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Current Therapy and Recent Advances in the Management of Retinoblastoma REVIEW ARTICLE Current therapy and recent advances in the management of retinoblastoma 1,4,5 Rachna Meel , ABSTRACT Venkatraman Radhakrishnan2,3,5, Retinoblastoma is the most common intraocular malignancy in children. The survival 2,3,5 Sameer Bakhshi of retinoblastoma patients and visual outcome has improved dramatically in the 1Oculoplastics and Ocular developed world. This can be attributed to early tumor recognition and advances in the Oncology Service, 2Department management of retinoblastoma. Chemoreduction followed by adjuvant consolidative of Medical Oncology, 3Dr. B.R.A. treatment has replaced external beam radiotherapy as the primary modality of treatment Institute Rotary Cancer Hospital, for intraocular retinoblastoma. Further, histopathological high-risk factors have been 4 Dr. Rajendra Prasad Centre for identified in enucleated eyes, allowing use of prophylactic chemotherapy to take care 5 Ophthalmic Sciences, All India of possible micrometastasis. The survival in case of extraocular retinoblastoma is still Institute of Medical Sciences, low, and the reported survival rate ranges between 50% and 70%. In developing New Delhi, India countries, the overall survival of retinoblastoma patients remains low, primarily due to a delayed presentation, resulting in larger proportions of extraocular disease compared Address for correspondence: with the developed world, where majority of the disease is intraocular. Greater efforts Dr. Sameer Bakhshi, Additional Professor of Pediatric need to be directed toward early tumor recognition in order to improve the survival of Oncology, Department of Medical retinoblastoma patients in the developing world. In this article, we provide an overview Oncology, Dr. B.R.A. Institute of the current clinical management of retinoblastoma. Rotary Cancer Hospital, All India Institute of Medical Sciences, New Delhi, India. Key words: Recent advances, retinoblastoma, treatment E-mail: [email protected] Extraocular retinoblastoma is very rare in developed INTRODUCTION countries (reported incidence: approximately 2–5%).[5] Retinoblastoma is the most common intraocular malignancy In developing nations, extraocular disease contributes to half of all retinoblastoma cases presenting to a tertiary in children, and is reported to affect 1 in 15,000 to 1 in [6] 18,000 live births.[1] It represents almost 4% of all pediatric care referral center. A combination of poverty, illiteracy, alternative systems of medicine and lack of access to malignancies. Approximately 250–300 children are newly healthcare resources account for this high rate of advanced diagnosed with retinoblastoma each year in the United disease in developing countries. States, and substantially higher rates occur in developing [2,3] countries. Studies from India show a two- to three-fold In this article, we will review the current state of art for higher incidence of tumors of the eye (majority of which [4] managing retinoblastoma. We searched the PubMed for will be retinoblastoma in children <15 years of age). important articles on recent advances in the treatment of retinoblastoma over the last 2 decades, and reviewed them Also, while over 95% children with retinoblastoma with special reference to the state of retinoblastoma in India. survive in the developed world, only 50% children with retinoblastoma survive worldwide.[3] This can be explained by a delay in presentation and, consequently, a DIAGNOSIS AND INVESTIGATIONS greater number of cases with extraocular invasion seen in developing countries. Clinical profile Retinoblastoma generally presents any time from birth to Access this article online 5 years of age, although in rare cases it may present later. Quick Response Code: In the United States, the mean age at presentation is 18 Website: www.ijmpo.org months. There is no sex predilection. Retinoblastoma is unilateral in approximately two-thirds of cases and bilateral DOI: in the remaining one-third. 10.4103/0971-5851.99731 The most common presentation is with cat’s eye reflection 80 Indian Journal of Medical and Paediatric Oncology | Apr-Jun 2012 | Vol 33 | Issue 2 Meel, et al.: Advances in retinoblastoma in the pupil. Other less common clinical presentations available, handmade fundus diagrams documenting the site, include a uveitis-like picture, aseptic orbital cellulitis, size and numbers of retinal tumors, vitreous and subretinal phthisis bulbi, hyphema, buphthalmos, red, painful eye with seeds and retinal detachment are to be drawn at each EUA. glaucoma and cloudy cornea, proptosis and even fungating mass. Patients with metastasis may present with bone pains, Imaging vomiting and headache or scalp masses in addition. Family The diagnosis of retinoblastoma is generally made on history may be present in less than 10% of the cases. indirect ophthalmoscopy. Imaging studies are used for (1) confirmation of diagnosis in difficult cases, (2) when there In a study conducted at the All India Institute of is opaque media precluding indirect ophthalmoscopy and Medical Sciences, the median age of presentation of (3) to evaluate the presence of extraocular extension or retinoblastoma patients was 2.5 years (median age for associated cerebral lesion in trilateral cases. unilateral retinoblastoma was 3 years and for bilateral retinoblastoma was 2 years). Sixty-nine percent of the The imaging diagnosis of retinoblastoma is based on cases were unilateral and 30.5% were bilateral. There was documentation of an intraocular mass with calcification. a male predominance, with a male to female ratio of 1.6:1. If an ultrasound is available in the outpatient department/ The most common first symptom noted by parents was clinic, mass with calcification may be picked up in most white reflex, followed by redness or squint. Proptosis was cases. However, if it is not available or calcification is not the most common symptom (31.3%) at presentation apart picked up on ultrasound, a computed tomography (CT) from white reflex. The median duration of symptoms scan is recommended for documenting the same. before presentation was 7.2 months. Sixty percent of the patients presented with intraocular disease, 32.72% with Although magnetic resonance imaging (MRI) is more locally advanced disease and 10.16% with metastatic disease sensitive than CT scan for picking up extraocular extension, [Table 1].[7] CT scan is more widely used in developing countries because of the ease of availability and affordability. Clinical evaluation Although a CT scan may detect extraocular extension in All children with suspected retinoblastoma undergo a majority of the cases, some cases are likely to be missed a preliminary clinical evaluation in the clinic, at initial out if MRI is not done routinely. visit, consisting of visual acuity assessment, the pupillary examination, slit-lamp examination and indirect MRI will still be indicated in cases where there is a doubt of ophthalmoscopy. Subsequently, all patients undergo extraocular extension on CT scan. MRI has the advantage examination under anesthesia (EUA), consisting of of distinguishing tumor with secondary retinal detachment a intraocular pressure measurement using a portable from other causes of subretinal effusion or detachment, like tonometer, corneal diameters, slit-lamp examination for coat’s disease, primary hyperplastic vitreous and retinopathy [11] evidence of iris neovascularization, hyphema or anterior of prematurity. Also, some authors believe that segment involvement in the form of iris nodules or performing CT scan in cases with bilateral retinoblastoma hypopyon; binocular indirect ophthalmoscopy with 360 may increase the risk of secondary malignancies later in [12] degrees of scleral depression; and fundus photographs survivors; MRI does not have any such risk. Currently, (RETCAM) documenting all lesions. If RETCAM is not MRI is the standard imaging modality used to rule out extraocular extension. Table 1: Clinical features of retinoblastoma Once the diagnosis is established, the disease is staged Indian study[7] Studies from based on the clinical and imaging findings, and intraocular North America and Europe[8-10] retinoblastoma is classified in order to determine Median age at presentation appropriate line of treatment. (Unilateral retinoblastoma) 30 months 24 months (Bilateral retinoblastoma) 24 months 13 months Classification of intraocular retinoblastoma Sex (Male: Female) 1.6:1 1:1 The Reese‑Ellsworth classification was developed in the Laterality, % 70 unilateral 70 unilateral era where radiotherapy was the mainstay for treating Most common symptom Leukocoria Leukocoria retinoblastoma. With the emergence of chemoreduction Buphthalmia and proptosis, % 31.3 1‑2 as the core of therapy for intraocular retinoblastoma, the Stage of disease, % variables affecting the outcome of treatment have changed. Intraocular 60 90 Vitreous and subretinal seeds have been identified as the Locally advanced/ metastatic 35 10 major cause of treatment failure or relapse. The recently disease developed International Classification for Intraocular Indian Journal of Medical and Paediatric Oncology | Apr-Jun 2012 | Vol 33 | Issue 2 81 Meel, et al.: Advances in retinoblastoma Retinoblastoma[13] takes into account the factors that affect lymph nodes has a rate of overall survival that is comparable the outcome (globe salvage and survival) in the present to nonmetastatic extraocular retinoblastoma[14] [Table 3]. treatment scenario [Table 2]. Metastatic work-up Staging of retinoblastoma Initial metastatic work-up consists of lumbar
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