Macular Retinoblastoma: Evaluation of Tumor Control, Local Complications, and Visual Outcomes for Eyes Treated with Chemotherapy and Repetitive Foveal Laser Ablation

doi:10.1016/j.ophtha.2006.06.042

Ophthalmology

Volume 114, Issue 1, January 2007, Pages 162-169

Presented at: American Academy of Ophthalmology meeting, October 2005, Chicago, Illinois.

https://doi.org/10.1016/j.ophtha.2006.06.042 Get rights and content

Objective

To determine tumor control rates, complication rates, and visual acuity (VA) for patients with macular retinoblastoma undergoing systemic chemotherapy and foveal diode laser ablation.

Design

Noncomparative retrospective case series.

Participants

All patients with retinoblastoma in the macula at the Bascom Palmer Eye Institute between 1991 and 2004 were evaluated. Patients included in the study were managed by the same clinician with a planned therapeutic strategy.

Methods

Patients with Reese–Ellsworth groups I to IV disease underwent 4 to 9 cycles of systemic chemotherapy with vincristine, etoposide, and carboplatin, and patients with group V disease underwent 6 to 10 cycles with or without cyclosporine. All tumors underwent repetitive diode laser ablation (2–24 sessions) applied to the foveal and extrafoveal portions of tumors at each visit until tumors were deemed inactive for at least 6 months.

Main Outcome Measures

Recurrence requiring external beam radiation therapy or enucleation; VA; and complications including iris atrophy, peripheral focal lens opacity, peripheral anterior synechiae, and foveal neovascular membrane.

Results

Forty-four eyes of 33 patients were treated. Eyes were classified as Reese–Ellsworth group I (1 [2%]), II (6 [12%]), III (3 [7%]), IV (5 [9%]), or V (29 [67%]). Thirty-eight eyes (86%) had successful tumor control and avoided enucleation at a median follow-up of 36 months. At 3 years, tumor control rates were 100% for Reese–Ellsworth groups I to IV and 83% for group V. All eyes requiring enucleation were in Reese–Ellsworth group V. No eyes required external beam radiation. The most common complications were iris atrophy (61%) and focal lens opacity (14%). Strabismus was noted in 16% of eyes. Snellen VA measured 20/40 or better in 36% of eyes, 20/80 or better in 57%, and 20/400 or better in 86%. An increasing number of laser applications and chemotherapy cycles was not associated with decreased VA, strabismus, or development of an afferent pupillary defect but was associated with development of local complications.

Conclusions

A unique approach to the application of diode laser therapy characterized by repetitive foveal treatments and aggressive chemotherapy resulted in tumor control rates that exceed those previously published. Furthermore, despite laser application directly to the fovea, 57% of patients retained 20/80 or better vision.

Section snippets

Materials and Methods

All patients with retinoblastoma located in the macula treated at the Ocular Oncology Service, Bascom Palmer Eye Institute between May 1991 and April 2004 were reviewed retrospectively. For the purposes of this study, the macula was defined as the area within the vascular arcades. Only patients who were treated initially with chemotherapy and diode laser ablation therapy were included in this review. Exclusion criteria for treatment with chemotherapy included tumor invasion into the optic nerve

Results

Clinical characteristics of the patients in this study are detailed in Table 1. Eyes were classified as Reese–Ellsworth group I (1 [2%]), II (6 [12%]), III (3 [7%]), IV (5 [9%]), or V (29 [67%]). Tumors underwent a median of 9 sessions of laser applications (range, 2–24). Overall, 38 eyes (86%) had successful tumor control and avoided enucleation at a median follow-up of 36 months (range, 3–100). All 15 eyes (100%) in Reese–Ellsworth groups I to IV had successful tumor control at 3 years (95%

Discussion

In this study, we evaluated one consistent therapeutic strategy utilized at a major ocular oncology center. All of the patients in this sample with Reese–Ellsworth groups I to IV disease had their eyes successfully salvaged with this treatment approach alone, avoiding external beam radiation and enucleation (Table 4). This approach resulted in a remarkably high globe salvage rate, comparable to or better than those in recent large studies by Shields et al,³⁰ Rodriguez-Galindo et al,²⁵ and

References (35)

A.C. Moll et al.
Second primary tumors in hereditary retinoblastoma: a register-based study, 1945–1997Is there an age effect on radiation-related risk?
Ophthalmology
(2001)
D.H. Abramson et al.
Third (fourth and fifth) nonocular tumors in survivors of retinoblastoma
Ophthalmology
(2001)
M.J. Greenwald et al.
Treatment of intraocular retinoblastoma with carboplatin and etoposide chemotherapy
Ophthalmology
(1996)
C.L. Shields et al.
Combined chemoreduction and adjuvant treatment for intraocular retinoblastoma
Ophthalmology
(1997)
M.W. Wilson et al.
Multiagent chemotherapy as neoadjuvant treatment for multifocal intraocular retinoblastoma
Ophthalmology
(2001)
C.L. Shields et al.
Chemoreduction plus focal therapy for retinoblastoma: factors predictive of need for treatment with external beam radiotherapy or enucleation
Am J Ophthalmol
(2002)
L. Desjardins et al.
Functional results after treatment of retinoblastoma
J AAPOS
(2002)
D.H. Abramson et al.
Transpupillary thermotherapy as initial treatment for small intraocular retinoblastomaTechnique and predictors of success
Ophthalmology
(2004)
D.H. Abramson et al.
Second nonocular tumors in survivors of bilateral retinoblastoma: a possible age effect on radiation-related risk
Ophthalmology
(1998)
F.P. Li et al.
Hereditary retinoblastoma, lipoma, and second primary cancers
J Natl Cancer Inst
(1997)

F.L. Wong et al.

Cancer incidence after retinoblastoma: radiation dose and sarcoma risk

JAMA

(1997)

T.G. Murray et al.

In vitro efficacy of carboplatin and hyperthermia in a murine retinoblastoma cell line

Invest Ophthalmol Vis Sci

(1997)

T.G. Murray et al.

Subconjunctival carboplatin therapy and cryotherapy in the treatment of transgenic murine retinoblastoma

Arch Ophthalmol

(1997)

B.L. Gallie et al.

Chemotherapy with focal therapy can cure intraocular retinoblastoma without radiotherapy

Arch Ophthalmol

(1996)

J.E. Kingston et al.

Results of combined chemotherapy and radiotherapy for advanced intraocular retinoblastoma

Arch Ophthalmol

(1996)

A.L. Murphree et al.

Chemotherapy plus local treatment in the management of intraocular retinoblastoma

Arch Ophthalmol

(1996)

C.L. Shields et al.

Chemoreduction in the initial management of intraocular retinoblastoma

Arch Ophthalmol

(1996)

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Retinoblastoma is lethal by metastasis if left untreated, so the primary goal of therapy is to preserve life, with ocular survival, visual preservation and quality of life as secondary aims. Historically, enucleation was the first successful therapeutic approach to decrease mortality, followed over 100 years ago by the first eye salvage attempts with radiotherapy. This led to the empiric delineation of a window for conservative management subject to a “state of metastatic grace” never to be violated.
Over the last two decades, conservative management of retinoblastoma witnessed an impressive acceleration of improvements, culminating in two major paradigm shifts in therapeutic strategy. Firstly, the introduction of systemic chemotherapy and focal treatments in the late 1990s enabled radiotherapy to be progressively abandoned. Around 10 years later, the advent of chemotherapy in situ, with the capitalization of new routes of targeted drug delivery, namely intra-arterial, intravitreal and now intracameral injections, allowed significant increase in eye preservation rate, definitive eradication of radiotherapy and reduction of systemic chemotherapy.
Here we intend to review the relevant knowledge susceptible to improve the conservative management of retinoblastoma in compliance with the “state of metastatic grace”, with particular attention to (i) reviewing how new imaging modalities impact the frontiers of conservative management, (ii) dissecting retinoblastoma genesis, growth patterns, and intraocular routes of tumor propagation, (iii) assessing major therapeutic changes and trends, (iv) proposing a classification of relapsing retinoblastoma, (v) examining treatable/preventable disease-related or treatment-induced complications, and (vi) appraising new therapeutic targets and concepts, as well as liquid biopsy potentiality.
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To evaluate the ocular treatment outcomes of focal laser consolidation during systemic chemoreduction for Group B tumors in the posterior fundus.
Single-institution retrospective chart review from 1995 to 2016.
Patients with Group B retinoblastoma with at least 1 tumor in the posterior fundus.
Evaluation of tumor response to chemotherapy and laser consolidation.
Change in the tumor size with treatment, and the association of timing of laser consolidation to the horizontal and vertical diameter of the final chorioretinal scar.
Forty Group B eyes (22 right eyes and 18 left eyes) were included in the analysis. Mean age at diagnosis was 6.4 months (range 0–24 months). Of the 40 eyes, 35 were treated with both systemic chemotherapy and laser, 4 with chemotherapy only, and 1 eye with laser without chemotherapy. Mean age at initial laser treatment was 7.7 months (standard deviation 5.9 months) and mean number of laser sessions was 6 (standard deviation 5 sessions). The overall globe salvage rate was 95% (38/40 eyes). Mean horizontal and vertical diameters of the tumors in this group showed statistically significant decreases from diagnosis to all subsequent visits (P = 0.0024). The median percent reductions in the horizontal and vertical diameters of the tumors treated with both chemotherapy and laser from diagnosis to the final visit were 13% and 14%, respectively; the overall scar area showed a 13% decrease. For tumors receiving chemotherapy prior to laser therapy, the median reduction in tumor area was 18% from diagnosis to the final examination. Small tumors were found to have a 52% increase in final scar size from diagnosis, whereas larger tumors demonstrated a 37% decrease.
The overall success in treating Group B tumors with chemotherapy and laser was very favorable when considering scar size and globe salvage rates. The size of the chorioretinal scar at the end of treatment was on average 13% smaller than the original tumor size, with greater reductions being noted when chemotherapy preceded laser treatment and when the tumor size at diagnosis was greater than 4.5 mm. A small subset of perifoveal lesions was treated successfully with chemotherapy, alone without laser consolidation.
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Either way, as a focal treatment it is commonly used in eyes treated with systemic chemotherapy,27 as well as in eyes treated with IAC.9 Interestingly, Schefler and associates investigated the impact of systemic chemotherapy and TTT on macular retinoblastoma (Reese-Ellsworth groups I-V) in respect to visual function and found that 11 of 14 (79%) had VA ≥20/200 at final visit.15 These excellent results, however, were not repeated in the present study.
To analyze the long-term visual acuity, strabismus, and nystagmus outcomes in Group D retinoblastoma following multimodality treatments in a national retinoblastoma referral center.
Retrospective interventional case series.
A 13-year retrospective chart review of Group D eyes treated initially with intravenous chemotherapy (IVC) and followed up for at least 1 year from last treatment. Risk factors for final visual acuity (VA) were analyzed, and rate of strabismus and nystagmus at last follow-up visit were calculated.
One hundred and four Group D eyes (92 patients) presented to our center during the study period, of which 32 (27 patients) met the inclusion criteria. Following IVC (vincristine, etoposide, and carboplatin), adjuvant treatments included intraophthalmic artery chemotherapy in 5 (16%) eyes, plaque brachytherapy in 5 (16%), transpupillary thermotherapy (TTT) in 18 (56%), and cryotherapy in 24 (75%) eyes. On last examination, 64.41 ± 6.76 months from presentation, mean final VA was 20/283 (logMAR equivalent of 1.15 ± 0.15). On univariate analysis, presentation age, foveal retinoblastoma (at initial examination), use of TTT, and tumor–foveola distance (at last visit) were found to be significant risk factors for worse VA (P < .026). On multivariate analysis, however, only TTT was found to be significant (P = .010). At last visit, 6 of 27 (22%) patients had nystagmus and 12 of 20 (60%) bilaterally salvaged patients had strabismus (n = 10 exotropia and n = 2 esotropia).
After multimodality treatments initiated with IVC, 50% of salvaged Group D retinoblastoma eyes had <20/200 vision, with TTT being a risk factor for worse vision; 60% had strabismus; and 22% had nystagmus.
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Manuscript no. 2005-942.

The authors report no financial interests in any of the products mentioned in the article.

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Original ArticleMacular Retinoblastoma: Evaluation of Tumor Control, Local Complications, and Visual Outcomes for Eyes Treated with Chemotherapy and Repetitive Foveal Laser Ablation

Objective

Design

Participants

Methods

Main Outcome Measures

Results

Conclusions

Section snippets

Materials and Methods

Results

Discussion

Ophthalmology

Ophthalmology

Ophthalmology

Ophthalmology

Ophthalmology

Am J Ophthalmol

J AAPOS

Ophthalmology

Second nonocular tumors in survivors of bilateral retinoblastoma: a possible age effect on radiation-related risk

Ophthalmology

Hereditary retinoblastoma, lipoma, and second primary cancers

J Natl Cancer Inst

Cancer incidence after retinoblastoma: radiation dose and sarcoma risk

JAMA

In vitro efficacy of carboplatin and hyperthermia in a murine retinoblastoma cell line

Invest Ophthalmol Vis Sci

Subconjunctival carboplatin therapy and cryotherapy in the treatment of transgenic murine retinoblastoma

Arch Ophthalmol

Chemotherapy with focal therapy can cure intraocular retinoblastoma without radiotherapy

Arch Ophthalmol

Results of combined chemotherapy and radiotherapy for advanced intraocular retinoblastoma

Arch Ophthalmol

Chemotherapy plus local treatment in the management of intraocular retinoblastoma

Arch Ophthalmol

Chemoreduction in the initial management of intraocular retinoblastoma

Arch Ophthalmol

Original Article
Macular Retinoblastoma: Evaluation of Tumor Control, Local Complications, and Visual Outcomes for Eyes Treated with Chemotherapy and Repetitive Foveal Laser Ablation