Retinoblastoma

- Recommendations

1-Work up for newly diagnosed retinoblastoma

We recommend bilateral examination under anaesthesia and full ophthalmology assessment for all patients suspected to have retinoblastoma.

Strong recommendation, high quality level of evidence (Systematic review and meta- analysis) ^(13)(21-23)

We recommend MRI of brain and orbits with IV contrast prior to therapy in all patients 

Strong recommendation, high quality level of evidence (Systematic review and meta- analysis) ^(13)(21-23)

For all tumors stage II and above - according to IRSS-  we recommend metastatic work up: Bilateral bone marrow biopsies, bone scan, CSF cytology and whole spine MRI

Strong recommendation, high quality level of evidence (Systematic review and meta- analysis, Multicenter Registry-Based Study) ^(24-26)

Pathology is not recommended for initial confirmation of diagnosis prior to therapy. 

Strong recommendation, moderate quality level of evidence (Expert consensus review) ⁽²⁷⁾

We recommend family counseling for all children with RB.

Strong recommendation, moderate quality level of evidence (Expert consensus review)⁽²⁸⁾

2- Treatment of Unilateral Intraocular Retinoblastoma

Surgery  

We recommend enucleation for:

· IIRC Group E

· Failed eye salvage with local treatment and systemic chemotherapy in groups C and D

·  Unilateral advanced intraocular group D disease with no hope of useful vision.

Strong recommendation, high quality level of evidence (Retrospective reviews, SIOP guideline recommendations)^(29-31)

Optic nerve resection margin is recommended to be at least 10 mm

Strong recommendation, moderate quality level of evidence (Retrospective review of clinical trials)⁽³²⁾

Histopathological assessment and staging of the enucleated eye is recommended for all patients

Strong recommendation, high quality level of evidence (Systematic review and meta-analysis)⁽¹⁾

Treatment of Group A

We recommend local treatment for all group A eyes

Strong recommendation, high quality level of evidence (Systematic review and meta-analysis)⁽⁸⁾⁽⁹⁾

Treatment of Group B

We recommend both local treatment and systemic IV three drug chemotherapy (Vincristine-Carboplatin-Etoposide) for a total of 6 cycles with 21-28 days interval in between cycles.

Strong recommendation, high quality level of evidence (Prospective clinical trial, systematic review of COG trials)^(33)(34)

Treatment of Groups C and D 

We recommend both local treatment and systemic IV three drug chemotherapy (Vincristine-Carboplatin-Etoposide) for a total of 6 cycles with 21-28 days interval in between cycles.

Strong recommendation, high quality level of evidence (Prospective clinical trial, systematic review of COG trials)^(33)(34)

We recommend routine EUA with every 1 cycle and if progressive disease we recommend  enucleation and histopathology examination.

Strong recommendation, high quality level of evidence (Retrospective reviews, SIOP guideline recommendations)^(29-31)

If NO high risk features in pathology, we do not recommend further treatment after enucleation.

Strong recommendation, high quality level of evidence (Prospective clinical trial, systematic review of COG trials)^(33)(34)

If  high risk features are present in pathology, we recommend giving total 6 cycles of systemic IV three drug chemotherapy (Vincristine-Carboplatin-Etoposide) with 21-28 days interval in between cycles.

Strong recommendation, high quality level of evidence (Prospective clinical trial, systematic review of COG trials)^(33)(34)

We recommend starting systemic chemotherapy whithin 35 days of enucleation for high risk features

Strong recommendation, high quality level of evidence (Prospective clinical trial, systematic review of COG trials)^(33)(34)

Treatment of Group E

We recommend upfront enucleation for all group E eyes

Strong recommendation, high quality level of evidence (Prospective clinical trial, systematic review of COG trials)^(33)(34)

If NO high risk features in pathology, we do not recommend further treatment after enucleation.

Strong recommendation, high quality level of evidence (Prospective clinical trial, systematic review of COG trials)^(33)(34)

If  high risk features are present in pathology, we recommend giving total 6 cycles of systemic IV three drug chemotherapy (Vincristine-Carboplatin-Etoposide) with 21-28 days interval in between cycles.

Strong recommendation, high quality level of evidence (Prospective clinical trial, systematic review of COG trials)^(33)(34)

We recommend starting systemic chemotherapy whithin 35 days of enucleation for high risk features

Strong recommendation, high quality level of evidence (Prospective clinical trial, systematic review of COG trials)^(33)(34)

3-Treatment of Bilateral Intraocular Retinoblastoma 

We recommend dictating treatment protocol by the most advanced eye.

Strong recommendation, high quality level of evidence (Prospective clinical trial, systematic review of COG trials, Systematic review)^(34-36)

We recommend upfront enucleation of the most advanced eye followed by histopathology. If the better eye is group A, B or C, we recommend enucleation of group D eyes. If both eyes are group D we recommend chemoreduction and focal therapy for both eyes.

Strong recommendation, high quality level of evidence (Prospective clinical trial, systematic review of COG trials, Systematic review)^(34-36)

We recommend chemoreduction for groups B, C and D eyes as well as local therapy similar to unilateral intraocular treatment protocols.

Strong recommendation, high quality level of evidence (Prospective clinical trial)⁽³¹⁾

4- Treatment of Extraocular Retinoblastoma  

We recommend systemic chemotherapy followed by radiation therapy for stages II-III orbital and regional lymph node involvement.

Strong recommendation, moderate quality level of evidence (COG prospective clinical trial)⁽³⁷⁾

For stage IV metastatic eyes, we recommend systemic chemotherapy, followed by high dose chemotherapy and stem cell rescue.

Strong recommendation, moderate quality level of evidence (COG prospective clinical trial)⁽³⁷⁾

Recommended systemic chemotherapy regimen includes 4 cycles of 4 drug regimen (VCR-CDDP-CPM-ETOP) with 3 weeks between cycles.

Strong recommendation, moderate quality level of evidence (COG prospective clinical trial)⁽³⁷⁾

5- Surveillance

We recommend EUA every 3-4 weeks for patients receiving active anti-tumor treatment till the end of therapy.

Strong recommendation, high quality level of evidence (systematic reviews, SEER based analysis)^(38-40)

We recommend 1-2 months EUA starting at the end of therapy and continuing for 24 months thereafter for patients who present with unilateral disease and are younger than 2 years of age at presentation or bilateral disease of any age.

Strong recommendation, high quality level of evidence (systematic reviews, SEER based analysis)^(38-40)

We recommend life long follow up and counseling for bilateral RB patients and patients with positive family history of RB as well as sibling screening

Strong recommendation, high quality level of evidence (systematic reviews, SEER based analysis)^(38-40)

For sibling screening we recommend EUA at intervals:

•   Every 2 weeks since birth till 8 weeks of age,

•   then monthly till 1 year of age,

•    then every 3 months till 3 years of age,

then every 6 months till 7 years of age

Strong recommendation, high quality level of evidence (systematic reviews, SEER based analysis)^(38-40)

For unilateral retinoblastoma patients who are older than 2 years of age we recommend extending ophthalmology examination intervals post therapy, reaching 6 monthly by age of 5 and annually thereafter.

Strong recommendation, high quality level of evidence (systematic reviews, SEER based analysis)^(38-40)

We recommend that RB survivors treated with chemotherapy or EBRT , follow up at oncology clinic every 3 months then for longer intervals as clinically warranted.

Strong recommendation, high quality level of evidence (systematic reviews, SEER based analysis)^(38-41)