Oncology

Question 1

What cancers are associated with HNPCC (Lynch Syndrome)?

Answer 1

Colon cancer Endometrial cancer Gastric cancer Small bowel cancers CNS cancers eg glioblastoma Urinary tract cancers

Question 2

At what stages is chemotherapy used for lung cancer? What is the drug basis?

Answer 2

Defined role for adjuvant chemotherapy from stage 2 onwards, controversial in stage 1b

Use a cisplatin containing regimen. Alkylating agents have an adverse effect on survival

Question 3

What is the role of cetuximab and panitumumab in colorectal cancer?

Answer 3

These are EGFR antibodies

Can be used in metastatic colorectal cancer when it is left sided and KRAS, NRAS, BRAF wild type

Question 4

What are the side effects of FOLFOX?

Answer 4

5-FU - hand/foot, diarrhoea, coronary spasm

Irinotecan - anti-cholinergic (give with atropine)

Oxaliplatin - peripheral neuropathy

Question 5

What mutations are seen in prostate cancer?

Answer 5

PTEN mutation - more frequent in metastatic disease

TMPRSS2-ERG fusion gene - 50%

DNA repair abnormalities - 20%

Question 6

What is biochemical reccurent disease and what is its management in prostate cancer?

Answer 6

When PSA rises but no disease recurrence can be seen on imaging

Treat with androgen deprivation therapy

Question 7

What is the staging work up for prostate cancer?

Answer 7

Biospy and PSA
MRI pelvis

Bone scan

Can do PSMA PET scan which is very sensitive but not very specific

Question 8

What is the mechanism of action of abiraterone? When is it used?

Answer 8

It blocks 17a hydroxylase and c17, 20lyrase in teh adrenal to stop androgen production

Used in castrate resistant prostate cancer

Question 9

What is the mechanism of action of enzalutamide? When is it used?

Answer 9

A potent androgen receptor antagonist which blocks testosterone binding, receptor activation and nuclear translocation.

It is used in castrate resistant prostate cancer

Question 10

What drugs must be given with abiraterone?

Answer 10

Continue the baseline antiandrogen eg groselin

Must be paired with steroids to mitagate side effects due to acculmulation of steroid precursors (works on the CYP17 pathway in the adrenal gland)

Question 11

What are the most common driver mutations in melanoma?

Answer 11

BRAF - 40-50%

RAS - 20%

NF-1 - 10-15%

Question 12

When is chemotherapy used in prostate cancer? What agents are used?

Answer 12

Only in metastatic disease

Docetaxel upfront if high risk

As 2nd and 3rd line options

Cabazitaxel is another option for very refractory disease

Question 13

What is CDKN2A mutation associated with?

Answer 13

Familial melanoma

Question 14

What are the TKIs used in melanoma?

Answer 14

Dabrafenib + trametinib

Vemurafenib + gobimetinib

a BRAF and a MEK inhibitor - always paired

Used in BRAF mutated stage 3 and 4 disease

Question 15

What are the common mutations in clear cell renal cancer?

Answer 15

Chromosome 3p deletions

VHL inactivation

Question 16

What are the side effects of dabrafenib and trametinib?

Answer 16

Rash, photosensitivity, fever, fatigue and GI upset

Skin cancer risk reduced by the combination

Question 17

What is the HENG classification?

Answer 17

Used to risk stratify metastatic renal cell cancer:

• <1yr from diagnosis to treatment
• KPS <80%
• Anaemia
• Hypercalcaemia
• Neurophilia
• Thrombocytosis

Each give a point. 0 is good prognosis and >3 is poor

Question 18

What is the 1st line treatment for metastatic renal cancer? What are the other options for treatement?

Answer 18

If intermediate or high risk then dual check point inhibitors

Single agent PD-1

TKI - sunitinib and pazopanib 1st line then cabozantinib and axilinib

Evrolimus

Bevacizumab

Question 19

What is the most powerful prognostic factor in breast cancer?

Answer 19

Nodal status

Question 20

What are luminal A and B breast cancer?

Answer 20

Both are ER positive

A is HER2 negative

B is HER2 positive

Question 21

What is the malignancy risk with BRCA1 and 2?

Answer 21

BRCA 1:

• Breast Ca 50-80%
• Ovarian Ca 25-40%
• Prostate 30%

BRCA 2:

• Breast 40-70%
• Ovarian 15-20%
• Prostate 40%

Question 22

What type of breast cancer does BRCA1 and 2 get?

Answer 22

BRCA1: 70% triple negative

BRCA2: 15% triple negative (same as general population)

Question 23

What is neratinib?

Answer 23

A HER2 and EGFR inhibitor

Used in HER2 positive breast cancer in the adjuvant setting after completion of trastuzumab

Risks - diarrhoea and hepatotoxicity

Question 24

How do trastuzumab and pertuzumab differ?

Answer 24

Both a HER2 inhibitors used primarily in breast cancer

Pertuzumab binds to subdomain II and inhibits dimerization of HER2 with HER3

Trastuzumab binds to subdivision IV inhibiting cleavage and signalling

Question 25

What are the cyclin D inhibitors?

Answer 25

Palbociclib and ribociclib Tyrosine kinase inhibitors which inhibit CDK4/6 binding to its ATP pocket. CDK normally works with cyclin D for the G1-S transition. Used in 1st line ER positive metastatic breast cancer with an aromatase inhibitor Risks are myelosuppresion, prolonged QTc, hepatotoxicity

Question 26

What is the metabolism of tamoxifen?

Answer 26

Metabolised by CYP2D6 Altered by genetic variation Interactions with sertraline, escitalopram, citalopram

Question 27

What are the histological types of breast cancer? Which are more aggressive?

Answer 27

Ductal - 75-80%, more aggressive Lobar - tend to be lower grade and ER pos Others: Cribiform, tubular, mucinous - endocrine responsive Medullary, metaplastic - aggressive Secretory juvenille, adenoid cystic, apocrine - low risk

Question 28

What is trastuzumab emtansine? What is its use?

Answer 28

An antibody drup conguagte Anti-HER2 paired with a microtubule inhibitor Used for metastatic HER2 breast cancer as 2nd line

Question 29

What is the order of treatment for castrate resistant prostate cancer?

Answer 29

Abiraterone then enzalutamide the chemotherapy

Question 30

What is the downstream pathways of a VHL mutation?

Answer 30

Found on short arm of chromosome 3 Mutations in this or loss of 3p causes an accumulation of hypoxia inducible factors which then cause the transcription of factions such as VEGF

Question 31

How is seminoma and non-seminoma differentiated?

Answer 31

AFP is always normal in seminoma

Question 32

What type of testicular cancer is radiosensitive?

Answer 32

Only seminomas (AFP negative)

Question 33

What is the mechanism of action of PARP inhibitors?

Answer 33

Poly-ADP ribose polymerase Normal action is single strand DNA break repair as well as expression f inflammatory genes and programmed cell death. PARP inhibitors block PARP on the DNA inhibiting it as well as preventing other DNA damage repair proteins from working. This leads to a double strand break Double strand breaks are imposible to repair in teh setting of BRCA

Question 34

What are the indications for PARP inhibitors?

Answer 34

BRCA positive breast cancer - must be HER2 neg Metastatic prostate cancer with DNA repair mechanism defects High grade serous or endometrioid ovarian cancer

Question 35

What is the most important prognostic factor in head and neck cancers?

Answer 35

SIgnificantly better prognosis if there is p16 on immunohistochemistry. This is a marker of HPV association

Question 36

What infections are associated with head and neck cancers?

Answer 36

Nasopharyngeal - EBV Other - HPV infection

Question 37

What is the treatment for ALK positive metastatic lung cancer?

Answer 37

Crizotinib