MANAGEMENT OF RETINOBLASTOMA

Claudio Owino

RETINOBLASTOMA
Most common primary, malignant, intraocular tumor of childhood. Occurs in 1:20,000 live births. There is no sexual predilection and majority become apparent before the age of three years. Bilateral in 25-30% of the cases RBL results from malignant transformation of premature retinal cells before final differentiation.

Genetic Aspects
May be heritable or non-heritable. The predisposing gene (RPE 1 gene), is located at region 14 in the long arm of chromosome thirteen (i.e 13q 14) Non-Heritable- 60% of the cases.

(2) Heritable 40% of the cases.

Tumor arises at the somatic level in a single retinal cell. Single tumor with an average age at presentation of two years 85% of patients with unilateral RBL fall in this category Autosomal dominant with high penetrance. All bilateral cases & about 15% of unilateral cases Most hereditary cases are multifocal Have a predisposition to develop 2nd non-ocular malignancies including pinealoblatoma & osteogenic sarcoma.

Principles: Unaffected parent with one affected child have ~5% risk of producing another affected child. There are 40% chances of developing tumor in a sibling of a child with bilateral retinoblastoma If two or more siblings affected, the risk of subsequent children being affected rises to 50% A survivor of hereditary RBL has a chance of almost 40-50% that offspring will also develop the tumor

Genetic Counseling

Presentation
Leukocoria, (yellowish-white pupillary reflex)commonest presentation Strabismus (Squint) Secondary glaucoma Anterior segment invasion (multifocal iris nodules, pseudo-hypopyon) i.e. Red eye Orbital inflammation ( may mimic orbital cellulitis) Proptosis Metastases (to regional nodes and brain). Nystagmus may be seen in bilateral cases. On routine exam.

Clinical Evaluation & Staging

Clinical: history and presentation. Indirect Ophthalmoscopy: tumor size (DD). EUA: Radiological Investigations (Orbit & Brain)
in all clinically suspected cases both eyes to be evaluated thoroughly.

Haematological Evaluation

Ultrasonography: detects presence of calcification & calculates tumor dimensions CT scanning: detects calcification & shows involvement of the ON, orbital & CNS extension and presence of a pinealoblastoma MRI: superior to CT for ON evaluation& for detection of a pinealoblastoma.
Hb., FBC, LFTs,RFTs, ESR, LDH, etc.

 Group I: Very favorable prognosis

REESE-ELLSWORTH CLASSIFICATION

Group II: Favorable prognosis

A. Solitary tumor, less than 4 disc diameters (dd) in size, at or behind the equator. B. Multiple tumors, none over 4dd, at or behind the equator A.Solitary lesion 4-10dd in size, at or behind the equator B. Multiple tumors, 4-10 dd in size, behind the equator A. Any lesion anterior to the equator B. Solitary tumors larger than 10dd behind the equator A. Multiple tumors; some larger than 10 dd behind the equator. B. Any lesion extending anteriorly to the ora serrata A.Massive tumors involving over half the retina. B.Vitreous seeding.

Group III: Doubtful prognosis

Group IV: Unfavorable prognosis

Group V: Very unfavorable prognosis

STAGING(ST. JUDES)
Stage I: Tumor confined to the retina (May be unifocal or multifocal). Stage II: Tumor confined to globe Stage III: Extra-ocular extension(regional) Stage IV: Distant metastases
Beyond cut end of ON Thru sclera into orbital contents With vitreous seeding Extending to choroid & ON head

Thru optic nerve to the brain Blood-borne to soft-tissue & bone Bone marrow metastases

 OBJECTIVES

Management

Survival of the patient Preservation of the globe Focus on VA comes later, after safety of the patient& globe is established.

Therapy is tailored to each individual case. Based on the overall situation including:
Threat of metastatic disease Risks for second cancers Systemic status Laterality of the disease Size & location of the tumor(s). Estimated visual prognosis

Management modalities

Intravenous chemoreduction: Thermotherapy: Cryotherapy: Laser photocoagulation: Plaque radiotherapy:

External Beam Radiation: Enucleation: Orbital Exenteration: Systemic Chemotherapy for metastatic disease

Cobalt 60; Iodine 125; Iridium 192,; Ruthenium 106.

Management- Contd
a)Small tumors(</= 4mm diameter).
Laser photocoagulation or trans-pupillary thermotherapy Cryotherapy

b)Medium Tumors: ( </=12 mm diameter and 6 mm thickness)

Plaque Radiotherapy. Chemotherapy: combination of carboplatin, vincristine and etoposide. May be followed by local treatment with cryotherapy. External beam radiation: Associated with a lot of complications such as cataract, radiation retinopathy, etc.
Chemoreduction and then local treatment such as cryotherapy and photocoagulation -Enucleation obtaining a long piece of optic nerve.

c) Large tumors

d) Extra-ocular extension
Orbital Exenteration

External beam radiotherapy

Metastatic disease is treated by high dose chemotherapy

Chemotherapy Protocol
Carboplatin: 560mg/m2 IV, day 1 Etoposide: 200mg/m2 IV, day 3 Vincristine: 1.4mg/m2 IV, day 22 Cyclophosphamide: 150mg/m2 PO, day 22 to 27 Repeat cycle every 28 days

Prognostic factors
ON involvement beyond the point of surgical transection is associated with 65% mortality rate. If ON is uninvolved the mortality rate is only 8% Choroidal invasion Tumor size and location: posterior tumors have a better survival rate Cellular differentiation. Older children tend to have a worse prognosis.

Differential Diagnosis
PHPV Persistent hyperplastic primary vitreous.
-Typically occurs in a microphthalmic eye and is unilateral in 90% of cases. -Characterized by a retrolental mass into which elongated ciliary processes are inserted.

Inflammatory cyclitic membrane: Coats disease Retinopathy of prematurity. Toxocaral granuloma. Retinal dysplasia Incontinentia pigmenti. Retinal astrocytoma. High retinal detachment

-Seen in toxocana endophlthalmitis or occasionally in severe intermediate uveitis.

Leucocorrhea

Extra-ocular extension

Treatment options at MTRH

Enucleation Orbital Exenteration Systemic Chemotherary

very low risk

All < 3 mm >1.5 mm from foveola or optic nerve

T1a

Squint

Cataract

FACTS AND FIGURES-KNH

Most present late, 50% with disease obviously outside the eye ball Average delay in presentation; 39 weeks Only 26% of retinoblastoma patients survive 3 years after diagnosis

Situation Analysis on retinoblastoma in Kenya

Similar challenges in all regions; included Lack of awareness among the medical workers as well as general public Poor referral network and long distances No psychosocial support for patients except at MTRH No support to affected families

Situation cont
o Delay in histopathology reports and lack of standardized reporting format o No standardized protocol for management of retinoblastoma patients o Lack of communication between peripheral centres and referral centres o Lack of follow up of patients o Chemotherapy drugs unavailable and expensive

Way forward
1. Streamline management of Retinoblastoma To come up with standardized protocol Histopathology to come with a standardized request and reporting forms Chemotherapy To come up with a regime of international standard - cost the regime - source for chemotherapy drugs

Way forward-Contd
2. Retinoblastoma Awareness Create awareness in health workers especially nurses in MCH
Use the media, retail chains, transport industry and communication industry to spread awareness Professional talks and articles in the media Sensitize DHMTs on retinoblastoma Design local posters on retinoblastoma

3. Partnership and resource mobilization 4.Psycho-Social & Family Support

Nothing is impossible

If we dont sort ourselves out!!!!!!!!!!

THANK YOU