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Retinoblastoma — master index

Last curated: 2026-09-01 · status: audited (built by codex, independently audited by claude on 2026-09-01; all 19 pages promoted to curated)

The condition in five sentences. Retinoblastoma is a malignant tumour of the developing retina, diagnosed in approximately 8,000 children annually, usually after both RB1 alleles are inactivated in a susceptible cone-lineage cell (Dimaras 2015, PMID 27189421). Knudson inferred the two-hit model from 48 cases, making this childhood eye cancer foundational to tumour-suppressor biology (Knudson 1971, PMID 5279523). In 4,064 children from 149 countries, three-year survival was 99.5% (95% CI 98.8–100.0) in high-income and 57.3% (52.1–63.0) in low-income countries, tracking cT4 presentation of 0.8% versus 42.9% (Global Study Group 2022, PMID 35839812). Treatment orders life, globe and then useful vision through enucleation, systemic/focal therapy, IAC and intravitreal therapy. Heritable survivors—not survivors as one undifferentiated group—had overall subsequent-malignancy SIR 11.9 and 33.1% cumulative incidence at 50 years, while non-heritable survivors had SIR 0.8 (Schonfeld 2021, PMID 33473166).

Start here: overview. Research frontier: OPEN-QUESTIONS.md. Growth history: LOG.md.

At a glance

Layer Built content
Canonical wiki pages 19/19, all curated
Distinct live-resolved PMIDs cited 367, all re-fetched at audit (367 in wiki pages)
Distinct live-resolved NCT IDs cited 12, all re-queried at audit
Landmark paper notes 5
Guideline/consensus/review records catalogued 10
Verified patient organizations 4
Open questions 20 (12 Tier 1, 8 Tier 2)
Dots-not-yet-connected junctions 14
Claim→citation pairs checked at audit 800 reference lines, 1,385 inline citations, 214 quantitative bullets, 145 statistics rows

Reading paths

Need Path
Rapid orientation Overviewpresentation/diagnosisred flags
Genetics and family risk RB1 geneticstesting/counsellingsurvivorship
Intraocular treatment Classificationsystemic chemotherapyIACintravitreal/intracameral
Advanced disease Enucleation/pathologyextraocular/metastatic/trilateral
Global outcomes Epidemiologyaccess disparitypatient experience
Research design Molecular pathogenesistrial landscapeopen questions

Shared border with melanoma

The border is heritable retinoblastoma, not retinoblastoma survivorship as a whole. Schonfeld reports any-SMN SIR 11.9 (95% CI 10.4–13.5) in heritable and 0.8 (0.5–1.2) in non-heritable survivors; melanoma risk is significantly increased in the heritable group, while 3.1–17 is a range across melanoma, CNS, oral-cavity and breast sites rather than a melanoma-specific point estimate (PMID 33473166). A separate Danish cohort estimated melanoma SIR 26.78 (95% CI 9.78–58.30), and that figure is attributed only to that cohort (Gregersen 2020, PMID 33090227). Cross-links: melanoma germline predisposition and melanoma special populations. Retinoblastoma in children and uveal melanoma in adults remain separate by age and biology.

Pages

File Scope Status
overview.md condition map, two-hit history, treatment and inequity curated
epidemiology-and-global-burden.md incidence, age, laterality, income-stratified survival curated
rb1-genetics-and-heritability.md two-hit model, germline/somatic, mosaicism, 13q curated
genetic-testing-and-counselling.md assay design, cascade and reproductive counselling curated
molecular-pathogenesis-and-cell-of-origin.md cone lineage, progression, MYCN/RB1-wild-type curated
clinical-presentation-and-diagnosis.md leukocoria, strabismus, EUA, imaging, biopsy boundary curated
classification-and-staging.md ICRB/IIRC, cTNMH and IRSS curated
systemic-chemotherapy.md VEC/CEV, chemoreduction and adjuvant therapy curated
intra-arterial-chemotherapy.md OAC/IAC efficacy, vascular toxicity and access curated
intravitreal-and-intracameral-chemotherapy.md vitreous/aqueous seeds and injection safety curated
focal-therapy-and-brachytherapy.md laser, cryotherapy, thermotherapy and plaque curated
enucleation-and-high-risk-pathology.md indications, histopathology, adjuvant therapy, prosthesis curated
extraocular-metastatic-and-trilateral-disease.md orbital/systemic/CNS spread and trilateral disease curated
second-cancers-and-survivorship.md heritability-stratified SMN risk and surveillance curated
global-access-and-outcome-disparity.md stage, delay, abandonment and systems curated
vision-outcomes-and-patient-experience.md useful vision, QOL, eye loss and family experience curated
guidelines.md document synthesis and disagreements curated
clinical-trials-landscape.md live NCT status and trial gaps curated
red-flags-and-safety-concerns.md diagnostic/procedural/survivorship safety curated

Literature layer

Resource Contents Status
BIBLIOGRAPHY.md 365 wiki-cited live-resolved PMIDs grouped and cross-indexed curated
notes/ five landmark notes curated
guidelines/REGISTRY.md guideline lineages, disagreements and watch list curated
statistics/STATISTICS.md 90+ sourced quantitative rows curated
patient-voice/README.md method and ethics curated
patient-voice/organizations.md four verified organizations curated
patient-voice/themes.md seven aggregate themes curated
patient-voice/sources.md annotated sources and exclusions curated

Curation state

Built by codex on 2026-09-01 and independently audited by claude on 2026-09-01. Every one of the 367 cited PubMed identifiers was re-fetched live at audit; all resolved, and author, year, journal and title matched the citation as written in all 800 numbered reference lines and 1,385 inline citations. All 12 ClinicalTrials.gov identifiers were re-queried against the v2 API and their recorded status and phase matched the live registry. Three off-topic records that had entered by title indexing (two palbociclib trials in glioma/oligodendroglioma, one RB1-in-multiple-myeloma review) were removed, a fourth (a neuroblastoma cell-line study) was relabelled as mechanistic background, three fabricated DOIs in landmark notes were corrected, and one citation that existed only in OPEN-QUESTIONS.md was given a wiki home and catalogued. All 19 pages are curated.

Verification is abstract-level throughout: no claim on these pages depends on full text beyond the abstract of the record it cites.