melphalan and Choroid-Neoplasms

Uveal melanoma is the most common primary intraocular tumour in adults. After treatment of the primary tumour, up to 50% of patients will ultimately develop metastases. Treatment options for metastases are limited. When uveal melanoma metastases are confined to the liver, isolated hepatic perfusion (IHP) could be a treatment option. Herein, we report the results of a small group of patients with uveal melanoma metastases of the liver treated with IHP. Eight patients with uveal melanoma metastases confined to the liver underwent IHP with high-dose melphalan (200 mg) for 1 h. Toxicity was graded according to the National Cancer Institute Common Toxicity Criteria and tumour response was assessed according to World Health Organization criteria. The tumour response rate (complete or partial remission) was 50%. The median time to progression was 6.7 months (range, 1.7-16.9 months). The overall median survival was 9.9 months (range, 4.7-34.6 months), with a 1 year survival of 50% and a 2 year survival of 37.5%. Three patients experienced grade 3-4 hepatotoxicity which was transient within 3 months. Although only a small group of patients has been treated and evaluated so far, IHP is a treatment option for uveal melanoma metastases confined to the liver which can result in tumour responses and may lead to survival benefits in a selective group of patients.

Topics: Adult; Aged; Antineoplastic Agents, Alkylating; Chemotherapy, Cancer, Regional Perfusion; Choroid Neoplasms; Disease Progression; Female; Humans; Liver Neoplasms; Male; Melanoma; Melphalan; Middle Aged; Skin Neoplasms; Survival Rate; Time Factors; Treatment Outcome; Uveal Neoplasms

Choroidal melanoma, a common intraocular malignant tumor, relies on local radiotherapy and enucleation for treatment. However, cancer recurrence and visual impairment remain important challenges. Here, a therapeutic artificial vitreous body (AVB) hydrogel based on tetra-armed poly(ethylene glycol) was developed to control the recurrence of choroidal melanoma and preserve vision after vitrectomy. AVB loaded with melphalan (Mel) and anti-programmed cell death ligand-1 (αPDL1), was injected after surgical resection in the choroidal melanoma mouse model. Afterwards, the sequentially released Mel and αPDL1 from AVB could achieve a synergistic antitumor effect to inhibit tumor recurrence. AVB with similar physical properties to native vitreous body could maintain the normal structure and visual function of eye after vitrectomy, which has been evidenced by standard examinations of ophthalmology in the mouse model. Thus, the immunotherapeutic AVB may be a promising candidate as an infill biomaterial to assist surgical treatment of intraocular malignant tumors.

Topics: Animals; Choroid Neoplasms; Hydrogels; Immunotherapy; Melanoma; Melphalan; Mice; Neoplasm Recurrence, Local; Vitrectomy; Vitreous Body

To report treatment of vitreous seeding of choroidal melanoma with monthly injections of intravitreal melphalan.. Case report.. A 70-year-old white woman noted floaters in her left eye, and further examination revealed visual acuity of 20/30 in both eyes. Funduscopically, there was a mushroom-shaped choroidal melanoma in her left eye, measuring 9 mm in basal dimension and 4.8 mm in thickness. Notably, there was apical retinal invasion of melanoma with mild vitreous hemorrhage, without vitreous seeding. The tumor was treated with iodine-125 plaque radiotherapy using an apex dose of 70 Gy over 99 hours, designed to include the retinal invasion. The melanoma demonstrated complete regression into a nearly flat scar of 1 mm and remained stable over 4 years. Five years after radiotherapy, there were diffuse vitreous pigmented seeds of presumed melanoma origin, emanating from the site of retinal necrosis. This progressively worsened over the following 18 months, suspicious for viable melanoma cells, as visual acuity concurrently declined to 20/100. Treatment with intravitreal melphalan (10 μg/0.05 mL) was delivered on a monthly basis for 12 cycles, resulting in vitreous seeds regression, and preservation of the eye. Final visual acuity was 20/200. There were no treatment-related complications.. Intravitreal melphalan can be considered in cases of vitreous seeding from uveal melanoma.

Topics: Aged; Antineoplastic Agents, Alkylating; Choroid Neoplasms; Female; Fluorescein Angiography; Humans; Intravitreal Injections; Melanoma; Melphalan; Neoplasm Seeding; Retinal Neoplasms; Retrospective Studies; Tomography, Optical Coherence; Vitreous Body

To report the occurrence and management of secondary choroidal infiltration in two retinoblastoma (rb) patients.. Fundus examination and imaging with spectral domain optical coherence tomography (SD-OCT), B-scan ultrasonography (B-scan), and ultrasound biomicroscopy (UBM).. Case 1: A 19-month-old girl with multifocal unilateral group B rb pretreated with intravenous chemotherapy (IVC) was referred for further management. At 3.5 years of age, routine 3-Tesla magnetic resonance imaging (3T-MRI) revealed an asymptomatic pinealoblastoma that underwent resection and adjuvant intensive IVC. Concomitant ophthalmic follow-up revealed a recurrence 8.3 × 2.8 mm at the posterior pole nasally to the optic disc on B-scan, localized within the choroid on SD-OCT and 3T-MRI. With high dose IVC ongoing, total regression of the choroidal mass was confirmed on SD-OCT already after 3 weeks. At 6-month follow-up, choroidal and pineal tumors were in complete remission. Sadly, the child died of intravascular disseminated coagulation-like disease after the 5th IVC. Case 2: A heavily pretreated 20-month-old girl with bilateral rb was referred for persistent vitreous seeding in her remaining eye (OD). Three months after intravitreal chemotherapy and chemothermotherapy, a hemorrhagic mass was observed inferior to the primary tumor. Two weeks later, an underlying peripheral choroidal mass 16 × 6 mm was documented by UBM and confirmed by 3T-MRI. Complete resolution was achieved 3 weeks after combined intra-arterial chemotherapy (IAC) of melphalan-topotecan. No recurrence or metastasis was observed at 34-month follow-up.. Isolated massive choroidal invasion can be treated conservatively with IVC or IAC in selected cases. SD-OCT, UBM, and B-scan ultrasonography are instrumental in the detection and follow-up of choroidal lesions.

Topics: Antineoplastic Combined Chemotherapy Protocols; Choroid Neoplasms; Conservative Treatment; Fatal Outcome; Female; Fluorescein Angiography; Humans; Infant; Infusions, Intra-Arterial; Magnetic Resonance Imaging; Melphalan; Microscopy, Acoustic; Neoplasm Recurrence, Local; Retinal Neoplasms; Retinoblastoma; Tomography, Optical Coherence; Topotecan

To describe histopathologic observations in eyes enucleated after intra-arterial chemotherapy (IAC) for retinoblastoma (Rb).. Retrospective histopathologic analysis of 8 eyes.. The eyes were enucleated for tumor viability (n = 4), neovascular glaucoma (n = 2), anaphylactic reaction from IAC (n = 1), and persistent retinal detachment with poor visualization of the tumor (n = 1). Of the 2 eyes judged clinically with complete tumor regression and the 5 with viable tumor, the findings were confirmed on histopathology. The Rb response ranged from minimal (n = 1) to moderate (n = 1) to extensive (n = 4) to complete regression (n = 2). Viable vitreous seeds (n = 4 eyes), invasion into the optic nerve (n = 3), reaching the lamina cribrosa in 2 cases, and invasion into the choroid (n = 1) were observed. Histopathologic evidence of ischemic atrophy involving the outer retina and choroid was found in 4 eyes. One eye treated at another center with IAC and enucleated by our team for recurrence was observed to have extensive choroidal and outer retinal atrophy. This case showed orbital vascular occlusion and subendothelial smooth muscle hyperplasia. Intravascular birefringent foreign material was observed in 5 cases within occluded vessels, stimulating a granulomatous inflammatory response. The foreign material comprised cellulose fibers (n = 3), synthetic fabric fibers (n = 1), or unknown composition (n = 2). Thrombosed blood vessels were identified in 5 eyes and involved ciliary arteries in the retrobulbar orbit (n = 5), scleral emissarial canals (n = 1), small choroidal vessels (n = 1), and central retinal artery (n = 1).. Retinoblastoma can be controlled with IAC, but histopathology of enucleated eyes reveals that ocular complications including thromboembolic events can occur.

Topics: Antineoplastic Agents, Alkylating; Chemotherapy, Cancer, Regional Perfusion; Child; Child, Preschool; Choroid Neoplasms; Eye Diseases; Eye Enucleation; Female; Fluorescein Angiography; Fluoroscopy; Humans; Infant; Injections, Intra-Arterial; Male; Melphalan; Neoplasm Invasiveness; Neoplasm Seeding; Ophthalmic Artery; Optic Nerve Neoplasms; Retinal Neoplasms; Retinoblastoma; Retrospective Studies; Thromboembolism; Vitreous Body

Topics: Animals; Anterior Chamber; Antibiotics, Antineoplastic; Choroid Neoplasms; Humans; Melanoma; Melphalan; Neoplasm Transplantation; Olivomycins; Rabbits; Thiotepa