RPA MONC Flashcards
Adjuvant chemotherapy in stage 2 colon cancer
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)
what agent causes peripheral neuropathy in FOLFOX
Oxaliplatin
Duration of adjuvant therapy in stage 3 colon cancer
6 months for high risk (T4 N2)
and 3 months in low risk
capecitadine SE
(prodrug of 5FU)
palmer planter erythema
what is the most useful clinical situation to test CEA
recurrence of bowel cancer
or monitoring of metastatic disease who produces this protein
AE of bevacizumab
HTN, proteinuria, thromboembolism, bleeding, leukopenia
EGFR in colon cancer vs lung cancer
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
Cetuximab rash
rash means response
which colorectal patients benefit from immunotherapy
MMR deficient (pembrolizumab)
where do bowel cancers metastasis first cf rectal cancer
bowel cancer drain through the portal system to the liver first where as rectal cancer go to lungs
surveillance program after colon cancer
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
breast tissue density
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
high scoring criteria for manchester scoring for genetic testing for breast cancer
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
BRCA1 mutation breast cancers hormone markers
majority triple negative (69% vs 15% in general population)
BRCA2 mutation breast cancers hormone markers
more similar to general population
77% ER positive 16% triple negative
bilateral risk reducing mastectomys in BRCA1/2
reduction by 90%
due to mets prior to mastectomy or microremnants
bilateral risk reducing salpingooperectomy (BRRSO)
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
breast cancer risk modification w genetic predisposition
SERMS - 33% relative reduction
but assos risk of increased endometrial ca
aromatase inhibitors - works in post menopausal people. Reduces RR by ~ half
who might benefit from US with mammography
younger women, smaller and denser breasts
but generally not much evidence for US
MRI screening for breast cancer
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
what must be done in conjunction w WLE in breast cancer
radiotherapy to get the same benefits w mastectomy
when is postmastectomy radiotherapy considered
<40yr, >4cm primary, >4 lymph nodes, positive surgical margins
early stage breast ca treatment
surgery - WLE vs mastectomy radio therapy - always w WLE, w high risk mastectomy chemotherapy ?herceptin endocrine therapy monoclonal antibodies
prognostic markers in ealry stage breast cancer
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
most aggressive early breast cancer syndrome
basal like
“triple negative”
most benefit from adjuvant therapies
histology subtypes of breast cancer
ductal vs lobular (lower grade, ER+)
other types: endocrine responsive, high risk endocrine responsive, low risk endocrine non responsive)
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
which endocrine therapy block steroidogenesis
aromatase inhibitors
which endocrine therapy block receptors in breast tissue
SERMS - tamoxifen
first choice estrogen receptor positive breast cancer endocrine therapy post menopausal
aromatase inhibitors
AE of aromatase inhibitors
vasomotor symptoms, myalgias, mood change, osteoporosis
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
AE of SERMs
vasomotor symptoms
DVT
endometrial cancer
which endocrine therapy is better for bone
SERM as ER agonist in bone thus osteoprotective
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
endocrine therapy in premenopausal women
ovarian suppression w GnRH agonist in conjunciton w aromatase inhibitor
duration of trastuzumab
1 year
transtzuzumab emtansine
used in histological setting if there is residual disease if neoadjuvant therapy did not work
it’s chemotherapy attached to monoclonal
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
molecule risk analysis in breast cancer
oncotype dx
patented 21 gene expression assay
predictive value to response to chemotherapy
denosumab as adjuvant in breast cancer
osteoporosis dose
improved disease free survival
used in high risk group
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)
palbociclib and ribociclib
CDK4/6
metastatic breast cancer ER/PR+
used w fulvestrant
metabolised by CYP3A4
pertuzumab
see slides
which BRCA carries higher chance of breast cancer in men
brca2 7% (BRCA1 1%)
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)
MAP kinase pathway
RAs-> raf -> mek -> erk
which stimulates MF
BRAF mutated melanoma cells - MAP kinase pathway effects
upregulation of RAF
B-raf mutation prevalence melanoma
50% melanoma
B-raf inhibitor toxicity
rash fatigue photosensitivity arthralgias SCCs
what toxicity is not present when you use BRAF/MEK inhibitor dual combination
no SCCs
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
markers for doing poorly metastatic melanoma (3)
elevated LDH
high tumour burden
intracranial mets
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.
vismodigid
treat metastatic basal cell carcinoma via inhibition of sonic hedgehog
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
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)
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
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
MOA of abiraterone
inhibitors CYP17 irreversibly
can get upstream accumulation of steroid precursors causing hypokalaemia
give 10mg prednisolone indefinitely
see slides
MOA of enzalutamide
antiandrogen
broader mechanism of action than older antiandrogenics
metastatic prostate disease - chemotherapy
upfront chemotherapy docetaxel w GnRH agonist
used in high risk (>3 bone mets)
sequencing of therapy for metastatic prostate disease
abiraterone before enzalutamide
what type of renal cell carcinomas are the most common
clear cell
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).
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
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
pazopanib AE
pazopanib more likely LFT derangement and all hair turns white
Sunitinib AE
sunitinib more likely diarrhoea, rash, hypertension
first line therapy for poor prognosis in metastatic RCC
immunotherapy
RCC and radiotherapy
generally radioresistant but may be fairly effective for symptom palliation
bladder cancer cell
transitional cell epithelium
so renal tract cancers get same treatment
Bladder cancer staging
muscle invasive vs non muscle invasive
whether or not it invades through muscularis propriate
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
muscle invasive bladder cancer treatment
neoadjuvant or adjuvant chemo
cystectomy or radical radiotherapy
testicular cancer histology classification
seminoma -aFP always normal
non seminoma - AFP elevated
which testicular cancer have elevated AFP
non seminoma
staging of testicular germ cell cancer
stage 1 - testicles
stage 2 - nodal spread
stage 3 - metastasis
management of stage 1 testicular germ cell tumours
orchidectomy
seminoma - radiotherapy or chemo or surveillance
non-seminoma - chemo or surveillance - RADIO DOES NOT WORK
bleomycin AE
pneumonitis
Which testicular ca does not respond to radio
non seminoma
stage 1 testicular ca with beta HCG >5000 or AFP >10000
brain MRI
li-fraumeni syndrome
p53 mutation
38 fold increase in lung ca
what lung ca is familial retinoblastoma assoc w
small cell lung cancer
high yield to reduce tobacco use
increase tobacco tax
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
size of lung nodule that is significant of causing mortality
> 6mm
some smaller ones could still be cancer in their infancy though
what PET scan to use in lung cancer
PDG pet scan
glucose w radioactive isotope
what lung cancer is more assoc w smokers
squamous cell carcinoma
which lung cancer is more PD1/PDL1 positive
squamous cell carcinoma
what is the location of squamous cell carcinomas
central
commonest lung cancer in on smokers
adenocarcinoma (but smokes are still more common)
small cell lung cancer histology/characteristics
almost always assoc w smoking
neuroendocrine staining
central
aggressive
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
small cell extensive treatment
chemotherapy 4-6 cycles platinum based drug
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
what size of lung cancer would you not consider adjuvant therapy
<5mm
stage IV NSCLC no driver mutation treatment
chemo/immunotherapy
which type of lung cancer have driver mutations
not squamous cell carcinona
EGFR TKI availbale
erlotinib
gefitinib
afatinib
osimertinib (t790M and at relapse)
EGFR TKI AE
rash - predictor of response
GI symptoms
rarely pneumonitis
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
what TKI EGFRs have with less rash
osimertinib and newer generation TKIs as they are selective for mutant EGFRs
what TKI EGFRs is associated with prolonged QT interval
osimertinib
crizotininib
what is the most common mutation to acquire in 1st line TKI resistance
T790M
crizotinib AE
alk inhibitor + ros1
Visual disturbance
QT prolongation
pneumonitis
what can be used in combo with aromatase inhibitors for metastatic breast cancer
ribociclib and palbociclib
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
oral hydromorph to parentral hydromorphone
3:1
metastatic seminoma germ cell tumour prognosis
very good prognosis (>80% at 5 yr even in very advanced metastatic disease)
what thyroid cells are affected in medullary thyroid cancer
C cells - calcitonin producing
what is the most common type of thyroid cancer
papillary
what type of thyroid cancer doesn’t respond to to radioiodine
medullary cancers
when to perform lobectomy in papillary thyroid cancer
stage I only
larger tumours need iodione and radioablation
