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Year : 2017  |  Volume : 10  |  Issue : 3  |  Page : 133-134  

Classification of retinoblastoma: Evolution with time and the need for uniformity

Shri Bhagwan Mahavir Vitreoretinal Services, Sankara Nethralaya, Chennai, Tamil Nadu, India

Date of Web Publication5-Oct-2017

Correspondence Address:
Vikas Khetan
Senior Consultant, Shri Bhagwan Mahavir Vitreoretinal Services, Sankara Nethralaya, 18 College Road, Chennai - 600 006, Tamil Nadu
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Source of Support: None, Conflict of Interest: None

DOI: 10.4103/0974-620X.216017

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How to cite this article:
Maitray A, Khetan V. Classification of retinoblastoma: Evolution with time and the need for uniformity. Oman J Ophthalmol 2017;10:133-4

How to cite this URL:
Maitray A, Khetan V. Classification of retinoblastoma: Evolution with time and the need for uniformity. Oman J Ophthalmol [serial online] 2017 [cited 2023 Mar 31];10:133-4. Available from: https://www.ojoonline.org/text.asp?2017/10/3/133/216017

The classification systems of intraocular retinoblastoma (RB) have evolved steadily over time, parallel to the prevalent modalities of available treatment options. An ideal classification system should have two components: grouping (for globe salvage prognosis) and staging (survival prognosis).

The Reese–Ellsworth (RE) classification[1] was proposed in 1960s when external beam radiotherapy (EBRT) was the primary conservative treatment. It was developed to predict the prognosis following EBRT. It divided the eyes into five groups, progressing from very favorable (Group 1) to very unfavorable (Group 5) prognosis based on the absence or presence of clinical features known to be associated with poor response to EBRT and treatment failure. Large, multifocal, or peripheral tumors were associated with worse prognosis. However, EBRT itself was also associated with significant morbidity such as facial disfigurement and risk of second malignant neoplasms in patients with germline mutations.

In the mid-1990s, EBRT was largely replaced by systemic chemoreduction (CRD) with focal consolidation (such as cryotherapy, transpupillary thermotherapy) as the primary conservative therapy for RB. RE classification did not accurately predict the treatment response to CRD since tumor size, location, and focality were no longer the main limiting variables for treatment response. Factors like management of vitreous and subretinal seeding became more important in the CRD era. Hence, this paradigm shift was soon followed by a new classification system in 2003, the International Classification of Intraocular Retinoblastoma (ICRB). It provided the correlation of the natural history of intraocular tumor and likelihood of success with CRD.[2] It divided intraocular RB into five groups (A-E) with very low, low, moderate, high, and very high risk of treatment failure with CRD, respectively. However, two versions of this system have been proposed, the Philadelphia version[2] and the Children's Hospital Los Angeles (CHLA) version,[3] showing subtle but significant differences. In a study analyzing the impact of these differences, Novetsky et al. reported that 20% of eyes that were classified as Group E according to the Philadelphia group ICRB classification were reassigned to Group D by the CHLA group classification.[4] All these eyes had an intraocular tumor occupying more than 50% of the globe (a feature of Philadelphia version of Group E eyes), which failed to meet the destructive criteria of the CHLA version of Group E ICRB. The study further points out that, owing to these discrepancies in group definitions, there is a theoretical possibility that the same eye can be classified as Group E (very high risk) by the Philadelphia version and as Group B (low risk) according to the CHLA version IIRC, if it had a large intraocular tumor >50% of the globe but no vitreous/subretinal seeds, thus concluding that it is imperative to resolve the discrepancies between the two versions.

Another important aspect worth noting is that the International classification is meant for grouping of treatment naïve eyes with retinoblastoma. It is not uncommon for ocular oncologists (especially at tertiary eye care centers) to encounter patients with active/partially regressed RB having received some form of prior treatment (CRD or focal therapy) elsewhere. In such a scenario, it would be inappropriate to assign an ICRB grouping to the eyes based on the current status at that visit, due to the possibility of down grading of the tumor. It is imperative to go through the prior medical records of the patient to know the status of the eye at first presentation to assign the appropriate grouping and to plan further management.

The International staging system proposed by Chantada et al. in 2006 was the first such for retinoblastoma incorporating five distinct stages for survival prognosis, based on collective information gathered by the clinical ocular evaluation, imaging, systemic evaluation, and histopathology.[5]

In the past decade, there has been a rapid emergence of newer management options and strategies such as selective ophthalmic artery chemotherapy, intravitreal chemotherapy, and prenatal genetic testing for early detection of familial RB.[6],[7] Consequently, there is progressively increased salvage of life, eye and vision and the treatment algorithms are rapidly transforming. There is a need for a single uniform classification system for retinoblastoma including both intraocular and extraocular disease to be followed as a gold standard reference to ensure consistency in clinical research reports and management.

The eighth edition of “tumor, node, metastasis, and heritability” cancer staging system for retinoblastoma has been proposed to most accurately predict the salvage of the eye(s), metastasis, and death and is likely to gradually replace the popular ICRB classification as the gold standard.[8] This staging system incorporates intraocular (cT1–cT3) and extraocular tumor (cT4) and it also makes retinoblastoma the first cancer to include heritability (HX, H0, H1) in cancer staging.

   References Top

Reese AB, Ellsworth RM. The evaluation and current concept of retinoblastoma therapy. Trans Am Acad Ophthalmol Otolaryngol 1963;67:164-72.  Back to cited text no. 1
Shields CL, Mashayekhi A, Au AK, Czyz C, Leahey A, Meadows AT, et al. The international classification of retinoblastoma predicts chemoreduction success. Ophthalmology 2006;113:2276-80.  Back to cited text no. 2
Linn Murphree A. Intraocular retinoblastoma: The case for a new group classification. Ophthalmol Clin North Am 2005;18:41-53, viii.  Back to cited text no. 3
Novetsky DE, Abramson DH, Kim JW, Dunkel IJ. Published international classification of retinoblastoma (ICRB) definitions contain inconsistencies – An analysis of impact. Ophthalmic Genet 2009;30:40-4.  Back to cited text no. 4
Chantada G, Doz F, Antoneli CB, Grundy R, Clare Stannard FF, Dunkel IJ, et al. A proposal for an international retinoblastoma staging system. Pediatr Blood Cancer 2006;47:801-5.  Back to cited text no. 5
Abramson DH, Shields CL, Munier FL, Chantada GL. Treatment of retinoblastoma in 2015: Agreement and disagreement. JAMA Ophthalmol 2015;133:1341-7.  Back to cited text no. 6
Soliman SE, Dimaras H, Khetan V, Gardiner JA, Chan HS, Héon E, et al. Prenatal versus postnatal screening for familial retinoblastoma. Ophthalmology 2016;123:2610-7.  Back to cited text no. 7
Mallipatna AC, Gallie BL, Chévez-Barrios P, Lumbroso-Le Rouic L, Chantada GL, Doz F, et al. Retinoblastoma. In: Amin MB, Edge SB, Greene FL, Byrd DR, Brookland RK, Washington MK, et al., editors. AJCC Cancer Staging Manual. 8th ed. New York: Springer; 2017. p. 819-31.  Back to cited text no. 8


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