15 - Neoplasia 4

Question 1

What are the commonest types of cancer in adults and children?

Answer 1

Adults –> breast, lung, prostate and bowel

Children (under 14) –> leukaemias, CNS tumours and lymphomas

Question 2

What is the biggest cause of cancer-related death in the UK?

Answer 2

LUNG

Question 3

How do the survival rates from different malignant neoplasms vary?

Answer 3

5 year survival:

• Testicular and Melanoma (90-98%)
• Breast (87%)
• Lung (10%)
• Pancreatic (3%)
• Oesophageal (15%)

Question 4

When predicting the outcome of having a malignant neoplasm, what do you need to take into consideration?

Answer 4

• Availability of effective treatment

Question 5

What is the commonest way to assess the extent of a solid tumour?

Answer 5

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

Question 6

How is the TNM staging converted into a stage?

Answer 6

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

Question 7

How is lymphoma staged?

Answer 7

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

Question 8

Why is staging important?

Answer 8

Critical to predict outcome/survival and decide method of treatment

Question 9

How do you stage colorectal carcinoma?

Answer 9

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

Question 10

What is the grading system for cancer?

Answer 10

G1: well differentiated

G2: moderately differentiated

G3: poorly differentiated

G4: undifferentiated or anaplastic

Question 11

How is breast carcinoma graded?

Answer 11

Modified Bloom-Richardson system

Assess tubule formation, nuclear variation and numer of mitoses

Question 12

Normally staging is more important than grading for carcinomas, what are the exceptions to this?

Answer 12

Grading is important for prognosis of:

• Soft tissue sarcoma
• Primary brain tumours
• Lymphomas
• Breast cancer
• Prostate cancer

Question 13

What are the different ways of treating cancer?

Answer 13

• Radio
• Chemo
• Hormone therapy
• Targeted molecular therapies
• SURGERY

Question 14

What is adjuvant and neoadjuvant treatment?

Answer 14

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

Question 15

How does radiation therapy work?

Answer 15

- 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

Question 16

What are the different types of chemotherapy drugs?

Answer 16

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

Question 17

What is the least toxic way to treat cancer and how does it work?

Answer 17

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

Question 18

How can you test if a cancer can be targeted with hormone therapy?

Answer 18

Question 19

How can you target oncogene mutations in breast cancer to target drugs to?

Answer 19

• 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

Question 20

How can you target oncogene mutations in chronic myeloid leukaemia to target drugs to?

Answer 20

• BCR-ABL fusion protein oncogene
• Imatinib can inhibit the fusion protein causing CML

Question 21

How can the cancer immunity cycle be targeted to destroy cancer?

Answer 21

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

Question 22

Why are tumour markers important?

Answer 22

• 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

Question 23

What are some examples of tumour markers?

Answer 23

- 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

Question 24

What are oncofetal antigens?

Answer 24

Question 25

What does cancer screening involve and what are the established screening programs in the UK?

Answer 25

- 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

Question 26

What are the problems with cancer screening?

Answer 26

**- 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

Question 27

Describe the screening programs for cervical, breast and colorectal cancer.

Answer 27

**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

Question 28

What factors contribute to tumour dormancy?

Answer 28

- Hostile secondary site - Reduced angiogenesis - Immune attack

Question 29

How does nivolumab work?

Answer 29

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

Question 30

What kind of tumours can occur in the testis?

Answer 30

**- Seminoma:** common in 15 to 30 year olds **- Non-seminoma:** embryonal carcinoma, yolk sac carcinooma, teratoma, choriocarcinoma (women) Look for hCG, AFP

Question 31

A man has a lump removed from his testicle and a histology report is done, what would you name this lump?

Answer 31

Fibrous septae with lymphocytes within the septae. Fried egg seminoma cells

Question 32

What are B symptoms in Hodgkin's lymphoma, and what is their significance?

Answer 32

- Paraneoplastic syndrome - Pruitis is sometimes included, helps to determine staging of the lymphoma.

Question 33

What are the major side effects of tamoxifen?

Answer 33

- DVT - Endometrial proliferation and cancer - Liver changes - Tumor flare

Question 34

What does it mean if a breast tumour tests HER2 positive?

Answer 34

- 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

Question 35

Why should you be concerned if you suspect rectal adenocarcinoma in a patient and they have bloody stool?

Answer 35

- 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

Question 36

What tumour markers can be used for the following cancers: - Breast - Colorectal - Pancreatic - Germ cell - Ovarian - Prostate

Answer 36

Question 37

What is the significance of a raised PSA?

Answer 37

Shows prostate is inflammed

Question 38

How is a prostatic adenocarcinoma graded and why is it usually caught late stage?

Answer 38

- 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

Question 39

How does cervical carcinoma become invasive and what are the risk factors for developing this?

Answer 39

- 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

Question 40

Is castration helpful in treating prostatic carcinoma?

Answer 40

Yes

Question 41

Match up the following descriptions

Answer 41