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Selective Intra-arterial Chemotherapy (SIAC) in Retinoblastoma

Learn about the groundbreaking use of SIAC in managing Retinoblastoma to preserve vision, minimize late effects, and improve outcomes. Explore the technique, treatment strategy, staging, complications, and outcomes at GOSH.

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Selective Intra-arterial Chemotherapy (SIAC) in Retinoblastoma

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  1. Selective Intra-arterial Chemotherapy (SIAC) in Retinoblastoma Great Ormond Street Hospital, London, UK Lakshmi Kanagarajah, Catriona Duncan, Mette Jorgensen, Jane Herod, Adam Rennie, Fergus Robertson

  2. DISCLOSURES None

  3. RETINOBLASTOMA • 1 in 20,000 live births • 3% of all cancers in childhood • New cases/yr: UK 40 (2); US 300; Canada 20 • 1/3 familial / bilat - (AD Rb1 gene c/some 13) • Median pres age 8 months • 2/3 sporadic / unilateral - Median pres 28mo • >95% 5 yr ➔ 85% 20 yr survival (cf 20% dev world) • <5% extraocular Dx (cf 90% dev world)

  4. Aims: 1. Preserve life Dev 98% vs < 20% in developing extraocular RB – 20% cure (non-CNS better) 2. Preserve vision / cosmesis 3. Minimise late effects 10% second tumour at 20 years (Fam) sarcoma / melanoma radiation related tumours TREATMENT STRATEGY

  5. PROS: Max therapeutic / min toxic Limit marrow suppression / central venous catheter risks Salvage vision / cosmesis Avoid EBRT ? fewer late FX Why SIAC? CONS: Orbital / extraorbital risks (stroke etc) Limited in vitreous disease Metastatic concerns

  6. A B C D E Local therapies (laser, cryo, plaque) Local vitreous seeds Unsalvageable / destroyed / metastatic Diffuse vitreous seeds Small tumour limited areas Large tumour all areas STAGING: INTERNATIONAL INTRAOCULAR RETINOBLASTOMA CLASSIFICATION (IIRC) IV Chemotherapy (EBRT) enucleation Limited to retina Extra-retinal spread

  7. INTRAOPHTHALMIC CHEMOTHERAPY TECHNIQUE • 4F sheath femoral artery • IV heparin 75 iU/kg • 4F vertebral catheter • Magic 1.2F-1.8F microcatheter • IA GTN (30-50mcg boluses) • Choroidal blush • Antegrade OA flow • Limited cerebral escape • Melphalan / topetecan infusion over 30 minutes by oncologist • Iv dexamethasone post

  8. 329 treatments in 102 eyes in 92 children • SIAC per eye 1-7 mean 3.1 (1 failed access) • 43 boys, 42L 50R 10BL • Mean age 3.2 yr (6 months – 12.5 yr) • 63% bilateral (familial) disease • Protocol • All C/D eyes, refractory / relapsed IV chemo • IA treatment every 4 weeks x 3 • Melphalan and topetecan (melph only before 2014) • EUA - 2 weeks after each treatment INTRAOPHTHALMIC CHEMOTHERAPY (GOSH 2008-2016)

  9. JAMA 2016 12 papers 655 pts / 757 eyes 16 papers 458 pts / 521 eyes

  10. GOSH OUTCOMES

  11. GOSH COMPLICATIONS

  12. PHYSIOLOGICAL REACTION • >50% fall in ETV and / or >50% drop in SBP • Never in ‘naïve’ patient • worst on second, subsequent improvement • ? primed on first treatment (no chemo required) • Anaphylaxis work up neg. / no response to atropine • 1mcg / kg iv epinephrine boluses - maintain normotension (cf 10-100mcg/kg for anaphylaxis)

  13. CONCLUSION Very promising technique but morbidity Place in treatment algorithm? ? A-B / C-D-E ? Vitreous treatments Physiological reaction real but can be managed RCT: Primary IA vs IV chemotherapy*, but small numbers – needs collaboration * Shields et al 2016: IAC vs IVC UL / retrospective / non-matched

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