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Medical Oncology SCE > Scientific Basis of Malignancy > Flashcards

Scientific Basis of Malignancy Flashcards

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USMLE® Step 1 flashcards
1
Q

What are the instructions before and after PET-CT?

A

Patients are asked not to drink for 4-6 hours prior to scan, ensure CBG controlled prior and avoid children and pregnant women for the rest of the day.

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2
Q

What is the half life of FDG tracer?

A

70 minutes

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3
Q

What is the definition of Gy?

A

Absorption of energy (in Joules) per kg of matter

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4
Q

What is the inverse square law?

A

The principle that the dose reduction in radiation energy with distance is inversely proportional to the increase in distance from a radiation source.

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5
Q

What is the equivalent square in radiation?

A

Used to determine the equivalent field size of a radiation square if it is not square itself.

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6
Q

When is scatter factor applied?

A

When considering the effect of scattered electrons on a radiation beam hitting the surface of an object as the radiation beam is attenuated by the differential density of a new material or tissues

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7
Q

What does the linear quadratics equation describe?

A

Relationship between cell survival and delivered ionising radiation.

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8
Q

What are the alpha and beta values?

A

Describe the cells sensitivity to radiation. Alpha-beta ratio describes the fractionation sensitivity of the cells.

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9
Q

What does a high alpha/beta ratio mean?

A

Cells are less sensitive to the sparing effects of fractionation

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10
Q

What does a low alpha/beta ratio means?

A

Describes a tumour where there is a greater cell kill per unit dose at higher doses.

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11
Q

What is the CTV?

A

A volume encompassing the visible tumour or tumour bed with a margin to account for subclinical spread

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12
Q

What is the GTV?

A

A volume encompassing visible tumour on planning scan

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12
Q

What is the PTV?

A

Planning target volume which is added to the CTV to take into account for variations in patient set up and additional uncertainties.

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13
Q

What is the ITV?

A

Internal target volume which is used in 4D treatments to account for on treatment movement of the tumour (ie in a lung tumour during respiration)

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14
Q

What is the mechanism for radiation induced cell death in solid tumours?

A

Mitotic catastrophe, dsDNA breaks can causes lethal chromosomal aberrations which result in failure of chromosomal separation during anaphase and telophase.

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15
Q

What is the mechanism for radiation induced cell death in haematological malignancy?

A

Apoptosis

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16
Q

What are the benefits to fractionation?

A

Allows for re-oxidisation of cells (oxygen sensitises to RT), redistribution (movement of cells through different phases of cell cycle, some of which are more radiosensitive) and repair of normal tissues.

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17
Q

Which type of therapy does this refer to? ‘Using heavy proteins that can penetrate to variable depths of tissue dependent upon their energy and the energy is depositive at an accurate position preserving local normal structures.’

A

Proton therapy

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18
Q

What therapy does this describe?
‘Electrons are accelerated to high energy with linear accelerators that when they strike a target produce photons targeted at the tumour target volume?’

A

Photon therapy

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19
Q

What therapy does this describe?
‘Delivered through a linear accelerator for superficial targets to try and minimise damage to deeper tissues’

A

Electron therapy

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20
Q

What are advanced therapy medicinal products?

A

Medicines based on tissues, genes or cells.

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21
Q

What unit does NICE use to evaluate cost effectiveness of new medications?

A

Units of effectiveness expressed in cost per QALY gain (cost-utility analysis)

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22
Q

How quickly should the drug be available in your trust once approved by NICE?

A

90 DAYS

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23
Q

What is effect modification in the realms of trials?

A

When there is a third variable that inflenced the outcome of a study (a difference between the groups results in a true difference between the outcome)

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24
Q

What are confounding factors in a trial?

A

A factor that may be unevenly distributed amongst the randomised groups and may be responsible for the outcome rather than the variable being tested.

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25
Q

What is the first signal for a T cell in order to activate?

A

T cell binds to antigen as it is held in MHC complex on surface of antigen presenting cell. This released inflammatory cytokines.

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26
Q

What is the second signal required to activate T helper cell?

A

Interaction of CD28 or T cell with B7.1 or B7.2 (CD 80.86) on APC resulting in T cell proliferation.

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27
Q

Which cells are involved in regulating the interaction between CD28 on T cell and CD80/86 (B7.1/B7.2) on an APC?

A

CTLA4 and PD1 proteins (immune checkpoint molecules)

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28
Q

Where are PD1 cells expressed?

A

On several immune cells but highly expressed on T cells

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29
Q

Where are PDL1 cells expressed?

A

Tumour cells

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30
Q

What question is Chi-square test used to determine?

A

Whether there is a statistically significant difference between expected and observed frequencies in one of more group. Used in categorical data.
Similar to Fishers test but less exact.

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31
Q

What is T test used to compare?

A

Either two continuous variable for the same population (paired T test) or two unrelated groups (independent T test)

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32
Q

What is the purpose of a phase 0 trial?

A

Exploratory trial to facilitate demonstration of drug-target engagement with a selected biomarker.

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33
Q

What is the purpose of a Phase 1a trial?

A

Assess safety and tolerability of a drug, phase 1a involves dose escalation to determine maximum tolerated dose

34
Q

What is the purpose of Phase 1b trial

A

Following on from Phase 1a where maximum tolerated dose is determined, in Phase 1b cohort expansion is undertaken at one or more dose level to determine phase II dose

35
Q

What is the 3+3 dosing model in Phase 1 trials?

A

Cohorts of 3 patients at escalating dose levels. If 1/3 has a dose limiting toxicity then 3 more people are enrolled. If 1/6 has DLT then proceed to next dose escalation. If >1/6 then stop.

36
Q

What is the purpose of phase 2 trials?

A

To assess efficacy.

37
Q

What is the purpose of Phase 3 trials?

A

Larger cohort to compare new treatment to the standard of care.

38
Q

In clinical trials what is considered an adverse reaction?

A

An adverse event which is considered to have a causal relationship to the trial treatment. Adverse event is not considered to have a causal relationship.

39
Q

What is classed as a serious event/reaction in clinical trials (6 examples)?

A

Includes death, life threatening event, inpatient hospitalisation or prolongation of hospitalisation, persistent or significant incapacity of normal life or congenital abnormality.

40
Q

Who must be informed of a serious event during a clinical trial and in what time frame?

A

The sponsor must be informed with 24 hours for anyone who has consented to involvement in the trial, even if they have not started a treatment.

41
Q

Describe the trial design of a Basket study?

A

Targeted therapy is evaluated in multiple disease sites that have common molecular alterations (ie. pan tumour NTRK mutations)

42
Q

Describe the trial design of a Crossover study

A

Participants are randomly assigned to the study drug or placebo for a certain intervention period then switch to the alternative for a second intervention period

43
Q

Describe the trial design of an Umbrella study

A

Evaluates multiple targeted therapies for a single disease that is stratified into subgroups based of molecular alterations

44
Q

Describe the trial design of a case control study

A

Two study groups are compared, one has the disease or condition and one dose not. Very prone to recall bias.

45
Q

Describe PD in the context of the RECIST criteria

A

> 20% increase in sum of longer diameter or new lesions (must have 5 lesions to compare)

46
Q

Describe partial response in the context of the RECIST criteria

A

> 30% reduction in sum of all maximum tumour diameter

47
Q

What is the definition of PFS in clinical trials?

A

Time from inclusion in study to progression or death. Measure of efficacy.

48
Q

What does a confidence interval of 95% mean?

A

Accepting 5% chance that the incorrect conclusion was reached.

49
Q

What is the probability of a Type 1 error (false positive result) equivalent to?

A

P value (0.05) or Alpha

50
Q

What is beta in statistics?

A

The probability of a type II error occurring (false negative)

51
Q

With a hazard ratio of 0.68 for death at 5 years, how might you describe this to a patient?

A

Reduction in risk of death at 5 years by 32%.

52
Q

What can lead to a falsely high hazard ratio?

A

Population at risk group being too small.

53
Q

How do you calculate sensitivity of a test?

A

Proportion of patients correctly diagnosed by the test. Proportion of patients tested positive/total number of patients with the disease

54
Q

How do you calculate specificity of a test?

A

Proportion of health patients correctly receiving a negative test. Number of patients who test negative and do not have the condition/total number of patients who tested negative for the condition.

55
Q

How do you calculate an odds ratio?

A

Odds of exposure in cases/odds of exposure in controls

56
Q

What is Level 1 evidence?

A

One large RCT of good quality or meta-analyses of well conducted RCTs.

57
Q

What is level 2 evidence?

A

Small RCT or large randomised trials or meta-analyses with suspicion of bias

58
Q

What is level 3 evidence?

A

Prospective cohort studies

59
Q

What is level 4 evidence?

A

Retrospective cohort studies or case control studies

60
Q

What is Level 5 evidence

A

Studies without controls, case report or expert opinions

61
Q

On a forrest plot what is the line of null effect?

A

Line is placed at the value where there is no association between outcome and exposure.

62
Q

How do you interpret the point estimate of a study on a Forrest plot?

A

Bigger the square = bigger the study, line is 95% confidence interval. If crosses the line of null effect then true value could be null effect.

63
Q

What does a diamond on the Forrest plot represent?

A

Combined point estimate and confidence intervals of all the studies.

64
Q

How do you compare the heterogeneity of the studies on the Forrest plot?

A

Using statistical test called I-square of 12. If value >50% then may mean that studies are inconsistent for another reason that isnt chance.

65
Q

Name the two different censoring events that may be demonstrated on a Caplan Meier curve?

A

Uninformed censoring when patients did not reach the endpoint of the trial or informed censoring if patient dropped out of the trial therefore event never reached.

66
Q

In patients with brain metastases when may re-licensing (driving) be considered?

A

At 1 year if stable disease with no new sites.

67
Q

When does somnolenc syndrome typically present post WBR?

A

8-12 weeks following completion

68
Q

When would SRS (gamma knife) be fractionated)

A

If close to important structures, large lesions or volumes.

69
Q

What is the maximum total volume of treatment in SRS?

A

<20CC, usually 2cm is the upper limit for single metastases

70
Q

What is the percentage of people who with achieve local control with SRS?

A

80%

71
Q

SRS is commisioned according to which 5 criteria?

A

HPS >70, PS 0 or 1, total volume <20CC, absent or controllable extracranial disease, life expectancy >6m

72
Q

When would neurosurgery be preferable over SRS?

A

Large brain mets with mass effect/neurological symptoms. Particularly with posterior fossa locations.

73
Q

What is the difference between Steven Johnson Syndrome and TEN?

A

SJS affects <10% and TEN affects >30%

74
Q

How do you treat Myasthenic syndrome caused by IO

A

Supportive, pyridostigmine, plasma exchange/IVIGs

75
Q

In which malignancies is CAR-T cell therapy used?

A

ALL, DLBCL, primary mediastinal large B cell lymphoma and mantell cell lymphoma.

76
Q

How does cytokine release syndrome typically present?

A

Fever, tachycardia, increase RR, low BP and hypoxia

77
Q

What percentage of patients develop ICANS following CAR-T cell therapy and how does it present?

A

Up to 10%
Tremor, dysgraphia, dysnomia and impaired attention.

78
Q
A
79
Q

What is the difference between predictive and prognostic biomarkers?

A

Predictive biomarker gives information about the effect of a therapeutic intervention whereas a prognostic biomarker gives information about g the patients overall cancer outcome

80
Q

How do you calculate positive predictive value?

A

True test positive/those testing positive with the new test

81
Q

How do you calculate the negative predictive value?

A

Tells us about the accuracy of a negative test. Those testing negative that were negative/all those that tested negative.

82
Q

How to you calculate relative risk reduction?

A

Control event rate-exposure event rate/control event rate

Medical Oncology SCE (27 decks)

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