Selective ophthalmic artery infusion of chemotherapy for advanced intraocular retinoblastoma: initial experience with 17 tumors

Clinical article

Restricted access

Object

Retinoblastoma is the most common ocular neoplasm in children. Left untreated it spreads to the brain via the optic nerve. Traditional therapy is enucleation, and while this procedure is still the most common treatment worldwide, modern eye-preserving therapies can often spare the globe. However, patients with retinoblastoma often present in advanced stages of the disease when these globe-preserving strategies are often insufficient to prevent enucleation. In these challenging cases, direct infusion of chemotherapy into the ophthalmic artery has been attempted to achieve tumor control. The authors' aim in this study was to report on their initial experience with and clinical results for this approach.

Methods

The authors prospectively collected data on all cases of retinoblastoma treated with selective intraophthalmic melphalan at Bascom Palmer Eye Institute. All cases were classified as International Intraocular Retinoblastoma Classification (IIRC) Group D or Reese-Ellsworth Group Vb, had not responded to aggressive multimodal therapy consisting of chemotherapy and focal consolidating laser therapy, and were pending enucleation. Using digital subtraction angiography, a microcatheter was navigated under roadmap guidance into the ophthalmic artery, and melphalan was infused over 40 minutes. Early in the series, patients were treated with 3 or 5 mg of melphalan, but after low response rates occurred all eyes were treated with 7.5 mg of melphalan. All patients were examined with funduscopy while under anesthesia 3 weeks after treatment and every 3 months thereafter. Patients with persistent disease were retreated with repeat infusions of melphalan.

Results

Twenty-six procedures were performed to treat 17 tumors in 15 patients. Successful cannulation of the ophthalmic artery was achieved in all cases. The follow-up ranged from 3 to 12 months, with a mean of 8.6 months. Overall, 76% of the tumors responded to therapy and these cases were spared enucleation. The average number of treatments was 1.5 per tumor. Of the responders, 54% responded to a single dose of melphalan. Treatment with the higher dose of 7.5 mg up front was associated with a lower enucleation rate (0% vs 36%) as compared with the lower starting dose. Delayed vitreous hemorrhage occurred after 4 (15%) of 26 treatments, and these cases were treated with enucleation.

Conclusions

In this challenging group of advanced retinoblastomas refractory to aggressive multimodal therapy, virtually 100% of eyes are generally enucleated. In contrast, the authors' protocol of infusing melphalan directly into the ophthalmic artery led to a dramatic decrease in the enucleation rate to 23.5%. While it is now the treatment of choice for refractory retinoblastoma at their center, its role in less advanced disease remains to be elucidated.

Abbreviations used in this paper: ICA = internal carotid artery; IIRC = International Intraocular Retinoblastoma Classification.

Article Information

Address correspondence to: Eric C. Peterson, M.D., M.S., Lois Pope Life Center, 1095 NW 14th Terrace, 2nd Floor, Miami, Florida 33136. email: ececala@gmail.com.

Please include this information when citing this paper: published online February 4, 2011; DOI: 10.3171/2011.1.JNS10466.

© AANS, except where prohibited by US copyright law.

Headings

Figures

  • View in gallery

    Funduscopic images obtained before treatment with intraophthalmic melphalan (upper) and 3 weeks after treatment (lower). Note the near-complete resolution of a large nasal retinoblastoma with clearing of all vitreous seeding.

  • View in gallery

    Selective ophthalmic artery angiogram showing filling of ophthalmic vessels without reflux of contrast into the ICA.

References

  • 1

    Abramson DHDunkel IJBrodie SEKim JWGobin YP: A phase I/II study of direct intraarterial (ophthalmic artery) chemotherapy with melphalan for intraocular retinoblastoma initial results. Ophthalmology 115:139814042008

  • 2

    Abramson DHGamell LSEllsworth RMKruger EFServodidio CATurner L: Unilateral retinoblastoma: new intraocular tumours after treatment. Br J Ophthalmol 78:6987011994

  • 3

    Berman ELDonaldson CEGiblin MMartin FJ: Outcomes in retinoblastoma, 1974–2005: the Children's Hospital, Westmead. Clin Experiment Ophthalmol 35:5122007

  • 4

    Blacklock JBWright DCDedrick RLBlasberg RGLutz RJDoppman JL: Drug streaming during intra-arterial chemotherapy. J Neurosurg 64:2842911986

  • 5

    Dedrick RL: Arterial drug infusion: pharmacokinetic problems and pitfalls. J Natl Cancer Inst 80:84891988

  • 6

    Dondey JCStaffieri SMcKenzie JDavie GElder J: Retinoblastoma in Victoria, 1976–2000: changing management trends and outcomes. Clin Experiment Ophthalmol 32:3543592004

  • 7

    Inomata MKaneko A: Chemosensitivity profiles of primary and cultured human retinoblastoma cells in a human tumor clonogenic assay. Jpn J Cancer Res 78:8588681987

  • 8

    Khelfaoui FValidire PAuperin AQuintana EMichon JPacquement H: Histopathologic risk factors in retinoblastoma: a retrospective study of 172 patients treated in a single institution. Cancer 77:120612131996

  • 9

    Kiribuchi M: Retrograde infusion of anti-cancer drugs to ophthalmic artery for intraocular malignant tumors. Nippon Ganka Gakkai Zasshi 70:182918331966

  • 10

    Linn Murphree A: Intraocular retinoblastoma: the case for a new group classification. Ophthalmol Clin North Am 18:4153viii2005

  • 11

    Lutz RJDedrick RLBoretos JWOldfield EHBlacklock JBDoppman JL: Mixing studies during intracarotid artery infusions in an in vitro model. J Neurosurg 64:2772831986

  • 12

    Mohri M: [The technique of selective ophthalmic arterial infusion for conservative treatment of recurrent intraocular retinoblastoma.]. Keio Igaku 70:6796871993. (Jpn)

  • 13

    Shields CLGorry TShields JA: Outcome of eyes with unilateral sporadic retinoblastoma based on the initial external findings by the family and the pediatrician. J Pediatr Ophthalmol Strabismus 41:1431492004

  • 14

    Shields CLMashayekhi AAu AKCzyz CLeahey AMeadows AT: The International Classification of Retinoblastoma predicts chemoreduction success. Ophthalmology 113:227622802006

  • 15

    Shields CLRamasubramanian ARosenwasser RShields JA: Superselective catheterization of the ophthalmic artery for intraarterial chemotherapy for retinoblastoma. Retina 29:120712092009

  • 16

    Shook DRBeaudet LMDoppman JL: Uniformity of intracarotid drug distribution with diastole-phased pulsed infusion. J Neurosurg 67:7267311987

  • 17

    Suzuki SKaneko A: Management of intraocular retinoblastoma and ocular prognosis. Int J Clin Oncol 9:162004

  • 18

    Yamane TKaneko AMohri M: The technique of ophthalmic arterial infusion therapy for patients with intraocular retinoblastoma. Int J Clin Oncol 9:69732004

TrendMD

Metrics

Metrics

All Time Past Year Past 30 Days
Abstract Views 105 105 13
Full Text Views 123 123 5
PDF Downloads 134 134 6
EPUB Downloads 0 0 0

PubMed

Google Scholar