What is the treatment protocol for retinoblastoma?

Treatment Protocol for Retinoblastoma

The treatment of retinoblastoma must be individualized based on disease presentation, with the primary goal of saving life while preserving vision whenever possible. Treatment approaches vary depending on whether the disease is unilateral or bilateral, the stage of the disease, and genetic factors.

Initial Assessment and Classification

• Diagnosis should be clinically established before initiating treatment, as over 25 conditions can simulate retinoblastoma in young children 1
• Growth pattern (diffuse, unifocal, multifocal), bilaterality, and trilaterality (bilateral with involvement of the pineal gland) should be documented 2
• Tumors should be classified according to standardized staging systems to guide treatment decisions 1

Treatment Approaches by Presentation

Unilateral, Non-Metastatic Retinoblastoma

• Most patients with unilateral, non-metastatic retinoblastoma can be cured with enucleation (eye removal) alone 1
• Enucleation is indicated for eyes with large tumors, long-standing retinal detachments, neovascular glaucoma, or suspected optic nerve invasion 3
• For eyes with histologic risk factors after enucleation, adjuvant chemotherapy is recommended 1
• Orbital radiation should be added for patients with trans-scleral involvement or tumor present at the cut end of the optic nerve 1

Bilateral or Multifocal Disease

• Treatment approach is conservative, with enucleation reserved only for eyes with very advanced disease 1
• Chemotherapy combined with focal treatments is the standard approach, aiming to delay or avoid radiation therapy and enucleation 1
• For early intraocular stage (Reese-Ellsworth groups I-III and International Groups A-B), a two-drug combination of vincristine and carboplatin is recommended 1
• More advanced intraocular disease (Reese-Ellsworth groups IV-V and International Groups C-D) requires more intensive chemotherapy including etoposide 1

Chemotherapy Delivery Routes

Intravenous Chemotherapy (IVC)

• Generally used for germline mutation (bilateral, familial) retinoblastoma 4
• Provides excellent tumor control for groups A, B, and C and intermediate control for group D eyes 4
• Also indicated for orbital retinoblastoma and as adjuvant treatment in high-risk retinoblastoma 5
• Patients at high risk for metastases should receive intravenous chemotherapy 4

Intra-Arterial Chemotherapy (IAC)

• Used as primary therapy in selected cases for non-germline mutation (unilateral) retinoblastoma 4
• Also used as secondary therapy for recurrent solid retinoblastoma, subretinal seeds, and vitreous seeds 4
• Particularly effective for group C or D retinoblastoma and selected cases of group E tumor 5

Periocular Chemotherapy

• Employed to boost local chemotherapy dose in advanced bilateral groups D and E eyes 4
• Also used for localized recurrences 4
• Serves as an adjunct treatment in eyes with persistent/recurrent vitreous seeds 5

Intravitreal Chemotherapy

• Reserved for eyes with persistent/recurrent vitreous seeds 4, 5

Focal Treatments

• Applied during examinations under anesthesia every 4-6 weeks 1
• Cryotherapy for small anterior tumors 1
• Thermotherapy and laser photocoagulation for small posterior tumors 1
• Brachytherapy (ophthalmic plaque) for larger tumors 1, 3

Management of Metastatic Disease

• Patients with metastases require intensive chemotherapy and consolidation with autologous hematopoietic stem cell rescue 1
• Systemic and intrathecal chemotherapy with local and cranial radiotherapy has improved survival in patients with extraocular extension 3
• New chemotherapy modalities with hematopoietic stem cell rescue or local radiotherapy have increased survival of patients with distant metastasis 3
• Prognosis remains poor for patients with central nervous system involvement 3

Long-term Follow-up and Secondary Cancer Surveillance

• All at-risk infants should have ophthalmologic examination promptly after birth (within 24 hours if possible) to maximize visual sparing with early detection 2
• Patients with heritable retinoblastoma require surveillance for secondary malignancies, particularly skin cancer (melanoma) 2
• Breast cancer screening should follow local guidelines, with preference for non-radiation imaging modalities when possible 2
• CNS tumor surveillance is not routinely recommended for asymptomatic heritable retinoblastoma survivors, regardless of prior radiation exposure 2

Emerging Treatments

• Refinement of periocular chemotherapy administration using slow-release devices 1
• Suicide gene therapy with local delivery of herpes simplex thyrosine kinase gene followed by systemic ganciclovir 1
• Development of small-molecule inhibitors of the MDMX-p53 interaction 1
• Agents with good intraocular penetration, such as topotecan, are being investigated 1