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FRACP Shuyu > RPA MONC > Flashcards

RPA MONC Flashcards

1
Q

Adjuvant chemotherapy in stage 2 colon cancer

A

very small benefits (1-5%) w adjuvant chemotherapy
but previous studies showed superior response in FOLFOX (vs 5FU) which resulted in significant peripheral neuropathy

(MOSAIC study 2007)

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2
Q

what agent causes peripheral neuropathy in FOLFOX

A

Oxaliplatin

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3
Q

Duration of adjuvant therapy in stage 3 colon cancer

A

6 months for high risk (T4 N2)

and 3 months in low risk

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4
Q

capecitadine SE

A

(prodrug of 5FU)

palmer planter erythema

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5
Q

what is the most useful clinical situation to test CEA

A

recurrence of bowel cancer

or monitoring of metastatic disease who produces this protein

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6
Q

AE of bevacizumab

A

HTN, proteinuria, thromboembolism, bleeding, leukopenia

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7
Q

EGFR in colon cancer vs lung cancer

A

in lung cancer, small molecule TK EGFR-1 inhibitors are used in patients with EGFR mutations

where as in colon cancer, EGFR mabs are used if they are RAS (KRAS/NRAS) wildtype

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8
Q

Cetuximab rash

A

rash means response

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9
Q

which colorectal patients benefit from immunotherapy

A 
MMR deficient
(pembrolizumab)
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10
Q

where do bowel cancers metastasis first cf rectal cancer

A

bowel cancer drain through the portal system to the liver first where as rectal cancer go to lungs

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11
Q

surveillance program after colon cancer

A

first 2 years: 3 monthly CEAs + physical exam + 1-2 CT scans/year + colonoscopy at anniversary then 3-5 years after diagnosis then every 3-5 years after that

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12
Q

breast tissue density

A

dense tissue makes it more difficult for mammography and US to see cancer; more likely to present at a later stage
high risk from increased glandular tissue to fatty tissue

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13
Q

high scoring criteria for manchester scoring for genetic testing for breast cancer

A

the scoring is the sum of all first degree relatives on 1 side:

breast cancer age <30 +11
ovarian cancer <59 13
ovarian cancer >59 10
bilateral breast cancer

HER2 -4
LCIS -4

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14
Q

BRCA1 mutation breast cancers hormone markers

A

majority triple negative (69% vs 15% in general population)

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15
Q

BRCA2 mutation breast cancers hormone markers

A

more similar to general population

77% ER positive 16% triple negative

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16
Q

bilateral risk reducing mastectomys in BRCA1/2

A

reduction by 90%

due to mets prior to mastectomy or microremnants

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17
Q

bilateral risk reducing salpingooperectomy (BRRSO)

A

important to remove fallopian tubes as most “ovarian cancers” actually arise from cells in the fimbriae of the fallopian tube
80% risk reduction of ovarian cancer

guidelines recommend BRRSO 35-40 in BRCA 1 and to 45 in BRCA 2

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18
Q

breast cancer risk modification w genetic predisposition

A

SERMS - 33% relative reduction
but assos risk of increased endometrial ca

aromatase inhibitors - works in post menopausal people. Reduces RR by ~ half

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19
Q

who might benefit from US with mammography

A

younger women, smaller and denser breasts

but generally not much evidence for US

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20
Q

MRI screening for breast cancer

A

familial breast cancer (identified gene mutation or not) or radiotherapy for hodgkin lymphoma

reduces risk of stage 2 or high er Br Ca in this group by 70% risk reduction

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21
Q

what must be done in conjunction w WLE in breast cancer

A

radiotherapy to get the same benefits w mastectomy

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22
Q

when is postmastectomy radiotherapy considered

A

<40yr, >4cm primary, >4 lymph nodes, positive surgical margins

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23
Q

early stage breast ca treatment

A 
surgery - WLE vs mastectomy
radio therapy - always w WLE, w high risk mastectomy
chemotherapy ?herceptin
endocrine therapy
monoclonal antibodies
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24
Q

prognostic markers in ealry stage breast cancer

A 
tumour grade
nodal status
HER2 status
tumour size
ER/PR status
age at diagnosis
gene assay (oncotype DX) - how well you are likely to response to chemotherapy
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25
most aggressive early breast cancer syndrome
basal like "triple negative" most benefit from adjuvant therapies
26
histology subtypes of breast cancer
ductal vs lobular (lower grade, ER+) other types: endocrine responsive, high risk endocrine responsive, low risk endocrine non responsive)
27
chemotherapy regimens for early stage breast cancer
AC-T Doxorubicin and Cyclophosphamide, Followed by Paclitaxel or Docetaxel. TC docetaxel and cyclophosphamide dose dense regimens are more toxic but more effective at reducing cancer recurrence
28
which endocrine therapy block steroidogenesis
aromatase inhibitors
29
which endocrine therapy block receptors in breast tissue
SERMS - tamoxifen
30
first choice estrogen receptor positive breast cancer endocrine therapy post menopausal
aromatase inhibitors
31
AE of aromatase inhibitors
vasomotor symptoms, myalgias, mood change, osteoporosis
32
5 yr to 10 yr aromatas inhibitor
10 years HR 0.66 of recurrent disease or contralateral de novo breast cancer however no change in overall survival increased risk of osteoporosis MA17R trial
33
AE of SERMs
vasomotor symptoms DVT endometrial cancer
34
which endocrine therapy is better for bone
SERM as ER agonist in bone thus osteoprotective
35
Adjuvant therapy of in situ disease
women who did not have invasive disease (in situ) were resected and given adjuvant therapy recent data that low dose SERM for 3 years reduces 5 year development of invasive breast cancer from 11% to 6.4% the thought is that people who develop insitu cancers are at higher risk of developing more breast cancers moreover, there is a small effect on stopping any remnant disease to metastasise
36
endocrine therapy in premenopausal women
ovarian suppression w GnRH agonist in conjunciton w aromatase inhibitor
37
duration of trastuzumab
1 year
38
transtzuzumab emtansine
used in histological setting if there is residual disease if neoadjuvant therapy did not work it's chemotherapy attached to monoclonal
39
difference of MOA of neratinib vs trastuzumab
trastuzumab stops dimerization of HER2 receptors on the surface HER2 only causes effect if it dimerizes however there is escape mechanisms - e.g. if HER2 dimerizes with other HER molecules neratinib is a pan-HER TKI
40
molecule risk analysis in breast cancer
oncotype dx patented 21 gene expression assay predictive value to response to chemotherapy
41
denosumab as adjuvant in breast cancer
osteoporosis dose improved disease free survival used in high risk group
42
fulvestrant
selective estrogen receptor downregulator use w aromatase inhibitor better than aromatase inhibitor alone (but high risk disease is now used w aromatase inhibitor w GnRH)
43
palbociclib and ribociclib
CDK4/6 metastatic breast cancer ER/PR+ used w fulvestrant metabolised by CYP3A4
44
pertuzumab
see slides
45
which BRCA carries higher chance of breast cancer in men
brca2 7% (BRCA1 1%)
46
triple negative liver metastatic breast ca treatmnet
chemotherapy not CDK4 visceral mets is like threatening and more aggressive and should use agents w anti mitotic effects (E.g. Paclitaxel) rather than antimetabolite effects (e.g. capecitabine)
47
MAP kinase pathway
RAs-> raf -> mek -> erk | which stimulates MF
48
BRAF mutated melanoma cells - MAP kinase pathway effects
upregulation of RAF
49
B-raf mutation prevalence melanoma
50% melanoma
50
B-raf inhibitor toxicity
``` rash fatigue photosensitivity arthralgias SCCs ```
51
what toxicity is not present when you use BRAF/MEK inhibitor dual combination
no SCCs
52
why does PD-1 have action on the tumour environment compared with CTLA-4
normally when t cells are upregulated, the cancer cells will produce more PDL1, which was a way to get around the CTLA4 however, the PD-1 inhibitor was still able to act on it
53
markers for doing poorly metastatic melanoma (3)
elevated LDH high tumour burden intracranial mets
54
sonic hedgehog
implicated in BCC The hedgehog gene in the HH pathway codes for an extracellular protein, the sonic hedgehog (SHH) protein. SSH binds to the cell membrane receptor complex to start a cascade of cellular events leading to cell proliferation.
55
vismodigid
treat metastatic basal cell carcinoma via inhibition of sonic hedgehog
56
prostate cancer confined to the prostate management
risk stratify - tumour grade, size, extension, volume, PSA - predicted survival low risk -> active surveillance or observation intermediate/higher risk -> stage w CT CAP and WBBS and if truly local disease than radical prostatectomy or prostate radiotherapy (<74yr) then survey w 6 monthly PSAs
57
Prostate cancer recurrence
biochemical recurrence is common can contemplate salvage radiotherapy can consider imaging including PSMA PET if PSA >0.2 as if there is spread salvage radiotherapy wil be futile adjuvant antiandrogen therapy for 24mo (see slides)
58
metastatic prostate therapy management
GnRH agonists can have a pulse sudden increase in FSH, LH, testosterone with GnRH agonism, can flare metastatic prostate disease cover w GnRH antagonist
59
role of antiandrogens in metastatic prostate cancer
bicalutamid, nilutamide adjunct to GnRH agonists/antagonists as second line therapy for non metastatic castrate sensitive prostate cancer and historically for castrate resistant prostate cancer
60
MOA of abiraterone
inhibitors CYP17 irreversibly can get upstream accumulation of steroid precursors causing hypokalaemia give 10mg prednisolone indefinitely see slides
61
MOA of enzalutamide
antiandrogen | broader mechanism of action than older antiandrogenics
62
metastatic prostate disease - chemotherapy
upfront chemotherapy docetaxel w GnRH agonist | used in high risk (>3 bone mets)
63
sequencing of therapy for metastatic prostate disease
abiraterone before enzalutamide
64
what type of renal cell carcinomas are the most common
clear cell
65
what are VHL mutations
in clear cell variants in RCC small arm of chromosome 3 mutation/complete loss of 3p causes hypoxia inducible factors which causes transcription of the hypoxia inducible genes (inc VGEF).
66
poor prognostic factors for metastatic risk in RCC
less than 1 yr from diagnosis to systemic therapy karnofsky less than 80 high calcium anaemia neutrophil higher than the upper limit of normal (high immunogenecity) plt higher than the upper limit of normal
67
first line therapy for favourable prognosis in metastatic RCC
sunitinib and pazopanib chose based on toxicity profile pazopanib more likely LFT derangement and all hair turns white sunitinib more likely diarrhoea, rash, hypertension
68
pazopanib AE
pazopanib more likely LFT derangement and all hair turns white
69
Sunitinib AE
sunitinib more likely diarrhoea, rash, hypertension
70
first line therapy for poor prognosis in metastatic RCC
immunotherapy
71
RCC and radiotherapy
generally radioresistant but may be fairly effective for symptom palliation
72
bladder cancer cell
transitional cell epithelium so renal tract cancers get same treatment
73
Bladder cancer staging
muscle invasive vs non muscle invasive | whether or not it invades through muscularis propriate
74
non muscle invasive bladder cancer treatment
single dose intravesical chemotherapy if high grade, can give adjuvant immunotherapy BCG - raises IL-12, IFN-gamma stimualte Th1 activation and CD8+ cytolytic T cells increases intracellular NO levels, inhibiting tumour growth
75
muscle invasive bladder cancer treatment
neoadjuvant or adjuvant chemo | cystectomy or radical radiotherapy
76
testicular cancer histology classification
seminoma -aFP always normal | non seminoma - AFP elevated
77
which testicular cancer have elevated AFP
non seminoma
78
staging of testicular germ cell cancer
stage 1 - testicles stage 2 - nodal spread stage 3 - metastasis
79
management of stage 1 testicular germ cell tumours
orchidectomy seminoma - radiotherapy or chemo or surveillance non-seminoma - chemo or surveillance - RADIO DOES NOT WORK
80
bleomycin AE
pneumonitis
81
Which testicular ca does not respond to radio
non seminoma
82
stage 1 testicular ca with beta HCG >5000 or AFP >10000
brain MRI
83
li-fraumeni syndrome
p53 mutation | 38 fold increase in lung ca
84
what lung ca is familial retinoblastoma assoc w
small cell lung cancer
85
high yield to reduce tobacco use
increase tobacco tax
86
screening for lung cancer
low dose CT showed mortality benefit 20% reduction in RR however only 0.5% reduction in absolute risk ?cost effective currently not recommended in Australia
87
size of lung nodule that is significant of causing mortality
>6mm some smaller ones could still be cancer in their infancy though
88
what PET scan to use in lung cancer
PDG pet scan | glucose w radioactive isotope
89
what lung cancer is more assoc w smokers
squamous cell carcinoma
90
which lung cancer is more PD1/PDL1 positive
squamous cell carcinoma
91
what is the location of squamous cell carcinomas
central
92
commonest lung cancer in on smokers
adenocarcinoma (but smokes are still more common)
93
small cell lung cancer histology/characteristics
almost always assoc w smoking neuroendocrine staining central aggressive
94
small cell limited treatment
1 half of lung and sometimes the mediastinum (whether you can get a radiotherapy field around it w curative extent) concurrent chemoradiotherapy consider prophylactic crabial irradiation
95
small cell extensive treatment
chemotherapy 4-6 cycles platinum based drug
96
stage IIIb NSCLC
mediastinum involved but probably not curable w surgery limited to thorax tx: chemoradiotherapy chemotherapy followed by chemoradiotherapy practice changing last 18 months is addition of immunotherapy
97
what size of lung cancer would you not consider adjuvant therapy
<5mm
98
stage IV NSCLC no driver mutation treatment
chemo/immunotherapy
99
which type of lung cancer have driver mutations
not squamous cell carcinona
100
EGFR TKI availbale
erlotinib gefitinib afatinib osimertinib (t790M and at relapse)
101
EGFR TKI AE
rash - predictor of response GI symptoms rarely pneumonitis
102
treatment of TKI rash
grade 1 - topic emollients/steroids grade 2 - topical steroid cream + smollients grade 3 - doxycycline + topical steroid if rash is not improving or progressing, then TKI is stopped until this improves to a grade 1 and consideration of dose reduction
103
what TKI EGFRs have with less rash
osimertinib and newer generation TKIs as they are selective for mutant EGFRs
104
what TKI EGFRs is associated with prolonged QT interval
osimertinib | crizotininib
105
what is the most common mutation to acquire in 1st line TKI resistance
T790M
106
crizotinib AE
alk inhibitor + ros1 Visual disturbance QT prolongation pneumonitis
107
what can be used in combo with aromatase inhibitors for metastatic breast cancer
ribociclib and palbociclib
108
what is the proportion of metastatic castrate resistance prostate cancer whose disease will harbour a homologous recombination DNA repair?
30% HRD is homologous with a BRCA mutation
109
oral hydromorph to parentral hydromorphone
3:1
110
metastatic seminoma germ cell tumour prognosis
very good prognosis (>80% at 5 yr even in very advanced metastatic disease)
111
what thyroid cells are affected in medullary thyroid cancer
C cells - calcitonin producing
112
what is the most common type of thyroid cancer
papillary
113
what type of thyroid cancer doesn't respond to to radioiodine
medullary cancers
114
when to perform lobectomy in papillary thyroid cancer
stage I only | larger tumours need iodione and radioablation

FRACP Shuyu (65 decks)

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