Retinoblastoma
Original Editor - Kapil Narale
Top Contributors - Kapil Narale and Kim Jackson
Introduction[edit | edit source]
Retinoblastoma is the most common ocular cancer that occurs in the pediatric population. It is lethal if it is left untreated. [1]
Epidemiology[edit | edit source]
In high-income countries, retinoblastoma is known to be a curable disease, with close to 100% chance of survival. However, in middle- and low-income countries, the prognosis is extremely low. In addition, more than 80% of cases occur in these countries. [1]
It is estimated that the majority of retinoblastoma cases occur in Asia (53%), then Africa (29%), Latin America (8%), North America (3%), and Europe (6%). With this information it is seen that global retinoblastoma patient survival is <30%. It is seen that the survival rate is 40% (23‑70%) in low‑income countries, while it is 79% (54‑93%) in upper‑middle‑income countries. [1]
Assessment[edit | edit source]
Prior to examining the patient, a thorough assessment must be completed. If there is any family history of the condition, a germline mutation may be present, and the child may need to undergo systemic chemotherapy to prevent pineoblastoma, even with a unilateral presentation of the disease. [1]
An in-depth evaluation is warranted prior to determining the degree of the necessary treatment, and minimise and prevent from any secondary complications. [1]
The treatment decision for retinoblastoma is dependent on the International Classification of Retinoblastoma (ICRB) classification (similar to the ICF), the presence of extraocular clinical factors, germline test results, family psychosocial status, and available medical facility resources. If there is presence of a germline disease, genetic testing should be conducted in all cases of retinoblastoma, for the patient and the rest of their family. [1]
All patients should go through a baseline high‑resolution simple and contrast‑enhanced magnetic resonance imaging (MRI) of the brain and orbits. Special attention should be given for pineoblastoma or any features of disruption to the optic nerve. [1]
As a part of the assessment, complete blood count, urine sample, and a general physical examination are performed by the pediatric oncologist. Subsequent to the general physical examination, a detailed examination using anesthesia is conducted, where ICRB staging is confirmed, and the first treatment can be administered. [1]
Treatment[edit | edit source]
The response to the initial treatment can be an indication of long‑term outcome progressions. The decision made by the ocular oncologist, in regards to treatment, would be crucial, as the therapy provided would need to be a sufficient strength, while minimising any secondary toxic effects. [1] Enucleation has been the preferred mode of treatment, for advanced retinoblastoma, in low-middle-income countries. however, over the last 30 years, the globe-savaging techniques have been used. [1]
Although the management of retinoblastoma may differ from place to place, and from clinic to clinic, the overall structure of treatment involves a similar framework. [1]
Various treatment methods for retinoblastoma are discussed below:
Intravenous Chemotherapy[edit | edit source]
IVC is an important mechanism for retinoblastoma therapy. It consists of 2-4 chemotherapeutic agents, which are given monthly via a central or peripheral catheter for 6-9 continuous cycles. The most commonly used method consists of 3 drugs, vincristine, etoposide, carboplatin (VEC). There ae cases where cyclophosphamide may replace vincristine when tehre may be a concernf or neurotoxicity. Despite this, vincristine is more likely to cause myelosupression and hemorrhagic cytitis. Another difference between VEC and cyclophosphamide is that transfusion of blood components may be necessary, granulocyte colony‑stimulating factor is usually not needed with standard VEC doses, but is should be used with cyclophosphamide.
Intravenous chemotherapy is known to effectively reduce tumor size, therefore can be referred to as chemoreduction.
Focal consolidation with thermotherapy, involving cryotherapy or transpupillary thermotherapy, can help with tumor control. Cryotherapy followed by chemotherapy is seen to heighten drug availability to the intraocular spaces when given within 48 hours of the thermal disruption.
Indications for IVC consist of, patients with bilateral disease, confirmed germline mutation, family history of retinoblastoma, or instances with possible optic nerve or choroidal invasion. Another indication to use IVC would be patients weighing less than 6 kg that are waiting to receive intra‑arterial chemotherapy (IAC). This is referred to as ‘bridge therapy’. As well, IVC acts as protection with preventing long‑term secondary cancers, metastases, and pineoblastoma.
Signs, symptoms, and side effects of systemic chemotherapies can include transient alopecia, cytopenia, and fever. Systemic toxicity of IVC for retinoblastoma can generally be mild.
A scheduled prophylaxis is administered for Pneumocystis jirovecii pneumonia. Side effects or symptoms such as chemotherapy‑induced nausea, emesis, and constipation may be medically managed.
In terms of effects on the renal system, long‑term renal toxicity is unlikely to occur if chemotherapeutic agents provided in proper amounts and concentrations.
Infertility is unlikely to occur with recommended doses of IVC. There can be a risk of infertility in Males with the addition of melphalan, especially when a total dose of 140 mg/m2.
Another rare condition following the use of IVC is secondary acute myelogenous leukemia. This is correlated with increased doses of chemotherapy, with simultaneous external beam radiotherapy (EBRT) and other predisposing conditions.
Intra-Arterial Chemotherapy (IAC)[edit | edit source]
This method is especially used for unilateral tumors. This method is known to be costly, due to its complex procedure. DUe to its expense and specialization required, it is not used in developing countries.
It is performed in an angiography suite by an experienced neurosurgeon or interventional neuroradiologist. A microcatheter is directed by fluoroscopy to guide the chemotherapeutic agents with great precision into the ophthalmic artery.
IAC is seen to have a 10x higher chemotherapy dose, compared to IVC, that is transmitted into the eye. As mentioned for the IVC treatment, the chemotherapy treatment has 1-3 drugs transmitted into the eye, once a month, for an average of 3 sessions.
IAC has been more commonly used over the past decade, especially due to its efficacy with globe salvage in advanced retinoblastoma cases and refractory tumors.
Indications for IAC can include first‑line, and globe salvage therapies. It can be used as a primary therapy for non‑germline, unilateral, or as a secondary therapy for unilateral or bilateral advanced recalcitrant disease facing enucleation. IAC has high efficacy from preventing sub retinal and vitreous seeds, especially when proximal to the retina.
IAC can also be used as tandem therapy for advanced bilateral cases, minimal exposure (<2 cycles), and for a repeat treatment after an initial IAC treatment. However, tandem therapy may be questionable because of increased vascular toxicity in the eye with better acuity, an effect on pineoblastoma prevention that is unknown, and minimal effect on pre‑existing metastases, which can lead to higher chance of child mortality.
High risk retinoblastoma needs enucleation performed, and an additional 6‑9 cycles of high‑dose IVC to prevent metastatic disease. IAC is generally used for patients older than 3 or 4 months old, because of the smaller size and strength of vessels in younger individuals. In the younger individuals, bridge therapy with IVC is provided until the individual reaches a weight of 6 kg.
Signs, Symptoms, Side-effects[edit | edit source]
Even though localised delivery of chemotherapeutic agents is used, systemic toxicity is generally observed after IAC.
Transient neutropenia has been observed in 12% of patients.
Femoral artery occlusion and blue toe syndrome can occur. This can be managed and prevented using anticoagulation.
Complications that are more severe such as carotid artery dissection, stroke, and death, are possible, but hardly occur. The selection of appropriate treatments for individual patients is important. Undetected extraocular extension, optic nerve or massive choroidal invasion could lead to metastasis if a patient is treated with the use of IAC without systemic chemotherapy.
Periocular side effects are generally self‑limited. These include,
- Periorbital edema,
- Cutaneous hyperemia,
- Madarosis,
- Blepharoptosis,
- Scalp hair loss, and
- Extraocular dysmotility.
Serious ophthalmic vascular impairments can include,
- Choroidal occlusive vasculopathy,
- Branch or central retinal artery occlusion,
- Ophthalmic artery spasm or occlusion, or
- Vitreous hemorrhage, among others
Of the individuals treated primarily with IAC, rhegmatogenous retinal detachment, which may be secondary due to accelerated tumor regression of endophytic tumors, is reported in 8‑16% of cases.
Vascular impairments are not associated with reduced globe salvage, but can limit visual acuity. Risk for vascular impairments is similar whenever the IAC treatment is used.
Intraocular Chemotherapy[edit | edit source]
Resources[edit | edit source]
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