Oncology

Question 1

What part of the cell cycle does vinca alkaloids work on

Answer 1

M phase

Question 2

What drugs are Vin alkaloids

Answer 2

Vinblastine
Vincristine
Vinorelbine

Question 3

What cytotoxics are epipodophtlotoxin derivatives

Answer 3

Etoposide
Teniposide

Question 4

What phase does bleomycin work on?

Answer 4

G2

Question 5

What is the MoA of anti-metabolites? (e.g methotrexate, cytarabine)

Answer 5

Mimic normal cell components ( in S phase) to inhibit DNA replication

Question 6

What are pyrimidine analogue?

Answer 6

Capcitabine
Cytarabine
Gemcytabine
Fluouracil

Question 7

What phase of the cell cycle does Capecitabine work on?

Answer 7

S Phase

Question 8

What cytotoxics cause pulmonary fibrosis

Answer 8

Bleomycin
Cyclophosphamide

Question 9

Side effects of cyclophosphamide

Answer 9

Anorexia, cardiotoxicity, interstitial pulmonary fibrosis, bladder cancer

Question 10

What TKI are for BRAF mutation? (Met melanoma)

Answer 10

Dabrafenib, Vemirafenib
(80% of people will develop resistance)

Question 11

What TKI are for MEK mutation in Met Melanoma?

Answer 11

Use BRAF inhib (Vemirafenib/Dabrafenib) AND Trametinib

Question 12

What are SE if Dabrafinib/Vemirafenib + Trametinib?

Answer 12

Fever, drenching swears, tachycardia, rash, pruritis, photosensitivity (Vemirafenib)
HTN

Question 13

What is the only CTLA-4 inhibitor?

Answer 13

IPILIMUMAB

Question 14

Side effects of Cobimatinib?

Answer 14

Acneiform rash

Question 15

Side effects of CTLA-4?

Answer 15

Clinically significant toxicity in 20%
- GI toxicity/Colitis

Question 16

Are endocrinopathies more common in PD1 or CTLA4?

Answer 16

PD-1 inhib - nivolumab

Question 17

What are side effects of alkylating agents ( e.g cyclophosphamide)

Answer 17

Bone marrow depletion, N. V, late cancers.

Question 18

What is the MoA of Alkylating agents?

Answer 18

Prevent cell division, cross linking , prevent DNA synthesis leading to programmed cell death

Question 19

What are the side effects of Anthracyclines? (Doxorubicin, daurubicin)

Answer 19

Cardiotoxicity, myelosuppression, alopecia

Question 20

What is the MoA of Doxorubicin?

Answer 20

Multiple MoA: Free-radical formation, lipid peroxidation, direct membrane effects, enzyme interactions.

Question 21

What are the side effects of etoposide?

Answer 21

Diarrhoea, mucositis, nausea

Question 22

What is the medianism of action of Topoisimerase II inhibitors?

Answer 22

Inhibits the enzyme that manages the coiling of DNA leading to accumulation of cleaved DNA stand breaks and cell death

Question 23

What are side effects of mitotic inhibitors ( vincristine)

Answer 23

Neurotoxicity, myelosupression

Question 24

What is the MoA of Mitotic inhibitors?

Answer 24

Blocks microtubule formation presenting formation of the mitotic spindle (M-phase)

Question 25

What are the common mutations in melanoma?

Answer 25

BRAF (40-60%), 80-90% of these are V600E, eventually if treated with BRAF TKI will develop MEK mutation

Question 26

How can you tell if a dMMR in a colorectal cancer is somatic or germline?

Answer 26

If BRAF V600E found then can assume there is acquired MLH1 hypermethylation CRC. BRAFV600e only in <1% lynch syndrome (only applicable in CRC)

Question 27

What are the histological features of dMMR/ lynch syndrome

Answer 27

Mucinous histology, poor differentiation, right sided, lymphocytic infiltrate, absence of intraglandular neutrophil necrosis

Question 28

What are the dimerised pairs for dMMR on immunohistochemistry

Answer 28

MLH1 and PMS2 = indicate dysfunctional MLH1 protein production MSH2 and MSH6 = indicate dysfunctional MSH2 protein production Isolated loss of PMS2, or MSH6

Question 29

What are causes of MLH1 gene dysfunction?

Answer 29

Hypermethylation MLH1 Somatic tumoural pathogenic variant Gernline pathogenic variant

Question 30

Do dMMR respond to immunotherapy?

Answer 30

Mismatch repair is a good indicator for response to immune checkpoint inhibitors

Question 31

What is Ca125

Answer 31

Marker of ovarian cancer Inc in 80% advacned epithelial ovarian ca.

Question 32

Can you use Ca125 as a screening tool?

Answer 32

No <50% increased at atge 1

Question 33

What can cause elevation of Ca125?

Answer 33

Advanced ovarian Ca, breast, colon, lung cancers, Mentruation , endo, fibroids, liver disease, diverticulitis

Question 34

Whats the most common ovarian cancer?

Answer 34

Surface epithelium ( 85-90%) - Serous - 50% High grade serous - Mucious 10-15% Endometroid Clear cell

Question 35

Treatment of III-IV epithelial ovarian cancer?

Answer 35

Debulking Surgery + Chemo (Platinum + taxane, carboplatin + paclitaxel)

Question 36

What is olaparib?

Answer 36

PARP inhibitor - used in BRCA + ovarian and breast Ca - cell death by synthetic lethality Parp repairs single stranded DNA breaks

Question 37

What ovarian cancer should always undergo BRCA testing?

Answer 37

High grade serous

Question 38

Side effect of paclitaxel?

Answer 38

Neuropathy

Question 39

Side effect of doxorubicin?

Answer 39

Irreversible cardiotoxicity by apoptosis of cardiomyocytes

Question 40

Which testiculat cancer DOESN'T produce AFP?

Answer 40

Pure seminoma

Question 41

Side effects Bleomycin?

Answer 41

Cough, stretch marks, blistering, alopecia, mucositis

Question 42

Cisplatin side side effects

Answer 42

Highly emetogenic, delayed emesis, renal impairment Ototoxicity Peripheral neuropathy

Question 43

What enzyme deficiency is dangerous in fluropyrimidine use?

Answer 43

Dihydropyrimidine dehydrogenase deficiency - inability to metabolise 5FU - can lead to fatal toxicity Early mucositis and myelosupression

Question 44

What would you see in someone with dihydropyrimidine dehydrogenase deficiency if given 5FU?

Answer 44

Early myelosuppression and severe mucositis.

Question 45

What are the toxicities of fluropyrimidines?

Answer 45

5FU/Capcitebine - Mucositis - Diarrhoea - N + V - Coronary artery vasospasm - Myelosuppression

Question 46

What are the side effects of irinotecan?

Answer 46

diarrhoea Myelosuppressino Fatigue Topoisomerase inhib

Question 47

What are the side effects of Oxaliplatin?

Answer 47

Peripheral neuropathy, cold dysaethesia, fatigue, infusion reactions

Question 48

What deficiency is important in use of irinotecan?

Answer 48

UAT181 deficiency (seen in gilberts syndrome) - can lead to fatal toxicity

Question 49

What is required to use EGFR inhibitors (cetuximab) in CRC and why?

Answer 49

Must be RAS/RAF/HER2 wild type - because these are downstream in the MAPK pathway so inactivation of the TKI will do nothing.

Question 50

What targeted therapy is used if there is BRAF/RAS mutation in CRC?

Answer 50

VGEF inhibitors - bevacizumab Also used in R) CRC

Question 51

Who should have bowel screening prior to age 50?

Answer 51

- 2 first degree relatives with CRC - One first degree relative <50 w CRC - Personal Hx CRC - Familial coloractal cancer syndrome

Question 52

What bacteria is associated with colon cancer?

Answer 52

Strep Gallolyticus ( prev S.Bovis)

Question 53

What is the pattern of inheritance of HNPCC?

Answer 53

AD with high penetrance.

Question 54

What does APC gene deletion give

Answer 54

FAP - Autosomal dominant inheritance and high penetrance. CRC by age 40

Question 55

What is the pattern of inheritence for MUTYH associated polyposis?

Answer 55

AR

Question 56

How many nodes are required to be removed to be considered adequate in CRC resection?

Answer 56

12-14

Question 57

What is microsttellite instability?

Answer 57

Large repeat sequences of DNA

Question 58

BRAF, EGFR, ALK, HER2 BCR-ABL mutations are tumour suppressor genes or oncogenes?

Answer 58

Oncogene / mutation = oncogene addiction

Question 59

Which has higher risk of VTE Tamoxifen or letrozole ( aromatase inhibitors)

Answer 59

Tamoxifen has increased risk VTE + Increase risk endometrial cancer Tamox - Tumours and thrombosis

Question 60

What risk is increased with use of letrozole compared to tamoxifen?

Answer 60

Osteoporosis (Used in post-menopausal old ass osteoporotic ladies)

Question 61

What chemotherapy agents cause hand-foot syndrome? (palmer-planar erythrodysesthesia)

Answer 61

5FU, Doxorubicin

Question 62

What is the cause of chestpain in someone on a 5FU infusion?

Answer 62

Coronary vasospasm - stop the infusion

Question 63

how many lymph nodes need to be resected to say node negative for CRC?

Answer 63

minimum 14

Question 64

What is the (RACP) conversion ratio of PO morphine to SC morphine?

Answer 64

2:1 (divide PO dose by 2 to get the SC dose)

Question 65

What is the (RACP) conversion of Morphine to oxycodone?

Answer 65

2:1 ( 20mg morphine = 10mg oxycodone)

Question 66

Where does colon cancer metastasize first?

Answer 66

Liver

Question 67

Where does rectal cancer met first?

Answer 67

Lung (rectum drains by IVC)

Question 68

What are further treatments after resection gorT3-4 rectal cancer?

Answer 68

Long course chemoradiotherapy - due to risk of local recurrence being high

Question 69

What side of the colon does FAP more often get CRC?

Answer 69

Left, MUYT associated get Right sided

Question 70

What molecular pathway is most comonly mutated in right colorectal cancers?

Answer 70

BRAF

Question 71

What type of cancer is spindle cells in?

Answer 71

GIST

Question 72

What is the treatment of GIST?

Answer 72

Tumour <10cm - resect if not metastatic + imatinib If metastatic = imatinib alone

Question 73

What is the RACP conversion of SC to PO morphine?

Answer 73

1mg SC = 3mg PO

Question 74

What is the conversion of hydromorphone to morphine ( PO and PO )

Answer 74

1mg hydromorphone = 7.5mg morphine

Question 75

What is the important mutation in GIST tumours?

Answer 75

cKIT

Question 76

Other than CRC what cancers are inc risk in HNPCC?

Answer 76

Endometrial + pancreatic