Journal of Pediatric Ophthalmology and Strabismus

Original Article 

Clinical Profile, Management, and Outcome of Retinoblastoma in Singapore

Fiona Pin Miao Lim, MBBS; Shui Yen Soh, MBBS, MRCPCH (UK); Jayant Venkatramani Iyer, MBBS, GDFM, MMed (Ophth); Ah Moy Tan, MBBS, MMed (Paeds), FRCP; Handa Swati, MBBS, FRCS (Glasg), MCI(NUS); Boon Long Quah, MBBS, MMed (Ophth), FRCS (Ed)

Abstract

Purpose:

To analyze the clinical manifestations and treatment outcomes for patients with retinoblastoma in Singapore from 1997 to 2010.

Methods:

Medical records of 51 patients (67 eyes) diagnosed as having retinoblastoma were analyzed. Data on laterality, genetics, presentation, disease severity, treatment, and prognosis were collected.

Results:

The mean age of presentation was 25.7 ± 19.9 months. Sixteen (31.4%) of the patients had bilateral disease, of whom 2 had an associated pineal tumor. Leukocoria was the most common sign. Two had metastasis at diagnosis. Only 3 patients (5.9%) had a family history. Using the International Intraocular Retinoblastoma Classification, 6.0% were Group A, 6.0% were Group B, 3.0% were Group C, 38.8% were Group D, and 49.2% were Group E. Chemotherapy and focal therapy were administered for 4 of 35 (12.9%) patients with unilateral retinoblastoma (50% had successful globe preservation) and 13 of 16 (81.3%) patients with bilateral retinoblastoma (42.3% had successful globe preservation). Overall, globe preservation was achieved in 100% of Groups A, B, and C, and 23.1% of Group D cases. The 5-year survival rate overall, for unilateral retinoblastoma, and for bilateral retinoblastoma was 91%, 97%, and 76% respectively.

Conclusion:

The overall 5-year survival rate is comparable to international data in most developed countries. However, most patients presented with advanced disease, making the rate of globe preservation lower than in some developed countries. Better education of the public and healthcare professionals may increase awareness and enable early detection of the disease.

[J Pediatr Ophthalmol Strabismus 2013;50:106–112.]

From Singapore National Eye Centre (FPML, JVI); and the Department of Paediatric Haematology/Oncology (SYS, AMT) and Ophthalmology Service (HS, BLQ), K.K. Women and Children’s Hospital, Singapore.

The authors have no financial or proprietary interest in the materials presented herein.

Address correspondence to Boon Long Quah, MBBS, MMed(Ophth), FRCS (Ed), Department of Paediatric Ophthalmology, K.K. Women and Children’s Hospital, 100 Bukit Timah Road, 229899 Singapore. E-mail: quah.boon.long@snec.com.sg

Received: June 27, 2012
Accepted: October 15, 2012
Posted Online: December 18, 2012

Abstract

Purpose:

To analyze the clinical manifestations and treatment outcomes for patients with retinoblastoma in Singapore from 1997 to 2010.

Methods:

Medical records of 51 patients (67 eyes) diagnosed as having retinoblastoma were analyzed. Data on laterality, genetics, presentation, disease severity, treatment, and prognosis were collected.

Results:

The mean age of presentation was 25.7 ± 19.9 months. Sixteen (31.4%) of the patients had bilateral disease, of whom 2 had an associated pineal tumor. Leukocoria was the most common sign. Two had metastasis at diagnosis. Only 3 patients (5.9%) had a family history. Using the International Intraocular Retinoblastoma Classification, 6.0% were Group A, 6.0% were Group B, 3.0% were Group C, 38.8% were Group D, and 49.2% were Group E. Chemotherapy and focal therapy were administered for 4 of 35 (12.9%) patients with unilateral retinoblastoma (50% had successful globe preservation) and 13 of 16 (81.3%) patients with bilateral retinoblastoma (42.3% had successful globe preservation). Overall, globe preservation was achieved in 100% of Groups A, B, and C, and 23.1% of Group D cases. The 5-year survival rate overall, for unilateral retinoblastoma, and for bilateral retinoblastoma was 91%, 97%, and 76% respectively.

Conclusion:

The overall 5-year survival rate is comparable to international data in most developed countries. However, most patients presented with advanced disease, making the rate of globe preservation lower than in some developed countries. Better education of the public and healthcare professionals may increase awareness and enable early detection of the disease.

[J Pediatr Ophthalmol Strabismus 2013;50:106–112.]

From Singapore National Eye Centre (FPML, JVI); and the Department of Paediatric Haematology/Oncology (SYS, AMT) and Ophthalmology Service (HS, BLQ), K.K. Women and Children’s Hospital, Singapore.

The authors have no financial or proprietary interest in the materials presented herein.

Address correspondence to Boon Long Quah, MBBS, MMed(Ophth), FRCS (Ed), Department of Paediatric Ophthalmology, K.K. Women and Children’s Hospital, 100 Bukit Timah Road, 229899 Singapore. E-mail: quah.boon.long@snec.com.sg

Received: June 27, 2012
Accepted: October 15, 2012
Posted Online: December 18, 2012

Introduction

Retinoblastoma is the most common primary intraocular tumor of childhood.1 It is also the most common eye cancer in Singapore in children younger than 15 years.2 Worldwide, the incidence is approximately 1 in 15,000 to 20,000 live births each year.3 It is highly malignant and the mortality rate reaches 99% if it is left untreated. However, with current treatment, less than 5% of these children succumb to the disease in industrialized nations with medical care, such as in the United States.3,4 In contrast, elsewhere in the developing world, a majority of the children present with advanced retinoblastoma and more than 50% die of the disease.4 Many authors have attributed poor survival in developing countries to late presentation, missed diagnosis, and high numbers that default treatment.5,6

The treatment trends for retinoblastoma have changed worldwide during the past two decades. Current treatment options include enucleation, chemotherapy, focal therapy (laser therapy/cryotherapy), radiotherapy, and intra-arterial chemotherapy.7,8 In recent years, there has been a move toward globe-preserving treatment. In the past two decades, many groups have demonstrated the efficacy of systemic chemoreduction combined with focal therapy in both unilateral and bilateral retinoblastoma with varying rates of success.7–16 However, in eyes with extensive retinoblastoma in which there is no hope for useful vision, enucleation remains the primary treatment of choice.4,7

We analyze the demographics, clinical profile, and treatment outcomes of patients in a tertiary care hospital in Singapore from 1997 to 2010.

Patients and Methods

The Department of Paediatric Ophthalmology and Paediatric Haematology/Oncology at K.K. Women’s and Children’s Hospital (KKH) serves as the tertiary center for retinoblastoma in Singapore and neighboring countries in the Southeast Asian region. The Singapore Childhood Cancer Registry is a national cancer registry that includes all children aged 15 years and younger who were diagnosed as having cancer.

Data were obtained from the Singapore Childhood Cancer Registry, hospital records with the disease diagnosis code “retinoblastoma,” and the Department of Paediatric Ophthalmology database. A retrospective chart review of all patients who were diagnosed as having retinoblastoma at KKH from January 1997 to September 2010 was performed.

Each of the eyes was classified according to the International Intraocular Retinoblastoma Classification (IIRC) and Tumor, Node, Metastases (TNM) classification. A detailed drawing of the fundus was made at each visit, indicating the location of tumors and vitreous seeding. All of the patients were evaluated by computed tomography or magnetic resonance imaging of the orbits.

Our treatment modalities consisted of chemotherapy, focal therapy, radiotherapy, and enucleation. In our center, globe salvaging treatment with chemotherapy, focal therapy, or both is offered to patients with bilateral disease and patients with IIRC Groups A, B, and C unilateral retinoblastoma. The chemotherapy regimen consisted of carboplatin, etoposide, and vincristine, given with or without high-dose cyclosporine for reversal of p-glycoprotein-mediated multi-drug resistance17–20 (Table 1). The chemotherapy regimen was repeated every 21 to 28 days for six cycles. Focal therapy (laser therapy or cryotherapy) is administered when the tumor is 2 disc diopters or less in size (IIRC Group A) or when there is significant reduction in tumor size after a few cycles of chemotherapy. All patients were followed up for at least 6 months after diagnosis.

Chemotherapy Regimen

Table 1: Chemotherapy Regimen

The age at diagnosis and presentation, severity of eye disease according to IIRC and TNM classification, retinoblastoma gene mutational analysis results, treatment given, and visual outcome and survival for each group were recorded. The statistical analysis was performed using SPSS software (version 13; SPSS, Inc., Chicago, IL).

Results

There were 57 patients with retinoblastoma seen at KKH from January 1997 to September 2010. Six had come only for a second opinion and did not receive any treatment here, excluding them from the study. Of the 51 patients included in the study, 37 were diagnosed and completed treatment and at least 6 months of follow-up at KKH, whereas 14 received only partial treatment or defaulted follow-up with us.

Demographics (Table 2)

We reviewed the patient records of the 51 patients (67 eyes). Thirty-two were Singaporeans and 19 were foreigners who were mostly from the Southeast Asian region. The median follow-up duration was 3 years (range: 0 to 13 years). Thirty-six (70.6%) were Chinese, 6 (11.8%) were Malay, 3 (5.9%) were Indian, and 6 (11.8%) were Other. Only 3 patients (5.9%) in our cohort had a family history of retinoblastoma. The mean age of presentation was 25.7 months (standard deviation = 19.9) for the entire cohort. The mean age of onset for bilateral disease was 15.4 months (standard deviation = 9.6) compared to 30.2 months (standard deviation = 21.4) for unilateral disease. Sixteen (31.4%) of the patients had bilateral disease, of whom 2 had associated pineal tumor detected on magnetic resonance imaging.

Patient Characteristics

Table 2: Patient Characteristics

Presenting Symptoms and Signs

Leukocoria was the most common presenting symptom (70.6%), followed by strabismus (17.6%), poor vision (15.7%), and red and painful eye (15.7%). In only 3 patients (5.9%), retinoblastoma was discovered on routine examination. The most common presenting sign was leukocoria in 44 patients (86.3%), followed by strabismus (17.6%). The median duration of symptoms before diagnosis was 6 weeks (range: 0 to 200 weeks). A majority (82.4%) of the symptoms were detected by family members. Two had metastasis at diagnosis: one had bone marrow metastasis, the other had metastasis to marrow, spine, and liver.

Pineal Tumor

For the 2 patients in our cohort with pineal tumor, both were Chinese female infants and did not have a family history of cancer. The first patient presented at 24 months of age with bilateral leukocoria. She was diagnosed as having bilateral advanced disease (IIRC Groups D and E) at presentation and responded poorly to chemotherapy, eventually requiring bilateral enucleation. This patient subsequently defaulted follow-up and eventually died of metastatic disease. The second patient presented at 14 months old with unilateral leukocoria. Although she was diagnosed as having bilateral advanced disease (IIRC Groups D and E) at presentation, she responded well to chemotherapy. Repeat brain magnetic resonance imaging after six cycles of chemotherapy revealed resolution of the pineal tumor. Although she eventually required unilateral enucleation, she recovered without any relapse to date (6 years after presentation).

Genetic Testing

Ten patients (19.6%) had retinoblastoma gene testing, of whom 4 had germline mutation, 5 had non-germline mutation, and 1 was a mosaic. Only 3 patients with bilateral disease had retinoblastoma gene testing and all had germline mutation. Of the 7 patients with unilateral disease who underwent retinoblastoma gene testing, only 1 had germline mutation.

IIRC (Table 3)

The IIRC of the eyes at presentation for unilateral disease were as follows: 2.9% Group A, 2.9% Group B, 0% Group C, 45.7% Group D, and 48.6% Group E. None of the patients with unilateral retinoblastoma had extraocular disease at presentation. The IIRC of the eyes at presentation for bilateral disease were as follows: 9.4% Group A, 9.4% Group B, 6.3% Group C, 31.3% Group D, and 43.8% Group E. Seven of the patients had bilateral advanced disease (IIRC Groups D and E) at time of diagnosis. Two of the patients with bilateral retinoblastoma had extraocular disease at presentation.

IIRC

Table 3: IIRC

Treatment Outcome (Figure 1)

Primary enucleation was the treatment of choice in 31 patients (88.6%) with unilateral retinoblastoma, all of whom were IIRC Groups D and E. Treatment to preserve the eye with focal therapy and systemic chemotherapy was attempted in 4 patients with unilateral retinoblastoma and was successful in 2 patients (1 IIRC Group A and 1 IIRC Group B); the other 2 (both IIRC Group D) required eventual enucleation.

Treatment Outcome

Figure 1: Treatment Outcome

Of the 16 patients with bilateral retinoblastoma, 13 were treated with chemoreduction first. Two patients with advanced disease in 1 eye and early disease (IIRC Group A) in the other eye did not receive chemotherapy. Both had enucleation of one eye and focal therapy of the other eye. Neither suffered recurrence following focal therapy to date (5 and 7 years posttreatment, respectively). The third patient had bilateral advanced disease (IIRC Group E) with no hope of useful vision at presentation. The parents declined chemotherapy or radiotherapy and opted for bilateral enucleation instead.

Of the 13 patients who underwent chemotherapy as initial treatment, 9 had eventual enucleation of one eye. One patient had bilateral enucleation in view of poor response to chemotherapy and bilateral advanced disease (IIRC Group E) with pinealoblastoma. The parents declined radiotherapy. The remaining three died before enucleation was done, two from advanced metastatic retinoblastoma and the other from severe sepsis secondary to chemotherapy.

Only 2 patients in our cohort, both with extensive extraocular disease, received radiotherapy. Of the 26 eyes that received globe-preserving treatment in patients with bilateral retinoblastoma, globe preservation was achieved in 11 eyes (42.3%) (Figure 2).

Treatment and outcome of retinoblastoma in Singapore.

Figure 2. Treatment and outcome of retinoblastoma in Singapore.

Survival Outcome

The overall 5-year survival rate for retinoblastoma in our cohort was 91%. The 5-year survival rate for unilateral and bilateral retinoblastoma was 97% and 76%, respectively (Figure 3).

Kaplan–Meier survival rates of patients. Rb = retinoblastoma.

Figure 3. Kaplan–Meier survival rates of patients. Rb = retinoblastoma.

Four patients with bilateral retinoblastoma died. All had bilateral advanced disease at presentation, including two who presented with metastatic disease. The first two were foreign patients who defaulted treatment and follow-up and returned with extensive extraocular and metastatic disease refractory to chemotherapy and radiotherapy. The third patient had an associated pinealoblastoma that did not respond to chemotherapy. The latter had also defaulted follow-up and returned with metastatic disease. The last patient with metastatic disease to the marrow at presentation died of severe sepsis secondary to chemotherapy.

One patient with multifocal unilateral disease defaulted treatment initially and presented with advanced unilateral disease with invasion of the optic nerve when she returned. She eventually underwent enucleation but died of tumor metastasis and poor response to systemic chemotherapy.

Discussion

The estimated annual incidence of retinoblastoma worldwide is approximately 1 in 15,000 newborns.4 In Singapore, the average annual incidence is approximately 2.4 cases per 1 million children.21 Timely diagnosis of retinoblastoma is important because retinoblastoma detected early is highly curable. In Singapore, the median time from recognition of symptoms to diagnosis is 6 weeks. The mean age of diagnosis is 26 months in Singapore, compared to 18 months in America,22 25 months in Turkey,23 and 21.2 months in Korea.9 As in many other studies,1,8,9,24 the patients with unilateral retinoblastoma presented later than those with bilateral retinoblastoma. In our study, retinoblastoma occurred almost equally in males and females.

The most common symptom for which patients sought further treatment in our study was leukocoria (70.6%). In an earlier report by Aung et al., leukocoria was also the most common presenting symptom seen in 50% of the patients.25 In Taiwan and Korea, leukocoria was also the most common presenting symptom seen.9,24 However, this is a late sign because leukocoria suggests that there is a large tumor.

The goals of management of retinoblastoma are to save the life of the child, to salvage the eye, and to salvage the vision. It is of interest to note that even in Singapore, one of the most advanced industrialized nations in Southeast Asia, enucleation is the most frequent form of treatment modality employed. This can be explained by the fact that our patients with unilateral retinoblastoma often present late with advanced intraocular disease (IIRC Groups D and E) and enucleation is the best treatment option without the side effects of chemotherapy. Chemotherapy was mainly attempted in patients with IIRC Groups A, B, and C in unilateral retinoblastoma. This is in contrast to some other countries,8,9 whereby chemoreduction is attempted in all patients with unilateral retinoblastoma with IIRC Group D. For bilateral retinoblastoma, chemotherapy is the primary treatment for most patients. Only two patients had radiotherapy in our study due to extensive disease not responsive to chemotherapy. Only 19.6% of our patients had retinoblastoma gene testing, compared to 97% reported by Mallipatna et al. in Toronto.8 This can be explained by the high cost of the test deterring parents from taking it. We are currently working on finding means to lower the cost of retinoblastoma gene testing to make it more affordable for our patients. We also routinely make an effort to check the retinas of our patients’ families.

The 5-year overall survival rate of retinoblastoma was 91% in our study, which is slightly lower than that reported in Europe (95%)26,27 and the United States (> 96%),22 but higher than in most parts of Asia, where the overall survival rate ranges from 35% to 86%.6,23,24,28,29 The lower survival rate compared to Western countries could be attributed to the late stage of diagnosis and the high number of patients who defaulted treatment and follow-up. Differences in cultural beliefs leading to the choice of traditional alternative medication over Western medicine in our region and a large proportion of non-Singaporean residents who had to travel to seek medical follow-up contributed to the high numbers who defaulted follow-up and treatment in our study. There has to be greater education and awareness of the disease for parents.

Globe preservation with focal therapy and chemotherapy for both unilateral and bilateral retinoblastoma was achieved in 100% (4 of 4) of Group A, 100% (4 of 4) of Group B, 100% (2 of 2) of Group C, and 23.1% (6 of 26) of Group D cases. Our rate of globe preservation for Groups A, B, and C is comparable to that in most developed countries,9–13 but is lower for Group D. The lower rates of globe preservation can be attributed to the lack of response to standard chemotherapy used in Western countries in our Southeast Asian patients and lower threshold for enucleation in our center after weighing the risks and benefits of chemotherapy. A recent study done in Korea showed success in globe preservation in 66.7% of Group C and 26.7% in Group D cases, but the overall 5-year cumulative survival rate in that study was 35%.9

In view of poor outcome with late presentation and frequent default from follow-up, our study illustrates the importance of early diagnosis and treatment. Compliance with treatment and follow-up is crucial in treatment success.

Our study has its limitations, such as a retrospective design in a single tertiary center, the small sample size, the high rate of default on follow-up from foreign patients, and a non-uniform chemotherapy regimen over 13 years. Currently, we are moving toward a uniform systemic chemotherapy treatment protocol for intraocular retinoblastoma.

A large proportion of the children with retinoblastoma in our study presented with advanced retinoblastoma at the time of diagnosis. Because early stage disease is more easily treated compared to advanced disease, better education of the public and healthcare professionals may increase awareness and enable early detection of disease. Compliance with treatment and follow-up is also essential to improve outcome and possibly long-term survival rate.

References

  1. Mahoney MC, Burnett WS, Majerovics A, Tanenbaum H. The epidemiology of ophthalmic malignancies in New York State. Ophthalmology. 1990;97:1143–1147.
  2. Lee SB, Au Eong KG, Saw SM, Chan TK, Lee HP. Eye cancer incidence in Singapore. Br J Ophthalmol. 2000;84:767–770 doi:10.1136/bjo.84.7.767 [CrossRef] .
  3. Shields CL, Shields JA. Diagnosis and management of retinoblastoma. Cancer Control. 2004;11:317–327.
  4. Shields CL, Meadows AT, Leahey AM, Shields JA. Continuing challenges in the management of retinoblastoma with chemoreduction. Retina. 2004;24:849–862 doi:10.1097/00006982-200412000-00003 [CrossRef] .
  5. Bekibele CO, Ayede AI, Asaolu OO, Brown BJ. Retinoblastoma: the challenges of management in Ibadan, Nigeria. J Pediatr Hematol Oncol. 2009;31:552–555 doi:10.1097/MPH.0b013e31819c5275 [CrossRef] .
  6. Chantada GL, Qaddoumi I, Canturk S, et al. Strategies to manage retinoblastoma in developing countries. Pediatr Blood Cancer. 2011;56:341–348 doi:10.1002/pbc.22843 [CrossRef] .
  7. Shields CL, Shields JA. Retinoblastoma management: advances in enucleation, intravenous chemoreduction, and intra-arterial chemotherapy. Curr Opin Ophthalmol. 2010;21:203–212 doi:10.1097/ICU.0b013e328338676a [CrossRef] .
  8. Mallipatna AC, Sutherland JE, Gallie BL, Chan H, Heon E. Management and outcome of unilateral retinoblastoma. J AA-POS. 2009;13:546–550 doi:10.1016/j.jaapos.2009.09.004 [CrossRef] .
  9. Chung SE, Sa HS, Yoo KH, Sung KW, Harn DI. Clinical manifestations and treatment of retinoblastoma in Korea. Br J Ophthalmol. 2008;92:1180–1184 doi:10.1136/bjo.2008.140046 [CrossRef]
  10. Shields CL, De Potter P, Himelstein BP, Shields JA, Meadows AT, Maris JM. Chemoreduction in the initial management of intraocular retinoblastoma. Arch Ophthalmol. 1996;114:1330–1338 doi:10.1001/archopht.1996.01100140530002 [CrossRef] .
  11. Greenwald MJ, Strauss LC. Treatment of intraocular retinoblastoma with carboplatin and etoposide chemoreduction. Ophthalmology. 1996;103:1989–1997.
  12. Friedman DL, Himelstein B, Shields CL, et al. Chemoreduction and local ophthalmic therapy for intraocular retinoblastoma. J Clin Oncol. 2000;18:12–17.
  13. Beck MN, Balmer A, Dessing C, Pica A, Munier F. First-line chemoreduction with local treatment can prevent external-beam irradiation and enucleation in low-stage intraocular retinoblastoma. J Clin Oncol. 2000;18:2881–2887.
  14. Shields CL, Honavar SG, Meadows AT, et al. Chemoreduction plus focal therapy for retinoblastoma: factors predictive of need for treatment with external beam radiotherapy or enucleation. Am J Ophthalmol. 2002;133:657–664 doi:10.1016/S0002-9394(02)01348-X [CrossRef] .
  15. Shields CL, Honavar SG, Meadows AT, Shields JA, Demirci H, Naduvilath TJ. Chemoreduction for unilateral retinoblastoma. Arch Ophthalmol. 2002;120:1653–1658 doi:10.1001/archopht.120.12.1653 [CrossRef] .
  16. Brichard B, De Bruycker JJ, De Potter P, Nevan B, Vermylen C, Cornu G. Combined chemoreduction and local treatment in the management of intraocular retinoblastoma. Med Pediatr. 2002;38:411–415 doi:10.1002/mpo.1355 [CrossRef] .
  17. Gallie BL, Budning A, DeBoer G, et al. Chemotherapy with focal therapy can cure intraocular retinoblastoma without radiotherapy. Arch Ophthalmol. 1996;114:1321–1328 doi:10.1001/archopht.1996.01100140521001 [CrossRef] .
  18. Chan HS, DeBoer G, Thiessen JJ, et al. Combining cyclosporin with chemotherapy controls intraocular retinoblastoma without requiring radiation. Clin Cancer Res. 1996;2:1499–1508.
  19. Shields CL, Honavar SG, Meadows AT, et al. Chemoreduction plus focal therapy for retinoblastoma: factors predictive of need for treatment with external beam radiotherapy or enucleation. Am J Ophthalmol. 2002;133:657–664 doi:10.1016/S0002-9394(02)01348-X [CrossRef] .
  20. Chan HS, Gallie BL, Munier FL, Beck Popovic M. Chemotherapy for retinoblastoma. Ophthalmol Clin North Am. 2005;18:55–63 doi:10.1016/j.ohc.2004.11.002 [CrossRef] .
  21. Saw SM, Tan N, Lee SB, Au Eong KG, Chia KS. Incidence and survival characteristics of retinoblastoma in Singapore from 1968–1995. J Pediatr Ophthalmol Strabismus. 2000;37:87–93.
  22. Broaddus E, Topham A, Singh AD. Survival with retinoblastoma in the USA: 1975–2004. Br J Ophthalmol. 2009;93:24–27 doi:10.1136/bjo.2008.143842 [CrossRef] .
  23. Ozkan A, Pazarli H, Celkan T, et al. Retinoblastoma in Turkey: survival and clinical characteristics, 1981–2004. Pediatr Int. 2006;48:369–373 doi:10.1111/j.1442-200X.2006.02223.x [CrossRef] .
  24. Chen YH, Lin HY, Hsu WM, Lee SM, Cheng CY. Retinoblastoma in Taiwan: incidence and survival characteristics from 1979 to 2003. Eye (Lond). 2010;24:318–322 doi:10.1038/eye.2009.80 [CrossRef] .
  25. Aung L, Chan YH, Yeoh EJ, Tan PL, Quah TC. Retinoblastoma: a recent experience at the National University Hospital, Singapore. Ann Acad Med Singapore. 2009;38:693–698.
  26. Sanders BM, Draper GJ, Kingston JE. Retinoblastoma in Great Britain, 1969–80: incidence, treatment, and survival. Br J Ophthalmol. 1988;72:576–583 doi:10.1136/bjo.72.8.576 [CrossRef] .
  27. Moll AC, Kuik DJ, Bouter LM, et al. Incidence and survival of retinoblastoma in The Netherlands: a register based study, 1862–1995. Br J Ophthalmol. 1997;81:559–562 doi:10.1136/bjo.81.7.559 [CrossRef] .
  28. Su WW, Kao AY. Retinoblastoma in Taiwan: the effect of a government-sponsored national health insurance program on the treatment and survival of patients with retinoblastoma. J Pediatr Ophthalmol Strabismus. 2006;43:358–362.
  29. The Committee for the National Registry of Retinoblastoma. Survival rate and risk factors for patients with retinoblastoma in Japan. Jpn J Ophthalmol. 1992;36:121–131.

Chemotherapy Regimen

RegimenDrug Doses
VECIntravenous vincristine 1.5 mg/m2 (0.05 mg/kg for patients younger than 36 months; maximum 2 mg) slow bolus on day 1. Intravenous etoposide 150 mg/m2 (5 mg/kg for patients younger than 36 months) in 150 mL/m2 dextrose-saline over 1 hour on day 1. Intravenous carboplatin 560 mg/m2/dose (18.6 mg/kg for children younger than 36 months) in 120 mL/m2 of dextrose-saline over 1 hour on days 1 and 2.
VEC + CSAIntravenous cyclosporine 33 mg/kg in 66 mL/kg 0.9% saline on days 1 and 2, with 11 mg/kg given 1 hour before and 22 mg/kg given over 2 hours after chemotherapy. Intravenous carboplatin 28 mg/kg diluted to 2 mg/mL in 5% dextrose given over 30 minutes on day 1. Intravenous vincristine 0.025 mg/kg for cycle 1 and 0.05 mg/kg (maximum 2 mg per cycle) for subsequent cycles given as slow bolus on day 2. Intravenous etoposide 12 mg/kg diluted to 0.4 mg/mL in 0.9% saline given over 25 minutes, immediately after vincristine on day 2, or intravenous teniposide 230 mg/m2 (7.7 mg/kg for patients younger than 36 months) in 330 mL/m2 0.9% saline over 15 minutes.

Patient Characteristics

CharacteristicNo.
Gender, no (%)
  Male25 (49)
  Female26 (51)
Laterality, no (%)
  Unilateral35 (68.6)
    Left20 (57.9)
    Right15 (42.7)
  Bilateral16 (31.4)
Race, no. (%)
  Chinese36 (70.6)
  Malay6 (11.8)
  Indian3 (5.9)
  Othera6 (11.8)
Family history, no (%)
  Yes3 (5.9)
  No48 (94.1)
Mean age at diagnosis (months)
  Unilateral30.2
  Bilateral15.4
  All25.7
Presenting symptoms (%)
  Leukocoria70.6
  Strabismus17.6
  Poor vision15.7
  Red painful eye15.7
  Otherb15.7
Presenting signs (%)
  Leukocoria86.3
  Strabismus17.6
  Otherc39.2

International Intraocular Retinoblastoma Classification (IIRC)

IIRCUnilateral DiseaseBilateral Disease
Group A1 (2.9%)3 (9.4%)
Group B1 (2.9%)3 (9.4%)
Group C0 (0%)2 (6.3%)
Group D16 (45.7%)10 (31.8%)
Group E17 (48.6%)14 (43.8%)
Total35 (100%)32 (100%)

10.3928/01913913-20121211-01

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