Pilot trial of sunitinib therapy in patients with von Hippel-Lindau disease.

BACKGROUND: Von Hippel-Lindau (VHL) disease induces vascular neoplasms in multiple organs. We evaluated the safety and efficacy of sunitinib in VHL patients and examined the expression of candidate receptors in archived tissue. METHODS: Patients with VHL were given four cycles of 50 mg sunitinib daily for 28 days, followed by 14 days off. Primary end point was toxicity. Modified RECIST were used for efficacy assessment. We evaluated 20 archival renal cell carcinomas (RCCs) and 20 hemangioblastomas (HBs) for biomarker expression levels using laser-scanning cytometry (LSC). RESULTS: Fifteen patients were treated. Grade 3 toxicity included fatigue in five patients. Dose reductions were needed in 10 patients. Eighteen RCC and 21 HB lesions were evaluable. Six of the RCCs (33%) responded partially, versus none of the HBs (P = 0.014). LSC revealed that mean levels of phosphorylated vascular endothelial growth factor receptor-2 were lower in HB than in RCC endothelium (P = 0.003) and mean phosphorylated fibroblast growth factor receptor substrate-2 (pFRS2) levels were higher in HB (P = 0.003). CONCLUSIONS: Sunitinib treatment in VHL patients showed acceptable toxicity. Significant response was observed in RCC but not in HB. Greater expression of pFRS2 in HB tissue than in RCC raises the hypothesis that treatment with fibroblast growth factor pathway-blocking agents may benefit patients with HB.

Vitreous relapse following primary chemotherapy for retinoblastoma: is adjuvant diode laser a risk factor?

AIMS: To evaluate rates of vitreous relapse among retinoblastoma patients treated with primary chemotherapy and assess diode laser as a potential risk factor for relapse. METHODS: Retrospective review of all patients treated with primary chemotherapy at a large ocular oncology centre. Eyes that developed vitreous relapse were coded with regard to Reese-Ellsworth Group, laterality, time to relapse, type of relapse (vitreous base or non-vitreous base relapse), treatments used (including adjuvant diode laser), and ocular preservation. Individual tumour foci treated with laser hyperthermia were also coded for laser parameters including power settings, number of treatments, and concomitant administration of systemic chemotherapy (chemothermotherapy). RESULTS: 15 of 106 eyes (14.15%) developed vitreous relapse over a 6 year period. Mean time to relapse was 7.2 months after chemotherapy was completed. Five cases (33%) were of the vitreous base variety. Ocular salvage was attempted in 11 cases using a variety of methods; one patient was lost to follow up. Six of the remaining 10 eyes (60%) were salvaged. Eight of 38 eyes (21%) treated with systemic chemotherapy and laser hyperthermia developed vitreous relapse compared with seven of 68 eyes (10%) treated with primary chemotherapy alone (p<0.005). Laser settings, number of hyperthermia treatments, and the concomitant use of systemic chemotherapy (chemothermotherapy) were not associated with higher rates of vitreous relapse. CONCLUSION: Nearly one in seven eyes with retinoblastoma treated with primary chemotherapy may develop vitreous relapse. The administration of diode laser hyperthermia appears to increase this risk. Despite additional therapy a number of these eyes succumb to enucleation.

Familial retinoblastoma: where and when?

PURPOSE: To determine when patients with a family history of retinoblastoma and previously normal eye exam develop intraocular disease, and where the new retinoblastoma tumors occur. METHODS: A retrospective chart review of retinoblastoma patients. RESULTS: Sixty-two percent of the first eyes (eyes having a previously normal examination) were diagnosed with retinoblastoma by 6 months of age, 90% by 12 months and 100% by 28 months. For the second eye, 27% were identified by 6 months, 64% by 12 months, 91% by 30 months and 100% by 44 months. The younger the age at initial diagnosis of retinoblastoma, the greater the likelihood that tumors will initially be found in the posterior pole. Macular tumors were diagnosed very early (mean 4 months) and once a retinoblastoma focus had appeared in one eye no new tumors developed in the macula of either eye. CONCLUSION: The timing, location, and number of new retinoblastoma tumors follows a predictable pattern.

The topography of bilateral retinoblastoma lesions.

PURPOSE: The anatomic location of intraocular retinoblastoma foci was investigated in patients with bilateral retinoblastoma. The study was designed to evaluate the retinal topography of intraocular tumors and their time course of presentation. METHODS: A retrospective study of 565 eyes with bilateral retinoblastoma was conducted. Data included patient age at detection of each tumor and tumor location within the retina. Intraocular location was characterized in three ways: 1) superior versus inferior retina; 2) nasal versus temporal retina; and 3) macular to peripheral retina, defined as four circular zones. RESULTS: There was a direct correlation between patient age at tumor detection and retinal topography. This relationship followed a central-to-peripheral distribution, with macular tumors presenting earliest and anterior retinal tumors presenting last. Twenty-nine (100%) macular tumors were detected at the time of initial diagnosis, and none presented after 15.5 months of age. When controlled for surface area tumors were located equally in all circular zones. CONCLUSION: There is a time course in which tumors in different parts of the retina come to clinical presentation. All macular tumors in this study and the majority of tumors in the posterior pole were detected before age 24 months. The authors provide possible explanations for these findings and their implications for treatment.