Intraarterial chemotherapy for retinoblastoma in low and lower-middle-income countries – Can we break the barriers? : Indian Journal of Ophthalmology

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Intraarterial chemotherapy for retinoblastoma in low and lower-middle-income countries – Can we break the barriers?

Honavar, Santosh G

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Indian Journal of Ophthalmology 71(2):p 325-326, February 2023. | DOI: 10.4103/IJO.IJO_227_23
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“The chance for a cure, the chance to live, should not be an accident of geography.”- HRH Princess Dina Mired

Retinoblastoma is more common in low and lower-middle-income countries (LLMC) and manifests at a relatively more advanced stage with suboptimal outcome.[1,2] The introduction of intravenous chemotherapy (IVC) three decades ago heralded a paradigm change in the management of retinoblastoma.[3] The simple and cost-effective IVC protocol using commonly available drugs could be easily adapted by LLMC. This, coupled with the emergence of ocular oncology as a potent subspecialty with rapid percolation of higher training standards, well-trained ophthalmic onco-pathologists, and supportive pediatric oncologists in LLMC, with access to focal therapy, brachytherapy, and safe enucleation, and understanding of the indications and significance of adjuvant therapy resulted in life, eye, and vision salvage comparable to the developed world.[3]

This temporary state of bliss was busted by intraarterial chemotherapy (IAC), a technically demanding and relatively expensive form of treatment.[4] Primary treatment with one-to-three drug super-selective ophthalmic artery IAC has currently emerged as the standard of care for advanced unilateral retinoblastoma.[4] Acceptable expanded indications for IAC include bilateral retinoblastoma and secondary IAC in refractory or recurrent tumors following IVC.[4] There is general agreement that IAC shortens the treatment time, provides better outcomes in group D and E retinoblastoma [Fig. 1] and has a beneficial role as salvage therapy.[4] IAC has lower systemic morbidity, thus minimizing the need for hematological support while the child is under active management for retinoblastoma and improving the overall quality of life.[4] This issue of the Indian Journal of Ophthalmology carries an article that shows the effectiveness of three-drug secondary IAC in salvaging about 50% of eyes.[5]

Figure 1:
Fundus image of a 2-year-5-month-old child with group D retinoblastoma at presentation (a) and the outcome with complete regression following 3 cycles of primary super-selective ophthalmic artery intraarterial chemotherapy with a combination of topotecan, carboplatin, and melphalan

Poor accessibility and affordability build barriers and breed inequity

About 90% of children with cancer live in LLMC.[6,7] Childhood cancer is the fifth leading cause of death amongst 5 to 14-year-olds in India.[6,8] India has a meager allocation of 1.3% of the gross domestic product on public health care.[6] Private health services are expensive and childhood cancer is managed mostly in advanced tertiary settings in major cities. All these barriers cumulatively result in about 70% of the population being denied of timely access and optimal management.[6,9]

The cost of care can be direct (actual cost of delivering the intervention) and indirect (lost wages to the caregivers and other potential opportunity costs). The direct cost of care for retinoblastoma depends on several factors – the cost of drugs, procedures, professional fees, and hospitalization. The cost of care is borne by the family, employer, insurer, government, a combination of the above or may be supported by the charity. The impact of the direct cost of care on the families depends on prevailing healthcare policies, insurance coverage, admissibility of socialized medicine, etc., For most families in the LLMC, the cost of care can be daunting enough to push them into a situation of financial toxicity and distress.

The cost of care for retinoblastoma varies widely across the world and in each country, there is variation across points of service delivery. For example, the cost of enucleation in India ranges from INR 10000 to 50000 (USD 120-600), IVC from INR 5000 to 20000 (USD 60-240), and IAC from INR 80000 to 150000 (USD 1000 – 2000). A study from China reported that the average direct cost for retinoblastoma treatment was USD 9422 ± 3709 per patient during the first year.[10] Of this amount, chemotherapy-related expenses were USD 2991 ± 3083, transportation and accommodation cost USD 2560 ± 1348), general anesthesia accounted for USD 1081 ± 2,711 and enucleation was USD 900 ± 1015.[10] The cost for IAC and chemotherapy drugs was USD 1224 ± 754 and USD 517 ± 134 respectively.[10] In the United States, the cost of care is significantly higher – about USD 10000 for examination under anesthesia, USD 10000 for focal laser, USD 17000 per session of IVC, USD 40000 for each IAC, and USD 48000 for enucleation.[11] The per-session cost of IAC is higher than IVC across the world, but the disparity is very large in India.

While retinoblastoma is generally managed by ophthalmologists trained in ocular oncology in the setting of tertiary care stand-alone eye hospitals (mostly with in-house facilities for IVC), IAC is typically performed at large multi-specialty healthcare facilities with vascular intervention suite (VIS), and trained interventional radiologists, which escalates the cost of care. It is estimated that fewer than 10% of children with retinoblastoma in India receive IAC. While most of the retinoblastoma treatment centers have access to excellent interventional neuroradiologists, the cost of the procedure seems to be the barrier to the use of IAC even in deserving clinical situations.

How can we make IAC accessible?

The cost of IAC includes the cost of facility hospital admission, VIS, professional fees, cost of drugs, and hardware. In India, the cost of the microcatheter is high and contributes to a major part of IAC expenditure. The following measures may improve physical accessibility to make the logistics of IAC smooth and address financial affordability to bring down the cost of care:

  1. Establish Regional IAC Centers: Designation of VIS in major cities and regions with trained manpower to perform IAC as per the standard protocol as Retinoblastoma IAC Centers – these could be the IAC hubs, spokes being ocular oncologists in the region.
  2. Bring down the cost of the hardware: a. Microcatheters to be considered as life- and eye-saving devices and exempted from customs duty and goods and services tax; b. Cap on trade margin for microcatheters; and c. Explore the possibility of indigenous manufacture of high-quality pediatric microcatheters.
  3. Financial support: a. Inclusion of IAC for retinoblastoma in government-supported health schemes; b. Insurance coverage for IAC; c. Support for deserving families through Prime Minister’s National Relief Fund, Rashtriya Arogya Nidhi, Health Minister’s Cancer Patient Fund, and Chief Minister’s Relief Fund; and d. Augmentation of support by non-governmental organiztions.

All these measures could be comprehensively addressed as part of the National Policy for Childhood Cancers, a much-needed initiative to provide optimal care and outcome for this vulnerable group. The chance to cure should not be an accident of geography but the result of a concerted effort to transcend the barriers and bring equity into childhood cancer care.

“We need to change the narrative. Health is not a cost. It is an investment. Investing in health is the most important thing a country can do for the future of its population.” - Dr. Salomón Chertorivski


1. Global Retinoblastoma Study Group. The Global Retinoblastoma Outcome Study:A prospective, cluster-based analysis of 4064 patients from 149 countries Lancet Glob Health 2022;10:e1128–40.
2. Wong ES, Choy RW, Zhang Y, Chu WK, Chen LJ, Pang CP, et al. Global retinoblastoma survival and globe preservation:A systematic review and meta-analysis of associations with socioeconomic and health-care factors Lancet Glob Health 2022;10:e380–9.
3. Rao R, Honavar SG. Retinoblastoma Indian J Pediatr 2017;84:937–44.
4. Manjandavida FP, Stathopoulos C, Zhang J, Honavar SG, Shields CL. Intra-arterial chemotherapy in retinoblastoma-A paradigm change Indian J Ophthalmol 2019;67:740–54.
5. Kumari N, Jain N, Saboo S, Parthasarathy R, Gupta V, Mahajan A, et al. Intra-arterial chemotherapy in refractory and advanced intraocular retinoblastoma Indian J Ophthalmol 2023;71:436–43.
6. Faruqui N, Bernays S, Martiniuk A, Abimbola S, Arora R, Lowe J, et al. Access to care for childhood cancers in India:Perspectives of health care providers and the implications for universal health coverage BMC Public Health 2020;20:1641.
7. Bhakta N, Force LM, Allemani C, Atun R, Bray F, Coleman MP, et al. Childhood cancer burden:A review of global estimates Lancet Oncol 2019;20:e42–53.
8. Institute for Health Metrics and Evaluation (IHME). GBD Compare. Seattle: University of Washington, IHME; 2017.
9. Rudrappa S, Agarkhed DV, Vaidya SS. Healthcare systems: India Ratliff J, Albert TJ, Cheng J, Knightly J Quality Spine Care: Healthcare Systems, Quality Reporting, and Risk Adjustment. Cham: Springer International Publishing; 2019. 211–24.
10. Zhou Y, Cai S, Jin M, Jiang C, Xu N, Duan C, et al. Economic burden for retinoblastoma patients in China J Med Econ 2020;23:1553–7.
11. Aziz HA, Lasenna CE, Vigoda M, Fernandes C, Feuer W, Aziz-Sultan MA, et al. Retinoblastoma treatment burden and economic cost:Impact of age at diagnosis and selection of primary therapy Clin Ophthalmol 2012;6:1601–6.
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