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Cancer managment > Principles of Cancer treatment > Flashcards

Principles of Cancer treatment Flashcards

1
Q

Learning Objectives
◼ At the end of session, you will be able to
explain cancer growth kinetics/metastasis
identify goals of cancer therapy
discuss therapeutic modalities
evaluate response and toxicity
 explain the “protocol” concept in cancer
treatment
identify factors affecting the effectiveness of
chemotherapy treatment

A

1

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2
Q

Tumor growth is ___ during the __ phase. It will exhibit a __ which may increase at a later stage.

A
  1. logarithmic
  2. initial
  3. constant doubling time
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3
Q

The period of __ is characterized by the __ phase, where the establishment of the tumor within the host occurs. The tumor is not detectable at this stage.

A
  1. immunosuppression

2. early lag

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4
Q

The clinically silent period is characterized by the __ phase, which shows latent growth prior to detection. At this point, the tumor is undetectable because it is __.

A
  1. log

2. below the detection limit

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5
Q

The clinical detection limit for tumors is at __ tumor cells, ~30 generations after the period of immunosuppression. It is usually detected at __ and once detected, the tumor appears to __.

A
  1. ~1g or 10^9
  2. 1g or (10^10 cells)
  3. grow quickly
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6
Q

The stationary stage occurs ~10 generations after the clinically silent period and is characterized by the __ phase at ~1kg tumor or 10^12 cells (lethal size). This occurs due to the __.

A
  1. plateau

2. limited space for growth

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7
Q

Tumor factors that affect its growth include: ratio of __, __ and TD (doubling time). Host factors that affect tumor growth include: __, presence of other cell populations, space restriction and necrosis.

A
  1. cell division to cell loss
  2. growth fraction
  3. vasculature
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8
Q

Doubling time (TD) is time taken for a tumor to double its mass and Solid tumors have __ TD than hematological malignancies. __ in TD are expected and urgency to treat cancer also relates to __.

A
  1. longer: (2-3months vs. 24h)
  2. Large variations
  3. speed of cancer growth
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9
Q

The initial phase of metastasis is characterized by __. The second phase of invasion and movement occurs __. The final phase of anchorage occurs via __.

A
  1. dissolution of the basement membrane by lytic enzymes released by tumor cells eg proteases
  2. through the defect due to increased cell motility and decreased cell to cell adhesiveness
  3. Binding of tumor to basement membrane through the mediation of altered receptors on the cell surface
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10
Q

The 2 main pathways of metastasis are via __.
Often, metastasis can begin early even before the tumor is clinically detectable, with __ of patients turning up with metastatic disease or clinically silent metastasis.

A
  1. the blood and lymphatic system

2. 1/3

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11
Q 
Common (to many solid tumors) metastatic sites include: 
l\_\_,
l\_\_,
l\_\_,
b\_\_,
b\_\_,
s\_\_,
a\_\_
A
  1. liver
  2. lung
  3. lymph nodes
  4. bone
  5. brain
  6. skin
  7. adrenal glands
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12
Q

Metastatic pattern varies with tumor type: i.e. Colon cancer to __ and prostate cancer to __.

A
  1. liver

2. bone

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13
Q

Treatment of cancers with secondary metastatic disease is more complex because __. Treatment efficiency is best when the ___ or when we can arrest __.

A
  1. we need to tx both primary and secondary tumors
  2. tumor burden is small with a high growth fraction
  3. angiogenesis
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14
Q

For cancer treatment, our goals are __ (if possible), to provide __ (palliative) and to ultimately maintain __. Clinical trials for experimental therapies may be used considered when __.

A
  1. curative
  2. symptomatic relief
  3. quality and duration of life
  4. there are no longer any registered therapeutic options left
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15
Q

Ideally, anti-cancer treatment should be safe, __with few side effects. We want to return the patient to __.

A
  1. discriminating towards cancer cells

2. former state of health

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16
Q

Surgery is curative for __ cancers and is important in diagnosis, staging (finding extent of involvement), __, reconstruction and __.

A
  1. localized
  2. relief of symptoms
  3. prevention
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17
Q

Surgery can be an adjunct to other forms of cancer treatment by __. Particularly in hormonal therapy/ectopically expressed hormones, surgery can __.

A
  1. reducing size of tumor to increase efficacy

2. remove the source

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18
Q

Radiation destroy cancer cells by __ and selectively destroys __. Radiocurability depends on the size, location, type and radiosensitivity of tumor.

A
  1. generating free radicals to damage DNA

2. cells in rapid division

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19
Q

Radiation therapy may be delivered externally or via brachytherapy/interstitial brachytherapy where __. The dose is measured in __ (energy absorbed in treatment volume).

A
  1. radiation (implants) that are placed very close to or
    inside the tumor
  2. Gray (Gy)
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20
Q

To minimize normal tissue damage in radiotherapy, we may use __ radiotherapy (curative intent) or new technologies such as conformal radiotherapy, radioimmunotherapy, “heavy” ion, charged particle therapy. The dose limiting factor is ___, with early effects in ___ and late effects in organs.

A
  1. fractionated
  2. normal tissue damage
  3. rapidly dividing tissues
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21
Q

Radiotherapy plays a role in bone marrow transplants via __. It can supplement surgery (when clearance of margin cannot be achieved), relief __and__ (external beam/strontium 89).

A
  1. total body irradiation

2. obstruction and pain

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22
Q

Chemotherapy is most useful for __. It is often an adjunct to palliation and other cancer treatment modalities. It may be __ in nature and has the greatest effect on __.

A
  1. treatment of systemic or disseminated disease (including micro-metastases)
  2. endocrine or biologic
  3. actively dividing cells
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23
Q

Because Chemotherapy drugs __ (1st order kinetics), there is a need to repeat treatment cycles. __ results in better clinical outcomes. They typically have a __ therapeutic index.

A
  1. kill a constant proportion of cells rather than a constant number
  2. Earlier treatment
  3. narrow
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24
Q

If the intent of tx is CURATIVE, our tolerance of side effects is __ and our special concern is on _____ side effects (due to influence on rest period between cycles) and___ side effects (affects return to former state of health). Challenges would include: ____

A
  1. high
  2. delayed
  3. long-term
  4. avoid treating those who are already cured
25
Q

If the intent is to extend life, our tolerance of side effects is __ and our concern is on __. We would typically administer treatment when __.

A
  1. moderate
  2. value of added time
  3. added time outweighs side effects
26
Q

If the intent is palliative, our tolerance of side effects is __ and our concern is on __. We would typically administer treatment when __. __ are generally not a concern.

A
  1. low
  2. symptom control
  3. giving treatment improves QoL
  4. Long term toxicities
27
Q

Combination chemotherapy can improve treatment outcomes as it achieves _______, _____ against multiple cell lines and __________ of resistant cell lines.

A
  1. Max cell kill within acceptable toxicity
    [increased sensitivity with lowered doses (toxicity)]
  2. broadens coverage
  3. slows down the emergence
28
Q

Combination chemotherapy has certain caveats such as potentially causing ____and____ for the patient, being __/__ to administer and the the __ can only be determined via clinical trial and error.

A
  1. multiple toxicities (more side effects) and greater pt discomfort
  2. complicated/expensive
  3. impact of dose effect
29
Q

Tumors show different responses to different combinations of chemotherapy, leading to development of protocols. Their efficacy are established via __ and may differ from center to center.

A

clinical trials (empirically)

30
Q

Protocols may be named after the __ of chemotherapy agents and typically feature __ although single agent protocols are possible as well. They have a specific __, __ and __ per cycle.

A
  1. constituents
  2. synergistic combinations
  3. dose, schedule and duration
31
Q

Chemotherapy agent doses are almost always in __ due to it providing a more accurate __ and being more closely correlated to __.

A
  1. Body surface area (BSA)
  2. cross-species comparison of activity and toxicity
  3. cardiac output (determines liver and kidney blood flow), influencing elimination.
32
Q

The formula for BSA calculation is __. It is critical to verify __ to avoid dosing errors.

A
  1. BSA (m^2) = sq root[weight (kg) x height (cm)/3600]

2. potentially inaccurate BSA

33
Q

Administration schedules are typically designed to __, along a ‘drug rest’ period to allow __ (empirically determined in clinical trials).

A
  1. achieve maximum therapeutic benefit with minimal toxicity

2. normal cells to recover

34
Q

Dose intensity is referred to amount of drug given per unit time. It is directly correlated to __. We may modify the dose intensity by either __ or __. Dose intensity is usually maintained and should be reduced only __.

A
  1. treatment response
  2. reducing the interval
  3. increasing the dose
  4. in threatening toxicities
35
Q

Dose intensity adjustments for chemotherapy are typically done to __ or __ (alongside appropriate supportive treatment).

A
  1. reduce toxicity

2. reflect new changes in clinical evidence

36
Q

The stepwise consideration for chemotherapy selection begins with __, __, consideration of ___ and ___ related variables, before moving onto toxicity (risk vs benefit) considerations.

A
  1. histology
  2. staging
  3. prognostic and patient
37
Q

__ of drug, protocol, site/blood supply of tumor, __ (PK factors) of patient and __ all contribute to chemotherapy response.

A
  1. Efficacy
  2. elimination
  3. tolerance
38
Q

Increasing sensitivity of treatment may improve patient response but __. Generally, if a patient relapses within 6 months of treatment, we should __. Our preferred treatment goal is __ to avoid relapse.

A
  1. cannot prevent relapse of resistant cell lines
  2. avoid using the same drugs again
  3. to overcome resistance
39
Q

Cancer cells may exhibit various mechanisms of resistance similar to bacteria which include:

  • __ (transport)
  • __ (reducing active levels)
  • __ (reducing concentration)
  • __ (recovery)
  • __ (avoidance)
A
  1. Decrease in cellular uptake or increase in efflux of drug
  2. Decrease in drug activation
  3. Increase in drug degradation
  4. Increase ability to repair DNA
  5. Use alternate biochemical pathways
40
Q

Desirable characteristics for combination therapy:

  1. Effectiveness i.e. __
  2. Different __
  3. No antagonism
  4. Agents should be given in a dose equivalent to that used when the drug is given alone
  5. Different __
  6. Increase the overall intensity of therapy
A
  1. have > 20% response rate when used alone
  2. dose limiting toxicities
  3. MOA
41
Q

Larger tumors are harder to treat as there is a higher likelihood of __ and __. Chemotherapy is less likely to be target __ cells (majority) and __ is expected to be poorer as well.

A
  1. metastasis and drug resistance
  2. non-proliferating
  3. drug distribution
42
Q

Drug penetration is likely to be lower at areas of poor blood supply (i.e. __) and sanctuary sites (i.e. __), often requiring higher doses and special delivery modes.

A
  1. central necrosis in large tumors

2. CNS, testis

43
Q

The patient’s overall health status has a profound influence on chemotherapy response. The __ and __ are subjective guides that are also useful in comparison of toxicities.

A
  1. ECOG Performance Status Criteria

2. Karnofsky Performance Status Criteria

44
Q

Immunocompromised patients tend to have a poorer prognosis as __. As such, __ should be avoided.

A
  1. they typically require a reduction in dose intensity

2. immunosuppressant use for minor ailments

45
Q

Elimination affects chemotherapy toxicity by __ and monitoring is essential before/during treatment or when patient shows signs of toxicity. Dose reduction for impaired elimination is often __.

A
  1. affecting drug exposure duration

2. empirical (~25%)

46
Q

__ is the most common dose limiting toxicity for chemotherapy. Therefore, prior __/__ can result in accumulative damage, __ to avoid life threatening aplasia..

A
  1. Myelosuppression
  2. Chemotherapy/Radiotherapy
  3. lowering the dose intensity of subsequent treatment
47
Q

Myelosuppression recovers more slowly among __ patients but good __ and __ status allows for safe full dose administration.

A
  1. aged
  2. major organ function
  3. nutritional
48
Q

Cancer patients with certain concomitant diseases (i.e. __) may be harder treat.

A

DM, dialysis

49
Q

Neoadjuvant chemotherapy is commonly given before surgery to eradicate __, debulk the tumor, reducing the __ and __ of surgery.

A
  1. micro-metastases
  2. extent
  3. disfigurement
50
Q 
Response rate reflects the % of patients who had tumor regression following therapy. 
Complete Response (CR) refers to the \_\_ of tumour for \_\_ with the return of \_\_.
A
  1. complete disappearance of all clinical evidence
  2. at least 1 month
  3. Performance status
51
Q

Partial Response (PR) refers to __ tumour, with no new area of disease and __. The measurement can be made using diameter (longest breadth and length).

A
  1. > or = 50% decrease of measurable

2. no evidence of progression

52
Q 
Disease Progression (DP) refers to \_\_, appearance \_\_ or tumour induced death. 
Stable Disease (SD) refers to a measurable tumour that does not meet the the criteria for CR or PR or DP. The tumour size \_\_.
A
  1. increase of measurable tumour by >25%,
  2. of new lesion
  3. does not increase or decrease in size by >25%
53
Q

In literature, the reporting of Overall response rate or objective response rate refers to __.
Clinical Benefit refers to __.

A
  1. Complete Response (CR) + Partial Response (PR)

2. Complete Response (CR) + Partial Response (PR) + Stable Disease (SD)

54
Q

Duration of response refers to the time from the first documentation of response to the recurrence (i.e. ___ time) or progression of the tumor (i.e. time ___ ). In patients with complete response (CR), the duration of response is the __ time.

A
  1. Disease free interval time
  2. to disease progression
  3. Disease free survival time
55
Q

Toxicities in chemotherapy are evaluated using the __. There are 24 categories organized by __ and __, with 5 grades (0 being the lowest).

A
  1. Common Toxicity Criteria (CTC)

2. pathophysiology and anatomy

56
Q

At CTCAE Grading level 1, we would __. At grade 2, we would __. At grade 3 and 4, we would make treatment modifications i.e. __.

Common Terminology Criteria for Adverse Events (CTCAE)

A
  1. proceed with treatment
  2. monitor while proceeding with treatment
  3. changing dose intensity or providing prophylaxis
57
Q

__ toxicities often are objective, with clear guidelines to with-hold treatment or delay, while __ toxicities are often subjective with variable individual thresholds.

A
  1. Hematological

2. Non-Hematological

58
Q

Karnofsky Performance Status is a measure of __. It runs from 0% (dead) to 100% (fully normal functions).

A

level of activity of which a patient is capable

59
Q

ECOG Performance Status is a simple, commonly used measure. It runs from grade 0 (equivalent to KPS _%) to grade 4 (equivalent to KPS _%). We usually would not start treatment if the patient is at ECOG grade __.

A
  1. 90-100%
  2. 10-20%
  3. 3 and above

Cancer managment (4 decks)

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