Program Book

Ruth A. Kleinerman1, Chu-ling Yu1, Mark P. Little1, Yi Li2, David H.
Abramson3, Johanna H. Seddon4, and Margaret A. Tucker1 (kleinerr@
mail.nih.gov)
1. Division of Cancer Epidemiology and Genetics, National Cancer Institute,
National Institutes of Health, Department of Health and Human Services,
Rockville, MD
2. Department of Biostatistics and Computational Biology, Dana Farber
Cancer Institute, Boston, MA
3. Ophthalmic Oncology Service, Memorial Sloan Kettering Cancer
Center, New York, NY
4. Ophthalmic Epidemiology and Genetics Service, Tufts-New England
Medical Center, Boston, MA
Purpose. To evaluate the risk of a non-ocular second cancer (SC) in
long-term survivors of retinoblastoma (Rb) according to classification of
germline mutation, based on family history of Rb and laterality.
Methods. We assembled a cohort of 1,852 1-year survivors of
retinoblastoma. SCs were confirmed by pathology reports. Classification
of RB1 germline mutation, inherited or de novo, was inferred by laterality
of Rb and positive family history of Rb. Standardized incidence ratios and
cumulative incidence for all SCs combined and for soft tissue sarcomas,
bone cancers and melanoma were calculated. The influence of host and
therapy related risk factors for SC was assessed by Poisson regression
for bilateral survivors.
Results. We observed a relative risk (RR) of 1.10 (95% Confidence
interval (CI), 0.84-1.44) for SCs in bilateral survivors associated with a
family history of Rb, adjusted for treatment, age and length of followup.
The risk for melanoma was elevated for survivors with a family
history of Rb (RR=2.38, 95%CI 1.04-5.09), but not for bone or soft tissue
sarcomas. The cumulative incidence of SCs at 50 years after diagnosis
of bilateral Rb, with adjustment for competing risk of death, was higher
for survivors with a family history (44%, 95%CI, 35%-54%) than without
(38%, 95%CI, 31-44%).
Conclusions. Rb survivors with bilateral disease and an inherited
germline mutation may be at slightly higher risk of a SC compared
to those with a de novo germline mutation, in particular melanoma,
perhaps due to shared genetic alterations.
Financial disclosure. None
2039 RB33
A NOVEL, ORAL, NON-INVASIVE METHOD OF DELIV-
ERY FOR THE GLYCOLYTIC INHIBITOR 2-DEOXY-D-
GLUCOSE IN THE TREATMENT OF RETINOBLASTOMA
Christina L. Decatur, Yolanda Piña, Samuel Houston, Ludimila Cavalcante,
Theodore Lampidis, Timothy G. Murray (cdecatur@med.miami.edu)
Bascom Palmer Eye Institute, University of Miami Miller School of
Medicine, Miami, Florida, USA.
Purpose. The aim of the current study is to assess the impact of oral
delivery of the glycolytic inhibitor 2-deoxy-D-glucose (2-DG) on tumor
burden and hypoxia in the LHBETATAG retinal tumor model.
Methods. The study protocol was approved by the University of Miami
Institutional Animal Care and Use Review Board Committee. LHBETATAG
transgenic mice (n=25) received oral delivery of either 2-DG (0.02%) in
custom made food pellets, or control food pellets without 2-DG, and
were divided into three groups: (1) a group treated for 8 weeks, from 4
to 12 weeks of age (8 weeks early tx); (2) a group treated for 18 weeks,
from 4 to 22 weeks of age (18 weeks early tx); and (3) a group treated
RETINOBLASTOMA
Abstracts
46
for 8 weeks, from 17 to 25 weeks of age (8 weeks late tx). At the time of
enucleation, all eye samples were snap frozen and analyzed for tumor
burden and hypoxia using histopathology and immunohistochemistry
techniques. Percentages of the different variables were statistically
analyzed using ANOVA.
Results. Following oral delivery of 2-DG, there was a significant
difference between all treatment groups on tumor burden (p=0.049). A
78% reduction of tumor burden was found in the 18 weeks early treated
group (p=0.0034). Both the early and late treated groups did not show
any difference from the control (p=0.61 and p=0.58, respectively). A
91% reduction in hypoxia was found in the 18 weeks early treated group
(p=0.061). Although there was a large reduction in hypoxia in both the 8
weeks early and late treated groups (85% and 45%, respectively), they
did not show any difference from the control (p=0.4 and p=0.37, respectively).
Conclusions. Reduction of tumor burden and hypoxia with oral delivery
of 2-DG presents a novel approach as a potential therapeutic treatment
of retinoblastoma. The use of glycolytic inhibitors as adjuvants to
therapeutic strategies, (e.g., chemotherapy, vessel targeting) as a
therapeutic strategy offers a new approach for enhancing current
retinoblastoma treatments.
Financial disclosure. This work was supported by the American Cancer Society and the
University of Miami Sylvester Comprehensive Cancer Center. NIH center grant P30EY014801 and
by the unrestricted grant to the University of Miami from Research to Prevent Blindness.
1352 RB34
VITREOUS INJECTION THERAPY OF MELPHALAN FOR
RETINOBLASTOMA
Shigenobu Suzuki, Akihiro Kaneko (sgsuzuki@ncc.go.jp)
1. Department of Ophthalmic Oncology, National Cancer Center Hospital
2. Yokohama City University Hospital
Purpose. To describe the adverse events and prognosis of retinoblastoma
patients treated with vitreous injection therapy.
Methods. A retrospective review of retinoblastoma patients treated with
vitreous injection therapy until 2009. Injected drug was melphalan, and
the dose ranged from 8 to 24 microgram. All vitreous injections were
performed as salvage treatments, and concomitant treatments were
selected depend on the eye condition: radiotherapy, chemotherapy,
arterial injection, laser therapy, cryotherapy, brachytherapy, and ocular
hyperthermia.
Results. 896 injections were performed for 237 eyes of 227 patients.
Mean follow-up period was 91 months.
Adverse events: Extraocular tumor extension occurred in one eye treated
at the early time of this technique (0.4%), which had anterior chamber
spread and dense vitreous seeds. Systemic metastasis occurred in ten
patients, but nine of them were not related to vitreous injections, and
only in one patient (0.4%) we could not eliminate the association of
vitreous injection. Other adverse events were vitreous hemorrhage (two
eyes, 0.8%), retinal detachment (one eye, 0.4%), chorioretinal atrophy
(two eyes, 0.8%), and iris atrophy (three eyes, 1.3%). There was no case
of endophthalmitis.
Prognosis: In total, 135 eyes (58%) were salvaged. For 83 eyes with active
vitreous seeds without large residual retinal tumors, 68% of eyes were
salvaged. More than half eyes without initial macular tumor kept visual
acuity better than 0.5 (Landolt ring).
Conclusions. Vitreous injection therapy is effective for vitreous seeds,
and causes few adverse events. Good visual acuity means the limited
damage for the eye.
Financial disclosure. None