• Users Online: 150
  • Print this page
  • Email this page

Table of Contents
Year : 2021  |  Volume : 4  |  Issue : 1  |  Page : 40-45

Post-enucleation retinoblastoma: Outcome analysis and evaluation of prognostic features

1 Department of Pediatric Hematology/Oncology, King Faisal Specialist Hospital and Research Center, Riyadh, Saudi Arabia
2 Department of Ophthalmology; Department of Pathology, College of Medicine, King Saud University, Riyadh, Saudi Arabia
3 King Faisal Specialist Hospital and Research Center, Riyadh, Saudi Arabia
4 Division of Pediatric Ophthalmology, King Khaled Eye Specialist Hospital, Riyadh, Saudi Arabia

Date of Submission03-Jun-2020
Date of Decision30-Jun-2020
Date of Acceptance15-Jul-2020
Date of Web Publication09-Dec-2020

Correspondence Address:
Amani Al-Kofide
Department of Pediatric Hematology/Oncology, King Faisal Specialist Hospital and Research Center, P.O. Box 3354, Riyadh 11211
Saudi Arabia
Login to access the Email id

Source of Support: None, Conflict of Interest: None

DOI: 10.4103/JNSM.JNSM_58_20

Rights and Permissions

Background: The aim is to assess if International Classification for Retinoblastoma (ICRB) and American Joint Committee on Cancer Staging System (AJCC) for patients with advanced Retinoblastoma (RB) who underwent enucleation correlated in predicting the successful outcome of chemotherapy. Materials and Methods: Medical records of fifty-eight pediatric patients (age ≤14 years) who underwent enucleation at King Khalid Eye Specialist Hospital, and treated post enucleation at KFSH and RC from 2012 to 2016 were reviewed. Results: RB was unilateral in 30 (51.7%), bilateral in 26 (44.8%) and trilateral in 2 (3.4%). One (1.7%) had metastatic disease. Sixty-one enucleation was performed on 58 patients; unilateral in 55 (94.8%) and bilateral in the 3 (5.2%) cases. Disease was ICRB Group E in 43 (70.5%), Group D in 11 (18.0%), Group C and A in 3 (4.9%) each, and Group B in 1 (1.6%) at diagnosis (P < 0.001). The median age at diagnosis was the highest in Group E compared to other groups (P = 0.254). All patients received chemotherapy. Nine (18.8%) patients classified as Group D or E as per the ICRB classification turned out to be pT1 or pT2a (low-risk), while one classified as Group C was of stage pT1. Probability of 5-year overall survival for the whole cohort was 93.0% (±4.0%); 94.5% (±3.8%) for Group E (2 mortalities) and 80.0% (±17.9%) for Stage D with one event of mortality (P: 0.972). Conclusion: Older children presented with ICRB Group E. Group E eyes had a high pTNM risk group than Group D. ICRB tends to correlate with pTNM. The ICRB classification is essential for decision making on enucleation; however, AJCC pTNM classification plays a pivotal role in deciding on postenucleation adjuvant treatment.

Keywords: Enucleation, ocular, outcome, retinoblastoma

How to cite this article:
Al-Kofide A, Alkatan HM, Khafaga Y, Siddiqui K, Jafri R, Ayas M, AlMesfer SA. Post-enucleation retinoblastoma: Outcome analysis and evaluation of prognostic features. J Nat Sci Med 2021;4:40-5

How to cite this URL:
Al-Kofide A, Alkatan HM, Khafaga Y, Siddiqui K, Jafri R, Ayas M, AlMesfer SA. Post-enucleation retinoblastoma: Outcome analysis and evaluation of prognostic features. J Nat Sci Med [serial online] 2021 [cited 2023 Feb 9];4:40-5. Available from: https://www.jnsmonline.org/text.asp?2021/4/1/40/303906

  Introduction Top

Retinoblastoma (RB) is the most common intraocular pediatric malignancy, with an incidence of 1/15,000–20,000 live births worldwide.[1] Overall it represents 4% of all pediatric malignancies.[2] Whereas the survival rate in developed countries reaches up to 95%, it still carries a poor prognosis in underdeveloped countries, due to delayed diagnosis and extraocular dissemination of the disease.[3] In Saudi Arabia, RB is diagnosed relatively late.[4],[5] Predominantly a childhood cancer, it affects children <15 years of age, with a median age of diagnosis of 12 months for bilateral and 24 months for the unilateral cases, respectively.[6] Although the disease is heralded by some distinguished clinical signs, when the diagnosis is delayed, it may require aggressive therapy and a possible need for enucleation of the affected eye.[7] The disease trend in North America has been stable for >2 decades.[8] In Saudi Arabia, the pattern seems to be changing mainly due to improved health awareness and medical care.[9]

Classification and staging of RB are the cardinal steps in planning an appropriate treatment plan and predicting outcome. Over the years, several systems have evolved, with the International Intraocular RB Classification (IIRC), the International Classification for RB (ICRB), and cTNM are used for disease confined to the globe, while International RB Staging System (IRSS) and cTNM are used for extraocular disease.[10]

Enucleation is considered a viable treatment option for RB, especially for unilateral disease.[11] Enucleation, however, results in various cosmetic challenges[12] as well as parental stress.[13] Therefore, it is imperative that a careful decision be made based on disease classification and burden.

Keeping in view the potential success of enucleation in treating high-risk unilateral RB, coupled with short-term and long-term complications, it is critical to review patient data and histopathological risk features (of enucleated globes) using the American Joint Commission on Cancer (AJCC) staging to enable management decision-makers to evaluate how the treatment options may impact the outcome of children with RB.

We, therefore, conducted a retrospective study at our center to evaluate patients with RB who underwent enucleation based on ICRB classification and continued adjuvant treatment based on the AJCC (7th edition) classification.

  Materials and Methods Top


King Khalid Eye Specialist Hospital (KKESH) is a state-of-the-art referral center in Saudi Arabia for children with RB for evaluation, focal and surgical treatment, since its establishment in 1984. Later, patients are referred to King Faisal Specialist Hospital and Research Centre (KFSHRC) for radiation and systemic chemotherapy, when indicated.

Ninety-one RB patients were registered at the Department of Pediatric Hematology/Oncology (KFSHRC), Riyadh, Saudi Arabia, between 2012 and 2016. Records of 58 pediatric patients (age ≤ 14 years), who underwent enucleation, were reviewed retrospectively. Data on demographics, diagnosis, treatment-related parameters, and outcomes were extracted from prospectively maintained clinical databases and through medical charts review. All patients underwent chemotherapy as chemo-reduction (a method of reducing tumor volume to allow for more focused, less damaging therapeutic measures) and/or chemoprevention (involves the chronic administration of a synthetic, natural, or biological agent to reduce or delay the occurrence of malignancy). Chemo-reduction was utilized in 52 (85.2%), chemoprevention in 5 (8.2%) and chemo-reduction and chemoprevention in 4 (6.6%) eyes. A total of 358 chemotherapy cycles were administered; thirty-five patients received six cycles and eleven received nine cycles per patient (mean: 6, minimum 1, maximum 9). Four (6.9%) patients received thermotherapy, 1 (1.7%) cryotherapy, and 1 (1.7%) trans-pupillary intravenous carboplatin before being referred to our institution for chemotherapy.

Statistical considerations

All continuous data are presented as median with minimum and maximum points. Independent samples Kruskal–Wallis test was used to compare the age at diagnosis for various ICRB groups. Kaplan–Meier curves were drawn for survival analysis and tested for any difference between the survival times using the Breslow test in univariate setting.


The study was conducted after taking approval from the Institutional Review Board (IRB) of King Khalid Eye Specialist Hospital.

Being a retrospective study, no consent/assent was taken from the patients and/or the guardians. A waiver of informed consent/assent was sought from the IRB of the hospital.

  Results Top

Among the cohort, 30 (51.7%) were female. The median age at diagnosis was 1.7 years (range, 3.0 months–8.0 years). RB was unilateral in 30 (51.7%), bilateral in 26 (44.8%), and trilateral in two (3.4%) patients [Table 1]. One (1.7%) female child with unilateral RB had metastatic disease at presentation. Sixty-one (70.9%) enucleations were performed in 58 patients.
Table 1: Characteristics of the cohort, chemotherapy cycles and enucleation (n=58 patients)

Click here to view


Enucleation was unilateral in 55 (94.8%) and bilateral in the 3 (5.2%) patients. Among those who had unilateral enucleation, 50 (90.9%) underwent primary enucleation followed by chemoprevention due to high-risk features, and 5 (9.1%) underwent enucleation during chemotherapy. Two (66.7%) patients had bilateral enucleation – first enucleation before chemotherapy and second postchemotherapy, while one patient had bilateral enucleation before receiving chemotherapy.


In terms of ICRB classification, disease was Group E in 43 (70.5%), Group D in 11 (18.0%), Group C and A in 3 (4.9%) each, and Group B in 1 (1.6%) at diagnosis (P < 0.001). The median age at diagnosis was highest in Group E compared to other groups; however, the difference was not statistically significant [[Figure 1], P = 0.254]. Information on AJCC classification (pTNM) at enucleation was available on 48 patients only. Nine (18.8%) patients classified as Group D or E as per the ICRB classification turned out to be pT1 or pT2a (low-risk), while one classified as Group C was of stage pT1. On the other hand, two patients with ICRB Group A turned out to be high-risk patients on enucleation [[Table 2], P = 0.474]. Postenucleation external beam orbital radiotherapy (EBORT) with a standard dose of 45 Gy was given to 10 (17.2%) patients, of whom 6 (60%) were with Group E. One patient received bilateral EBORT due to bilateral disease. All those who received EBORT were alive at last contact. Eight of them were in complete remission (CR), one had stable disease and for one patient disease evaluation was not possible due to ongoing treatment at the last follow-up visit.
Figure 1: Age at diagnosis by International Classification for Retinoblastoma Groups

Click here to view
Table 2: Patients treated with external beam orbital radiotherapy according to international classification for retinoblastoma classification (n=48)

Click here to view

Overall survival

There were three (5.2%) mortalities (two in bilateral and one in unilateral disease) in our cohort of patients. With a median follow-up of 32.4 months (95% confidence interval: 23.3–41.5), probability of 5-year overall survival (OS) for the whole cohort was 93.0% (±4.0%); 94.5% (±3.8%) for Group E (2 mortalities) and 80.0% (±17.9%) for Stage D with one event of mortality [[Figure 2], P: 0.972]. The cumulative probability of event-free survival at 5-years for all patients was 83.6% (±5.8%).
Figure 2: Overall survival based on clinical groups at diagnosis

Click here to view

Patients with stage pT1 or pT2a when combined into one group (n = 10, no deaths) fared better than those with stage pT2b and above (n = 38, with two deaths) in terms of OS (100% vs. 94.0% ± 4.1%). However, the difference did not achieve statistical significance [P: 0.453, [Figure 3]].
Figure 3: Overall survivals according to the American Joint Commission on Cancer Classification

Click here to view

Of 45 evaluable patients at the last follow-up, 41 (91.1%) were in CR, two (4.4%) had progressive disease and two (4.4%) were alive with stable disease. One patient with bilateral RB succumbed to her illness due to progressive disease.

  Discussion Top

Despite acquiring the status of a unique clinico-pathologic entity in the 18th century,[14] treatment of RB still poses a significant challenge to neuro-ophthalmologists and oncologists, mainly due to a lack of a proper classification system to address the burden of the disease especially in eyes with multiple tumors.[15] In underprivileged countries, the delayed diagnosis could result in disease progression, extraocular metastasis, and increased mortality.[16] In contrast, RB is curable in >95% of patients in developed countries where advanced stage disease is rarely encountered.[17]

RB is usually manifested by leukocoria and strabismus. Children with a positive family history of RB should be considered at high risk in which diagnosis can be confirmed by fundoscopy and ocular ultrasound. A multidisciplinary approach with a team of specialists from ophthalmology, pediatric oncology, and pathology and radiation oncology is usually required in order to achieve a favorable outcome. Treatment options include enucleation, focal treatment (cryotherapy, local chemotherapy, and plaque brachytherapy), systemic chemotherapy and external beam radiotherapy based on tumor stage, number of tumor foci, tumor site and size within the eye(s), presence of vitreous seeding and extraocular spread.

In a recently concluded study, Alkatan et al. published interesting demographics of pediatric orbital lesions in Saudi Arabia, based on age and geographic region.[9] They reviewed the orbital lesions of 106 patients by tissue diagnosis for 14 years and found that neoplasms accounted for only 37% of all such lesions, with rhabdomyosarcoma being the most common neoplasm and interestingly no cases of orbital involvement secondary to RB seen, in contrary to a previous national similar study a few years earlier where advanced RB and/or RB recurrence in the socket with secondary orbital involvement were the commonest encountered orbital malignancy in children (33%).[18] This paradigm shift in RB presentation reflects improved therapy, better access to healthcare and increased awareness of the RB in Saudi Arabia in recent years.

The principal objectives of a successful RB treatment are life salvage with the prevention of metastases and globe salvage and improved quality of life. Patients with advanced-stage disease such as Stage D and E have diffuse retinal involvement and obscuration of the macula and are difficult candidates for globe salvage.[19]

Enucleation is considered as the mainstay of treating unilateral locally advanced RB. While it has proven to be effective in the majority of cases, it is associated with many untoward drawbacks like cosmetic issues,[12] parental stress,[13] and impaired motor function in survivors affecting the quality of life.[20] Improved survival rates in recent studies are related to better tumor characterization and evaluation of the local extent by computed tomography/magnetic resonance imaging, improved screening for metastatic disease, and the use of adjuvant radiotherapy/systemic chemotherapy in tumors with high-risk features. Furthermore the evolution of newer treatment modalities such as ophthalmic artery chemosurgery has replaced enucleation in many unilateral RB cases, without compromising the patient's survival.[21]

RB is staged according to Tumor, Node, and Metastasis (TNM), which includes the AJCC pathological staging for enucleated globes with advanced RB or the IIRC. Patients with IRSS Stage 0 or 1, where the disease is still confined to the eye with a disease-free contralateral eye, can be effectively cured by enucleation alone. With further progression and spread of the disease, enucleation alone may not be as effective.

Department of Pediatric Hematology/Oncology at KFSHRC is a regional tertiary care center, managing patients with RB, and we tend to encounter a significant number of hereditary cases pertaining to the practice of consanguineous marriages prevalent in the Middle-Eastern society.[22],[23],[24] The goal of this study was to review enucleated RB cases and to determine the impact of available classification systems such as ICRB and AJCC (7th edition) TNM classification in influencing the clinical decision for enucleation, and for postenucleation treatment plan based on the histopathological staging.

All fifty-eight patients (61 eyes) received chemotherapy at some point in time during their treatment. 52 (85.2%) received chemo-reduction, and 5 (8.2%) chemo-prevention and 4 (6.6%) received a combination of both. The decision for postenucleation chemotherapy was guided by the AJCC classification for tumor staging with the high-risk features of stage T2b as our cut-off limit for chemotherapy. Only 2/38 were eligible for chemotherapy treatment after enucleation since most of these patients have been originally classified as Stage A. Our results demonstrate an OS of 80% and 94.5% in Stage D and Stage E respectively which may emphasize the effectiveness of chemotherapy in tandem with other treatment modalities, including enucleation. It could be explained by disease down-staging in patients who received chemo-reduction before enucleation. A significant OS difference of 100% and 0% in intermediate-risk and high-risk groups, respectively, by AJCC (7th edition) classification, was observed. This may indicate a more prognostic power for AJCC risk stratification as compared to other staging systems.

Overall, ten patients (17.2%) received postenucleation EBORT, with a standard dose of 45 Gy, of whom 6 patients had stage E (60%). In modern practice, the role of external beam radiotherapy is diminishing due to long-term toxicity, namely secondary cancers, orbital bone hypoplasia, adverse cosmetic effects, cataract, and retinopathy. Novel radiation techniques and modalities such as intensity-modulated radiotherapy and Proton therapy could help in reducing toxicity. EBORT must be avoided, particularly in the early stages of RB, which can be successfully treated with chemotherapy and local focal treatment with or without surgery. EOBRT should be considered only when focal treatment modalities are not clinically applicable. Radiation is particularly morbid in hereditary RB, not only with regard to later dysmorphic orbital changes but more importantly, due to a very high incidence of second malignant tumors, overall 51% at 50 years from diagnosis, compared to 5% in unilateral RB.[25],[26] A conservative approach to the use of orbital radiation is therefore warranted, especially in familial disease. A German study found out that for hereditary cases, long-term OS rate was reduced in patients treated with eye-preserving radiotherapy compared with enucleation alone. Why this difference was observed is speculative. Certainly, the risk of extra-global relapse should be the sum of the risks associated with each eye separately. In bilateral disease, commonly, the eye with less advanced disease is not enucleated, and it could be that the added risk from the enucleated eye is large.

Nonetheless, about 80% of RB patients present with a locally advanced stage, and only 20% of early-stage RB patients are curable with chemosurgery. Chemotherapy fails to achieve desirable results in more than two-thirds of advanced-stage disease, hence requiring EBORT with the lowest possible effective radiation dose to avoid treatment-related toxic effects.[27] The impact of radiation on the improved outcome is well demonstrated in our Stage E patients.

There is no agreement on the Reese-Ellsworth classification and ICRB, as different centers use different versions with different stratification definition for Stage D and E tumors.[28] These differences in definition make interpretation of data and comparison of treatment results between different centers extremely difficult. Hence, the importance of correlating the clinical staging of groups E and D retinoblastoma with other consistent staging/classification systems such as the AJCC for better prognostication, and inter-centric data comparison. The TNM classification is based on the anatomic spread of the primary tumor (T), Lymph Node Involvement (N), and Systemic spread (M). The histopathological assessment of the RB tumor in enucleated globes is of paramount importance and should be performed with careful attention to the ON level of invasion and degree of choroidal invasion as well as any intra-scleral or extraocular extension. The eventual pathological staging as described in the AJCC 7th edition used in our current study (and a more recent 8th edition that we are starting to implement) determines the eligibility for postenucleation chemotherapy since it has been linked to survival and prognosis.[29] Out of 58 patients, AJCC classification was available for 48 patients in our cohort: nine (18.8%) of T1, T2a patients were classified as Stage D or Stage E, and 2/38 tumors classified as AJCC high risk (T2b or worse) were clinically Stage A [Table 2], but still received postenucleation chemotherapy based on their high-risk tumor histopathological features. Overall, 10/58 patients received postenucleation external beam orbital radiation (EBORT) based on high-risk pathological features. High-risk pathological criteria for adjuvant chemotherapy used at KFSHRC included massive choroidal invasion, positive ON resection margin, and/or scleral penetration. Indications for postenucleation adjuvant EBORT included positive ON resection margins, and scleral penetration. These high-risk features for extra-ocular relapse were confirmed in several other studies.[30],[31],[32] At 5-years follow-up, of 45 available patients, 41 (91.2%) were disease-free, 2 (4.4%) had stable disease in the contralateral remaining eye, and 2 (4.4%) had progressive disease.


We conclude that both ICRB and AJCC (7th edition) staging systems are pivotal for therapeutic choices and prognostic evaluation. Chemotherapy along with local therapy is the mainstay of treatment for early-stage RB, while postenucleation adjuvant external beam orbital radiotherapy is indicated in advanced stages such as D and E. Further, the overall management of RB needs to be improved by early detection using appropriate clinical assessment and identification of the histopathological nature of the disease by AJCC classification.

Financial support and sponsorship


Conflicts of interest

There are no conflicts of interest.

  References Top

Dimaras H, Kimani K, Dimba EA, Gronsdahl P, White A, Chan HS, et al. Retinoblastoma. Lancet (London, England) 2012;379:1436-46.  Back to cited text no. 1
Shields CL, Shields JA. Basic understanding of current classification and management of retinoblastoma. Curr Opin Ophthalmol 2006;17:228-34.  Back to cited text no. 2
Rodrigues KE, Latorre Mdo R, de Camargo B. Delayed diagnosis in retinoblastoma. J Pediatr (Rio J) 2004;80:511-6.  Back to cited text no. 3
Mullaney PB, Karcioglu ZA, al-Mesfer S, Dowaidi M. Retinoblastoma referral patterns in Saudi Arabia. Ophthalmic Epidemiol 1996;3:35-46.  Back to cited text no. 4
Karcioglu ZA, al-Mesfer SA, Abboud E, Jabak MH, Mullaney PB. Workup for metastatic retinoblastoma. A review of 261 patients. Ophthalmology 1997;104:307-12.  Back to cited text no. 5
Cassoux N, Lumbroso L, Levy-Gabriel C, Aerts I, Doz F, Desjardins L. Retinoblastoma: Update on current management. Asia Pac J Ophthalmol (Phila) 2017;6:290-5.  Back to cited text no. 6
Lu JE, Francis JH, Dunkel IJ, Shields CL, Yu MD, Berry JL, et al. Metastases and death rates after primary enucleation of unilateral retinoblastoma in the USA 2007-2017. Br J Ophthalmol 2019;103:1272-7.  Back to cited text no. 7
Darwich R, Ghazawi FM, Rahme E, Alghazawi N, Burnier JV, Sasseville D, et al. Retinoblastoma incidence trends in Canada: A national comprehensive population-based study. J Pediatr Ophthalmol Strabismus 2019;56:124-30.  Back to cited text no. 8
Alkatan HM, Al Marek F, Elkhamary S. Demographics of pediatric orbital lesions: A tertiary eye center experience in Saudi Arabia. J Epidemiol Glob Health 2019;9:3-10.  Back to cited text no. 9
Fabian ID, Reddy A, Sagoo MS. Classification and staging of retinoblastoma. Community Eye Health 2018;31:11-3.  Back to cited text no. 10
Fabian ID, Stacey AW, Johnson KC, Chowdhury T, Duncan C, Reddy MA, et al. Primary enucleation for group D retinoblastoma in the era of systemic and targeted chemotherapy: The price of retaining an eye. Br J Ophthalmol 2018;102:265-71.  Back to cited text no. 11
Mourits DL, Hartong DT, Lissenberg-Witte BI, Bosscha MI, Tan HS, Moll AC. Cosmetic results of enucleation and/or external beam radiation therapy in 195 retinoblastoma survivors. Acta Ophthalmol 2018;96:631-40.  Back to cited text no. 12
Hamama-Raz Y, Rot I, Buchbinder E. The coping experience of parents of a child with retinoblastoma-malignant eye cancer. J Psychosoc Oncol 2012;30:21-40.  Back to cited text no. 13
Grossniklaus HE. Retinoblastoma. Fifty years of progress. The LXXI Edward Jackson memorial lecture. Am J Ophthalmol 2014;158:875-91.  Back to cited text no. 14
Damato B, Afshar AR, Everett L, Banerjee A, Hetts SW. The University of California, San Francisco Documentation system for retinoblastoma: Preparing to improve staging methods for this disease. Ocul Oncol Pathol 2019;5:36-45.  Back to cited text no. 15
Mattosinho CC, Moura AT, Oigman G, Ferman SE, Grigorovski N. Time to diagnosis of retinoblastoma in Latin America: A systematic review. Pediatr Hematol Oncol 2019;36:55-72.  Back to cited text no. 16
Lukamba RM, Yao JA, Kabesha TA, Budiongo AN, Monga BB, Mwembo AT, et al. Retinoblastoma in Sub-Saharan Africa: Case studies of the republic of côte d'ivoire and the democratic republic of the Congo. J Glob Oncol 2018;4:1-8.  Back to cited text no. 17
Johnson TE, Senft SH, Nasr AM, Bergqvist G, Cavender JC. Pediatric orbital tumors in Saudi Arabia. Orbit 1990;9:205-15.  Back to cited text no. 18
Kaliki S, Mittal P, Mohan S, Chattannavar G, Jajapuram SD, Mohamed A, et al. Bilateral advanced (group D or E) intraocular retinoblastoma: Outcomes in 72 Asian Indian patients. Eye (Lond) 2019;33:1297-304.  Back to cited text no. 19
Weintraub N, Reshef N, Pe'er J, Frenkel S, Rot I, Shoshani N, et al. The impact of monocular vision on motor function and quality of life in survivors of retinoblastoma. Pediatr Blood Cancer 2019;66:e27623.  Back to cited text no. 20
Abramson DH, Fabius AW, Issa R, Francis JH, Marr BP, Dunkel IJ, et al. Advanced unilateral retinoblastoma: The impact of ophthalmic artery chemosurgery on enucleation rate and patient survival at MSKCC. PLoS One 2015;10:e0145436.  Back to cited text no. 21
Warsy AS, Al-Jaser MH, Albdass A, Al-Daihan S, Alanazi M. Is consanguinity prevalence decreasing in Saudis? A study in two generations. Afr Health Sci 2014;14:314-21.  Back to cited text no. 22
Hoodfar E, Teebi AS. Genetic referrals of Middle Eastern origin in a western city: Inbreeding and disease profile. J Med Genet 1996;33:212-5.  Back to cited text no. 23
el-Hazmi MA, al-Swailem AR, Warsy AS, al-Swailem AM, Sulaimani R, al-Meshari AA. Consanguinity among the Saudi Arabian population. J Med Genet 1995;32:623-6.  Back to cited text no. 24
Eng C, Li FP, Abramson DH, Ellsworth RM, Wong FL, Goldman MB, et al. Mortality from second tumors among long-term survivors of retinoblastoma. J Natl Cancer Inst 1993;85:1121-8.  Back to cited text no. 25
Wong FL, Boice JD Jr., Abramson DH, Tarone RE, Kleinerman RA, Stovall M, et al. Cancer incidence after retinoblastoma. Radiation dose and sarcoma risk. JAMA.1997;278:1262-7.  Back to cited text no. 26
Kim JY, Park Y. Treatment of retinoblastoma: The role of external beam radiotherapy. Yonsei Med J 2015;56:1478-91.  Back to cited text no. 27
Abramson DH, Shields CL, Munier FL, Chantada GL. Treatment of retinoblastoma in 2015: Agreement and disagreement. JAMA Ophthalmol 2015;133:1341-7.  Back to cited text no. 28
Alsharif HH, Maktabi A. Histopathological Characteristics and Classification for Prognostic Indicators. Retinoblastoma, Past, Present and Future: IntechOpen. Avaialble from: https://www.intechopen.com/books/retinoblastoma-past-present-and-future/histopathological-characteristics-and-classification-for-prognostic-indicators. [Last accessed 20-05-2020]  Back to cited text no. 29
Shields CL, Shields JA, Baez K, Cater JR, De Potter P. Optic nerve invasion of retinoblastoma. Metastatic potential and clinical risk factors. Cancer 1994;73:692-8.  Back to cited text no. 30
Heinrich T, Messmer EP, Höpping W, Havers W, Sauerwein W. Risk of metastasis in retinoblastoma. Klin Monbl Augenheilkd 1991;199:319-24.  Back to cited text no. 31
Chantada GL, Dunkel IJ, Antoneli CB, de Dávila MT, Arias V, Beaverson K, et al. Risk factors for extraocular relapse following enucleation after failure of chemoreduction in retinoblastoma. Pediatr Blood Cancer 2007;49:256-60.  Back to cited text no. 32


  [Figure 1], [Figure 2], [Figure 3]

  [Table 1], [Table 2]


    Similar in PUBMED
   Search Pubmed for
   Search in Google Scholar for
 Related articles
    Access Statistics
    Email Alert *
    Add to My List *
* Registration required (free)  

  Materials and Me...
  In this article
Article Figures
Article Tables

 Article Access Statistics
    PDF Downloaded125    
    Comments [Add]    

Recommend this journal