15 - Neoplasia 4 Flashcards
What are the commonest types of cancer in adults and children?
Adults –> breast, lung, prostate and bowel
Children (under 14) –> leukaemias, CNS tumours and lymphomas
What is the biggest cause of cancer-related death in the UK?
LUNG
How do the survival rates from different malignant neoplasms vary?
5 year survival:
- Testicular and Melanoma (90-98%)
- Breast (87%)
- Lung (10%)
- Pancreatic (3%)
- Oesophageal (15%)
When predicting the outcome of having a malignant neoplasm, what do you need to take into consideration?
- Availability of effective treatment
What is the commonest way to assess the extent of a solid tumour?
TNM staging system
T: size of primary tumour T1 to T4
N: extent of regional node metastases via lymphatics N0 to N3
M: extent of distant metastatic spread via blood M0 to M1
How is the TNM staging converted into a stage?
T, N, M score converted into stage I to IV
Stage I: early local disease
Stage II: advanced local disease
Stage III: regional metastasis
Stage IV: advanced disease with distant metastasis
EACH CANCER HAS ITS OWN STAGING SYSTEM
How is lymphoma staged?
Ann Arbor Staging
Stage I: lymphoma in single node region
Stage II: two separate regions on one side of the diaphragm
Stage III: spread to both sides of the diaphragm
Stage IV: disseminated involvement of one or more extra-lymphatic organs e.g bone marrow or lung
Why is staging important?
Critical to predict outcome/survival and decide method of treatment
How do you stage colorectal carcinoma?
Dukes staging (but TNM preferred)
A: invasion into but not through the bowel
B: invasion through the bowel wall
C: involvement of lymph nodes
D: distant metastases
What is the grading system for cancer?
G1: well differentiated
G2: moderately differentiated
G3: poorly differentiated
G4: undifferentiated or anaplastic
How is breast carcinoma graded?
Modified Bloom-Richardson system
Assess tubule formation, nuclear variation and numer of mitoses
Normally staging is more important than grading for carcinomas, what are the exceptions to this?
Grading is important for prognosis of:
- Soft tissue sarcoma
- Primary brain tumours
- Lymphomas
- Breast cancer
- Prostate cancer
What are the different ways of treating cancer?
- Radio
- Chemo
- Hormone therapy
- Targeted molecular therapies
- SURGERY
What is adjuvant and neoadjuvant treatment?
Adjuvant: treatment given after surgical removement to eliminate subclinical disease and rellapse
Neoadjuvant: treatment given to reduce size of primary tumour and make it operable prior to surgical excision
How does radiation therapy work?
- High dose radiation targeted at a tumour whilst shielding the surrounding healthy tissue
- Given in fractionated doses to minimise tissue damage
- X rays or ionising radiation kill dividing cells, normally in G2, due to DNA damage and apoptosis
- Double stranded DNA breakages prevent M phase completing so apoptosis
What are the different types of chemotherapy drugs?
All target the proliferating cells and there are non-specific
- Antimetabolites: mimic DNA substrates in replication so cancer cannot replicate e.g fluorouracil
- Alkylating and Platinum-based agents: cross link DNA helix so cannot replicate, e.g cisplasin (testicular) and cyclophosphamide
- Antibiotics: work in lots of ways, doxorubicin inhibits DNA topoisomerase needed for DNA synthesis, bleomycin causes double stranded DNA break
- Plant Derived drugs: e.g vincristine which blocks microtubule assembly and interferes with mitotic spindle formation
What is the least toxic way to treat cancer and how does it work?
Hormone therapy
- Lots of cancers have upregulation of receptors and these can be targeted
- SERMs: e.g tamoxifen binds to oestrogen receptor preventing oestrogen binding. On hormone receptor positive breast cancer
- Androgen blockade: prostate cancer
How can you test if a cancer can be targeted with hormone therapy?
How can you target oncogene mutations in breast cancer to target drugs to?
- Trastuzumab (Herceptin) and Imatinib (Gleevec)
- Block HER2 receptors as they are overexpresed in breast cancer. HER2 gene is the oncogene
- Easier to block the oncogene than replace TSG protein
How can you target oncogene mutations in chronic myeloid leukaemia to target drugs to?
- BCR-ABL fusion protein oncogene
- Imatinib can inhibit the fusion protein causing CML
How can the cancer immunity cycle be targeted to destroy cancer?
Block immune checkpoints
- Ipilmumab: tumour cells normally bind to Tcells and stop them being activated but ipilmumab block this
- Nivolumab: binds to PD-1 so it cannot inactivate T cells. unmasks the cancer cell
Why are tumour markers important?
- Possibly help in diagnosis
- Useful for measuring tumour burden to see if treatment is effective and to follow up to see if there is a relapse
What are some examples of tumour markers?
- Hormones: e.g human chorioic gondotrophin (HCG) from testicular tumour
- Oncofetal antigens: e.g alpha fetoprotein (AFP) released by hepatocellar carcinoma and carcinoembryonic antigen from GI cancer (CEA)
- Specific proteins: prostate-specific antigen (PSA) released by prostate carcinoma
- Mucins/Glycoproteins: CA-125 released by ovarian cancer
What are oncofetal antigens?
What does cancer screening involve and what are the established screening programs in the UK?
- Looking for early signs of disease in healthy people
- Detecting cancer as early as possible when the chance of cure is highest
- Cervical, breast and bowel cancer screening well established
What are the problems with cancer screening?
- Lead time bias: artefactual improvement
- Length bias: screening only really detects slow growing cancers
- Overdiagnosis: detects tumours that would never grow fast enough to kill
Describe the screening programs for cervical, breast and colorectal cancer.
Breast: Women aged 50 to 71 and registered with a GP every 3 years, high risk or family history may have earlier. Done by X-ray mammogram
Cervical: smear test over age 25 to 49 every 3 years, 50 to 64 every 5 years and over 65 only if one of your last three tests was abnormal
Colerectal: Bowel scope men and women age 55 one off and if polyps found maybe colorectomy. Age 60-74 bowel screening test at home every two years
What factors contribute to tumour dormancy?
- Hostile secondary site
- Reduced angiogenesis
- Immune attack
How does nivolumab work?
Binds to receptors on the T-cells that would normally induce apoptosis so T-cells dont die, and can become hyperactive to destroy more cancer cells
What kind of tumours can occur in the testis?
- Seminoma: common in 15 to 30 year olds
- Non-seminoma: embryonal carcinoma, yolk sac carcinooma, teratoma, choriocarcinoma (women)
Look for hCG, AFP
A man has a lump removed from his testicle and a histology report is done, what would you name this lump?
Fibrous septae with lymphocytes within the septae. Fried egg seminoma cells
What are B symptoms in Hodgkin’s lymphoma, and what is their significance?
- Paraneoplastic syndrome
- Pruitis is sometimes included, helps to determine staging of the lymphoma.
What are the major side effects of tamoxifen?
- DVT
- Endometrial proliferation and cancer
- Liver changes
- Tumor flare
What does it mean if a breast tumour tests HER2 positive?
- HER2 is a receptor that stimulates growth of the cell
- If positive means there is an upregulation of this receptor
- Can use herceptin that blocks receptor
Why should you be concerned if you suspect rectal adenocarcinoma in a patient and they have bloody stool?
- Means it has ulcerated and therefore more likely to be malignant
- Ulceration occurs due to necrosis as the surface of the tumour as tumour is growing so fast it is outgrowing it’s blood supply before angiogenesis can occur
What tumour markers can be used for the following cancers:
- Breast
- Colorectal
- Pancreatic
- Germ cell
- Ovarian
- Prostate
What is the significance of a raised PSA?
Shows prostate is inflammed
How is a prostatic adenocarcinoma graded and why is it usually caught late stage?
- Benign prostate cancers grow on inner prostate so impinge on urethra quickly
- Malignant usually grow on outskirts so has to grow large before causes symptoms. Also, back pain can be first symptom and this is a sign of metastasis to the spine
How does cervical carcinoma become invasive and what are the risk factors for developing this?
- CIN1
- CIN2
- CIN3 (in situ but will invade at next stage)
Any factors predisposing to HPV infection, e.g multiple sexual partners and sexual activity from young age
Match up the following descriptions
