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.
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.
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.
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.
- MacCarthy A, Birch JM, Draper GJ, et al. Retinoblastoma in Great Britain 1963–2002. Br J Ophthalmol. 2009;93:33–37. doi:10.1136/bjo.2008.139618 [CrossRef]
- Shields CL, Shields JA, Shah P. Retinoblastoma in older children. Ophthalmology. 1991;98:395–399. doi:10.1016/S0161-6420(91)32283-8 [CrossRef]
- Kaliki S, Shields CL, Gupta A, et al. Newly diagnosed active retinoblastoma in adults. Retina. 2015;35:2483–2488. doi:10.1097/IAE.0000000000000612 [CrossRef]
- Abramson DH, Frank CM, Susman M, Whalen MP, Dunkel IJ, Boyd NW 3rd, . Presenting signs of retinoblastoma. J Pediatr. 1998;132:505–508. doi:10.1016/S0022-3476(98)70028-9 [CrossRef]
- Biswas J, Mani B, Shanmugam MP, Patwardhan D, Kumar KS, Badrinath SS. Retinoblastoma in adults: report of three cases and review of the literature. Surv Ophthalmol. 2000;44:409–414. doi:10.1016/S0039-6257(99)00132-0 [CrossRef]
- Wells JR, Aaberg TM, Shields CL, Comer GM, Grossniklaus HE. Retinoblastoma in a 48-year-old woman. Retin Cases Brief Rep. 2011;5:22–25. doi:10.1097/ICB.0b013e3181e17fa6 [CrossRef]
- 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.
- 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.
- Kovács AF. Response to intraarterial induction chemotherapy: a prognostic parameter in oral and oropharyngeal cancer. Head Neck. 2006;28:678–688. doi:10.1002/hed.20388 [CrossRef]
- 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]