Oncology

Question 1

Cancer in the UK

Answer 1

The most common causes of cancer in the UK are as follows*

1. Breast
2. Lung
3. Colorectal
4. Prostate
5. Bladder
6. Non-Hodgkin’s lymphoma
7. Melanoma
8. Stomach
9. Oesophagus
10. Pancreas

The most common causes of death from cancer in the UK are as follows:

1. Lung
2. Colorectal
3. Breast
4. Prostate
5. Pancreas
6. Oesophagus
7. Stomach
8. Bladder
9. Non-Hodgkin’s lymphoma
10. Ovarian

*excludes non-melanoam skin cancer

Between 5 and 10% of all breast cancers are thought to be hereditary. Mutation in the BRCA1 and BRCA2 genes also increase the risk of ovarian cancer. For colorectal cancer around 5% of cases are caused by hereditary non-polyposis colorectal carcinoma (HNPCC) and 1% are due to familial adenomatous polyposis. Women who have HNPCC also have a markedly increased risk for developing endometrial cancer - around 5% of endometrial cancers occur in women with this risk factor.

Question 2

Cytotoxic agents

Answer 2

Cytotoxic

Cyclophosphamide

Alkylating agent - causes cross-linking in DNA

Haemorrhagic cystitis, myelosuppression, transitional cell carcinoma

Cytotoxic antibiotics

Bleomycin

Degrades preformed DNA

Lung fibrosis

Doxorubicin

Stabilizes DNA-topoisomerase II complex inhibits DNA & RNA synthesis

Cardiomyopathy

Antimetabolites

Methotrexate

Inhibits dihydrofolate reductase and thymidylate synthesis

Myelosuppression, mucositis, liver fibrosis, lung fibrosis

Fluorouracil (5-FU)

Pyrimidine analogue inducing cell cycle arrest and apoptosis by blocking thymidylate synthase (works during S phase)

Myelosuppression, mucositis, dermatitis

6-mercaptopurine

Purine analogue that is activated by HGPRTase, decreasing purine synthesis

Myelosuppression

Cytarabine

Pyrimidine antagonist. Interferes with DNA synthesis specifically at the S-phase of the cell cycle and inhibits DNA polymerase

Myelosuppression, ataxia

Acts on microtubules

Vincristine, vinblastine

Inhibits formation of microtubules

Vincristine: Peripheral neuropathy (reversible) , paralytic ileus
Vinblastine: myelosuppression

Docetaxel

Prevents microtubule depolymerisation & disassembly, decreasing free tubulin

Neutropaenia

Topoisomerase Inhibitors

Irinotecan

Inhibits topoisomerase I which prevents relaxation of supercoiled DNA

Myelosuppression

Others

Cisplatin

Causes cross-linking in DNA

Ototoxicity, peripheral neuropathy, hypomagnesaemia

Hydroxyurea (hydroxycarbamide)

Inhibits ribonucleotide reductase, decreasing DNA synthesis

Myelosuppression

Question 3

Neoplastic spinal cord compression

Answer 3

Spinal cord compression is an oncological emergency and affects up to 5% of cancer patients. Extradural compression accounts for the majority of cases, usually due to vertebral body metastases. It is more common in patients with lung, breast and prostate cancer

Features

back pain - the earliest and most common symptom - may be worse on lying down and coughing

lower limb weakness

sensory changes: sensory loss and numbness

neurological signs depend on the level of the lesion. Lesions above L1 usually result in upper motor neuron signs in the legs and a sensory level. Lesions below L1 usually cause lower motor neuron signs in the legs and perianal numbness. Tendon reflexes tend to be increased below the level of the lesion and absent at the level of the lesion

Management

high-dose oral dexamethasone

urgent oncological assessment for consideration of radiotherapy or surgery

Question 4

Tumour markers

Answer 4

Tumour markers may be divided into:

monoclonal antibodies against carbohydrate or glycoprotein tumour antigens

tumour antigens

enzymes (alkaline phosphatase, neurone specific enolase)

hormones (e.g. calcitonin, ADH)

It should be noted that tumour markers usually have a low specificity

Monoclonal antibodies

Tumour marker

Association

CA 125 - Ovarian cancer

CA 19-9 - Pancreatic cancer

CA 15-3 - Breast cancer

Tumour antigens

Tumour marker

Association

Prostate specific antigen (PSA) - Prostatic carcinoma

Alpha-feto protein (AFP) - Hepatocellular carcinoma, teratoma

Carcinoembryonic antigen (CEA) - Colorectal cancer

S-100 - Melanoma, schwannomas

Bombesin - Small cell lung carcinoma, gastric cancer, neuroblastoma

CA 15-3 is a tumour marker in breast cancers