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Teaching pack: Retinoblastoma

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9 slides generated from the cancer page, with a quiz from the open benchmark and speaker notes that cite the sources. Arrow keys move between slides; Print gives one slide per page.

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  1. Teaching pack · Cancer · paediatric

    Retinoblastoma

    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 poor countries many children still die because it is found too late.

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  2. What it is

    In two paragraphs

    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 often fatal. 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.

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  3. Standard of care

    What is given today, by setting

    SettingApproachGuideline
    Advanced unilateral (group E, no vision potential)Primary enucleation with long optic nerve segment; adjuvant chemotherapy (VEC) for high-risk pathology; orbital implant.not mapped
    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.not mapped
    Extraocular / metastaticIntensive multi-agent chemotherapy with autologous stem-cell rescue; radiotherapy to orbit; CNS disease has poor prognosis.not mapped
    Surveillance and geneticsSerial examinations under anaesthesia until ~7 years; germline RB1 testing; screening of at-risk relatives from birth; lifelong second-cancer awareness in carriers.not mapped
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  4. State of the art

    Where the field stands

    • 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 death from orbital and metastatic disease where it is not (Global Retinoblastoma Study, 2020).
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  5. History

    How we got here

    1. 1809Wardrop recommends enucleation for 'fungus haematodes'
    2. 1971Knudson's two-hit hypothesis
    3. 1986RB1 cloned (Friend, Weinberg, Dryja)
    4. 1996Systemic chemoreduction with focal therapy replaces radiation (Shields, Gallie)
    5. 2008Intra-arterial melphalan via ophthalmic artery (Abramson)
    6. 2012Intravitreal melphalan for vitreous seeds (Munier)
    7. 2017Aqueous humour as liquid biopsy (Berry)
    8. 2020Global Retinoblastoma Study: survival tied to national income (JAMA Oncol)
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  6. Pipeline

    What is coming

    • Melphalan (including hepatic delivery system) (product)
    • Liquid biopsy (ctDNA) (technology)
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  7. Open problems

    What nobody has solved

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

    Check understanding

    1. What questions should someone newly diagnosed with triple-negative breast cancer ask before surgery?
      Answer
      Whether chemo-immunotherapy before surgery (KEYNOTE-522) is planned and why; germline BRCA testing; PD-L1 and HER2-low status; TIL score; clinical trial options; fertility preservation; breast-conserving versus mastectomy and sentinel node approach; what response (pCR/RCB) will mean for treatment afterwards.
    2. What is a liquid biopsy used for in cancer care today?
      Answer
      A blood test reading tumour DNA fragments: to genotype a tumour when tissue is scarce, to track resistance mutations (EGFR T790M, ESR1), to detect minimal residual disease after surgery, and, experimentally, to screen for cancer.
    3. What is brachytherapy and where is it essential?
      Answer
      Placing a radioactive source directly inside or next to the tumour; essential in cervical cancer, used in prostate (seeds or HDR), breast, skin, and eye melanoma.
    4. Who should have germline genetic testing when diagnosed with cancer?
      Answer
      All patients with TNBC, ovarian, pancreatic, or metastatic prostate cancer, increasingly all breast cancer, and anyone with suggestive family history; results change surgery, drug choice (PARP inhibitors), and family screening.
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  9. Sources

    Read the primary sources

    • 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/
    • Wikipedia: https://en.wikipedia.org/wiki/Retinoblastoma
    • Guideline: https://www.cancer.gov/types/retinoblastoma/hp/retinoblastoma-treatment-pdq
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