Qs Flashcards
Diagnosis of melanoma
Over 6mm, assymetric, uneven borders, shades of colour, enlargement, FIRM
Two major types and their Subtypes of melanoma
Rapid growth phase which inc superficial spreading which is commonest, lentigo maligna, acral lentiginous
And vertical growth phase inc nodular which has poor prognosis,
Prognostic factors in melanoma
Dermal thickness is most critical, ulceration upstages all else, LDH important in metastatic disease
Staging in melanoma
Stage 0 is in Situ, 1 is under 2mm without ulceration or under 1mm with ulceration
Stage 2 is more than 2mm without ulceration or more than 1mm with ulceration
Stage 3 is LN
Main site of met in melanoma
Lung
Management of stage 1-3 melanoma
Wide local surgical excision .
For stage 3 also do lymph node resection (TLND)
If over 1mm or if over 0.75mm but with high risk features- do sentinel node biopsy . And if this is positive only do complete LN dissection
Commonest mutation in melanoma
BRAF
Management of metastatic melanoma
Surgical resection of Mets
If BRAF mutant, do combo BRAF (dabrafenib>vemurafenib, only dabrafenib has CNS activity and inhibits all V600) with MEK (trametinib) inhibitor. Another targeted therapy is cKIT (imatinib) also can be used (this activates RAS)
Second line is immunotherapy or if wild type BRAF- nivo/ipi combo esp for CNS disease
What happens if BRAF inhibitor used in their own
Higher risk of keratoacanthoma and squamous fell cancer
Immunotherapy SEs and management
Pseudoprogression with antiCTLA4 (thus don’t scan too early), GI immunotoxicity esp with ipi, whilst nivo causes more hypothyroidism. Mx- symptom relief alone if mild, if moderate steroids . If severe may need additional mycophenolate
Grade 4 colitis May need prolonged steroid weaning and TNF blockage and bowel resection
List mutations causing breadt cancer and which has highest causative link
BRCA (esp 1), TP53 (Li Fraumeni has highest!), STKII (Peutz Jegher), MSH/MLH
Role and pathogens is of PARP inhibitor in BRCA breast cancer
Like BRCA, PARP is another DNA base excision repair - they result in higher mutations causing genomic instability - tumor selective cell death via synthetic lethality
Commonest breast cancer type
Invasive carcinoma not otherwise specified
Describe staging of breast cancer
Stage 1 is small and node negative
Stage 2 is large and/or under 4 LNs, stage III is inflammation on chest wall or more than 4 LNs.
Screening in normal risk, moderately high risk and high risk women
Normal risk mammogram every 2 from age 50-74
Moderately increased risk is if one FDR under 50 years, 2 SDR with one under 50 in same side of family, annual mammogram from age 40. If two FDR in same side both over 50, annual mammogram from 50
If high risk (2 or more FDR under 50)- MRI annually from age 30
Management of stages 1-3 breast cancer
Wide local excision with RTX (sane outcomes as mastectomy) - mastectomy preferred if multi centric tumors, high tumor to breadt ratio, risk reduction, contraindication to RTX (e.g. prev RTX to same field lymphoma)
If high risk mastectomy parients (triple neg or node pos tumor over 5cm) also do RTX
Need to do sentinel biopsy in all at axillary . If pos- LN clearance
Describe the adjuvant systemic breast cancer therapies in non metastatic disease
If ER pos and low risk- endocrine . If ER pos and high risk- endocrine AND chemo If HER2 pos , trastizumab AND chemo If triple neg- chemo Bisphosphonate increases survival!
Endocrine therapy for premenopausal is OFS (surgery or GNRH agonist with Goserelin) with AI (anastrozole) best, next is tamoxifen
Another endocrine therapy is fulvestrant (selective estrofen receptor degradation)
If postmenopaisal- AI alone, or tamoxifen
HER2 inhibitor last are trastuzumab and pertumab sometimes uses jointly
SEs of AIs, tamoxifen and HER2 blockers
AIs- hot fluishes, osteoporosis, vaginal dryness, CVD risk, higher cholesterol, AIMSS
Tamoxifen- hot flushes, VTE risk, uterine cancer (only in post menopausal- as when used in post menopause there’s low estrogen and thus tamoxifen agonist effects predominate , NAFLD
In premenopausal can increase OP risk but protects bone in post menopausal women
Trastuzumab- reversible myosin shunning , reduces LVEF by 10%- can rechallenge once EF improves
Management of metastatic breast cancer
ER pos- endocrine first WITH AI and chemo (and OFS if premenopausal- give chemo first if severely symptomatic or high volume of disease) and CDK4/6 inhibitors (prevent G1 to S progression- inc ribociclib, palbociclob)
If HER2 pos- herceptin and chemo
Chemo used is taxanes and anthracyclines inc doxorubicin
Indication for chemo in ovarian cancer and what agent is used
Carboplatin, pacitaxel used.
Adjuvant chemo used if high grade or clear cell histology , stage 2 and beyond
Indication for radiotherapy in ovarian cancer
Stage iii , palpitation
Management of low risk, intermediate risk and high risk endometrial cancers (and define risks)
Low risk is stage 1 under 50% myometrial invasion- surg alone
If intermediate LN clearance- stage 1 but over 50% myometrium, surg +/- brachytherapy
If high risk- pelvic radiotherapy, local brachytherapy, chemo and surg
Management of advanced invasive cervical cancer
Chemo radiation with cisplatin (no surg)
Management of metastatic cervical cancer
Carbo/pacitaxol +/- Bevacizumab
Is NSAID RF for gastric cancer
No is chemoproctive
Management of gastric cancer with and without nodal involvement
If T1aN0 under 2cm confined to mucosa - surg resection alone
If above T1N0- surg and chemo (if adeno- commonest) or chemorad if squamous
If medically fit also do LN dissection
Chemo used in gastric cancer
FLOT
5FU, docetaxel, leucovirin, oxaplatin
Management of metastatic gastric cancer
If advanced gastric cancer - PD1 blocker
If HER2 positive- herceptin- increases survival in metasisis
Chemo for pancreatic cancer
FOLFIRINOX (folinic acid, 5-FU, irinotican, oxaplatin) or gemcitabine alone which has less toxicity
Erlotinib also has a role
Neuadjuvant chemorad for borderline resectable cancers
Describe role of PSMA in prostate cancer screening
Highly specific and sensitive - it’s a PET scan with prostate specific membrane antigen and able to identify Mets earlier
Management of castrate sensitive prostate cancer
ADT (GnRH agonist like Goserelin or antagonist like degarelax) - if using GNRH agonist esp if bone Mets present MUST use testosterone antagonists like flutamide 7 days prior to 7 days after to reduce flare phenomenon
If high volume disease - also use doxetaxel
Abirarerone shown effective not on PBS
Management of castrate resistant prostate cancer
ADT, docetaxel and androgen receptor antagonists
Abiraterone blocks 17a hydroxylase
Enzalutamide is androgen receptor antagonist . Ketaconazole is adrenal androgen inhibitor
Wide effects of abiraterone and enzalatumids
Abiraterone blocks 17a hydroxylase which leads to
1. Build up for aldosterone and subsequent hyperaldosteronism
- Low production of 17 hydroxyprogesterone -> low cortisol -> thus give with pred
- Commonly causes transminitis
Enzatumide- HTN, reduced cognition and confusion, fatigue, seizures (contraindicated in epilepsy)
Implication of AR-V7 mutation in blood in prostate cancer
Predicts response to abiraterone and enzulatamide
Predicts of relapse in prostate cancer
Gleeson score, PSA doubling time under 10 months
Role of VHL mutation in renal cell cancer
VHL keeps hypoxia induction factors in check-> HIF normally promotes angiogenesis and when mutated uncontrolled HIF
First line management in advanced renal cell cancer
And second line
TKI- sunitinib has longer survival and higher toxicity than sorafenib (both VEGF inhibitor)
No role for surgery
Cytoreductive chemo also done, minimal benefit
In second line- immunotherapy, mTOR, Bevacizumab
What’s better treatment in advanced RCC
Note if intermediate or poor risk advanced RCCs- combined immuno better than sunitinib!!
Side effects of TKIs
Mucositis, stomatitis, HTN, diarrhoea, hypothyroidism, Hand foot mouth syndrome, PRES
Tumor marker in seminoma and nonseminoma
Seminoma= NORMAL AFP, any BCG, any LDH
Non seminoma = AFP high, BCG & LDH also high
Describe staging in testicular cancer
Stage 1 is limited to testes, 2 is LN, 3 is distant Mets
Management of stage 1 seminoma, and stage 2
What if residual disease
Stage 1 orchiectomy
Stage 2- orchdectomy and high dose carboplatin
If residual disease under 3cm- just surveillance
If one or more retroperitoneal LN, LN dissection
Management of stage 1 and 2 nonsemionas
Stage 1= if no RFs, just orchiectomy
If RFs (e.g. lymphovascular invasion)or stage 2= Orchiectomy plus BEP OR RPLND
Management of metastatic testicular cancer
BEP (bleomycin, etoposide, cisplatin) resect residual mass. If relapsed- represents cisplatin resistance - mx with vinblastine, ifofamide
Describe staging in lung cancer
T1 is under 3cm, T2 is 3-7cm, T3 is over 7cm
Stage 1B- T2NO
Stage 2B- T3N1
Stage 3A- T4N2
Stage 3Band C- T4N3
Stage 4- Mets
Management of stage 1 and 2 lung cancer
Surg if FEV1 over 80%
If unfit- RTX
Adjuvant chemo cisplatin (if can’t tolerate carboplatin)
Do LN biopsy for staging
Management of stage 3 lung cancer
If resectable- resect and chemoradiotherapy . If borderline resectable consider neoadjuvant chemorad first
If unresectable tumor- chemorad wirh etoposine and cisplatin - main is radiation and chemo just
PD1 blocker durvalimab for 12 months post chemorad shown to improve survival
Approach to and management of stage 4 non small cell cancer
Need to classify as adenocarcinoma vs squamous cell
Adenocarcinoma- if EGFR, use first gen TKI gefitinib although 3rd gen osimertinib better as overcomes T790M mutation . If ALK pos, 3rd gen TKI approved alectanib as has CNS penetration. If ROS1 translocation can use cirzotinib
Note KRAS commonest mutation but no treatment
If no driver mutation- and PD1 levels over 50 use pembrolizumab. If under 50 use chemo alone
If squamous cell- if PDL1 over 50- Pembro, If PDL1 under 50, pembro and chemo
SE of ALK TKIs
Visual changes, long QT, neutropenia
Evidence for early pal care in NSCLC
Improved PFS, QOL and mood
Management of mesothelioma
Radical extrapleral pnemonectomy (but risk in other lung), palliative chemo cisplatin, pemetrexed, Bevacizumab. Some respond to PD1 blocker
Management of small cell lung cancer
Limited stage disease - chemorad and if responds - cranial irradiation,
Extensive stage- chemo alone and consider palliative RTX. Adding PDL1 improves survival but not on PBS and used as second line
Paraneoplastic seen in Squamous , and small cell
Squamous - hypercalcemia, HPOA
Small cell- SIADH , Lambert Eaton (ptosis, absent deep tendon reflexes)
Serum neurone specific enolase in 75% (also dopa decarboxylase, calcitonin)
Cause of HNPCC, FAP and MUTYH syndromes- location and of the unit
HNPCC more likely right sided, 10% have synchronous. These are Lynch syndrome . Due to MMR mutations (most common is MSH2)
FAP- tumor suppressor genes on chromosome 5, controls beta caretin (involved in cell-cell adhesion)- must do sigmoidoscopy from age 12 and duodenal screen from age 25
MUTYH associated polyposis- aut recessive , base repair gene.
How does lynch syndrome associated endometrial cancer different from normal tome
Lynch affects lower uterine segment, more type 2 features (higher grade, older age, occur in obesity, early menarche)- if diagnosed should do early colonscopes
Screening guidelines in CRC
For average risk - FOBT every 2 years from 50-74 (or scope 10 yearly)
For moderately high risk (one FDR under 55, 2 FDR at any age, one FDR and one SDR from same family at any age)- FOBT every 2 years from 40-49 then scope every 5 years from 50
High risk - 3FDR or SDR at any age with one under 55 years , or 3 FDR any age)- FOBT from age 35 till 45 then scope from 45 five yearly
Low dose aspirin in moderate in high risk
Management of stage 1, 2, 3 CRC
Stage 1- surg
Stage 2- surg and if high risk adjuvant chemo
Stage 3- surg and 6 months FOLFOX (folinic acid, 5-FU, oxaplatin, ironotican also used often, latest chemo approved is lonsurf ) and radiation (which is sensitiser)
Management of metastatic CRC
If curable - aggro therapy. Resect if oligometsstatic. If borderline resectable- chemo then surg resection.
If unresectable- chemo +/- targeted therapy- inc Bevacizumab (VEGF inhibitor) and EGFR inhibitor cetuximab (only if RAS wild type, LEFT tumors$
Surveillance after surgery for CRC
After surgery for first two years clinical review every 3 months and 6 monthly CT staging
Years 3-5- CEA, annual CT
Colonscopy at onset and 2nd yearly!
List the ECOG categories
0= asymptomstic
1= symptomatic but well/active
2= resting <50% in bed of waking hours
3= resting over 50% of waking hours
4= bed bound
Where does microtuble production occur
G2
Describe Li Fraumeni syndrome
Inherited familial predisposition to wide range of cancers- due to p53 mutation tumor suppressor mutations- causing soft tissue and bone sarcomas , breadt cancer and brain tumors
Describe peutz jegher syndrome
Aut dominant develops benign haemarthomastous polyps in GIT and hyperpigmented macules on lips and oral mucosa- higher risk of cancers of liver/lungs/breast/ovarian
Cancers of MEN1, 2a, 2b
MEN 1 (3Ps)- pituitary, pancreatic, parathyroid
MEN2a= 2Ps, 1Ms= phaochromacytoma, parathyroid, medullary thyroid cancer
MEN2b= 1P,2Ms= phaeochromocytoma, medullary thyroid cancer, Marfanoid/mucosal neuroma
What does tumor market Ca125, CEA, Ca15.3, Ca19.9
CEA- colon cancer
Ca125= ovarian
Ca15.3= breast
Ca19.9= pancreatic/biliary cancer
Mutations in
- APML
- AML (good and bad)
- CML
- MDS
- MPD
- Burkitts
- Mantle cell lymphoma
- Follicular lymphoma
- CLL (good and bad)
APML= t(15;17)
AML poor prognosis- monosomy 7, FLT3 mutant, del5q, del17
Good prognosis- t(8,21)Inv(16)
CML- t(9;22)BCR-ABL
MPD- JAK2 V617F mutation
MDS- 5q minus syndrome
Burkitt lymphoma - MYC, chromosome 8 t(8;14)
Mantle cell lymphoma- cyclin D1 (chromosome 11)- t(11,14)
Follicular lymphoma- Bcl2 chromosome 18 t(14;18)
CLL - good is 13q deletion, bad is del17q which correlated with p53
Management of AML
If fit , induce with 7 days cytarabinr and 3 days anthrocyclines. Consolidate HIDAC . Then observe vs stem cell if at high risk
If FLY3 mutant- add midostaurin
If CD33 pos- add gemtuzumab
If unfit- Aza and low dose cytarabine
If relapse - BSC vs BMAT
Management of ALL
ALL is commonest in young
If over 45- hyper CVAD (cyclo, vincristine, adaramycin, dex), MTX and cytarabine (for CNS prophylaxis) as induction. If Ph+= add imatinib
Then consolidate with same . Maintenance with MTX, 6-MP, pred
Cont for 2 yrs
If refractory- BLINATUMOMAB for B ALL & CAR T cells for T cells under 25 yrs
MAnagemrnt of CML
They’re Ph pos- BCR-ABL
Imatinib/dasatinib
2nd line is interferon and cytarabine
If developed T3151 mutation here - use ponatinib here
SEs if BCR-ABL TKI
Pleural effusion, pancreatitis, vascular risk, DM
CML vs leukamoid reaction
CML shows WBC with low ALP score, in leukemoid toxic granules (aka dhole bodies) and left shift neutrophils
What’s richters transformation
transformation of B cell chronic lymphocytic leukemia (CLL) or hairy cell leukemia into a fast-growing diffuse large B cell lymphoma
CLL mx
Early stage watch
If symptoms- FCR (fludarabine, cyclo, ritux)
If unfit- Ritux, chlorambucil, or ibrutinib (BTK inhibitor- squeezes CLL cells from LN to periphery
If delq17 present in CLL, how does this change management
Give ibrutinib or venetoclax (BH3 mimetic), obinutuzumab (antiCD20)
Lymphomas associated with EBV, HHV8, HTLV1, Hep C
EBV - Butkitts, Hodgkin, HIV associated lymphoma, PTLD
HTLV1= Human T cell lymphoma/leukaemia
Hep C= marginal zone lymphoma
HHV 8= primary effusion lymphoma
In Hodgkin RS cells seen. What markers are they positive for
CD15 and 30
Commonest cause of SVC obstruction in young
Hodgkin
Management of Hodgkin lymphoma
Limited stage- ABVD (adriamycin, bleomycin, vinblastine, docurbrazine) and RTX. If advanced - larger course ABVD called eBEACOPD
IF relapsed- brentuximab (antiCD30), PD1 inhibitor and auto SCT
Describe Ann Arbor system
For HD divided into A where no sx or just prutitis and B into B symptoms
And also as 1 single LN, 2 as 2 or more LN on same side of diaphragm , and 3 as LNs on both sides of diaphragm , and 4 as spread beyond LN
NonHodgkin lymphoma inc follicular lymphoma.
Describe their management
Follicular - commonest , mx of stage 1 is curative RTX, stage 3 and 4 and asymptomatic is watch
If stage 3 and 4 but symptomatic CHOP (cyclo, hydrodanorubicin, vincristinr, pred) and obinutumab (antiCD20). Maintainance 2 yrs with ritux or obinutumab
If refractory/relapsed- ibrutinib (BTK inhibitor) , BH3 mimetic (venoteclax), idelalisib (phosphodiesterase 3 kinase inhibitor )
NonHodgkin lymphoma inc DLBCL, mantle cell, burkitts and splenic marginal zone lymphomas
Describe their management
Universally CD20 positive, R-CHOP.
Similar to obinutumab for follicular lymphoma, polatuzomab developed but not approved .
Mantle cell lymphoma - chemo, venetoclex, ibrutinib
Burkitts- heavy chemo CODOXM-IVAC
MGUS vs smouldering myeloma vs myeloma
MGUS- M protein under 3 and plasma cell under 10% with no CRAB
Smouldering myeloma- M protein over 3, PC over 10%, and no CRAB
Myeloma- any M protein, PC over 10 and CRAB
Describe management of myeloma
If transplant candidate (only under 70)- cyclo, bortezomib, dex, melphalan, autoSCT as induction
Then maintenance steroids and thalidomide if standard risk vs bortezomib if intermediate risk
If non transplant- lenalidomodr and dex , it bortezomib and melphalan, or pred and cyclo
List the ankylating agents
Cyclophosphamide, melphalan, tamezolamide, platinum based (cisplatin)
List topoisomerase inhibitors and where it acts
Acts on G2
Inc topoisomerase 1 - ironotican
2- etoposide, anthracyclines (doxorubicin)
List mitotic inhibitors and their mechanism
Vinca alkaloids destroy microtubules inc vincristine
Taxanes are microtubule stimulators inc docitaxel
List the subclasses of antimetabolites all of which work at S phase
Antifolate
is MTX, pyramidine antagonist is 5FU, cytarabine
Purine analogues are aza
Purine antagonist is fludarabine
Ribonucleotide reductase inhibitors are hydroxyurea
Most extravascation causing agents and their mx
Anthrocyclines mx by ICE, dimethylsulfoide
Vinca alkaloids mx heat and hyalurasinase
Unique SE of cytarabine
Cerebellar neuronal effects and conjunctivitis
Which chemo agent causes radiation recall teaction
Donarubicin
