1. Management of retinoblastoma
Dr Roopsi Sharma
DNB JR
MAX Hospital ,Saket

2. STAGING and CLASSIFICATION
• Reese–Ellsworth system of classifying
retinoblastoma (1964)
• Predicts the outcome after EBRT.
Based on
 no,of lesion, size of lesion
Location of lesion and viterous seeding

3. Reese–Ellsworth system of classifying
retinoblastoma (1964)
Group I: Very favorable
A:Solitary tumor, less than 4 DD, at or behind the
equator
B: Multiple tumors, none larger than 4 DD, all at or behind the
equator
Group II: Favorable
A: Solitary tumor, 4–10 DD, at or behind the equator
B: Multiple tumors, 4–10 DD, all at or behind the equator
Group III: Doubtful
A: Any lesion anterior to the equator
B: Solitary tumors, larger than 10 DD, behind the equator

4. Reese–Ellsworth system of classifying
retinoblastoma (1964)
Group IV: Unfavorable
A: Multiple tumors, some larger than 10 DD
B:Any lesion extending anterior to the ora
serrata
Group V: Very unfavorable
A: Massive tumors involving more than half of
the retina
B:Vitreous seeding

5. RE system DEMERITS:
• Doesn’t take into account retinal detachment or subretinal
tumor seeding, prognostic factors for vision preservation.
• Small anterior tumors were placed in group 3 or 4 because
they were not usually controlled by ExRT technique in use
at that time; but they are quite responsive to modern RT
techniques, cryotherapy or RT plaque therapy.
• Vitreous seeding classified as group 5b although local
vitreous seeding can often be treated with RT plaque.

6. International classification of
retinoblastoma- 2006
 Group A : small intraretinal tumors away from the disc and foveola.
• No tumor greater than 3 mm in diameter
• Located at least (3 mm) from fovea or 1.5 mm) from Optic disc.
Group B : all remaining discrete tumors confined to retina
 All other tumors confined to retina not in group A
 Subretinal fluid (without subretinal seeding) <3 or 3 mm from base of
the tumor
Group C : local subretinal fluid or seeding
 Local subretinal fluid alone >3 to 6or<6 mm from the tumor
 Viterous seeding or subretinal seeding <3 or 3 mm from tumor

7.  Group D : diffuse subretinal fluid or seeding
• Subretinal fluid alone >6 mm from the tumor
• Viterous seeding or subretinal seeding >3mm from tumor.
 Group E: presence of one or more of these poor prognostic factors
 More than 2/3 of the globe filled with tumor
 Tumor in the anterior segment
 Tumor in or on the ciliary body
 Iris neovascularization
 Neovascular glaucoma
 Opaque media from hemorrhage.
 Phthisical or prephthisical eye
 Orbital cellulitis-like presentation
Modified from Shields CL etal:internation classification predicts
chemoreduction success,opthamology 113:2276-2280,2006

8. International retinoblastoma staging
system proposed - 2006
Stage 0: Patient treated conservatively
stage-1 : eye eneucleated ,completely resected
histologicaly
stage-2 : eye eneucleated ,micoscopic residual
tumor
stage-3 : regional extension
3a- overt orbital disease
3b- preauricular or cervical lymphnode extension

9. • stage-4: metastatic disease
• 4a- heamatogenous metastasis without CNS
involvement
• 1- single lesion
• 2- multiple lesion
• 4b-CNS extension with or without any other site
of regional or metastatic disease
• 1-prechiasmatic lesion
• 2. CNS mass
• 3. leptomeningeal and cerebrospinal fluid disease

10. Goal of treatment
• Save life (main goal)
• Preserve useful vision
• Attention on late functional and craniogenic
effect as sequale to treatment.

11. TREATMENT
MODALITIES:
 Surgery: Enucleation, exenteration
 Focal therapies
 Cryotherapy
 Laser hyperthermia
 Laser photocoagulation
 Radioactive plaque applications
 External beam radiotherapy
 Chemotherapy

12. ENUCLEATION
Indications
• U/L or B/L Rb when eye is blind.
• Presence of neovascular glaucoma.
• When disease cannot be controlled by chemo or local treatment.
• Tumor invasion into anterior chamber
• Direct visulization of an active tumor is obstucted by condition like –
hemorrhage ,corneal opacity or cataract.
In c/o B/L Rb:
Eye with RD, Vitreous hemorrhage, glaucoma, painful blind eye should
be enucleated and other eye should be treated as per the disease
status.

13. Structures removed:
• Gentle removal of intact eye globe, without
perforation to avoid seeding of orbit.
• Optic nerve long segment (15mm) for presence of
tumor extension.
• Enucleation is curative in 95 % of patient with u/l ds .
• Now a days orbital implants are used at mosr centers.

14. EXENTERATION
Indications:
• Extensive local tumor breaching the globe- orbital involvement.
• (exenteration in this situation generally is followed by postoperative
radiotherapy and chemotherapy)
• Recurrence of tumor in the socket after enucleation.
Structures removed:
• The globe
• Extraocular muscles
• Lids
• Optic nerve
• Orbital fat

15. FOCAL THERAPIES
Small tumors( 3-6mm)
Used in combination with chemo
Used as a part of consevative therapy to
avoid enucleation and EBRT in u/l ds .

16. PHOTOCOAGULATION
INDICATIONS:
• Tumors up to 4.5 mm at the base and up to 2.5 mm thick, not close to the macula or disk, with no
evidence of viteros seeds .
• Tumors situated at or posterior to equator of the eye
• May be used for small tumor recurrences after irradiation.
• Local control of intraocular disease post chemoreduction
TECHNIQUE:
Argon laser, diode laser, or xenon arc photocoagulation are used
• Based on obliteration of the retinal vessels.
• 2-3 monthly sessions are required
• LOCAL TUMOR CONTROL: 70%
Shields JA et al:The expanding role of laser photocoagulation for intraocular tumors. The 1993 H. Christian
Zweng Memorial Lecture Retina. 1994;14(4):310-22

17. Complications
Transient serous retinal detachment
• Retinal traction
• Retinal hole
• Visually significant retinal vascular occlusion.

18. CRYOTHERAPY
INDICATIONS:
• Small equatorial and peripheral lesion that <3.5 mm at the base and <2mm in
height
• Local recurrence
• Tumor persistence after irradiation
• In conjunction with chemotherapy
TECHNIQUE:
Nitrous oxide probe (-80 C), 1-2 monthly session of triple freeze thaw cycle
SIDE EFFECTS: transient serous retinal detachment, retinal tear, localized preretinal
fibrosis.

19. Transpupillary thermotherapy
PRINCIPLE:
• thermotherapy has synergistic effect with chemotherapy9 ( carboplatin) – enhances the platinum
DNA adduct thus – antitumor effect .
INDICATIONS:
• Small (< 3mm) tumors, posterior to the equator
• Larger tumors, post chemotherapy.
TECHNIQUE:
• With diode laser ,focused heat at sub photocoagulation level- 42C to 60C for 5-20 min to tumor is
applied with relatively sparing of retinal vessels from photocoagulation.
• Local control of 70-80 %
COMPLICATIONS:
• Retinal traction, fibrosis, transient serous retinal detachment,.

20. RADIOACTIVE PLAQUE APPLICATION
INDICATIONS:
1.Primary plaque therapy – localized RB typically limited to 1-2 foci not involving optic disc or macula.
2. In conjunction with chemoreduction therapy- -small or moderate size lesion including those with focal
viterous seeding immediately overlying the tumor
3. Tumors <16/16mm at base and <8mm in thickness..
4. Local failure after other therapy (EBRT, chemotherapy, laser, cryotherapy)
ADVANTAGES (vs EBRT)
• Better dose localization
• Lesser risk of cataract
• Minimal risk of bone hypoplasia
• Lesser risk of second malignancies

21. PLAQUE TYPES and features
• Co60 :
• I125 : (27 to 35 kev, half- life – 60 days)- gamma rays
emitter.
• Au198, Ir192,Ru106- beta emitter
• Ir-192- (295-612kev,halflife- 74 days)
• Ru-106:( 3.5 Mev,,374 days)

22. TECHNIQUE:
1. Tumor anatomy assessed by USG
2. Incision at limbus
3. Dummy plaque with 2mm margin
4. Retention Sutures placed in sclera
5. Dummy replaced with radioactive
plaque
6. Retention sutures secured
7. Conjunctiva closed
8. Plaque removed after treatment
completion.

24. DOSAGE
• Target dose -40 Gy to the tumor apex for I-125 at 40-80 cGy/hr., and 120 Gy at
tumor base ( scleral dose)(Tumor Control = 83%; Philadelphia)
• As adjuvant after chemo: 35Gy., and 1 month after chemotherapy to reduce
toxicity.
COMPLICATIONS:
• Retinopathy ( 5 yr acturial rate= 27%)
• Cataracts(31%) (plaque used post EBRT)
• Maculopathy (25%)
• Papillopathy (26%)
• Glaucoma (11%) ( post EBRT)

25. EXTERNAL BEAM RADIOTHERAPY
INDICATIONS:
• When RB is multifocal or close to the macula or optic nerve with preserved vision
• Large tumors not amenable to focal therapies
• Vitreous seeding
• Secondary therapy to salvage chemoreduction and focal therapy failures
• Tumors involving cut end of optic nerve
• To palliate or consolidate the systemic therapy of metastatic disease.
GOALS:
• Tumoricidal dose to the entire retinal and vitreous, since
 All retinal cells have a genetic neoplastic potential
 Vitreous seeding may have occurred
 Tumor may have spread via sub retinal space
• Opposite eye irradiation be avoided if uninvolved.
• Sparing of lacrimal glands, cornea.

26. LATERAL BEAM MEGAVOLTAGE TECHNIQUE
Lateral field:
Ant border: at lateral edge of bony orbit
Posterior border: at apex of orbit
Superior border: at superior bony ridge
Inferior border: at inferior bony ridge.
• Direct lateral field if opposite eye is enucleated.
• If opposite eye present then beam slightly angled posteriorly to avoid exit
radiation to other eye.

27. ADVANTAGES: ‘D’ shaped field produced after
sheilding pituitary and alveolar processes, saves
tooth buds and pituitary.
SHORTCOMINGS: underdosage of the retina b/w
oraserrata anteriorly and equator of the globe to
save the contralateral eye.

28. DIRECT ANTERIOR FIELD ( McCormick et al)
Borders:
Superior: superior orbital margin
Inferior: inferior orbital margin
Lateral: lateral bony canthus
Medial: midline
• ADVANTAGES : Treats entire eye
Saves opposite eye
Easy to set up, reproducible
Homogenous dose to entire retina and vitreous.
• DISADVANTAGES: Cataract almost inevitable
Lacrimal gland dosage produces impaired tear production.
Exit beam through brain.

29. PROTON BEAM:
ADVANTAGES:
• Superior dose distribution
• Sparing of other eye because of stopping characteristics
• In B/L cases tissue lying in between two eyes can be saved
• Lowering the risk of radiation induced malignancies.
DISADVANTAGES:
• High bone dose while producing spread out proton beam.

30. CONFORMAL RADIATION THERAPY
ADVANTAGES: Possible to spare lens while
irradiating whole of retina.
-Substantially less dose to
surrounding soft tissue and bones.
DISADVANTAGES:
Higher integral dose increases risk of second
malignancies.

31. ExRT DOSAGE:
 dose to treat a retinoblastoma with ExRT is
40-45 Gy.- 1.8 Gy to 2 Gy/#
Dose modification needed when using RT
after chemotherapy for consolidation

32. Chemotherapy-
Used in three basic situations:
1. To locally control the intraocular disease:
Chemotherapy is used in neoadjuvant setting to
reduce the size of large tumors to a size suitable
for eradication by focal therapies
(chemoreduction).
2. To produce regression of metastatic disease
3. To prevent recurrence or metastases of locally
advanced Rb (Adj. CT)
Chemo is seldom used as a sole treatment modality.

33. Intraocular ( Subconjunctival): Carboplatin
Intrathecal: Methotrexate, cytarabine ( Brain mets, trilateral Rb)

34. LATE EFFECTS OF RADIOTHERAPY
1.Secondary Malignant Neoplasms
• Childeren woth heriditary retinoblastoma are
3 fold increased risk as compared to non
hereditary.
Cumulative incidence of secondary malignancy
after 50 years of diagnosis-
• 36 % in hereditary
• And 5.7 % in sporadic.

35. In hereditary group
• standard incidence -22 times the expected
incidence after RT and 7 times without RT.
In sporadic cases – incidence of second
neoplasm (breast cancer) 2.8 times the
normal population.
• Childeren who recived RT in 1 yr of life have
higher risk of developing second cancer
withinfield of radiation.

36. • Osteogenic sarcoma (m/c)-75%
• Soft tissue sarcoma and melanoma(25%)
• Epithelial tumors(in late adulthood) – lung
,breast ,and colon
• Lipoma

37. • 2. Bony orbital abnormalites.: Post RT and post
enucleation, significant risks of orbital mal development
and midfacial growth retardation has been observed.
• EBRT (>35Gy) , to < 6month old children accentuates the
risk
3.Cataract:Clinically significant posterior pole cataract
Anterior field techniques -85%
lens sparing techniques-28%

44. EXTRAOCULAR RETINOBLASTOMA
• Locoregional including orbital
infilteration,tumor extending into optic nerve
or to cut end of the nerve ,and lymphatic
spread to preauricular lymphnodes.
2..cns disssemination
3.Trilateral retinoblastoma
4. Metastatic retinoblastoma.

45. Orbital and locoregional
retinoblastoma
• Orbital RB occurs as aresult of progression of
the tumor via emissary vessels and sclera.
• Treatment – systemic chemotherapy and
radiotherapy.- 60-85% cure rate.
• Pt with macroscopic disease- initial chemo f/b
surgery (obivates the need of orbital
exenteration).---post op chemo and
radiation 40-45 Gy (consolidative therapy)

46. • Pt with isolated optic nerve involvement –
• Systemic chemo with radiation to entire orbit
(36 Gy ) and 9-10 Gy boost to chiasma (total
45Gy)

47. CNS disease-
• Occurs by direct extension by optic nerve.
• Rx- platinum based chemotherapy+
craniospinal irradiation( 23.4 Gy – 36 Gy to
neuraxis and a boost to 45 Gy to sites of overt
or nodular ds)

48. Trilateral retinoblastoma

49. CONCLUSIONS
• Early detection and treatment can save the vision in retinoblastoma.
• With the advent of neoadjuvant chemoradiation , treatment goal has now
shifted from enucleation to visual preservation in most of patients.
• Combined approach of Ophthalmologist, Radiation Oncologist, Pediatric
Oncologist, Medical Physicist, Pathologist, Radiologist, Geneticist with
individualization of treatment often leads to favorable outcome in terms
of overall survival and vision preservation.