How is retinoblastoma treated?

Retinoblastoma is one of the solid tumors of childhood, most successfully treated with timely diagnosis and therapy using modern methods (brachytherapy, photocoagulation, thermochemotherapy, cryotherapy, chemotherapy). Overall survival, according to various literature data, varies from 90 to 95%. The main causes of death in the first decade of life (up to 50%) are the development of an intracranial tumor synchronously or metachronically with retinoblastoma, a poorly controlled tumor metastasis beyond the CNS, the development of additional malignant neoplasms.

The choice of a method of treatment of retinoblastoma depends on the size, location and number of foci, the experience and capabilities of the medical center, the risk of involving the second eye. Most children with unilateral tumors have a fairly advanced stage of the disease, often without the possibility of preserving the vision of the affected eye. That is why enucleation often becomes the method of choice. If the diagnosis is made early, alternative treatment may be undertaken in an effort to preserve vision - photocoagulation, cryotherapy or radiation.

Treatment of bilateral lesions largely depends on the spread of the disease on each side. Bilateral enucleation can be recommended in the event that the disease is so common that there can be no question of preserving the vision. More often only the more affected eye is removed or, if the visual function is at least slightly preserved, from enucleation they refuse and treat the disease conservatively. The initial irradiation course, even in patients with advanced stages of the disease, leads to a tumor regression, vision can be partially preserved. If extraocular detection is found, other methods are used. Spreading into orbit, brain, bone marrow indicates a poor prognosis. Such patients need chemotherapy and irradiation of the orbit or CNS.

When enucleation is necessary to determine the extent of penetration of the tumor into the optic nerve or the shell of the eye. The degree of penetration into the optic nerve and sclera determines the risk of metastases. Such patients need chemotherapy, and in some cases, irradiation of the orbit. An important technical point of enucleation is the removal of a sufficiently long portion of the optic nerve together with the eyeball. Even after 6 weeks after the operation, an artificial eye can be placed. Cosmetic defect arises due to the fact that in small children, after the removal of the eye, the normal growth of the orbit slows down. This also occurs after irradiating the bones of the orbit.

The advantage of cryotherapy and photocoagulation compared with irradiation in fewer complications and the possibility of repeated courses of treatment. The disadvantage of the methods is that they are ineffective with a large mass of the tumor. In addition, they can cause the appearance of a scar on the retina with a greater loss of vision than during irradiation (extra care is needed when involving the optic nerve exit site).

Radiation therapy is traditionally used for large tumors involving the optic nerve, with multiple lesions. Single-sided solitary tumors less than 15 mm in diameter and less than 10 mm in thickness, located more than 3 mm from the optic nerve disc, can be treated topically with radioactive plates using cobalt ( ⁶⁰ Co), iridium ( ¹⁹² I) or iodine ( ¹²⁵ I) surrounding tissues. Retinoblastoma is referred to as radiosensitive tumors. The purpose of irradiation is sufficient local control with preservation of vision. Recommended doses: 40-50 Gy in the fractionation mode for 4.5-6 weeks. With the involvement of the optic nerve or germination in the orbit, radiation therapy is required for the entire orbital region at a dose of 50-54 Gy) for 5-6 weeks. In the presence of trilateral retinoblastoma with the involvement of the pineal region, craniospinal irradiation is recommended.

Indications for the treatment of retinoblastoma

Procedure	Indication
Enucleation	There is no way to keep sight
	Neo-acellular glaucoma
	Impossibility of tumor control by conservative methods
	Impossibility to examine the retina after conservative therapy
Cryotherapy	Small primary or recurrent tumors in the anterior part of the retina
	Small relapses after irradiation
Photocoagulation	Small primary or recurrent tumors in the posterior parts of the retina
	Neovascularization of the retina in radiation retinopathy

Recently, much attention has been paid to reducing the likely side effects by using the method of irradiation from lateral ports, the introduction of intensive chemotherapy with autotransplantation of hematopoietic stem cells. Standard chemotherapy regimens did not show significant efficacy, as intraocular penetration of chemotherapy drugs is reduced, and the tumor expresses the membrane glycoprotein p170 and rapidly becomes resistant. The drugs used in the combined treatment of retinoblastoma include vincristine, platinum preparations, cyclophosphamide, etoposide, doxorubicin. Considering that in 90% of patients the process is limited, the control over the tumor is predominantly localized.

With the relapse and metastatic spread of the process, the prognosis is extremely unfavorable.

Survival of patients with retinoblastoma reaches 90%, so the main areas of therapy are associated with attempts to preserve visual function and reduce the number of complications. The early detection of carriers of the mutant RB gene and its direct substitution are promising.

[1], [2], [3], [4], [5]