Journal of Pediatric Ophthalmology and Strabismus

Short Subjects 

Intra-arterial Chemotherapy for Adult Onset Retinoblastoma in a 32-Year-Old Man

Tejal Magan, MBBS; Chloe T. L. Khoo, BS; Pascal M. Jabbour, MD; Dwain G. Fuller, MD; Carol L. Shields, MD

Abstract

A 32-year-old man with active unilateral group D retinoblastoma that was recurrent following external beam radiotherapy was treated with intra-arterial chemotherapy, leading to tumor regression. Additional plaque radiotherapy and intravitreal chemotherapy were required for complete control. Final visual acuity was 20/40. In selected cases, adult-onset retinoblastoma can be managed with intra-arterial chemotherapy. [J Pediatr Ophthalmol Strabismus. 2016;53:e43–e46.]

Abstract

A 32-year-old man with active unilateral group D retinoblastoma that was recurrent following external beam radiotherapy was treated with intra-arterial chemotherapy, leading to tumor regression. Additional plaque radiotherapy and intravitreal chemotherapy were required for complete control. Final visual acuity was 20/40. In selected cases, adult-onset retinoblastoma can be managed with intra-arterial chemotherapy. [J Pediatr Ophthalmol Strabismus. 2016;53:e43–e46.]

Introduction

Retinoblastoma is the most common pediatric intraocular malignancy, with 95% of cases diagnosed before 5 years of age.1 In an assessment of 400 consecutive cases of retinoblastoma by Shields et al., 366 (91.5%) were detected before 5 years and only 34 (8.5%) were diagnosed at 5 years or older, 6 (1.5%) at 10 years or older, and 3 (0.8%) at 15 years or older.2 Of the 34 cases in older patients, 26 were active retinoblastoma and 8 were inactive retinocytoma. In that series, the oldest patient with active disease was 18 years old. Kaliki et al. described a series of 8 patients with adult-onset (> 20 years old) active retinoblastoma from two major oncology centers in India and the United States.3 They found that the average age of presentation in this older group was 30 years and all had advanced disease, classified as International Classification of Retinoblastoma (ICRB) groups D (n = 3) or E (n = 3) or with orbital invasion (International Retinoblastoma stage 3a) (n = 2). Older studies have confirmed a low rate (2%) of retinoblastoma in patients older than 10 years at diagnosis.4

Current treatment options in any age group include enucleation, radiotherapy, or chemotherapy, generally via the intravenous or intra-arterial route. Published series of retinoblastoma in older patients (combined total: n = 34) revealed that treatment included enucleation (n = 27, 79%), intravenous chemotherapy (n = 1, 3%), external beam radiotherapy (n = 4, 12%), and exenteration (n = 2, 6%).2,3 In recent years, intra-arterial chemotherapy has gained popularity for retinoblastoma, generally for young infants 3 months and older. The use of intra-arterial chemotherapy for retinoblastoma in adults has not yet been a key focus. We evaluate the role of intra-arterial chemotherapy in a 32-year-old adult with active retinoblastoma.

Case Report

A 28-year-old man noted blurred vision for 6 months in the left eye and was diagnosed as having retinoblastoma, classified by the ICRB as group D. On examination, visual acuity was 20/20 in each eye. The right eye was normal and the left eye revealed a solid retinal mass of 11 mm in basal dimension and 6.8 mm in thickness with extensive diffuse vitreous seeding in all quadrants (Figure 1A). Ultrasonography demonstrated a calcified intraocular mass, suggesting the diagnosis of retinoblastoma, despite the older patient age (Figure 1B). The patient was treated with external beam radiotherapy, with regression of the mass and vitreous seeds.


A 28-year-old man was newly diagnosed with group D retinoblastoma in the left eye. At presentation [elsewhere], retinoblastoma measured 11 mm in basal dimension and 6.8 mm in thickness with (A) extensive vitreous seeding, best documented on (B) ultrasonography. External beam radiotherapy (EBRT) was provided. Following EBRT, (C) tumor recurrence on the posterior margin with (D) recurrent vitreous seeding was documented. Intra-arterial chemotherapy was provided with complete resolution of tumor and vitreous seeds. Following intra-arterial chemotherapy, (E) tumor regression was documented and (F) all vitreous seeds were calcified. Later, minor solid tumor recurrence necessitated plaque radiotherapy and the tumor has remained regressed for 32 months following intra-arterial chemotherapy.

Figure 1.

A 28-year-old man was newly diagnosed with group D retinoblastoma in the left eye. At presentation [elsewhere], retinoblastoma measured 11 mm in basal dimension and 6.8 mm in thickness with (A) extensive vitreous seeding, best documented on (B) ultrasonography. External beam radiotherapy (EBRT) was provided. Following EBRT, (C) tumor recurrence on the posterior margin with (D) recurrent vitreous seeding was documented. Intra-arterial chemotherapy was provided with complete resolution of tumor and vitreous seeds. Following intra-arterial chemotherapy, (E) tumor regression was documented and (F) all vitreous seeds were calcified. Later, minor solid tumor recurrence necessitated plaque radiotherapy and the tumor has remained regressed for 32 months following intra-arterial chemotherapy.

Nearly 48 months later, solid tumor recurrence was documented, measuring 8 mm in basal dimension and 3.5 mm in thickness (Figure 1C). Widespread vitreous seeds were recurrent (Figure 1D). Visual acuity was still 20/20 in each eye. Treatment options included enucleation or intra-arterial chemotherapy; however, the patient preferred globe salvage so intra-arterial chemotherapy was delivered with three cycles of melphalan (7.5 mg) and topotecan (1 mg) over a period of 5 months without complication. The tumor demonstrated complete regression with 90% calcification (Figure 1E). Subsequently, posterior vitreous detachment with dense vitreous hemorrhage was noted with reduced visual acuity of 20/100 in the left eye, but the macula was still intact (Figure 1F). Intravitreal chemotherapy was provided using four cycles of melphalan (20 µg/0.1 cc) and two cycles of additional topotecan (20 µg/0.1 cc) for suspected vitreous tumor seeding and as a precaution for possible vitrectomy with blood removal, if necessary. The vitreous blood cleared over a period of 22 months without vitrectomy.

Eighteen months following intra-arterial chemotherapy, solid minor tumor recurrence was detected and managed with plaque radiotherapy. At 14 months after plaque radiotherapy and 32 months after intra-arterial chemotherapy, the patient remained tumor free without local recurrence or distant metastasis. At 80 months after initial presentation, cataract surgery with intraocular lens implantation and capsulotomy was performed, resulting in a final visual acuity of 20/40.

Discussion

Retinoblastoma is rarely detected in adults.2,3,5–7 To date, the oldest adult diagnosed as having active retinoblastoma at our center was 48 years old and in the literature the oldest adult patient with active retinoblastoma was a 74-year-old man.6,7 Due to its rarity, conditions other than retinoblastoma are initially considered in these patients. Kaliki et al. highlighted the challenges in diagnostic acumen for retinoblastoma in adults when they noted that 3 of 8 (37.5%) cases in their series had previous misdiagnoses of retinal vasoproliferative tumor, amelanotic choroidal melanoma, or choroidal metastasis.3 In a series of 34 older children and adults with retinoblastoma, Shields et al. found previous misdiagnoses in 7 (21%) cases, including vitreous hemorrhage, endophthalmitis, or Coats disease.2 In our case, the classic features strongly suggested the diagnosis of retinoblastoma, despite the patient's age of 28 years.

Most published cases of adult retinoblastoma have been managed with enucleation.2,3,5,6 Unique to our case, intra-arterial chemotherapy was considered as secondary therapy following failed external beam radiotherapy. Intra-arterial chemotherapy has already proven to be organ-preserving therapy for other head and neck cancers in adults, including advanced squamous cell carcinoma with minor toxicities.8,9

To our knowledge, this is the oldest patient in the literature treated with intra-arterial chemotherapy for retinoblastoma control.10 Intra-arterial chemotherapy has been found to provide outstanding globe salvage in 72% of primary cases and 62% of secondary cases, as in this case.10 Intra-arterial chemotherapy offers some advantages over intravenous chemotherapy, with fewer anticipated systemic toxicities, but balanced against a potential low risk for local ocular ischemic events with intra-arterial chemotherapy.10 There were no ocular complications following intra-arterial chemotherapy in this case. There was no evidence of retinal or choroidal vascular comprise. The slightly reduced visual acuity of 20/40 could be related to subclinical radiation-related papillopathy or maculopathy because this patient received both external beam radiotherapy and plaque radiotherapy but there was no ophthalmoscopically visible sign of radiation changes. Furthermore, part of the visual reduction could be related to mild vitreous hemorrhage and posterior capsular opacification. Fortunately, the combination of therapies, especially intra-arterial chemotherapy and intravitreal chemotherapy, allowed globe salvage.

We describe a case of adult-onset retinoblastoma that was controlled ultimately with intra-arterial chemotherapy, plaque radiotherapy, and intravitreal chemotherapy, leading to stable regressed tumor scar and 20/40 visual acuity at nearly 3 years of follow-up. This approach could be useful in selected cases of adult-onset retinoblastoma.

References

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  7. Finlay JR, Byron H. Retinoblastoma in the adult: review of literature and report of a case associated with benign melanoma. Acta XIX Concil Ophthalmol. 1962;2:1168–1178.
  8. Kerber CW, Wong WH, Howell SB, Hanchett K, Robbins KT. An organ-preserving selective arterial chemotherapy strategy for head and neck cancer. AJNR Am J Neuroradiol. 1998;19:935–941.
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  10. Shields CL, Manjandavida FP, Lally SE, et al. Intra-arterial chemotherapy for retinoblastoma in 70 eyes: outcomes based on the international classification of retinoblastoma. Ophthalmology. 2014;121:1453–1460. doi:10.1016/j.ophtha.2014.01.026 [CrossRef]
Authors

From the Ocular Oncology Service, Wills Eye Hospital, Thomas Jefferson University, Philadelphia, Pennsylvania (TM, CTLK, CLS); St. George's, University of London, London, United Kingdom (TM); Sidney Kimmel Medical College, Thomas Jefferson University, Philadelphia, Pennsylvania (CTLK); the Division of Neurovascular and Endovascular Surgery, Neurosurgery Department, Thomas Jefferson University, Philadelphia, Pennsylvania (PMJ); and Texas Retina Associates, Dallas, Texas (DGF).

Supported by Eye Tumor Research Foundation, Philadelphia, PA (CLS).

The authors have no financial or proprietary interest in the materials presented herein.

Correspondence: Carol L. Shields, MD, Ocular Oncology Service, 840 Walnut Street, Suite 1440, Philadelphia, PA 19107. E-mail: carolshields@gmail.com

Received: November 17, 2015
Accepted: March 24, 2016
Posted Online: July 30, 2016

10.3928/01913913-20160722-01

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