Menu

  1. Home
  2. /
  3. Pediatric Ophthalmology–II
  4. /
  5. FP850 : Intra-arterial Chemotherapy in Intraocular Retinoblastoma management at a tertiary care Institute.

Share this post

Dr. Usha Singh, U05383, Dr. Deepak Bansal, Dr. Mangat R Dogra, Dr. Vivek Gupta

Abstract

Aim: To study the safety and efficacy of intra-arterial chemotherapy (IAC) in the management of intraocular retinoblastomas at a tertiary care institute.

Methods: Clinical data, international classification, treatment outcomes and complications were studied in patients with intraocular disease who underwent intraarterial chemotherapy.

Results: There were twelve patients (13 eyes) with average age of 18.25 months at presentation. Primary treatment was given in eight. Each eye received 1 to 3 cycles of IAC, using melphalan and/or topotecan. None had intracatheterization complications. Post IAC response of disease was evaluated in terms of tumor size, vitreous seeds, subretinal seeds, subretinal fluid and retinal detachment. Overall globe salvage rate was 84.6% at an average follow up of 19.5 months.

Conclusion: Intraarterial chemotherapy though technically challenging, offers a safe and effective treatment modality of retinoblastoma without the side effects of intravenous chemotherapy.

Introduction:

Intra-arterial chemotherapy (IAC) for retinoblastoma (RB), was first used in 1958, by administeringone injection of triethylenemelamine in the carotid artery which showed successful regression of the tumor.The purpose of IAC is to deliver concentrated chemotherapeutic drug into the eye and reduce its systemic toxicity. Later in 1987 the Japanese1delivered melphalan to the retinoblastoma eye via endovascular route after balloon occlusion of the distal internal carotid artery. With rapid advancement in endovascular techniques, this delivery became super selective in 2008 when Abramson et al2 did selective cannulation of the ophthalmic artery. Since then subsequent studies came up which concluded that IAC was safe, with globe salvage reaching 72-82% after primary IAC3,4.

Material and Methods:

This study was a retrospective, nonrandomized, interventional case series. The clinical data review of all retinoblastoma patients treated with IAC at the Retinoblastoma Clinic, Advanced Eye Center of PGIMER was done between November2013 and May 2017 was done.

IAC catheterization procedure was performed by the interventional neuro-radiologist in the intervention room under general anesthesia. Data was analysed for clinical findings, management, complications, and outcomes. All pre and post IAC treatments to the eye and patient were recorded. Pre IAC ocular examination under anesthesia was performed to the assess patient for laterality, tumor growth pattern, number of tumors per eye, international classification of RB, intraocular pressure (Schiotz tonometer), and status of anterior and posterior chamber involvement. Ultrasound MRI and fundus imaging was done for all patients to diagnose, asses and group and or stage the disease. Complete blood counts and basic coagulation tests were done at baseline and blood counts repeated after every IAC.Informed consent was taken after explaining the pros and cons of IAC. Post IAC examination with retinal drawings and imaging was done to assess the response of the tumor. Each tumor was measured for greatest basal diameter and thickness, associated retinal detachment, subretinal seeds, and vitreous seeds. Local treatment (photocoagulation, cryotherapy) was applied if indicated. Globe salvage was defined as preservation of the globe with control of disease. Loss of eye leading to enucleation was considered a failure.

 Results:

There were twelve patients (13 eyes) with average age of 18.25 months at presentation. There were equal number of males and females. Seven had unilateral disease, and none had family history of RB. Chief presenting complaint was white reflex in all. Duration of Symptoms ranged from 3 to 365 days (mean: 88.42 days).Six eyes had group D disease, 4 had group B, 2 had group C, 1 had group E and none had group A disease. Primary IAC was delivered to 4 eyes. Total 21 catheterisations were done of which 2 failed. Direct cannulation of ophthalmic artery ostium was done in 12. Other arterial routes used were internal maxillary artery in 4, middle meningeal artery in 2 and superficial temporal artery in 1. Each eye received 1 to 3 cycles of IAC, using melphalan and/or topotecan. Topotecan was given to two eyes in combination with melphalan. None had intra-catheterization complications.Group wise response and reduction of the tumour mass, vitreous seeds, subretinal seeds and retinal detachment was seen in majority (Table 1). Local side effects were seen in the form of choroidal atrophy in 4, lid edema in 2, cheek swelling in 1 and development of new tumours were seen after IAC in 3 patients. Post IAC additional treatment was received by 7 patients, of which 2 were enucleation.  The cause of enucleation in these 2 patients were poor response to IAC in one and development of multiple new tumours in another. Overall globe salvage rate was 84.6% at a follow-up of 19.5 (range 7-41) months.

Discussion:

Intraarterial chemotherapy is a newer endovascular technique in the armamentarium of retinoblastoma treatment modalities for achieving high globe salvage rates. With the current refinement of endovascular catheterisation, chemotherapeutic drug is directly delivered into the ophthalmic artery2. We retrospectively analysed the safety of this procedure and outcome in the treated eyes.

This study found response of the tumour and seeds when IAC is used as both primary and secondary treatment modality. Only one of the 4 patients receiving primary IAC had poor response, which ultimately led to enucleation of the eye. Melphalan being the most effective with a short half-life was used in all patients. The reduction in tumour mass, subretinal seeds, vitreous seeds and retinal detachment rates ranged from 75-100% in majority (76.9%). Over all globe salvage rate in this series was high(84.6%). Literature meta-analysis of IAC for retinoblastoma in non-duplicative studies in 757 eyes has found a success rate of 66%5. In case the catheterisation of ophthalmic artery is inappropriate or difficult due to anatomic variations, alternative retrograde approach has been used6. We used alternative arterial route via middle meningeal, internal maxillary and superficial temporal arteries in 7 of the 21 catheterisations. Systemic complications after IAC such as stroke and neurological complications have been reported, however they were nil in our study. Procedure related local complications were mild and seen in 54% of patients. Although literature does not address this issue, three eyes developed new lesions after IAC in our study.

The selection bias and moderate follow-up in our patient is a limitation. In order to study recurrence, metastasis and death longer follow-up is required as they can occur more than 5 years after treatment. Globe salvage is valuable after IAC only when it is achieved without major systemic complications and risk to life. We validate IAC in selective cases of retinoblastoma but until well- established indications are laid down; it should be used with caution.

References:

  1. Yamane T, Kaneko A, Mohri M. The technique of ophthalmic arterial infusion therapy for patients with intraocular retinoblastoma. Int J Clin Oncol. 2004;9:69-73.
  2. Abramson DH, Dunkel IJ, Brodie SE, Kim JW, Gobin YP. A phase I/II study of direct intraarterial (ophthalmic artery) chemotherapy with melphalan for intraocular retinoblastoma initial results. Ophthalmology. 2008;115:1398-404, 14041.
  3. Gobin YP, Dunkel IJ, Marr BP, Brodie SE, Abramson DH. Intra-arterial chemotherapy for the management of retinoblastoma: Four-year experience. Arch Ophthalmol. 2011;129:732-7.
  4. Shields CL, Manjandavida FP, Lally SE, Pieretti G, Arepalli SA, Caywood EH, et al. Intra-arterial chemotherapy for retinoblastoma in 70 eyes: Outcomes based on the international classification of retinoblastoma. Ophthalmology. 2014;121:1453-60.
  5. Yousef YA, Soliman SE, AstudilloPPP,DurairajP, Dimaras H,Chan HSL et al. Intra-arterial Chemotherapy for Retinoblastoma: A Systematic Review.JAMA Ophthalmol. 2016;134(5):584-591. doi:10.1001/jamaophthlmol.2016.0244
  6. Saglam M, Sarici A, Anagnostakou V, Yildiz B, Kocer N, Islak C et al.An alternative technique of the superselective catheterization of the ophthalmic artery for intra-arterial chemotherapy of the retinoblastoma: retrograde approach through the posterior communicating artery to the ophthalmic artery.2014;56: 751.

TABLE: 1 Clinical data of patients receiving Intrarterial chemotherapy

Case U/L or B/L ICRB Group Primary/ Secondary Before IAC Number of IAC Cycles Drug Dosage (mg; average dose in case of multiple cycles) Regression/ Response Globe salvage rate Yes/NO Recurrence
Reduction in tumour mass Vitreous seeds Sub retinal seeds RD
1 U/L E Primary – 1 Melphalan 4 75% 100% 100% 100% Yes No
2 B/L D1 Secondary VEC x 6 1 Melphalan 4 75% – 100% 100% No; enucleated New lesions after 6 months
3 B/L B Secondary VEC x 3 2 Melphalan 4 100% – – 100% Yes No
4 U/L D3 Primary – 1 Melphalan 4.2 <25% 0% 0% 0% No enucleated No
5 U/L B Secondary VEC x 3 2 Melphalan 4 >75% – – – Yes No
6 U/L C1 Secondary VEC x 3 1 Melphalan 4 100% – 100% – Yes No
7 U/L D1 Primary – 2 Melphalan 4.5 >75% – 50% 100% Yes No
8 U/L C1 Primary – 2 Melphalan 4.5 100% – 100% – Yes No
9 B/L D1 Secondary VEC x 4 2 Melphalan 5.5 >50% – 100% 100% Yes New lesions
10 B/L D1 Secondary VEC x 2 1 Melphalan 5.5 >75% – 100% – Yes No
11 U/L B Secondary VEC x 2 1 Melphalan 4 >80% – 80% – Yes New Lesion
12 B/L Right eye D2 Secondary VEC x 2 3 Melphalan+ Topotecan 5+0.2, 4+0.4 topotecan >75% – >80% >80% Yes No
Left eye B Secondary VEC x 2 2 Melphalan+ Topotecan 5+0.2, 4+0.4 topotecan >75% – – – Yes No
U/L: Unilateral, B/L: Bilateral, IAC: Intra‑arterial chemotherapy, VEC: Intravenous chemotherapy consisting of vincristine, etoposide, and carboplatin, RD: Retinal

detachment, ICRB: International Classification of Retinoblastoma

 

Leave a Comment