• Pediatric Ophth/Strabismus

    The authors report a case series of three infants with leptomeningeal trilateral retinoblastoma (TRB) with suprasellar tumors treated with a multifaceted chemotherapy regimen that led to tumor response and longer survival than ever reported for a leptomeningeal TRB patient.

    For induction, the authors used their Toronto Protocol, which consists of high-dose cyclosporine A (CSA), an inhibitor of the multidrug resistance P-glycoprotein (p170), to modulate a high dose of carboplatin, etoposide and vincristine sulfate. Intraventricular topotecan hydrochloride combined with cytarabine was given via an Ommaya reservoir. To avoid craniospinal irradiation, they used supralethal-dose chemotherapy as consolidation therapy, with rescue of the bone marrow by autologous peripheral stem cell transplant.

    One patient remained relapse-free 3.4 years after diagnosis and three years after transplant. The other patients survived for 14 and 32 months, respectively.

    The treatment, which avoids both radiation therapy and surgery, was delivered as part of a prospective clinical trial. The study reports all cases of TRB treated between 2000 and 2008 at one children's hospital in Toronto.

    The authors say that a possible advantage of this chemotherapy regime that may have prolonged survival may have been the addition of CSA, which not only reverses multidrug resistance in retinoblastoma tumor cells but also inhibits the p170-rich vascular endothelial cells that form the blood-brain barrier limiting the entry of chemotherapeutic drugs into the central nervous system.

    They conclude that the significant extension of survival among these patients suggests that this protocol may in some instances offer the potential for a cure for leptomeningeal TRB.