Neoplasm 4

Question 1

What are the 4 most common cancers

Answer 1

Breast, lung, prostate and bowel carcinomas account for approximately half of all new cancers in the UK (53%).
All epithelial = carcinomas- epithelial cells constantly bombarded with carcinogens
Range in numbers from 35-45000
Everything else around 12000 highest and lower

Question 2

What age group os cancer associated with

Answer 2

The great majority is diagnosed in people aged over 65 but only a small proportion in people up to age 24. In children younger than 14, leukaemias, central nervous system tumours and lymphomas are most common.

Question 3

Describe the survival rates/mortality of different types of cancer

Answer 3

The survival for different cancer types in the UK is very variable. The 5 year survival rates for testicular cancer (98%), melanoma (90%) and breast cancer (87%) are substantially better than pancreatic (3%), lung (10%) and oesophageal cancers (15%). Lung is the biggest cause of cancer-related deaths in the UK. Go to the Cancer Research UK website and explore the ‘Cancerstats’ section for a thorough
description of UK cancer statistics.

Question 4

What are 5 cancers with a very ppoor survival

Answer 4

Oesophagus, stomach, brain, lung, pancreas

Question 5

What a re factors to consider to predict outcome?

Answer 5

Determining which individuals will have a favourable outcome for malignant neoplasms is far from exact. Factors to consider include age and general health status, the tumour site, the tumour type, the grade (i.e. differentiation), the tumour stage (see below) and the availability of effective treatments.

Question 6

What is the TNM system?

Answer 6

TUMOUR STAGE IS A MEASURE OF THE MALIGNANT NEOPLASM’S OVERALL BURDEN: The commonest method for assessing the extent of tumour is the TNM staging system that is standardised across the world for various types of cancer. 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 via lymphatics, for example N0 to N3. M denotes the extent of distant metastatic spread via the blood, e.g. M0 or M1.

Question 7

What is tumour stage

Answer 7

A measure of the malignant neoplasms overall burden
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) and stage IV is advanced disease with distant metastasis (i.e. any T, any N and M1).
See slide

Question 8

What is Ann Arbor staging?

Answer 8

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 9

What is dukes staging?

Answer 9

Staging is a powerful predictor of survival. 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 10

What is grading

Answer 10

Not as standardised, more subjective
TUMOUR GRADE DESCRIBES THE DEGREE OF DIFFERENTIATION OF A NEOPLASM: The principles behind grading were described in neoplasia 1. 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. For example, this system is used for squamous cell carcinoma and colorectal carcinoma.

Question 11

What is the bloom Richardson grading system

Answer 11

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 (pleomorphism) and number of mitoses

Question 12

What is tumour grade important for

Answer 12

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 13

Briefly describe treatment of cancer

Answer 13

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 14

Define adjuvant and neoadjuvant treatment

Answer 14

Adjuvant treatment is given after surgical removal of a primary tumour to eliminate subclinical disease. Neoadjuvant treatment is given to reduce the size of a primary tumour prior to surgical excision.

Question 15

Describe radiation therapy

Answer 15

RADIATION THERAPY KILLS PROLIFERATING CELLS BY TRIGGERING APOPTOSIS OR INTERFERING WITH MITOSIS: 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 4 types of chemotherapy drugs

Answer 16

CHEMOTHERAPY DRUGS AFFECT PROLIFERATING CELLS IN VARIOUS WAYS: Several classes of chemotherapy agents exist.
Antimetabolites mimic normal substrates involved in DNA replication, e.g. Fluorouracil.
Alkylating and platinum-based drugs, e.g. cyclophosphamide and cisplatin, cross-link the two strands of the DNA helix.
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.
Plant-derived drugs include vincristine, which blocks microtubule assembly and interferes with mitotic spindle formation
Har loss, marrow suppression -> immuno compromised, not very nuanced, toxic, targets rapidly dividing cells

Question 17

What is hormone therapy?

Answer 17

HORMONE THERAPY IS RELATIVELY NON-TOXIC TREATMENT FOR CERTAIN MALIGNANT TUMOURS: 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 18

What are cancer specific drugs

Answer 18

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.

Question 19

What is the cancer immunity cycle

Answer 19

See slide
The cancer immunity cycle highlights points where immune treatments can be used. Examples include nivolumab and ipilimumab, which block immune checkpoints.
3 - acc activates t. Checkpoint to stop T cell becoming overactivaled. Ipilimumab stopso check point - super activated T cell, goes off and kills cancer cells. Nivolumab - can express ligand that shuts T cell from killing
Both are immune checkpoint inhibitors

Question 20

What are tumour markers

Answer 20

TUMOUR MARKERS ALLOW THE MONITORING OF CANCER BURDEN: 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. Tumour markers include hormones (e.g. human chorionic gonadotrophin released by testicular tumours), ‘ oncofetal’ antigens (e.g. alpha fetoprotein released by hepatocellar carcinoma), specific proteins (e.g. prostate-specific antigen released by prostate carcinoma) and mucins/glycoproteins (e.g. CA-125 released by ovarian cancer). There are several others and you should read about these in your textbook.

Question 21

What is cancer screening

Answer 21

CANCER SCREENING INVOLVES LOOKING FOR EARLY SIGNS OF DISEASE IN HEALTHY PEOPLE: Cancer screening attempts to detect cancers as early as possible when the chance of cure is highest. However screening can have problems such as lead time bias, length bias and over diagnosis. In the UK there are established national screening programmes for cervical, breast and bowel cancer. For general information about screening in the UK, please see:

Question 22

What is lead tiem bias

Answer 22

Let’s take a look at a chart we saw earlier. Here the disease starts in 1985, is diagnosed in 1992 and the person dies of that disease in 1995. How long is his survival? Three years.

lead time bias

Now we institute an effective screening program. The disease starts in 1985 and is detected by the screening program in 1989. The person dies of the disease in 1995. How long was the survival? Six years. Screening seems to have increased their survival time, correct?

lead time bias

You have also noted that in either situation, it is 10 years from the time the disease started until the person dies. If our measure is survival time, we can easily produce a lead time bias. In this example, there is actually no benefit of the screening process, in terms of survival. The person still died in 1995. They know about the disease for three years longer; that is the effect of the screening. This example demonstrates a lead-time bias of three years.

lead time bias

An effective screening progam for a life-threatening disease should extend life. .Screening studies with an outcome of survival time are subject to lead-time bias that can favors the screening process when there is not actual benefit to the program.

Another way to represent the lead time bias is on a survival curve:

graph

Gordis, L. Epidemiology. Philadelphia: Saunders and Company, 1996

In this graph, at time zero 100% of the people are alive. After five years, 30% are alive. We have instituted a screening program which detects disease one year earlier. In this case, five years following the screening diagnosis gets us out to a 50% survival rate for individuals five years following screening diagnosis. We have a lead time bias of a 20% increased survival to five years. All that has been done here is to move diagnosis back one year!

Instead, we need to look at the mortality rates from the disease, i.e. the mortality rates in the exposed group and the nonexposed group. Mortality rates are the ‘gold standard’ for measuring the effect of early screening and treatment, not survival time.

Question 23

What is length bias

Answer 23

Let’s use this graph to consider the effect of length bias:

length bias

Disease onset is at zero and each line represents an individual. The bottom person, for instance, has a very slow growth rate of disease. The top line, with the steepest slope, represents someone with aggressive disease. This person has rapid growth and dies (D). The individuals with slower growth lived to the point where they get screened (S).

A screening initiative is more likely to detect slow-growing disease. There is not much that a researcher can do about this type of bias other than to realize it is likely to occur.