Abstract 809: Prenatal and postnatal management of infants at 100%-risk for developing retinoblastoma

Abstract

Abstract Purpose: Prenatal diagnosis by amniocentesis of infants at 100%-risk of developing retinoblastoma (RB) is possible when the familial RB1 mutation is known in the parent. Since retinal tumors may develop in the third trimester, we assessed the success of a protocol of early delivery of such infants for early institution of therapy with the aim of optimizing outcome. Methods: Since 1999, we treated ten 100%-risk infants with early delivery in a Special Pregnancy Unit, at 32-37 weeks gestation and when deemed to be safe by their obstetrician. From birth, weekly dilated indirect fundoscopy, and/or contact imaging, and/or optical coherent tomography (OCT) examinations were performed with no sedation, with 3-weekly examinations under anesthesia (EUAs) only started once the first tumor was identified, or by the age of 3 months. The tumors were ablated by focal laser therapy and/or cryotherapy. In selected cases, subtenons topotecan (local chemotherapy that causes little side-effects systemically), was used to reduce the sizes of tumors that were too large, or near the optic nerve, or affecting the macula, for focal therapy ablation. When possible, low-dose or single-agent systemic chemotherapy was avoided to avoid induction of the multidrug resistance (MDR) P-glycoprotein in the tumors. If indicated, short-course but high-dose cyclosporin (CSA) MDR-circumventing high-dose carboplatin-etoposide-vincristine (CEV) chemotherapy was given as soon as the infant's immature renal function normalized. Secondary malignancy-inducing radiation and/or eye enucleation was only used for tumors progressing under this regimen. Results: At median followup of 5.7 years (range 0.7-11.7 years), both eyes were saved in 9 children, seven with 20/20-20/50 vision in at least one eye (two were too young for vision-testing), and only one child required radiation and then enucleation of one eye, but retained 20/30 vision in the remaining radiated eye. Five children were only treated with focal laser therapy and/or cryotherapy, two with added subtenons topotecan, four with 1 to 4-cycle CSA-modulated CEV, and one with 2-cycle non-CSA-modulated/dose-adjusted CEV because of immature renal function. Conclusions: This protocol warrants multicenter trial to confirm the favorable efficacy with low toxicity and excellent vision preservation. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 103rd Annual Meeting of the American Association for Cancer Research; 2012 Mar 31-Apr 4; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2012;72(8 Suppl):Abstract nr 809. doi:1538-7445.AM2012-809