Reti on Blast Oma

7/30/2019 Reti on Blast Oma

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Grand RoundsTerry J. Alexandrou, MD

Department of Ophthalmology and Visual ScienceThe University of Chicago

1/4/2006



HPI – Patient T.F.

12/12/2005

16 month old A.A. male presents with a 1 monthhistory of “a left white pupil” and “left eyeturning outwards”, according to mom.



PMH

• None

• Full term – uncomplicated delivery



Meds and Allergies

• Medications: None

• Allergies: NKDA



Family History

None

Has a non-identical twin.



Always Listen to Mom!!!



EXAM Visual acuity:

OD – Fix and FollowOS – Unable to fix or follow; Pt. becomes agitated with

occlusion of the right eyePupils: +LAPD

Variable Exotropia – 30-40 prism diopters

Anterior Exam:- Cornea, AC, iris, lens normal OU

Fundus Exam:- Difficult, however able to see a moderately large whitemass in the left eye. Right eye appears normal.



• How would you pursue a diagnosis?



Superior Cut



Inferior Cuts



Exam Under Anesthesia



Left Eye



Differential?



Retinoblastoma

Coat’s Disease Ocular toxocariasisRetinal Astrocytic HamartomaPersistent Hyperplastic Primary Vitreous (PHPV)Retinopathy of Prematurity



Retinoblastoma

Epidemiology

Most common intraocular malignancy in children

1/15,000-1/20,000 live births

~300 new cases annually in the United States

No racial predilection

Occurs equally in males and females



Genetics – The Retinoblastoma Gene

Tumor Suppressor Gene

Chromosome 13 q 14

Knudson’s “Two -Hit” Hypothesis – recessive at a cellularlevel

Autosomal Dominant Inheritance



Genetics

Non – Heritable Form (60%)- Average age at Diagnosis is 24 months- Normal Life expectancy if cured of the eye tumor- Unilateral- Risk of additional cancers same as general population

Sporadic (93%) is not equivalent to Non-Heritable



Genetics

Heritable Form (40%)- Family History in 7-10%- New Germline Mutation in 30%- Average age at diagnosis is newborn to 12 months

- Multiple, bilateral tumors in 85 %- Predisposed to various cancers throughout life

- midline intracranial tumor (pineal and suprasellar region)-osteosarcomas and soft tissue sarcomas (teenage)

- melanomas and brain tumors (middle age)- lung and bladder cancer (later life)



Clinical Presentation

Leukocoria (54-62%)Strabismus (18-22%)

Red eye

Excessive TearingCorneal clouding (2/2 elevatedIOP)

HypopyonDiscoloration of the iris (2/2

neovascularization)ProptosisSpontaneous Globe perforation

“Cat’s Eye” appearance



Diagnosis

Complete general historyExam under anesthesiaUltrasongraphyCTMRI



Treatment Options

EnucleationChemoreduction with Local tumor ablationCryotherapy

External-Beam Radiation TherapyBrachytherapy

Treatment options in T.F.?



International Classification for Intraocular Retinoblastoma

A) Group A (Very Low Risk) - Small discrete intraretinal tumors away from the foveola and disc

- All tumors are 3 mm or smaller in greatest dimension, confined to the retina and - All tumors are located further than 3 mm from the foveola and 1.5 mm from the optic disc

B) Group B (Low Risk) - All remaining discrete retinal tumors without seeding - All tumors confined to the retina not in group A - Any tumor size and location with no vitreous or subretinal seeding

C) Group C (Moderate Risk) - Discrete local disease with minimal focal subretinal or vitreous seeding

-Tumor(s) must be discrete- Subretinal fluid, present or past, without gross seeding, involving up to one quadrant of retina- Local subretinal seeding, present or past, less than 5 mm from the tumor- Focal fine vitreous seeding close to discrete tumor

D) Group D (High Risk) - Diffuse disease with significant vitreous and/or subretinal seeding

- Tumor(s) may be massive or diffuse- Subretinal fluid, present or past up to total retinal detachment- Diffuse subretinal seeding, may include subretinal plaques or tumor nodules- Diffuse or massive vitreous disease may include "greasy" seeds or avascular tumor masses

E) Group E (Very High Risk)



Enucleation



Path – Gross Specimen



Path - Micro

Not ready as of 1/3/06



Is Enucleation enough? Are there any indications for adjuvant

chemotherapy in this patient?

What pathologic features are risk factors formetastatic disease in the future?



Pathologic features implicated in the past

Involvement of:- Choroid - controversial

- Optic nerve – posterior to lamina cribosa- residual tumor in optic nerve stump

- Sclera

- Anterior Chamber



CHILDREN’S ONCOLOGY GROUP

“A Study of Unilateral Retinoblastoma With and Without Histopathologic High-Risk Features

and the Role of Adjuvant Chemotherapy”



Study Chair: Murali Chintagumpala, MD (Baylor)Study Members :

Joan O’ Brien, MD (Ophthalmology, UCSF) Julie Stoner, Ph.D (Biostatistics, Nebraska)Katherine K. Matthay, MD (Hematology/Oncology, UCSF)

Anna T. Meadows, MD (Oncology, Children’s Hospital of Philadelphia) Ann M. Leahey, MD (Oncology, Children’s Hospital of Philadelphia) Arupa Ganguly, Ph.D (Human Genetics, Penn)Robert Zimmerman, MD (Neuro-Radiology, Philadelphia)Mary Herdy, CCRP (Michigan State University)Marcus H. Pettigrew (Research Coordinator, COG)

Study Pathologists :Daniel Albert, MD (Wisconsin)Ralph Eagle, MD (Wills)Patricia Chevez-Barrios, MD (The Methodist Hospital)



GOALS AND OBJECTIVES

1) Prospectively determine the prevalence of high-risk histopathologic features.

2) Demonstrate that patients without certain high-risk features canbe successfully treated with enucleation alone.

3) Estimate the event-free survival and overall survival in patientswith certain high-risk features who are treated with adjuvantchemotherapy.

4) Estimate the incidence of toxicities associated with the proposedadjuvant chemotherapy.



Eligibility Criteria

• Age: 0 to 6 years

• Diagnosis: All newly diagnosed children with Unilateral Retinoblastoma whoundergo enucleation as initial therapy

• Performance Level: Lansky score > 50

• Prior Therapy: No prior therapy other than enucleation

• Baseline MRI of the brain

• Organ Function Requirements: For patients with high-risk features who areto receive chemotherapy



Unilateral Disease

High-Risk Histopathologic

Features for which Adjuvant Therapy

is Indicated

No High-Risk

HistopathologicFeatures for which Adjuvant Therapy

is indicated

NoMetastatic

Disease

6 cycles of Chemotherapy Observation

MetastaticDisease

NoMetastatic

Disease

Follow-up Off Protocol Therapy

May enter other protocolsFollow-up



High-Risk Histopathologic Features

a) Posterior Uveal Invasion (includes choroidal invasion)

b) Any degree of concomitant choroid and optic n. involvement

c) Tumor involving the optic n. posterior to the lamina cribosa as anindependent finding

d) Scleral invasion

e) Anterior Chamber seeding

f) Ciliary body infiltration

g) Iris infiltration



High-Risk Histopathologic Features for which Adjuvant Therapy is Indicated

a) Massive choroid replacement (Posterior Uveal invasion grades IIC andIID)

b) Any posterior uveal involvement with any optic nerve involvementc) Optic nerve involvement posterior to the lamina cribosa

Posterior Uveal InvolvementI: Posterior uveal invasion absentII: Posterior uveal invasion present

IIA: largest dimension of tumor on slide < 1 mmIIB: largest dimension between 1-3 mmIIC: largest dimension > 3 mmIID: posterior uveal tumor noted grossly



Treatment Plan

• Treatment to start within 4 weeks of enucleation

• Consists of 6 cycles of Carboplantin, Etoposide and Vincristine givenevery 4 weeks

• Long term follow-up of patients



Financial considerations

12/12/05- New Ophth Patient $187.00

12/13/05- CT under anesthesia $3,112

12/15/05- Exam under anesthesia $9,075

12/21/05

- Enucleation $16,259

No payments received yet.



Practice based learning

1) Complete exam should be performed on parentsand siblings of retinoblastoma patients

2) Always listen to the parents – we have the

patients in our office for 30 minutes

Systems based Learning

1) Coordinate efforts between different specialties

Reti on Blast Oma

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