Retinoblastoma

Question 1

what causes retinoblastoma

Answer 1

biallelic loss of RB1 gene

Question 2

what is the role of the Rb1 gene

Answer 2

• maintain genomic stability, epigenetic processes

Question 3

what is the most common recurrent gene mutation in RB

Answer 3

BCOR (BCL6 corepressor)

Question 4

what is the most common recurrent gain in RB?

Answer 4

myc-n amplification (still overall very rare)

Question 5

what are the two main types of RB?

Answer 5

non-hereditary and hereditary

Question 6

what is non-hereditary RB?

Answer 6

• due to a mutation in both alleles of a somatic cell
• median time to diagnosis of 30 months
• approx 75% of patients

Question 7

what is hereditary RB?

Answer 7

due to germline biallelic inactivation of RB1, median time to diagnosis of 15 months

Question 8

risk factors for developing RB

Answer 8

paternal exposure to welding fumes, ionizing radiation, working in the metal industry

Question 9

presentation of RB

Answer 9

leukocoria (65-75%)
strabismus (10-15%)
nystagmus (5-10%)

Question 10

how is RB staged

Answer 10

based on if there is extraretinal extension or extraocular disease (orbital or extra orbital)

Question 11

general treatment options for RB

Answer 11

intra-arterial chemo
systemic chemo
focal therapies
RT

Question 12

what systemic chemotherapy agents are used in RB

Answer 12

vincristine
carboplatin
etoposide

Question 13

what intra-arterial chemo is used in RB

Answer 13

melphalan +/- carboplatin/topotecan

Question 14

what focal therapies are used in RB

Answer 14

cryotherapy
thermotherapy
photocoagulation
can also use brachytherapy

Question 15

when is enucleation indicated

Answer 15

always for group E disease (> 2/3 of globe filled with tumour, tumour in atnerior segment or ciliary body, invading iris)

Question 16

what percent of unilateral vs bilateral RB have germline mutations?

Answer 16

unilateral - 15% have germline mutations

bilateral - 100% have germline

Question 17

how do you perform surveillance for RB?

Answer 17

genetic testing of all family members (need sequencing) along with dilated eye exams q4wks in babies (while waiting for genetic results, and for those found to have germline RB1 inactivation)

Question 18

what is most common SMN in RB patients?

Answer 18

25-40% are osteosarcoma (also soft tissue sarcomas, melanoma, lung cancer etc)

Question 19

what is trilateral RB

Answer 19

asynchronous midline intracranial tumor, occurs in approx 5% of bilateral RB usually 2-3 yrs after diagnosis - need to screen with MRIs every 6 months

Question 20

what defines group A tumour

Answer 20

small < 3mm, far from fovea and optic disk

Question 21

what defines group B tumours

Answer 21

may be > 3mm but is confined to the retina

Question 22

what defines group C tumours

Answer 22

local subretinal fluid or vitreous seeding

Question 23

what defines group D tumours

Answer 23

diffuse subretinal fluid or seeding

Question 24

what defines group E tumours

Answer 24

> 2/3 of globe filled with tumour

poor prognosis features - tumour in anterior segment, invasion of iris/cilary body

Question 25

metastatic work up for RB

Answer 25

bone scan
bone marrows
CSF
MRI brain