree of differentiation of a neoplasm. Not as standardised as staging, but usually G1 is well-differentiated, G2 is moderately differentiated, G3 is poorly differentiated and G4 is anaplastic. This system is used for squamous cell carcinoma and colorectal carcinoma.
Grading is more important for planning treatment /prognosis in certain types of cancer such as soft tissue sarcoma, primary brain tumours, lymphomas, breast and prostate cancer
Describe the modified Bloom Richardson grading for breast cancer
G1: tubules
G2: mitoses (number of mitotic figures)
G3: nuclear pleomorphism
Each given a score then total score to decide grade
Not really used any more! Used Nottingham prognostic index scoring for the past 20 years but have to know Bloom-Richardson for exam
Big survival drop between G2 and G3.
What is the difference between adjuvant and neoadjuvant treatment of cancer?
Adjuvant: given after surgical removal of a primary tumour to eliminate subclinical disease
Neoadjuvant: given to reduce the size of a primary tumour prior to surgical excision
Surgical excision can be thought of as curative treatment
How is radiation therapy used to treat cancer?
Radiotherapy: focused on the tumour with shielding of surrounding healthy tissue. Given in fractionated doses to minimise normal tissue damage. X-rays/other types of ionising radiation used to kill rapidly dividing cells, especially in G2 of the cell cycle.
Mechanism:
- causes direct or free radical induced DNA damage that is detected by the cell cycle checkpoints, triggering APOPTOSIS
- double stranded DNA breakages cause damaged chromosomes that prevent M phase from completing
Why is radiotherapy given in multiple small doses?
X-ray energy is absorbed by some tissues and some of the energy passes straight through. Multiple doses culminating in the same dose overall gives more differential effects on cancer cells so more get destroyed
How does chemotherapy affect proliferating cells?
AFFECT ALL PROLIFERATING CELLS AS NON-SPECIFIC
ANTIMETABOLITES: mimic normal substrates involved in DNA replication, e.g. fluorouracil which mimics uracil
ALKYLATING and PLATINUM-based drugs e.g. cyclophosphamide and cisplatin: cross-link the two DNA strands in the helix
ANTIBIOTICS: act in several ways. E.g. doxorubicin inhibits DNA topoisomerase needed for DNA synthesis, while bleomycin causes ds DNA breaks
PLANT-DERIVED drugs: e.g. vincristine, which blocks microtubule assembly and interferes with mitotic spindle formation
How might hormones be used to target malignant tumours?
Relatively non-toxic
E.g. selective oestrogen receptor modulators (SERMs) e.g. TAMOXIFEN bind to oestrogen receptors, preventing oestrogen from binding. Used to treat hormone receptor positive breast cancer
E.g. androgen blockage used in prostate cancer
Give 2 examples of oncogenes that are targeted by cancer therapy
Trastuzumab (HERCEPTIN): as 25% of breast cancers have gross over-expression of the HER-2 gene and Herceptin can block Her-2 signalling
Imatinib (GLEEVEC): CML shows a chronic chromosomal rearrangement (t9:22) creating an abnormal Philadelphia chromosome in which an oncogenic fusion protein (BCR-ABL) is encoded. Imatinib inhibits the fusion protein
What are tumour markers? Give some examples
Substances released by cancer cells into the circulation, which are most useful for monitoring tumour burden during treatment and follow up (with some role in diagnosis).
Examples:
- Hormones e.g. human chorionic gonadotrophin released by testicular tumours
- Oncofetal antigens e.g. alpha fetoprotein released by hepatocellular carcinoma
- Specific proteins e.g. prostate-specific antigen released by prostate carcinoma
- Mucins/glycoproteins e.g. CA-125 released by ovarian cancer
- Carcinoemrbyonic antigen (CEA), CA 19-9 and K-RAS mutations for colon cancers
- Oestrogen e.g. endometrial carcinoma
What are the problems associated with cancer screening?
Lead time bias
Length bias
Over diagnosis (especially in prostate cancer in elderly men, will most likely die of something else first as is very slow growing)
Describe the national cancer screening programmes for the UK
Cervical: women aged 25 to 49 receive invitations every 3 years and aged 50 to 64 every 5 years. Sample of cells from cervix assessed microscopically, aiming to identify when in CIN I or II (confined to lower or lower and middle thirds of epithelium respectively)
Breast: all women aged 50-70 who are registered with a GP are invited for a mammogram every 3 years
Bowel: all men and women aged 60-74 who are registered with a GP, every 2 years. 60-74 foecal occult blood test (send foecal sample). New one off test for over 55s where can insert thin instrument to remove polyps at GP if high risk
Which sorts of tumours occur commonly in the testis? Which is most common in teenagers?
Germ cell:
- Seminomas
- Non seminomas: teratoma, embryonal carcinoma, choriocarcinoma, yolk sac tumours
Very rarely in men >60 lymphoma can start here
What markers are commonly raised in non-seminoma testicular cancer?
Alpha feta protein
HCG
Lactate dehydrogenase
What are the characteristic cells in Hodgkin’s lymphoma? They are necessary for diagnosis of HL, but not unique to it
Reed-Sternberg cells: malignant lymphocytes (usually a B cell). Histologically appear very large with a pale cytoplasm and two or more oval lobulated nuclei
What are B symptoms in Hodgkin’s lymphoma and what is their significance?
Systematic systems: fever, weight loss and night sweats
Indicates poorer prognosis
Describe the T1 to T4 stages from the TMN classification for breast cancer
Diameter of primary tumour:
- T1: 2cm or less
- T2: 2-5cm
- T3: bigger than 5cm
- T4: invades the chest wall
Describe the diagnosis of prostate cancer
Hard craggy prostate and PSA in double digits indicates prostate cancer. Biopsy shows fibrous tissue.
Graded using GLEASON system: grades 1-5. Grade 1 most similar to normal prostate tissue; however, only grades 3-5 are cancer. Grade 4 glands start to fuse, grade 5 is sheets.
In real life don’t report grades 1 and 2
Where is the common site of metastasis for prostate cancer?
Bone
Especially the lumbar spine
Risk factors for cervical carcinoma
HPV 16 and HPV 18 Ages 25-34 Multiple sexual partners Smoking Immunosuppression
Describe the sequence events which occur in the cervical epithelium to produce cervical carcinoma
CIN: cervical intraepithelial neoplasia:
- CIN I in lower 1/3 of epithelium
- CIN II in lower and middle 1/3s
- CIN III full thickness
Micro-invasion of basement membrane
Invasive: if deeper than 5mm or wider than 7mm; formal staging required
Abnormalities in which gene may be identified in some breast cancers?
Retinoblastoma gene
Why might castration be indicated in prostate cancer?
Reduces testosterone supply to the tumour and patient
What is the commonest cause of cancer death in the UK?
Lung
What is Ewing’s sarcoma?
A rare bone cancer of children and adolescents
What is a Wilm’s tumour?
Aka nephroblastoma
Kidney cancer affecting children
What type of tumour produces vanillyl mandelic acid?
Pheochromocytoma (adrenal tumour of chromaffin cells)
What type of tumour is associated with Aspergillus flavus?
Hepatocellular carcinoma
What type of tumour commonly produces ectopic ADH production?
Small cell carcinoma of lungs
What is choriocarcinoma?
Tumour of uterus where placental cells would usually be
Often produces HCG
What type of thyroid tumour can produce calcitonin?
Medullary carcinoma
