1. Studied for effect of delayed enucleation on mortality
Eligibility: Intraocular retinoblastoma; no extraocular or metastatic disease at diagnosis
(N = 600)
Primary exclusion (n = 46)
Bilateral advanced RB (n = 44)
Died from chemotherapy toxicity (n = 2)
Studied for effect of delayed enucleation on mortality
(n = 554)
IIRC Group D (n = 202)
Died from RB metastasis (n = 6)
IIRC Group E (n = 352)
Died from RB metastasis (n = 16)
Secondary exclusion (n = 44)
Received < 1 cycle of pre-enucleation chemotherapy (n = 15)
Received non-systemic chemotherapy salvage therapy (n = 29)
Intra-arterial chemotherapy (n = 18)
Pars plana vitrectomy endoresection (n = 6)
Plaque radiotherapy (n = 3)
Stem cell transplantation (n = 1)
Immunotherapy (n = 1)
FIG 1. CONSORT diagram.
Studied for effect of pre-enucleation systemic chemotherapy on mortality
(n = 510)
IIRC Group D (n = 177)
Died from RB metastasis (n = 4)
IIRC Group E (n = 333)
Died from RB metastasis (n = 16)

2. A B Children with IIRC group D eyes Children with IIRC group E eyes
< 3.5 months from diagnosis to enucleation
< 2 months from diagnosis to enucleation
> 3.5 months from diagnosis to enucleation
> 2 months from diagnosis to enucleation
Log-rank P = .018
Log-rank P = .017
FIG 2. Kaplan-Meier curves of disease-specific survival (DSS) of children with enucleated Groups D and E eyes. (A) DSS of children with group D eyes enucleated < 3.5 months and > 3.5 months from diagnosis. (B) DSS of children with group E eyes enucleated < 2 months and > 2 months from diagnosis.
No. at risk
< 3.5 months dx to enu 97 93 89 72 20
> 3.5 months dx to enu
105 99 92 66 17 1
No. at risk
< 2 months dx to enu
268
227
212
174 68 6
> 2 months dx to enu 84 75 65 56 34 1

3. Primary enucleation
1 to 3 cycles of pre-enucleation chemotherapy
≥ 4 cycles of pre-enucleation chemotherapy
Log-rank P = .031
No. at risk
Primary enucleation
214
182
173
139 44 6
1 to 3 cycles of chemotherapy 72 60 55 50 33
≥ 4 cycles of chemotherapy 47 42 30 20 1
FIG 3. Kaplan-Meier curves and Cox proportional hazard regression model of disease-specific survival of children with enucleated Group E eyes who received primary enucleation, 1 to 3 cycles of pre-enucleation chemotherapy and ≥ 4 cycles of pre-enucleation chemotherapy.
Group n
Events
HR (95% CI) P
Primary enucleation
214 8
0.77 (0.16 to 3.61)
.74
1 to 3 chemotherapy cycles 72 2
3.35 (1.16 to 9.67)
.025
≥ 4 chemotherapy cycles 47 6

4. A B
Low-risk eyes without pre-enucleation chemotherapy
Low-risk eyes without post-enucleation chemotherapy
Low-risk eyes with pre-enucleation chemotherapy
Low-risk eyes with post-enucleation chemotherapy
High-risk eyes without pre-enucleation chemotherapy
High-risk eyes without post-enucleation chemotherapy
High-risk eyes with pre-enucleation chemotherapy
High-risk eyes with post-enucleation chemotherapy
Log-rank P < .001
Log-rank P < .001
No. at risk
LR eyes w/o chemo
196
176
170
136 41 5
LR eyes w/ chemo
208
191
146 73 2
HR eyes w/o chemo 79 64 59 46 13 1
HR eyes w/ chemo 27 21 14 10
No. at risk
LR eyes w/o chemo
291
268
252
197 45 2
LR eyes w/ chemo
151
135
129
114 76 5
HR eyes w/o chemo 15 11 6 3
HR eyes w/ chemo 97 80 71 54 18 1
FIG 4. Kaplan-Meier curves and Cox proportional hazard regression model of disease-specific survival (DSS) of children with enucleated low-risk (LR) and high-risk (HR) eyes (A) DSS of children who received pre-enucleation chemotherapy compare with those who did not. (B) DSS of children who received post-enucleation compare with those who did not.
Group n
Events
HR (95% CI) P
LR eyes w/o chemo
196 2
0.94 (0.13 to 6.70)
.95
LR eyes w/ chemo
208
HR eyes w/o chemo 79 6
5.21 (1.89 to 14.29)
< .001
HR eyes w/ chemo 27 10
Group n
Events
HR (95% CI) P
LR eyes w/o adjuvant chemo
291 4
0.49 (0.054 to 4.35)
.52
LR eyes w/ adjuvant chemo
151 1
HR eyes w/o adjuvant chemo 15 7
0.20 (0.074 to 0.52)
.001
HR eyes w/ adjuvant chemo 97 10