ASCO Review Flashcards
Anal cancer staging T1 vs T2 and treatment
T1 <2, T2 2-5 cm
Treat T1 with local excision unless high risk features like poorly differentiated
otherwise chemo/rads with 5-FU mitomycin
After definitive treatment recheck with DRE and anoscopy when
if residual disease then
8-12 weeks DRE and anoscopy
if residual disease, salvage surgery with APR (abominoperineal resection) removes anus, rectum and necesitates ostomy
Treatment lines metastatic anal cancer
carbo/taxol preferred first line
Then nivo or pembro
then 5-FU/cis, FOLFOX, DCF
incidentally found gallbladder adenocarcinoma on cholecystectomy, T size at which surgical oncologic staging is needed.
T1b or higher (muscle layer not lamina propria should have
CT CAP to r/o mets
then go back to surgery for hepatic resection, lymph nodes, bile duct excision
treat with adjuvant capecitabine especially if positive nodes
First line treatment for biliary tract malignancies
check for which targetable mutations
other lines
cis/gem + durvalumab (ABC-02 trial showed sig survival benefit in all comers), if immotherapy CI, then still give cis/gem
check for NTRK, MSI-H, RET (selpercatinib), BRAF V600E (dabrafenib/trametinib), FGFR2 fusions or rearrangements (pemigatinib/futibatinib), IDH1 (ivosidenib), HER2 (trastuzumab+pertuzumab_
other chemo
FOLFOX
gem/abraxane
which patient with cholangio is a candidate for liver transplantation as a curative option
unresectable perihilar or hilar cholangio, <3 cm, no mets, no nodes
PSC or other underlying liver disorders are ok
Pemigatinib moa, use and risks
FGFR2 fusion or rearrangement
cholangio and others
GI toxicity, hyperphosphatemia, occular toxicity (must see eye doctor regularly corneal and retinal issues)
Futibatinib moa, use risks
compare to pemigatinib
FGFR2 gene fusion or rearrangement
irreversible FGFR1-4 inhibitor
resistance to acquired resistance mutations to other inhibitors, maybe less occular SE
BRAF mutation in colon ca significance
poor prognosis, they will be KRAS wt
FOLFIRI Bev is an option
encorafenib+cetuximab or panitumumab can be tried after oxali therapy
Adjuvant treatment for colon cancer by stage and other factors
Stage III disease favor FOLFOX/CAPEOX over 5-FU alone
for low risk stage III (<T4, <N2): 3 months of CAPEOX or 3-6 mo FOLFOX (reduced neuropathy)
For high risk group stage III (T4 N1 or N2): 6 months FOLFOX
However, Age >70 (stage II or III), no added benefit of FOLFOX vs 5-FU. 6 mo of 5-FU.
In stage II, survival benefit not demonstrated for FOLFOX over 5-FU
- therefore unless high risk factors present, would do 5-FU alone
Colon cancer oligometastatic disease treatment
resect primary and resect or radiate oligomets, treat with adjuvant FOLFOX for 6 mo
stage II colon cancer (T,N) indications for chemo
T3-4 N0
T3 invades through muscularis (but not into visceral peritoneum or other
adj organs T4)
Adj chemo if:
not MSI-H and
T4
or
T3 with high risk: poorly differentiated, LVI, PNI, bowel obstruction or perforation, <12 LN evaluated, positive margin, tumor budding
anti-EGFR therapy in colon cancer, who gets it
left sided tumors that are KRAS/NRAS/BRAF WT
First line treatment for metastatic colon cancer by molecular markers
FOLFOX bevacizumab
FOLFOX cetuximab for (KRAS/NRAS/BRAF WT and Left)
MSI-H: pembro or dostarlimab or nivo or ipi/nivo
FOLFIRINOX bev if visceral disease and young
subsequent lines of therapy in colon metastatic disease
if progressed on cetuximab regimen switch to bevacizumab regimen
FOLFOX–>FOLFIRI
HER2- Trastuzumab+ pertuzumab/lapatinib/tucatinib or ENHER2
KRASG12C: sotorasib or adagrasib + cetuximab
Lonsurf +/- bev
regorafenib 80 mg start with uptitration to 160 days 1-21
lonsurf MOA and use
trifluridine and tipiracil (thymidine phosphorylase inhibitor which prevents degredation)
2 mo OS benefit
suveillance by stage colon
Stage I–> colonoscopy only
Stage II-III
colo in 1 year
then CEA Q3-6 for 2 years then every 6 for 5 years
CT CAP every 6-12 mo for 5 years
IV oligo mets- CT every 3-6 mo for 2 years then every 6-12 for 5
significance of subserosal tumor deposits in colon cancer staging
upstages to stage III even in the absence of node positivity
pseudomyxoma peritonei
low-grade mucinous carcinoma with diffuse peritoneal involvement
observe vs resect and HIPEC
GEJ tumors are treated like what
esophageal adenocarcinoma
esophageal staging, define T 4a vs T4b and why important
T4a- involves the pericardium, pleura, diaphragm, peritonieum, azygous vein
T4b- involves trachea, great vessels, vertebral body or heart
T4b are unresectable but if not metastatic could be treated with definitive chemo/rads (5-FU and oxaliplatin)
barretts esophagus predisposes to what. Treat with RFA at what level of barretts.
esophageal adenocarcinoma
treat high grade dysplasia with RFA
low grade dysplasia can be treated with PPI/repeat EGDs
esophageal adenocarcinoma localized treatment by stage
difference for esophageal squamous
MSI-H
Tis (high grade dysplasia, T1a= endoscopic resection/ablation
T1b= submucosal invasion
T2= muscularis
T1b- T2 low risk <3 cm well differentiated: surgery
cT2 with high risk (>3 cm mass, LVI, poorly differentiated) or nodes or T3-T4a; preop chemo/rads (carbo/taxol weekly for 5 weeks or FOLFOX 3 cycles every 2 weeks with radiation)
PET before surgery!
cT4b: definitive chemo-rads
PET before surveillance, if persistent, then surgery if possible
Squamous: same as above up for Tis and T1a
cT2N0 high risk, nodes, cT3-4: pre-operative chemo/rads (carbo/taxol) or definitive chemo/rads
cT4b= definitive chemo/rads
MSI-H:
- neoadjuvant or perioperative checkpoint inhibitor therapy
cervical esophageal cancers treatment and definition
<5c from cricopharyngeous muscle should be treated with definitive chemo/rads due to difficulty with surgery in that area
indication for bronchoscopy as a part of the work up in esophageal cancer
cancer at or above carinoa, bronchoscopy performed to rule out a fistula
GEJ cancer, could consider what for staging
laparoscopy as these tumors are more high risk for occult metastatic disease
adjuvant therapy in eosphageal cancer with surgery upfront (no chemo or rads)
R0 node negative or positive: surveillance
R1 or R2 resection: chemo/rads 5-FU/oxaliplatin
adjuvant therapy in esophageal cancer with upfront chemo or rads
R0 with CR: observation
R0 without CR: nivolumab
R1 or R2: chemo/rads with FOLFOX preferred (only if RT not given upfront)
lymph nodes during surgery considered adequate
colon versus esophageal versus gastric
12 vs 15 vs 15
metastatic esophageal adenocarcinoma treatment
what actionable mutations to check to decide first line
how does this change for squamous
HER2
- FOLFOX+ trastuzumab +/- pembro
MSI-H
- pembro
- dostarlimab
- ipi/nivo
- FOLFOX with nivo or pembro
PD-L1 CPS <5
FOLFOX
PD-L1 CPS>5
- FOLFOX and nivo
PD-l1 CPS>10
- FOLFOX and pembro
Squamous
- FOLFOX + nivo regardless of CPS
- FOLFOX pembro (still CPS>10)
- FOLFOX alone
- ipi/nivo
second line for esophageal adeno
special order for GEJ
HER2 next lines
squamous
docetaxel
paclitaxel
irinotecan
FOLFIRI
ramucirumab/paclitaxel or ramucirumab alone for EGJ only (cat 1)
lonsurf in 3rd line EGJ only (cat 1)
ENHER2 if HER2 overexpressing
Squamous:
- if no immunotherapy before then give nivo
then the same as above
esophageal follow up plan after definitive treatment
visits 3-6 mo for 2 years
imaging or EGD is not recommended without symptoms
who gets adjuvant therapy in gastric cancer after surgery without and what do you give
pT3, pT4, or N+
5-FU x1, 5-FU chemo/rads, then 5-FU x3 if not a complete D2 dissection
if complete D2 dissection then 6 mo XELOX
R1 or R2 resection: FOLFOX chemo/radiation
metastatic gastric adeno treatments and targets to test
No targets:
- FOLFOX
PD-L1 CPS>5
- FOLFOX with nivolumab
HER 2
- FOLFOX and trastuzumab +/- pembro
MSI-H
- pembro
- dostarlimab
- ipi/nivo
- FOLFOX with nivo or pembro
metastatic gastric adenocarcinoma second and subsequent lines
2nd line all cat 1
Ramucirumab +/- paclitaxel
Docetaxel
Paclitaxel
Irinotecan
FOLFIRI
3rd line
Lonsurf (cat 1)
HER 2
- Enhertu
Hereditary diffuse gastric cancer presentation and mutation/inheritance, treatment
AD mutation in CDH1
young gastric cancer with lifetime risk of 70-80%
women risk of lobular breast cancer, also prostate cancer
prophylactic total gastrectomy versus intense screening
Localized gastric cancer treatment by stage
cT1 surgery or ER
T2= invades into muscularis propria
resectable cT2 or higher perioperative chemotherapy (FLOT sandwich)
Restage with PET prior to surgery
unresectible cT2 or higher: chemorads or neoadj chemo
restage with PET and surgery if possible or surveillance
ramicirumab moa
VEGFR2 antagonist (receptor blocker)
bevacizumab MOA
VEGF-A antibody
diffuse seborrheic keratoses aka leser-trelat sign
paraneoplastic development of seborrheic keratoses in GI malignancies also breast and lymphomas
milan transplant criteria for HCC
single tumor 2-5 cm or <3 measuring <3 cm in size
no macrovascular involvement
no extrahepatic extension
AFP <1000
Child pugh C treatment options
tremelimumab+ durva does not restrict by child-pugh
no other options indicated
LI-RADS criteria apply only to patients with cirrhosis or chronic hepatitis
CT or MRI multiphasic with arterial phase hyperenhancement and delayed phase washout or enhancing capsule appearance
<1 cm lesions should be monitored on repeat US
sorafenib child pugh
B7
HCC treatment by line in metastatic disease
1st: atezo bev (child pugh A)
tremelimumab+durva
or sofafenib, lenvatinib, durva pembro
2nd line
regorafenib (A)
cabozantinib (A)
Ramucirumab (AFP>400 and A)
lenvatinib (A)
sorafenib (B7)
nivo (B)
ipi/nivo (A)
pembro (A)
which HCC drug has a AFP cut off and what is it
RAMUCIRUMAB APF >400
local therapy for HCC, use and criteria
use if liver-only disease, not a resection or transplant candidate
ablation for <3 can be curative, 3-5 is for prolongation of survival
> 5 cm should be considered for arterial-directed therapy such as chemoembolization or radioembolization (Y90)
- contraindicated if bili >3
radiation is also option
adjuvant treatment for pancreatic adeno s/p resection
mFOLFIRINOX or gem+ cape
elderly: gem or 5-FU bolus with lecovorin
blood antigen associated with no production of CA19.9
lewis antigen
resectability of a pancreatic adeno by vessel involvement, which ones are bad
resectable
- no contact with celiac, common hepatic artery or AMA
<180 contact with SMV or portal
unresectable with >180 of
- SMA
- celiac
- contact with aortic
- tumor thrombus in SMV/PV
borderline
- contact with common hepatic
- SMA <180
- celiac <180
- SMV or PV >180
- IVC contact
treatment for metastatic pancreatic adeno
first line
- gem
- gem erlotinib
- FOLFIRINOX
- gem/abraxane
2nd line (NOT FOLFIRINOX in 2nd line technically)
- gem/abraxane
- capcitabine
- gemcitabine
confusing drug used in pancreatic adeno treatment different between adjuvant and metastatic
gem cape important in adjuvant but gem abraxane is favored in metastatic
olaparib for pancreatic adeno
germline BRCA1 or 2
first-line platinum-based chemo
stable disease for 16 weeks
olaparib maintenance
germline genetic testing in pancreatic adeno when
anyone with the diagnosis
immunotherapy for MSI-H pancreatic adeno
pembro, dostarlimab
rectal cancer local therapy by stage
T1- transanal local excision
T1-2- transabdominal resection
T3 N0 low risk high- TAR
T3-4 or N any–> check MMR status
if pMMR: total neoadjuvant therapy with chemo/RT then chemo or vise versa then restage then surgery
Or now if eligible for sphincter sparing surgery do FOLFOX, restage, surgery or chemo/rads if poor response then surgery
for rectal, After TAR, what is adjuvant therapy for:
T1
T2
T3
N1
T1-2 observe
T3 or N1 chemo RT then chemo or vice versa
bevacizumab and surgery
bevacizumab avoid in
6-8 weeks
Stroke, MI, TIA, bleeding
rectal cancer local and metastatic MSI-H
treatment of metastatic disease that is MSS
local dMMR checkpoint inhibitor therapy for up to 6 months with restaging every 2-3 months
surveillance or if persistent chemo/RT and TAR
checkpoint inhibitor if dMMR and metastatic
normal MSS:
- treat like colon cancer
- test same markers
- EGFR therapy indicated if KRAS wt as these are left sided
head and neck cancers of the lip localized treatment
surgical resection
no neck dissection if T1-3, dissect if N2c bilateral
adj radiation if high-risk features like close margin, LVI/PNA, N2/3 nodes, T3/4 primary
consider chemo/rads if pos margins, extra nodal extension
WHO nasopharyngeal SCC subtypes (3) and treatment if local or metastatic
type 1 keratinizing EBV (USA #1)
type 2 non-keratinizing differentiated
type 3 (bad) undifferentiated non-keratinizing most common and EBV +
T1- RT to nose and neck
T2- RT +/- chemo with high risk
N1 or N3 chemo/rads or induction
T3-4 N1-3 induction then chemo/rads preferred (cat 1) gem/cis or 5-fu/cis/doce if induction and EBV
metastatic cis/gem +/- pembro or nivo
head and neck PET restage after radiation timeline
12 weeks or 4 months
hypopharyngeal SCC (glottic larynx) treatment differs how
T4a is invasion of the thyroid cartilage
T4a is treated with surgery and neck dissection and thyroidectomy
T4b is treated with chemo/rads and invades the prevertebral fascia, encases the carotid, involves the mediastinal structures
head and neck metastatic disease first-line
testing for actionable mutations
PD-L1 testing and foundation one
all comers: pembro/cis or carbo/5-FU
PD-L1 CPS>1 can give pembro alone
other options if not immunotherapy candidate includes cetuximab/cis or carbo/5-FU
head and neck chemo RT options
induction options
cisplatin
carbo
carbo/5-FU
cetuximab
induction: 5-FU/cisplatin/docetaxel (no survival benefit)
Second-line options head and neck metastatic
if no prior immunotherapy: nivo or pembro
otherwise:
carbo/docetaxel or paclitaxel/cetux
docetaxel
cetuximab
paclitaxel
IVA thymoma chemo option
cisplatin, doxorubicin, cytoxan induction then surgery, adjuvant chemo and radiation
oral cavity local treatment by stage
T1-2: surgery or definitive RT
- resect primary and neck direction or SLN biopsy
- no nodes or high risk observe
- node without other high risk–>RT
- high risk features like close margin, T3-4, N2-3, PNI/LVI: RT
-very high risk features extranodal extension or positive margin: chemo/RT
T3-T4a N1-3: surgery still preferred with neck dissection
- high risk features guide adjuvant as above
head and neck oropharynx local treatment by stage
T1-2 N0-1 surgery and high risk feature adjuvant assessment or RT alone
T3-4 N0-1 chemo/RT or surgery with neck dissection with adj RT or chemo/RT by risk factors
N2-3 chemo/RT or surgery with adj RT or chemo/RT by risk factors
define oropharynx
base of tongue, tonsil, posterior pharyngeal wall, soft palate
HPV+ staging difference versus HPV-
N3 disease (large node >6) is still stage III versus IVB
treatment of localized NUT midline carcinoma
surgery + adjuvant chemorads
thymic carcinoma treatment unresectable or metastatic
unresectable- chemo/rads with carbo/taxol
met carbo/taxol
define hypopharynx and treatment by stage
pyriform sinus, posterior pharyngeal wall, post-cricoid area
T1-2 low risk RT or surgery
T2-3 N0-3 induction chemo or surgery or chemo/rads
T4a–> surgery!!!
T4b–> chemo/rads
PD-L1 level for single agent pembro in head and neck
PD-L1 CPS> or equal to 1
gardasil version for HPV head and neck prevention
gardasil 9, 9 HPV types, 9 valent
adenoid cystic carcinomas local and metastatic treatment
local- surgery, adjuvant radiation with high-risk features including intermediate grade or T3-4 disease (pretty much all get adjuvant RT)
combination chemo with cisplatin, vinorelbine, gem, doxorubicin, cyclophosphamide (avoid paclitaxel alone)
lenvatinib
test for NGS and HER2
Lung adenocarcinoma IHC typically
TTF-1 napsin A+
WT-1 is found on which tumors
mesothelioma, ovarian serous, wilms tumors, desmoplastic small round cell tumors
ovarian serous carcinoma IHC
CK7+/CD20-, PAX8+ WT1+ mesothelin+
mesothelioma IHC
CK7+, calretinin, WT1, CK5/6, mesothelin, D2-40
TTF-1 is found on what tumors
thyroid and lung
markers to to distinguish HCC from intrahepatic cholangio
albumin in situ hybridization and MOC3 negative in HCC
upper vs lower GI tumors IHC
Lower GI CK20+ CK7-
Upper usually CK7+ and CK20-
IHC for GIST tumor
CD117+ KIT+ CD99
IHC CDX2 location
GI tract
melanoma markers IHC
S-100, HMB-45, SOX11
TMPRSS2:ETS rearrangement is found in which tumor and gene mutation
prostate and PTEN
CUP with SCC in neck node should:
- test HPV, EBV, thyroid markers (PAX8, TTF-1, thyroglobulin)
- get full exam and pet and if primary is not found, then they undergo tonsillectomy bilaterally as this is the most likely primary source.
if negative, then neck dissection
if positive then treat per algorithm for oropharynx by stage
carcinoma markers IHC
pan-keratin (AE1/AE3), CAM5.2
squamous cell markers IHC
CK 5/6, p63, p40
germ cell tumors IHC
negative for CK7/CK20, OCT3/4, SALL4, CD30, Glypican-3, PLAP
gain of ch12p
mediastinal CUP treatment by age
<45 treat as high stage Germ cell tumor (VIP or BEP), >50 treat as NSCLC lung adeno
BRAF drug combos matched correctly
which combo can be used in adjuvant melanoma treatment
what should you check before starting
Vemurafenif/cobimetinib (skin issues and SCC of skin)
encorafenib/binimetinib
dabrafenib/trametinib (DT, pyrexia, CHF)
only DT can be used as adjuvant treatment in melanoma stage III only
EKG for QTc
c-kit mutations can be found in which solid tumors commonly
treatment option
mucosal melanoma
imatinib for kit exon 11 and 13
melanoma indications for SLNB
positive node next steps
stage IB T1b <0.8 ulcerated or 0.8-1
complete LN dissection or surveillance of the lymph node basin
melanoma staging and adjuvant treatment
Stage I-IIA
Stage IIb or higher treat with adjuvant pembro
- T3bN0 (>2 mm with ulceration or unspecified or >4mm without)
Stage III or higher treat with adjuvant pembro or braf therapy
- nodes made you III
- microsatellosis or intransit mets make you N1 or stage III
margin goals for melanoma
based on depth
1 cm margin for <1-2
2 cm margin for >2
merkel vs small cell lung cancer IHC
CK20 is positive in merkle cell
TTF-1 is negative in merkel cell and positive in small cell LC
vismodegib moa and use
SHH hedgehog pathway inhibitor used in basal cell carcinoma
virus associated with merkel cell
polyomavirus
adjuvant radiation option in melanoma when
head and neck location, neurotropism, pure desmoplastic subtype, close margins, local recurrence, extra capuslar extension, parotid node involved, >2 cervical or axillary nodes involved, >3 inguinalfemoral nodes,
PD-1 vs PD-L1 which immunotherapy is which and what is ipi and what is relatlimab
Nivo is PD-1
Pembro is PD-L1
ipi is CTLA-4
relatlimab is LAG-3
treat metastatic cutaneous SCC
pembro and cemiplimab (PD-1)
second line for metastatic Basal cell
cemiplimab (PD-1) but only after SHH therapy
MGMT mutation is what
good prognostic sign and a good likelihood of temodar response
grade 2 oligodendroglioma treatment
resection of tumor
low risk features age <40, observe
high risk features if >40 or subtotal resection, offer RT and adjuvant PCV x6 os and pfs benefit
WHO grade 3 oligodendromas treatment
resect and then treat with RT and then PCV x 6
HER2 FISH analysis
HER2 ratio <2 and copy number less than 4 is negative
HER2 ratio >2 and copy number >4 is positive
more complex in the middle with positivity definite as:
HER2 ratio <2 is positive if copy number is >6 and IHC 2+ or higher
HER2 <2 and copy number 4-6 with IHC repeated as 3+
Her2 >2 and copy number <4 if repeat IHC 3+
HER2 ratio <2 but copy number 4-6 equivocal, other testing ordered
generally when to recommend AI+ ovarian suppression
pre-menopausal, node positive or higher risk women
What is the oncotype cut-off for chemo for pre-menopausal and post-menopausal for node-positive and negative disease?
pre-menopausal:
- node-negative 16
- node-positive should get chemo regardless of oncotype score
post-menopausal
- 26 node negative
- 26 1-3 nodes positive
- always offer chemo >4 nodes
criteria for the addition of pertuzumab to TCHP per trial
tumor >2 cm in size
adjuvant her2 therapy if surgery first
tumor >1cm give adjuvant chemo with trastuzumab
if N+ given adj chemo with HP
if <1 cm can consider chemo with trastuzumab especially if HR-
management of pagets disease of the breast
> 90% of cases have occult malignancy, treat with mastectomy
sarcoma after breast radiation and treatment
angiosarcoma, treated with mastectomy or metastatic paclitaxel or AIM
antidepressants contraindicated in tamoxifen use
paroxetine or fluoxetine
role of bisphosphonate therapy in adjuvant setting
improved survival in post-menopausal patients (natural or induced)
zometa use if high risk of recurrence
oncotype less than what auto stages you to IA
11 or less
margetuximab-cmkb moa and use
4th line option for HER2+ metastatic BC, given with chemotherapy, it is a Fc engineered HER2 monoclonal antibody
Elacestrant moa nd use
ESR1 mutated metastatic breast cancer via guardant 360 testing, given as monotherapy after progression on one line of endocrine therapy
oral SERD
lynch syndrome cancers, genes, screening start
colon/gi, endometrial, ovarian
msh2, mlh1, msh6, pms2
age 20-25, 30s for MSH6
lifraumenti gene and cancers
p53 gene
sarcoma (esp osteosarcoma), breast, chroid pluexus, brain tumors, adrenocortical cancers
cowden syndrome, gene and cancer types
PTEN
breast, endometrial, colon, rcc, follicular thyroid
harmartomas, harmatoumatous polyps, skin tumors, macrocephaly, autism
Gardners FAP gene and issues, treatment
APC gene mutation
GI cancers, papillary thyroid
CHRPE congenital hypertrophy of the retinal pigment epithelium, benign bone tumors, desmoid tumors, hepatoblastoma, cysts, medulloblastoma (turcot syndrome)
treat with proctocolectomy, thyroid US, colo afed 10
peutz- jeghers gene and issues
STK11 cancer of breast, colon/GI, pancreas and sex cord stromal ovarian or sertoli testicular
harmartomatous polyps and hyperpigmented macules in the mouth, nose, eyes, genitals and fingers
BRCA 1gene, chromosome, risks
ch17, DNA repair, breast cancer exp triple negative, ovarian, melanoma, pancreas
MRI at 25, mammogram at 30
BSO by 35-40
BRCA 2, chromosome, risks
ch13, breast, ovarian, prostate, pancreas, melanoma
carney-stratakis syndrome triad, mutation
GIST, paragangliomas, pulmonary chondromas
SDH mutation
Gorlin syndrome mutation and issues
PTCH1 or SUFU tumor suppressors
basal cell carcinomas
mandibular tumors, jaw problems, prominent skull
meduloblastomas
MUTYH associated polyposis
germline MUTYH
test if >10 adenomas
older age than FAP and fewer polyps
recessive
juvenile polyposis syndrome mutation and presentation/screening
BMPR1A and SMAD4
colon polyps- harmatomatous
surveillance at age 12
SMAD 4 causes telangiectasias of the skin and nasal mucosa (epistaxis and rectal bleeding)
hereditary diffuse gastric cancer gene, inheritance, treatment
whats the other cancer risk and when does screening start
CDH1 e-cadherin
gastrectomy
lobular breast cancer, age 30
werner syndrome, gene and risk
WRN
premature aging
osteosarcoma and soft tissue sarcomas
CHEK2 mutations risk and screening
mammogram at 40
colonoscopy screening at 40
PALB2 mutation riskB and screening
breast cancer risk, screening at 30
slight ovarian cancer risk
pancreatic cancer
muir-torre syndrome is what and what risk
lynch syndrome + skin stuff (sebaceous gland adenomas and keratoacanthomas)
MLH and MSH2 with AD pattern
Turcot syndrome mutation and risk
lynch/FAP overlap
MLH PMS2 genes or APC!
colon cancer and brain tumors
emberger syndrome is what and what gene
GATA2 gene
deafness, lymphedema, leukemia syndrome
also cirrhosis, pancytopenia, cerebellar atropy
BAP-1 tumor syndrome
spitz tumors, uveal melanoma, mesothelioma, RCC, melanoma, basal cell
CDKN2 mutation carriers have what types of cancer and what else and what syndrome name
pancreatic cancer and melanoma
FAMMM syndrome familial atypical multiple mole melanoma syndrome
neurofibromatosis type 2 tumors
vestibular schwannomas or acoustic neuromas
MEN 1 which mutation and which cancers
menin mutation
parathyroid
pancreatic islet tumor
pituitary
MEN IIA mutation and cancers
RET mutation
medullary thyroid
pheochromocytoma
parathyroid
MEN IIB
RET
marfanoid
medullary thyroid
pheo
Men 4
CDNK1B
parathyroid adenoma
pituitary tumors
adrenal tumors
kidney cancer
testicular or reproductive cancers
RAD51c mutations risks and treatment
breast cancer screening at 40
~20% risk of ovarian cancer, BSO recommended 45
CMMRD presentation and gene
MMR gene mutation biallelic
early childhood cancers including brain tumors, leukemias and lynch spectrum cancers with many polyps
cafe au lait and hyperpigmented skin lesions,
DICER1 sydnrome
childhood tumors
pleuropulmonary blastomas
cystic nephromas
sertoli leydig tumors
mutlinodal goiter
ATM mutation
breast cancer risk screening at 40, MRI 35
small ovarian risk
moderate pancreatic risk
what is CHRPE and what is it associated with
congenital hypertrophy of the retinal pigment epithelium
FAP
BRIP1 mutation association and treatment
ovarian cancer risk (BRCA1 interaction protein gene 1)
- BSO at age 45
breast cancer risk
NF1
cafe au lait/pigmented skin
neurofibromas of the skin
lisch nodules of the eyes, optic gliomas
malignant peripheral nerve sheath tumor
GIST
pheochromocytoma
macrocephaly, short stature
breast cancer risk, screen at 30
VHL tumors
hemangioblastomas, retinal angiomas, clear cell RCC, pheochromocytoma, pancreatic neuroendocrine tumors
Dermatofibrosarcoma protuberans, translocation and gene result and treatment
t(17;22) fuses COL1A1 to PDGF which leads to PDGFRB
treat with imatinib, resection
Desmoid tumor treatment, mutation, associated syndrome
observe for spontaneous regression, sorafenib (cat 1), NSAIDS, imatinib, pazopanib, MTX and vinblastine
CTNBB1
gardners syndrome FAP
GIST mutations and drug sensitivity
Imatinib- KIT and PDGFRA except resistant exon 18 (D842V)
Avapritinib- for exon 18 resistance mutations (D842V)
NTRK, BRAF- associated target therapies
SDH deficient- sunitinib
GIST IHC
SDHB, CD117, DOG1, CD34 also look for mutations in KIT and PDGFRA
Adjuvant therapy GIST what determines this
location, size and mitotic rate
low risk resected- observe
gastric: <2 cm (regardless of high or low mitoses) is low
size up to 10 cm with low mitoses are still low risk
non-gastric:
- generally 0-5 cm with <5 mitoses=low
- >5 mitoses and <2 is high
int or high
GIST imatinib duration and dose per mutation
KIT 11 normal dose 400 daily
KIT 9 double the dose helps with better response
36 months for high risk post-op
second line, third line, fourth line GIST metastatic
sunitinib, regorafenib, ripretinib (switch control kinase)
then pazopanib, dasatinib (D842V mutation), sorafenib, nilotinib, ponatinib, everolimus +TKI, cabozantinib
ewing sarcoma treatment and translocation
t(11;22) CD99+, FISH EWS gene
neoadjuvant chemo VAC/IE for 9 weeks, then surgery and then adjuvant chemo or chemo/rt with + margins
chondrosarcomas and types treatment
normal chondrosarcoma treat with surgery and observe
if undifferentiated treat like osteosarcoma if mesenchymal treat like ewings
osteosarcoma treatment
low grade or parosteal: resect and ajuvant chemo if high risk features
int-high grade or undifferentiated: neoadjuvant chemo with cisplatin/doxorubicin or high dose MTX, cisplatin and doxorubcin followed by surgery and adjuvant chemo
metastatectomy
Giant cell tumor of the bone treatment
express RANK ligand, therefore can be treated with denosumab which blocks RANK ligand
good response to neoadjuvant chemo in bone tumors
<10% viable tumor is a good response to chemo
treat kaposis sarcoma if visceral disease, virus associated
doxil or paclitaxel, second line is pomalidomide, can also use immunotherapy; hhv-8
Inflammatory myeofibroblastic tumors mutation and drug
ALK gene rearrangements and crizotinib and related drugs
epithelioid hemagioendothelioma mutation
WWTR1 protein TAZ-CAMTA1 fusion gene t(1;13)
breast cancer with lymphedema chronically at risk for which sarcoma and treatment
angiosarcoma, surgical resection
tenosynovial giant cell tumors aka pigmented villonodular synovitis aka diffuse type giant cell tumor treated with and mutation
CSR1, treatment with pexidartinib (cat 1 liver tox), imatinib, nilotinib,
metastatic liposarcoma or leiomyosarcoma treatment
1st and 2nd line
AIM or single agents of this like doxorubicin
trabectedin or eribulin (liposarcoma)
KIT exon 17 mutation in GIST means what for treatment
resistance to imatinib and sunitinib so try regorafenib
which sarcomas respond to immunotherapy
myxofibrosarcoma, UPS, dediff liposarcs, cut angiosarcs, undiff sarcs
rhabdomyosarcoma treatment
pleomorphic vs non-pleomorphic
non: VAC (vincristine dactinomycin and cyclophosphamide
pleo: doxo/ifos. mesna or ifos epi mesna
epithelioid sarcoma mutation and treatment
INI1, SMARCB-1 which allows EZH2 to drive tumor growth
tazemetostat is a EZH2 inhibitor
PEComa treatment and mutation
TSC1/2 mTOR complex overexpression treated with sirolimus
alveolar soft part sarcoma treatment
surgically resect or surveillance
atezolizumab or pembro
pazopanib or sunitinib
adjuvant NSCLC lung cancer treatment by stage
what chemo/immuno
stage II (generally nodes involved or >5 cm) or higher are offered treatment with chemo followed by immunotherapy or osimertinib if EGFR mut
IB (3-5 cm in size T2, N0) with high-risk features also considered (poor diff, vascular inv, only a wedge resection, visceral pleural inv or no node dissection)
re-resection or RT if positive margins
Stage III consider adjuvant RT after chemo
adjuvant chemo/immuno
adeno: cis/pemetrexed x4 with atezo pd-l1 >1%
squam: cis/gem or cis/doce or cis etop x4 with atezo pd-la >1%
treatment options by stage for NSCLC
I surgery (up to T3N1)
II surgery (up to T3N1)
III generally chemo/rads if N2 or T4 or T3 with invasion
ROS + metastatic disease treatment
1st, 2nd lines
brain
crizotinib, entrectinib
lorlatinib, ceritinib, or chemo
entrectinib, lorlatinib for brain
ALK metastatic treatment
1st line alectinib, brigatinib (pneumonitis), lorlatinib, ceritinib
2nd line: lorlatinib
if used crizotibib then alectinib, brigatinib, lorlatinib, certinib
3rd line lorlatinib
brain: alect, brig or lorlat, cert?
all cause brady cardia
ceritinib and crizotinib cause qtc
metastatic squamous NSCLC no targetable mutations
1st line
2nd line
carbo/taxol or nabpaclitaxel pembro (all comers
ramicirumab/docetaxel
gem
nab/paclitaxel
metastatic adenocarcinoma no targetable mutations
carbo/pem/pem
ramicirumab/docetaxel
gem
nab/paclitaxel
pembro pdl1>1 if not given upfront
multiple nodules in the same node for lung cancer staging
stage T3
N3 disease NSCLC, what stages does this correspond to and what does that mean for treatment
contralateral hilar or mediastinal lymphadenopathy or any supraclavicular or scalene, upstages to IIIB, chemo/rads +durva not surgery
N2 definition, stage and treatment
metastasis in ipsilateral mediastinal or subcarinal nodes,
upstages to stage III which means chemo/rads +durva
EGFR-mutated metastatic treatment lines
mutations
exon 19del or 21 L858R
- osimertinib (ILD, Qtc, CHF)
(afat, gefit, dacomit, erlot+/- ramucirumab or bev)
if started not osi:
- then if T790M+ switch to osimertinib
- if negative continue treatment or switch to chemo based treatments
S768I, L861Q and G719X
- afat or osi
- if afat is started check T790M and switch if + on progression
20 insertion
- amivantamab
- mobocertinib (oral)
pancoast tumor NSCLC treatment differs how
neoadj chemo followed by surgery
extensive stage SCLC 1st line and subsequent
carbo/etop x6 + atezo
<6 mo relapse
- lurbinectedin
- topotecan
- paclitaxel, docetaxel
> 6 mo relapse could retrial as above
EGFR mechanisms of resistance to therapy
EGFR 790M mutation or MET amplification
immunotherapy in EGFR or ALK
generally not helpful
some benefit with atezo+ bev+ carbo+paclitaxel in the mutated groups
sotorasib use and moa and electrolyte issue
2nd line KRAS g12c mutated NSCLC, causes hypocalcemia , hepatotoxicity, ILD
RET mutation treatments
Selpercatinib (hepatotox, HTN, QTc, bleeding)
Pralsetinib
Cabozantinib
METex14 skipping mutation
capmatinib
tepotinib
(crizotinib)
lorlatinib side effect
hyperlipidemia
start rosuvastatin as it is low CTP450
lung nodule plan
solid nodule 6-8 mm repeat CT scan
> 8 mm CT or PET in 3 or biopsy
crizotinib side effect
visual disturbances like flashing lights or floaters, liver enzyme elevation and diarrhea
T3 invasion of the chest wall, proximal airway or T4 resectable mediastinum if resectable (IIIA T3 N0-1)
treat with neoadj chemo then surgery
checkpoint 816 lung ca trial
stage IB-IIIA resectable NSCLC given neoadjuvant chemo+nivo or placebo then surgery
improves EFS
improves PCR
manage siadh in sclc
tolvaptan vasopressin antagonist
erlotinib things
take on empty stomach
smokers need to increase dose to 300 mg
causes rash
chemo/rads treatment is given with what in local NSCLC curative intent
DURVALUMAB always pdl1 does not matter
indications to forgo adjuvant RAI thyroid
papillary tumor <2 cm, all foci less than 1 cm if multifoal, no Tg antibodies, unstimulated ttg post op low <1, neg post-op US
std work up in medullary thyroid cancer and treatment of local disease
calcitonin level, cea, screening for RET germline mutations, screen for pheochromocytoma
surgery with b/l neck dissection if >1 cm
no RAI
MEN 2 mutations in RET thyroid plan
total thyroidectomy by 1 year if high risk mutation and by age 5 if lower risk mutation
treat metastatic medullary thyroid cancer
observe if asymptomatic or cabozantinib or vandetanib both are RET and VEGF inhibitors
metastatic papillary thyroid cancer treat
radioactive iodine scan (2 months apart from CT scan which interferes
if uptake treat with RAI (100-200)
if no uptake check RET mutation status (selpercatinib, pralsetinib), BRAF status (DT)
1st line: lenvatinib, sorafenib
2nd line: cabozantinib
metastatectomy
Post-operative TSH suppression goals
high risk <0.1
low risk <0.5
liberalize after few years to 2
tumor markers in thyroid cancer
thyroglobulin in papillary
calcitonin in medullary
(>150 prompts imaging post-local therapy)
carcinoid of the appendix surgical plan
<2 cm appendectomy ok
>2 needs r hemi colectomy/ if neg SSTR-PET
treat metastatic NET of pancreas or other well-differentiated areas
octreotide, everolimus, sunitinib, capecitabine and temozolomide
alpha blocker drug prior to pheo surgery
terazosin, doxazosin, prazossin and phenoxybenamine
carcinoid causes what heart thing
serotonin thickens the R cardiac valves, causes R heart failure, tricuspid regurg or pulmonary stenosis
moa and use of telotristat ethyl
tryptophan hydrolyase inhibitor for diarrhea due to serotonin from carcinoid tumors
papillary thyroid staging
age <55 with distant met is stage II disease
- treat with thyroidectomy then RAI
age >55 with lung mets is IVB with poor prognosis
HPV co-testing is indicated for women of what age
> 30
chemoradiation + brachy for which stages of cervical cancer
IB3, and then IIB, III, IVA
aka huge tumor or invades things
IB3= >4 cm tumor
parametrial invasion or invasion into
nodes
cisplatin or carbo weekly
cervical treatment stage IB1, IB2 and IIA1
tumors <4 cm!
IIA1 is tumor with extention beyond uterus but not to wall or lower vagina
surgical resection with hysterectomy with cervix removed and lymph node dissection
fertility-sparing is a radical trachelectomy and pelvic lymph node direction
adjuvant treatment after surgery with high-risk factors for cervical
positive nodes, positive margins, parametrium involvement, LVI
staging imaging
chemo/rads and brachytherapy (cat 1)
treatment for metastatic cervical cancer
carbo/cis + taxol + bev
carbo/cis +taxol bev + pembro (pdl1>1)
topotecan/taxol/bev (allergy)
2nd line
pembro if not previously received (>1)
tisotumab vedotin (ADC)
cemiplimab
gardasil 9 HPV types
which one is adenocarcinoma
6, 11,16,18, 31, 33, 45, 52, 58
18 is adenocarcinoma
salvage cervical ca surgery after definitive treatment
pelvic exenteration
or chemo/rads +brachy
vulvar cancer treatment local
<2 cm with <1 mm invasion simple vuvlectomy
> 2 cm with more than 1mm invasion radical partial vulvectomy and lymph nodes
Endometrial cancer adjuvant treatment
stage I
IA endometrium only or less than half myometrium: observe or brachy if grade 3
IB invades more than half the myometrium then
stage II brachy and EBRT if high grade
Stage III (invading things) or high risk histology (serous, clear cell, carcinosarcoma, undifferentiated) chemo/rads then carbo/taxol x6
III or IVA after surgery, add brachytherapy
gestational trophoblastic disease metastatic treatment
risk stratify
low risk methotrexate
second line in slight increase is dactinomycin or hysterectomy
poor response etoposide methotrexate actinomycin cyclophosphamide vincristine
endometrial metastatic disease treatment lines
test for what
HER 2, MMR
low grade or endometrioid
- AI therapy, megase/tamoxifen
carbo/taxol/pembro (except carcinosarcoma)
carbo/taxol dostarlimab
next line is len pembro in pMMR
carcinosarcoma:
- carbo/taxol +/- dostarlimab
- ifosfamide +/- paclitaxel or cis
MSI H
- pembro
- dostarlimab
- nivo or avelumab
tisanlizumab vedotin moa and use and risk
metastatic cervical cancer seond line
corneal and conjunctival issues, need to see eye doctor prior to each dose, eye drop steroids pre-med
pneumonitits
adjuvant treatment for endometrial stromal sarcoma or adenosarcoma that are low-grade
AI or other hormone treatments
management of localized RCC
T1= <7 cm cm stage I= partial nephrectomy, ablation or surveillance
T1a <4 cm partial nephrectomy is preferred
stage II >7 cm only kidney partial or radical nephrectomy
stage III (extends into veins or perinephric tissues or N+)radical nephrectomy: radical or partial if clinically needed
adjuvant therapy for RCC
surveillance for stage I
Stage II adjuvant pembro if grade 4 or sarcomatoid or surveillance
Stage III adjuvant pembro or surveillance
pazopanib moa use and risks
RCC front line favorable risk not immunotherapy candidates, in later lines metastatic, multi TKI to VEGF, c-KIT and PDGFR
LFT elevation
metastatic RCC treatment lines
favorable first
axi-pemb
cabo-nivo
len-pem
(surveillance, axi, IL-2)
poor first
ipi/nivo
axi-pem
cabo-nivo
len-pem
cabo alone
(pazopanib, sunitinb, temsirolimus)
subsequent lines
- len evero
- axi
- cabo
if no IO then axi-pem, ipi/nivo, len-pem, nivo
3rd line
- tivozantinib
papillary renal cell driven by what mutation and what syndrome
MET mutations
hereditary papillary RCC
chromophobe RCC what syndrome and what other symptoms
birt-hogg-dube FLCN gene folliculin
oncocytomas, angiomyolipomas
clear cell and papillary rcc
cysts/blebs, spontaneous ptx
tumors of the follicles
hereditary leiomyomatous and RCC syndrome gene
fumerase hydratase
adrenal adenomas, uterine lyomyatat, cutaneous leiomyata
tuberous sclerosis tumors and gene
TSC CNS tubers, renal cysts and clear cell rcc, angiomyolipomas, subependymal giant cell astrocytoma, retinal hamartomas
skin facial tumors, skin patches, thickened skin, shagreen patch
treat angiomyolipomas associated with tuberous sclerosis
everolimus
RCC IHC
CK7 and 20 are negative
PAX2 and PAX8 positive
carbonic anhydrase, CD10
medullary RCC treatment
who gets this
carbo/gem is first line
sickle cell trait
treatment of non-clear cell rcc
cabozantinib preferred
then len/evero, nivo, cabo/nivo, pembro, sunitinib
treatment of ovarian cancer by stage
IA-IV: hysterectomy/BSO, comprehensive staging and debulking
IA or IB (tumor in one or both ovaries with capsule intact no malignant washings) (not HG serous or grade 3 endometrioid): observe
Otherwise: stage II-IV IV platinum chemo
stage II- anything out of the ovary itself)
carbo/taxol +/- bev (+ maint bev)
treatment difference for mucinous carcinoma
FOLFOX bev for mucinous
germ cell tumor adjuvant
BEP x4
unless stage ia grade1 immature terratoma or dysgerminoma observe
granulosa verus sertoli-leydig ovarian cancers
granulosa secretes estrogen–> endometrial cancer risk
also secretes inhibin which can be measured and help with diagnosis
sertoli-leydig–> testosterone
low-grade serous carcinomas treatment
adjuvant treat with chemo (Carno/taxol) if stage II or higher, consider maint letrozole
metastatic disease:
- MEK inhibitors (trametinib)
- check BRAF
- mormone therapy
- chemo
role of olaparib in ovarian cancer
maintenance only (not single agent) in BRCA mutated disease
or in second remission after platinum if not used in first line in all comers
Niraparib or rucaparib can be used in all comers if bev was not used upfront but not in second remission if unmutated
if bev used upfront and BRCA mutated or HR deficiency give bev and olaparib maintenance
mirvetuximab sorvtansine-gynx moa and use
folate receptor alpha directed antibody for use in metastatic disease platinum resistant ovarian cancer with one prior lineof therapy including bev
side effect keratopathy/occular toxicity
platinum resistant ovarian lines
cycolophos bev
docetaxel
etoposide oral
gem
doxil
taxol +/-bev
topotecan +/- bev
bev
mirvetuximab soratvansine (after bev)
endometriosis and ovarian ca type
clear cell
low risk observe after TURBT
papillary urethelial of low malig potential
low grade Ta, <3, solitary lesion
sqamous bladder tumor management
urachal management
resect
adenocarcinoma or urachal if needs chemo think about FOLFOX, resect the urachal ligament with umbilicus and nodal dissection
plasmacytoid urolothelial or micropapillary mutation
CDH1, aggressive
EV target and conjugate and SE
nectin-4, platinum, rashes and occular toxicity
testicular staging
stage I is no nodes regardless of T
stage II is nodes regardless of T
stage III is metastatic disease and/or Nodes with very high tumor markers
erdafitinib target and toxicity
FGFR2 or 2 second line
hyperphosphatemia
occular disorders, must have upfront and constant eye exams
seminoma stage I treatment
surveillance
Carbo AUC7 x1
radiation
seminoma must have
pure seminoma features on pathology, normal AFP (b-hcg can be elevated)
Stage I non-seminoma treatment
surveillance
RPLND
BEP x1
minor b-hcg elevations cause
hypogonadism, hyperthyroidism, marijuana
treat stage IIA/B seminoma
Node +
BEP x3 or EP x4
or
Radiation
treat stage IIC (N3 aka node >5cm) or III seminoma
risk stratify
good - BEPx3 or EPx4
int risk (mets other than lung)- BEPx4 or VIP x4
treat stage II non-seminoma also IIIA (only lung mets)
BEPx3 or EP x4
RPLND
IIIB and IIIC non-seminoma
non-pulmonary mets or very high post op tumor markers or mediastinal primary
BEPx4, VIP x4
testicular residual masses by type and size
seminoma 3 cm, markers, PET eval or watch, then surgically resect, if seminoma give 2 cycles of adjuvant chemo EP or TIP or VIP
non-seminoma 1 cm, surgically resect, if residual non-seminoma then chemo x2 cycles (EP, VIP or TIP)
tumor markers in testicular, half lives
AFP 5-7 days
b-hcg 1-2 days
IS- stage is residual tumor marker elevation after surgery (BEPx3 or EPx4)
who gets a brain MRI in testicular staging
post-op b-hcg >5000, AFP >10,000
extensive lung mets or visceral mets
choriocarcinoma dominant pathology
neuro sx
second line chemo regimens in testicular
TIP or VeIP (vinblastine)
third line high dose chemo with stem cell rescue
treatment of penile SCC
stage I wide local excision, or if high grade partial penectomy
Stage II partial penectomy with LND
Stage III nodes neoadj TIP
paclitaxel infusion reaction vs allergy which part of the formula
cremophor in paclitaxel can cause flushing and a rash, rune more slowly
can switch to docetaxel if still bad
moa methotrexate
dihydrofolate reductase antimetabolite
DPD vs UGA1A1
5-FU (cytopenias and other se) vs irinotecan (diarrheaO)
moa fulvestrant
estrogen receptor antagonist
letermovir
prevents CMV reactivation
opioid conversion help
oral morphine, IV divide by 3
oral morphine x10 for tramadol
oral morphine oxycodone divided by 1.5-2
oxy 10= dilaudid 4= morphine 15=traadol 150
AST ALT elevation grading in immunotherapy toxicity and manage
x2 ULN is grade 1 continue and monitor/work up
x3-5 is grade 2 hold and monitor q3-5d and consider steroid if not improved on first recheck
> 5 grade 3
hold and start steroids
> 20 grade 4 permanent stop
no infliximab
bullous rash with immunotherapy grade and manage
> 30% BSA= grade 3 permanent d/c due to c/f SJS
vincristine vs paclitaxel moa
vincristine is a microtubule destablizing agent
paclitaxel is a microtubule stablizing agent
pancreatitis as immunotherapy se
grade 2 is CT or lab findings (consider hold)
grade 3 is symptomatic with pain and vomiting and elevation/CT findings (hold and give steroids)
grade 4 is life threatening (perm d/c)
grapefruit juice and imatinib
increase drug levels
sunitinib side effects and moa
VEGF 2, 3, PDGFR, C-KIT
HTN, CHF, hypothyroidism, adrenal insufficiency
TDM-1 is what drug and what is the linker
ado-trastuzumab emtansine
maytansinoid is a tubule polymerization inhibitor
treat neuropathy
duloxetine
what does CTLA4 bind with that is interrupted by ipilimumab
CD28 and CD80, CD86 (B7)
nausea meds moa
NK1
5-HT3
name the components of a high emetogenic cocktail (name a few drugs or combos)
aprepitant
ondansetron
two above plus dex and olanzapine
AC
cisplatin
ifosfamide
carbo AUC 4
Enhertu
sacituzumab govitecan
