retinoblastoma case report latest with reference

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Case report

RETINOBLASTOMA

Presenter : 1. Maskur Ramadhan S.Ked (100100083)

2. Muhammad Akbar Batubara S.Ked (100100321)

Supervisor : dr. Yazid Dimyati SpA (K)

Introduction

Retinoblastoma is an embroyonal malignancy of the retina and is the most

common intraocular tumor in children. Although the survival rate of children in the

USA and developed countries with retinoblastoma is extremely high, retinoblastoma

progresses to metastasis disease and death in over 50% of children worldwide.

Furthermore the associated loss of vision and the side effects of therapy are significant

problems that remain to be adressed¹.

Epidemiology

Approximately 250-350 new cases of retinoblastoma are diagnosed each year in

USA, with no know gender and or racial predilection. The cumulative lifetime

incidence of retinoblastoma is approximately 1:20000 live births, and the

retinoblastoma accounts for 4% of all pediatric malignancies. The median age of this

diagnosis is approximately 2 yr, and over 90% of cases are diagnosed in the children

under the age of 5. Overall about 2 thirds to 3 quarters of children with retinoblastoma

have unilateral tumors, with the remainder have bilateral retinoblastoma. Bilateral

retinoblastoma is more common in younger children, particularly in those diagnosed

under the age of 1 yr.¹

Retinoblastoma can be either her ditary or sporadic. Hereditary cases usually are

diagnosed at younger age and are multifocal and bilateral, while sporadic cases

usually diagnosed in older children who tend to have unilateral, unifocal involvement.

The hereditary form always associated with the loss of function of Retinoblastoma

gene (RB1) via gene mutation or gene deletion. ,The RB1 gene is located on

chromosome 13q14 and encodes the retinoblastoma protein (Rb), a tumor supressor

protein that controls cell cycle phase transition that has role in apoptosis and cell

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differentiation. Many different causative mutation have been identified including

translocation, deletion, insertions, point mutations, and epigenetic modifications such

as gene methylation, The nature of predisposing mutation can affect the penetrane and

expressivity of retinoblastoma development.

According to Knudson’s two hit model of oncogenesis, two mutational events are

required for retinoblastoma tumor development. In the hereditery form of

retinoblastoma the first mutation of RB1 gene is inherited through germinal cells and

the secong mutation occurs subsequently in somatic retinal cells. Second mutations

that lead to retinoblastoma often results in loss in normal allele and concomitant loss

of heterozygosity. Most children with hereditary retinoblastoma have spontaneous

new germinal mutations, and both parents have wild type retinoblastoma genes. In the

sporadic form, the two mutations occurs in somatic retinal cells. Heterozygous

carriers of oncogenic RB1 mutations demonstrate variable phenotypic expression.²

Clinical manifestations

Retinoblastoma clasically presents with leukocoria, a white pupillary reflex,

white often is first noticedwhen a red reflex is not present at a routine newborn or well

child examination or in a flash phtograph of the child. Strabismus often is the initial

presenting complaint. Orbital inflammation, hyphema, and pupil irregularity can

occur with advancing disease. Pain can occur if secondary glaucoma is present. Only

about 10% of retinoblastoma cases are detected by routine ophthalmologic screening

in the context of a positive family history.¹

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Staging

The International Retinoblastoma Staging System (IRSS) may be used for staging retinoblastoma.

There are several staging systems for retinoblastoma. The IRSS stages are based on

how much cancer remains after surgery to remove the tumor and whether the cancer

has spread.

Stage 0The tumor is in the eye only. The eye has not been removed and the tumor was treated

without surgery.

Stage IThe tumor is in the eye only. The eye has been removed and no cancer cells remain.

Stage IIThe tumor is in the eye only. The eye has been removed and there are cancer cells left

that can be seen only with a microscope.

Stage IIIStage III is divided into stages IIIa and IIIb:

In stage IIIa, cancer has spread from the eye to tissues around the eye socket.

In stage IIIb, cancer has spread from the eye to lymph nodes near the ear or in

the neck.

http://www.cancer.gov/Common/PopUps/popDefinition.aspx?id=45762&version=Patient&language=English

















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Stage IVStage IV is divided into stages IVa and IVb:

In stage IVa, cancer has spread to the blood but not to the brain or spinal cord.

One or moretumors may have spread to other parts of the body such as the

bone or liver.

In stage IVb, cancer has spread to the brain or spinal cord. It also may have

spread to other parts of the body.6

Diagnosis

Retinoblastomas are usually found when a child is brought to a doctor because he

or she has certain signs or symptoms. Most types of cancer can be found by physical

exam and imaging tests, but treatment is usually not begun until the diagnosis is

confirmed by a biopsy. During a biopsy, the doctor removes a sample from the tumor

and sends it to a lab to be looked at under a microscope. But biopsies are not usually

done to diagnose retinoblastoma for 2 reasons. First, taking a biopsy specimen from a

tumor in the eye cannot be done easily without harming the eye and risking spreading

cancer cells outside the eye. Second, retinoblastoma can be diagnosed accurately by

doctors who have experience with this disease, and it is unlikely to be confused

with other eye problems in children.3

Medical history and physical exam

If your child has signs or symptoms of retinoblastoma, the doctor will examine

your child’s eyes and get a complete medical history. The doctor will ask about the

child’s symptoms and may ask about any family history of retinoblastoma or other

cancers. This information is important when deciding if more tests and exams are

needed. Your family history is also useful for determining whether other relatives

could possibly pass this gene on to their children or develop this cancer themselves (if

they are young children) and might benefit from genetic counseling. If a

retinoblastoma is suspected, the doctor will refer you to an ophthalmologist (a doctor

who specializes in eye diseases), who will examine the eye closely to be more certain

about the diagnosis. The ophthalmologist will use special lights and magnifying

lenses to lookinside the eye. Usually, the child needs to be under

generalanesthesia(asleep) during the exam so that the doctor can take a careful and








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detailed look If a diagnosis of retinoblastoma seems likely based on the eye exam,

imaging tests will be

done to help confirm it and to find out how far it may have spread within the eye and

possibly to other parts of the body. Usually an ophthalmologist who specializes in

treating cancers of the eye (called an ocular oncologist) will make the final

determination. This doctor should also be part of the team of doctors treating the

cancer.

Imaging tests3

Imaging tests use x-rays, sound waves, magnetic fields, or radioactive substances to

create pictures of the inside of the body. Imaging tests may be done for a number of

reasons including:

To help tell if a tumor in the eye is likely to be a retinoblastoma

To determine how large the tumor is and how far it has spread

To help determine if treatment has been effective

Children with retinoblastoma may have one or more of these tests.

Ultrasound

Ultrasound uses sound waves to create images of tissues inside the body, such

as the inner parts of the eye. For this test, a small ultrasound probe is placed up

against the eyelid or eyeball. The probe gives off sound waves and detects the echoes

that bounce off the tissues inside and around the eye. The echoes are converted by a

computer into an image on a computer screen. Ultrasound is one of the most common

imaging tests for confirming the diagnosis of retinoblastoma. It is painless and does

not expose the child to radiation, but the child may need to be sedated (made sleepy)

so that the doctor can get a good look at the eye. This test can be very useful when

tumors in the eye are so large they prevent doctors from seeing inside the whole eye

because ultrasound can “see through” tissues. Optical coherence tomography (OCT)

is a similar type of test that uses light waves instead of sound waves to create very

detailed images of the back of the eye.

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Magnetic resonance imaging (MRI) scan

MRI scans are often used for retinoblastomas because they provide very

detailed images of the eye and surrounding structures without using radiation. This

test is especially good at looking at the brain and spinal cord. Most children with

retinoblastoma will have at least one MRI scan. For children with bilateral

retinoblastomas (tumors in both eyes), many doctor continue to do MRI scans of the

brain for several years after treatment to look for tumors of the pineal gland

(sometimes called trilateral retinoblastoma). Unlike CT scans (described next), MRI

scans use radio waves and strong magnets to create images instead of x-rays. A

contrast material called gadolinium may be injected into a vein before the scan to see

details better. MRI scans may take up to an hour. Your child may have to lie inside a

narrow tube, which is confining and can be upsetting. Newer, more open MRI

machines can help with this, but the test still requires staying still for long periods of

time. The machines also make buzzing and clicking noises that may be disturbing.

Young children may be given medicine to help keep them calm or even asleep during

the test.3

Computed tomography (CT) scan

The CT scan is an x-ray test that produces detailed cross-sectional images of

parts of the body. CT scans can help determine the size of a retinoblastoma tumor and

how much it has spread within the eye and to nearby areas. Normally, either a CT or

an MRI scan is needed to do this, but usually not both. Because CT scans give off

radiation, which might raise a child’s risk for other cancers in the future, most doctors

prefer to use MRI. However, a CT scan can show deposits of calcium inthe tumor

much better than an MRI, which can be very helpful when the diagnosis of

retinoblastoma is not clear. Instead of taking one picture, like a regular x-ray, a CT

scanner takes many pictures as it rotates around your child while he or she lies on a

table. A computer then combines these pictures into images of slices of the part of the

body being studied. Before the scan, your child may receive an IV (intravenous)

injection of a contrast dye that helps better outline structures in the body. The dye

may cause some flushing (a feeling of warmth, especially in the face). Some people

are allergic and get hives. Rarely, more serious reactions like trouble breathing or low

blood pressure can occur. Be sure to tell the doctor if your child has any allergies or

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has ever had a reaction to any contrast material used for xrays. CT scans take longer

than regular x-rays, but not as long as MRI scans. A CT scanner with a narrow table

in the middle opening. Your child will need to lie still on the table while the scan is

being done. During the test, the table slides in and out of the scanner. Your child may

need to be sedated before the test to stay still and help make sure the pictures come

out well.3

Bone scanA bone scan can help show if the retinoblastoma has spread to the skull or other

bones. Mostchildren with retinoblastoma do not need to have a bone scan. It is

normally used only whenthere is a strong reason to think retinoblastoma may have

spread beyond the eye.For this test, a small amount of low-level radioactive material

is injected into a vein(intravenously, or IV). (The amount of radioactivity used is very

low and will pass out of thebody within a day or so.) The material settles in areas of

damaged bone throughout the skeleton over the course of a couple of hours. Your

child then lies on a table for about 30minutes while a special camera detects the

radioactivity and creates a picture of the skeleton.Younger children may be given

medicine to help keep them calm or even asleep during the test.This test shows the

entire skeleton at once. Areas of active bone changes appear as “hot spots” on the

skeleton – that is, they attract the radioactivity. These areas may suggest the

presence of cancer, but other bone diseases can also cause the same pattern. To help

tell these apart, other tests such as plain x-rays or MRI scans of the bone might be

needed. For more detailed information on imaging tests, see our document.3

Other tests

Some other types of tests are not commonly needed for retinoblastomas, but they may

be helpful in some situations.

Biopsy

For most cancers, a biopsy (removing a tissue sample from the tumor and

looking at it under a microscope) is needed to make a diagnosis. Trying to biopsy a

tumor at the back of the eye can often damage the eye and may spread tumor cells, so

this is almost never done to diagnose retinoblastoma. Instead, doctors make the

diagnosis based on eye exams and on imaging tests such as those listed above. This is

why it is very important that the diagnosis of retinoblastoma is made by experts.

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Lumbar puncture (spinal tap)

Retinoblastoma may grow along the optic nerve, which connects the eye to the

brain. If the cancer has spread to the surface of the brain, this test can often find

cancer cells in samples of cerebrospinal fluid (the fluid that surrounds the brain and

spinal cord). Most children with retinoblastoma do not need to have a lumbar

puncture. It is normally used only when there is a reason to think retinoblastoma may

have spread into the brain. For this test, the doctor first numbs an area in the lower

part of the back over the spine. The child is typically given anesthesia so they will

sleep and not move during the procedure. This can help ensure the spinal tap is done

cleanly. A small, hollow needle is then placed between the bones of the spine to

withdraw a small amount of the fluid. The fluid is then looked at under a microscope

to check for cancer cells.3

Bone marrow aspiration and biopsy

These 2 tests may be done to see if the cancer has spread to the bone marrow,

the soft, inner part of certain bones. These tests are usually not needed unless the

retinoblastoma has spread to tissues next to the eye and doctors suspect that the cancer

may have also spread through the bloodstream to the bone marrow. The tests are

typically done at the same time. The samples are usually taken from the back of the

pelvic (hip) bone, but in some cases they may be taken from other bones. In bone

marrow aspiration, the skin over the hip and the surface of the bone may be numbed

with a local anesthetic. This test can be painful, so the child will probably be given

other medicines to reduce pain or even be asleep during the procedure. A thin, hollow

needle is then inserted into the bone, and a syringe is used to suck out (aspirate) a

small amount of liquid bone marrow. A bone marrow biopsy is usually done just after

the aspiration. A small piece of bone and marrow is removed with a slightly larger

needle that is pushed down into the bone. Once the biopsy is done, pressure is applied

to the site to help stop any bleeding.

The samples are then looked at under a microscope to see if tumor cells are

present.3

Hearing test.

Children with retinoblastoma taking certain chemotherapy drugs may have

their hearing tested (audiology test). In a young child, a normal newborn hearing

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screen can serve as a baseline.7

Differential diagnosis5

Other causes of leukocoria

Persistent hyperplastic primary vitreous

Coats disease

Cataract

Endophthalmitis from Toxocaracanis

Choroidal coloboma

Retinopathy of prematurity

Treatment

Management of a child with retinoblastoma requires a multidisciplinary

approach. Ophthalmologists, pediatric oncologists, pediatric radiation oncologists,

pathologists, genetic counselors, social workers, nurses, and others play important

roles in the cure of the disease, salvage of vision, and support of the child with vision

loss and potential long-term sequelae. Many therapeutic options are available, and the

indications for a specific modality or a combination of modalities vary with each

patient. Furthermore, management varies for children with intraocular disease and

extraocular spread of the tumor. Most patients with unilateral disease present with

advanced intraocular disease and therefore usually undergo enucleation, which results

in a cure rate >95%. Children with involvement of both eyes at diagnosis usually

require multimodality therapy (chemotherapy, local therapies). Failure to control

disease in children with bilateral disease may lead to external beam radiation (EBR)

therapy. Enucleation is usually reserved for eyes with recurrent disease and no useful

vision.4

Management of Intraocular Disease

Staging of the disease has facilitated the assessment of treatments and

measurement of outcomes in oncology. The Reese-Ellsworth (R-E) classification for

intraocular retinoblastoma, developed in the 1960s, was used during the last 40 years

in assessing outcomes of therapy, and this classification facilitated the comparison of

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results from various studies. The R-E classification was devised to predict prognosis

in eyes that were treated with EBR therapy. The classification scheme has five

groups. Eyes with disease consistent with the lower groups have a lower risk for

enucleation following EBR and group V eyes have the highest risk for enucleation.

With the advent of other therapies, including chemotherapy, which has increasingly

replaced EBR therapy in the treatment of intraocular disease, the usefulness of the R-

E scheme is less apparent. Several alternative schemes have been proposed recently

by Shields et al. and by Murphreeamong others. The classification proposed by

Murphree is the basis for several protocols for the treatment of intraocular

retinoblastoma within the Children's Oncology Group (COG). While the R-E

classification and the classification proposed by Murphree and others

address intraocular disease, another classification system has been proposed by

Chantada et al to address extraocular disease and microscopic disease following

enucleation.4

Enucleation

Most children with unilateral retinoblastoma present with advanced disease, and

most of them require enucleation. Other indications for enucleation are for children

with bilateral disease where enucleation may be indicated for the eye with the most

advanced disease that does not respond to chemotherapy (rarely, enucleation is

indicated for both eyes), for the eye that has failed all known effective therapies, when

active tumor is present in an eye with no vision, when glaucoma is present as a result

of neovascularization of the iris or tumor invasion into the anterior chamber, and

when direct visualization of an active tumor is obstructed by conditions including

hemorrhage, corneal opacity, or cataract. Enucleation is curative in >95% of patients

with unilateral disease. Care should be taken to avoid perforation of the globe during

surgery and to obtain a long segment of the optic nerve in order to minimize the

chance of leaving tumor at the surgical margin. Orbital implants made of silicone,

plastic, hydroxyapatite, and MedPore are used at major treatment centers. By

connecting the implants to the orbital muscles, excellent cosmetic appearance can be

achieved. Complications such as wound dehiscence and conjunctival erosion,

although rare, may be seen with all types of implants.4

EBR Therapy

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EBR therapy is an effective means of curing retinoblastoma. The most common

indication for EBR is for the eye in a young child with bilateral retinoblastoma who

has active or recurrent disease after completion of chemotherapy and local therapies.

Children with small tumors within the macula that do not respond to chemotherapy or

have recurrent disease following chemotherapy can benefit from EBR. With EBR

therapy, the entire tumor-bearing area of the globe is included along with at least 1 cm

of the optic nerve. The prescribed dose to the tumor ranges from 42 Gy to 46 Gy, with

the radiosensitive lens receiving significantly less. Preservation of the eye with

control of the disease using EBR therapy is in the range of 58%–88%. Radiation

therapy has only a 50% local control rate in R-E groups IV and V disease, with a 95%

rate of preservation of the eye in R-E groups I–III. In a report of 63 R-E group Vb

eyes (tumors with vitreous seeds) that were irradiated at initial diagnosis, the ocular

survival rate was 53.4% at 10 years. However, the probability of developing a second

cancer following initial EBR therapy for group Vb disease in patients with bilateral

disease was 29.7% by 10 years after diagnosis.

Patients with hereditary disease who received EBR therapy are reported to have

a cumulative incidence of second cancers of 35%, compared with 6% for those who

did not receive EBR. Furthermore, patients who are <1 year of age and who receive

radiation therapy are several times more likely to develop second and subsequent

malignancies than those who are >12 months of age and receive radiation therapy. In

a cohort of patients with hereditary retinoblastoma, a strong relationship between

radiation dose and the development of soft tissue sarcomas was reported.

In subsequent follow-up of this cohort, significantly higher risks for melanoma,

cancers of the bone, nasal cavities, and brain, and soft tissue sarcomas (with an excess

of leiomyosarcoma) were documented. Cataracts, optic nerve damage, total retinal

vascular occlusion, vitreous hemorrhage, and facial and temporal bone hypoplasia are

other complications associated with EBR therapy. Proton beam radiation therapy

offers promise in reducing the significant long-term side effects associated with

conventional EBR therapy.4

Brachytherapy

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Brachytherapy involves the placement of a radioactive implant (plaque), usually

on the sclera adjacent to the base of a tumor. Iodine-125 (125I), gold, and more recently

ruthenium have been used. The intention is to deliver a dose of 4,000–4,500

cGytransclerally to the apex of the tumor over a period of 2–4 days. This treatment is

limited to tumors that are <16 mm in base and 8 mm in thickness, and can be used as

the primary treatment or, more frequently, in patients who had failed initial therapy

including previous EBR therapy. This modality can also be used when there is a

peripheral tumor with focal vitreous seeding around it. Relative contraindications

include larger tumors and those that involve the macula. Good tumor control has been

reported with this modalit. Side effects are less common than with EBR and include

optic neuropathy, radiation retinopathy, and cataract formation. Second malignancies

do not appear to be associated with this type of local therapy. An orbital implant

with 125I seeds was shown to be effective in treating patients who were at high risk for

orbital recurrence after enucleation.

Thermotherapy

Thermotherapy involves the application of heat directly to the tumor, usually in

the form of infrared radiation. A temperature between 45°C and 60°C is the goal of

this therapeutic approach and is below the coagulative threshold and therefore spares

the retinal vessels from coagulation. Thermotherapy alone can be used for small

retinoblastomas that are ≤3 mm in diameter without vitreous or subretinal seeds. In a

study of 91 tumors, 92% of the tumors that were <1.5 mm in diameter were controlled

with thermotherapy alone.4

Chemothermotherapy

Larger tumors or tumors with subretinal seeds are usually treated with a

combination of thermotherapy and chemotherapy. Tractional and vaso-occlusive

complications that can be seen with thermotherapy alone appear to be less frequent

when thermotherapy is used in combination with chemotherapy

(chemothermotherapy). Chemotherapy and thermotherapy are delivered within hours

of each other. In one study of 188 retinoblastomas, tumor control was achieved in

86% of cases. The complications of chemothermotherapy included focal iris atrophy,

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paraxial lens opacity, sector optic disk atrophy, retinal traction, optic disk edema,

retinal vascular occlusion, retinal detachment, and corneal edema.

Chemothermotherapy may be especially useful for patients with small tumors

adjacent to the fovea and optic nerve, where radiation therapy or laser

photocoagulation may result in significant visual loss.4

Laser Photocoagulation

Laser photocoagulation is recommended only for small posterior tumors. The

treatment is delivered with an argon or diode laser or a xenon arc. The purpose of this

treatment is to coagulate all the blood supply to the tumor. Indirect ophthalmoscope

laser photocoagulation has significantly improved the delivery of photocoagulation.

Effective therapy usually requires 2–3 sessions at monthly intervals. Complications of

this treatment include retinal detachment, retinal vascular occlusion, retinal traction,

and preretinal fibrosis.

Cryotherapy

Cryotherapy induces tumor tissue to freeze rapidly, resulting in damage to the

vascular endothelium with secondary thrombosis and infarction of the tumor tissue.

Cryotherapy may be used as primary therapy for small peripheral tumors or for small

recurrent tumors previously treated with other modalities. Tumors are typically

treated three times per session, with one or two sessions at monthly intervals. Ninety

percent of tumors<3 mm in diameter are cured permanently, and complications are

few and rarely serious .Transient conjunctival edema and transient localized serous

retinal detachments can occur. Vitreous hemorrhage can be observed in large or

previously irradiated tumors.

Chemotherapy

Chemotherapy has been used to treat intraocular retinoblastoma since the early

1990s. Chemotherapy is used to reduce the size of the tumor to allow local

ophthalmological therapies, including cryotherapy and laser photocoagulation, or

thermotherapy, to eradicate the remaining disease. This combination of therapies has

been promoted to avoid EBR therapy and/or enucleation and thereby decrease the

potential for long-term side effects while salvaging some useful vision. The common

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indications for chemotherapy for intraocular retinoblastoma include tumors that are

large and that cannot be treated with local therapies alone in children with bilateral

tumors. Chemotherapy can also be used in patients with unilateral disease when the

tumors are small but cannot be controlled with local therapies alone. Such patients

constitute only 10%–15% of all patients with unilateral disease. Most patients with

unilateral disease are diagnosed with advanced intraocular disease and undergo

enucleation. Numerous studies have been published that show that chemotherapy is

very effective in eliminating the need for EBR/enucleation in R-E group I–III eyes,

while proving to be significantly less successful in eyes with group IV or V disease .

Selected patients with group IV disease have also had a very good response to

chemotherapy, and EBR and enucleation were avoided. The chemotherapy regimen

commonly used consists of carboplatin, vincristine, and etoposide. Cyclosporine has

been used in addition to these three agents in some institutions in order to try to

overcome drug resistance. Others have used carboplatin and vincristine without

etoposide and older studies used cyclophosphamide and doxorubicin. The

chemotherapy regimens from the different groups of investigators vary in the number

and frequency of chemotherapy cycles. All these regimens are well tolerated, with the

expected side effects of myelosuppression and its consequences, which include

invasive bacterial infections. Ototoxicity and renal toxicities are rare. There is also the

potential risk for second malignancies, especially when using etoposide (an

epipodophyllotoxin). The RE groups I–III and part of group IV correspond to group

B disease of the new international classification scheme that is a modification of the

one proposed by Murphree. Patients who have group B disease will be treated with

carboplatin and vincristine in the proposed COG trial, and their event-free survival

(EFS) at 2 years will be estimated, where an event is described as the need for

nonprotocol chemotherapy or EBR/enucleation.

Chemotherapy alone is not very effective in avoiding EBR/enucleation in

patients with R-E group V eyes, especially those with vitreous seeds. Friedman

etal.showed that only 53% of 30 group V (C, D, or E in the proposed classification)

eyes could be controlled with chemotherapy alone. Data from Chan et al. and

Villablanca et al. suggested that approximately 40% of group C and 70% of group D

eyes failed systemic chemotherapy alone. Based on these data, the trial proposed by

the COG involves systemic chemotherapy with carboplatin, vincristine, and etoposide

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along with subtenon carboplatin for group C and D eyes .. Eyes with diffuse vitreous

seeding present a particularly difficult management problem and, as mentioned above,

rarely respond to chemotherapy alone. Although EBR therapy is modestly successful

in patients with vitreous seeds, new approaches are needed. A recent phase I study

using adenoviral vectors to deliver the herpes simplex thymidine kinase gene

followed by ganciclovir demonstrated durable clinical and histopathologic responses

in heavily pretreated patients with vitreous seeds .4

Management of Extraocular Disease

Patients with extraocular disease have a very poor prognosis with respect to

survival. Recently, there have been encouraging data to suggest that patients with

regional extraocular disease may benefit from a combination of conventional

chemotherapy and EBR and those with distant metastatic disease may benefit from

high-dose chemotherapy and EBR in conjunction with bone marrow stem cell

transplantation. Regional extraocular disease includes patients with orbital,

preauricular disease and patients with tumor found at the optic nerve surgical margin.

Chantada et al. reported a 5-year EFS rate of 84% in 15 patients with orbital or

preauricular disease treated with chemotherapy that included vincristine, doxorubicin,

and cyclophosphamide or vincristine, idarubicin, cyclophosphamide, carboplatin, and

etoposide. These patients also received EBR of 4,500 cGy administered to the optic

nerve chiasm for patients with orbital disease and to the involved nodes for those with

preauricular lymphadenopathy. A subsequent study showed that 12 patients with

positive optic nerve surgical margins were all event-free survivors following

chemotherapy as above and orbital radiation therapy of 4,000–4,500 cGy. A similar

successful study was reported from Brazil.

Patients with metastatic extraocular disease have a poor prognosis when treated

with regimens of conventional doses of chemotherapy. There are several reports now

suggesting that high-dose chemotherapy with stem cell rescue combined with EBR

for areas of bulky disease at diagnosis is beneficial, with some long-term survivors

among patients with metastatic disease not involving the central nervous system

(CNS). It is rare for a patient with metastatic CNS involvement to survive using the

therapies described above. The proposed trial by the COG for patients with metastatic

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disease involves conventional chemotherapy, stem cell harvest, high-dose

chemotherapy with stem cell rescue, and EBR of involved sites.4

PROGNOSIS

Approximately 95% of children with retinoblastoma are cured with modern

treatment in the USA. Current efforts using chemotherapy in combination with focal

therapy are intended to preserve useful vision and avoid external-beam radiation or

enucleation. Routine ophthalmologic examinations should continue until children are

over age 7 yr. Unfortunately the diagnosis of retinoblastoma in many children from

third-world countries is delayed, resulting in spread of the tumor outside of the orbit.

The prognosis for these children with retinoblastoma that has spread outside of the

eye is poor. Children with germ line RB1 mutations are at significant risk for

development of second malignancies, especially osteosarcoma and also soft tissue

sarcomas and malignant melanoma. The risk of second malignancies is further

increased by the use of radiation therapy. Other radiation-related late adverse effects

include cataracts, orbital growth deformities, lacrimal dysfunction, and late

retinal vascular injury.1

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The aim of this paper is to report a case of retinoblastoma

CASE REPORT

Name : MN

Age : 3 years 11 months old

Sex : Male

Date of Admission : 02nd February 2015

Main Complaint : Eye looks like a cat eye

History: This main complaint is experienced by patients in 8 months ago, and had

brought to treatment within 4 months ago to the regional hospital of Banda Aceh.

History of red eye (+) experienced by patients within 5 months ago. Headache (+)

patients experienced since 1 month ago. at this point the patient is not in a state of

fever.

History of previous illness: Patients had previously been treated in regional hospitals

of Banda Aceh and was examined orbital CT scan with contrast, with the results of

the mass in the Vitreous Dextra with calcification.

History of drugs : Nothing

Pregnant History

1st child in the family. Mother was 27 years old during pregnancy. There is no history

of fever, hypertension, diabetic mellitus, and herbal medicine consumption.

Birth History

Spontaneous; attended by nurses; BW 2100 gram; cyanotic (-). Abnormality at birth:

(-)

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Immunization History

Till date all type of immunization completed

(BCG, Polio, Measles, Hep B, DPT)

Feeding History

From birth till 9th Months Old: Breast milk + formula milk

History of Growth and Development

-NIL-

Physical Examination

Generalized status

Body weight: 14 Kg, Body length: 94 cm

BW/age: z = < 0

BL/age : z = -2

BW/BL: z = 0

Interpretation : normal nutrition

Praesens status

Level of Consciousness: Compos Mentis, Blood pressure 110/60 mmHg, HR: 90

bpm, RR: 26 bpm, body temperature: 37oC, body weight : 14 Kg, body length : 94

cm.

Anemic (-), Icteric (-), Cyanosis (-), Edema (-), Dyspnea (-).

Localized status

Head :

Eye: Right eye : light reflex (-), ciliary injection (+), conjuctiva injection (+), white

formation covering lower part of cornea.

Left eye : Light Reflex (+), Pupil Ø 3mm

Conjuctiva palpebra inferior anaemic (-/-), sclera icteric (-/-).

Nose and ear: normal

Mouth: normal

19

Neck :

Lymph node enlargement (-).

Thorax:

Symmetrical fusiformis, Chest retraction(-), HR : 90 bpm, regular, murmur (-),

RR: 26 x/i, regular, ronkhi (-/-)

Abdomen:

Soepel, normoperistaltic. Liver, spleen and renal were unpalpable.

Extremities:

Pulse 90 bpm, regular, adequate pressure and volume, warm acral, Capillary Refill

Time < 3”.

Urogenital:

Male, normal

Laboratory Findings on HAM Hospital ( 2nd February 2015), outgoing patient:

Table 1

Parameters Value Normal Value

Complete Blood Count

Hemoglobin 11,3 g % 13 – 18

Leucocyte 9,36 x103 /mm3 4.000 – 11.000

Trombocyte 425.000 /uL 150.000 – 450.000

Hematocrite 33.7 % 39 – 54

Eritrocyte 4.48 mil/mm3 4.50 – 6.50

MCV 79.70 fl 82-100

MCH 26.70 pg 24 – 30

MCHC 33,5 g/dl 28 – 32

RDW 12.70 % 14.9 – 18.7

PDW 9.2 fl 10 – 18

MPV 8.70 fl 7.2 – 10.0

20

Leucocytes Count :

Neutrophil % 36.40 37 – 80

Lymphocyte % 46.80 20 – 40

Monocyte % 8.10 2 - 8

Eosinophil % 6.50 1 – 6

Basophil % 0.200 0 – 1

Neutrophil absolute 103/μL 3.59 1.9-5.4

Lymphocyte absolute 103/μL 4.36 3.7 – 10.7

Monocyte absolute 103/μL 0.76 0.3 – 0.8

Eosinophil absolute 103/μL 0.61 0.20 – 0.50

Basophil absolute 103/μL 0.02 0 – 0.1

Table 2

Result Normal

Liver

Bilirubin Total 0.28 mg/dL <1

Bilirubin Direk 0,08 mg/dL 0-0.02

Fosatase alkali (ALP) 309U/L <449

AST/SGOT 24U/L <38

ALT/SGPT 13U/L <41

Renal

Ureum 20.9 mg/dL <50

Kreatinin 0.50 mg/dL 0.17-0.42

AsamUrat 4.7 mg/dL <7,0

21

AP Chest Xray (0 2nd february 2015)

Cor tidak membesar

Sinuseas dan diafragma normal

Hilus normal

Corakan bronkovaskular normal

Tidak tampak bercak lunak

Result: Tidak tampak kardio megali, tidak tampak TB paru aktif

22

CT scan (18th October 2014)

Differential Diagnosis:

23

Working Diagnosis:

Retinoblastoma OD

Management:

Bed Rest

Diagnostic Planning:

Bone Marrow Puncture

Follow Up

02nd February 2015

S Red Eye (+), head pain (+)

O Sens: Compos Mentis, . Icteric (-). Edema (-). Cyanosis (-) Dyspnoe (-). Body Temperature :

370C . Body weight: 14 kg, Body length: 94 cm.

Head Eye: Right eye : light reflex (-), ciliary injection (+), conjuctiva injection (+),

white formation covering lower part of cornea.


Nose, Ear: normal

Mouth: normal

Neck Lymph node enlargement (-).

Thorax Symmetrical fusiformis, Chest retraction (-), HR : 96 bpm, regular, murmur (-),

RR: 24 bpm , regular, ronkhi (-/-).

Abdomen Soepel. Normoperistaltic. Liver, spleen and renal unpalpable.

Extremities Blood pressure: 100/70 mmHg, Pulse 96 bpm, regular, adequate pressure and

volume, warm acral, Capillary Refill Time < 3”,

Genital male, within normal limit

A Retinoblastoma OD

P - Bed Rest

- Waiting for Laboratory Issue

Planning: Bone Marrow Puncture

3rd February 2015

S Red Eye (+), head pain (+)

24


370C . Body weight: 14 kg, Body length: 94 cm.




Nose, Ear: normal

Mouth: normal


Thorax Symmetrical fusiformis, Chest retraction(-), HR : 92 bpm, regular, murmur (-),






A Retinoblastoma OD

P - Bed Rest

Planning: - Take out the last laboratory issue (2/2/2015)

- Bone Marrow Puncture

4th February 2015

S Right Eye looks like cat eye, fever (-)


36,7o C . Body weight: 14 kg, Body length: 94 cm.



Left eye : Light Reflex (+), Pupil Ø 3mm, conjunctiva palpebra Inferior pale (-)

Nose, Ear: normal

Mouth: normal


Thorax Symmetrical fusiformis, Chest retraction (-), HR : 96 bpm, regular, murmur (-),






25

A Retinoblastoma OD

P - Bed Rest


- Waiting for Bone Marrow Puncture Result

- Plan for Chemotherapy

Discussions

Theory Case

26

The median age of this diagnosis is

approximately 2 yr, and over 90% of

cases are diagnosed in the children under

the age of 5. Overall about 2 thirds to 3

quarters of children with retinoblastoma

have unilateral tumors, with the

remainder have bilateral retinoblastoma.

Bilateral retinoblastoma is more common

in younger children, particularly in those

diagnosed under the age of 1 yr.

Patient is 3 years 11 months old, with

unilateral retinoblastoma.

Retinoblastoma clasically presents with

leukocoria, a white pupillary reflex, white

often is first noticed when a red reflex is

not present at a routine newborn or well

child examination or in a flash phtograph

of the child. Strabismus often is the initial

presenting complaint. Orbital

inflammation, hyphema, and pupil

irregularity can occur with advancing

disease. Pain can occur if secondary

glaucoma is present. Only about 10% of

retinoblastoma cases are detected by

routine ophthalmologic screening in the

context of of a positive family history.

Patient had leukocoria ,

Orbital inflamation (+)

Imaging

Ultrasonography, CT Scan, MRI, bone

scan, lumbar puncture, biopsy, bone

marrow aspiration and biopsy

Ct scan had been done and shows

calcification on oculi dextra resulting

retinoblastoma

Treatment

Management of intraocular disease

Enucleation

EBR therapy

27

brachytheraphy

chemotheraphy

thermal therapy

chemothermotheraphy

Chemotheraphy has been the therapy for this patient

28

Conclusions

The conclusion of this paper is a boy, 3 year 11 months old, diagnosed with

Retinoblastoma OD, which is confirmed by the results of CT scan with contrast.

The patient received :

- Bed Rest


- Plan for Chemotherapy

29

References

1. Zage E. Peter and Herzog E. Cynthia, Retinoblastoma in Kliegman RM, Behrman

RE, Stanton BF, Schor NF, Geme III JWS, 2011. NelsonTextbook of Pediatrics,

19th Edition, Saunders Elsevier Inc, 1768-1769.

2. Hurwitz RL, Shields CL, Shields JA, et al. Retinoblastoma. In: Pizzo PA, Poplack

DG, eds. Principles and Practice of Pediatric Oncology. 6th ed. Philadelphia, Pa:

Lippincott Williams & Wilkins; 2011: 809–837.

3. A Guide for parents for Retinoblastoma at St. Jude Children Research Hospital:

http://www.stjude.org/SJFile/a4522_what_is_retinoblastoma.pdf.

4. Murali C, Patricia C B, Evelyn A P, Sharon E P and Richard H; Retinoblastoma:

Review of Current Management: Society of translational Oncology, AlphaMed

press; http://theoncologist.alphamedpress.org/content/12/10/1237.full

5. Stephen V.L, Ben L, Retinoblastoma in Nepal: case report and review: Bujo Case

Reports,Vol II; 2014.

6. Staging of Retoinoblastoma; National Cancer Institute;

http://www.cancer.gov/cancertopics/pdq/treatment/retinoblastoma/patient/page2

updated on 6th November 2014.

7. Ann-M L, MD, Kim E., MD, Kristin; Retinoblastoma, The Children’s Hospital of

Philadelphia: 2014.

http://www.cancer.gov/cancertopics/pdq/treatment/retinoblastoma/patient/page2

http://theoncologist.alphamedpress.org/content/12/10/1237.full

http://www.stjude.org/SJFile/a4522_what_is_retinoblastoma.pdf

retinoblastoma case report latest with reference

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