Staging and Classification for Intraocular Retinoblastoma
Friday May 9, 2014 | Abby White, WE C Hope CEO
Staging and eye classification summarises the information doctors gain from diagnostic tests and examinations. This process helps doctors determine best treatment options, and define potential for cure and eye salvage before treatment begins.
Doctors and researchers also need a simple, memorable tool to quickly and effectively communicate with one another when describing the degree of cancer in a child’s eye, and compare impact of different therapies. An agreed quality classification system is thus vital to development of effective multicenter clinical trials and evaluation of clinical study results, to enable second opinions and parental ability to make informed treatment decisions. A high quality classification system will be reviewed frequently and revised as needed in response to the changing treatment environment.
Without a simple, clear and consistently used staging / classification system, doctors, patient families and health policymakers are unable to effectively compare and interpret results of published clinical studies. They cannot make quality treatment recommendations / decisions or funding plans in the best interests of the patient.
When retinoblastoma appears on clinical exam to be contained in the eye, it is called “intraocular retinoblastoma”. Each eye is classified independently to indicate likelihood that a treatment can safely save the eye, and give the best vision. Stage for a bilaterally affected child is based on the worst affected eye, as an indicator of risk to the child’s life.
When an eye might be classified into one of two groups, the higher risk group should be selected. This reduces risk of eye loss or life threatening relapse due to under-treatment.
Staged 1a – 5b, this system was developed nearly 50 years ago by Dr. Algernon Reese and Dr. Robert Ellsworth, prominent New York retinoblastoma specialists of the day. Divided into 5 stages, each with two sub-stages, eyes are staged according to size and location of tumours observed during examination under anaesthesia. Each stage predicts potential to save the eye with external beam radiotherapy (EBRT), the primary vision-salvage therapy at the time.
Today, radiotherapy is reserved as a last resort to save a second eye, where all other treatments have failed or are unavailable. As a result, the Reese-Ellsworth Classification is not much used.
International Intraocular Retinoblastoma Classification
Grouped A to E, this system was developed by an international collaborative group under the leadership of Dr. Linn Murphree, paediatric ophthalmologist at Children’s Hospital of Los Angeles. This system predicts eye outcome when treated with combination chemotherapy and laser/cryotherapy, the most widely used primary eye salvage treatment for the last 25 years.
Today, the IIRC is the most commonly used method to indicate disease in each eye, and determine appropriate treatment. Each eye is staged according to size and location of tumours and other features observed during examination under anaesthesia.
The IIRC was validated through the World Retinoblastoma Survey involving 25 retinoblastoma treatment centres on six continents. Diagnostic features / classification and treatment outcome data was submitted to a secure online database for 1,527 children (1,919 eyes) diagnosed between 1997-2002. This survey found the IIRC to be an effective tool in predicting potential for eye salvage children with retinoblastoma in one or both eyes.
TNM (Tumour, Node, Metastasis) classification
TNM is developed, updated, and monitored for accurate use, by the American Joint Commision on Cancer and the Union for International Cancer Control (AJCC/UICC). Each type of cancer has unique features to determine TNM classification.
TNM staging includes both clinical (cTNM) and pathological (pTNM) findings. Version 7 TNM for retinoblastoma, publisehd in 2010, links to features relevant to the International Intraocular Retinoblastoma Classification for individual eyes.
Broadly speaking, the following can be used as a guide in translating between IIRC and TNM classifications for the eye.
- IIRC Groups A-C = TNM cT1a-cT1c: retinoblastoma is likely to be well controlled with modern therapies, while preserving vision in the eye.
- IIRC Group D = TNM cT2 retinoblastoma is has less than 50% chance to be controlled, with only 50% chance to save the eye.
- IIRC Group E = TNM cT3: retinoblastoma is at serious risk to be spreading outside the eye; immediate surgery to remove the eye is essential to protect the child’s life.
Significance of Seeding in Eye Classification
Seeds are tiny tumour fragments that brake off the larger mass and float into nearby fluids such as blood, the lymphatic system or cerebro-spinal fluid (fluid bathing the brain). This is how malignant cancer spreads from its original site into surrounding tissues or reappears in other parts of the body. The larger the tumor, and the faster it grows, the more likely it is to break apart and allow the cancer to spread.
In retinoblastoma, appearance of small seeds close to the original tumour is always a precursor to widespread seeding in the vitreous (fluid-filled centre of the eye). As seeds settle in the subretinal and vitreous fluid, they become more adept at growing, multiplying and spreading further. Potential to save the eye decreases as seeds grow in number and spread widely. Therefore, subretinal and vitreous seeding are important predictors of a treatment’s potential to save the eye and protect the child’s life.
An eye with seeds is classified by the IIRC as follows:
- Group C: fine vitreous seeding close to discrete tumour and / or subretinal seeding less than 3 mm from the tumour.
- Group D: diffuse or massive vitreous or subretinal seeds.
- Group E: vitreous seeds in combination with tumour in the front portion of the eye, glaucoma (high eye pressure), aseptic orbital cellulitis (inflammation of tissues surrounding the eye without infection), phthisis bulbi (a shrunken eye, non functioning eye) and haemorrhage that prohibits thorough examination of the eye.
In contrast, the REC does not describe subretinal seeding at all, and classifies any eye with vitreous seeds as 5b. So an eye classified REC 5b may be grouped by the IIRC as C, D or E. A child with a REC 5b / IIRC Group C eye will likely have a much better outcome than a child with a 5b /D eye. Attempting therapy to save a 5b / E eye risks the child’s life.
Results based on REC may suggest a treatment under evaluation to be more effective in curing advanced intraocular retinoblastoma than is the reality, Thus, the Reese-Ellsworth Classification cannot effectively predict potential for eye salvage with modern therapies, or support meaningful evaluation of results from clinical study of these therapies.
When cancer is contained in the eye and treated appropriately, and both eyes receive regular, frequent examinations, risk to the child’s life is minimized. Appropriateness of modern therapies can only be determined by classification of each eye using a system designed to predict outcome from such therapies.
Ask your child’s doctor which system is being used, and what your child’s classification / staging means in terms of potential to save sight and risk to life.