# Retinoblastoma

Source: https://onco.cc/cancers/retinoblastoma/  
OnCo record `retinoblastoma` (Cancer). Data CC BY-NC 4.0, attribute "Data from OnCo (onco.cc)"; commercial use needs a licence.

## TL;DR

An eye cancer of infants caused by loss of the RB1 gene, the first tumour-suppressor gene ever found. In rich countries almost every child survives and most eyes are saved by chemotherapy delivered through the eye's artery; in low-income countries, where most cases occur, survival depends on finding it early, and that is the global gap.

## Summary

Retinoblastoma arises from biallelic loss of RB1 in developing retinal cells (Knudson's two-hit hypothesis, 1971; RB1 cloned 1986), or rarely from MYCN amplification with intact RB1. Heritable disease (~40%, germline RB1) is usually bilateral and multifocal, presents earlier, and carries lifelong risk of second cancers (osteosarcoma, melanoma, sarcomas), especially after radiation. Leukocoria and strabismus are the presenting signs; diagnosis is clinical and by imaging (biopsy is avoided), and staging uses the International Intraocular Retinoblastoma Classification (groups A-E) and the TNMH system.

Treatment aims first at life, then at eye and vision. Advanced unilateral eyes (group E) are enucleated with pathologic high-risk features guiding adjuvant chemotherapy; salvageable eyes receive intra-arterial melphalan via the ophthalmic artery (Abramson, 2008), systemic chemoreduction (carboplatin, etoposide, vincristine) with focal laser/cryotherapy, and intravitreal melphalan for vitreous seeds. External-beam radiation is avoided in germline carriers. Extraocular and metastatic disease is treated with intensive chemotherapy and autologous stem-cell rescue; trilateral disease (pineal) is rarely curable. Aqueous-humour cell-free DNA (2017) is the first liquid biopsy for a tumour that cannot be biopsied. Genetic counselling and screening of siblings and offspring are integral.

## Fields

- Kind: Cancer
- Last checked: 2026-09-08
- Tags: gap-fill; paediatric; eye; hereditary
- Group: paediatric
- Burden: About 1 in 16,000-18,000 live births (~8,000 children per year worldwide); survival >95% in high-income countries but 30-60% in low-income countries where most cases occur.
- Subtypes: Heritable (germline RB1; usually bilateral); Non-heritable unilateral (somatic RB1); MYCN-amplified RB1-wild-type (infants, aggressive); Trilateral retinoblastoma (with pineoblastoma); Retinoma (benign precursor)
- Biomarkers: Germline RB1 testing (proband and family); IIRC group A-E and TNMH stage; High-risk pathology after enucleation (massive choroidal invasion, post-laminar optic nerve, scleral invasion); Aqueous humour cfDNA (6p gain, RB1 status); MYCN amplification; MRI of brain for pineal/optic nerve involvement

## Sections of this record

The page is a hub with ten sections in reading order; large sections have their own page. The same plan as JSON: https://onco.cc/api/v1/cancers/retinoblastoma/sections.json

- Overview (on the hub): The TL;DR, the family this cancer belongs to, the organ, who gets it and what the state of the art is. https://onco.cc/cancers/retinoblastoma/#overview [4 state-of-the-art points]
- What it is (on the hub): Anatomy, the subtypes and how they differ, how it is staged, and where advanced disease spreads. https://onco.cc/cancers/retinoblastoma/#what-it-is [5 subtypes]
- Finding it (on the hub): How it shows itself, how it is confirmed, what screening exists, and the biomarkers clinicians test for. https://onco.cc/cancers/retinoblastoma/#finding-it [6 biomarkers]
- Treating it (on the hub): The standard of care by setting, the medicines, surgery and radiotherapy named in it, and the regimens behind them. https://onco.cc/cancers/retinoblastoma/#treating-it [4 settings, 1 regimen, 3 decisions with options]
- Evidence (on the hub): Trials recruiting now, the landmark trials, the key papers and what they mean, the latest literature, and the milestones year by year. https://onco.cc/cancers/retinoblastoma/#evidence [1 trial, 1 key paper, 8 milestones]
- The science (on the hub): The molecular landscape: the targets and how often each appears, the pathways, the mechanics stages and the preclinical models. https://onco.cc/cancers/retinoblastoma/#science [3 targets, 2 pathways]
- Where you are (own page): Cases by country, the UK and NHS pathway and other country lenses, and the expert centres with trials on record. https://onco.cc/cancers/retinoblastoma/where-you-are/ [3 centres]
- Living with it (on the hub): The decisions you may face, the aids that walk through them, the warnings on record, the first sixty days and the questions to ask. https://onco.cc/cancers/retinoblastoma/#living-with-it [16 questions, 6 red cards]
- What is coming (own page): Everything in development, the open problems and what is being done about them, the roadmaps, and what changed on this record. https://onco.cc/cancers/retinoblastoma/coming/ [6 medicines, 1 trial, 4 open problems]
- Data (own page): Every connected record, the notes, the JSON, Markdown and RDF twins, and where the record came from and when it was checked. https://onco.cc/cancers/retinoblastoma/data/ [39 connected records]

## Standard of care

- Advanced unilateral (group E, no vision potential): Primary enucleation with long optic nerve segment; adjuvant chemotherapy (VEC) for high-risk pathology; orbital implant. ([Vincristine](https://onco.cc/drugs/vincristine/), [Etoposide](https://onco.cc/drugs/etoposide/), [Carboplatin](https://onco.cc/drugs/carboplatin/))
- Eye-salvage (groups B-D, bilateral): Intra-arterial melphalan (± topotecan, carboplatin) via ophthalmic artery, or systemic chemoreduction (vincristine, etoposide, carboplatin) with consolidating laser, cryotherapy or plaque brachytherapy; intravitreal melphalan for vitreous seeds. ([Melphalan (including hepatic delivery system)](https://onco.cc/drugs/melphalan/), [Carboplatin](https://onco.cc/drugs/carboplatin/), [Etoposide](https://onco.cc/drugs/etoposide/), [Vincristine](https://onco.cc/drugs/vincristine/), [Topotecan](https://onco.cc/drugs/topotecan/), [Brachytherapy](https://onco.cc/technologies/brachytherapy/))
- Extraocular / metastatic: Intensive multi-agent chemotherapy with autologous stem-cell rescue; radiotherapy to orbit; CNS disease is the hardest to cure. ([Cyclophosphamide](https://onco.cc/drugs/cyclophosphamide/), [Carboplatin](https://onco.cc/drugs/carboplatin/), [Etoposide](https://onco.cc/drugs/etoposide/), [Autologous stem cell transplant (high-dose therapy)](https://onco.cc/technologies/autologous-stem-cell-transplant/), [IMRT / IGRT (modern external beam)](https://onco.cc/technologies/imrt-igrt/))
- Surveillance and genetics: Serial examinations under anaesthesia until ~7 years; germline RB1 testing; screening of at-risk relatives from birth; lifelong second-cancer awareness in carriers. ([Germline (hereditary) testing](https://onco.cc/technologies/germline-testing/))

## State of the art

- Intra-arterial chemotherapy saves eyes that would have been removed, with globe salvage ~70-90% in group D and few systemic effects.
- Radiation has been almost eliminated because of second cancers in RB1 carriers.
- Aqueous-humour cfDNA gives molecular information without biopsy.
- The gap is global: >90% survival where diagnosis is early, versus much lower survival with orbital and metastatic disease where it is not (Global Retinoblastoma Study, 2020).

## Open problems

- Late diagnosis in low-income countries; paediatric ophthalmology access is the lever.
- Second primary cancers in RB1 carriers across life.
- Vision outcomes after eye salvage.
- Metastatic and CNS disease.

## Sources

- Wikipedia: https://en.wikipedia.org/wiki/Retinoblastoma
- NCI PDQ: retinoblastoma: https://www.cancer.gov/types/retinoblastoma/patient/retinoblastoma-treatment-pdq
- Global Retinoblastoma Study (JAMA Oncol 2020): https://doi.org/10.1001/jamaoncol.2019.6716
- World Eye Cancer Hope: https://wechope.org/

## Connected records

- cancers: [Childhood cancers (all types)](https://onco.cc/cancers/childhood-cancers/), [Hepatoblastoma](https://onco.cc/cancers/hepatoblastoma/), [Neuroblastoma (paediatric)](https://onco.cc/cancers/neuroblastoma/), [Pineoblastoma](https://onco.cc/cancers/pineoblastoma/), [Rare cancers of childhood (NCI PDQ umbrella)](https://onco.cc/cancers/rare-childhood-cancers/), [Wilms tumour (nephroblastoma)](https://onco.cc/cancers/wilms-tumor/)
- technologies: [Autologous stem cell transplant (high-dose therapy)](https://onco.cc/technologies/autologous-stem-cell-transplant/), [Brachytherapy](https://onco.cc/technologies/brachytherapy/), [Cytotoxic chemotherapy](https://onco.cc/technologies/cytotoxic-chemotherapy/), [Germline (hereditary) testing](https://onco.cc/technologies/germline-testing/), [Global oncology and access in low- and middle-income countries](https://onco.cc/technologies/global-oncology-access/), [IMRT / IGRT (modern external beam)](https://onco.cc/technologies/imrt-igrt/), [Liquid biopsy (ctDNA)](https://onco.cc/technologies/liquid-biopsy/), [MRI](https://onco.cc/technologies/mri/)
- targets: [CDKN1A](https://onco.cc/targets/cdkn1a/), [TP53](https://onco.cc/targets/tp53/)
- drugs: [Carboplatin](https://onco.cc/drugs/carboplatin/), [Cyclophosphamide](https://onco.cc/drugs/cyclophosphamide/), [Etoposide](https://onco.cc/drugs/etoposide/), [Melphalan (including hepatic delivery system)](https://onco.cc/drugs/melphalan/), [Topotecan](https://onco.cc/drugs/topotecan/), [Vincristine](https://onco.cc/drugs/vincristine/)
- companies: [Children's Oncology Group (COG)](https://onco.cc/companies/childrens-oncology-group/)
- institutions: [Fox Chase Cancer Center](https://onco.cc/institutions/fox-chase/), [Memorial Sloan Kettering Cancer Center](https://onco.cc/institutions/mskcc/), [St. Jude Children's Research Hospital](https://onco.cc/institutions/st-jude/)
- pathways: [Drivers, passengers & the two-hit model](https://onco.cc/pathways/oncogene-activation-two-hit/), [p53 / RB / cell-cycle checkpoint](https://onco.cc/pathways/p53-cell-cycle/)
- terms: [Germline vs somatic mutations](https://onco.cc/terms/germline-vs-somatic/), [Hereditary cancer syndromes](https://onco.cc/terms/hereditary-cancer-syndromes/), [Somatic mutation theory of cancer](https://onco.cc/terms/somatic-mutation-theory/)
- key papers: [Global Retinoblastoma Presentation and Analysis by National Income Level](https://onco.cc/key-papers/paper-global-retinoblastoma-study-jama-oncol/)
- collections: [Alex's Lemonade Stand Foundation (ALSF)](https://onco.cc/collections/alexs-lemonade-stand/)
- trials: [Retinoblastoma Phase II Expanded Access Clinical Trial](https://onco.cc/trials/nct06679634/)

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JSON: https://onco.cc/api/v1/entities/retinoblastoma.json