We previously described our initial experience with superselective ophthalmic artery delivery of chemotherapy for advanced retinoblastoma and emphasized that it was both effective and safe for both the patient and eye.1,2 In each of those cases, only 1 eye was treated with this novel technique. We now report on the first 4 patients with advanced (Reese-Ellsworth group V) bilateral disease in whom initial management was bilateral treatment accomplished during the same treatment session.
Four children with bilateral Reese-Ellsworth group V retinoblastomas (4 with bilateral Vb, 1 with Vb in one eye and Va in the fellow eye; international classification, C:4, D:1, and E:3) were initially treated with a superselective arterial infusion (ophthalmic artery) of chemotherapy and were followed up every 3 to 4 weeks with examinations while under anesthesia. The chemotherapy was delivered to both eyes in the same session by first passing a catheter into 1 ophthalmic artery and infusing chemotherapy, retracting the catheter back to the aorta, and then extending it into the fellow carotid artery and up into the fellow ophthalmic artery (tandem therapy). Focal therapy with laser hyperthermia (transpupillary thermotherapy) to small tumors and cryotherapy to intermediate tumors was subsequently performed (Figure).
Pretreatment and corresponding posttreatment fundus appearance. Transpupillary thermotherapy (TTT) laser and cryotherapy applications are listed for each eye.
There were 2 boys and 2 girls in the study group; their ages at treatment were 6 months, 5 months, 15 months, and 19 months. One child had a family history of retinoblastoma and all had bilateral disease at initial diagnosis. The macula was involved with the tumor in all cases. Pretreatment electroretinography (ERG) was performed on 6 of the 8 eyes; flicker potentials were 22.1 μV, 22.4 μV, 33.4 μV, 71.7 μV, and 105.5 μV, and “barely detectable” in 1 case. Follow-up ranged from 8 to 17 months (mean, 12.75 months), and 2 of the patients were followed up for more than 1 year. Melphalan was used alone in 2 patients and melphalan plus topotecan was used in 2 patients. Sessions were performed at 3- to 4-week intervals, and the total number of sessions ranged from 1 to 3 (mean, 2.5). One patient had only 1 session. No patient received external beam radiation or plaque therapy. The total doses of melphalan per tandem session (adding the dose from the right and left eyes) was 4 mg in 1 session, 5 mg in 8 sessions, and 5.5 mg in 1 session; for topotecan, doses were 0.3 mg in 3 sessions, 0.5 mg in 1 session, and 1 mg in 1 session. Topotecan was added for the eyes with more advanced disease.
All patients are alive and free of metastatic disease. No eye needed to undergo radiation or enucleation after intraarterial chemosurgery. There have been no intraoperative or postoperative vascular complications. No patient has received a port or transfusion of any type, required hospitalization, or developed fever/neutropenia. There have been no grade 4 events. One patient developed grade 3 neutropenia with each of 3 infusions of melphalan (total doses: 5, 5, and 4 mg).
All tumors and the vitreous seeds in each case showed significant reduction in size within 3 weeks of treatment. The most recent ERG results were classified as poor (0.2-25.0 μV), fair (25.1-50.0 μV), good (50.1-75.0 μV), and excellent (>75.0 μV). Of the 6 eyes having evaluable ERGs before treatment, the ERG results were poor in 1, fair in 3, good in 1, and excellent in 1. After all treatments, the ERG results improved in 3 eyes, stayed the same in 1 eye, and diminished in 2 eyes. Posttreatment ERGs were available for 8 eyes and were poor in 3, good in 1, and excellent in 4.
Pretreatment and final posttreatment RetCam (Clarity Medical Systems Inc, Pleasanton, California) photographs of each of the eyes are presented in the Figure. Some eyes had transpupillary thermotherapy laser or cryotherapy (for small tumors in the eye).
The concept of intraarterial chemotherapy for retinoblastoma was introduced by Reese et al3 more than 50 years ago. The alkylating agent triethylene melanamine was used via puncture sites in the carotid artery on the side of the eye to be treated. Reese et al reported good results in hundreds of eyes but other investigators (lead by A. Kaneko, MD)4,5 introduced selective chemotherapy for retinoblastoma. These investigators developed a catheter that is passed from the groin (femoral artery) into the carotid artery on the side to be treated. A balloon in the catheter is then inflated, occluding the carotid, and chemotherapy is infused proximal to the occlusion. Our technique involves superselective infusion directly into the ophthalmic artery. Unlike systemic chemotherapy for retinoblastoma, the technique has fewer systemic adverse effects; requires no port, hospitalizations, or transfusions; and may be curative alone. This study highlights the fact that now both eyes of the same patient can be treated with this technique during the same session of anesthesia, and despite the “double dose” of chemotherapy, there were no significant systemic adverse effects. The eyes experienced no significant adverse effects either and the ERG results actually improved in half of the eyes for which measurements were available before treatment. In 2 cases, the ERG results diminished after treatment (from fair to poor in one case and fair to flat in another). This child's ERG results did not diminish when only melphalan was used; when topotecan was added in the last session, the ERG results in both eyes decreased. We have subsequently changed the dose of topotecan and continue to use this agent without problems.
Bilateral intraarterial chemotherapy for bilateral retinoblastoma (tandem therapy), even when advanced (Reese-Ellsworth group V), appears to be safe for the patient and eye and can avoid the use of multiagent systemic chemotherapy, enucleation, and/or radiation in any form for children with bilateral Reese-Ellsworth V eyes. Our protocol for treatment began in May 2006, but longer follow-up is needed to see if any future complications will develop.
Correspondence: Dr Abramson, Ophthalmic Oncology Service, Memorial Sloan-Kettering Cancer Center, 70 E 66th St, New York, NY 10065 (firstname.lastname@example.org).
Financial Disclosure: None reported.
Funding/Support: This study was supported in part by a grant from The Fund for Ophthalmic Knowledge Inc.
Abramson DH, Dunkel IJ, Brodie SE, Marr B, Gobin YP. Bilateral Superselective Ophthalmic Artery Chemotherapy for Bilateral Retinoblastoma: Tandem Therapy. Arch Ophthalmol. 2010;128(3):370-372. doi:10.1001/archophthalmol.2010.7