melphalan and Neoplasm-Seeding

Retinoblastoma is the most common primary intraocular tumor of childhood. Accurate diagnosis at an early stage is important to maximize patient survival, globe salvage, and visual acuity. Management of retinoblastoma is individualized based on the presenting clinical and imaging features of the tumor, and a multidisciplinary team is required to optimize patient outcomes. The neuroradiologist is a key member of the retinoblastoma care team and should be familiar with characteristic diagnostic and prognostic imaging features of this disease. Furthermore, with the adoption of intra-arterial chemotherapy as a standard of care option for globe salvage therapy in many centers, the interventional neuroradiologist may play an active role in retinoblastoma treatment. In this review, we discuss the clinical presentation of retinoblastoma, ophthalmic imaging modalities, neuroradiology imaging features, and current treatment options.

Topics: Humans; Infusions, Intra-Arterial; Melphalan; Neoplasm Seeding; Retinal Neoplasms; Retinoblastoma; Retrospective Studies; Salvage Therapy

Retinoblastoma is a deadly eye cancer in children, leading to death in 50%-70% of children in undeveloped nations who are diagnosed with it. This malignancy is the most common intraocular tumor in childhood worldwide. The good prognosis in developed nations is related to early detection and advanced treatments. With the advent of intraarterial chemotherapy, neurosurgeons have taken a central role in the treatment of this pediatric condition. Intraarterial chemotherapy is a novel treatment for retinoblastoma whereby chemotherapeutic agents are precisely delivered into the ophthalmic artery, minimizing systemic toxicity. This procedure has shown impressive results and has allowed a dramatic decrease in the rate of enucleation (eye removal) in advanced and refractory retinoblastoma. Recent reports have raised some concerns about the risk of ocular vasculopathy, radiation-related toxicity, and the potential for metastatic disease after intraarterial chemotherapy. In the authors' experience of more than 3 years, tumor control is excellent with globe salvage at 67% and vascular events less than 5%, mostly related to improvement in technique. The role of this novel approach in the management of retinoblastoma has yet to be defined. As more centers are adopting the technique, the topic will decidedly become the focus of intensive future research. In this paper, the authors review and discuss current data regarding intraarterial chemotherapy for retinoblastoma.

Topics: Antineoplastic Agents, Alkylating; Eye Enucleation; Humans; Injections, Intra-Arterial; Melphalan; Neoplasm Seeding; Ophthalmic Artery; Research Design; Retinal Neoplasms; Retinoblastoma

Retinoblastoma with vitreous seeding has been one of the most challenging conditions for eye-preservation therapy. Several modalities for treating vitreous seeding were reviewed in order to analyze the problems associated with them. External beam radiotherapy has been the most reliable method to treat vitreous seeding. However, recurrence after external beam radiotherapy needs other types of treatments to preserve the eyeballs. Due to the progress of investigations concerning retinoblastoma, chemotherapy has become the most promising method to cure not only recurrence but also primary tumors. Systemic chemotherapy can rarely cure vitreous seeding, but local chemotherapy using vitreous injections of melphalan can preserve about 50% of the eyeballs with vitreous seeding. Currently, animal experiments are being conducted to study the efficacy and safety of vitreous surgery combined with infusion of anticancer drugs for eradication of vitreous seeds and maintenance of visual function.

Topics: Animals; Antineoplastic Agents, Alkylating; Brachytherapy; Combined Modality Therapy; Humans; Injections; Melphalan; Neoplasm Seeding; Rabbits; Retinal Neoplasms; Retinoblastoma; Thiotepa; Vitreous Body

To evaluate the efficacy and toxicity of intravitreal carboplatin plus melphalan for the treatment of vitreous seeds in eyes with retinoblastoma (RB).. This retrospective series at a tertiary referral center included 22 consecutive RB patients who had received intravitreal carboplatin (16 μg per 0.05 ml) combined with melphalan (30 μg in 0.03 ml) [IVi (Ca-Me)] for treatment of vitreous seeds. Tumor control and drug toxicities were recorded.. There were 22 eyes of 22 patients, divided into primary group (n = 13) without history of previous intravitreal chemotherapy (IViC) and refractory group (n = 9) with history of previous IViC using melphalan and/or topotecan. The demographics and clinical findings of the primary and refractory groups did not differ significantly. The 6-month follow-up revealed complete vitreous seed control (77% vs. 89%, p = 0.47). Vitreous seed recurrence was detected in 1 eye of each group at 6 months. During the next 18-month follow-up period, no recurrence of seed was observed. The response to IVi (Ca-Me) was not significantly influenced by previous IViC (p = 0.70), primary systemic or intra-arterial chemotherapy (p = 0.45), or the type of regression (p = 0.35). The most common tumor treatment complications were retinal detachment (RD) (n = 2), early hypotony (n = 2) and late hypotony (n = 4, unrelated), cataract (n = 2), and severe pigment dispersion (n = 1). Enucleation was performed in 8 eyes, for total RD (n = 1), phthisis bulbi (n = 5), and extensive solid tumor recurrence (n = 2). There was no case of orbital invasion, systemic metastasis, or death.. Based on this interventional case series for primary and refractory vitreous RB seeds, carboplatin plus melphalan therapy may be effective with few toxic side effects.

Topics: Antineoplastic Agents, Alkylating; Carboplatin; Humans; Infant; Intravitreal Injections; Melphalan; Neoplasm Recurrence, Local; Neoplasm Seeding; Retinal Neoplasms; Retinoblastoma; Retrospective Studies; Vitreous Body

Current melphalan-based intravitreal regimens for retinoblastoma (RB) vitreous seeds cause retinal toxicity. We assessed the efficacy and toxicity of topotecan monotherapy compared with melphalan in our rabbit model and patient cohort.. Rabbit experiments: empiric pharmacokinetics were determined following topotecan injection. For topotecan (15 μg or 30 µg), melphalan (12.5 µg) or saline, toxicity was evaluated by serial electroretinography (ERG) and histopathology, and efficacy against vitreous seed xenografts was measured by tumour cell reduction and apoptosis induction.. retrospective cohort study of 235 patients receiving 990 intravitreal injections of topotecan or melphalan.. Intravitreal topotecan 30 µg (equals 60 µg in humans) achieved the IC. Taken together, these experiments suggest that intravitreal topotecan monotherapy for the treatment of RB vitreous seeds is non-toxic and effective.

Topics: Animals; Antineoplastic Agents, Alkylating; Humans; Intravitreal Injections; Melphalan; Neoplasm Seeding; Rabbits; Retinal Neoplasms; Retinoblastoma; Retrospective Studies; Topotecan; Vitreous Body

To report our experience in the management of cataracts presumably due to intravitreal chemotherapy administration in eyes with vitreous disease associated with retinoblastoma.. This retrospective study consisted of a cohort of five eyes of five retinoblastoma patients who developed cataracts secondary to intravitreal chemotherapy administration and who then underwent cataract surgery. All patients underwent lensectomy and anterior vitrectomy with/without intraocular lens implantation via clear corneal approach. All cases were administered intraoperative intravitreal melphalan (35-40 mcg) and topotecan (10-20 mcg) at the end of cataract surgery as a preventive measure against retinoblastoma spread. Injections were repeated as needed in monthly follow-ups. Main outcome measures were enucleation rate and disease-free survival time.. The age at surgery ranged between 5 and 10 years. Follow-up time varied from 12 to 16 months. Treatment-free period before surgery ranged between 3 and 20 months. Time from last injection to cataract detection was: 2, 2, 10, 6, and 7 months; and time from last injection to cataract surgery was: 8, 3, 20, 7, and 15 months in cases 1-5, respectively. None of the eyes required enucleation. Tumor control was achieved in all patients at the end of follow-up.. Injection of melphalan and topotecan into anterior parts of the vitreous may lead to cataract formation. This can be safely managed with lensectomy and anterior vitrectomy and the use of intravitreal administration of melphalan and topotecan at the conclusion of the surgery as a precautionary measure against the potential risk of extraocular spread.

Topics: Antineoplastic Agents, Alkylating; Cataract; Child; Child, Preschool; Humans; Infant; Intravitreal Injections; Melphalan; Neoplasm Seeding; Retinal Neoplasms; Retinoblastoma; Retrospective Studies; Topotecan; Vitreous Body

Topics: Antineoplastic Agents, Alkylating; Hemorrhage; Humans; Infant; Intravitreal Injections; Melphalan; Neoplasm Seeding; Retinal Neoplasms; Retinoblastoma; Retrospective Studies

Current melphalan-based regimens for intravitreal chemotherapy for retinoblastoma vitreous seeds are effective but toxic to the retina. Thus, alternative agents are needed. Based on the known biology of histone deacetylases (HDACs) in the retinoblastoma pathway, we systematically studied whether the HDAC inhibitor belinostat is a viable, molecularly targeted alternative agent for intravitreal delivery that might provide comparable efficacy, without toxicity.. In vivo pharmacokinetic experiments in rabbits and in vitro cytotoxicity experiments were performed to determine the 90% inhibitory concentration (IC90). Functional toxicity by electroretinography and structural toxicity by optical coherence tomography (OCT), OCT angiography, and histopathology were evaluated in rabbits following three injections of belinostat 350 µg (2× IC90) or 700 µg (4× IC90), compared with melphalan 12.5 µg (rabbit equivalent of the human dose). The relative efficacy of intravitreal belinostat versus melphalan to treat WERI-Rb1 human cell xenografts in rabbit eyes was directly quantified. RNA sequencing was used to assess belinostat-induced changes in RB cell gene expression.. The maximum nontoxic dose of belinostat was 350 µg, which caused no reductions in electroretinography parameters, retinal microvascular loss on OCT angiography, or retinal degeneration. Melphalan caused severe retinal structural and functional toxicity. Belinostat 350 µg (equivalent to 700 µg in the larger human eye) was equally effective at eradicating vitreous seeds in the rabbit xenograft model compared with melphalan (95.5% reduction for belinostat, P < 0.001; 89.4% reduction for melphalan, P < 0.001; belinostat vs. melphalan, P = 0.10). Even 700 µg belinostat (equivalent to 1400 µg in humans) caused only minimal toxicity. Widespread changes in gene expression resulted.. Molecularly targeted inhibition of HDACs with intravitreal belinostat was equally effective as standard-of-care melphalan but without retinal toxicity. Belinostat may therefore be an attractive agent to pursue clinically for intravitreal treatment of retinoblastoma.

Topics: Animals; Annexin A5; Antineoplastic Agents, Alkylating; Disease Models, Animal; Electroretinography; Fluorescein Angiography; Histone Deacetylase Inhibitors; Hydroxamic Acids; Intravitreal Injections; Maximum Tolerated Dose; Melphalan; Neoplasm Seeding; Rabbits; Retina; Retinal Neoplasms; Retinoblastoma; Retrospective Studies; Sulfonamides; Tomography, Optical Coherence; Vitreous Body; Xenograft Model Antitumor Assays

To compare retinal toxicity as measured by electroretinogram, ocular, and patient survival in retinoblastoma treated with intravitreal melphalan at two concentrations (25 vs. 30 µg).. Single-center, retrospective analysis of retinoblastoma eyes receiving 25-µg or 30-µg intravitreal melphalan from September 2012 to January 2019. Ocular toxicity was measured by electroretinogram of evaluable injections in 449 injections in 136 eyes. A repeated-measures linear mixed model with a random intercept and slope was applied to account for repeated measures for each eye.. Average decline in electroretinogram after each additional injection was -4.9 µV (95% confidence interval -6.3 to -3.4); electroretinogram declined by -4.6 µV (95% confidence interval -7.0 to -2.2) after 25-µg injections and -5.2 µV (95% confidence interval -6.6 to -3.8) after 30-µg injections (P = 0.66). Injection at a new clock site hour was associated with a -3.91-µV lower average (95% confidence interval -7.8 to -0.04).. Electroretinogram-measured toxicity in retinoblastoma eyes treated with intravitreal injections was not found to be different across 25-µg and 30-µg injections. There were no cases of extraocular extension or metastatic deaths in our patient population.

Topics: Adolescent; Antineoplastic Agents, Alkylating; Child; Child, Preschool; Electroretinography; Female; Follow-Up Studies; Humans; Infant; Infant, Newborn; Intravitreal Injections; Male; Melphalan; Neoplasm Seeding; Retinal Neoplasms; Retinoblastoma; Retrospective Studies; Treatment Outcome; Vitreous Body

The use of intravitreal chemotherapy has revolutionized the treatment of advanced intraocular retinoblastoma, as intravitreal melphalan has enabled difficult-to-treat vitreous tumor seeds to be controlled, leading to many more eyes being saved. However, melphalan hydrochloride (MH) degrades rapidly in solution, increasing logistical complexity with respect to time between medication preparation and administration for intravitreal administration under anesthesia for retinoblastoma. A new propylene glycol-free melphalan (PGFM) formulation has greater stability and could therefore improve access and adoption of intravitreal chemotherapy, allowing more children to retain their eye(s). We compared the efficacy and toxicity of both formulations, using our rabbit xenograft model and clinical patient experience. Three weekly 12.5 μg intravitreal injections of MH or PGFM (right eye), and saline (left eye), were administered to immunosuppressed rabbits harboring human WERI-Rb1 vitreous seed xenografts. Residual live cells were quantified directly, and viability determined by TUNEL staining. Vitreous seeds were reduced 91% by PGFM (p = 0.009), and 88% by MH (p = 0.004; PGFM vs. MH: p = 0.68). All residual cells were TUNEL-positive (non-viable). In separate experiments to assess toxicity, three weekly 12.5 μg injections of MH, PGFM, or saline were administered to non-tumor-bearing rabbits. Serial electroretinography, optical coherence tomography (OCT) and OCT-angiography were performed. PGFM and MH both caused equivalent reductions in electroretinography amplitudes, and loss of retinal microvasculature on OCT-angiography. The pattern of retinal degeneration observed on histopathology suggested that segmental retinal toxicity associated with all melphalan formulations was due to a vitreous concentration gradient-effect. Efficacy and toxicity were assessed for PGFM given immediately (within 1 h of reconstitution) vs. 4 h after reconstitution. Immediate- and delayed-administration of PGFM showed equivalent efficacy and toxicity. In addition, we evaluated efficacy and toxicity in patients (205 eyes) with retinoblastoma vitreous seeds, who were treated with a total of 833 intravitreal injections of either MH or PGFM as standard of care. Of these, we analyzed 118 MH and 131 PGFM monotherapy injections in whom serial ERG measurements were available to model retinal toxicity. Both MH and PGFM caused reductions in electroretinography amplitudes, but with no statistical differ

Topics: Animals; Antineoplastic Agents, Alkylating; Electroretinography; Female; Fluorescein Angiography; Humans; In Situ Nick-End Labeling; Infant; Intravitreal Injections; Male; Melphalan; Neoplasm Seeding; Pharmaceutical Preparations; Rabbits; Retina; Retinal Neoplasms; Retinoblastoma; Retrospective Studies; Tomography, Optical Coherence; Treatment Outcome; Tumor Cells, Cultured; Vitreous Body; Xenograft Model Antitumor Assays

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 evaluate clinical outcomes and enucleation rates after intravitreal melphalan (IVM) alone and after IVM combined with intravitreal topotecan (IVT) for the treatment of vitreous disease, and to a lesser extent subretinal and retrohyaloid seeds, in patients with retinoblastoma.. A retrospective analysis of 77 eyes of 72 consecutive patients.. Demographic data, classification of tumors, seed type (dust, sphere or cloud) before injection and at the end of follow-up, injection type (IVM or IVM+IVT), doses of IVM and IVT, number of injections, follow-up time, enucleation status and side effects were recorded. Cox regression analysis and log-rank test for Kaplan-Meier curves were performed.. Of 77 eyes, 40 received IVM alone (group 1) and 37 received IVM+IVT (group 2). Enucleation rates were 62.5% (n=25) in group 1 and 10.8% (n=4) in group 2 (p=0.001). Median eye survival was 23.6 months in group 1 and 25.6 months in group 2. Mantel-Cox test revealed statistically significant differences between Kaplan-Meier curves of group 1 and 2 (p=0.022). Multiple Cox regression analysis showed a significantly elevated enucleation rate associated with: IVM only treatment group (p=0.019) and pre-injection cloud type of seeding (p=0.014).. The combined use of intravitreal melphalan and topotecan provides significantly better results in terms of avoiding enucleation and vitreal and subretinal seed control.

Topics: Antineoplastic Agents, Alkylating; Child, Preschool; Drug Therapy, Combination; Eye Diseases; Eye Enucleation; Female; Follow-Up Studies; Humans; Infant; Intravitreal Injections; Kaplan-Meier Estimate; Male; Melphalan; Neoplasm Seeding; Proportional Hazards Models; Retinal Diseases; Retinal Neoplasms; Retinoblastoma; Retrospective Studies; Topoisomerase I Inhibitors; Topotecan; Treatment Outcome; Vitreous Body

To evaluate the efficacy, complications, and clinical characteristics, including the ocular toxicity, of intravitreal melphalan(IVM) treatment for vitreous seeding in Chinese retinoblastoma patients.. This was a retrospective, non-comparative analysis including 30 consecutive eyes of 23 patients with viable persistent or recurrent vitreous seeding following retinoblastoma treatment. All of the eyes received IVM injections (20-33 μg). Vitreous seeding control, determination of the ocular toxicity, and the clinical characteristics of intravitreal melphalan treatments were observed.. The mean patient age at the time of the injection was 28 months (median = 22 months, range = 12-50 months). In total, 80 injections were administered in 30 eyes, the overall enucleation-free survival rate was 83.3% (25/30). The complications included retinal pigment epithelium (RPE) and choroidal atrophy (19/30, 63.3%), pupillary synechiae (13/30, 43.3%), iris atrophy (12/30, 40%), retinal vascular occlusion (12/30, 40.0%), optic atrophy (6/30, 20%), vitreous hemorrhage (3/30, 10%), persistent hypotonia and phthisis bulbi (4/30 13.3%), and cataracts (8/30, 26.6%). Twelve eyes demonstrated grade 3 or greater IVM-associated retinal or anterior segment toxicity post injection. Mean dosage given showed significant difference between the groups. There were no significant differences in the retinal toxicity grades regarding the seed classification or seed regression patterns.. Intravitreal melphalan is an effective treatment for refractory vitreous seeding from retinoblastoma, but exhibits both anterior and posterior segment toxicity in Chinese patients.

Topics: Antineoplastic Agents, Alkylating; Child, Preschool; Female; Humans; Infant; Intravitreal Injections; Male; Melphalan; Neoplasm Seeding; Retinal Neoplasms; Retinoblastoma; Retrospective Studies; Vitreous Body

Intravitreal injection of chemotherapy in retinoblastoma eyes with vitreous seeds may lead to a risk of extraocular tumour dissemination that has not been assessed so far.. To develop a sensitive and clinically feasible technique to assess for potential retinoblastoma cell reflux after intravitreal injection of melphalan.. Filter papers were cut in 6 mm diameter circles and sterilised before use. Eyes with retinoblastoma vitreous seeds (group D, International Classification) received weekly intravitreal melphalan injections (20 µg or 30 µg/dose) followed by cryotherapy as part of local treatment. Immediately after finishing the injection and cryotherapy, filter papers were placed on the injection site and on the cryoprobe tip to assess for the expression of the cone-rod homeobox gene (CRX) by real-time qPCR as a surrogate of retinoblastoma RNA. The assay was developed and validated to determine sensitivity, linearity, recovery, repeatability and reproducibility.. The assay for quantitation of CRX expression was linear in the range of 1 to 1000 cells. The lowest limit of detection was one retinoblastoma cell and allowed to recover 100% of the cell load in external supplementation. A total of 14 eyes received 22 cycles of intravitreal melphalan and were evaluated for potential extraocular tumour cell dissemination using the developed technique. None of the cycles were positive for CRX in samples from the scar or from the cryoprobe tip.. A sensitive and simple method of tumour cell assessment has been developed that can be used in the clinics to assess for potential extraocular dissemination after intravitreal injections to assure its performance.

Topics: Antineoplastic Agents, Alkylating; Biomarkers, Tumor; Cryotherapy; Homeodomain Proteins; Humans; Intravitreal Injections; Melphalan; Neoplasm Seeding; Real-Time Polymerase Chain Reaction; Reproducibility of Results; Retinal Neoplasms; Retinoblastoma; Retrospective Studies; RNA, Neoplasm; Trans-Activators; Tumor Cells, Cultured

To compare the efficacy and toxicity of treating class 3 retinoblastoma vitreous seeds with ophthalmic artery chemosurgery (OAC) alone versus OAC with intravitreous chemotherapy.. Retrospective cohort study.. Forty eyes containing clouds (class 3 vitreous seeds) of 40 retinoblastoma patients (19 treated with OAC alone and 21 treated with OAC plus intravitreous and periocular chemotherapy).. Ocular survival, disease-free survival and time to regression of seeds were estimated with Kaplan-Meier estimates. Ocular toxicity was evaluated by clinical findings and electroretinography: 30-Hz flicker responses were compared at baseline and last follow-up visit. Continuous variables were compared with Student t test, and categorical variables were compared with the Fisher exact test.. Ocular survival, disease-free survival, and time to regression of seeds.. There were no disease- or treatment-related deaths and no patient demonstrated externalization of tumor or metastatic disease. There was no significant difference in the age, laterality, disease, or disease status (treatment naïve vs. previously treated) between the 2 groups. The time to regression of seeds was significantly shorter for eyes treated with OAC plus intravitreous chemotherapy (5.7 months) compared with eyes treated with OAC alone (14.6 months; P < 0.001). The 18-month Kaplan-Meier estimates of disease-free survival were significantly worse for the OAC alone group: 67.1% (95% confidence interval, 40.9%-83.6%) versus 94.1% (95% confidence interval, 65%-99.1%) for the OAC plus intravitreous chemotherapy group (P = 0.05). The 36-month Kaplan-Meier estimates of ocular survival were 83.3% (95% confidence interval, 56.7%-94.3%) for the OAC alone group and 100% for the OAC plus intravitreous chemotherapy group (P = 0.16). The mean change in electroretinography responses was not significantly different between groups, decreasing by 11 μV for the OAC alone group and 22 μV for the OAC plus intravitreous chemotherapy group (P = 0.4).. Treating vitreous seed clouds with OAC and intravitreous and periocular chemotherapy, compared with OAC alone, resulted in a shorter time to regression and was associated with fewer recurrences requiring additional treatment and fewer enucleations. The toxicity to the retina does not seem to be significantly worse in the OAC plus intravitreous chemotherapy group.

Topics: Antineoplastic Combined Chemotherapy Protocols; Carboplatin; Child, Preschool; Cohort Studies; Disease-Free Survival; Electroretinography; Female; Humans; Infusions, Intra-Arterial; Intravitreal Injections; Kaplan-Meier Estimate; Male; Melphalan; Neoplasm Seeding; Ophthalmic Artery; Retina; Retinal Neoplasms; Retinoblastoma; Retrospective Studies; Topotecan; Vitreous Body

Intravitreal chemotherapy has emerged as an important modality for treating vitreous seeding in retinoblastoma. A classification system has been described as predictive of response to intravitreal melphalan (IVM) in patients treated predominantly with primary intra-arterial chemotherapy. The objective of this study is to evaluate the outcomes of retinoblastoma treated with intravenous chemotherapy and IVM as salvage for vitreous seeding, and further to determine whether vitreous seed classification (dust, spheres, cloud) is predictive of the total number and dose of IVM injections required for treatment in this cohort.. A nonrandomized retrospective review.. Retinoblastoma patients treated at a single center with intravenous chemotherapy and IVM.. Retrospective review of patients with vitreous seeding from retinoblastoma treated with intravenous chemotherapy and IVM from 2012 to 2016.. Primary outcome measure was eradication of seeds and globe salvage. Secondary measures included IVM-associated toxicity and complications.. Overall, 28 eyes of 25 patients were included, with a total of 110 IVM injections. By seed classification, eyes with dust (n = 15) required a median of 3 injections, spheres (n = 8) required 4 injections, and clouds (n = 5) required 6 injections. Spherical seeds were only seen in recurrent vitreous seeding. Of the 28 treated eyes, 9 were enucleated, 6 for recurrent retinal disease, resulting in an overall globe salvage rate of 68%. The salvage rate secondary to active retinoblastoma was 79%. Dust classification was the most prevalent seeding type of the 9 enucleated eyes. There was 100% regression of vitreous seeds after intravitreal injection and no eye was treated with radiation or enucleated for seeding. Twelve eyes demonstrated grade 3 or greater IVM-associated retinal or anterior segment toxicity post injection. Mean follow-up was 33 months (range, 9-51 months).. IVM is an effective treatment for vitreous seeding after intravenous chemotherapy for retinoblastoma. As with eyes treated with intra-arterial chemotherapy, seed classification is predictive of the total number and dose of IVM injections in eyes treated with intravenous chemotherapy. Eyes with clouds required significantly more injections than eyes with dust or spheres.

Topics: Antineoplastic Agents, Alkylating; Antineoplastic Combined Chemotherapy Protocols; Carboplatin; Child; Child, Preschool; Cryotherapy; Etoposide; Female; Follow-Up Studies; Humans; Infant; Infusions, Intravenous; Intravitreal Injections; Laser Coagulation; Male; Melphalan; Neoplasm Seeding; Retinal Neoplasms; Retinoblastoma; Retrospective Studies; Salvage Therapy; Vincristine; Vitreous Body

The risk of extraocular extension from injecting chemotherapy into eyes with retinoblastoma is minimally understood; however, understanding this risk is important because of the increasing use of intravitreous chemotherapy.. To evaluate the risk of extraocular extension in eyes with retinoblastoma that have received intravitreous chemotherapy injections.. This retrospective cohort study was performed in 655 patients at 10 retinoblastoma centers in North and South American, European, Israeli, and Chinese centers. Physicians at the retinoblastoma centers administered more than 120 intravitreous chemotherapy injections in eyes with retinoblastoma from February 1, 1999, through February 28, 2017.. Risk of extraocular extension with secondary observational variables, including injection and precautionary techniques.. A total of 3553 intravitreous chemotherapy injections (3201 melphalan hydrochloride, 335 topotecan hydrochloride, and 17 methotrexate sodium) were administered to 704 eyes in 655 patients with retinoblastoma (mean [SD] age of patients at the time of the initial injections, 31.6 [11.6] months; 348 male [53.1%]). There were no extraocular tumor events related to prior intravitreous injections. This finding resulted in a calculated proportion of zero extraocular events per eye. According to the rule of 3, the risk is no greater than 0.08% injections. All 10 centers included in this study used at least 2 presumed precautionary injection methods (lowering of intraocular pressure, cryotherapy, ocular surface irrigation, ultrasonic biomicroscopy surveillance of the injection site, and subconjunctival chemotherapy deposition).. With use of at least 2 presumed precautionary safety methods, no extraocular extension of tumor events occurred. According to the rule of 3, this finding suggests that the risk is no greater than 0.08% injections.

Topics: Antineoplastic Agents; Child, Preschool; Cryotherapy; Female; Humans; Infant; Intravitreal Injections; Male; Melphalan; Methotrexate; Microscopy, Acoustic; Neoplasm Seeding; Retinal Neoplasms; Retinoblastoma; Retrospective Studies; Risk Factors; Topotecan

To investigate the efficacy and toxicity of intravitreous melphalan for treatment of retinoblastoma, as a single agent or with concomitant topotecan.. A total of 130 eyes of 120 patients with retinoblastoma receiving 630 intravitreous (melphalan, topotecan) or topotecan periocular injections. A total of 83 (64%) of these eyes were treated with concomitant ophthalmic artery chemosurgery (OAC).. Retrospective cohort study.. Indirect ophthalmoscopy and clinical imaging were used to evaluate clinical response. Ocular survival and disease-free survival were estimated using Kaplan-Meier methods in 130 eyes. Ocular toxicity was evaluated by clinical findings and electroretinography (ERG) on 244 evaluable injections in 63 patients using 30-Hz flicker responses. Analysis was performed using linear mixed effects models with a random intercept and slope for each patient and a fixed effect for number of injections, in addition to any other fixed effect of interest.. Ocular survival, disease-free survival, ERG: peak-to-peak ERG amplitudes in response to 30-Hz photopic flicker stimulation.. There were no disease- or treatment-related deaths, and no patient developed externalization of tumor or metastatic disease. Two-year Kaplan-Meier estimates of ocular survival and disease-free survival were 94.2% (95% confidence interval, 89.2-99.4) and 86.2% (95% confidence interval, 78.7-94.5), respectively. There was a significant association between the number of injections and diminished ERG responses, such that on average each intravitreous melphalan injection was associated with a 5.3-μV decrease in ERG amplitude (P < 0.001). Concomitant intra-arterial chemotherapy (P = 0.01) and greater inherent ocular pigment also were significantly associated with a reduction in ERG (P = 0.045). Patient age and weight, new injection site location, addition of topotecan, concomitant focal treatment, and time interval between injections were not significantly associated with toxicity.. Intravitreous melphalan is an effective treatment for vitreous seeding in retinoblastoma, resulting in high rates of ocular survival and disease-free survival. However, in this study, each injection of melphalan was associated, on average, with a decrement in ERG response. The findings suggest increased toxicity (1) when OAC is given within 1 week of the intravitreous injection and (2) in more deeply pigmented eyes.

Topics: Antineoplastic Agents, Alkylating; Antineoplastic Combined Chemotherapy Protocols; Child, Preschool; Cohort Studies; Disease-Free Survival; Electroretinography; Female; Humans; Infant; Injections, Intraocular; Intravitreal Injections; Male; Melphalan; Neoplasm Seeding; Ophthalmic Artery; Ophthalmoscopy; Retina; Retinal Neoplasms; Retinoblastoma; Retrospective Studies; Topoisomerase I Inhibitors; Topotecan; Treatment Outcome; Vitreous Body

To investigate the impact of intravitreal chemotherapy on intraocular pressure (IOP) in children with retinoblastoma.. This was a retrospective study of 10 eyes of 10 patients with retinoblastoma (7 males, 3 females, mean age: 33.6 ± 9.4 months) with vitreous seeding injected with intravitreal melphalan and topotecan. IOP was measured with Tonopen (Reichert, Inc., Buffalo, NY) at baseline prior to injecting and then repeatedly following each intravitreal injection.. Mean pre-injection IOP was 8.2 ± 2.3 mm Hg (range: 4 to 12 mm Hg). Mean IOP 1 to 30 seconds after intravitreal melphalan (first injection) was 45.4 ± 14.3 mm Hg. The IOP of 89.5% of patients declined to 29 mm Hg or less in a mean 153.3 ± 97.5 seconds. Mean IOP 1 to 30 seconds after intravitreal topotecan (second injection) was 44.5 ± 11.0 mm Hg, which decreased to 31.0 ± 5.0 mm Hg by 150 seconds after injection. No significant relationship was found between age and post-injection IOP elevation. IOP exceeded the calculated mean arterial perfusion pressure in four encounters.. Intravitreal chemotherapy caused a transient rise in IOP. Post-injection IOP elevations can reach levels that may exceed mean arterial pressure. [J Pediatr Ophthalmol Strabismus. 2017;54(3):185-190.].

Topics: Adolescent; Adult; Antineoplastic Agents, Alkylating; Dose-Response Relationship, Drug; Drug Therapy, Combination; Female; Humans; Intraocular Pressure; Intravitreal Injections; Male; Melphalan; Neoplasm Seeding; Retinal Neoplasms; Retinoblastoma; Retrospective Studies; Topoisomerase I Inhibitors; Topotecan; Treatment Outcome; Vitreous Body; Young Adult

To evaluate the therapeutic outcome of intravitreal melphalan injection in the management of vitreous disease in patients with retinoblastoma. We particularly aimed to assess whether higher melphalan dose with lower number of injections was more effective and associated with fewer side effects.. This retrospective, interventional, noncomparative, and nonrandomized study included 39 eyes of 37 patients. Vitreous seeds were classified as dust, sphere, and cloud types. Intravitreal injections were performed through pars plana free of any visible tumor using 30-G needle. Response of the seeds (disappearance, conversion into inactive debris, or progression) and enucleation rate were determined as outcome measures.. All patients previously received systemic or intra-arterial chemotherapy. Vitreous seeding was primary in 54% of eyes and secondary in 46% of eyes. Vitreous seeds were classified as dust in 9 (23.1%) eyes, sphere in 24 (61.5%) eyes, and cloud in 6 (15.4%) eyes. Melphalan dose varied between 20 and 40 µg and 20 (51.3%) eyes received >30 µg. The total number of injections was 70 (range 1-5, mean 1.8 per eye). Various types of regression were obtained in 27 (69.2%) eyes. Sphere-type seeds were the most responsive to melphalan. Nonresponse and disease progression were noted in 12 (30.8%) eyes. After a mean follow-up of 11.8 months, 17 (44%) eyes were enucleated. Vitreous hemorrhage (18%) and retinal pigment epithelial alterations (8%) were the most common side effects.. Intravitreal melphalan at 30-40 µg in 1 or 2 injections proved effective in 69.2% of eyes with vitreous disease.

Topics: Antineoplastic Agents, Alkylating; Child; Child, Preschool; Disease Progression; Female; Humans; Infant; Intravitreal Injections; Logistic Models; Male; Melphalan; Neoplasm Seeding; Retinal Neoplasms; Retinoblastoma; Retrospective Studies; Vitreous Body; Vitreous Hemorrhage

We aimed to evaluate the therapeutic effect and complications of combined intravitreal melphalan and intravenous/intra-arterial chemotherapy as a primary approach for retinoblastoma with vitreous seeds.. In this retrospective case series, eight eyes from eight retinoblastoma patients with vitreous seeds were included. All eyes received 20-30 μg of intravitreal melphalan accompanied by intravenous and intra-arterial chemotherapy. Triple freeze-thaw cryotherapy was performed when withdrawing the needle from the eye to prevent tumor dissemination.. Tumors and vitreous seeds regressed in all eyes. The mean number of intravitreal melphalan injections was 3.25 (median 3.50, range 2-4). Globe salvage was attained in seven of eight eyes (87.5 %). Enucleation was performed in one case, in which the pathologic section showed no residual tumor and tumor-free resection margins. Serous retinal detachment was observed in four eyes (50 %), and vitreous hemorrhage developed in two (25 %). Retinal pigment epithelium atrophy or mottling was found in three eyes (37.5 %). There were no cases of extraocular tumor extension or remote metastasis.. Combined intravitreal melphalan and intravenous/intra-arterial chemotherapy was effective for tumor and vitreous seeding control, but vision-threatening complications such as vitreous hemorrhage or serous retinal detachment occurred in half the cases.

Topics: Antineoplastic Agents, Alkylating; Antineoplastic Combined Chemotherapy Protocols; Child, Preschool; Combined Modality Therapy; Female; Humans; Infusions, Intra-Arterial; Infusions, Intravenous; Intravitreal Injections; Male; Melphalan; Neoplasm Seeding; Retinal Neoplasms; Retinoblastoma; Retrospective Studies; Vitreous Body

To investigate on the safety and efficacy of intravitreous chemotherapy for retinoblastoma seeding in a relatively large cohort and provide information on the necessary number of injections and long-term control.. Retrospective interventional case series of 40 consecutive eyes with viable vitreous seeding after standard treatment of retinoblastoma. All eyes received intravitreal melphalan injection (20-30 μg) and additional topotecan (20 μg) as needed using the trans pars plana route with triple freeze-thaw cryotherapy at needle withdrawal for prevention of extraocular seeding for planned six cycles.. The mean patient age at presentation was 36 months, and interval to need for vitreous injection was 14 months. Viable vitreous (n = 40 eyes) and additional subretinal (n = 2 eyes) seeds were documented. There was a total of 192 injections using melphalan (n = 148) and/or topotecan (n = 44) with mean number of injections per eye of melphalan at 4 (median, 4; range, 1-6) and topotecan at 3 (median, 3; range, 1-5). Fewer than six planned melphalan injections (n = 31 cases, 78%) were necessary because of rapid and complete vitreous seed control (n = 30 eyes) or melphalan allergy (n = 1 eye). Fewer than six planned topotecan injections (n = 14 cases, 100%) were necessary because of rapid and complete vitreous seed control in all cases. At median 3-year follow-up, therapeutic success with continued seed regression was observed in all 40 eyes (100%). Globe salvage was attained in 35 cases (88%), and enucleation (n = 5) was necessary for extensive recurrent subretinal seeds (n = 2), neovascular glaucoma with vitreous hemorrhage (n = 2), and hemorrhagic retinal necrosis (n = 1). Side effects included focal retinal pigment epithelial mottling at the site of injection (n = 12), minor focal paraxial lens opacity (not requiring cataract surgery) (n = 11), transient focal vitreous hemorrhage (n = 5), transient hypotony (n = 3), transient retinal hemorrhage (n = 2), optic disc edema (n = 1), and hemorrhagic retinal necrosis (n = 1). There was no case of endophthalmitis, extraocular tumor extension, metastasis, or death.. Intravitreal melphalan and/or topotecan injection for retinoblastoma vitreous seeding provides lasting tumor control at 3 years with approximately 4 injections.

Topics: Adolescent; Adult; Antineoplastic Combined Chemotherapy Protocols; Child; Child, Preschool; Eye Neoplasms; Female; Follow-Up Studies; Humans; Infant; Intravitreal Injections; Male; Melphalan; Neoplasm Seeding; Retinal Neoplasms; Retinoblastoma; Retrospective Studies; Topotecan; Vitreous Body

Topics: Antineoplastic Agents, Alkylating; Eye Neoplasms; Humans; Melphalan; Neoplasm Seeding; Retinal Neoplasms; Retinoblastoma; Vitreous Body

Topics: Antineoplastic Agents, Alkylating; Eye Neoplasms; Humans; Melphalan; Neoplasm Seeding; Retinal Neoplasms; Retinoblastoma; Vitreous Body

Topics: Antineoplastic Combined Chemotherapy Protocols; Carboplatin; Child, Preschool; Etoposide; Eye Enucleation; Fluorescein Angiography; Humans; Infusions, Intra-Arterial; Intravitreal Injections; Magnetic Resonance Imaging; Male; Melphalan; Neoplasm Invasiveness; Neoplasm Recurrence, Local; Neoplasm Seeding; Optic Nerve Neoplasms; Retinal Neoplasms; Retinoblastoma; Treatment Failure

To compare outcomes of intra-arterial chemotherapy for retinoblastoma as primary therapy before (Era I) and during (Era II) the intravitreal chemotherapy era.. In this retrospective interventional case series at a tertiary referral center, 66 eyes of 66 patients with untreated unilateral retinoblastoma were used. intraarterial chemotherapy into the ophthalmic artery under fluoroscopic guidance was performed using melphalan in every case, with additional topotecan as necessary. Intravitreal chemotherapy using melphalan and/or topotecan was employed as needed for active vitreous seeding. Globe salvage was measured based on the International Classification of Retinoblastoma (ICRB) during two eras.. The two eras encompassed 2008 to 2012 (intraarterial chemotherapy alone, Era I) and 2012 to 2015 (intraarterial chemotherapy plus intravitreal chemotherapy, Era II). Over this period, there were 66 patients with unilateral untreated retinoblastoma treated with primary intra-arterial chemotherapy. A comparison of features (Era I vs Era II) revealed no significant difference in mean patient age (24 vs 24 months), ICRB groups, mean largest tumor diameter (19 vs 17 mm), mean largest tumor thickness (10 vs 10 mm), vitreous seed presence (56% vs 59%), subretinal seed presence (67% vs 62%), retinal detachment (70% vs 66%), or vitreous hemorrhage (0% vs 5%). There was no significant difference in mean number of intra-arterial chemotherapy cycles (3 vs 3.1) or intraarterial chemotherapy dosages. Following therapy, there was a significant difference (Era I vs Era II) in the need for enucleation overall (44% vs 15%, P = .012), especially for group E eyes (75% vs 27%, P = .039). Four of the eyes that initiated therapy in Era I later required intravitreal chemotherapy during Era II. The enucleation rate was 0% for groups B and C in both eras and non-significant for group D (23% vs 13%). There were no patients with stroke, seizure, limb ischemia, extraocular tumor extension, secondary leukemia, metastasis, or death.. The current era of retinoblastoma management using intra-arterial chemotherapy plus additional intravitreal chemotherapy (as needed for vitreous seeding) has improved globe salvage in eyes with advanced retinoblastoma. [J Pediatr Ophthalmol Strabismus. 2016;53(5):275-284.].

Topics: Antineoplastic Agents, Alkylating; Child; Child, Preschool; Eye Enucleation; Female; Humans; Infant; Infusions, Intra-Arterial; Intravitreal Injections; Male; Melphalan; Neoplasm Seeding; Ophthalmic Artery; Retinal Neoplasms; Retinoblastoma; Retrospective Studies; Topoisomerase I Inhibitors; Topotecan

A 32-year-old man with active unilateral group D retinoblastoma that was recurrent following external beam radiotherapy was treated with intra-arterial chemotherapy, leading to tumor regression. Additional plaque radiotherapy and intravitreal chemotherapy were required for complete control. Final visual acuity was 20/40. In selected cases, adult-onset retinoblastoma can be managed with intra-arterial chemotherapy. [J Pediatr Ophthalmol Strabismus. 2016;53:e43-e46.].

Topics: Adult; Antineoplastic Combined Chemotherapy Protocols; Brachytherapy; Combined Modality Therapy; Humans; Infusions, Intra-Arterial; Male; Melphalan; Neoplasm Recurrence, Local; Neoplasm Seeding; Retinal Neoplasms; Retinoblastoma; Topotecan; Ultrasonography; Visual Acuity; Vitreous Body

Isolated limb infusion (ILI) with melphalan is a minimally invasive, effective treatment for in transit melanoma. We hypothesized that burden of disease (BOD) would correlate to treatment response.. We retrospectively analyzed a prospectively collected database from two academic centers. BOD was stratified as high or low (low ≤ 10 lesions, none >2 cm). Response rates were measured 3 months post-ILI. Multivariable analysis (MV) was used to evaluate the association between the response and BOD. Kaplan-Meier methods with log-rank tests and MV Cox proportional hazard models were used to analyze overall survival (OS) and progression free survival (PFS).. Sixty (38 %) patients had low and 100 (62 %) high BOD. Patients with low BOD had an overall response rate (ORR) of 73 % with 50 % CR, compared with an ORR of 47 % with 24 % CR in patients with high BOD (p = 0.002). MV analysis of preoperative, intraoperative, and postoperative parameters showed no significant impact on 3-month response. Patients with a CR at 3 months demonstrated improved PFS over the remainder of the cohort, but OS was similar. Low BOD patients had an increased median PFS of 6.9 versus 3.8 months (p = 0.047) and a increased median OS of 38.4 versus 30.9 months (p = 0.146).. Lower BOD is associated with an increased ORR and CR rate with statistically significantly improved PFS in patients undergoing ILI for in transit extremity melanoma. BOD provides useful prognostic information for patient counseling and serves as a marker to stratify patient risk groups.

Topics: Adult; Aged; Aged, 80 and over; Antibiotics, Antineoplastic; Antineoplastic Agents, Alkylating; Antineoplastic Combined Chemotherapy Protocols; Chemotherapy, Cancer, Regional Perfusion; Dactinomycin; Female; Humans; Leg; Male; Melanoma; Melphalan; Middle Aged; Multivariate Analysis; Neoplasm Seeding; Retrospective Studies; Skin Neoplasms

Topics: Antineoplastic Combined Chemotherapy Protocols; Female; Humans; Male; Melphalan; Neoplasm Seeding; Retinal Neoplasms; Topotecan; Vitreous Body

Topics: Antineoplastic Combined Chemotherapy Protocols; Female; Humans; Male; Melphalan; Neoplasm Seeding; Retinal Neoplasms; Topotecan; Vitreous Body

Assess the usefulness of second-course ophthalmic artery chemosurgery (OAC) for patients with intraocular retinoblastoma that recurred after prior OAC. This study evaluated the efficacy and toxicity of second-course OAC.. Single-arm retrospective study of 29 eyes of 30 patients treated with second-course OAC at Memorial Sloan Kettering Cancer Center between May 2006 and July 2013, with a median follow-up of 25.9 months.. Retinoblastoma patients who underwent a course of OAC, with a minimum of 2 months of progression-free follow-up at monthly examinations, but who subsequently received additional OAC for recurrent tumor.. To determine efficacy, Kaplan-Meier survival estimates were generated and the Mantel-Cox test was used to compare curves. To determine toxicity, electroretinography (ERG) amplitudes were measured in response to 30-Hz photopic flicker stimulation before and after OAC treatment; systemic adverse events were graded according to the Common Terminology Criteria for Adverse Events version 4.0 (CTCAE 4.0).. For efficacy, ocular progression-free survival, ocular event-free survival (e.g., enucleation, external-beam radiation, or intravitreal melphalan), and ocular survival. For toxicity, peak-to-peak comparisons between ERG studies before and after OAC treatment and CTCAE 4.0-graded systemic adverse events.. Fifty percent of all recurrences were within 4.4 months and 90% were within 16 months of completion of the first course of OAC. The 2-year Kaplan-Meier ocular survival, event-free survival, and progression-free survival estimates after second-course OAC were 82.8% (95% confidence interval [CI], 60.1%-93.2%), 57.3% (95% CI, 36.1%-73.7%), and 26.5% (95% CI, 11.0%-45.0%), respectively. All eyes without vitreous seeding were progression free, whereas eyes with vitreous seeding were associated significantly with worse ocular survival after second-course OAC (P = 0.03). After second-course OAC, 90% of eyes had stable or improved ERG responses. Of all evaluable cases, there was no increased risk of systemic toxicity during the second course compared with the initial course of OAC.. Retinoblastoma eyes requiring second-course OAC after initial OAC treatment have good salvage rates, and the treatment has an acceptable ocular and systemic toxicity profile. However, these eyes often require additional (third- or fourth-course) OAC or other treatment methods because of progression of disease after second-line OAC, particularly if vitreous seeds are present at the time of initial OAC failure.

Topics: Adolescent; Antineoplastic Agents, Alkylating; Child; Child, Preschool; Disease-Free Survival; Electroretinography; Female; Humans; Infant; Infusions, Intra-Arterial; Male; Melphalan; Neoplasm Recurrence, Local; Neoplasm Seeding; Ophthalmic Artery; Retina; Retinal Neoplasms; Retinoblastoma; Retreatment; Retrospective Studies; Salvage Therapy; Treatment Outcome; Vitreous Body

Topics: Antineoplastic Combined Chemotherapy Protocols; Child, Preschool; Eye Neoplasms; Female; Fovea Centralis; Humans; Infusions, Intra-Arterial; Intravitreal Injections; Melphalan; Neoplasm Seeding; Retinal Neoplasms; Retinoblastoma; Tomography, Optical Coherence; Topotecan; Vitreous Body

To evaluate the clinical characteristics of the 3 classifications of vitreous seeds in retinoblastoma-dust (class 1), spheres (class 2), and clouds (class 3)-and their responses to intravitreal melphalan.. Retrospective, bi-institutional cohort study.. A total of 87 patient eyes received 475 intravitreal injections of melphalan (median dose, 30 μg) given weekly, a median of 5 times (range, 1-12 times).. At presentation, the vitreous seeds were classified into 3 groups: dust, spheres, and clouds. Indirect ophthalmoscopy, fundus photography, ultrasonography, and ultrasonic biomicroscopy were used to evaluate clinical response to weekly intravitreal melphalan injections and time to regression of vitreous seeds. Kaplan-Meier estimates of time to regression and ocular survival, patient survival, and event-free survival (EFS) were calculated and then compared using the Mantel-Cox test of curve.. Time to regression of vitreous seeds, patient survival, ocular survival, and EFS.. The difference in time to regression was significantly different for the 3 seed classes (P < 0.0001): the median time to regression was 0.6, 1.7, and 7.7 months for dust, spheres, and clouds, respectively. Eyes with dust received significantly fewer injections and a lower median and cumulative dose of melphalan, whereas eyes with clouds received significantly more injections and a higher median and cumulative dose of melphalan. Overall, the 2-year Kaplan-Meier estimates for ocular survival, patient survival, and EFS (related to target seeds) were 90.4% (95% confidence interval [CI], 79.7-95.6), 100%, and 98.5% (95% CI, 90-99.7), respectively.. The regression and response of vitreous seeds to intravitreal melphalan are different for each seed classification. The vitreous seed classification can be predictive of time to regression, number, median dose, and cumulative dose of intravitreal melphalan injections required.

Topics: Adolescent; Antineoplastic Agents, Alkylating; Child; Child, Preschool; Cohort Studies; Disease-Free Survival; Eye Neoplasms; Follow-Up Studies; Humans; Infant; Intravitreal Injections; Melphalan; Neoplasm Seeding; Retinal Neoplasms; Retinoblastoma; Retrospective Studies; Survival Rate; Vitreous Body

To investigate the safety and efficacy of intravitreal injection of melphalan for retinoblastoma.. A retrospective chart review of all patients who were administered intravitreal injections of melphalan for retinoblastoma between 1990 and 2011. A total of 264 eyes of 250 patients were included. All ocular adverse events, systemic prognosis, ocular prognosis, and visual acuity were investigated.. The total number of intravitreal injections administered was 1,067; each eye received between one and 25 injections. A postoperative subconjunctival tumor developed in one eye. None of the eyes suffered infections or uveitis, and all other adverse events including chorioretinal atrophy displayed incidences of less than 1.5 %. At 5 postoperative years, the cumulative incidence of cataract surgery was 3.1 % among the eyes that were treated without ocular hyperthermia. Distant metastasis or intracranial invasion occurred in 11 patients, all of whom had high-risk pathological factors for metastasis such as optic nerve invasion, but refused to receive adjuvant chemotherapy. Sixty-eight percent of the eyes achieved complete vitreous seed remission, but recurrence occurred in 19 % of these eyes after 10.0 ± 4.9 months. In addition, 47 and 27 % of the eyes without primary macular tumors retained visual acuity of >0.5 and >1.0, respectively.. The risk of extraocular tumor spreading following intravitreal injections is low, and other adverse events are rare. Sixty-eight percent of the treated eyes achieved complete vitreous seed remission, and about half of them retained practical levels of vision. The intravitreal injection of melphalan is a safe and effective treatment for vitreous seeds.

Topics: Adolescent; Antineoplastic Agents, Alkylating; Child; Child, Preschool; Female; Humans; Infant; Intravitreal Injections; Male; Melphalan; Neoplasm Recurrence, Local; Neoplasm Seeding; Retinal Neoplasms; Retinoblastoma; Retrospective Studies; Vitreous Body; Young Adult

Intra-arterial melphalan chemotherapy (IAC) continues to demonstrate excellent utility in the treatment of retinoblastoma. We present the case of a 3-month-old boy diagnosed with with unilateral, advanced stage 5B retinoblastoma and a Coats' response in the right eye. After laser therapy he received 3 doses of IAC. Intraretinal hemorrhaging, first noted after the second dose and worsening after the third, preceded complex exudative retinal detachment. With little visual potential and evidence of atropy, the eye was enucleated. This case illustrates that intraretinal hemorrhage may serve as an early predictor of treatment failure.

Topics: Antineoplastic Agents, Alkylating; Eye Enucleation; Humans; Infant; Infusions, Intra-Arterial; Male; Melphalan; Neoplasm Seeding; Neoplasm Staging; Retinal Detachment; Retinal Hemorrhage; Retinal Neoplasms; Retinoblastoma; Treatment Failure; Visual Acuity; Vitreous Body

To describe the efficacy of intravitreal chemotherapy (IViC) preceded by intra-arterial chemotherapy (IAC) for the treatment of advanced stage retinoblastoma. This non-comparative interventional case series retrospectively reviewed the medical records of six patients who presented within months of each other with unilateral retinoblastoma, Reese-Ellsworth stage Vb/D of ABC classification in the affected eye. After clinical and ophthalmoscopic evaluation, they underwent MRI to exclude local and CNS dissemination. The IAC was given to treat retinal masses and intravitreal injections to treat vitreous seeding. Patients had received two cycles (six infusions) of IAC, and from six up to ten melphalan injections into the vitreous, with an interval of 7-10 days between them. From one to four intravitreal injections were performed for partial remission or consolidation. No permanent complications of procedures have been reported. All patients underwent to bimonthly MRI examination, during treatment and every 3 months for 1 year after last injection, to exclude orbital dissemination. Successful control (100 %) of tumor masses and vitreous seeds was achieved in all cases at 12 months follow-up. Complications were posterior lens opacity, acute ischemic papillitis, partial CVR thrombosis, hypotonia (case 1), partial vitreous hemorrhage (case 4). No complications appeared in cases 2, 3, 5, and 6. No intraocular or orbital tumor recurrence or retinoblastoma metastases (follow-up range, 12-33 months) were observed. Sequential IAC and intravitreal melphalan for advanced retinoblastoma allowed to provide retinal and vitreous seed control.

Topics: Antineoplastic Agents, Alkylating; Antineoplastic Combined Chemotherapy Protocols; Child, Preschool; Female; Humans; Infant; Injections, Intra-Arterial; Intravitreal Injections; Male; Melphalan; Neoplasm Seeding; Retinal Neoplasms; Retinoblastoma; Retrospective Studies; Topotecan

The major cause of failure in the management of retinoblastoma is the persistence/recurrence of vitreous seeds (VS). This study reports the efficacy and complications of standard lower-dose (20 µg) intravitreal melphalan for VS.. Retrospective review of all patients with active VS treated with lower-dose intravitreal melphalan (20 µg/0.1 mL) on a monthly basis until complete VS regression was achieved.. A total of 14 injections were delivered to seven eyes of seven patients (range: 1-4; median: 2). At a median follow-up of 20 months (range: 12-32 months), complete regression of VS was achieved in all cases (100%), and globe salvage was achieved in six cases (86%). One eye required enucleation for solid tumor recurrence. Side effects of retinal pigment epithelium mottling at the site of injection was noted in two eyes (29%).. The 2-year results of this study suggest that standard lower-dose (20 µg) intravitreal melphalan is safe and highly effective for the management of viable VS from retinoblastoma.

Topics: Antineoplastic Agents, Alkylating; Child, Preschool; Female; Follow-Up Studies; Humans; Infant; Intravitreal Injections; Male; Melphalan; Neoplasm Recurrence, Local; Neoplasm Seeding; Retinal Neoplasms; Retinoblastoma; Retrospective Studies; Vitreous Body

The aim of this study is to evaluate the pathological findings of the eye after intravitreal melphalan for viable vitreous seeding from retinoblastoma. All enucleated eyes receiving an intravitreal injection of melphalan (10-50 μg in 0.05 cc) were evaluated for histological changes. Of 25 treated cases, 8 eyes needed enucleation because of phthisis, parent request, or new tumor development. One of the cases was excluded from the study because of a history of intra-arterial chemotherapy with melphalan. There was no case of needle-site scleral involvement by retinoblastoma cells. In two eyes receiving 50 μg melphalan, no viable retinoblastoma cell was detectable in the eye. Severe gliosis, vascular occlusion, retinal necrosis, hemorrhage and neovascularization were seen. Histologically, intravitreal melphalan for recalcitrant or recurrent vitreous seeds from retinoblastoma appears to provide acceptable vitreous seed control. It seems that higher doses could be destructive causing ischemic necrosis in the retina, severe gliosis and secondary neovascular changes as well as having a destructive effect on retinoblastoma cells.

Topics: Antineoplastic Agents, Alkylating; Child, Preschool; Eye Enucleation; Humans; Infant; Intravitreal Injections; Melphalan; Neoplasm Seeding; Retinal Neoplasms; Retinoblastoma; Retrospective Studies; Vitreous Body

Recurrent or persistent vitreous seeds following treatment of retinoblastoma poses difficult management and often leads to enucleation.. To describe the technique and evaluate the efficacy and complications of intravitreal melphalan for vitreous seeding from retinoblastoma.. This retrospective noncomparative analysis was conducted at a tertiary referral center. The study included 11 consecutive eyes of 11 patients with viable persistent or recurrent vitreous seeds following treatment of retinoblastoma.. All eyes received intravitreal melphalan injection (20-30 µg) by transconjunctival pars plana route with concomitant triple-freeze cryotherapy at the injection site during needle withdrawal for prevention of extraocular seeding. Each patient was offered planned 6 monthly cycles.. Vitreous seed control and complications of therapy.. The mean patient age at vitreous injection was 37 months (median, 27 months; range, 16-82 months). Viable vitreous seeds involved 2 (n = 1), 3 (n = 4), or 4 (n = 6) quadrants. The solid intraretinal retinoblastoma and subretinal seeds showed regression in all eyes following intravenous chemotherapy (n = 6) or intra-arterial chemotherapy (n = 5). There were a total of 55 injections, with a mean number per patient of 5 (median, 6; range, 2-6). Fewer than 6 injections (n = 5) were delivered owing to complete vitreous seed control and parental desire to avoid more injections. By a mean of 9 months' follow-up (median, 9 months; range, 6-16 months), therapeutic success with complete vitreous seed regression was achieved in all 11 cases (100%). Globe salvage was attained in all cases (100%). Further vitreous seed development did not occur in any case. Complications included focal retinal pigment epithelial mottling near the site of chemotherapy injection (2 eyes) and nonaxial posterior lens opacity (2 eyes). There was no case of extraocular tumor extension, hypotony, or phthisis bulbi.. These preliminary short-term results suggest that intravitreal melphalan injection for persistent or recurrent vitreous retinoblastoma seeding can provide tumor control with minimal toxicity and complications.

Topics: Antineoplastic Agents, Alkylating; Child; Child, Preschool; Combined Modality Therapy; Cryotherapy; Eye Neoplasms; Female; Humans; Infant; Intravitreal Injections; Male; Melphalan; Neoplasm Recurrence, Local; Neoplasm Seeding; Retinal Neoplasms; Retinoblastoma; Retrospective Studies; Vitreous Body

Demonstrating the usefulness and complications of multiagent intravitreal chemotherapy is necessary for successful treatment in patients with recalcitrant vitreous seeding of retinoblastoma.. To determine the efficacy and complications of combined intravitreal chemotherapy (melphalan hydrochloride and topotecan hydrochloride) for viable vitreous seeding from retinoblastoma.. This retrospective study was conducted in a hospital setting. Trans-pars plana intravitreal injection of melphalan hydrochloride (40 µg in 0.04 mL of diluent) combined with topotecan hydrochloride (8-20 µg in 0.04 mL of balanced salt solution) was performed in 9 eyes, followed by injection site cryotherapy.. Complete regression of vitreous seeds of retinoblastoma.. Nine eyes, initially classified as group D (n = 6) or E (n = 3) according to International Classification of Retinoblastoma categorization, received a standard 6 cycles of intravenous chemotherapy and/or intra-arterial chemotherapy and subsequently developed recurrent viable vitreous seeds. Intravitreal administration of melphalan combined with topotecan produced complete control of vitreous seeds in all 9 eyes following a mean of 1.9 injections (median, 2; range, 1-3 injections). In 3 cases (33%), tumor control was achieved with a single injection, whereas in 6 (67%) cases, 2 or 3 injections were necessary. Three patients (33%) subsequently underwent enucleation because of recurrent tumor and persistent anterior chamber lesions. During a mean 15.2 months of follow-up (median, 16; range, 7-25 months), there was no recurrence of new tumor or vitreous seeds in the remaining 6 eyes. Complications included temporary hypotonia of 2 weeks or less (2 [22%]), temporary epithelial defect (1 [11%]), and vitreous hemorrhage (1 [11%]). There was no case of episcleral or orbital retinoblastoma extension or remote retinoblastoma metastasis. There was no change in the a and b waves of bright-flash electroretinograms.. Administration of combined intravitreal melphalan and topotecan in eyes not subsequently enucleated appears to be safe and effective for resistant or recurrent vitreous seeds from retinoblastoma. In 3 of the cases (33%), tumor control was achieved with a single injection.

Topics: Antineoplastic Combined Chemotherapy Protocols; Child, Preschool; Female; Humans; Infant; Intravitreal Injections; Male; Melphalan; Neoplasm Seeding; Recurrence; Retinal Neoplasms; Retinoblastoma; Retrospective Studies; Topotecan; Vitreous Body

Intravitreal melphalan is emerging as an effective treatment for refractory vitreous seeds in retinoblastoma, but there is limited understanding regarding its toxicity. This study evaluates the retinal and systemic toxicity of intravitreal melphalan in retinoblastoma patients, with preclinical validation in a rabbit model.. Clinical and preclinical, prospective, cohort study.. In the clinical study, 16 patient eyes received 107 intravitreal injections of 30 μg melphalan given weekly, a median of 6.5 times (range, 5-8). In the animal study, 12 New Zealand/Dutch Belt pigmented rabbits were given 3 weekly injections of 15 μg of intravitreal melphalan or vehicle to the right eye.. Electroretinogram (ERG) responses were recorded in both humans and rabbits. For the clinical study, ERG responses were recorded at baseline, immediately before each injection, and at each follow-up visit; 82 of these studies were deemed evaluable. Median follow-up time was 5.2 months (range, 1-11). Complete blood counts (CBCs) were obtained on the day of injection at 46 patient visits. In the animal study, ERG responses were obtained along with fluorescein angiography, CBCs, and melphalan plasma concentration. After humane killing, the histopathology of the eyes was evaluated.. For the clinical study, we measured peak-to-peak ERG amplitudes in response to 30-Hz photopic flicker stimulation with comparisons between ERG studies before and after intravitreal melphalan. For the animal study, we collected ERG parameters before and after intravitreal melphalan injections with histopathologic findings.. By linear regression analysis, over the course of weekly intravitreal injections in retinoblastoma patients, for every additional injection, the ERG amplitude decreased by approximately 5.8 μV. The ERG remained stable once the treatment course was completed. In retinoblastoma patients, there were no grade 3 or 4 hematologic events. One week after the second injection in rabbits, the a- and b-wave amplitude declined significantly in the melphalan treated eyes compared with vehicle-treated eyes (P<0.05). Histopathology revealed severely atrophic retina.. Weekly injections of 30 μg of melphalan can result in a decreased ERG response, which is indicative of retinal toxicity. These findings are confirmed at an equivalent dose in rabbit eyes by ERG measurements and by histopathologic evidence of severe retinal damage. Systemic toxicity with intravitreal melphalan at these doses in humans or rabbits was not detected.

Topics: Animals; Antineoplastic Agents, Alkylating; Blood Cell Count; Child; Child, Preschool; Drug Evaluation, Preclinical; Electroretinography; Female; Fluorescein Angiography; Humans; Infant; Intravitreal Injections; Male; Melphalan; Neoplasm Seeding; Prospective Studies; Rabbits; Regression Analysis; Retinal Neoplasms; Retinoblastoma; Vitreous Body

Topics: Antineoplastic Agents, Alkylating; Humans; Intravitreal Injections; Male; Melphalan; Neoplasm Seeding; Retinal Neoplasms; Retinoblastoma; Vitreous Body

Treatment of vitreous seeds in retinoblastoma is challenging because of relatively poor chemotherapeutic drug penetration by standard intravenous or intra-arterial routes. Intravitreal monotherapy with melphalan is effective but has a narrow therapeutic window. The authors describe a case of massive vitreous seeding successfully controlled after combination intravitreal chemotherapy using melphalan and topotecan with preserved anatomic outcome.

Topics: Antineoplastic Combined Chemotherapy Protocols; Child, Preschool; Eye Neoplasms; Female; Humans; Intravitreal Injections; Melphalan; Neoplasm Seeding; Retinal Neoplasms; Retinoblastoma; Topotecan; Vitreous Body

Topics: Antineoplastic Agents, Alkylating; Child; Humans; Intravitreal Injections; Male; Melphalan; Neoplasm Seeding; Retinal Neoplasms; Retinoblastoma; Vitreous Body

To assess the efficacy of less than 3 cycles of intra-arterial chemotherapy (IAC) for retinoblastoma.. Retrospective, nonrandomized, interventional case series.. Eight patients.. Intra-arterial chemotherapy.. Tumor control and globe salvage.. Eight patients received fewer than 3 cycles of IAC for retinoblastoma because there was complete tumor control with no residual viable tumor (n = 7) or poor response (n = 1) with little hope that further therapy would benefit the patient. In 3 cases, additional vascular compromise precluded further IAC. The treatment was primary in 6 cases and secondary after failure of other treatment in 2 cases. The 8 eyes were classified (International Classification of Retinoblastoma) as group C (n = 2), group D (n = 3), group E (n = 1), and secondary treatment (n = 2). At initial examination, the main tumor showed a mean basal diameter of 16 mm, a thickness of 8.6 mm, vitreous seeds (n = 2), subretinal seeds (n = 6), and iris neovascularization (n = 1). Three patients were treated with a single cycle of IAC, and 5 patients were treated with 2 cycles of IAC. After IAC, complete tumor response was found in 7 eyes (88%) and partial response was found in 1 eye (13%). Over a mean of 13 months follow-up, there was intraretinal tumor recurrence (n = 1), subretinal seed recurrence (n = 1), and no case of vitreous seed recurrence. Globe salvage was achieved in 2 of 2 group C eyes (100%), 3 of 3 group D eyes (100%), 0 of 1 group E eye (0%), and 1 of 2 secondary treatment eyes (50%). Globe salvage was achieved in 6 of 8 eyes (75%), and 2 of 8 eyes (25%) required enucleation.. One or 2 cycles of IAC can be sufficient for selected eyes with group C or D retinoblastoma, with remarkable tumor control.. The author(s) have no proprietary or commercial interest in any materials discussed in this article.

Topics: Antineoplastic Combined Chemotherapy Protocols; Carboplatin; Eye Enucleation; Eye Neoplasms; Female; Humans; Infant; Infusions, Intra-Arterial; Male; Melphalan; Neoplasm Seeding; Retinal Neoplasms; Retinoblastoma; Retreatment; Retrospective Studies; Salvage Therapy; Treatment Outcome; Vitreous Body

The preservation of globe integrity has always been a major concern during the treatment of retinoblastoma for fear of extraocular or metastatic spread. Intravitreal chemotherapy has been attempted as a desperate salvage therapy only for eyes with refractory retinoblastoma. Published data on the safety and efficacy of this route are, however, limited.. A modified technique of intravitreal injection in eyes with retinoblastoma is described. All children with retinoblastoma who received one or more intravitreal injections using this technique were retrospectively reviewed concerning ocular complications of the injection procedure as well as clinical or histopathological evidence of tumour spread.. 30 eyes of 30 children with retinoblastoma received a total of 135 intravitreal injections, with a median follw-up duration of 13.5 months. No extraocular spread was seen on clinical follow-up in any patients and there was no tumour contamination of the retrieved entry sites histopathologically analysed among the five enucleated eyes. No significant ocular side effects were observed except transient localised vitreous haemorrhage (3/135).. This technique is potentially safe and effective at a low cost and may play a promising role, especially in the treatment of recurrent and/or resistant vitreous disease in retinoblastoma, as an alternative to enucleation and/or external beam radiotherapy. However, this treatment should not replace the primary standard of care of retinoblastoma and should not be considered in group E eyes. Its application should be approved by an ophthalmological-oncological team and it should be performed by an experienced eye surgeon in a tertiary referral centre after careful selection of a tumour-free injection site.

Topics: Antineoplastic Agents; Carboplatin; Child, Preschool; Eye Neoplasms; Female; Humans; Infant; Infant, Newborn; Intravitreal Injections; Male; Melphalan; Microscopy, Acoustic; Neoplasm Seeding; Paracentesis; Retinal Neoplasms; Retinoblastoma; Retrospective Studies; Sterilization; Vitreous Body

Tumour control of vitreous seeds remains challenging owing to their resistance to radiation and systemic chemotherapy.. To describe the short-term efficacy of intravitreal melphalan for vitreous disease in retinoblastoma using a new injection technique and dose.. This study is a retrospective non-comparative review of 23 consecutive heavily pretreated patients (23 eyes) with active vitreous seeding and eligible for intravitreous chemotherapy (IViC). They received a total of 122 intravitreal injections of melphalan (20-30 μg) given every 7-10 days. The ocular status was objectively monitored under anaesthesia with fundus photography.. All patients are alive without evidence of extraocular spread (95% CI 82.19% to 100%). Concomitant treatments, including other chemotherapeutic modalities, were used until complete sterilisation of the retinal seeding source and subretinal seeds. Globe retention was achieved in 87% (20/23) of cases. All retained eyes were in complete remission after a median follow-up period of 22 months (range 9-31 months). The Kaplan-Meier estimate of ocular survival rates at 2 years was 84.14% (95% CI 62.48% to 95.28%). A localised peripheral salt-and-pepper retinopathy was noted in 10 eyes (43%) at the site of injection.. This study reports the first clinically documented case series of patients with retinoblastoma treated with IViC. Despite a possible confounding effect of concomitant chemotherapy prescription using other routes of administration in four of the successfully treated eyes (20%), IViC achieved an unprecedented success rate of tumour control in the presence of vitreous seeding. Of note, none of the treated eyes required external beam irradiation to control the vitreous seeding. Further studies are required to assess IViC retinal toxicity and to better delineate its role in the management of retinoblastoma.

Topics: Antineoplastic Agents, Alkylating; Child, Preschool; Eye Neoplasms; Female; Follow-Up Studies; Humans; Infant; Infant, Newborn; Intravitreal Injections; Male; Melphalan; Neoplasm Seeding; Retinal Neoplasms; Retinoblastoma; Retreatment; Retrospective Studies; Treatment Outcome; Vitreous Body

To evaluate the efficacy and complications of intravitreal chemotherapy for viable vitreous seeding from retinoblastoma.. Intravitreal injection of melphalan (8-50 μg in 0.05 mL) followed by injection site cryotherapy.. Among 12 treated cases, success with control of vitreous seeds was achieved in 10 of 12 cases at immediate follow-up (0-3 months), 8 of 10 cases at short-term follow-up (3-6 months), and 6 of 10 cases at long-term (>6 months) follow-up. Among those 8 cases that received an 8- to 10-μg dose, control was achieved in 6 of 8 cases at immediate follow-up, 5 of 7 cases at short-term follow-up, and 3 of 7 cases at long-term follow-up. Complications with the 8- to 10-μg dose were minor and included preretinal hemorrhage and retinal vasculitis with retinal pigment epithelial alterations. Of those 4 that received a 50-μg dose, immediate, short-term, and long-term control was 100%, but complications of cataract, vitreous hemorrhage, subretinal hemorrhage, severe hypotonia, and phthisis lead to enucleation in 2 cases. There was no case of orbital tumor recurrence or retinoblastoma metastasis (follow-up range, 8-66 months).. Intravitreal melphalan for recurrent vitreous seeds from retinoblastoma appears to provide vitreous seed control in some patients. A high dose (50 μg) of melphalan is toxic and should be avoided.

Topics: Antineoplastic Agents, Alkylating; Child; Child, Preschool; Follow-Up Studies; Humans; Infant; Intravitreal Injections; Melphalan; Neoplasm Recurrence, Local; Neoplasm Seeding; Radiotherapy, Adjuvant; Retinal Neoplasms; Retinoblastoma; Treatment Outcome; Vitreous Body

To describe tumor control following intra-arterial chemotherapy (IAC) for retinoblastoma.. A retrospective interventional series in which 17 patients were treated with ophthalmic artery injection of melphalan, 5 mg, was undertaken to determine retinoblastoma control.. Of 190 children with retinoblastoma, 17 (9%) were treated with IAC. Catheterization was successful in 37 of 38 attempts. The treatment was primary in 13 cases (1 failed catheterization) and secondary in 4. The median retinoblastoma base was 20 mm and the median retinoblastoma thickness was 9.0 mm. Iris neovascularization was present in 5 cases. Following IAC, complete response of the main tumor was found in 14 cases (88%) and partial response was found in 2 (12%). Eyes with complete response and followed up for a minimum of 1 year (n = 10) showed no solid tumor recurrence. Of 11 eyes with subretinal seeds, 9 (82%) had complete response, 1 (9%) had partial response, and 1 (9%) had recurrence. Of 9 eyes with vitreous seeds, 6 (67%) had complete response, 2 (22%) had partial response, and 1 (11%) had recurrence. Globe salvage was achieved in 8 of 12 eyes (67%) treated with primary IAC, including 2 of 2 group C eyes, 4 of 4 group D eyes, and 2 of 6 group E eyes according to the International Classification of Retinoblastoma. Globe salvage was achieved in 2 of 4 eyes (50%) treated secondarily after failure of other methods.. Of 12 eyes managed with IAC as primary treatment, globe salvage was achieved in 67%. Eyes classified as group C or D showed 100% globe salvage, whereas group E had 33% salvage. Of 4 eyes managed with IAC as secondary treatment, globe salvage was achieved in 50%.

Topics: Antineoplastic Agents, Alkylating; Cerebral Angiography; Chemotherapy, Cancer, Regional Perfusion; Child; Child, Preschool; Electroretinography; Eye Neoplasms; Female; Fluorescein Angiography; Fluoroscopy; Humans; Infant; Injections, Intra-Arterial; Male; Melphalan; Neoplasm Seeding; Ophthalmic Artery; Retinal Neoplasms; Retinoblastoma; Retrospective Studies; Treatment Outcome; Vitreous Body

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: Antineoplastic Agents, Alkylating; Chemotherapy, Cancer, Regional Perfusion; Eye Neoplasms; Female; Humans; Injections, Intra-Arterial; Male; Melphalan; Neoplasm Seeding; Retinal Neoplasms; Retinoblastoma; Vitreous Body

Isolated limb perfusion (ILP) is an effective treatment modality for multiple in-transit melanoma metastases confined to the limb. Recurrences after ILP, however, occur in approximately 50% of patients and are a challenge for further treatment. The efficacy of repeat ILPs to prolong local control in this patient category is evaluated in this article.. We used a prospective database in a tertiary referral center. Out of 100 tumor necrosis factor (TNF)-based ILPs with TNF and melphalan (TM-ILPs) in melanoma patients between March 1991 and July 2003, 25 repeat ILP procedures were performed in 21 patients in whom prior ILP treatment failed. All patients had bulky and/or numerous lesions and were treated with mild hyperthermic TM-ILP by using 2 to 4 mg of TNF and 10 to 13 mg/L of limb volume for the leg and arm, respectively.. The complete response rate was 76%, a partial response occurred in 20%, and no change was recorded in 4%. There was no difference in the complete response rate or local toxicity between first and repeat perfusions. Local recurrence occurred in 72%; the median time to local progression was 14 months. The 5-year survival rate was 47%, which compares favorably with known survival rates of stage IIIA/AB patients. The median follow-up of the patients was 26 months.. Patients who experience treatment failure after previous ILP treatment respond very well to repeat perfusion, and prolonged local control can thus be obtained. The subgroup of patients qualifying for repeat ILP represents a relatively favorable biological behavior of the melanoma.

Topics: Adult; Aged; Aged, 80 and over; Antineoplastic Agents, Alkylating; Arm; Chemotherapy, Cancer, Regional Perfusion; Disease Progression; Drug Therapy, Combination; Female; Humans; Leg; Male; Melanoma; Melphalan; Middle Aged; Neoplasm Seeding; Retreatment; Skin Neoplasms; Treatment Failure; Tumor Necrosis Factor-alpha