L17: Neoplasia 4

Question 1

Where does cancer rank in terms of lethal disease?

Answer 1

Second most
>14 million new cases worldwide in 2012
Estimated 9.6 million deaths in 2018

Question 2

In the UK in 2015 how many people were diagnosed with malignant neoplasms?

Answer 2

360,000

Question 3

What are the most common cancers in men and women in the UK?

Answer 3

Men- prostate, lung, bowel
Women- Breast, lung, bowel
Make up >50% cancers in the UK (53%)

Question 4

What is the most common age group to be affected?

Answer 4

Over 65 yrs
Small proportion up to 24
Children under 14 normally have leukaemias, CNS tumours and lymphomas

Question 5

What is the survival rate for different neoplasms?

Answer 5

Survival rates for different cancers is variable 
Women ↑ survival rate--> more likely to seek medical advice, notice changes more, men more likely to be embarrassed
Survival rate doubled in last 40 years
50% people diagnosed survive 10 years 
5 year survival rate
-Testicular cancer 98%
- Melanoma 90%
- Breast cancer 87%

Question 6

Which neoplasms have the worst survival rates?

Answer 6

Pancreas <25% 1 year survival rate

Lung, brain and stomach also very low

Question 7

Which cancer is the biggest cause of cancer-related deaths?

Answer 7

Lung cancer

One of the most common

Question 8

How have survival rates changed? Why?

Answer 8

Most cancers have had a big improvement in survival rate
Advancement in treatment
Public health campaigns
Pancreas–> no change
Lung cancer–> little improvement–> main cause of death

Question 9

Testicular cancer used to have a poor prognosis, nowadays it has the best survival rate, how come?

Answer 9

Treatment got better–> platinum based treatments
Public health campaigns–> encouraged men to check
Detect early, treat early

Question 10

What needs to be considered when predicting the outcome for malignant neoplasms?

Answer 10

Age, 
general health status, 
tumour site, 
tumour type, 
grade (differentiation), 
stage  
availability of treatment

Question 11

What is meant by health status?

Answer 11

Performance stage

How well patient will be able to tolerate treatment

Question 12

How are tumours staged?

Answer 12

Measure of malignant neoplasms overall burden on the body
Measured using the TNM staging system
Standardised across the world for certain cancers

Question 13

What is the TNM staging system?

Answer 13

TNM gives you a status which is converted to a stage
T- Tumour size–> size of primary tumour T1- T4
N- Nodes–> describe extent of regional node metastasis via lymphatics e.g. N0- N3 (N0 - no lymph node involvement, N1- one lymph node or group …)
M- Metastases–> extend of distant metastatic spread via the blood M0 (no metastases) or M1 (metastases)

Question 14

How is the TNM status converted to a stage?

Answer 14

Stage I- IV
Varies for each cancer but in general
Stage I- Early local disease (T1-2, N=0, M=0)
Stage II- Advanced local disease (T3-4, N=0, M=0)
Stage III- Regional metastasis (T1-4, N=1+, M=0)
Stage IV- Advanced disease with any distant metastasis (any T, any N, M1)

Question 15

What is the staging system for lymphoma called? How does it work?

Answer 15

Ann Arbor staging
Stage I –> Lymphoma in single node region
Stage II –> Indicate two separate regions but on same side of diaphragm
Stage III –> Indicates spread on opposite sides of diaphragm
Stage IV –> Indicates diffuse or disseminated involvement of one or more extra-lymphatic organs such as bone marrow or lung

Question 16

What has been used for staging of colorectal cancers?

Answer 16

Dukes staging
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
TNM is the preferred system worldwide

Question 17

What does the tumour grade describe?

Answer 17

How well differentiated a tumour is
Low grade/ G1–> well differentiated
G2–> moderately differentiated
High grade/ G3–> Undifferentiated or anaplastic

Question 18

What do we mean by differentiated?

Answer 18

How well it resembles the original tissue

Question 19

What is tumour grade used for?

Answer 19

Planning treatment and estimating prognosis

Question 20

What grading systems is used by breast carcinomas?

Answer 20

Bloom-Richardson system

Assess tubule formation, nuclear variation and number of mitoses (mitotic figures)

Question 21

What are the methods for treating cancers?

Answer 21

Surgery
Radiotherapy 
Chemotherapy
Hormone therapy 
Treatment targeted to specific molecular alterations 
Immune system targeted therapy

Question 22

What is the mainstay of cancer treatment?

Answer 22

Surgery
Precise role varies in each cancer
Most successful for remission (cure)–> never be 100% sure about microtumours
Good for early non metastasised tumour
Idea is to remove whole tumour with a wide enough border to ensure you have it all

Question 23

What is the difference between Adjuant and Neoadjuvant treatment?

Answer 23

Both given when treatment is surgery
Adjuvant treatment–> after –> eliminate subclinical disease (attempt to eliminate microtumours)
Neoadjuvant treatment–> before –> shrinkage of tumour before surgery –> hopefully remove whole thing

Question 24

How does radiation therapy work?

Answer 24

Kills proliferating cell by triggering apoptosis or interferring with mitosis
Directed on tumour, shielding of surrounding tissues
Cells in G2 phase of cell cycle
High dosage–> direct or free radical induced DNA damage, detected by cell checkpoints, triggering apoptosis
Double strand DNA breakages cause damaged chromosomes that prevent M phase from completing

Question 25

How is radiation therapy best delivered?

Answer 25

Fractionated doses
Minimise normal tissue damage
Chance for normal tissue to recover
Bigger differential between normal cells and cancer cells

Question 26

What type of radiation is used?

Answer 26

X-rays

Others that are ionising

Question 27

How does chemotherapy work?

Answer 27

Affect proliferating cells in different ways

Several classes

Question 28

How does chemotherapy work?

Answer 28

Affect proliferating cells in different ways 
Several classes
--> Antimetabolites
--> Alkylating and platinum based drugs
--> Antibiotics 
--> Plant-derived drugs

Question 29

How do antimetabolites work?

Answer 29

Mimic normal substrated involved in DNA replication
Act as antagonists stop DNA replication
e.g. flurouracil

Question 30

How do alkylating and platinum based drugs work?

Answer 30

Cross link the two strands of DNA helix

e.g. eyclophosphamise and cisplatin

Question 31

How do antibiotics work?

Answer 31

Act in different ways

e. g. doxorubicin–> inhibits DNA topoisomerase–> needed for DNA synthesis (topoisomerase important for unwinding DNA helix to relieve tension)
e. g. bleomycin–> causes double-stranded DNA breaks

Question 32

How do plant-derived drugs work?

Answer 32

Block microtubule assembly and interferes with mitotic spindle formation
e.g. vincristine

Question 33

What is the downside to chemotherapy?

Answer 33

Unable to differentiate between normal cells and cancer cells 
Side effects
--> Hair loss
--> Pain 
--> Mouth ulcers
--> Bruise easily 
--> Weakened immune system 
--> Nausea/vomiting
--> Constipation/ Diarrhoea
--> Rashes 
--> Neuropathy

Question 34

How does hormone therapy work?

Answer 34

Relatively non-toxic approach
Act as antagonists
Bind to receptors preventing hormone from binding

Question 35

What examples are there of hormone therapy?

Answer 35

Selective oestrogen receptor modulators (SERMs), Tamoxifen–> bind to oestrogen receptor–> prevents oestrogen from binding–>treat breast cancer
Androgen blockade used for prostate cancer

Question 36

How does oncogene therapy work? Give an example?

Answer 36

Oncogenes are formed by mutations
Oncogenes promote cell proliferation
Inhibiting the actions of oncogenes can slow proliferation
Trastuzumab (Herceptin) and Imatinib (Gleevec)
–> 1/4 of breast cancer over expression of HER-2 gene, Herceptin can block Her-2 signalling
Imatinib inhibits fusion proteins (formed from rearrrangement (t9:22)–> Philadelphia chromosome–> oncogene fusion protein BCR-ABL)

Question 37

What is immunotherapy?

Answer 37

Developing therapy
Based on the idea of helping the immune system fight cancer
Recognise and attack cancer cells
Nivolumab–> Help kill cancer cells
Ipilimumab–> Interferes with priming and activation of T cells

Question 38

What are tumour markers? How are they used?

Answer 38

Substances released from cancer cells into circulation

Role in diagnosis but more importantly monitor cancer burden during treatment and follow up

Question 39

What are the tumour markers?

Answer 39

Hormones
Oncofetal antigens –> things produced in tumour and developing foetus
Specific proteins
Mucins/ glycoproteins

Question 40

What does cancer screening aim to do?

Answer 40

Detect cancers as early as possible
Before the onset of symptoms
Highest change of ‘cure’

Question 41

What are the potential issues with screening programmes?

Answer 41

Subject to

• Lead time bias–> Diagnose tumours earlier, live same amount of time, live same amount of time but knowing they are unwell
• Over diagnosis–> Tumour meets threshold in screening but actually if left may have never caused a problem, no potential to progress
• Size and stage of tumour and growth overtime–> tumour present in between screenings–> grows quickly, symptoms develop before next screening session (basically missed because it sudden appear and grows rapidly)