Management Of Retinoblastoma Research Articles

Ocular features of the organoid nevus syndrome.

The purpose of the study was to demonstrate the ocular features of organoid nevus syndrome. A 10-day-old male infant was referred for management of retinoblastoma as a result of the presence of intraocular calcification. The examination showed a cutaneous lesion in the midline, epibulbar vascular lesions, and a cutaneous nodule at the lateral canthus. Fundus evaluation showed circumpapillary flat discoloration, which appeared hyperdense on ultrasound. All these features were consistent with organoid nevus syndrome. The cutaneous lesion was consistent with nevus sebaceous, the epibulbar lesion with choristoma, and the fundus lesion with cartilaginous choristoma. The presence of intraocular calcification often leads to a mistaken diagnosis in organoid nevus syndrome. Appropriate identification is important to diagnose this multisystem disorder.

Management and outcome of unilateral retinoblastoma

Two-thirds of retinoblastoma cases are unilateral, with most presenting with an advanced stage of disease. Primary enucleation is usually the preferred treatment. Conservative therapy may save less involved eyes. We retrospectively reviewed the presentation, age at diagnosis, classification, genetic status, treatment, and long-term outcome of 130 patients with unilateral retinoblastoma (1988-2008). The mean age at presentation was 26 months. Based on retinoblastoma gene (RB1) status in tumors, germ-line status was defined in 92% of patients; 13% had a germ-line mutation. The primary treatment of 106 patients was enucleation. Severe disease at presentation (International Intraocular Retinoblastoma Classification [IIRC] group E) was significantly (p < 0.001) associated with adverse histopathological risk factors. Of the 16 patients who underwent eye-conserving therapy, treatment was successful in 9 (IIRC group A, 1; B, 5; C, 3). Two patients with a pertinent family history were diagnosed early and were treated solely with focal therapy. Three patients retained vision of 6/18 or better in the treated eye (median follow-up, 33 months; range, 2-120 months). Seven patients (IIRC group: B, 2; C, 4; D, 1) eventually underwent enucleation. One patient died of metastases following delayed parental consent for enucleation and refusal of prophylactic chemotherapy for high-risk histopathologic features. Chemotherapy/focal therapy can save selected eyes, but primary enucleation is preferred for advanced unilateral retinoblastoma. "Conservative" treatment is an option when there is good potential for useful vision without prolonged, costly therapy with potential side effects. Simple enucleation reduces the risk of masking high-risk pathology and promotes early return to normal life.

Frontiers in the Management of Retinoblastoma

To provide an overview of the current clinical management of retinoblastoma by discussing the trends in the categorization, treatment, and recent advances in molecular diagnostics as well as therapy for retinoblastoma. Literature review and commentary. Selected articles from the medical literature and the authors' clinical and research experience were reviewed critically. Retinoblastoma has evolved from a deadly childhood cancer to a largely curable cancer within the past 40 years. Current treatment strategies aim to salvage the eye and provide the best visual outcome possible. Using the international classification system to stratify intraocular retinoblastoma into treatment groups, the multicenter Children's Oncology Group treatment protocols use 2- to 3-drug chemoreduction with focal consolidative therapy for most categories of disease. Furthermore, collaborative efforts are being directed toward a better understanding of genotype-phenotype relationships in retinoblastoma that will be useful in the multidisciplinary management of this disease. Molecular targeting therapy is emerging as a potential strategy to individualize therapy. Finally, improvements in local drug delivery methods and vehicles are providing solutions for the problem of systemic toxicity from existing chemotherapy regimens. The management of retinoblastoma has become a prototype for other ophthalmic diseases and systemic cancers in which genetic information and molecular targets are being used to design more elegant treatment strategies.

Retinoblastoma: An overview for advanced practice nurses

To provide an overview of the current literature surrounding the detection and management of retinoblastoma as well as care for the long-term survivor to serve as a guide for advanced practice nurses. Comprehensive review of the literature on retinoblastoma including case studies, journal reviews, retrospective studies, and briefs. Retinoblastoma is a pediatric intraocular malignancy usually detected in the primary care setting. Typically asymptomatic, primary care providers will often identify the presence of retinoblastoma upon routine eye exam. Prompt diagnosis and commencement of treatment are paramount as delay in diagnosis leads to higher morbidity and mortality. Treatment options vary depending on the extent of disease. Although current survival rates for retinoblastoma exceed 90%, individual visual outcome and survival are dependent upon early detection and prompt referral. In addition to research and education of survivors and families, advanced practice nurses play a key role in early detection and maintaining the current survival rate.

005: A 20-year review of the management and outcome of unilateral retinoblastoma

005: A 20-year review of the management and outcome of unilateral retinoblastoma

Analysis of ototoxicity in young children receiving carboplatin in the context of conservative management of unilateral or bilateral retinoblastoma

Carboplatin plays an important role in the conservative management of retinoblastoma, but is associated with risk of ototoxicity in these young children whose sensory prognosis may be also compromised by their loss of vision. This retrospective study analyzed the impact of carboplatin on hearing in the context of conservative management of children with retinoblastoma. Data for 175 children treated at the Institut Curie between 1994 and 2002 were analyzed. Median age at diagnosis was 8 months (0-60). Carboplatin was administered on 3 days (200 mg/m(2)/day) or 5 days (160 mg/m(2)/day) with etoposide and with diode-laser therapy at the dose of 560 mg/m(2) (chemothermotherapy). Median cumulative dose of carboplatin was 2,880 mg/m(2) (560-6,160). Ototoxicity was investigated by pure-tone audiometry and scored by Brock's grading scale before and after treatment. The median follow-up of hearing assessment was 5 years (1.8-11). Ototoxicity was detected in 8 children: 3 grade 1, 1 grade 2, and 2 grade 4. The two patients with grade 4 hearing-loss required a hearing aid. Two children developed bilateral high frequency hearing-loss, considered to be secondary to carboplatin but with less than Brock grade 1. Ototoxicity was observed for a median cumulative dose of carboplatin of 3,120 mg/m(2) (1,200-5,830). Only one child developed ototoxicity during treatment. All other cases were discovered after the last dose of carboplatin with a median interval of 3.7 years (0-7.6). No other risk factor for ototoxicity was able to account for these lesions. Children receiving carboplatin require long-term audiometric follow-up.

Management of retinal tumors

AbstractThe course will include the management of retinoblastoma and the treatment of retinal angiomas. Practical management of retinoblastoma will be described. The techniques of treatment include enucleation, radiotherapy by external beam or proton beam, plaque brachyterapy , chemoreduction and chemothermotherapy, laser treatment and cryotherapy. The techniques will be detailed and the indications will be given. Advance unilateral retinoblastoma is often an indication for enucleation. Conservative management is performed as often as possible especially in bilateral retinoblastoma. We shall give the methods to avoid extra ocular retinoblastoma like orbital recurrence or metastasis. We shall describe the rules for follow up of the patients after treatment and for screening for early diagnosis in familial retinoblastoma. Guidelines for genetic counselling will be also given. Retinal capillary hemangangiomas can be unique or multiple in case on Von Hippel Lindau disease. Treatments of the angiomas include laser therapy and cryotherapy for bigger angiomas Vitrectomy with endolaser can be needed in rare instances and radiotherapy has been used in selected cases. Cavernous hemangiomas of the retina are rare; they usually are stable with no need for therapy.

Demographics, clinical profile, management and outcome of retinoblastoma

10051 Background: Retinoblastoma is the most common intraocular tumor in children. Comprehensive data on the clinical spectrum and outcome of protocol-based management in a large clinical series wi...

Management of retinoblastoma with proximal optic nerve enhancement on MRI at diagnosis

In North America, retinoblastoma rarely presents with gross clinical evidence of tumor involving the optic nerve. Extent of microscopic tumor infiltration into the postlaminar optic nerve is a significant risk factor for metastasis, especially if there is tumor at the cut end. Due to poor outcomes in patients with metastatic disease, historical treatment for patients with clinical evidence of extraocular optic nerve involvement has included upfront enucleation followed by aggressive adjuvant chemotherapy. Additional orbital irradiation is advocated for individuals with optic nerve involvement at the surgical margin. Little is known about the role of neoadjuvant therapy in the setting of orbital optic nerve enhancement on magnetic resonance imaging (MRI) at diagnosis. A retrospective review of consecutive retinoblastoma cases at Childrens Hospital Los Angeles over a 3-year period (2004-2006) found to have gadolinium contrast enhancement in the proximal portion of optic nerve on MRI at diagnosis. Nine patients fit the inclusion criteria. Two had secondary glaucoma of a sufficient degree to cause an enlarged eye (buphthalmos). Median age at presentation was 17 months (2-36 months). All patients received neoadjuvant chemotherapy prior to enucleation. Only two received external beam radiation. All are disease-free with a median follow-up of 22 months (12-41 months). Neoadjuvant chemotherapy is well tolerated prior to enucleation of retinoblastoma-containing eyes associated with contrast enhancement of the proximal optic nerve on MRI at diagnosis. Such an approach may be used to decrease intensity or duration of chemotherapy and need for external beam radiation.

Spectrum of RB1 gene mutations and loss of heterozygosity in Mexican patients with retinoblastoma: Identification of six novel mutations

RB1 mutation detection has greatly improved the clinical management of retinoblastoma and provides critical information to predict the risk of inheriting the disease. We screened for RB1 gene sequence alterations in both peripheral blood and tumor specimens from a total of 48 Mexican retinoblastoma patients using an SSCP-based screening approach followed by sequencing. Overall, 21 (43.8%) cases were bilateral and 27 (56.2%) were unilateral. Interestingly, 51.8% of unilateral patients developed the tumor before age 1 year and 10 of which (71.4%) were diagnosed before the age of 6 months. Thirteen different oncogenic mutations were detected in 14/48 (29.2%) patients, 9 of which were germline (64.3%). Six of these mutations are novel (IVS3-1G>T, 125X, 389X, 610X, 750X and -149G>T). The most frequent types of mutation were frameshift and nonsense (30.8% each). Moreover, 5 intronic variants were identified, two of which are novel (g.41908 C/A and g.161976del6T). Loss of heterozygosity of the RB1 gene as assessed by intron1/BamHI and intron17/XbaI intragenic markers was 50.0% (18 of 36 informative cases), being higher in tumors with known mutations (76.9% vs 34.8%). This low mutation detection rate and the earlier age at diagnosis in unilateral retinoblastoma cases suggest that other RB1 inactivating mechanisms could be present in the retinoblastoma development. In this study, mutation analysis was not helpful to distinguish sporadic and hereditary retinoblastoma, so, other approaches are needed to improve the molecular diagnosis of retinoblastoma and supports further investigations of Mexican retinoblastoma patients.

Team management, twinning, and telemedicine in retinoblastoma: A 3‐tier approach implemented in the first eye salvage program in Jordan

This study evaluated the outcome of retinoblastoma patients, when employing a telemedicine-based twinning program in Jordan. This cohort study included patients at the King Hussein Cancer Centre (KHCC; Amman, Jordan) who received consultations for retinoblastoma from March 2003 to September 2006. A collaborative program was established with the International Outreach Program at St. Jude Children's Research Hospital in Memphis, Tennessee. Cases were discussed using an Internet consultation service where fundus images, clinical history, and proposed treatment were reviewed. Selected cases were further discussed via videoconferencing and electronic mail. Thirty-three children with retinoblastoma (20 bilateral) were treated at KHCC. The median age at diagnosis was 7 months for patients with bilateral retinoblastoma and 35 months for patients with unilateral retinoblastoma. Of the 20 patients with bilateral disease, 12 were newly diagnosed and 8 had received prior treatment. Our success in the bilateral cases was most evident in the previously untreated group, in which only six eyes (25%) were enucleated and four eyes (17%) were irradiated. Of the 13 patients with unilateral retinoblastoma, 12 underwent enucleation, and 6 required radiation. Neither group experienced mortality. Twinning has positively impacted survival and ocular salvage in Jordan. By partnering a team of professionals with mentors willing to provide close supervision, the highly specialized management of retinoblastoma can be successfully implemented in a developing country.

Conservative Treatments of Intraocular Retinoblastoma

To describe the efficacy of conservative management of retinoblastoma by an association of conservative ocular therapies and chemothermotherapy. Phase II prospective nonrandomized trial. Eighty-three children were included (115 eyes). Conservative ocular therapies and chemothermotherapy (intravenous carboplatin followed by transpupillary thermotherapy to the tumor) after chemoreduction by 2 cycles of carboplatin and etoposide. Use of external beam therapy and ocular tumor control. One hundred fifteen of the 147 affected eyes were eligible for conservative management. Nineteen children had unilateral lesions (22.8%), and 64 (77.1%) had bilateral lesions. Sixty-six children received neoadjuvant chemotherapy before ocular therapy, which consisted of one or a combination of several techniques: chemothermotherapy (65 children [86 eyes]) with a mean of 3 cycles per child, thermotherapy alone (22 children [24 eyes]), cryoapplication (49 children [58 eyes]), and iodine 125 brachytherapy (26 children [29 eyes]). Tumor control was achieved for 97 eyes (84%). At the end of the study, external beam radiotherapy (EBR) was necessary for a total of 9 children (11%) and 13 eyes (12%). Enucleation was necessary for a total of 23 eyes (20%), because of complications in 5 cases. Neoadjuvant chemotherapy with 2 cycles of carboplatin and etoposide followed by ocular therapy and chemothermotherapy achieves satisfactory tumor control and permits a low need for EBR.

World disparities in risk definition and management of retinoblastoma: A report from the International Retinoblastoma Staging Working Group

Following from the publication of the International Retinoblastoma Staging System, an open internet discussion group was created at the www.cure4kids.org resource. The results of a survey distributed among participants are discussed. Although most patients with retinoblastoma were treated under prospective protocols, there was a wide variation in the definition of risk criteria and in the criteria for giving adjuvant chemotherapy following enucleation. Definition of high-risk histological features and the criteria for use of adjuvant therapy will be standardized in future studies. Internet meetings are a valuable mechanism for enabling participation from under-resourced countries in the development of cooperative studies.

Forget-Me-Nots in the Care of Children with Retinoblastoma

The management of retinoblastoma has gradually evolved over the past years from enucleation to radiotherapy to current techniques of chemotherapy. Eyes with massive retinoblastoma filling the globe are still managed with enucleation, whereas those with small, medium, or even large tumors can be managed with chemoreduction followed by tumor consolidation with thermotherapy or cryotherapy. Despite multiple or large tumors, visual acuity can reach 20/40 or better in many cases, particularly those eyes with extramacular tumors. Previous complications of dry eye, cataract, retinopathy, and facial deformity that were found following external beam radiotherapy are not anticipated following chemoreduction. Recurrence from subretinal and vitreous seeds can be problematic. Long-term follow up for second cancers is advised.

Current treatment and management of retinoblastoma

Retinoblastoma was traditionally treated with enucleation and external-beam radiotherapy. However, in the past decade, systemic chemotherapy has become the primary globe-salvaging approach. This approach is generally combined with focal treatment, allowing for tumor consolidation following initial chemoreduction. A recently developed classification scheme may improve our ability to predict outcomes with this treatment modality. The Children's Oncology Group has initiated a series of prospective multicenter trials to improve treatment outcomes with systemic chemotherapy.

Paclitaxel in the Treatment of Retinal Tumors of LH beta-Tag Murine Transgenic Model of Retinoblastoma

The purpose of this study was to investigate tumor control efficacy of paclitaxel in the treatment of retinal tumors harbored by the LH beta-Tag murine transgenic model of retinoblastoma. LH beta-Tag-positive mice (n = 5) 10 weeks of age received two 20-microL subconjunctival injections delivered with a 72-hour interval to right eyes only. Paclitaxel was dissolved in 100% dimethyl sulfoxide (DMSO) and delivered at doses of 0.5 mg, 0.25 mg, 0.125 mg, 0.0625 mg, 0.0313 mg, and 0.0152 mg in a 20-microL volume. Control mice received two subconjunctival injections of DMSO or of saline solution to right eyes only or they remained untreated. Eyes were analyzed at 16 weeks of age for residual tumor burden, which was measured by gauging the cross-sectional area of largest tumor focus. Linear regression analysis of tumor burden demonstrates a statistically significant (P < 0.001) dose-response relationship between paclitaxel concentration and tumor size. Transient ocular toxicities were observed after treatment, but most had subsided at the time of analysis, 6 weeks after injection. After histologic assessment, the 0.25-mg paclitaxel dose had effectively reduced tumor burden and was associated with minimal toxicity, including mild conjunctival chemosis and fibrosis, corneal epitheliopathy, and corneal edema. Subconjunctival delivery of paclitaxel effectively inhibits intraocular tumor burden in the LH beta-Tag model of retinoblastoma. This treatment modality may represent a novel strategy for the clinical management of retinoblastoma.

Secondary Acute Myelogenous Leukemia in Patients with Retinoblastoma: Is Chemotherapy a Factor?

To describe a series of patients with secondary acute myelogenous leukemia (sAML) and retinoblastoma (RB). Retrospective observational cases series. Ocular and pediatric oncologists at referral centers in Europe and the Americas and the RB databases at the National Institutes of Health and the Ophthalmic Oncology Service at Memorial Sloan-Kettering Cancer Center. Physician survey, retrospective database review, and literature search. History of RB and development of sAML, management of RB (surgery, radiotherapy, chemotherapy), age at diagnosis of RB and leukemia, French-American-British (FAB) subtype, and current status of patient (alive or dead). Fifteen patients with sAML were identified; 13 occurred in childhood. Mean latent period from RB to AML diagnosis was 9.8 years (median, 42 months). Nine cases were of the M2 or M5 FAB subtypes. Twelve patients (79 %) had received chemotherapy with a topoisomerase II inhibitor, 8 (43%) had received chemotherapy with an epipodophyllotoxin. Ten children died of their leukemia. Acute myelogenous leukemia is a rare secondary malignancy among retinoblastoma patients, many of whom were treated with primary or adjuvant chemotherapy. Additional studies are needed to assess potential risk factors contributing to sAML development in this cohort.

Demographics, clinical profile, management, and outcome of retinoblastoma in a tertiary care center in southern India

20011 Background: Retinoblastoma is the most common malignant intraocular tumor in children. The estimated incidence of retinoblastoma in India is about 2,000 a year. However, there is scant data on the clinical manifestations and outcome of retinoblastoma in India. Methods: In this retrospective case series, the medical records of 460 consecutive cases of retinoblastoma from January 1990 to December 2004 were analyzed for demographics, clinical profile, treatment and outcome (survival, organ and function salvage). Results: An integrated Ocular Oncology Service was established at the treatment center in the year 2000 and a specialized Children’s Eye Cancer Center was founded in 2004. The annual referral increased from &lt;20 a year before 2000 to 38 in 2000, and 120 in 2005. Two hundred and six (45%) patients were economically underprivileged. A majority (303, 66%) presented &lt;3 years of age. There were 277 (60%) males. Although 188 (41%) were bilateral, family history was forthcoming in only 19 (4%). Of 648 involved eyes, 531 (82%) eyes were symptomatic. Leucocoria (71%) was the most common symptom, followed by visual loss (12%), eyelid edema or proptosis (7%), squint (6%), pain (2%), redness (2%), enlarged eyeball (2%), or shrunken eyeball (1%). The tumor was intraocular in 609 (94%) eyes while 39 (6%) were extraocular. Enucleation was the most common primary treatment for intraocular retinoblastoma (236 of 451, 52%), followed by chemoreduction coupled with focal therapy (26%), focal therapy alone (11%), external beam radiation (55) or chemotherapy alone (4%). Histopathologic risk factors predictive of metastasis were found in 152 of 277 (55%) eyes that underwent enucleation. Chemoreduction with focal therapy resulted in eye and vision salvage in 109 of 118 (92%). At the final follow-up (minimum 24 months), 434 (94%) were alive and well. Conclusions: Retinoblastoma has excellent prognosis for survival, eye salvage and vision salvage with the current management modalities. An integrated approach involving a team of a pediatric oncologist and an ocular oncologist at a comprehensive tertiary care center may augment referrals and help implement systematic treatment strategies. No significant financial relationships to disclose.

Genetics and management of retinoblastoma

Retinoblastoma is the most common intraocular tumor in childhood. In majority of early stage retinoblastoma, the eyeballs as well as vision can be preserved with chemotherapy and local intraocular therapy with laser or photocoagulation. However, more than half the patients in India and other developing nations present in advanced stage of the disease. This article reviews the genetics, clinical approach, and treatment options for retinoblastoma focussing on advances in chemotherapy for intraocular retinoblastoma (chemoreduction), as well as improvement in survival in advanced retinoblastoma with surgery, chemotherapy, radiotherapy, and bone marrow transplantation.

VEGF-Targeted RNA Interference Suppresses Angiogenesis and Tumor Growth of Retinoblastoma

Vascular endothelial growth factor (VEGF) is one of the most important angiogenic growth factors for tumor angiogenesis which has been verified to be involved in neovascularization of retinoblastoma. Here, we sought to explore whether RNA interference (RNAi) targeting VEGF could inhibit retinoblastoma angiogenesis and tumor growth. Stable transfection of the two human retinoblastoma cell lines SO-RB50 and HXO-RB44 with VEGF-targeted small interfering RNA (siRNA) expression plasmid significantly inhibited VEGF expression determined by real-time polymerase chain reaction (PCR), enzyme-linked immunosorbent assay and Western blot, whereas the control transfection showed no effects. The chemically synthesized VEGF siRNA dramatically suppressed tumor angiogenesis (CD34 immunohistochemistry) and tumor growth in the SO-RB50 subcutaneous xenograft model. Significant downregulation of VEGF expression both on messenger RNA and protein levels in VEGF-siRNA-treated SO-RB50 subcutaneous xenograft was confirmed by real-time PCR and Western blot compared to control. Our data demonstrate the suppression function on angiogenesis and tumor growth of retinoblastoma by VEGF-targeted RNAi. This novel therapeutic strategy promises to play a part in the clinical management of retinoblastoma.