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Principles of Cancer treatment Flashcards

1
Q

Describe the Gomperzian Growth Curve

A

The Gompertzian growth curve describes the complex pattern of tumour growth
o 3 defined phases – lag/log/stationary phases
o Once detectable, tumour appears to grow quickly

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2
Q

What does the slope of Gomperzian Growth Curve depends on?

A

ratio of cell division to cell loss
Growth fraction
TD (doubling time)

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3
Q

Tumour growth dependency on host factors

A

Necrosis
Vasculature
Presence of other cell populations
Space restrictions

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4
Q

Do solid tumours have longer TD than haematological malignancies?

A

Yes, 2-3 months vs 24 hours

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5
Q

What is doubling time

A

Time taken for a tumour to double its mass

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6
Q

Main pathways of metastasis and what is the mechanism of action?

A

Through blood and lympathic system

Mechanism: dissolution of basement membrane by lytic enzymes released by tumour cells eg proteases

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7
Q

Following dissolution of basement membrane, how does metastasis occur?

A
  • Invasion and movement through the defect due to increased cell motility and decreased cell to cell adhesiveness
  • Binding of tumor to basement membrane through the mediation of altered receptors on the cell surface (predispose teh lodging of tumour seeds)
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8
Q

Metastatic patterns with colon cancer and prostate cancer?

A

Colon cancer → liver

Prostate cancer → bone

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9
Q

Common metastatic sites

A

Liver, lung, lymph node, bone, brain, skin, adrenal glands

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10
Q

Goals of cancer therapy

A
  • curative
  • maintenance of quality and duration of life
  • symptom relief (palliative treatment)
  • clinical trials for experimental therapies (only when cannot cure)
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11
Q

Characteristics of ideal treatment

A
  • Anticancer treatment should be safe, effective and discriminating
  • Actions should be limited to cancer cells
  • Should have few side effects
  • Should return the patient to former state of health
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12
Q

Types of cancer treatment

A

Surgery
Radiation
Chemotherapy

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13
Q

What is surgery used for?

A

Used to cure localised disease
Commonly used to treat primary cancer or localised metastatic masses
Play major roles in diagnosis, staging, relief of symptoms, reconstruction and prevention

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14
Q

What can surgery do?

A
  • Pain or symptom relief
  • Reduce size of tumor to increase efficacy of RT, Cx or other therapy
  • Remove source of ectopically expressed hormones or for hormonal therapy
  • Restore function, cosmesis, quality of life
  • Preventive: remove moles, polyps
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15
Q

What is radiotherapy? What does it target and what is the mechanism of action?

A

Destruction of cancer cells by ionising radiation
Target of damage thought to be cellular DNA
Mechanism of action is generation of free radicals
Cancer cells in rapid division may be selectively destroyed by RT

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16
Q

What does radiocurability depend on?

A

Size and location of tumour
Type of tumour
Tumour radiosensitivity

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17
Q

Is radiotherapy often used as adjunct to surgery and palliation?

A

Yes

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18
Q

How is radiation therapy delivered by?

A

External beam - radiation from a machine outside body

Brachytherapy/interstitial brachytherapy - uses radiation 9implants) that is placed very close to or inside the tumour

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19
Q

How is dose of radiation therapy measured? How is it expressed?

A

Energy absorbed in treatment volume, expressed in Gray (Gy)

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20
Q

What is the typical dose of radiation for glioma and breast cancer?

A

Glioma ~60 Gy

breast cancer ~50Gy

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21
Q

What is the dose-limiting factor in radiation therapy?

A

Normal tissue damage (early - rapidly dividing tissues; late effects - organs)

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22
Q

How to minimise normal tissue damage with RT?

A
  • Fractionate
  • Conformal radiotherapy
  • Radioimmunotherapy
  • “heavy” ion
  • charged particle therapy
23
Q

What are serious radiation toxicities?

A

BoLLS In RBF

Bone marrow - pancytopenia/aplasia
Lung - pneumonitis/fibrosis
Liver - hepatitis
Stomach - ulcer/hemorrhage
Intestine - ulcer/perforation
Rectum - stricture/ulcer
Brain - infarct/necrosis
Fetus - death
24
Q

Other uses of radiotherapy

A

Total body irradiation
Supplement surgery
Palliation of pain
Relief of obstruction/compression

25
What is chemotherapy? What is it useful for? | Subsets of chemotherapy?
Drug therapy for the treatment of cancer It is most useful for treatment of systemic or disseminated disease Subsets: Endocrine, biologic
26
Basic principles of chemotherapy
1. Drug kills a constant proportion of tumour cells rather than a constant number of cells 2. It has greatest effect on cells that are actively dividing 3. Drugs have a narrow TI, thus treatment is a balance between toxic effects and efficacy 4. Combination chemotherapy can be used to improve tx outcome
27
Why are smaller tumours more responsive to chemotherapy?
smaller tumours have a higher growth fraction → greater number of proliferating cells If growth fraction is low, the fraction of cells killed by chemotherapy is small.
28
Advantages of combination chemotherapy
- Maximum cell kill within acceptable toxicity - Broad coverage against multiple cell lines - Slower emergence of resistant strains
29
Disadvantages of combination chemotherapy
- Multiple toxicities with greater patient discomfort - Impact of dose effect - Complicated to administer - More expensive
30
Application of treatment principles
Drug kills constant proportion → Repeat treatment cycles Greatest effect on cells actively dividing → Treat asap, when disease in early stage Drugs have narrow TI → Know intent of treatment, monitor for SE Combination chemo where possible
31
How are protocols dosed?
In BSA (more closely correlated with cardiac output which determines blood flow to liver and kidney and subsequently influences drug elimination)
32
What is the purpose of schedule of administration? What is "drug rest" for?
To achieve optimal therapeutic benefit with minimal toxicity | "drug rest" to allow for normal cells to recover
33
Effect of dose intensity on treatment outcome?
Reducing dose intensity → reduce response to treatment
34
How can you intensify a protocol? | What must be added?
Increase the doses of the drugs in the protocol or reduce the interval If reducing interval, must add haemopoeitic growth factors (more myelosuppression)
35
What is selection of chemotherapy regimen based on?
``` Histological documentation of tumour type Stage of disease Prognostic variables Patient -related variables Toxicities Risk vs Benefits ```
36
Incurable cancers
Metastatic lung cell, breast, colon, cervical, head and neck
37
Factors affecting response to chemotherapy
Drug (dose intensity, scheduling, cell-cycle specificity) Tumour (resistance, stage, anatomic site, blood supply) Patient (drug tolerance, renal, hepatic function)
38
Drug related factors
PK Mode of action Drug distribution to the tumour microenvironment Combination chemotherapy
39
What problems do combination chemotherapy overcome?
Sensitivity - tumours may be non-responsive at clinically achievable doses Toxicity - avoid the use of high doses resistance - inherent genetic instability commonly leads to non-random mutation that confers resistance
40
Advantages of combination chemotherapy
1. Maximum cell kill within acceptable toxicity 2. Broad coverage against multiple cell lines 3. Slow emergence of resistant strains
41
Disadvantages of combination therapy
1. Multiple toxicities with greater patient discomfort 2. Impact of dose effect 3. Complicated to administer 4. May be more expensive
42
desirable characteristics for combination therapy
- Agents must be effective when used alone - Should have different dose-limiting toxicities - Should not antagonise each other when combined - Should be given in a dose equivalent to that used when the drug is given alone - Agents should have different pharmacological action - Increase the overall intensity of therapy directed at the cancer
43
Tumour related factors
Tumour growth kinetics Tumor size Site of tumour and tumour vascularisation Tumour cell heterogeneity - resistance
44
Relationship of tumour growth kinetics to response to therapy? What implications does this have?
Small tumour burden + high growth fraction | Early detection/screening programs are important
45
How does tumour size affect response to therapy?
In large tumours most of the cells are not proliferating and are less likely to be killed by chemotherapeutic agents The larger the tumour, - the greater probability of metastasis - the greater the probability of drug-resistant cells - poor drug distribution
46
How does site of tumor and tumor vascularisation affect response to therapy?
Sanctuary sites (CNS, testis) has poor drug penetration → higher doses needed, special delivery mode Poor blood supply: large tumor → central necrosis
47
Mechanisms of tumor cell resistance to antineoplastic drugs
Decreased drug accumulation (decreased drug uptake, increased efflux, altered intracellular trafficking of drug) Altered drug metabolism (Decreased drug activation, increased drug degradation) Increased repair to drug induced damage (to DNA, protein or membrane) Drug target altered
48
What are patient related factors
``` Patients overall health status Immunocompetency Organ(s) functions Treatment history Patient's age ```
49
What is the difference between curative vs palliative?
Curative - intense short term but reversible toxicity is acceptable if there is no other alternative; long term permanent toxicities to be avoided where possible Palliative - aim is to improve overall QOL. Intense short term toxicity is undesirable and long term toxicities are generally not a consideration
50
What is palliative chemotherapy
Involves administration of systemic therapy to control residual disease/metastases and reduce existing cancer symptoms (pain, obstruction) May be used together with surgery and or radiotherapy
51
What is neoadjuvant chemotherapy?
Systemic tx given before surgery to "debulk" the tumour, reducing the extent and disfigurement of surgery Can also help to eradicate micro-metastases
52
Adjuvant chemotherapy
Involves administration of systemic therapy to eradicate any residual micro-metastases and prevent them from growing into clinically evident disease It is used together with surgery and/or radiotherapy
53
Factors affecting choice of treatment (surgery/RT/Cx)?
Type of tumour, stage and rate of growth Patient (age, organ function, performance status) Cost Availability

Oncology (1 decks)

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