A ruptured tumor cell can spread cancer
Retinoblastoma (brief information)
Retinoblastoma is a cancer of the eye. This text provides information on the clinical picture, frequency, possible causes and symptoms as well as the diagnosis, treatment and prognosis of the disease.
Author: Maria Yiallouros, created on: 04/04/2016, approval: Dr. med. Christine Jurklies; PD Dr. med. Petra Temming, last changed: 12.06.2020 doi: 10.1591 / poh.retino-patinfo.kurz.1.20120611
Retinoblastoma is a rare cancer of the eye. It arises in the retina and occurs almost exclusively in childhood. A distinction is made between a hereditary and a non-hereditary form of the disease. In the first case there is a predisposition for the development of this type of cancer, in the second case the cancer develops spontaneously, i.e. as a result of a new change in a retinal cell.
Retinoblastoma can affect one or both eyes. Usually only one eye is affected (unilateral or unilateral retinoblastoma); in about a third of children, the disease affects both eyes (bilateral or bilateral retinoblastoma). If the latter is the case, this is almost always an indication of hereditary retinoblastoma. Unilateral retinoblastomas, on the other hand, are usually not hereditary. The tumors can form either in one place in the eye (unifocal) or in several places (multifocal).
Retinoblastomas usually grow quickly. They can spread within the eyeball and, starting from there, also into the eye socket and along the optic nerve into the central nervous system (CNS), in advanced cases also via the blood and / or lymphatic system to other organs. If left untreated, the disease is almost always fatal. Only in rare cases (1-2%) does the tumor regress on its own; one then speaks of a spontaneous regression.
Retinoblastoma is the most common (intraocular) malignant tumor that occurs in children. In Germany, around 40 children under the age of 15 develop this form of cancer every year. This means that for every 18,000 children born alive, there is one child with retinoblastoma. Overall, however, retinoblastomas are rare: According to the German Children's Cancer Register (Mainz), they account for around 2% of all malignant diseases in children and adolescents.
Retinoblastoma usually occurs in infants and young children, which means that it almost always occurs before the age of five. About 80% of the sick children are younger than four years. After the age of six, retinoblastomas develop extremely rarely.
The cause of the development of a retinoblastoma are two genetic changes (mutations) in the precursor cells of the retina, the so-called retinoblasts. Such changes can occur spontaneously in individual retinal cells. But they can also be present in the germ cells (and thus also in all body cells) and are then inheritable.
In the majority of patients - around 60% - it is a non-hereditary form of retinoblastoma, that is, the mutations en arise in isolation (sporadically) and are located exclusively in the tumor cells. About 40% of retinoblastomas, however, are hereditary. In about a quarter of these cases - that is, in a total of 10-15% of all patients - other illnesses in the family are already known (one then speaks of a familial retinoblastoma); in all other hereditary retinoblastomas the disease arises again.
Regardless of whether it is hereditary or non-hereditary retinoblastoma, the genetic changes are always in the so-called retinoblastoma gene, which is located on chromosome 13. Since each chromosome is duplicated, there are also two retinoblastoma gene alleles in each cell. A tumor can only develop if both alleles are changed. Details on the genetic classification of retinoblastomas and the frequency of their occurrence as well as their development can be found in our text "Heredity / Genetics of Retinoblastoma".
Signs of illness
Very small retinoblastomas usually do not cause any symptoms; the disease often lasts for a long time without any symptoms (symptom e). Symptoms usually only arise when the tumor is larger or grows into other parts of the eye. This can lead to impaired vision or even blindness. Due to the different visual acuity of the two eyes, a squint can occur. This is the case in around 25 to 30% of patients.
The most common initial symptom in over two thirds of sick children, however, is the white lighting up of the pupil (leukocoria) in certain light conditions, for example when taking photos - in contrast to a red or black pupil in the healthy eye. This white pupil, also known as the cat's eye, is an indication of extensive tumor growth behind the lens. Children are less likely to have painful, reddened or swollen eyes due to increased intraocular pressure.
You should watch out for the following warning signs in your child:
- A whitish-yellow color in one or both pupils (leukocoria)
- Squint or decrease in visual acuity / visual disorder
- Redness or swelling of the eye; Eye pain
The appearance of one or more of these symptoms does not necessarily mean that you have retinoblastoma or another tumor disease. Some of these symptoms can also have relatively harmless causes that have nothing to do with a tumor. Nevertheless, it is advisable to consult a doctor as soon as possible to clarify the cause. If retinoblastoma (or other malignant disease) is indeed present, early diagnosis is the best prerequisite for successful treatment of the disease.
Children from families with a hereditary increased risk of disease have to undergo regular ophthalmological examinations - even if there are no symptoms or symptoms - so that retinoblastoma can be detected at an early stage and appropriate treatment measures can be initiated in good time.
If the (pediatric) doctor finds evidence of retinoblastoma through the medical history (anamnesis) and physical examination, he will refer the patient to a hospital that specializes in this form of cancer (ophthalmological or pediatric oncology treatment facility). If retinoblastoma is suspected, various examinations are necessary, first to confirm the diagnosis, but then also to determine which form of retinoblastoma it is (hereditary or non-hereditary) and how far the disease has spread.
The most important examination to detect a retinoblastoma is the ophthalmoscopic examination. The fundus of the eye is examined with the help of ophthalmoscopes and a strong light source. If a retinoblastoma is actually found, further examinations are necessary in order to determine the exact spread of the tumor. The most important examination methods include ultrasound (sonography) and magnetic resonance imaging (MRT). In addition, a pediatrician examination is carried out.
In rare cases, for example in extremely advanced disease and / or before chemotherapy, further examinations may be added (for example an X-ray examination of the chest, an examination of the cerebrospinal fluid (lumbar puncture), the bone marrow (bone marrow puncture) and / or the bones (skeletal scintigraphy).
The diagnosis is not limited to the sick child. Since retinoblastoma can be hereditary, an ophthalmological examination of the siblings and parents as well as a molecular genetic analysis of blood samples (genetic test) are necessary to clarify inheritance risks. When all the necessary examinations have been completed, the treatment team can work with you to decide which treatment measures will best help your child.
For the treatment of patients with retinoblastoma, the available forms of treatment are surgery, radiation (brachytherapy or percutaneous radiation therapy), laser therapy, cryotherapy and chemotherapy.
Which procedures are used primarily depends on whether one or both eyes are affected by the tumor, how far the disease has progressed at the time of diagnosis (disease stage) and whether one or both eyes can still be expected to have vision after treatment . The age of the child is also taken into account when planning the treatment. Goal of every therapy is the complete destruction or removal of the tumor and thus the healing of the cancer. The preservation of life is fundamentally above the preservation of eyesight.
In principle, two treatment strategies are possible:
- the surgical removal of the tumor by removing the eye (enucleation)
- an eyeball-preserving therapy using radiation, laser, cryotherapy and / or chemotherapy
An eyeball-preserving therapy is usually only possible if the retinoblastoma is detected early. Its aim is to inactivate the tumor and at the same time to preserve the eyesight without taking any risk to life. If the disease is already advanced, the removal of the eye is usually unavoidable. If there are daughter tumors (metastases), chemotherapy and / or radiation therapy is carried out in addition to the operation.
Treatment of patients with unilateral retinoblastoma
If there is a unilateral retinoblastoma, it is Removal of the diseased eye (enucleation) the most common and also the safest treatment method, since with a functioning partner eye the risks of other treatment strategies can be avoided. For non-hereditary retinoblastomas, complete cure can be achieved with this treatment.
In some cases, if the tumor is still small, a Eyeball-Preserving Therapy Possible options: For very small tumors, eye-preserving therapies with the help of laser coagulation, cryotherapy or local radiation therapy, known as brachytherapy, are possible. Patients with larger tumors can be treated with systemic chemotherapy or intra-arterial chemotherapy (see below). However, eye-preserving treatment only makes sense if, in addition to controlling the tumor, adequate eyesight is maintained.
However, unilateral retinoblastomas are usually recognized very late, i.e. in advanced stages of the disease; the affected eye is then often already blind. In this case, removing the eye does not mean a change in perception or poor orientation for the child.
If the tumor can be completely removed by surgery, no further treatment is required afterwards. However, if the tissue examination of the removed eye shows that the tumor was very extensive or had already exceeded the organ border, chemotherapy is carried out after the enucleation in order to destroy any tumor cells or small metastases that may have remained in the body. Percutaneous radiation therapy is rarely required.
Treatment of patients with bilateral retinoblastoma
If your child has bilateral retinoblastoma, the doctors try to bring the tumor completely under control through an individual combination of the available therapy methods and at the same time to maintain the visual function in at least one eye.
The therapy of choice is initially one local treatment. Individual small retinoblastomas can be safely destroyed with local forms of therapy (laser coagulation, cryotherapy or brachytherapy). However, repeated application is often required. If the tumors are already too large for this type of treatment, in some cases a Chemotherapy with the aim of reducing the size of the tumor (Chemoreduction) in order to subsequently make a local treatment (i.e. laser, cryotherapy or brachytherapy) possible.
Often, however, the disease has progressed so far in one of the two eyes that preserving the eyeball does not make sense and therefore one Enucleation he follows. In cases where chemotherapy is being considered for the treatment of the better eye, enucleation of the more affected eye can sometimes be waited for. Because the therapy can lead to a strong tumor regression, so that an eyeball-preserving treatment is still possible. However, if the inferior eye is already blind or there is infiltration of the anterior segment of the eye or the optic nerve, there is no alternative to enucleation.
If the disease also progresses in the second, initially better eye (tumor involvement of the optic nerve or the choroid; vitreous seeding), then the only eyeball-preserving therapy is often the only one percutaneous radiation. Again, this only takes place under the condition that sufficient eyesight is maintained. If this is not the case, the second eye must also be removed so as not to endanger the life of the child.
Since the risk of developing a second tumor is significantly higher after radiation therapy, efforts are now being made to avoid percutaneous radiation therapy if possible, especially in the first year of life. However, the effectiveness of percutaneous radiation in the very radiation-sensitive retinoblastoma remains undisputed.
With the aim of further reducing the need for eyeball removal or percutaneous radiation therapy and, if possible, also avoiding or reducing the side effects of intravenous chemotherapy, i.e. (systemic) chemotherapy affecting the whole body, new treatment methods have been developed for some time and tested.
In intra-arterial chemotherapy, a cytostatic agent (e.g. melphalan) is specifically administered into the eye via an artery of the eye. A catheter is inserted into the inguinal artery and advanced past the heart to the area of the ocular artery of the affected eye. From there, the administered drug is distributed in the downstream vascular system and thus also in the tumor vessels of the retinoblastoma.
Studies and Registers
Since retinoblastoma is a very rare disease (in Germany and Austria around 44 children per year fall ill), there is so far only a small amount of data that can be used as a basis for a risk-adapted (i.e. one adapted to the patient's relapse risk) and evidence-based (i.e. , a statistically secured) selection of the most suitable therapy methods in each individual case.
In contrast to other malignant cancers that can occur in childhood and adolescence, there are currently no controlled, standardized therapy guidelines for patients with retinoblastoma, for example in the context of a therapy optimization study. For this reason, the clinical registry was opened at the end of 2013 RB registry opened. It is intended to collect data on the epidemiology and course of retinoblastoma over a period of several years with the aim of improving knowledge about the disease and its response to various therapies.
All children and adolescents under the age of 18 who have been diagnosed with retinoblastoma and / or an RB1 mutation in the germline for the first time and have not yet received any previous treatment can be included in the retinoblastoma registry throughout Germany and Austria. The head office of the register is located at the University Children's Hospital Essen under the direction of PD Dr. med. Petra Temming.
Patients with hereditary retinoblastoma also have the option of participating in a European study examining the occurrence of secondary tumors after retinoblastoma disease (Study "Screening for Second Tumors in Children with Hereditary Retinoblastoma"). As part of this screening study, magnetic resonance imaging (MRI) of the head is performed once a year. Entry criteria for the study are: hereditary retinoblastoma, previous radiation exposure and an age between 8 and 18 years.
Over 95% of children with retinoblastoma can now be cured of their disease in the long term thanks to modern diagnostic and treatment methods. Children with unilateral retinoblastoma have healthy eyes without impaired vision and can lead normal lives. Even in the majority of children with bilateral retinoblastoma, at least one eye remains with sufficient residual visual acuity.
The prognosis for the individual patient depends to a large extent on how far the disease has progressed at the time of diagnosis (disease stage) and whether there is a hereditary or non-hereditary retinoblastoma.
Retinoblastomas that are confined to the eye - or eyes - at the time of diagnosis (intraocular retinoblastoma) are better treated than diseases that are more advanced in their growth; they are therefore in principle associated with a more favorable prognosis.
Patients with hereditary retinoblastoma have an overall less favorable overall prognosis than patients with the non-hereditary form. This is related to the fact that the hereditary disease, regardless of the treatment, has a genetically determined increased risk of developing a second malignant tumor (for example a soft tissue tumor or an osteosarcoma). This risk increases if the eyeball is irradiated as part of the treatment. About 5% of children with a hereditary, initially unilateral retinoblastoma develop a retinoblastoma on the opposite side within one and a half years after the initial illness.
- Kaatsch P, Grabow D, Spix C: German Childhood Cancer Registry - Anual Report 2018 (1980-2017). Institute of Medical Biostatistics, Epidemiology and Informatics (IMBEI) at the University Medical Center of the Johannes Gutenberg University Mainz 2019 [URI: http://www.kinderkrebsregister.de/ typo3temp / secure_downloads / 22605/0 / 2df4719687ba2596d4216218a4f4632763b64847 / jb2018s.pdf] KAA2019
- Temming P, Arendt M, Viehmann A, Eisele L, Le Guin CH, Schündeln MM, Biewald E, Astrahantseff K, Wieland R, Bornfeld N, Sauerwein W, Eggert A, Jöckel KH, Lohmann DR: Incidence of second cancers after radiotherapy and systemic chemotherapy in heritable retinoblastoma survivors: A report from the German reference center. Pediatric blood & cancer 2017, 64:71 [PMID: 27567086] TEM2017
- Temming P, Viehmann A, Arendt M, Eisele L, Spix C, Bornfeld N, Sauerwein W, Jöckel KH, Lohmann DR: Pediatric second primary malignancies after retinoblastoma treatment. Pediatric blood & cancer 2015, 62: 1799 [PMID: 25970657] TEM2015
- Temming P, Eggert A, Bornfeld N, Sauerwein W, Göricke S, Lohmann DR: [Diagnosis and treatment of retinoblastoma: current strategies for effective tumor control and preservation of vision]. Clinical Monthly Sheets for Ophthalmology 2013, 230: 232 [PMID: 23508752] TEM2013a
- Shields CL, Shields JA: Intra-arterial chemotherapy for retinoblastoma: the beginning of a long journey. Clinical & experimental ophthalmology 2010, 38: 638 [PMID: 20584015] SHI2010a
- Shields CL, Shields JA: Retinoblastoma management: advances in enucleation, intravenous chemoreduction, and intra-arterial chemotherapy. Current opinion in ophthalmology 2010, 21: 203 [PMID: 20224400] SHI2010
- Lohmann D: The Genetics of Retinoblastoma. WIR information sheet of the campaign for children with cancer (Bonn) 2007, 1:31 [URI: http://www.kinderkrebsstiftung.de/ fileadmin / KKS / files / zeitschriftWIR / 2007_1 / WIR_01_07_S31-33.pdf] LOH2007
- Jurklies C: The retinoblastoma - diagnosis and therapy. WIR information sheet of the campaign for children with cancer (Bonn) 2007, 1:26 [URI: http://www.kinderkrebsstiftung.de/ fileadmin / KKS / files / zeitschriftWIR / 2007_1 / WIR_01_07_S26-31.pdf] JUR2007
- Wieland R, Havers W: Retinoblastome, in: Gadner H, Gaedicke G, Niemeyer CH, Ritter J: Pediatric hematology and oncology. Springer Medizin Verlag 2006, 823 [ISBN: 3540037020] WIE2006
Heredity / genetics of retinoblastoma
Details can be found here
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