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World J Ophthalmol. Feb 12, 2015; 5(1): 31-35
Published online Feb 12, 2015. doi: 10.5318/wjo.v5.i1.31
Recent advances in management of retinoblastoma: A review
Bhavna Chawla, Gautam Lokdarshi, Rajendra Prasad Centre for Ophthalmic Sciences, All India Institute of Medical Sciences, New Delhi 110029, India
Sushmita Pathy, Department of Radiotherapy, IRCH, All India Institute of Medical Sciences, New Delhi 110029, India
Author contributions: Chawla B contributed to the conception and design, literature search, writing the article, critical revision of the article; Lokdarshi G and Pathy S contributed to writing the article, literature search; all authors final approval of the article.
Open-Access: This article is an open-access article which was selected by an in-house editor and fully peer-reviewed by external reviewers. It is distributed in accordance with the Creative Commons Attribution Non Commercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited and the use is non-commercial. See: http://creativecommons.org/licenses/by-nc/4.0/
Correspondence to: Bhavna Chawla, MS, Additional Professor, Ocular Oncology and Pediatric Ophthalmology Service, Rajendra Prasad Centre for Ophthalmic Sciences, All India Institute of Medical Sciences, Ansari Nagar, New Delhi 110029, India. bhavna2424@hotmail.com
Telephone: +91-11-26593088 Fax: +91-11-26588919
Received: July 11, 2014
Peer-review started: July 12, 2014
First decision: September 28, 2014
Revised: October 27, 2014
Accepted: October 31, 2014
Article in press: November 3, 2014
Published online: February 12, 2015
Processing time: 192 Days and 17 Hours

Abstract

The management of retinoblastoma has evolved significantly over recent years. Current treatment options aim to preserve the globe as well as vision with minimum morbidity. High resolution imaging has improved tumor detection and is useful for prognosticating cases and monitoring response to treatment. Targeted chemotherapy such as intra-arterial and intra-vitreal chemotherapy has shown promising results and these routes are being increasingly employed world-wide for globe preservation. The advent of new radiotherapy techniques has led to improved radiation delivery to the target and more conformal treatment plans with better normal tissue sparing. This review aims to highlight newer advancements in the field of diagnosis and management of retinoblastoma that have been introduced in recent times, with a special emphasis on globe-preserving therapy.

Key Words: Retinoblastoma; Recent advances; Chemotherapy; Radiotherapy

Core tip: The management of retinoblastoma has improved significantly over the past few decades. There has been a paradigm shift from enucleation towards conservative treatment modalities that aim at vision and globe salvage. The purpose of this article is to review the literature on various key developments in the field of retinoblastoma, with particular emphasis on globe-conserving treatment.



INTRODUCTION

The diagnosis and management of retinoblastoma (RB) often presents as a challenge to the ophthalmologist. Recent advances have contributed towards improving the clinical outcome of the most common intraocular malignancy seen in children. Evolution in imaging techniques has facilitated accurate diagnosis and staging of RB. There has been a paradigm shift from enucleation towards conservative treatment modalities that aim at vision and globe salvage. The introduction of intra-arterial and intra-vitreal chemotherapy in recent times has shown encouraging results. The advent of newer radiotherapy techniques have led to greatly improved radiation delivery to the target and more conformal treatment plans with better normal tissue sparing. The purpose of this article is to review the literature on various key developments in the field of RB, with particular emphasis on globe-conserving therapies. A brief overview of these recent advances is highlighted below.

IMAGING

Imaging plays a key role in the diagnosis of RB. With the introduction of high-resolution three-dimensional (3D) Fast Spin Echo (FSE) magnetic resonance imaging (MRI) and high resolution ultrasound, the diagnosis of RB is no longer a dilemma. Although computed tomograph scan is very useful in detecting calcification which can sometimes be missed on ultrasonography, it has been reported that high-resolution three-dimensional (3D) FSE T2 weighted imaging with thin sections (0.4 mm) and high Signal to Noise Ratio (SNR) can also detect calcification[1]. Gradient-echo T2 weighted MRI is also effective in detecting calcified structures[1]. Recently, it has been observed that the difference in Apparent Diffusion Co-efficient values on diffusion-weighted MRI can be helpful in differentiating between viable and necrotic tumor[2]. In addition, this modality can also be used to monitor the response of tumor to chemotherapy in cases of trilateral RB as well as in those eyes that are treated with globe salvaging therapies[2,3]. The presence of vitreous haemorrhage can pose difficulty in delineating the tumor, which can be overcome by T1-weighted MR images without the use of gadolinium-based contrast material[4]. Apart from its diagnostic value, MRI is also an established imaging modality for staging of RB[5]. Contrast-enhanced T1-weighted MR imaging with fat saturation is recommended to rule out optic nerve involvement as well as extra scleral involvement[6]. The sensitivity and specificity of MR imaging for depicting post-laminar optic nerve invasion has been reported to range from 50%-90%[4,5]. A retrospective study by Song et al[7] in cases of unilateral RB concluded that focal strong enhancement and enlarged optic nerve on MR films had better correlation with optic nerve invasion than optic nerve enhancement, tumor size and tumor location[7]. It is noteworthy that in some children, this enhancement can be due to aseptic cellutis or inflammation of soft tissues rather than true invasion[8]. A short course of systemic steroids and repeat MR imaging facilitates accurate staging in such cases and has been found to be useful in guiding further management[8].

Another application of imaging in RB is the use of high resolution ultrasound to detect the tumor in the fetus at its earliest stage[9]. Investigators have used high resolution ultrasound at 37 wk of gestation to detect a 2-3 mm elevated lesion in a fetus at risk of heritable RB[9]. Being a rapidly growing tumor, doubling time for RB is considered approximately 15 d[10]. Therefore, it has been suggested that infants proven to carry the family’s RB1 mutant allele can be delivered a few weeks early, to optimize the chances of retaining good vision with minimally invasive therapy[11].

CHEMOTHERAPY

Although enucleation is accepted as the standard treatment for advanced tumors, local and site selective delivery of chemotherapeutic drugs has shown encouraging results in salvaging the globe as well as vision in many eyes otherwise destined for enucleation. These newer therapeutic approaches are discussed briefly.

Super-selective intra-arterial chemotherapy

This novel approach has evolved rapidly over the last few years and has shown encouraging results in both early and advanced tumors[12,13]. Being a site directed therapy, it has considerably fewer systemic side-effects in comparison to conventional intra-venous chemotherapy. Over the last few decades, the selectivity of the technique has improved from using sites such as the internal carotid artery, supra-orbital artery and superficial temporal artery, to the currently used ophthalmic artery[14-18]. Melphalan is the drug of choice for intra-arterial chemotherapy and heparin (70 U/kg) is the anticoagulant used. There is no standardised dosing schedule, however, the conventional dose ranges from 3-5 mg per sitting[13,16,17]. Recently, Abramson et al[16] and Gobin et al[17] have recommended intra-arterial chemotherapy as a safe and effective treatment for advanced intra-ocular RB. Although intra-arterial chemotherapy has the advantage of fewer systemic side effects as compared to intravenous chemotherapy, some investigators consider melphalan as a more toxic agent than those drugs which are used for intravenous chemotherapy[19]. Exposure to fluoroscopy related radiation and ophthalmic artery occlusion are other concerns[19]. It has been suggested that a selective ophthalmic artery angiogram instead of carotid angiogram can be used to minimise radiation exposure[13]. Though not yet established as a primary treatment, intra-arterial chemotherapy has also been used as a first line treatment in less advanced cases of intraocular RB[12]. There are other investigators who consider it as a part of a multi-modal therapeutic approach[13,18]. Intra-arterial chemotherapy has been reported to be associated with an overall success rate of 55%-100% in salvaging the globe, in addition to the advantage of very low systemic toxicity[12,13]. Recently, Francis et al[20] have demonstrated that Carboplatin ± topotecan ophthalmic artery chemosurgery (OAC) can allow for prompt regression of tumors and can be curative as a single agent in combination with focal techniques, with ocular survival of 89.9% at two years. Furthermore, Carboplatin ± topotecan infusions have low hematologic and ocular toxicity and no statistically significant influence on electroretinogram responses, and can be used in conjunction with melphalan-containing OAC[20]. It has been recommended that children, especially less than 6 mo of age at the start of treatment with carboplatin, should routinely undergo thorough long-term audiologic monitoring[21]. Recently, a single-centre retrospective study has compared the relative incidence of new intraocular lesions after treatment with carboplatin through intravenous (systemic) and OAC in naïve eyes, or those with prior treatment (systemic chemotherapy/ external beam radiotherapy)[22]. The incidence reported were 56%, 2.4% and 8% respectively[22]. The systemic chemotherapy treated patients had multiple new lesions within months of treatment, as compared to fewer new lesions in the OAC group[22]. It was noted that previously irradiated eyes showed delayed appearance of new lesions. The new lesions were more common at a younger age and were usually located in the peripheral retina, which can be explained by the centrifugal development of retina[22].

Intravitreal chemotherapy

Another local route for drug delivery that has shown promising results in RB is intra-vitreal chemotherapy (IViC)[23,24]. However, this route is recommended only as salvage therapy for recurrent or recalcitrant vitreous seeds and should not be considered as a primary treatment[19]. In a study by Munier et al[23] in RB cases with recalcitrant vitreous seeds, melphalan was injected intravitreally in a dose of 20-30 μg (0.1 mL of 0.2 mg/mL) using anti-reflux procedure, followed by triple freeze-thaw cryoapplication to sterilize the needle track[23]. The procedure was carried out every 7-10 d and was repeated upto eight injections if a response could be documented, until complete seed fragmentation was observed or complete response was achieved[23]. Complete response was established if the seeds (1) completely disappeared (vitreous seeding regression type 0); or were converted into (2) refringent and/or calcified residues (vitreous seeding regression type I); (3) amorphous, often non-spherical, inactive residues (vitreous seeding regression type II); or (4) a combination of the last two (vitreous seeding regression type III)[23]. The authors recommended that IViC could be repeated if vitreous recurrence occurred[23]. In their study, a success rate of 84.14% at 2 years was achieved[23].A localised peripheral salt-and-pepper retinopathy at the injection site was the only complication noted in 10 eyes (43%)[23]. Another retrospective study on intra-vitreal chemotherapy by Shields et al[24] showed 100% (11/11) success rate with 1 to 4 cycles of monthly IViC (melphalan 20-30 μg) at 2 year follow-up[24].

Sub-conjunctival /sub-tenon chemotherapy

It has been observed that systemic chemotherapy alone may not be sufficient to treat Group C (eyes with focal vitreous or subretinal seeding and discrete retinal tumors of any size and location) and Group D (eyes with diffuse vitreous or subretinal seeding and/or massive, nondiscrete endophytic or exophytic disease) cases[25,26]. Local injections of chemo-therapeutic agents like sub-tenon or sub-conjunctival carboplatin have been used with varying degrees of success, usually as an adjuvant to systemic chemotherapy to avoid enucleation and external beam radiotherapy in cases of group C and group D retinoblastoma with vitreous/subretinal seeds. The Children’s Oncology Group recommends use of 20 mg sub-tenon carboplatin along with chemoreduction and focal consolidation for Group C and D tumors[27]. Leng et al[28] have reported a favourable outcome with the use of sub-conjunctival carboplatin in RB tumors that progressed despite ablative therapy[28].

RADIATION THERAPY

Despite the established role of radiotherapy (RT) in RB, treatment modalities were shifted to primary chemotherapy combined with local treatment options such photocoa-gulation, cryotherapy and thermotherapy[29,30]. The high incidence of radiation induced growth deformities and second malignancies was attributed to external beam radiotherapy and RT was therefore reserved for tumours refractory to chemotherapy and local therapies. However, the assessments of risk by RT were based on outcomes of radiation delivery in the old era[31,32]. In recent times, there has been substantial advancement in radiation therapy and the advent of newer radiotherapy techniques has led to greatly improved radiation delivery to the target and more conformal treatment plans with better normal tissue sparing. These newer radiotherapy techniques which include intensity modulated radiotherapy, stereotactic radiotherapy volumetric modulated arc therapy (VMAT), proton therapy, and helical tomotherapy (HT) provide highly accurate radiation delivery[33].

Proton beam therapy provides uniform dose coverage of the target and unlike photon beams, has no exit dose and distributes no energy beyond the target. These unique properties reduce the incidence of late effects of radiation. A study by Sethi et al[34] compared the risk of second malignancies in survivors of RB treated with photon and proton radiation therapy[34]. The observed 10 year cumulative incidence of RT induced second malignancies were significantly different in proton and photon modalities (P = 0.015)[34]. However, proton therapy is expensive and is currently not widely available. In another study on the dosimetric comparison of various RT techniques by Eldebawy et al[33], it was concluded that inverse image guided radiotherapy using VMAT or HT provides superior conformity index and improved orbital bone and brain sparing[33].

Plaque Brachytherapy is commonly used for recurrent and residual disease after failure with chemotherapy and local therapy. The American Brachytherapy Society Ophthalmic Oncology Task Force (ABS-OOTF) recommends primary brachytherapy for unilateral anterior lesions[35]. Small tumours less than 15 mm in base and up to 10 mm in thickness in the absence of vitreous seeding are eligible[35]. The choice of radionuclide is decided according to local availability and intraocular dose distribution. I125 and Pd103 are used in North America, whereas I125 and Ru106 are used in Europe. Dosimetry of plaques presents a unique challenge which is due to the steep dose gradient within the tumour and presence of critical structures within few millimetres of the radioactive source. However, the TG-129 reports that adoption of heterogeneous dose calculation methods in clinical practice would result in dose variation of > 10% and requires careful assessment[36].

GUIDELINES FOR PATIENT FOLLOW-UP

After completion of therapy, regular follow-up is extremely important in these children in order to detect any recurrence of tumor, new lesion, or metastatic disease. It is recommended to follow-up all affected cases till the age of 16 years and to conduct screening of unaffected relatives or mutation carriers till the age of five (reference: 2013 Copyright American Cancer Society) or seven years (reference: NHS England/E04/S(HSS)/a, Copyright NHS Commissioning Board, 2013).

To summarize, the management of RB has evolved significantly over the last few years. Worldwide, there is an increasing trend towards preservation of the globe and vision in RB affected children. Newer advancements in diagnostic and therapeutic modalities have resulted in improved treatment outcomes in these children. Familiarity with these diagnostic and treatment modalities is essential for optimum management.

Footnotes

P- Reviewer: de la Serna IL S- Editor: Ji FF L- Editor: A E- Editor: Wu HL

References
1.  Razek AA, Elkhamary S. MRI of retinoblastoma. Br J Radiol. 2011;84:775-784.  [PubMed]  [DOI]  [Cited in This Article: ]  [Cited by in Crossref: 30]  [Cited by in F6Publishing: 24]  [Article Influence: 1.8]  [Reference Citation Analysis (0)]
2.  de Graaf P, Pouwels PJ, Rodjan F, Moll AC, Imhof SM, Knol DL, Sanchez E, van der Valk P, Castelijns JA. Single-shot turbo spin-echo diffusion-weighted imaging for retinoblastoma: initial experience. AJNR Am J Neuroradiol. 2012;33:110-118.  [PubMed]  [DOI]  [Cited in This Article: ]  [Cited by in Crossref: 47]  [Cited by in F6Publishing: 47]  [Article Influence: 3.9]  [Reference Citation Analysis (0)]
3.  Bonci GA, Rosenblum MK, Gilheeney SW, Dunkel IJ, Holodny AI. Diffusion-weighted imaging to assess treatment response in a child with trilateral retinoblastoma. Pediatr Radiol. 2013;43:1231-1234.  [PubMed]  [DOI]  [Cited in This Article: ]  [Cited by in Crossref: 5]  [Cited by in F6Publishing: 5]  [Article Influence: 0.5]  [Reference Citation Analysis (1)]
4.  Rauschecker AM, Patel CV, Yeom KW, Eisenhut CA, Gawande RS, O’Brien JM, Ebrahimi KB, Daldrup-Link HE. High-resolution MR imaging of the orbit in patients with retinoblastoma. Radiographics. 2012;32:1307-1326.  [PubMed]  [DOI]  [Cited in This Article: ]  [Cited by in Crossref: 20]  [Cited by in F6Publishing: 23]  [Article Influence: 2.1]  [Reference Citation Analysis (0)]
5.  Chawla B, Sharma S, Sen S, Azad R, Bajaj MS, Kashyap S, Pushker N, Ghose S. Correlation between clinical features, magnetic resonance imaging, and histopathologic findings in retinoblastoma: a prospective study. Ophthalmology. 2012;119:850-856.  [PubMed]  [DOI]  [Cited in This Article: ]  [Cited by in Crossref: 43]  [Cited by in F6Publishing: 35]  [Article Influence: 2.9]  [Reference Citation Analysis (0)]
6.  Sirin S, Schlamann M, Metz KA, Bornfeld N, Schweiger B, Holdt M, Schuendeln MM, Lohbeck S, Krasny A, Goericke SL. Diagnostic image quality of gadolinium-enhanced T1-weighted MRI with and without fat saturation in children with retinoblastoma. Pediatr Radiol. 2013;43:716-724.  [PubMed]  [DOI]  [Cited in This Article: ]  [Cited by in Crossref: 21]  [Cited by in F6Publishing: 21]  [Article Influence: 1.9]  [Reference Citation Analysis (0)]
7.  Song KD, Eo H, Kim JH, Yoo SY, Jeon TY. Can preoperative MR imaging predict optic nerve invasion of retinoblastoma? Eur J Radiol. 2012;81:4041-4045.  [PubMed]  [DOI]  [Cited in This Article: ]  [Cited by in Crossref: 20]  [Cited by in F6Publishing: 21]  [Article Influence: 1.8]  [Reference Citation Analysis (0)]
8.  Chawla B, Duraipandi K, Sharma S. MRI in retinoblastoma with orbital cellulitis. Ophthalmology. 2013;120:1308-1309.e1-4.  [PubMed]  [DOI]  [Cited in This Article: ]  [Cited by in Crossref: 10]  [Cited by in F6Publishing: 10]  [Article Influence: 0.9]  [Reference Citation Analysis (0)]
9.  Paquette LB, Miller D, Jackson HA, Lee T, Randolph L, Murphree AL, Panigrahy A. In utero detection of retinoblastoma with fetal magnetic resonance and ultrasound: initial experience. AJP Rep. 2012;2:55-62.  [PubMed]  [DOI]  [Cited in This Article: ]  [Cited by in Crossref: 25]  [Cited by in F6Publishing: 18]  [Article Influence: 1.5]  [Reference Citation Analysis (0)]
10.  Abramson DH, Schefler AC, Beaverson KL, Rollins IS, Ruddat MS, Kelly CJ. Rapid growth of retinoblastoma in a premature twin. Arch Ophthalmol. 2002;120:1232-1233.  [PubMed]  [DOI]  [Cited in This Article: ]  [Cited by in Crossref: 19]  [Cited by in F6Publishing: 19]  [Article Influence: 0.9]  [Reference Citation Analysis (0)]
11.  Bristowe A, Staffieri S, Fink M.  Managing fetuses at high risk of retinoblastoma: lesion detection on screening MRI(Presented at 2nd Asia-Pacific perinatal imaging (US and MRI) symposium). Tamwood: Vancouver and Whistler 2014; .  [PubMed]  [DOI]  [Cited in This Article: ]
12.  Abramson DH, Marr BP, Brodie SE, Dunkel I, Palioura S, Gobin YP. Ophthalmic artery chemosurgery for less advanced intraocular retinoblastoma: five year review. PLoS One. 2012;7:e34120.  [PubMed]  [DOI]  [Cited in This Article: ]  [Cited by in F6Publishing: 1]  [Reference Citation Analysis (0)]
13.  Thampi S, Hetts SW, Cooke DL, Stewart PJ, Robbins E, Banerjee A, Dubois SG, Char D, Halbach V, Matthay K. Superselective intra-arterial melphalan therapy for newly diagnosed and refractory retinoblastoma: results from a single institution. Clin Ophthalmol. 2013;7:981-989.  [PubMed]  [DOI]  [Cited in This Article: ]  [Cited by in Crossref: 48]  [Cited by in F6Publishing: 47]  [Article Influence: 4.3]  [Reference Citation Analysis (0)]
14.  Reese AB, Hyman GA, Tapley ND, Forrest AW. The treatment of retinoblastoma by x-ray and triethylene melamine. AMA Arch Ophthalmol. 1958;60:897-906.  [PubMed]  [DOI]  [Cited in This Article: ]  [Cited by in Crossref: 89]  [Cited by in F6Publishing: 94]  [Article Influence: 3.9]  [Reference Citation Analysis (0)]
15.  Kiribuchi M. Retrograde infusion of anti-cancer drugs to ophthalmic artery for intraocular malignant tumors. Nihon Ganka Gakkai Zasshi. 1966;70:1829-1833.  [PubMed]  [DOI]  [Cited in This Article: ]
16.  Abramson DH, Dunkel IJ, Brodie SE, Kim JW, Gobin YP. A phase I/II study of direct intraarterial (ophthalmic artery) chemotherapy with melphalan for intraocular retinoblastoma initial results. Ophthalmology. 2008;115:1398-1404, 1404.e1.  [PubMed]  [DOI]  [Cited in This Article: ]  [Cited by in Crossref: 297]  [Cited by in F6Publishing: 305]  [Article Influence: 19.1]  [Reference Citation Analysis (0)]
17.  Gobin YP, Dunkel IJ, Marr BP, Brodie SE, Abramson DH. Intra-arterial chemotherapy for the management of retinoblastoma: four-year experience. Arch Ophthalmol. 2011;129:732-737.  [PubMed]  [DOI]  [Cited in This Article: ]  [Cited by in Crossref: 289]  [Cited by in F6Publishing: 315]  [Article Influence: 24.2]  [Reference Citation Analysis (0)]
18.  Suzuki S, Kaneko A. Management of intraocular retinoblastoma and ocular prognosis. Int J Clin Oncol. 2004;9:1-6.  [PubMed]  [DOI]  [Cited in This Article: ]
19.  Boughton B. Intravitreal Chemotherapy for Retinoblastoma: Promising but Controversial. Eyenet. 2013;31-33 Available from: http://www.aao.org/publications/eyenet/201309/oncology.cfm.  [PubMed]  [DOI]  [Cited in This Article: ]
20.  Francis JH, Gobin YP, Dunkel IJ, Marr BP, Brodie SE, Jonna G, Abramson DH. Carboplatin +/- topotecan ophthalmic artery chemosurgery for intraocular retinoblastoma. PLoS One. 2013;8:e72441.  [PubMed]  [DOI]  [Cited in This Article: ]  [Cited by in Crossref: 39]  [Cited by in F6Publishing: 43]  [Article Influence: 3.9]  [Reference Citation Analysis (0)]
21.  Qaddoumi I, Bass JK, Wu J, Billups CA, Wozniak AW, Merchant TE, Haik BG, Wilson MW, Rodriguez-Galindo C. Carboplatin-associated ototoxicity in children with retinoblastoma. J Clin Oncol. 2012;30:1034-1041.  [PubMed]  [DOI]  [Cited in This Article: ]  [Cited by in Crossref: 121]  [Cited by in F6Publishing: 106]  [Article Influence: 8.8]  [Reference Citation Analysis (0)]
22.  Abramson DH, Francis JH, Dunkel IJ, Marr BP, Brodie SE, Gobin YP. Ophthalmic artery chemosurgery for retinoblastoma prevents new intraocular tumors. Ophthalmology. 2013;120:560-565.  [PubMed]  [DOI]  [Cited in This Article: ]  [Cited by in Crossref: 20]  [Cited by in F6Publishing: 25]  [Article Influence: 2.1]  [Reference Citation Analysis (0)]
23.  Munier FL, Gaillard MC, Balmer A, Soliman S, Podilsky G, Moulin AP, Beck-Popovic M. Intravitreal chemotherapy for vitreous disease in retinoblastoma revisited: from prohibition to conditional indications. Br J Ophthalmol. 2012;96:1078-1083.  [PubMed]  [DOI]  [Cited in This Article: ]  [Cited by in Crossref: 240]  [Cited by in F6Publishing: 238]  [Article Influence: 19.8]  [Reference Citation Analysis (0)]
24.  Shields CL, Manjandavida FP, Arepalli S, Kaliki S, Lally SE, Shields JA. Intravitreal melphalan for persistent or recurrent retinoblastoma vitreous seeds: preliminary results. JAMA Ophthalmol. 2014;132:319-325.  [PubMed]  [DOI]  [Cited in This Article: ]  [Cited by in Crossref: 105]  [Cited by in F6Publishing: 111]  [Article Influence: 11.1]  [Reference Citation Analysis (0)]
25.  Friedman DL, Himelstein B, Shields CL, Shields JA, Needle M, Miller D, Bunin GR, Meadows AT. Chemoreduction and local ophthalmic therapy for intraocular retinoblastoma. J Clin Oncol. 2000;18:12-17.  [PubMed]  [DOI]  [Cited in This Article: ]
26.  Chan HSL, Heon E, Budning A.  Improvement of the cure rate of intraocular retinoblastoma without significantly increasing toxicity with higher dose carboplatin teniposide in a cyclosporine multidrug reversal regimen (Presented at the 10th International Symposium on Retinoblastoma). Florida. Tamwood: Vancouver and Whistler 2001; .  [PubMed]  [DOI]  [Cited in This Article: ]
27.  Shields CL, Shields JA. Retinoblastoma management: advances in enucleation, intravenous chemoreduction, and intra-arterial chemotherapy. Curr Opin Ophthalmol. 2010;21:203-212.  [PubMed]  [DOI]  [Cited in This Article: ]  [Cited by in Crossref: 189]  [Cited by in F6Publishing: 209]  [Article Influence: 14.9]  [Reference Citation Analysis (0)]
28.  Leng T, Cebulla CM, Schefler AC, Murray TG. Focal periocular carboplatin chemotherapy avoids systemic chemotherapy for unilateral, progressive retinoblastoma. Retina. 2010;30:S66-S68.  [PubMed]  [DOI]  [Cited in This Article: ]  [Cited by in Crossref: 14]  [Cited by in F6Publishing: 17]  [Article Influence: 1.2]  [Reference Citation Analysis (0)]
29.  Shields CL, Mashayekhi A, Cater J, Shelil A, Meadows AT, Shields JA. Chemoreduction for retinoblastoma. Analysis of tumor control and risks for recurrence in 457 tumors. Am J Ophthalmol. 2004;138:329-337.  [PubMed]  [DOI]  [Cited in This Article: ]  [Cited by in Crossref: 66]  [Cited by in F6Publishing: 67]  [Article Influence: 3.4]  [Reference Citation Analysis (0)]
30.  Shields CL, Meadows AT, Leahey AM, Shields JA. Continuing challenges in the management of retinoblastoma with chemotherapy. Retina. 2004;24:849-862.  [PubMed]  [DOI]  [Cited in This Article: ]  [Cited by in Crossref: 83]  [Cited by in F6Publishing: 89]  [Article Influence: 4.7]  [Reference Citation Analysis (0)]
31.  Marees T, Moll AC, Imhof SM, de Boer MR, Ringens PJ, van Leeuwen FE. Risk of second malignancies in survivors of retinoblastoma: more than 40 years of follow-up. J Natl Cancer Inst. 2008;100:1771-1779.  [PubMed]  [DOI]  [Cited in This Article: ]  [Cited by in Crossref: 204]  [Cited by in F6Publishing: 214]  [Article Influence: 13.4]  [Reference Citation Analysis (0)]
32.  Kleinerman RA, Tucker MA, Tarone RE, Abramson DH, Seddon JM, Stovall M, Li FP, Fraumeni JF. Risk of new cancers after radiotherapy in long-term survivors of retinoblastoma: an extended follow-up. J Clin Oncol. 2005;23:2272-2279.  [PubMed]  [DOI]  [Cited in This Article: ]  [Cited by in Crossref: 357]  [Cited by in F6Publishing: 297]  [Article Influence: 15.6]  [Reference Citation Analysis (0)]
33.  Eldebawy E, Parker W, Abdel Rahman W, Freeman CR. Dosimetric study of current treatment options for radiotherapy in retinoblastoma. Int J Radiat Oncol Biol Phys. 2012;82:e501-e505.  [PubMed]  [DOI]  [Cited in This Article: ]  [Cited by in Crossref: 19]  [Cited by in F6Publishing: 19]  [Article Influence: 1.5]  [Reference Citation Analysis (0)]
34.  Sethi RV, Shih HA, Yeap BY, Mouw KW, Petersen R, Kim DY, Munzenrider JE, Grabowski E, Rodriguez-Galindo C, Yock TI. Second nonocular tumors among survivors of retinoblastoma treated with contemporary photon and proton radiotherapy. Cancer. 2014;120:126-133.  [PubMed]  [DOI]  [Cited in This Article: ]  [Cited by in Crossref: 128]  [Cited by in F6Publishing: 132]  [Article Influence: 12.0]  [Reference Citation Analysis (0)]
35.  American Brachytherapy Society - Ophthalmic Oncology Task Force, Electronic address: paulfinger@eyecancer. com, ABS – OOTF Committee. The American Brachytherapy Society consensus guidelines for plaque brachytherapy of uveal melanoma and retinoblastoma. Brachytherapy. 2014;13:1-14.  [PubMed]  [DOI]  [Cited in This Article: ]  [Cited by in Crossref: 183]  [Cited by in F6Publishing: 222]  [Article Influence: 20.2]  [Reference Citation Analysis (0)]
36.  Chiu-Tsao ST, Astrahan MA, Finger PT, Followill DS, Meigooni AS, Melhus CS, Mourtada F, Napolitano ME, Nath R, Rivard MJ. Dosimetry of (125)I and (103)Pd COMS eye plaques for intraocular tumors: report of Task Group 129 by the AAPM and ABS. Med Phys. 2012;39:6161-6184.  [PubMed]  [DOI]  [Cited in This Article: ]  [Cited by in Crossref: 127]  [Cited by in F6Publishing: 146]  [Article Influence: 12.2]  [Reference Citation Analysis (1)]