Table V.

Summary of Studies Treating Retinoblastoma with High Risk Features after Enucleation

Source	Location	Study Type	High Risk Features Defined	Total Number of pts	# of eyes enucleated up front	Chemotherapy for enucleated eyes with High risk pathology	Radiation	Outcome
Kaliki, 201119	Philadelphia, PA	Retrospective	Invasion into anterior segment, >=3mm post. uvea, PLONI, or post uvea + optic nerve involved.	51 (32 UL, 19 BL)	46/52	6 courses of Vincristine 0.05 mg/kg, Etopophos 5mg/kg, Carboplatin 18.6 mg/kg.	None	All patients alive without mets @ 66 mo
Luna-Fineman, 201120	Central America	Prospective	Massive choroidal, scleral, or optic nerve beyond the lamina cribrosa involvement.	171 (129 UL, 42 BL)	6+	Enucleation only for tumor confined to retina. Enucleation followed by 6 courses of VCR 1.5mg/m2, Etoposide 100mg/m2 (× 3days), Carboplatin 500 mg/m2 [2-3 course of chemo first if buphthalmos was present] if + high risk features.	Radiation for eyes with local regional extension (40-50 Gy).	89 alive, 44 dead, 34 abandoned tx, 4 refused tx after enrollment.
Gao, 201121	Shanghai, China	Retrospective	Not defined.	133 (107 UL, 26 BL)	123	6 courses of VCR 1.5mg/m2, Etoposide 150mg/m2 (× 2days), and Carboplatin 560mg/m2.	As salvage therapy.	Cumulative probability of survival -98% at 60 months
Chantada, 20105	Buenos Aires, Argentina	Prospective	1)Post-laminar optic nerve involvement (PLONI) with full choroid or scleral invasion, 2) tumor at the optic nerve resection margin, 3)any scleral invasion, or 4) PLONI with tumor more than 1mm beyond the lamina cribrosa or >20% of whole optic nerve stump.	114 (all UL)	95	Group 3: High risk features. Enucleation followed by 8 cycles of chemotherapy – Carboplatin 500mg/m2 × 2days, Etoposide 100mg/m2 × 3days, Cyclophosphamide 65mg/kg/day, and Idarubicin 10mg/m2/day, and VCR 1.5mg/m2/day.	Group 3 – after enucleation if + tumor invasion to optic nerve cut end -45 Gy.	5 y EFS 94%
Atchaneeyasakul, 200922	Bangkok, Thailand	Retrospective	Massive choroid invasion, extensive tumor necrosis, tumor angiogenesis, optic nerve head invasion.	90 (59 UL, 31 BL)	51 UL 31 BL	6 cycles of Carboplatin, Etoposide, and VCR.	Yes, for 7 patients.	11 alive with disease, 66 alive without disease, 7 dead
Chantada, 20044	Buenos Aires, Argentina & New York City, NY	Retrospective	Involvement of the anterior chamber, choroid (isolated), PLONI, sclera.	224 (all UL)	All	No chemo for isolated choroid or anterior chamber. PLONI (+) margin – Before 1994 – 19 wks of VDC, 6 wks intrathecal chemo. After 1994 – 8 wks of chemo (VCR/Cyclophosphamide/Idarubicin + Etoposide/Carboplatin). PLONI (-) margin–Before 1994 -19 weeks of VDC & 6 weeks intrathecal chemo. After 1994 – 8 wks of chemo (Vcr/Cyclophosphamide + Etoposide/Carboplatin).	PLONI with invasion at cut end -40-45Gy	3 y EFS 90% 3y OS 96%

Abbreviation: UL, unilateral; BL, bilateral; VCR, vincristine; PLNOI, post laminar optic nerve invasion; VDC, vincristine, doxorubicin, and cyclophosphamide