Other Onc - Skin, Lung, Thyroid

Question 1

What are common mutations in Melanoma?

Answer 1

BRAF (40%)

• BRAF V600E (80%)
• BRAF V600K (5-30%)
  other: NRAS, C kit, NFI, CTNN31

Question 2

What is the EGFR Pathway?

Answer 2

EGFR > RAS > RAF > MEK > ERK

Question 3

What is the treatment for melanoma?

Answer 3

BRAFi

• Vemurafenib (V600E)
• Dabrafenib, Encorafenib (all BRAF)
  1. BRAFi + MEKi
• Vemurafenib + Cobimetinib
• Dabrafenib + Trametinib
  2. Immunotherapy
• PD1
• CTLA4
• C kit (Imatinib)

Question 4

What is the general management of NSCLC according to staging?

Answer 4

Stage 1 (no nodes)/Stage 2 (hilar nodes): RESECT + CHEMO
Stage 3 (mediastinal nodes):
- NEOADJ CHEMO > RESECT
- CHEMO+RT + Durvalumab
Stage 4 (mets): Palliative Chemo (Platinum doublet) + PD1 (if wild type)
- if PDL1 is high can use pembrolizumab as MONOTHERAPY

• PD1/PDL1 not great in EGFR and ALK driver mutations

Question 5

What is the management of NSCLC- Squamous Ca?

Answer 5

PDL -: Chemo/Immuno
PDL >50%: Pembrolizumab
Chemo: Platinum Doublet
Immuno: Nivolumab (PD1) + Ipilimumab (CTLA4)

Question 6

What is the management of NSCLC non-squamour ca?

Answer 6

DRIVER MUTATION
EGFR (Osimertinib) - T790M resistance
- non smoker asian female
- exon 19 deletion
ALK (Crizotinib, alectinib, lorlatinib)
- chr 2 rearrangement: EML4- ALK fusion gene
- Adenocarcinoma, young light smoker
- Alectinib for CNS
ROS1 (Crizotinib, entrectinib)
KRAS (Sotorasib)

if it fails > CHEMO/IMMUNO
Chemo - Platinum doublet + pemetrexed (antifolate)
Immuno - Pembrolizumab/Atezolizumab IF PD1> 50%

Question 7

What is the management of SCLC according to stages?

Answer 7

limited (one hemithorax/ipsilated nodes): CHEMORT + prophylactic Brain irradiation
Extensive (not limited): Chemo + Atezolizumab (PDL1)
Chemo: Cisplatin + Etoposide

Question 8

What Enzyme metabolises Capecitabine?

Answer 8

DPD - Dihydropyrimidine dehydrongenase

Question 9

Most potent chemotherapy when extravasated

Answer 9

Vesicants: tissue necrosis - anthracyclines, alkylating agents (

Question 10

What US features are associated with increased risk of thyroid ca?

Answer 10

1. microcalcifications
2. nodule hypoechogenicity
3. irregular margins
4. taller than wide

Question 11

What are the genetic mutations associated with Papillary Thyroid Ca ?

Answer 11

RAS
BRAF
RET/PTC (MEN!!)
TERT

Pap is more common than follicular *

Question 12

What genetic mutations are associated with follicular thyroid ca?

Answer 12

RAS
PIK3A
PAX/PPAR Gamma

Question 13

How to manage Thyroid Cancer?

Answer 13

1. SURGERY
2. ?TSH suppression - depends on risk status of tumour (lower risk, don’t need to suppress TSH too much)
3. Radioiodine: ablate normal tissue for ADJ tx to micromets (intermediate/high risk)
4. External Beam Radiation Therapy
   USE Thyroglobulin to monitor for recurrence (Check Thyroglobulin antibodies incase false neg)

Question 14

How to manage Metastatic Thyroid Ca?

Answer 14

1. Lenvantinib (TKI - VEGF, FGFR, RET, KIT)
2. Vendetanib - Medullary Thyroid (VEGF, EGFR, RET)

Targeted

1. Dabrafenib (BRAF) in anaplastic
2. Trametinib (MEK1/2) in anaplastic
3. Carbozanitinib (VEGFR) in Medullary
4. Selpercanitinib (RET) in Medullary (MEN2)

Question 15

What is the difference between MEN1 and MEN2?

Answer 15

MEN1 (menin gene) PPP - pituitary, parathyroid, pancreas,
MEN2A (RET) - PMP - Parathyroid, Medullary thyroid, phaeochromocytoma
MEN2B (RET) - MMP - Marfanoid, Medullary thyroid, phaeochromocytoma

Question 16

What Biologics are high risk for thyroid issues?

Answer 16

PDL1/PD1

CTLA4

Question 17

What is the management for immunotherapy associated hyperthyroidism?

Answer 17

Symptomatic Mx: Propanolol/Atenolol
TSHr Ab +VE - Carbimazole
Painful Thyroiditis - Prednisone + Taper

Question 18

When do you consider treating immunotherapy associated hepatotoxicity?

Answer 18

ALT/AST - 5-20x ULN - start steroids, stop immunotherapy
if HIGH BILI/INR - IV methylpred
if getting worse on PO Steroid > IV Steroid > MMF > Tacrolimus

Question 19

What is the management of Immunotherapy associated gastrotoxicity?

Answer 19

Mild - 4+ diarrhoea 
- Loperamide
Moderate - 4-6 diarrhoea
- WH immunotherapy
Severe - >7 diarrhoea 
- WH immunotherapy + IV methylpred

Steroid > infliximab > MMF/Tacrolimus

Question 20

What is the management of Immunotherapy associated Pneumonitis?

Answer 20

Grade 1: Radiographic Change - Ground Glass/ NSIP
- ? maybe delay immunotherapy
Grade 2: Mild/Mod Sx 
- WH immunotherapy
- Treat if infection, if not STEROID
Grade 3: Severe - Hypoxic
- Stop immunotherapy 
- IV methylpred + empiric Abx - WORSE> Infliximab

Question 21

What is the mechanism of alkylating agents?

Answer 21

Crosslinks DNA
IE: -amide
Cyclophosphamide, Ifosfamide, Temozolamide

Question 22

What is the mechanism of anthracyclines?

Answer 22

topoisomerase II inhibitor
ie: -rubicin
Doxorubicin, epirubicin, mitoxantrone

Question 23

What is the mechanism of azathioprine?

Answer 23

Inhibit purine synthesis