{"entity":{"id":"retinoblastoma","kind":"cancer","name":"Retinoblastoma","aka":[],"tldr":"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.\n\nTreatment 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.","asOf":"2026-09-08","wikipedia":"https://en.wikipedia.org/wiki/Retinoblastoma","links":[{"label":"NCI PDQ: retinoblastoma","url":"https://www.cancer.gov/types/retinoblastoma/patient/retinoblastoma-treatment-pdq"},{"label":"Global Retinoblastoma Study (JAMA Oncol 2020)","url":"https://doi.org/10.1001/jamaoncol.2019.6716"},{"label":"World Eye Cancer Hope","url":"https://wechope.org/"}],"tags":["gap-fill","paediatric","eye","hereditary"],"related":["neuroblastoma","wilms-tumor","hepatoblastoma","rare-childhood-cancers"],"cancers":[],"sections":[],"technologies":["cytotoxic-chemotherapy","brachytherapy","germline-testing","liquid-biopsy","autologous-stem-cell-transplant","mri"],"targets":["tp53"],"drugs":["melphalan","carboplatin","etoposide","vincristine","topotecan","cyclophosphamide"],"companies":["childrens-oncology-group"],"institutions":["mskcc"],"pathways":["p53-cell-cycle"],"terms":["germline-vs-somatic"],"trials":[],"people":[],"bottlenecks":[],"keyPapers":["paper-global-retinoblastoma-study-jama-oncol"],"journals":[],"dependsOn":[],"notes":[],"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"],"standardOfCare":[{"setting":"Advanced unilateral (group E, no vision potential)","approach":"Primary enucleation with long optic nerve segment; adjuvant chemotherapy (VEC) for high-risk pathology; orbital implant.","refs":["vincristine","etoposide","carboplatin"],"guideline":{"version":"NCI PDQ; ABS/ISOO consensus","url":"https://www.cancer.gov/types/retinoblastoma/hp/retinoblastoma-treatment-pdq"}},{"setting":"Eye-salvage (groups B-D, bilateral)","approach":"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.","refs":["melphalan","carboplatin","etoposide","vincristine","topotecan","brachytherapy"],"guideline":{"version":"NCI PDQ"}},{"setting":"Extraocular / metastatic","approach":"Intensive multi-agent chemotherapy with autologous stem-cell rescue; radiotherapy to orbit; CNS disease is the hardest to cure.","refs":["cyclophosphamide","carboplatin","etoposide","autologous-stem-cell-transplant","imrt-igrt"]},{"setting":"Surveillance and genetics","approach":"Serial examinations under anaesthesia until ~7 years; germline RB1 testing; screening of at-risk relatives from birth; lifelong second-cancer awareness in carriers.","refs":["germline-testing"]}],"stateOfArt":["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)."],"history":[{"year":1809,"title":"Wardrop recommends enucleation for 'fungus haematodes'","note":"First curative approach.","refs":[]},{"year":1971,"title":"Knudson's two-hit hypothesis","note":"Statistical analysis of hereditary vs sporadic retinoblastoma predicts tumour-suppressor genes.","refs":[]},{"year":1986,"title":"RB1 cloned (Friend, Weinberg, Dryja)","note":"The first tumour-suppressor gene identified.","refs":["tp53"]},{"year":1996,"title":"Systemic chemoreduction with focal therapy replaces radiation (Shields, Gallie)","refs":["carboplatin"]},{"year":2008,"title":"Intra-arterial melphalan via ophthalmic artery (Abramson)","refs":["melphalan"]},{"year":2012,"title":"Intravitreal melphalan for vitreous seeds (Munier)","refs":["melphalan"]},{"year":2017,"title":"Aqueous humour as liquid biopsy (Berry)","refs":["liquid-biopsy"]},{"year":2020,"title":"Global Retinoblastoma Study: survival tied to national income (JAMA Oncol)","refs":[]}],"pipeline":["melphalan","liquid-biopsy"],"openProblems":["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."],"parent":"childhood-cancers"},"route":"/cancers/retinoblastoma/","neighbours":{"cancer":[{"id":"childhood-cancers","kind":"cancer","name":"Childhood cancers (all types)","route":"/cancers/childhood-cancers/"},{"id":"hepatoblastoma","kind":"cancer","name":"Hepatoblastoma","route":"/cancers/hepatoblastoma/"},{"id":"neuroblastoma","kind":"cancer","name":"Neuroblastoma (paediatric)","route":"/cancers/neuroblastoma/"},{"id":"pineoblastoma","kind":"cancer","name":"Pineoblastoma","route":"/cancers/pineoblastoma/"},{"id":"rare-childhood-cancers","kind":"cancer","name":"Rare cancers of childhood (NCI PDQ umbrella)","route":"/cancers/rare-childhood-cancers/"},{"id":"wilms-tumor","kind":"cancer","name":"Wilms tumour (nephroblastoma)","route":"/cancers/wilms-tumor/"}],"technology":[{"id":"autologous-stem-cell-transplant","kind":"technology","name":"Autologous stem cell transplant (high-dose therapy)","route":"/technologies/autologous-stem-cell-transplant/"},{"id":"brachytherapy","kind":"technology","name":"Brachytherapy","route":"/technologies/brachytherapy/"},{"id":"cytotoxic-chemotherapy","kind":"technology","name":"Cytotoxic chemotherapy","route":"/technologies/cytotoxic-chemotherapy/"},{"id":"germline-testing","kind":"technology","name":"Germline (hereditary) testing","route":"/technologies/germline-testing/"},{"id":"global-oncology-access","kind":"technology","name":"Global oncology and access in low- and middle-income countries","route":"/technologies/global-oncology-access/"},{"id":"imrt-igrt","kind":"technology","name":"IMRT / IGRT (modern external beam)","route":"/technologies/imrt-igrt/"},{"id":"liquid-biopsy","kind":"technology","name":"Liquid biopsy (ctDNA)","route":"/technologies/liquid-biopsy/"},{"id":"mri","kind":"technology","name":"MRI","route":"/technologies/mri/"},{"id":"rejuv-paed-second-cancers","kind":"technology","name":"Second cancers after childhood cancer: the risk by treatment, and why it is falling","route":"/technologies/rejuv-paed-second-cancers/"},{"id":"rejuv-paed-teeth-and-face","kind":"technology","name":"Teeth, jaws and facial growth after treatment in childhood","route":"/technologies/rejuv-paed-teeth-and-face/"}],"target":[{"id":"cdkn1a","kind":"target","name":"CDKN1A","route":"/targets/cdkn1a/"},{"id":"tp53","kind":"target","name":"TP53","route":"/targets/tp53/"}],"drug":[{"id":"carboplatin","kind":"drug","name":"Carboplatin","route":"/drugs/carboplatin/"},{"id":"cyclophosphamide","kind":"drug","name":"Cyclophosphamide","route":"/drugs/cyclophosphamide/"},{"id":"etoposide","kind":"drug","name":"Etoposide","route":"/drugs/etoposide/"},{"id":"melphalan","kind":"drug","name":"Melphalan (including hepatic delivery system)","route":"/drugs/melphalan/"},{"id":"topotecan","kind":"drug","name":"Topotecan","route":"/drugs/topotecan/"},{"id":"vincristine","kind":"drug","name":"Vincristine","route":"/drugs/vincristine/"}],"company":[{"id":"childrens-oncology-group","kind":"company","name":"Children's Oncology Group (COG)","route":"/companies/childrens-oncology-group/"}],"institution":[{"id":"fox-chase","kind":"institution","name":"Fox Chase Cancer Center","route":"/institutions/fox-chase/"},{"id":"mskcc","kind":"institution","name":"Memorial Sloan Kettering Cancer Center","route":"/institutions/mskcc/"},{"id":"st-jude","kind":"institution","name":"St. Jude Children's Research Hospital","route":"/institutions/st-jude/"}],"pathway":[{"id":"oncogene-activation-two-hit","kind":"pathway","name":"Drivers, passengers & the two-hit model","route":"/pathways/oncogene-activation-two-hit/"},{"id":"p53-cell-cycle","kind":"pathway","name":"p53 / RB / cell-cycle checkpoint","route":"/pathways/p53-cell-cycle/"}],"term":[{"id":"germline-vs-somatic","kind":"term","name":"Germline vs somatic mutations","route":"/terms/germline-vs-somatic/"},{"id":"hereditary-cancer-syndromes","kind":"term","name":"Hereditary cancer syndromes","route":"/terms/hereditary-cancer-syndromes/"},{"id":"somatic-mutation-theory","kind":"term","name":"Somatic mutation theory of cancer","route":"/terms/somatic-mutation-theory/"}],"paper":[{"id":"paper-global-retinoblastoma-study-jama-oncol","kind":"paper","name":"Global Retinoblastoma Presentation and Analysis by National Income Level","route":"/key-papers/paper-global-retinoblastoma-study-jama-oncol/"}],"collection":[{"id":"alexs-lemonade-stand","kind":"collection","name":"Alex's Lemonade Stand Foundation (ALSF)","route":"/collections/alexs-lemonade-stand/"}],"trial":[{"id":"nct06679634","kind":"trial","name":"Retinoblastoma Phase II Expanded Access Clinical Trial","route":"/trials/nct06679634/"}]}}