MANAGEMENT OF RETINOBLASTOMA

Claudio Owino

RETINOBLASTOMA

• Most common primary, malignant, intra-ocular 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. – 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

• (2) Heritable – 40% of the cases.– 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.

Genetic CounselingPrinciples:

• 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

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:

in all clinically suspected cases both eyes to be evaluated thoroughly.

Radiological Investigations (Orbit & Brain) 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.

Haematological Evaluation Hb., FBC, LFT’s,RFT’s, ESR, LDH, etc.

REESE-ELLSWORTH CLASSIFICATION

• Group I: Very 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

• Group II: Favorable prognosis– A.Solitary lesion 4-10dd in size, at or behind the equator– B. Multiple tumors, 4-10 dd in size, behind the equator

• Group III: Doubtful prognosis– A. Any lesion anterior to the equator– B. Solitary tumors larger than 10dd behind the equator

• Group IV: Unfavorable prognosis– A. Multiple tumors; some larger than 10 dd behind the equator.– B. Any lesion extending anteriorly to the ora serrata

• Group V: Very unfavorable prognosis– A.Massive tumors involving over half the retina.– B.Vitreous seeding.

STAGING(ST. JUDES)• Stage I: Tumor confined to the retina

(May be unifocal or multifocal).• Stage II: Tumor confined to globe

– With vitreous seeding– Extending to choroid & ON head

• Stage III: Extra-ocular extension(regional)– Beyond cut end of ON– Thru’ sclera into orbital contents

• Stage IV: Distant metastases – Thru’ optic nerve to the brain– Blood-borne to soft-tissue & bone– Bone marrow metastases

Management• OBJECTIVES

– 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:

– Cobalt 60; Iodine 125; Iridium 192,; Ruthenium 106.• External Beam Radiation:• Enucleation:• Orbital Exenteration:• Systemic Chemotherapy for metastatic

disease

Management- Cont’d • 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.

• c) Large tumors– Chemoreduction and then local treatment such as cryotherapy

and photocoagulation– -Enucleation obtaining a long piece of optic nerve.

• d) Extra-ocular extension– External beam radiotherapy– Orbital Exenteration

• 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:

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

Coat’s disease Retinopathy of prematurity. Toxocaral granuloma. Retinal dysplasia Incontinentia pigmenti. Retinal astrocytoma. High retinal detachment

Leucocorrhea Extra-ocular extension

Treatment options at MTRH

• Enucleation• Orbital Exenteration• Systemic Chemotherary

A very low risk All < 3 mm T1a

>1.5 mm from foveola or optic nerve

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

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 Analysis on retinoblastoma in

Kenya

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 patientso Chemotherapy drugs unavailable and

expensive

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

Way forward-Cont’d

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 don’t sort ourselves out!!!!!!!!!!

THANK YOU