RETINOBLASTOMA

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INTRODUCTION
Most common intraocular malignancy of childhood arising from

embryonic multipotent neural retinal cell.

Seventh MC solid tumor in childhood. Unifocal/multifocal. Unilateral (70%) or bilateral (30%). Sporadic (94%) or familial (6%). Non hereditary (50-60%) or hereditary (40-50%). Congenital disease though usually not recognized at birth.
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HISTORY
First mentioned by Petras Pawius in Amsterdam in

1597.

James Wardrop, a scottish surgeon first recommended

enucleation for saving lives in patients of retinoblastoma in 1809.

Verhoeff confirmed the origin from undifferentiated

retinal cells, named retinoblastoma in 1900s.

American Ophthalmology Society first adopted the

term retinoblastoma in 1926.

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EPIDEMIOLOGY
Median age Unilateral: 2 years, 80% cases are below 3 to 4 years. Bilateral: < 12 months. Incidence 1 in 15,000-20,000 live births in the US, higher in developing countries including India (about 1532 cases per year, highest in the world). No racial or gender predeliction. Associated in 0.05% cases of retinoblastoma. Cleft palate, dentinogenesis imperfecta, incontinentia pigmenti etc. with no mental impairment.

Congenital anomalies

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FORMS OF PRESENTATION

SPORADIC (Non- hereditary) Unilateral, unifocal. 60% of all cases. Present later. Children of the affected are normal. Chromosomal anomaly is a somatic mutation. Relatives have a low risk of RB development.

FAMILIAL (Hereditary) 85% bilateral, multifocal. 40% of all cases. Present earlier. Children of the affected have 45% chance of inheritance. Chromosomal anomaly is a germline mutation. Relatives have a high risk of RB development. Autosomal dominant with high penetrance.

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GENETICS
RB represents a prototypical model demonstrating genetic etiology

of cancer. It is caused by mutation of the RB gene, a TSG on long arm of chromosome 13 (13q14.1-q14.2). Normal individual inherits two copies of this gene one from each parent.

ALFRED KNUDSONS TWO HIT HYPOTHESIS (1971) Two separate loss of function mutations are required to inactivate both the homologous loci of the RB gene for malignant phenotype to be expressed

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GENETICS-SPORADIC RB
Two mutations are required for the development of retinoblastoma. Sporadic retinoblastoma

Child starts with two wild type alleles (RB+/RB+). Both alleles must mutate to produce the disease (RB/RB). Probability of both mutations occurring in the same cell is low; only one tumor forms (e.g., one eye). First hit occurs after conception in utero or in early childhood in retinal cells. All cells in body are not affected as germ cells are not involved. Second somatic mutation results in loss of other normal allele.

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GENETICS-HEREDITARY RB

Hereditary retinoblastoma
Child starts with heterozygous alleles (RB/RB+). Only one mutation is required to produce disease (RB/RB). Mutations resulting in loss of heterozygosity (LOH) are more

probable in rapidly dividing cells, and multiple tumors occur (e.g., both eyes). First hit occurs in utero in germ cells before conception or is inherited from a parent. All cells of body affected. Second hit occurs in any retinal cell. Increased risk for second malignancies

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IAEA Pediatric Radiation Oncology Training Dr Laskar Version 1 June 2009

MOLECULAR PATHOGENESIS
z

RB1 protein: cell cycle regulator, checkpoint between G1 & S-phase. Key factor in RB protien functioning is the phosphorylation status. Normally unphosphorylated and suppresses entry into S-phase by binding to E2F (transcription apparatus). Phosphorylation by cyclin/cdks abolishes inhibition & causes dissociation of E2F which binds to DNA & promotes progression through cell cycle.

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EVENTS IN CELL CYCLE

Note Rb Dephosphorylation

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Note Rb phosphorylation

Transcription apparatus
DNA G1

Rb protein inhibits gene transcription

G1 control point

Cyclin/cdk

Phosphorylated Rb protein moves away, allows gene transcription

P

DNA G1 G1 control point S

Phosphorylation of retinoblastoma protein by cyclin/cdk abolishes inhibition of gene transcription

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GENETIC COUNSELLING
z

z z z

Parents having a child with RB (at the time of enucleation or during treatment) & patients with family history of RB should undergo genetic counselling (blood sample only). Recommendation: examination at birth & 4 monthly thereafter until 4 years of age. Tumor tissue & blood required in sporadic cases while only blood sample sufficient in inherited cases. Molecular tests:
z z z

Direct analysis of the constitutional mutation of RB1 gene performed on constitutional DNA. Indirect analysis of the allele carrying the mutation. Tumor cell LOH evaluation.

Patients should be informed about the risk of transmission and of second primary malignant tumor development (20% at 10 years , 50% at 20 years & 90% at 30 years).

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PATTERNS OF GROWTH
TUMOR ENDOPHYTIC EXOPHYTIC MIXED DIFFUSE INFILTRATING

Arises from inner layers of retina. Fills the vitreous cavity Anteriorly reaches aqueous venous chanells May permeate through lymphatic channels. Visual disturbance & white eye reflex.
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Arises from outer layers of retina. Fills the subretinal space. Posteriorly causes serous RD. Choroidal invasion through Bruchs membrane. Proptosis & RD.

Most common growth pattern

No mass, only signs of endophthalmitis. Average age 6 years. Pseudohypopyon resembling inflammatory reaction. Diagnosis delayed & most difficult. UL & sporadic

PATTERNS OF GROWTH

Endophytic lesion White eye reflex.

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Exophytic lesion
Proptosis.

NATURAL HISTORY
z z z z

Rapidly progressive tumor. Untreated fills the eye & completely destroys the globe within 6 months i.e local extension is the rule. Metastasis (BM, bone, LNs and liver) is rare at presentation. Complete tumor regression may occur by unknown mechanism (occlusion of central retinal artery, severe inflammatory reaction and massive necrosis leading to pthisis bulbi).
ROUTES OF SPREAD
Anterior spread to Conjunctiva, Eyelids & Extra ocular tissue Lymphatic dissemination Hematogenous dissemination From orbital, bone or lymphatic invasion

Direct local Tumor infiltration

Subarachnoid Space Of optic nerve

Choroid invasion

CSF dissemination To brain & spine

Scleral invasion Orbital soft tissue, bone & IAEA Pediatric Radiation Oncology Training invasion Dr Laskar Version 1 brain June 2009

HISTOPATHOLOGY
z

Composed of uniform small round or polygonal mitotically active cells. Vaible tumor cells surround blood vessels & form pseudorosettes. Cells are arranged in three characteristic types:
z

z z

Flexner-Wintersteiner rosette: characteristic of RB but also seen in pineoblastoma & medulloepithelioma. Cells resembles retinoblasts of embryo. Also Homer-Wright rosette. Calcification +++ Fleurette Necrosis ++ Multifocality.

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CLINICAL PRESENTATION
z z

Developed countries: present with signs rather than symptoms, IO tumor without local extension. Developing countries: diagnosed only after an enlarged eye or gross orbital extension.

Leucokoria (60%): lack of red reflex of the eye in large tumors, RD, retrolental mass or vitreous opacification due tumor cells which is often noticed by the mother. 2. Strabismus (20%): disruption of fusional reflex due to loss of central vision from a tumor in the macula. 3. Rubeosis iridis (17%): MC in advanced cases due to extensive tumor necrosis releasing angiogenic factors. 4. Heterochromia. 5. Spontaneous hyphaema 6. Glaucoma: neovascular or closed angle. 7. Pseudohypopyon: seeding of AC in endophytic or diffuse infiltrating tumors. 8. Pain: glaucoma or inflammation. IAEA Pediatric Radiation Oncology Training 9. Proptosis of eye. Dr Laskar Version 1 June 2009 1.

DIFFERENTIAL DIAGNOSIS
LEOCOKORIA TOXOCARIASIS PHPV COATS DISEASE

Congenital:traid of convulsions, cerebral calcificaton & BL chorioretinitis + cataract + microphthalmus. Non congenital: in older children in UL eye due To localized inflammation by dead larvae. Diagnosed by ELISA IgM & angiography. Mimics endophytic RB.
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Embryonal vessels do not regress resulting in anterior RD or posterior subcapsular cataract. Associated with retinal dysplasia. No H/O prematurity or oxygen administration. Mimics endophytic RB

Congenital retinal telengiectasias. MC in males UL in first or second decade. Peripheral localized fusiform dilations of retinal vessel. Exudation rich in lipids & foamy macrophagess into subretinal space results in RD. Mimics exophytic RB.

DIAGNOSTIC EVALUATION

HISTORY: Administration of oxygen at birth, eating of dirt, association with dogs & FH of bone tumors or RB. SYMPTOMS & SIGNS: Ocular as well as systemic.

OPHTHALMOSCOPIC EUA: z Indirect ophthalmoscopy with pupillary dilation & general anesthesia. z Number, size, location (anterior or posterior), laterality, disc diameter, subretinal fluid or seeds noted and degree of exophthalmos measured. z Detailed mapping done with appropriate diagrams & description (relation with ora serrata, optic disc & macula). z Creamy pink or snow white mass projecting into the vitreous. z Poorly developed stroma gives way to tumor bits forming vitreal seeds z RD, vitreal opacification & hge make diagnosis difficult.
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STAGING
z

Though most cases are diagnosed clinically, imaging is done: z Confirm diagnosis.

Estimate tumor size. z Document intralesional calcium. z Assess for spread of tumor into optic nerve, choroid, sclera & orbit. z Detect ectopic disease in pineal or suprasellar region. Differentiating RB from other ocular lesions in child presenting with atypical features (only RD or opaque vitreous, atypical mass).
z

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OCULAR ULTRASOUND

z z z z

Demonstrates a mass more echogenic than the vitreous on B mode & highly reflective intrinsic echoes of fine calcifications on A mode. RD may also be seen in exophytic tumors. Accuracy: 80% (limited by vitreal opacities & RD). Limited evaluation of medial & lateral extension, extraocular disease. Colour doppler displays normal & tumor vasculature & differentiates subretinal or choroidal hge from neoplasms

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CT/MRI

9 90% show calcification 9 Dense homogenous 9 Extension to choroid, vitreous & sclera not reliable. 9 Detects intracranial disease
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9 3D multiplanar capability. 9 Hyperintense to vitreous on T1 & markedly hypointense on T2 9 Delineation of ON, IO & EO spread 9 Differentites between tumor, RD & subretinal fluid.

ROLE OF FNAC
z z z

z z z

Tissue biopsy confirmation not necessary: typical clinical & radiological findings. Resistance to performance of biopsy: may result in EO seeding & misdiagnosed as uveitis. FNAC with 30 G needle avoids vascularized conjunctiva of the limbus & the orbit, sclera & pars plana preventing possible spread of cells through the needle tract. Needle tract: peripheral cornea, AC, iris, ciliary body & tumor. Overall accuracy 95% Indicated only in selected patients: z diagnosis is ambiguous or z obvious EO extension.

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STAGING SYSTEMS-CLINICAL

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STAGING SYSTEMS-PATHOLOGICAL
St. JUDES STAGING I: Tumor unifocal/multifocal confined to retina A. Occupying one quadrant or less B. Occupying two quadrants or less C. Occupying more than 50% of retinal surface. II: Tumor unifocal/multifocal confined to globe A. With vitreous seeding B. Extending to optic nerve head C. Extending to choroid & optic nerve head. D. B+C E. Extending to emissaries. III: Extraocular extension of tumor (regional) A. Extension beyond cut end of ON. B. Extension through sclera into orbital contents. C. Extension through choroid & beyond cut end of ON. D. Extension through sclera into orbital contents and beyond cut end of ON. IV: Distant metastasis A. Extending through ON to brain. B. Blood borne metastasis to soft tissues & bone. C. Bone marrow involvement. IAEA Pediatric Radiation Oncology Training
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AJCC SYTEM: Clinical & Pathological

PROGNOSTIC FACTORS
z z

z z z z z z z z

Optic nerve invasion in the most important poor prognostic factor. Massive invasion of choroid, CB: increases possibility of hematogenous spread (60% risk of mets) & extension to extrascleral tissues (6 years DFS 90% in IO disease versus 10% for EO disease). Gross extraorbital extension has >90% risk of metastasis. Poorly differentiated tumor. Anterior chamber invasion, mortality 20 to 80%. Large tumor with vitreous seeding. Rubeosis iridis. Glaucoma. Bilateral tumors behave poorly as mortality resulta from second cancers & trilateral RB. Trilateral RB has almost 100% fatality.

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EXTENT OF INVASION OF ON

MORTALITY RATE

SURVIVAL

Superficial Upto Lamina cribrosa Posterior to Lamina cribrosa Positive transected margin Stump of ON >5mm

10% 29% 42% 80% better

Similar to uninvolved ON 90% 60% 20% better

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MANAGEMENT OF RB
Complex issue. Multidisciplinary approach: Ocular oncologist, pediatric oncologist,

radiation oncologist, radiologist and child psychologist. Treatment is tailored to each individual. Goals of treatment: Save life. Preserve vision or salvage eye (i.e. avoid enucleation). Minimize any complications or side effects of therapy. Choice of therapy: Risk of metastatic disease. Systemic status. Laterality of disease/size/location of tumor. Visual prognosis. Risk of second cancers.

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PRESENTATION

Disease:
Unilateral Limited Advanced Limited Advanced metastatic
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M/C presentation

Bi-lateral

TRADITIONAL TREATMENT OF RB
Unilateral Treated with enucleation, fellow eye observed till school age. More advanced side enucleation, less advanced side EBRT. BL enucleation if bilateral advanced disease.

Bilateral

metastatic

Systemic CT, palliative treatment

Treatment strategies have evolved over past few decades. Enucleation has decreased in number and trend towards vision/eye

preservation.
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Multidisciplinary approach.

TREATMENT OPTIONS

ENUCLEATION EXENTERATION EBRT FOCAL THERAPIES

PLAQUE

CHEMOREDUCTION

INTRAVENOUS SUBCONJUNCTIVAL TRANSPUPILLARY

RADIOTHERAPY LASER PHOTOCOAGULATION CRYOTHERAPY THERMOTHERAPY CHEMOTHERMOTHERA PY

SYSTEMIC CHEMOTHERAPY

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FLOW CHART: UNILATERAL NONADVANCED DISEASE

OF PATIENTS PREVIOUSLY TREATED WITH RADIOTHERAPY 60% REQUIRE FURTHER FOCAL THERAPY.

OF PATIENTS TREATED WITH EBRT 20% ULTIMATELY REQUIRE ENUCLEATION

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FLOW CHART: UNILATERAL ADVANCED DISEASE

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FLOW CHART: BILATERAL DISEASE

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ENUCLEATION
INDICATIONS Unilateral or bilateral RB completely filling the globe with no hope of visual salvage due to damage to entire retina. Tumor invasion in optic nerve, choroid, AC, pars plana or orbit. Painful glaucoma with loss of vision. Tumor unresponsive to other forms of conservative treatment. Inability to examine retina secondary to vitreous hge or cataract following conservative therapy.

PROCEDURE Involves removal of the eye leaving behind lids and extraocular muscles but removing the longest possible segment (10 to 15mm) of optic nerve in continuity with the globe. Care should be taken to avoid perforation of the globe to prevent seeding. Scleral perforation at the site of muscle insertions. Traction sutures in the muscles. ON snares or clamps should be avoided to prevent crush IAEA Pediatricartefact Radiation Oncology Training may be misinterpreted as invasion by tumor. which Dr Laskar Version 1 June 2009

ORBITAL IMPANLTS

Historically not used due to potential interference with palpation of the socket and clinical detection of orbital recurrence. However CT/MR allow detailed orbital analysis despite an implant. PMMA, hydroxyapatite and polyethylene implants are commonly used 4 to 6 weeks after enucleation.

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ROLE OF ADJUVANT THERAPY AFTER ENUCLEATION

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Orphanet Journal of Rare Diseases 2006, 1:31

CHEMOTHERAPY
GOALS OF CHEMOTHERAPY: Reduction of tumor size RD dealt with focal therapy is the standard of care in early stage disease. Reduce the use of EBRT which reduces second malignancies and orbitofacial growth anomalies in early stage. Reduce the need of enucleation in early stage. Reduce the risk of local and systemic relapse in advanced stage. Improve survival in metastatic disease.

1. 2. 3. 4.

Neoadjuvant: IORB - BL disease, UL disease not amenable to local therapy (6 to 12 cycles). EORB Orbit/bone involvement, TRB, metastatic spread (prolonged duration of CT 12 to 18 months). Adjuvant postoperative: High risk histopathological features. Salvage: recurrent disease in an only eye. IAEA Pediatric Radiation Oncology Training
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IAEA Pediatric Radiation Oncology Training Dr Laskar Version 1 June 2009

Wilson et al, AJO, 2005, VOL 140,NO 3, 397

EYE PRESERVATION AS PER STAGE

EYES PRESERVED RE Ito III EBRT ALONE EBRT+SALVAGE CT ALONE CT +SALVAGE CTRT 53% 96% 29% 94% RE IV to V 45% 66% 11% 66% 75%

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Visual results Limited by Macular involvement Tractional RD Hemorrhage

CHEMOREDUCTION NOT CHEMOTHERAPY

Chemoreduction alone: not effective even for early lesions. Reese-Ellsworth eye groups 1, 2, or 3: systemic chemotherapy +

local ophthalmic therapies can eliminate the need for enucleation or EBRT without significant systemic toxicity. Reese-Ellsworth eye groups 4 and 5: more effective therapy required Requirement RT: RE group V, tumor thickness >5 mm, VS, female gender, subretinal fluid, retinal tumor recurrence after previous chemoraduction. Enucleation requirement: RE group V, tumor base >15mm, thickness >5mm, age > 12 months, tumor proximity to foveola within 2mm. Cautious follow-up recommended: risk for late (upto 5 years) recurrent vitreous and subretinal seeds is substantial and proper treatment is critical for salvaging the eye. Chemoreduction averts the development of TRB.

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CRYOTHERAPY

Under GA, pencil like probe is placed precisely on the

sclera directly behind the intraocular focus of RB. Rapid freezing forms intracellular crystals which ruptures tumor cells and causes vascular occlusion. Fails if overlying VS present. 1 or 2 sessions at 1 month interval are required. Indication: Small primary or recurrent tumor in anterior retina i.e. equatorial and peripheral region or post EBRT residual tumor < 2mm thick and < 3.5 mm diameter. Complications: vitreous hemorrhage, choroidal effusion, retinal detachment, localized periretinal fibrosis and retinal tear.

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PHOTOCOAGULATION
Argon/Diode laser/Xenon arc. Light is focused through dilated pupil under GA and vessels are

coagulated which results in involution of tumor. Indications: Small primary or recurrent tumor in posterior part of retina < 2.5 mm thick and < 4.5 mm diameter.
Retinal neovascularization due to radiation retinopathy.
Most tumors require 2 to 3 sessions to be cured. Contraindications:

Tumor located at or near macula or pupillary area. Mushroom shaped tumors Tumors arising from a vitreous base.

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THERMOTHERAPY
Ultrasound/microwave/infrared radiation used to deliver

heat to eye. 42 to 600C (which is below coagulation threshold) of heat produces a grey white scar but does not photocoagulate retinal vessels. Synergistic effect with CTRT Indications: Thermotherapy alone: small tumors outside retinal arcade < 3mm diameter and 2 to 3mm thick without vitreous or subretinal seeds produces control rates of 86% Thermochemotherapy (TCT): rest of the tumors after tumor shrinkage following 2 to 3 cycles when they satisfy above size criteria (thickness>4mm associated with higher recurrences).

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THERMOTHERAPY
Mechanism of action: Membrane damage. Protein denaturation. Chromosomal damage. Disruption of biochemical pathways. Ischemic necrosis. Schedule: Thermotherapy alone: 300MW power for >/= 10 mins

upto45 to 600C at 1 monthly interval for 3 sessions produces grey white scar. TCT: 42 to 450C for 5 to 20 mins depending on size (upto 15 mm diameter) produces a light grey scar.

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THERMOTHERAPY
Complications: focal iris atrophy and focal para axial

lenticular opacity.

Advantage: suitable for small tumors adjacent to fovea and

optic nerve in which plaque therapy or laser photocoagulation would possibly induce more profound visual loss.

Disadvantage: Time consuming, tedious process that requires

careful observations, recordings, judgements and treatment adjustments in response to subtle tumor changes.

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LOCAL ADMINISTERED CARBOPLATIN

z

Being evaluated at present for advanced intraocular RB since achieves high concentration in vitreous humor. Subconjunctival: levels peak at 1 hr and diminishes thereafter slowly. Iontophoretic: levels slowly peak at 6 hrs. Could be combined with focal therapies and avoid systemic administration.
Abramson DH. Opthalmology 1999; 106:1947-50 Hayden BH. Arch Opthalmol 2000;118:1549-54 Simpson AE. Arch Opthalmol 2002;120:1069-74

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SCLERAL PLAQUE THERAPY

1929: Foster, Moore and Scott used Ra seeds 1948: Henry Stallard pioneered and refined the technique, initial Ra

applicator was replaced by cobalt 60 plaque. Curved applicator to fit the eye with suture holes for fixing. Left in place for 3 to 7 days to deliver 40 Gy to tumor apex and 100 to 200 Gy to tumor base. Disadvantage: No external shielding resulting in high radiation dose to orbital bones and the surgeon. 1970-80s: other radio-isotopes used e.g. I125, Ir192, Ru106 Plaque Energy Half life Penetration Co60 1.33-1.7MV 5.2 years I125 27-25Kev 60 days upto 10mm Ir192 295-612Kev 74 days Ru106 3.5Mev () 368 days upto 6mm
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RESULTS AND GAMMA THERAPY

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IJROBP 2006, Scheuler at al

POOR PROGNOSTIC FACTORS

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IJROBP 2006, Scheuler at al

I125 CLAWS FOR WHOLE EYE-STANNARD

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EBRT
Indications:

Lesions close to macula or optic nerve. Larger tumors with vitreous seeding. Recurrent disease. Adjuvant postoperative radiotherapy after enucleation in high risk pathologic features. Palliative radiotherapy Progression on chemoreduction

Target volume: entire retina upto ora serrata and atleast 1 cm of ON

accepting the potential for cataract formation. All retinal cells have neoplastic potential resulting in recurrences in retina as well as vitreous. RB is a multifocal disease. Tumor may even spread subretinally.

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EBRT-TARGET VOLUME

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Blach et al, IJROBP 1996

TARGET VOLUME
z

EBRT does not prevent the appearance of new tumors in clinically uninvolved retina. Therefore, the traditional belief that external beam radiation can treat the retina prophylactically should be seriously questioned. Focal treatment modalities (plaque brachytherapy, photocoagulation and/or cryotherapy), when clinically feasible, should be considered the treatment of choice for intraocular retinoblastoma. EBRT should be considered only when focal treatment modalities are not clinically indicated.

Hernandez, IJROBP, 1996

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TOTAL DOSE
a) Group I & II lesions 45Gy / 25# / 5wks (@1.8Gy / fr.) Daily treatment 45Gy / 18# / 6wks (@2.5Gy / fr.) Alternate day treatment b) Group III, IV, & V lesions 50.4Gy / 28# / 6wks (@1.8Gy / fr.) Daily treatment 50.4Gy / 20# / 7wks (@2.5Gy / fr.) Alternate day treatment c) Post operative Microscopic residual disease 45Gy / 25# / 5wks (@1.8Gy / fr.) Daily treatment 45Gy / 18# / 6wks (@2.5Gy / fr.) Alternate day treatment Gross residual disease 50.4Gy / 28# / 6wks (@1.8Gy / fr.) Daily treatment 50.4Gy / 20# / 7wks (@2.5Gy / fr.) Alternate day treatment d) Children <1year of age, radiation dose should be reduced: Microscopic disease (post op radiotherapy) 39.6Gy/22#/ 4.5wks Gross disease (definitive radiotherapy) 45Gy/25#/ 5wks

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Hernandez, IJROBP, 1996

TECHNIQUES 1. Classic single temporal portal 34 cm, anterior border at lateral bony canthus with posterior 150 tilt (Dshaped field). 2. Anterolateral differentially weighted beams with anterior lens shield.
Anterior border at the limbus for lateral field. Half beam block anteriorly. 4 to 6 MV photon field. Eyes closed to spare minoe salivary glands and eyelids. Anterior field with electrons to prevent underdosing of AC and prevent exit dose.

Underdosing of anterior structures of eye. Higher recurrences. Cataract formation still higher.

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Hernandez, IJROBP, 1996

3DCRT/IMRT/PROTONS

Four non co-planar fields All anterior oblique field:

sup,inf, med, lat. Less orbital hypoplasia. Minimize dose to opposite eye, optic chiasma, post. Pituitary, upper cervical spine. Tumor = 95% & orbit = 50%. More homogenous dose distribution. Less vitreal recurrence.

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FOLLOW UP
RECURRENCE OCCURS USUALLY WITH IN 3 YR. BUT FOLLOW UP DONE FOR INDEFINITE PERIOD FOR DIAGNOSIS OF SECND MALIGNANCY AND TUMOR CONTROL

OPTHALMOSCOPIC EXAMINATION : First year: every 2-3 months . Second year: every 3-4 months. 3-5 years: every 6 months. > 5 years : every one year..

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SECOND CANCERS

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SECOND CANCERS
z

Subsequent cancer risk in 963 hereditary patients (SIR, 19; 95% CI, 16 to 21) exceeded the risk in 638 nonhereditary Rb patients (SIR, 1.2; 95% CI, 0.7 to 2.0). Radiation further increased the risk of another cancer in hereditary patients by 3.1-fold (95% CI, 2.0 to 5.3). Hereditary patients continued to be at significantly increased risk for sarcomas, melanoma, and cancers of the brain and nasal cavities. The cumulative incidence for developing a new cancer at 50 years after diagnosis of Rb was 36% (95% CI, 31% to 41%) for hereditary and 5.7% (95% CI, 2.4% to 11%) for nonhereditary patients.
Klienerman, JCO 2005

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