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Selective Intra-arterial Chemotherapy (SIAC) in Retinoblastoma

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. DISCLOSURES. None. RETINOBLASTOMA. 1 in 20,000 live births 3% of all cancers in childhood

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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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