Principles of Cancer treatment Flashcards
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
1
Tumor growth is ___ during the __ phase. It will exhibit a __ which may increase at a later stage.
- logarithmic
- initial
- constant doubling time
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.
- immunosuppression
2. early lag
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 __.
- log
2. below the detection limit
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 __.
- ~1g or 10^9
- 1g or (10^10 cells)
- grow quickly
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 __.
- plateau
2. limited space for growth
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.
- cell division to cell loss
- growth fraction
- vasculature
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 __.
- longer: (2-3months vs. 24h)
- Large variations
- speed of cancer growth
The initial phase of metastasis is characterized by __. The second phase of invasion and movement occurs __. The final phase of anchorage occurs via __.
- dissolution of the basement membrane by lytic enzymes released by tumor cells eg proteases
- 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
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.
- the blood and lymphatic system
2. 1/3
Common (to many solid tumors) metastatic sites include: l\_\_, l\_\_, l\_\_, b\_\_, b\_\_, s\_\_, a\_\_
- liver
- lung
- lymph nodes
- bone
- brain
- skin
- adrenal glands
Metastatic pattern varies with tumor type: i.e. Colon cancer to __ and prostate cancer to __.
- liver
2. bone
Treatment of cancers with secondary metastatic disease is more complex because __. Treatment efficiency is best when the ___ or when we can arrest __.
- we need to tx both primary and secondary tumors
- tumor burden is small with a high growth fraction
- angiogenesis
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 __.
- curative
- symptomatic relief
- quality and duration of life
- there are no longer any registered therapeutic options left
Ideally, anti-cancer treatment should be safe, __with few side effects. We want to return the patient to __.
- discriminating towards cancer cells
2. former state of health
Surgery is curative for __ cancers and is important in diagnosis, staging (finding extent of involvement), __, reconstruction and __.
- localized
- relief of symptoms
- prevention
Surgery can be an adjunct to other forms of cancer treatment by __. Particularly in hormonal therapy/ectopically expressed hormones, surgery can __.
- reducing size of tumor to increase efficacy
2. remove the source
Radiation destroy cancer cells by __ and selectively destroys __. Radiocurability depends on the size, location, type and radiosensitivity of tumor.
- generating free radicals to damage DNA
2. cells in rapid division
Radiation therapy may be delivered externally or via brachytherapy/interstitial brachytherapy where __. The dose is measured in __ (energy absorbed in treatment volume).
- radiation (implants) that are placed very close to or
inside the tumor - Gray (Gy)
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.
- fractionated
- normal tissue damage
- rapidly dividing tissues
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).
- total body irradiation
2. obstruction and pain
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 __.
- treatment of systemic or disseminated disease (including micro-metastases)
- endocrine or biologic
- actively dividing cells
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.
- kill a constant proportion of cells rather than a constant number
- Earlier treatment
- narrow
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: ____
- high
- delayed
- long-term
- avoid treating those who are already cured
If the intent is to extend life, our tolerance of side effects is __ and our concern is on __. We would typically administer treatment when __.
- moderate
- value of added time
- added time outweighs side effects
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.
- low
- symptom control
- giving treatment improves QoL
- Long term toxicities
Combination chemotherapy can improve treatment outcomes as it achieves _______, _____ against multiple cell lines and __________ of resistant cell lines.
- Max cell kill within acceptable toxicity
[increased sensitivity with lowered doses (toxicity)] - broadens coverage
- slows down the emergence
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.
- multiple toxicities (more side effects) and greater pt discomfort
- complicated/expensive
- impact of dose effect
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.
clinical trials (empirically)
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.
- constituents
- synergistic combinations
- dose, schedule and duration
Chemotherapy agent doses are almost always in __ due to it providing a more accurate __ and being more closely correlated to __.
- Body surface area (BSA)
- cross-species comparison of activity and toxicity
- cardiac output (determines liver and kidney blood flow), influencing elimination.
The formula for BSA calculation is __. It is critical to verify __ to avoid dosing errors.
- BSA (m^2) = sq root[weight (kg) x height (cm)/3600]
2. potentially inaccurate BSA
Administration schedules are typically designed to __, along a ‘drug rest’ period to allow __ (empirically determined in clinical trials).
- achieve maximum therapeutic benefit with minimal toxicity
2. normal cells to recover
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 __.
- treatment response
- reducing the interval
- increasing the dose
- in threatening toxicities
Dose intensity adjustments for chemotherapy are typically done to __ or __ (alongside appropriate supportive treatment).
- reduce toxicity
2. reflect new changes in clinical evidence
The stepwise consideration for chemotherapy selection begins with __, __, consideration of ___ and ___ related variables, before moving onto toxicity (risk vs benefit) considerations.
- histology
- staging
- prognostic and patient
__ of drug, protocol, site/blood supply of tumor, __ (PK factors) of patient and __ all contribute to chemotherapy response.
- Efficacy
- elimination
- tolerance
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.
- cannot prevent relapse of resistant cell lines
- avoid using the same drugs again
- to overcome resistance
Cancer cells may exhibit various mechanisms of resistance similar to bacteria which include:
- __ (transport)
- __ (reducing active levels)
- __ (reducing concentration)
- __ (recovery)
- __ (avoidance)
- Decrease in cellular uptake or increase in efflux of drug
- Decrease in drug activation
- Increase in drug degradation
- Increase ability to repair DNA
- Use alternate biochemical pathways
Desirable characteristics for combination therapy:
- Effectiveness i.e. __
- Different __
- No antagonism
- Agents should be given in a dose equivalent to that used when the drug is given alone
- Different __
- Increase the overall intensity of therapy
- have > 20% response rate when used alone
- dose limiting toxicities
- MOA
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.
- metastasis and drug resistance
- non-proliferating
- drug distribution
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.
- central necrosis in large tumors
2. CNS, testis
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.
- ECOG Performance Status Criteria
2. Karnofsky Performance Status Criteria
Immunocompromised patients tend to have a poorer prognosis as __. As such, __ should be avoided.
- they typically require a reduction in dose intensity
2. immunosuppressant use for minor ailments
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 __.
- affecting drug exposure duration
2. empirical (~25%)
__ is the most common dose limiting toxicity for chemotherapy. Therefore, prior __/__ can result in accumulative damage, __ to avoid life threatening aplasia..
- Myelosuppression
- Chemotherapy/Radiotherapy
- lowering the dose intensity of subsequent treatment
Myelosuppression recovers more slowly among __ patients but good __ and __ status allows for safe full dose administration.
- aged
- major organ function
- nutritional
Cancer patients with certain concomitant diseases (i.e. __) may be harder treat.
DM, dialysis
Neoadjuvant chemotherapy is commonly given before surgery to eradicate __, debulk the tumor, reducing the __ and __ of surgery.
- micro-metastases
- extent
- disfigurement
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 \_\_.
- complete disappearance of all clinical evidence
- at least 1 month
- Performance status
Partial Response (PR) refers to __ tumour, with no new area of disease and __. The measurement can be made using diameter (longest breadth and length).
- > or = 50% decrease of measurable
2. no evidence of progression
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 \_\_.
- increase of measurable tumour by >25%,
- of new lesion
- does not increase or decrease in size by >25%
In literature, the reporting of Overall response rate or objective response rate refers to __.
Clinical Benefit refers to __.
- Complete Response (CR) + Partial Response (PR)
2. Complete Response (CR) + Partial Response (PR) + Stable Disease (SD)
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.
- Disease free interval time
- to disease progression
- Disease free survival time
Toxicities in chemotherapy are evaluated using the __. There are 24 categories organized by __ and __, with 5 grades (0 being the lowest).
- Common Toxicity Criteria (CTC)
2. pathophysiology and anatomy
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)
- proceed with treatment
- monitor while proceeding with treatment
- changing dose intensity or providing prophylaxis
__ toxicities often are objective, with clear guidelines to with-hold treatment or delay, while __ toxicities are often subjective with variable individual thresholds.
- Hematological
2. Non-Hematological
Karnofsky Performance Status is a measure of __. It runs from 0% (dead) to 100% (fully normal functions).
level of activity of which a patient is capable
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 __.
- 90-100%
- 10-20%
- 3 and above
