The Incidence, Prognosis And Treatment Of Malignant Neoplasms

Question 1

Which 4 types of cancer account for half of all new cancers in the UK?

Answer 1

Breast, prostate, trachea bronchus and lung, colon and rectum

= 53%

Question 2

Which types of cancer are most common in children?

Answer 2

In children younger than 14, leukaemias, central nervous system tumours and lymphomas are most common.

Question 3

Which type of cancer is responsible for the highest number of cancer-related deaths in the UK?

Answer 3

Lung cancer

Question 4

Which factors have to be considered to determine which individuals will have a favourable outcome from a malignant neoplasm?

Answer 4

Factors to consider include age and general health status, the tumour site, the tumour type, the grade (i.e. differentiation), the tumour stage and the availability of effective treatments.

Question 5

What is TNM staging?

Answer 5

The commonest method for assessing the extent of tumour is the TNM staging system that is standardised across the world.

• T refers to the size of the primary tumour and is typically expressed as T1 through to T4.
• N describes the extent of regional node metastasis, for example N0 to N3.
• M denotes the extent of distant metastatic spread, e.g. M0 or M1.

Question 6

How are the extent of tumours measured?

Answer 6

For a given cancer the T, N and M status are then converted into a stage from I to IV. The details vary for each cancer but very broadly speaking:

• stage I is early local disease and
• stage II is advanced local disease (i.e. N0, M0),
• stage III is regional metastasis (i.e. any T, N1 or more, M0)
• stage IV is advanced disease with distant metastasis (i.e. any T, any N and M1).

Question 7

What is Ann Arbor staging?

Answer 7

Lymphoma has its own special system called Ann Arbor staging. In brief, stage I indicates lymphoma in a single node region, stage II indicates two separate regions on one side of the diaphragm, stage III indicates spread to both sides of the diaphragm, and stage IV indicates diffuse or disseminated involvement of one or more extra-lymphatic organs such as bone marrow or lung.

Question 8

What is Dukes staging?

Answer 8

Dukes staging has been used for colorectal carcinoma (Dukes’ A: Invasion into but not through the bowel, Dukes’ B: Invasion through the bowel wall, Dukes’ C: Involvement of lymph nodes, Dukes’ D: Distant metastases) but TNM staging is the preferred system worldwide.

Question 9

Which staging system is used for squamous cell carcinoma and colorectal carcinoma?

Answer 9

In general, grading of malignant neoplasms is not as standardised as for staging. Typically, G1 is well-differentiated, G2 is moderately differentiated, G3 is poorly differentiated and G4 is undifferentiated or anaplastic. This system is used for squamous cell carcinoma and colorectal carcinoma.

Question 10

Which grading system is used in the grading of breast carcinoma?

Answer 10

For some cancers, an internationally recognised formal grading system is used. For example, breast carcinoma uses the Bloom-Richardson system, which assesses tubule formation, nuclear variation and number of mitoses

Question 11

When is tumour grade important?

Answer 11

Tumour grade is more important for planning treatment and estimating prognosis in certain types of malignancy, such as soft tissue sarcoma, primary brain tumours, lymphomas, and breast and prostate cancer.

Question 12

Generally, how is cancer treated?

Answer 12

Cancer can be treated by surgery, radiotherapy, chemotherapy, hormone therapy and treatment targeted to specific molecular alterations. Therapy that targets the immune system has recently shown enormous promise. Surgery is the mainstay of treatment for most cancers but the precise role for each type of treatment varies for each cancer and also depends on the cancer’s stage.

Question 13

What is adjuvant treatment?

Answer 13

• Given after surgical removal or a primary tumour
• Clinically disease free
• Given on premise of micro-metastases

Question 14

What is neoadjuvant treatment?

Answer 14

Given to reduce the size of a primary tumour prior to surgical excision

Question 15

How is radiotherapy used to treat cancer?

Answer 15

Radiotherapy is focused on the tumour with shielding of surrounding healthy tissue.

It is given in fractionated doses to minimise normal tissue damage.

X-rays or other types of ionising radiation are used and this kills rapidly dividing cells, especially in G2 of the cell cycle. This is because high dosage causes either direct or free-radical induced DNA damage that is detected by the cell cycle check-points, triggering apoptosis.

Double-stranded DNA breakages cause damaged chromosomes that prevent M phase from completing correctly.

Question 16

What are the different classes of chemotherapy drugs?

Answer 16

• Antimetabolites
• Alkylating
• Antibiotics
• Plant-derived

Question 17

How are antimetabolites used in chemotherapy?

Answer 17

Mimic normal substrates involved in DNA replication -competitive inhibitor e.g. Fluorouracil

Question 18

How are alkylating drugs used in chemotherapy?

Answer 18

Alkylating and platinum-based drugs, e.g. cyclophosphamide and cisplatin, cross-link the two strands of the DNA helix.

Question 19

How are antibiotic drugs used in chemotherapy?

Answer 19

Antibiotics act in several different ways, e.g. doxorubicin inhibits DNA topoisomerase, which is needed for DNA synthesis, while bleomycin causes double-stranded DNA breaks.

Question 20

How are plant-derived drugs used in chemotherapy?

Answer 20

Plant-derived drugs include vincristine, which blocks microtubule assembly and interferes with mitotic spindle formation

Question 21

What is the advantage of hormone therapy?

Answer 21

Relatively non-toxic for certain malignant tumours (however, has limited scope)

Question 22

How can hormone therapy be used in the treatment of breast/prostate cancer?

Answer 22

Selective oestrogen receptor modulators (SERMs), such as tamoxifen, bind to oestrogen receptors, preventing oestrogen from binding. They are used to treat hormone receptor-positive breast cancer. Androgen blockade is used for prostate cancer

Question 23

How can oncogenes be targeted by cancer genes?

Answer 23

Identifying cancer-specific alterations such as oncogene mutations provides an opportunity to target drugs specifically at cancer cells.

Two early examples were Trastuzumab (Herceptin) and Imatinib (Gleevec).

A quarter of breast cancers have gross over-expression of the HER-2 gene and Herceptin can block Her-2 signalling.

Chronic myeloid leukaemia (CML) shows a chromosomal rearrangement (t9:22) creating an abnormal ‘Philadelphia’ chromosome in which an oncogenic fusion protein (BCR-ABL) is encoded.

Imatinib inhibits the fusion protein. New potential targeted therapies continue to emerge. Drugs that block immune checkpoints are a new emerging area of treatment, such as nivolumab and ipilimumab.

Question 24

How are the substances released by cancer cells used?

Answer 24

Various substances are released by cancer cells into the circulation. Although some have a role in diagnosis, in general they are most useful for monitoring tumour burden during treatment and follow up.

Question 25

Give an example of a tumour marker

Answer 25

Tumour markers include hormones (e.g. human chorionic gonadotrophin released by testicular tumours), ‘oncofetal’ antigens (e.g. alpha fetoprotein released by heptatocellar carcinoma), specific proteins (e.g. prostate-specific antigen released by prostate carcinoma) and mucins/glycoproteins (e.g. CA-125 released by ovarian cancer).

Question 26

What is the purpose of cancer screening?

Answer 26

Cancer screening attempts to detect cancers as early as possible when the chance of cure is highest. In the UK there are established national screening programmes for cervical, breast and bowel cancer

Question 27

What are the problems associated with screening?

Answer 27

Screening can have problems such as lead time bias, length bias and over diagnosis.