Intro to Oncology Flashcards
1
Q
What is the lifetime probability of developing cancer?
Males?
Females?
A
Both sexes = 45%
Males = 45%
Females = 44%
2
Q
What are the 5 most common cancer deaths?
A
- Lung
- Colorectal
- Pancreas
- Breast
- Prostate
3
Q
What are the top 4 most commonly diagnosed cancers in 2024 in males?
A
- Prostate
- Lung
- Colorectal
- Bladder
4
Q
What are the top 4 most commonly diagnosed cancers in 2024 in females?
A
- Breast
- Lung
- Colorectal
- Uterine
5
Q
Define incidence
A
Number of new cases diagnosed with cancer in a specific period
6
Q
Define mortality
A
Number of cancer deaths in a specific period
7
Q
Define rates
A
Divide by population (expressed per 100,000)
8
Q
Define prevalence
A
Total number of people with cancer at a specific time
9
Q
What are 3 non-modifiable risk factors for cancer?
A
- Age >65
- Sex
- Genetics
10
Q
What are some modifiable risk factors for cancer? (8)
A
- Tobacco
- Sun exposure
- Alcohol consumption
- Physical inactivity
- Diet
- Obesity
- Vaccination (HPV, hepatitis)
- Minimizing exposure to radiation (healthcare), outdoor/indoor air pollution, radon gas
11
Q
What are the major characteristics of cancer cells? (4)
A
- Exhibit uncontrolled growth
- Ability to invade surrounding tissue
- Exhibit decreased cellular differentiation
- Ability to metastasize
12
Q
What are the characteristics of a benign tumor? (6)
A
- Some degree of growth control
- Encapsulated (non-invasive)
- Localized
- Typical of cell of origin (differentiated)
- Indolent (slow growth)
- Non-recurrent
13
Q
What are the characteristics of a malignant tumor? (6)
A
- Uncontrolled growth
- Invasive
- Metastatic
- Atypical (anaplastic, less differentiated)
- Aggressive (faster growth)
- Recurrent
14
Q
Tumor grading determines ______________
Tumor staging determines ______
A
aggressiveness
extent
15
Q
In tumor staging, what does T, N, and M stand for?
A
T = size of primary lesion
N = presence of lymph node involvement
M = presence of identifiable metastases
16
Q
Cancer grading and staging is important for (4)
A
- Prognosis
- Treatment planning
- Exchange of information
- Evaluation of treatment
17
Q
What are the 5 pillars to cancer therapy?
A
Act at tumor/cancer cell level:
1. Surgery
2. Radiation
3. Cytotoxic
4. Targeted Therapies
Act at patient level:
5. Immunotherapy
18
Q
Surgery is the most effective cancer treatment for what?
When is it not effective/feasible?
A
Solid tumors
1. Largely ineffective for metastasized or disseminated (blood/lymph or hematologic) cancers
2. Often not feasible for very large tumors
19
Q
Simply explain how radiation therapy works (2)
A
- Rapidly dividing cells are very sensitive to ionizing radiation; cancer cells preferentially destroyed due to higher growth rate
- Radioligand therapy (radiopharmaceuticals)
20
Q
Simply explain how drug (or systemic) therapy works (3)
A
- Utilized for disseminated / metastasized cancers and for treatment of micro-metastatic disease
- Different types of drug therapy utilized
- High Dose Chemotherapy & Stem Cell Transplant
- Utilized primarily for hematologic cancers
21
Q
Simply explain how immunotherapy works (1)
A
(Vaccines, monoclonal antibodies, CAR-T, T-cell engagers)
Engages the patient’s own immune system to destroy cancer cells
22
Q
Define cytotoxic drugs (chemotherapy)
A
Interfere with or damage DNA
23
Q
Define targeted drug therapy
A
Block, inhibit, attack specific proteins that are involved in the molecular processes driving tumor cell growth
- e.g., endocrine (hormone) therapies, Mab’s (monoclonal antibodies, TKI’s (tyrosine kinase inhibitors)
- Personalized medicine: if target can be identified in patient, referred to as personalized drug therapy
24
Q
Define immunotherapy
A
Activate one’s immune system against a cancer
- Vaccines, monoclonal antibodies, CAR-T, T-cell engagers (e.g., BiTE)
25
What is growth fraction (mitotic rate)? (3)
1. # cells in cycle / total # cells in tissue
2. Higher growth fraction early in tumor growth
3. Growth fraction decreases as tumor gets larger
- Cells become farther away from blood vessels and nutrient supply; accumulation of toxic metabolites; less cell to cell communication = may not be able to divide
26
What is the MOA of cytotoxic drugs? (5)
MOA of cytotoxic drugs is to interfere with synthesis or function of DNA/RNA causing ‘apoptosis’ or programmed cell death
1. Target is the processes within the cell cycle
2. Cause crosslinking and DNA strand breaks, leading to
abnormal base pairing, inhibiting transcription of DNA to RNA, and stopping protein synthesis and cell division
3. Occurs in all cells, but primary effects on rapidly dividing cells which do not have time for DNA repair
4. Cancer cells are among the most affected because they are among the most rapidly dividing cells
27
Explain how apoptosis works (3)
1. p53 suppressor gene (“guardian of the genome”)
2. Senses genomic damage; halts cell cycle and initiates DNA repair; if irreparable damage, p53 initiates cell death process or apoptosis
3. Process of apoptosis is the end result of irreparable damage to DNA caused by cytotoxic drugs
28
Cycle specificity is important primarily for dosing and scheduling. What to know about cell cycle specific drugs? (2)
1. Effective against cells in process of division
2. Most effective in tumors with high growth fraction
- Phase-specific agents:
* Also called ‘schedule-dependent drugs’
* Most effective in multiple repeated doses
- Phase non-specific agents:
* Can inflict damage at any point in cell cycle
* ‘Dose-dependent’ drugs
29
Cycle specificity is important primarily for dosing and scheduling. What to know about cell cycle non-specific drugs? (3)
1. Some activity against resting cells
2. ‘Dose-dependent’
3. Used in large tumors with low growth fraction
30
What are the goals of systemic therapy? (3)
1. Cure
- Elimination of all known tumor cells
2. Improve survival
- Tumor control
- Delay time to recurrence
3. Palliation
- Reduce tumor-related symptoms; improve quality of life; some tumor control
31
What are some common clinical trial endpoints in cancer? (4)
1. Response rate (RR)
- Complete response (CR), partial response (PR), stable disease (SD), progressive disease (PD)
2. Survival
- Overall survival (OS) is gold standard
- Surrogate endpoints for OS include:
* Progression-free survival (PFS), disease-free survival (DFS), relapse-free survival (RFS)
3. Quality of life (QoL)
4. Safety
32
What is induction chemotherapy? (2)
1. Primary treatment
2. Usually applied in hematologic malignancies; also applicable for advanced disease (1st line)
33
What is adjuvant chemotherapy? (2)
What is the goal?
1. Drug treatment given after primary tumor is controlled by definitive local treatment, e.g. surgery or radiation
2. Patient is clinically free of cancer, but at high risk for relapse (tumor re-growth)
3. Goal is CURE - destroy undetectable cancer cells
34
What is the premise of adjuvant chemotherapy? (2)
1. Microscopic, clinically undetectable cancer cells remain after surgery or radiation or at a distant metastatic site
2. These smaller populations of cancer cells are more susceptible to chemo and may be eradicated:
- Better vascular supply for drug penetration
- Higher growth fraction
- Not as diverse genetically, less resistance
35
Adjuvant chemotherapy - aggressive chemotherapy treatments often used, but what are the disadvantages? (2)
1. Cannot assess response
2. Short and long-term risk of aggressive chemo
36
What is consolidation therapy?
Treatment of subclinical, residual disease – term often applied in treatment of hematologic malignancies (e.g. leukemias) therapy after induction therapy has produced a complete remission
37
What is neo-adjuvant chemotherapy?
Use of drug therapy prior to local treatment, e.g., surgery or radiation
38
What is the goal of neo-adjuvant chemotherapy?
Increase effectiveness of local treatment by reducing tumor burden and destroying undetectable cancer cells susceptible to chemotherapy that may have metastasized early (also curative intent)
39
What is the advantage of neo-adjuvant chemotherapy?
Can evaluate response to the chosen chemotherapy drugs
40
What is maintenance therapy? (2)
1. Longer term, usually lower dose therapy, used to decrease recurrence rate, or progression rate
2. Can be used in both curative and non-curative settings
41
What is salvage therapy?
Treatment of relapsed (recurrent after previous control) or refractory (unresponsive to treatment) disease
42
What is local chemotherapy?
Local instillation of anticancer drugs
e.g. CSF, bladder instillation, intra-cavitary for malignant effusions, chemo-embolization of hepatic artery
43
What is the purpose of local chemotherapy? (3)
1. Deliver chemotherapy to relatively inaccessible sites
2. Provide high local concentrations
3. Avoid systemic toxicity
44
What is Conditioning Therapy prior to stem cell transplant (SCT)?
What is the premise?
1. High doses of cytotoxic drug(s) given – lethal to bone marrow
- Rescue with a SCT (autologous or allogeneic) with WBC growth factor (G-CSF) support
2. Premise: high doses overcome resistance of tumor to chemotherapy
45
What are the barriers to conditioning therapy? (2)
1. Patient age/fitness
2. Toxicities (acute and long-term)
46
What is lymphodelpleting therapy prior to CAR T-cell Rx?
Reduces the number of existing lymphocytes in the patient's body, creating space for the infused CAR T-cells to effectively expand and fight cancer cells
47
What are some common chemotherapy toxicities to be aware of? (5)
1. Bone marrow suppression, risk of infection (neutropenia)
2. Mucositis, stomatitis
3. Hair loss or thinning (alopecia)
4. Nausea or vomiting
5. Fatigue
48
What are the advantages for combination chemotherapy? (3)
1. Higher cell kill
2. Different MOA: heterogeneity of tumor
3. Prevent or slow development of tumor resistance
49
What are the disadvantages to combination chemotherapy? (3)
1. Multiple toxicities
2. May have to dose reduce in combination - compromised efficacy?
3. More complicated to administer
50
What is the goal of combination chemotherapy?
Balance increased efficacy with tolerable toxicity
- Sequential vs. concurrent
51
What are we thinking about when it comes to selection of drugs in chemotherapy? (5)
1. Show clinical activity against the tumor alone
2. Different MOA; more effective
3. Minimally overlapping toxicities
4. No cross resistance between drugs
5. Synergistic in combination
52
Initial dosage protocol of chemotherapy may be modified based on: (4)
1. Curability of tumor (less aggressive if non-curable)
2. Overall performance status (fitness)
3. Renal/liver function
4. Prior therapies (e.g. aggressive chemo or RT) – less able to
tolerate aggressive dosing)
53
Ongoing dosage modifications for chemotherapy may be required as patients proceed through treatment. Why? (2)
1. Usually for toxicity/tolerability concerns
2. Possible reduced efficacy?
54
Schedule of chemotherapy - planning interval between doses takes into account: (3)
1. Recovery of host tissue toxicity
2. How fast the tumor is growing (e.g. doubling time/ growth fraction)
3. MOA of drug: cell cycle specificity
55
Duration of chemotherapy:
How long for adjuvant treatment?
How about advanced disease?
1. Adjuvant: prescribed # of cycles and duration
2. Advanced disease: commonly given until evidence of disease progression (i.e. based on response and disease control) or as long as toxicity can be managed
56
Why does chemotherapy treatment sometimes fail? (6)
1. Toxicity to normal cells - dose limiting
2. Patient co-morbidities limit effective dosing
3. First order kinetics of cell kill
4. Failure to detect tumor in early stage
5. Limited drug access to tumor site
6. **Main reason is drug resistance - inherent or acquired**
57
What is tumor cell heterogeneity? (drug resistance) (2)
1. Spontaneous genetic mutations occur in tumor cell populations without exposure to drugs
2. Larger tumor masses have more mutations and a higher probability of drug-resistant cell lines
58
What is de novo drug resistance?
Abnormal p53 suppressor gene in some cases
59
What is selected drug resistance?
Resistant cells in a heterogeneous population become predominant
60
What is acquired drug resistance?
Examples?
Cells develop mechanisms of drug resistance, examples:
- Enzymes to inactivate drug
- P-glycoprotein: pump drug out of cell
- Enzymes to repair drug damage to DNA
- Mutation in protein receptor
- Another molecular pathway becomes dominant
61
Endocrine therapies are useful for hormone-sensitive cancers, such as: (3)
1. Prostate
2. Breast
3. Uterine (endometrial)
62
What is the goal of targeted drug therapy?
Improve efficacy and avoid the severe toxicities to normal cells from traditional cytotoxic chemotherapy
63
What are the types of targeted drug therapies? (2)
1. Monoclonal antibodies targeting tumor receptors
2. Small molecule, tyrosine kinase inhibitors (TKI’s)
64
How do small molecule compounds ("-nibs") work?
Act within a cancer cell to interfere with key proteins (produced by abnormal genes) in pathways essential to disease progression
- Example: imatinib, dasatinib
65
How do monoclonal antibodies ("-mabs") work?
Block extra-cellular proteins (antigens) or receptors outside the cell or on the cell surface that are involved in essential cancer cell functions (also may be used to deliver toxins to the cancer cell)
- Example: rituximab, trastuzumab
