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Suleiman SA, Qi Y, Pi Y, George Xu X. MONTE CARLO SIMULATION OF OUT-OF-FIELD ORGAN DOSES AND CANCER RISK IN TANZANIA FOR RADIATION THERAPY OF UNILATERAL RETINOBLASTOMA USING A 60Co UNIT. RADIATION PROTECTION DOSIMETRY 2018; 179:263-270. [PMID: 29216393 DOI: 10.1093/rpd/ncx269] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 06/20/2017] [Accepted: 11/20/2017] [Indexed: 06/07/2023]
Abstract
The use of 60Co teletherapy unit for the treatment of unilateral retinoblastoma (Rb) patients is a very common procedure in many developing countries including Tanzania. The aim of this study was to estimate organ-specific absorbed doses from an external beam radiation therapy 60Co unit for unilateral Rb and to assess the risks of the patients developing a secondary primary cancer. The absorbed dose estimations were based on a Monte Carlo method and a set of age-dependent computational male phantoms. The estimated doses were used to calculate the secondary cancer risks in out-of-field organs using the Biological Effects of Ionising Radiation VII risk models. The survival information and baseline cancer risks were based on relevant statistics for the Tanzanian population. The resulting out-of-field organ doses data showed that organs which are close to the target volume, such as the brain, salivary glands and thyroid glands, received the highest absorbed dose from scattered photons during the treatment of Rb. It was also found that the resulting photons dose to specific organs depends on the patient's age. Younger patients are more sensitive to radiation and also received higher dose contributions from the treatment head due to a larger part of the body exposed to the photon radiation. In all sites considered, the overall risks associated with radiation-induced secondary cancer were relatively lower than the baseline risks. Thus, the results in this article can help to provide good estimations of radiation-induced secondary cancer after radiation treatment of unilateral Rb using 60Co teletherapy unit in Tanzania and other developing countries.
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Affiliation(s)
- Suleiman Ameir Suleiman
- School of Nuclear Science and Technology, University of Science and Technology of China, Hefei, Anhui Province 230027, PR China
- Radiation Control Directorate, Tanzania Atomic Energy Commission, PO Box 743, Arusha, Tanzania
| | - Yaping Qi
- School of Nuclear Science and Technology, University of Science and Technology of China, Hefei, Anhui Province 230027, PR China
| | - Yifei Pi
- School of Nuclear Science and Technology, University of Science and Technology of China, Hefei, Anhui Province 230027, PR China
| | - X George Xu
- School of Nuclear Science and Technology, University of Science and Technology of China, Hefei, Anhui Province 230027, PR China
- Nuclear Engineering Program, Rensselaer Polytechnic Institute, Troy, NY 12180, USA
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Teixo R, Laranjo M, Abrantes AM, Brites G, Serra A, Proença R, Botelho MF. Retinoblastoma: might photodynamic therapy be an option? Cancer Metastasis Rev 2016; 34:563-73. [PMID: 25579236 DOI: 10.1007/s10555-014-9544-y] [Citation(s) in RCA: 12] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/02/2023]
Abstract
Retinoblastoma is a tumor that mainly affects children under 5 years, all over the world. The origin of these tumors is related with mutations in the RB1 gene, which may result from genetic alterations in cells of the germ line or in retinal somatic cells. In developing countries, the number of retinoblastoma-related deaths is higher due to less access to treatment, unlike what happens in developed countries where survival rates are higher. However, treatments such as chemotherapy and radiotherapy, although quite effective in treating this type of cancer, do not avoid high indices of mortality due to secondary malignances which are quite frequent in these patients. Additionally, treatments such as cryotherapy, thermotherapy, thermochemotherapy, or brachytherapy represent other options for retinoblastoma. When all these approaches fail, enucleation is the last option. Photodynamic therapy might be considered as an alternative, particularly because of its non-mutagenic character. Photodynamic therapy is a treatment modality based on the administration of photosensitizing molecules that only upon irradiation of the tumor with a light source of appropriate wavelength are activated, triggering its antitumor action. This activity may be not only due to direct damage to tumor cells but also due to damage caused to the blood vessels responsible for the vascular supply of the tumor. Over the past decades, several in vitro and in vivo studies were conducted to assess the effectiveness of photodynamic therapy in the treatment of retinoblastoma, and very promising results were achieved.
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Affiliation(s)
- Ricardo Teixo
- Unit of Biophysics, Faculty of Medicine, University of Coimbra, Azinhaga de Santa Comba, Celas, 3000-548, Coimbra, Portugal
| | - Mafalda Laranjo
- Unit of Biophysics, Faculty of Medicine, University of Coimbra, Azinhaga de Santa Comba, Celas, 3000-548, Coimbra, Portugal. .,CIMAGO, Faculty of Medicine, University of Coimbra, Azinhaga de Santa Comba, Celas, 3000-548, Coimbra, Portugal. .,IBILI, Faculty of Medicine, University of Coimbra, Azinhaga de Santa Comba, Celas, 3000-548, Coimbra, Portugal.
| | - Ana Margarida Abrantes
- Unit of Biophysics, Faculty of Medicine, University of Coimbra, Azinhaga de Santa Comba, Celas, 3000-548, Coimbra, Portugal.,CIMAGO, Faculty of Medicine, University of Coimbra, Azinhaga de Santa Comba, Celas, 3000-548, Coimbra, Portugal.,IBILI, Faculty of Medicine, University of Coimbra, Azinhaga de Santa Comba, Celas, 3000-548, Coimbra, Portugal
| | - Gonçalo Brites
- Unit of Biophysics, Faculty of Medicine, University of Coimbra, Azinhaga de Santa Comba, Celas, 3000-548, Coimbra, Portugal
| | - Arménio Serra
- Chemical Engineering Department, Faculty of Science and Technology, University of Coimbra, Pólo II, Pinhal de Marrocos, 3030-290, Coimbra, Portugal
| | - Rui Proença
- IBILI, Faculty of Medicine, University of Coimbra, Azinhaga de Santa Comba, Celas, 3000-548, Coimbra, Portugal.,Centre for Integrated Responsibility in Ophthalmology, Coimbra Hospital and University Centre (CRIO-CHUC), Praceta Mota Pinto, 3000-075, Coimbra, Portugal
| | - Maria Filomena Botelho
- Unit of Biophysics, Faculty of Medicine, University of Coimbra, Azinhaga de Santa Comba, Celas, 3000-548, Coimbra, Portugal.,CIMAGO, Faculty of Medicine, University of Coimbra, Azinhaga de Santa Comba, Celas, 3000-548, Coimbra, Portugal.,IBILI, Faculty of Medicine, University of Coimbra, Azinhaga de Santa Comba, Celas, 3000-548, Coimbra, Portugal
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Gao Y, Lu X. Decreased expression of MEG3 contributes to retinoblastoma progression and affects retinoblastoma cell growth by regulating the activity of Wnt/β-catenin pathway. Tumour Biol 2016; 37:1461-1469. [PMID: 26662307 DOI: 10.1007/s13277-015-4564-y] [Citation(s) in RCA: 51] [Impact Index Per Article: 5.7] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/28/2015] [Accepted: 12/01/2015] [Indexed: 02/06/2023] Open
Abstract
The aberrant expression of MEG3 has been found in some types of cancers; however, little is known concerning the function of MEG3 in retinoblastoma. To elucidate the roles of MEG3 in retinoblastoma, MEG3 expression was quantified in 63 retinoblastoma samples and corresponding nontumor tissues in this work. Moreover, retinoblastoma cell lines were transfected with pcDNA3.1-MEG3 or si-MEG3, after which proliferation, apoptosis, and expression of β-catenin were assayed. TOP-Flash reporter assay was also used to investigate the activity of the Wnt/β-catenin pathway. The results showed that MEG3 was downregulated in retinoblastoma tissues, and the level of MEG3 was negatively associated with IIRC stages and nodal or distant metastasis. More importantly, Kaplan-Meier survival analysis demonstrated that patients with low MEG3 expression had poorer survival and multivariate Cox regression analysis revealed that MEG3 was an independent prognostic factor in retinoblastoma patients. We also observed that MEG3 expression can be modulated by DNA methylation by using 5-aza-CdR treatment. In addition, overexpression of MEG3 suppressed proliferation, promoted apoptosis, and influences the activity of the Wnt/β-catenin pathway in retinoblastoma cell lines. Furthermore, we found that Wnt/β-catenin pathway activator rescued the anticancer effect of MEG3 in retinoblastoma. In conclusion, our study for the first time demonstrated that MEG3 was a tumor suppressor by negatively regulating the activity of the Wnt/β-catenin pathway in the progression of retinoblastoma and might serve as a prognostic biomarker and molecular therapeutic target.
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Affiliation(s)
- Yali Gao
- Department of Ophthalmology, Zhujiang Hospital of Southern Medical University, Guangzhou, 510282, People's Republic of China
- Department of Ophthalmology, Shenzhen People's Hospital, Shenzhen, 518020, People's Republic of China
| | - Xiaohe Lu
- Department of Ophthalmology, Zhujiang Hospital of Southern Medical University, Guangzhou, 510282, People's Republic of China.
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Bhavsar D, Subramanian K, Sethuraman S, Krishnan UM. Management of retinoblastoma: opportunities and challenges. Drug Deliv 2015; 23:2488-2496. [PMID: 25758593 DOI: 10.3109/10717544.2015.1016193] [Citation(s) in RCA: 23] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/13/2022] Open
Abstract
Nano-delivery systems have significantly evolved over the last decade for the treatment of cancer by enabling site-specific delivery and improved bioavailability. The widely investigated nanoparticle systems are biodegradable polyesters, dendrimers, liposomes, mesoporous silica and gold nanoparticles. These particles when conjugated with different targeting motifs enhance the therapeutic efficiency of the drug molecules and biocompatibility. However, the application of such systems towards the treatment of retinoblastoma (RB), a rapidly spreading childhood eye cancer, still remains in its infancy. Nanoparticle-based systems that have been investigated for RB therapy have displayed improved drug delivery to the most restricted posterior segment of the eyes and have increased intra-vitreal half-life of the chemotherapy agents highlighting its potential in treatment of this form of cancer. This review focuses on the challenges involved in the treatment of RB and highlights the attempts made to develop nano-dimensional systems for the treatment of RB.
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Affiliation(s)
- Dhiraj Bhavsar
- a School of Chemical & Biotechnology, Centre for Nanotechnology & Advanced Biomaterials, Sastra University , Thanjavur , Tamil Nadu , India and
| | - Krishnakumar Subramanian
- b L&T Ophthalmic Pathology Department , Vision Research Foundation , Sankara Nethralaya , Chennai , Tamil Nadu , India
| | - Swaminathan Sethuraman
- a School of Chemical & Biotechnology, Centre for Nanotechnology & Advanced Biomaterials, Sastra University , Thanjavur , Tamil Nadu , India and
| | - Uma Maheswari Krishnan
- a School of Chemical & Biotechnology, Centre for Nanotechnology & Advanced Biomaterials, Sastra University , Thanjavur , Tamil Nadu , India and
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Mayorga PA, Brualla L, Sauerwein W, Lallena AM. Monte Carlo study for designing a dedicated "D"-shaped collimator used in the external beam radiotherapy of retinoblastoma patients. Med Phys 2014; 41:011714. [PMID: 24387506 DOI: 10.1118/1.4855855] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/07/2022] Open
Abstract
PURPOSE Retinoblastoma is the most common intraocular malignancy in the early childhood. Patients treated with external beam radiotherapy respond very well to the treatment. However, owing to the genotype of children suffering hereditary retinoblastoma, the risk of secondary radio-induced malignancies is high. The University Hospital of Essen has successfully treated these patients on a daily basis during nearly 30 years using a dedicated "D"-shaped collimator. The use of this collimator that delivers a highly conformed small radiation field, gives very good results in the control of the primary tumor as well as in preserving visual function, while it avoids the devastating side effects of deformation of midface bones. The purpose of the present paper is to propose a modified version of the "D"-shaped collimator that reduces even further the irradiation field with the scope to reduce as well the risk of radio-induced secondary malignancies. Concurrently, the new dedicated "D"-shaped collimator must be easier to build and at the same time produces dose distributions that only differ on the field size with respect to the dose distributions obtained by the current collimator in use. The scope of the former requirement is to facilitate the employment of the authors' irradiation technique both at the authors' and at other hospitals. The fulfillment of the latter allows the authors to continue using the clinical experience gained in more than 30 years. METHODS The Monte Carlo code PENELOPE was used to study the effect that the different structural elements of the dedicated "D"-shaped collimator have on the absorbed dose distribution. To perform this study, the radiation transport through a Varian Clinac 2100 C/D operating at 6 MV was simulated in order to tally phase-space files which were then used as radiation sources to simulate the considered collimators and the subsequent dose distributions. With the knowledge gained in that study, a new, simpler, "D"-shaped collimator is proposed. RESULTS The proposed collimator delivers a dose distribution which is 2.4 cm wide along the inferior-superior direction of the eyeball. This width is 0.3 cm narrower than that of the dose distribution obtained with the collimator currently in clinical use. The other relevant characteristics of the dose distribution obtained with the new collimator, namely, depth doses at clinically relevant positions, penumbrae width, and shape of the lateral profiles, are statistically compatible with the results obtained for the collimator currently in use. CONCLUSIONS The smaller field size delivered by the proposed collimator still fully covers the planning target volume with at least 95% of the maximum dose at a depth of 2 cm and provides a safety margin of 0.2 cm, so ensuring an adequate treatment while reducing the irradiated volume.
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Affiliation(s)
- P A Mayorga
- FISRAD S.A.S., CR 64 A # 22 - 41, Bogotá D C, Colombia and Departamento de Física Atómica, Molecular y Nuclear, Universidad de Granada, E-18071 Granada, Spain
| | - L Brualla
- NCTeam, Strahlenklinik, Universitätsklinikum Essen, Hufelandstraße 55, D-45122 Essen, Germany
| | - W Sauerwein
- NCTeam, Strahlenklinik, Universitätsklinikum Essen, Hufelandstraße 55, D-45122 Essen, Germany
| | - A M Lallena
- Departamento de Física Atómica, Molecular y Nuclear, Universidad de Granada, E-18071 Granada, Spain
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Song HB, Jun HO, Kim JH, Yu YS, Kim KW, Min BH, Kim JH. Anti-apoptotic effect of clusterin on cisplatin-induced cell death of retinoblastoma cells. Oncol Rep 2013; 30:2713-8. [PMID: 24085287 DOI: 10.3892/or.2013.2764] [Citation(s) in RCA: 16] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/18/2013] [Accepted: 08/22/2013] [Indexed: 11/05/2022] Open
Abstract
Clusterin is a cytoprotective chaperone protein that is known to protect various retinal cells. It was also reported to be overexpressed in several types of malignant tumors, whose chemoresistance correlates with the expression of clusterin. Herein, we investigated the effect of clusterin on cisplatin-induced cell death of retinoblastoma cells. Firstly, evaluation of clusterin expression demonstrated that it was highly expressed in human retinoblastoma tissues and cell lines (SNUOT-Rb1 and Y79) particularly in the area between viable cells around vessels and necrotic zones in the relatively avascular area in human retinoblastoma tissues. Furthermore, the effects of cisplatin on retinoblastoma cells were evaluated. Cisplatin (1 µg/ml) significantly affected cell viability of SNUOT-Rb1 cells by inducing caspase-3-dependent apoptosis. Notably, the cell death due to cisplatin was prevented by 5 µg/ml of clusterin administered 4 h prior to cisplatin treatment by inhibiting cisplatin-induced apoptosis. Furthermore, overexpression of clusterin exerted its anti-apoptotic effect on cisplatin-induced apoptosis, and effectively prevented cisplatin-induced cell death. These data suggest that clusterin, found to be expressed in human retinoblastoma, may exert anti-apoptotic effects on cisplatin-induced apoptosis and prevent cell death. Therefore, clusterin can contribute to cisplatin resistance of retinoblastoma.
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Affiliation(s)
- Hyun Beom Song
- Fight against Angiogenesis-Related Blindness Laboratory, Clinical Research Institute, Seoul National University Hospital, Seoul, Republic of Korea
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Abstract
Retinoblastoma is the most common primary childhood ocular tumor, affecting nearly 3.5 per million children worldwide. A mutation in the RB1 gene, which presents as either germline or sporadic, along with additional mutational events, promote neoplastic growth in the retina. Fortunately, current treatment protocols result in success rates approaching 99% at specialized centers, with many children maintaining useful vision. Overall, treatment is guided by aggressiveness and size, and is classified by systems such as the Reese-Ellsworth System and the International Classification of Retinoblastoma. Due to advances in chemotherapy protocols combined with use of focal laser consolidation, treatment paradigms have shifted from enucleation to external beam radiation therapy to chemotherapy as globe-salvaging therapies. Smaller, less complex tumors may be controlled by plaque radiotherapy or focal laser ablative therapy. However, larger and more complex tumors, such as those that have vitreous or subretinal seeding, require methods of chemoreduction combined with focal consolidation to yield better outcomes. Standard chemotherapy protocols utilize vincristine, etoposide, and carboplatin with or without cyclophosphamide. Finally, there has been a recent push in local treatments for retinoblastoma to minimize systemic toxicities. These modalities include intravitreal or subconjunctival injections and more recently, direct chemotherapy administration into the ophthalmic artery. As a result, enucleation is used less often, but remains an important treatment for the most aggressive, refractory cases. The advancement of retinoblastoma treatment looks promising; however, worldwide access to these treatments and the lack of long-term follow-up of new local treatment modalities constitute current and future challenges.
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Brualla L, Mayorga PA, Flühs A, Lallena AM, Sempau J, Sauerwein W. Retinoblastoma external beam photon irradiation with a special ‘D’-shaped collimator: a comparison between measurements, Monte Carlo simulation and a treatment planning system calculation. Phys Med Biol 2012; 57:7741-51. [DOI: 10.1088/0031-9155/57/22/7741] [Citation(s) in RCA: 9] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/27/2022]
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Abstract
Ocular neoplasms, both primary and metastatic, may present with visual disturbance or vision loss and often are asymptomatic. Clinical ophthalmologic examination may demonstrate leukocoria, abnormal pupillary light reflex, or a mass lesion with or without retinal detachment or hemorrhage. Retinoblastoma in children and uveal melanoma and ocular metastases in adults are the most important ocular malignant neoplasms referred for imaging to aid with diagnosis and staging. Familiarity with their common imaging appearances, the common patterns of spread, and the diagnostic findings of greatest concern to the ocular oncologist will enhance accuracy of imaging interpretation. Clinical ophthalmologic examination and imaging using B-scan ultrasound, A-scan ultrasound, fluorescein angiography, computed tomography and magnetic resonance imaging have complementary roles in ocular tumor staging and treatment assessment.
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Affiliation(s)
- Amit Mahajan
- Department of Diagnostic Radiology, Yale New Haven Hospital, New Haven, CT, USA
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Setlur VJ, Parikh JG, Rao NA. Changing causes of enucleation over the past 60 years. Graefes Arch Clin Exp Ophthalmol 2009; 248:593-7. [DOI: 10.1007/s00417-009-1262-8] [Citation(s) in RCA: 24] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/22/2009] [Revised: 11/11/2009] [Accepted: 11/26/2009] [Indexed: 10/20/2022] Open
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Wilson MW, Rodriguez-Galindo C, Billups C, Haik BG, Laningham F, Patay Z. Lack of correlation between the histologic and magnetic resonance imaging results of optic nerve involvement in eyes primarily enucleated for retinoblastoma. Ophthalmology 2009; 116:1558-63. [PMID: 19545904 DOI: 10.1016/j.ophtha.2009.02.018] [Citation(s) in RCA: 33] [Impact Index Per Article: 2.1] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/23/2008] [Revised: 02/09/2009] [Accepted: 02/12/2009] [Indexed: 11/17/2022] Open
Abstract
PURPOSE To correlate the histologic and magnetic resonance imaging results of the optic nerve in eyes primarily enucleated for retinoblastoma. DESIGN Retrospective, clinicopathologic correlation. PARTICIPANTS Sixty-seven consecutive patients with retinoblastoma who underwent primary enucleation. METHODS The histologic results of 67 eyes from 67 patients with retinoblastoma who underwent primary enucleation between March 1997 and January 2008 were studied for evidence of optic nerve invasion. Two neuroradiologists independently reviewed available preoperative magnetic resonance imaging studies with special emphasis on nonenhanced T2-weighted and gadolinium-enhanced T1-weighted imaging for evidence of optic nerve invasion. A weighted kappa statistic was used to assess agreement between observers. MAIN OUTCOME MEASURES Correlation between neuroradiologists and histologic results. RESULTS Of the 67 eyes studied, 60 had preoperative magnetic resonance images, 58 of which were deemed appropriate for review by both neuroradiologists. Review of the histologic results showed optic nerve involvement in 62 (93%) of 67 eyes: 28 prelaminar (42%), 24 laminar (36%), and 10 postlaminar (15%). On review of the magnetic resonance scans, the first neuroradiologist identified optic nerve involvement in 57 (95%) of 60 eyes: 26 prelaminar (43%), 10 laminar (17%), and 11 postlaminar (18%). The second neuroradiologist identified optic nerve involvement in 46 (77%) of 60 eyes: 33 prelaminar (55%), 9 laminar (15%), and 4 postlaminar (7%). Moderate agreement existed between neuroradiologists (kappa, 0.55). Poor and fair agreement existed between each of the 2 neuroradiologists and histologic results, respectively (kappa, 0.29 and 0.17). Exophytic tumors showed the greatest disparity (kappa, -0.20 and -0.13) between magnetic resonance imaging and histologic results. CONCLUSIONS Limited correlation was found between magnetic resonance imaging and histologic results in assessing optic nerve invasion in eyes with retinoblastoma. Magnetic resonance imaging using routine imaging technologies, although useful in the evaluation of retinoblastoma, has limited usefulness in assessing the exact extent of optic nerve invasion; high-risk features of retinoblastoma such as postlaminar invasion remain best defined by histologic analysis. This study demonstrates that the interpretation of optic nerve involvement by a radiologist should not be the determining factor to defer enucleation in favor of neoadjuvant therapy.
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Affiliation(s)
- Matthew W Wilson
- Hamilton Eye Institute, Department of Ophthalmology, University of Tennessee Health Science Center, Memphis, Tennessee 38163, USA
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Kulkarni AD, van Ginkel PR, Darjatmoko SR, Lindstrom MJ, Albert DM. Use of combination therapy with cisplatin and calcitriol in the treatment of Y-79 human retinoblastoma xenograft model. Br J Ophthalmol 2009; 93:1105-8. [PMID: 19336429 DOI: 10.1136/bjo.2008.152843] [Citation(s) in RCA: 15] [Impact Index Per Article: 0.9] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/04/2023]
Abstract
BACKGROUND Retinoblastoma is the most common primary malignant intraocular neoplasm of childhood. The poor outcomes of patients with metastatic retinoblastoma have encouraged the search for new therapies. In the current study, the efficacy of combination therapy with calcitriol and cisplatin in athymic mice with subcutaneous Y-79 human retinoblastoma tumours was assessed. METHODS 60 athymic mice were subcutaneously injected with human Y79 retinoblastoma cells. Animals were randomised into four groups: group 1, 50 microg of cisplatin; group 2, 0.05 microg of calcitriol; group 3, 0.05 microg of calcitriol and 50 microg of cisplatin; group 4, control. The cisplatin was administered once a week, and the calcitriol was given five times a week. RESULTS There was a significant inhibition of tumour growth in animals treated with the combination therapy of calcitriol and cisplatin as compared with controls and cisplatin alone (p = 0.0001 and p = 0.0041 respectively). In terms of toxicity, serum calcium levels were increased, but there was no mortality and minimal nephrotoxicity in any of the groups. CONCLUSION The present study shows that cisplatin given in combination with calcitriol may be a viable multidrug therapy option in the treatment of high-risk retinoblastoma.
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Affiliation(s)
- A D Kulkarni
- Department of Ophthalmology and Visual Sciences, University of Wisconsin School of Medicine and Public Health, 600 Highland Avenue, Madison, WI 53792-4673, USA
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Kim H, Lee JW, Kang HJ, Park HJ, Kim YY, Shin HY, Yu YS, Kim IH, Ahn HS. Clinical results of chemotherapy based treatment in retinoblastoma patients: a single center experience. Cancer Res Treat 2008; 40:164-71. [PMID: 19688125 DOI: 10.4143/crt.2008.40.4.164] [Citation(s) in RCA: 16] [Impact Index Per Article: 0.9] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/27/2008] [Accepted: 11/14/2008] [Indexed: 11/21/2022] Open
Abstract
PURPOSE Retinoblastoma is the most common intraocular malignancy in children. Since the 1990s, chemotherapy was indicated for intraocular disease to reduce the frequency of enucleation and spare the complications associated with external beam radiation. In this study, we analyzed treatment results of retinoblastoma in our institute. MATERIALS AND METHODS Datas from children diagnosed with retinoblastoma and treated at Seoul National University Children's Hospital between 1986 and 2008 were analyzed retrospectively. We utilized cyclophosphamide, vincristine, adriamycin, and methotrexate (CVAM) for OPD-based adjuvant chemotherapy. From 1990, primary chemotherapy was administered to patients with intraocular disease for eyeball-saving and patients received a combination of etoposide, vincristine, cisplatin (or ifosfamide) as a moderately intensive regimen, or a combination of cisplatin, doxorubicin, etoposide, and cycophosphamide (CDEC) as a highly intensive regimen. RESULTS One hundred eighteen children were analyzed. There were 68 unilateral and 50 bilateral diseases. The median age at diagnosis was 1 year and Reese-Ellsworth stage V was the most common stage at the time of diagnosis. All patients were treated by chemotherapy-based multimodality methods, and primary chemotherapy was administered to 80 patients. The 10-year overall and event-free survival rate of all patients were 93.9% and 91.6%, respectively. Two patients who died were in the CDEC regimen group, but there was no significant statistical difference in survival rates by chemotherapy regimens. Fifty-six of 114 eyeballs were saved after primary chemotherapy-based treatment, and the eyeball-saving rate was 49.1%. Six patients relapsed after enucleation and 2 patients were treated successfully after autologous PBSCT. Osteosarcoma occurred in 2 patients as a secondary malignancy, and facial asymmetry after radiotherapy was the most common long-term sequelae. CONCLUSIONS In this study, the overall and event-free survival rates of retinoblastoma were satisfactory and eye-saving was possible with primary chemotherapy. Development of new chemotherapeutic regimens and a team approach are necessary to improve the eyeball-saving rate.
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Affiliation(s)
- Hyery Kim
- Division of Hematology/Oncology, Department of Pediatrics, Cancer Research Institute, Seoul National University College of Medicine, Seoul, Korea
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