Radiation retinopathy following plaque radiotherapy for posterior uveal melanoma.

OBJECTIVE: To identify the risk factors that lead to the development of radiation retinopathy following plaque radiotherapy for posterior uveal melanoma. Radiation retinopathy is a slowly progressive, occlusive vasculopathy characterized by radiation-induced endothelial damage. METHODS: Review of the medical records of patients with posterior uveal melanoma treated with plaque radiotherapy. RESULTS: Of 1300 patients with posterior uveal melanoma treated with plaque radiotherapy from July 1, 1976, through June 30, 1992, radiation retinopathy developed in 560 (43.1%). By using Kaplan-Meier survival estimates, we found that 5% of the patients had nonproliferative radiation retinopathy at 1 year (95% confidence interval [CI], 3%-6%) and 42% at 5 years (95% CI, 38%-45%). The proportion of patients with proliferative retinopathy was 1% at 1 year (95% CI, 0.2%-1.5%) and 8% at 5 years (95% CI, 5%-10%). Multivariate analyses showed that the subset of clinical variables best related to the development of nonproliferative radiation retinopathy were tumor margin of less than 4 mm from foveola (P<.001), tumor limited to the choroid (P = .002), and radiation dose rate of greater than 260 cGy/h to the tumor base (P = .02). The best subset of independent variables related to the development of radiation maculopathy were tumor of less than 4 mm to foveola (P<.001) and the use of radioisotope iridium 192 (192Ir) (P = .02) compared with iodine 125 (125I). From a multivariate model, the most important factors for the development of proliferative radiation retinopathy included diabetes mellitus (P = .01), radioisotope 192Ir (P = .01) compared with 125I, and tumor base of greater than 10 mm (P = .02). CONCLUSIONS: Radiation retinopathy is a common finding after plaque radiotherapy for choroidal melanoma, occurring in 42% of patients at 5 years. The main predictors of radiation retinopathy are posterior tumor location with margin near the foveola and high radiation dose rate to the tumor base.

Radiation complications and tumor control after plaque radiotherapy of choroidal melanoma with macular involvement.

PURPOSE: To determine the outcome of plaque radiotherapy in the treatment of macular choroidal melanoma and to identify the risk factors associated with the development of radiation complications, tumor recurrence, and metastasis. METHODS: Chart analysis of 630 consecutive patients (630 eyes) with macular choroidal melanoma managed by plaque radiotherapy between July 1976 and June 1992. RESULTS: The median largest basal tumor diameter was 10 mm, and the median tumor thickness was 4 mm. By means of Kaplan-Meier estimates, visually significant maculopathy developed at 5 years in 40% of the patients, cataract in 32%, papillopathy in 13%, and tumor recurrence in 9%. Vision decrease by 3 or more Snellen lines was found in 40% of the patients at 5 years. Sixty-nine eyes (11%) were enucleated because of radiation complications and recurrence. Twelve percent of the patients developed metastasis by 5 years and 22% by 10 years. Results of multivariate Cox proportional hazards analyses showed that the significant predictors for tumor recurrence were a distance of tumor margin from the optic disk of less than 2 mm (P = .003) and retinal invasion (P = .009). The significant variables that were predictive of metastasis included tumor thickness greater than 4 mm (P = .02) and largest basal tumor diameter greater than 10 mm (P = .03). CONCLUSIONS: Plaque radiotherapy offers a 91% 5-year local tumor control rate for macular choroidal melanoma. Despite good local tumor control, the risk for metastasis is 12% at 5 years and 22% at 10 years. In 11% of the patients, enucleation eventually became necessary because of radiation complications and tumor recurrence.

Plaque radiotherapy of uveal melanoma with predominant ciliary body involvement.

BACKGROUND: There are several options for management of ciliary body melanoma, including plaque radiotherapy, charged particle irradiation, local resection, and enucleation. The choice of therapy depends on many factors, and plaque radiotherapy is often used. OBJECTIVES: To determine the outcome of plaque radiotherapy in the management of ciliary body melanoma and to identify the risk factors associated with the development of radiation complications, tumor recurrence, metastasis, and melanoma-related death after plaque radiotherapy of ciliary body melanoma. METHODS: We analyzed the clinical records of 136 patients with ciliary body melanoma who were treated with plaque radiotherapy between July 1976 and June 1992. RESULTS: The median follow-up period was 70 months. Using Kaplan-Meier survival estimates, the most frequent radiation complication at 5 years' follow-up was cataract, developing in 48% of the patients, followed by neovascular glaucoma (21%), retinopathy (20%), scleral necrosis (12%), and vitreous hemorrhage (11%). Visual acuity decrease (by > or =3 Snellen lines) was noted in 40% of the patients at 5 years. Kaplan-Meier estimates showed that 8% of the patients developed recurrence, 28% had metastasis, and 22% died of melanoma-related causes by 5 years. Univariate analysis demonstrated that the factors predictive of radiation cataract were superonasal (P = .003) and inferior tumor meridian (P = .02) compared with inferonasal meridian and apex dose rate greater than 57 cGy/h (P = .05). The development of neovascular glaucoma was significantly related to iris involvement with the ciliary body tumor (P<.001). The factors predictive of development of radiation retinopathy were base dose rate greater than 230 cGy/h (P = .03) and the presence of diabetes mellitus (P = .05). The only predictor of metastasis was tumor thickness greater than 7 mm (P = .02). The risk factors for melanoma-related death were the presence of metastasis (P<.001), tumor thickness greater than 7 mm (P = .02), and recurrence (P = .02). Multivariate analyses showed that the most significant variables predictive of the development of scleral necrosis were intraocular pressure greater than 15 mm Hg (P<.001) and tumor thickness greater than 7 mm (P = .007). The most significant predictive factors for vitreous hemorrhage were visual acuity of 20/40 to 20/200 (P = .02) and intraocular pressure greater than 15 mm Hg (P = .02). The best subset of independent predictors of vision decrease were mushroom tumor shape (P = .002), age older than 61 years (P = .006), and superonasal meridian (P = .04). The risks for melanoma-related death were presence of metastasis (P<.001) and tumor thickness greater than 7 mm (P = .01). There was no group of significant variables predictive for radiation cataract, neovascular glaucoma, retinopathy, tumor recurrence, and metastasis in multivariate analysis. CONCLUSIONS: Plaque radiotherapy offers 92% 5-year local control rate for ciliary body melanoma. Metastasis occurs in 28% of the patients treated with this method by 5 years. Patients with tumors greater than 7 mm in thickness are at greater risk than patients with thinner tumors for metastatic disease and melanoma-related death. Major radiation complications include radiation cataract, neovascular glaucoma, retinopathy, and scleral necrosis.

Adenoid cystic carcinoma of the lacrimal gland simulating a dermoid cyst in a 9-year-old boy.

Adenoid cystic carcinoma of the lacrimal gland is a malignant neoplasm that is generally found in adults and is usually managed by orbital exenteration and supplemental external beam irradiation or chemotherapy. A recent report has suggested that the tumor may have a less malignant course in children. We describe a case of adenoid cystic carcinoma of the lacrimal gland that simulated a dermoid cyst clinically and radiographically in a 9-year-old boy. The patient was treated with local surgical resection of the mass, followed by orbital plaque brachytherapy. Based on a review of the literature and our recent experience, the advisability of a more conservative approach to this tumor in selected cases is discussed. Although no prognostic conclusions can be drawn on the basis of a single case report with short follow-up, the relatively earlier detection of this tumor made possible by modern orbital imaging studies may allow total removal at an earlier stage and prevent orbital exenteration in a patient with normal vision. Recent developments suggest that there may be a basis for reassessing the advisability of a radical approach to the management of adenoid cystic carcinoma of the lacrimal gland in selected cases.

Radiation therapy for uveal malignant melanoma.

The treatment of uveal melanoma is controversial. The treatment methods include enucleation and other techniques designed to preserve the eye, such as local resection, plaque radiotherapy, charged particle radiotherapy, laser photocoagulation, and thermotherapy. Plaque radiotherapy and charged particle radiotherapy provide tumor control and patient survival comparable with enucleation. Plaque radiotherapy may be associated with fewer anterior segment complications, but the posterior segment complications appear to be similar using either plaque radiotherapy or charged particle radiotherapy. Thermotherapy is emerging as an important adjuvant treatment to maintain control of uveal melanoma after radiotherapy.

Radiation therapy for macular degeneration: technical considerations and preliminary results.

PURPOSE: This study was undertaken to assess the toxicity and possible benefits from the administration of low-dose external-beam irradiation for Age-Related Macular Degeneration (ARMD). The premise of the treatment is that radiation induces regression and/or promotes inactivation of the subretinal neo-vasculature, resulting in reabsorption of fluid and blood thus reducing the risk for further leakage or bleeding, as well as subretinal fibrosis. Clinically, the beneficial effect could be translated into stabilization of visual acuity and prevention of progression of the wet type of ARMD with the possibility for some visual improvement. METHODS AND MATERIALS: Allegheny University Hospitals, Hahnemann, Department of Radiation Oncology, treated 278 patients prospectively beginning in January 1995 with low-dose irradiation for wet-type macular degeneration. Two hundred forty-nine patients were treated with a total dose of 14.40 Gy in eight fractions of 1.80 Gy over 10-13 elapsed days, and 27 patients with 20 Gy at 2 Gy per fraction over 12-15 days. The first two patients were treated to a total dose of 10.00 Gy in five fractions of 2.00 Gy. Patients were evaluated at 2-3 weeks and 2-3 months. A percentage (36.7%) of the patients had previously received laser treatments in the study eye, 21.9% once, 5% twice, 9.7% three or more. Subjective visual acuity and toxicity data was collected on all patients. RESULTS: At 2-3 weeks after treatment 195 patients (70%) retained their visual acuity without change, 68 patients (24.5%) stated they had improved vision, and 15 patients (4.8%) stated their vision continued to decrease. Two to 3 months after treatment, 183 patients (65.8%) had no change in their vision, 75 patients (27%) had an improvement in their vision, and 20 patients (7.2%) had a decrease in visual acuity. Transient acute reactions occurred in 14 of the 278 patients treated. CONCLUSION: Our observations in this group of 278 patients support the conclusion that many patients will have improved or stable vision after treatment with low-dose irradiation for age related wet type macular degeneration.

Intracavitary brachytherapy for carcinoma of the esophagus.

Local control of unresectable esophageal carcinomas remains a significant problem in spite of aggressive treatments. External beam radiation therapy, chemotherapy, and combined modality treatment have all been employed with limited success. Here we review the existing literature and our own experience with external beam radiation followed by low-dose-rate or high-dose-rate intracavitary radiation for carcinoma of esophagus. The addition of intracavitary brachytherapy to external beam irradiation is well tolerated, causes no significant toxicity, and improves local control. Low-dose-rate intracavitary boost compared to high-dose-rate intracavitary boost has the advantage of a greater margin of safety, requires a single application, does not require highly sophisticated computerized technology, and is accompanied with fewer high-grade toxicities. Combined modality therapy consisting of concomitant infusional chemotherapy, external beam irradiation, and low-dose-rate intracavitary boost needs to be investigated.

Brachytherapy in primary ocular tumors.

Patients with primary ocular tumors are seen infrequently in the medical profession, and most of these patients are referred to specialty centers which has resulted in a good study population. In the past, ocular tumors were treated with enucleation, but the current emphasis is now on organ preservation with sparing of all or partial visual acuity. In the management of these tumors, plaque brachytherapy and particle beam therapy have been used more frequently as an alternative to enucleation. A multi-institutional study, the Collaborative Ocular Melanoma Study (COMS), is currently underway, organized by the National Eye Institute. The COMS isotope of choice is Iodine-125 (I-125). Recurrence after plaque therapy is approximately 15%, although it may be as high as 37% at 15 years for metastatic disease. In one study, nondiffuse iris melanoma has been controlled in 93% of patients by custom plaques utilizing I-125. Plaque brachytherapy also utilizes I-125 for the treatment of retinoblastoma tumors either as primary therapy or following external beam radiation. Currently, through the utilization of plaque radiation therapy, enucleation may be avoided in the majority of patients, and many patients may retrieve some visual acuity. We will review plaque brachytherapy techniques, diagnosis, staging, and some of the pertinent literature of the two most frequently encountered primary ocular tumors: choroidal melanoma, sometimes referred to as uveal melanoma, with an incidence of approximately 1,500 new cases per year in the adult population; and retinoblastoma, the most common intraocular primary malignancy found in childhood, with a frequency of approximately 250 [corrected] new cases per year.

Cotransport of sodium with glutamine alanine and glucose in the isolated rabbit ileal mucosa

To investigate the effect of substrates during oral rehydration therapy, we studied intestinal cation cotransport (ICC) with glutamine (Gln) alanine (Ala) and glucose (Glu). The specific aims were to determine the biological effects of these three different cotransport systems on intestinal function. Isolated rabbit ileal mucosa preparations mounted in Ussing chambers were studied. ICC was determined by measuring short-circuit current (Isc) and potential difference (PD) while monitoring toissue resistance (TR). The data are reported as the mean ñ SEM of 4-6 experiments for each amino acid concentration. Increasing concentrations of Gln (10-5 to 10-2 M), Ala (10-5 to 10-1 M) and Glu (10-5 to 10-2 M) caused a significant (P<0.05) increase in ICC. Glin (30 mM) and Ala (0.1 M) had a maximal effects (Em (Glin)=100% anmd Em (Ala)=66%, P<0.05) which was higher than that obtained with 30 mM Glu (Em (Glu)=35%). When sodium was replaced with choline on the mucosal side. Ringer solution completeley abolished the response with Gln, Ala and Glu. The presence of all three substrates (10-2 M gln, 10-1 M Ala and 10-2 M Glu) in Ringer solution on the mucosal side caused a significant increase in ICC ( increase of short circuit current = III ñ 43 uA, P<0.05). These results demonstrate that Glin, Ala and Glu each increased sodium-dependent cation cotransport, and that sodium-dependent intestinal cation cotransport was higher with Gln than with Ala or Glu

Transport of glutamine, alanine and glucose by rabbit intestinal membrane

Malnutrition and dehydration are the immediated consequences of diarrheal diseases. To investigate the biological significance ofglutamine, alanine and glucose in the intestinal mucosa, we have used Ussing chambers to determine electrolyte transport by measuring short-circuit current (Isc), potential difference (PD) and tissue resistance (TR) in rabbit intestinal mucosa. Increasing doses (10-5 M to 10-1 M)of glutamine,alanine and glucose cause a significant increase in intestinal cation cotransport. Although glucose had a slightly earlier effect, 30mM glutamine and 0.1 M alanine had a maximal effect which was more than two times that caused by 30 nM glucose. The pD2 values for glucose, glutamine and alanine were 3.0, 2.5, and 2.0, respectively. The dose-response curves of these substrates suggest that the intestinal cotransport kinetics for glutamine is differentfrom that of glucose and alanine. Our results demonstrated that all three substrates cause a significant increase in Isc or PD, suggesting an increase in the intestinal mucosa cation cotransport. Glutamine has a larger effect on cation cotransport than alanine and glucose. These combinations should be studied further for the development of an oral rehydrating solution for diarrhea treatment which could prevent the resulting malnutrition, especially in those cases of prolonged diarrheal diseases