The Incidence, Prognosis and Treatment of Malignant Neoplasms

Question 1

There were 8.2 million cancer deaths in 2012, making it the world’s most lethal disease, what are the 4 most common types?

Answer 1

Breast, lung, prostate and bowel carcinomas accounted for 53% of new cancers in the U.K.

Question 2

The great majority of cancers are diagnosed in patient over 65 years old, which types are most common in children younger than 14?

Answer 2

Leukaemia, CNS cancers and lymphomas are the most common.

Question 3

Survival rates for different types of cancer are very variable. Name 3 that have good 5-year survival rates and 3 that have poor.

Answer 3

5 year survival rates for testicular (98%), melanoma (90%) and breast cancer (87%) are substantially better than pancreatic (3%), lung (10%) and oesophageal cancers (15%).

Question 4

The amount of deaths depends on incidence and survival rates, what is the biggest cause of cancer related deaths in the U.K.?

Answer 4

Lung cancer.

Question 5

Determining outcomes for malignant neoplasms is far from exact, which factors should be considered when estimating?

Answer 5

Age, general health status, tumour site, type, grade and stage, as well as the availability of effective treatments.

Question 6

What is tumour stage?

Answer 6

Tumour stage is a measure of a malignant neoplasm’s overall burden.

Question 7

The commonest assessment method of cancer stage is TNM - it is standardised across the world, what does it include?

Answer 7

T -size of the primary tumour (diameter/depth etc), typically T1-T4.
N - extent of regional metastasis (e.g. N0-N3).
M - extent of distant metastatic spread (perhaps M0-M1).
Each cancer has its own specific TNM and stage criteria.

Question 8

For a given cancer, TNM is converted into a stage I-IV and with different types it will be variable, but what could they describe?

Answer 8

Stage I is early local disease, stage II is advanced local disease, stage III is regional metastasis and IV is advanced disease with distant metastasis.

Question 9

Lymphoma has its own special system for cancer staging, name and describe it.

Answer 9

Ann Arbor staging: I - single node region, separate regions on the same side of the diaphragm, III - node regions on either side of the diaphragm, IV - diffuse/disseminated extra-nodal involvement (e.g. Liver or lungs).

Question 10

Staging is a powerful predictor of survival - explain how with Duke’s staging.

Answer 10

Duke’s staging is for colorectal carcinoma: A - invasion into, not through bowel wall (5yr SR 93%), B - through the bowel wall (77%), C - involvement of lymph nodes (48%) and D - distant metastasis (6%).

Question 11

What is tumour grade? Describe the different grades.

Answer 11

Tumour grade describes the degree of differentiation of a neoplasm. It is not as standardised as cancer staging, but typically, G1 is well, G2 is moderately, G3 is poorly differentiated and G4 is anaplastic - used for squamous cell and colorectal carcinoma.

Question 12

Give an example of a type of cancer and its internationally recognised formal grading system, what is it based on?

Answer 12

Breast carcinomas are graded with the Bloom-Richardson system, which assesses tubule formation, nuclear variation and number of mitoses.

Question 13

Cancer grading is more important for planning treatment and estimating prognosis in certain types of cancer, which ones?

Answer 13

Soft tissue sarcomas, primary brain tumours, lymphomas and breast/prostate cancer.

Question 14

List some different ways that cancer can be treated.

Answer 14

Cancer can be treated by surgery radiotherapy, chemotherapy, hormone therapy and treatment targeted to specific molecular alterations. Targeting the immune system has also recently shown enormous promise.

Question 15

Surgery is a mainstay treatment for most cancers, but its role depends on the cancer type and stage, what is adjuvant and neoadjuvant treatment?

Answer 15

Adjuvant treatment is given after the surgical removal of a primary tumour, to eliminate any subclinical disease (assuming there are micrometastases, even if clinically disease free).
Neoadjuvant treatment is given to reduce the size of a primary tumour, prior to surgical excision.

Question 16

What is the aim of surgery for cancer treatment?

Answer 16

Hopefully it will debulk the tumour before it spreads and is often seen as the ‘curative’ treatment.

Question 17

Radiotherapy kills proliferating cells by triggering apoptosis or interfering with mitosis, how is damage to normal tissue reduced?

Answer 17

The treatment is focused on the tumour with shielding of surrounding healthy tissue and given in fractionated doses to minimise normal tissue damage.

Question 18

How does chemotherapy specifically result in cancer cell death?

Answer 18

X-rays or other ionising radiation kills rapidly proliferating cells especially in G2 of the cell cycle. High doses cause either direct or free radical-induced DNA damage, detected by cell cycle checkpoints, triggering apoptosis. Double strand DNA breaks damage chromosomes, that prevent correct completion of M phase.

Question 19

Chemotherapy affects proliferating cells non specifically, so what side effects might be a consequence of the treatment?

Answer 19

GI upset, marrow suppression and hair loss.

Question 20

There are several classes of chemotherapy agents, with different methods. Explain the actions of and which classes the following drugs belong to: Fluorouracil, Cisplatin, Doxorubicin and Bleomycin and Vincristine.

Answer 20

The anti-metabolite Fluorouracil, mimics substrates in DNA replication.
The alkylating agent/platinum-based drug Cisplatin, crosslinks 2 strands of the DNA double helix. Antibiotics act in different ways, like Doxorubicin which inhibits a DNA synthesis enzyme and Bleomycin which causes double strand breaks. The plant-derived drug Vincristine, blocks microtubule assembly, interfering with mitotic spindle formation.

Question 21

Give one benefit and one draw back of hormone therapy as cancer treatment.

Answer 21

It is relatively non-toxic, but has a limited scope.

Question 22

Androgen blockade is used as hormone therapy in the treatment of prostate cancer, how does Tamoxifen treat hormone receptor positive (brown stain) breast cancer?

Answer 22

Tamoxifen is a Selective oestrogen receptor modulator (SERM), which bind to oestrogen receptors, stopping oestrogen from binding.

Question 23

Identifying cancer specific alterations, such as oncogene mutations provides an opportunity to target drugs specifically at cancer cells, how does Herceptin do this?

Answer 23

A quarter of breast cancer involves gross over expression of the HER-2 gene and Herceptin blocks HER-2 signalling.

Question 24

Identifying cancer specific alterations, such as oncogene mutations provides an opportunity to target drugs specifically at cancer cells, how does Imatinib do this?

Answer 24

Chronic Myeloid Leukaemia (CML) has chromosomal rearrangement (t9:22) with an abnormal ‘Philadelphia’ chromosome, in which the oncogenic fusion protein (BCR-ABL) is encoded. Imatinib inhibits the fusion of the protein.

Question 25

Nivolumab and Impikimubab are drug therapies for cancer that target what?

Answer 25

Immune checkpoints.

Question 26

Give a positive and a negative for cancer therapies targeted to specific molecular alterations.

Answer 26

There is less bystander damage, but genetic instability neoplastic cells means that mutations may escape targeting.

Question 27

Tumour markets include hormones (HCG - testicular), ‘oncofetal’ antigens (made in foetus and reexpressd in cancer), specific proteins and mixing/glycoproteins. What are they and why are they used?

Answer 27

Tumour markers are various substances released by cancer cells into circulation. Some have roles in diagnosis, but they are mostly useful for monitoring tumour burden during treatment and follow up.

Question 28

Cancer screening attempts to detect cancers as early as possible, when the chance of cure is highest, name 3 issues it has.

Answer 28

Lead time bias, length bias (bias to slower growing tumours) and over diagnosis.

Question 29

Cancer screening looks for early signs of disease in healthy people. List 3 established national screening programmes for cancer in the U.K.

Answer 29

Cervical, breast and bowel cancer.