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.

External beam radiation enhances antibody mediated radiocytotoxicity in human glioma cells in vitro.

Enhanced accumulation of monoclonal antibodies in tumor tissue has been observed as a result of external beam irradiation (EBR). This effect was mainly attributed to increased vascular leakage due to unspecific radiation damage of vascular endothelial cells. The aim of this study was to investigate the effects of EBR on expression and antibody-binding of epidermal growth-factor receptor (EGF-R) in human glioma cells in-vitro. High-grade glioma cells were irradiated with conventional x-rays (0-3600 Rad) and surface binding, internalization and radiocytotoxicity of 125I-labeled monoclonal antibody (MAb) 425, specific for human EGF-R, was tested. EBR showed a short-term dose and time dependent increase of specific MAb 425 binding and internalization in receptor positive cell lines U87-MG and A1207. This effect was probably due to a mitotic block and an increase in cellular volume. Combination of EBR and 125I-425 showed additive effects on cell vitality/survival and was more pronounced in contact inhibited cells as compared to cells growing in a log-phase. We assume that cells exposed to 125I-labeled MAb 425 are only able to accumulate a critical number of DNA double-strand breaks when the doubling-time is prolonged e.g. under contact-inhibition or radiation induced mitotic blockade. We conclude that EBR has no negative effects on EGF-R expression, MAb-binding and internalization. The combination of EBR and 125I-MAb 425 enhances cytotoxic efficacy and thus supports adjuvant use in the clinical management of high-grade glioma.

Adenocarcinoma of the prostate: innovations in management.

Adenocarcinoma of the prostate (CaP) in the Western world has become the most common noncutaneous human tumor. CaP is also the second most important cause of cancer deaths among the male population in the United States. Major progress was made in the past decade in better understanding this disease process, as well as in improved diagnostic accuracy. This improved diagnostic accuracy was due to wide application of prostate-specific antigen (PSA), use of transrectal ultrasound (TRUS), and greater awareness among clinicians of CaP. The use of PSA in clinical practice has resulted in a sharp increase in the number of patients diagnosed with capsule-confined tumors. The optimal treatment for capsule-confined CaP is in the process of being defined. Radical prostatectomy in the United States is currently the most commonly applied treatment for younger patients. Excellent treatment results with a 10-year actuarial survival > 80% are readily obtainable in properly selected patients. Nerve-sparing procedures helped reduce the high incidence of impotence that occurs in patients after radical retropubic prostatectomy. Radiotherapy remains the other curative treatment method in the management of CaP patients, with long-term survival rates similar to those reported in surgical series. Due to the problem of frequent preoperative tumor understaging, a routine use of postoperative irradiation to the prostatic fossa produces an excellent (> 95%) incidence of local tumor control. Management of patients with metastatic disease has undergone a considerable evolution with the development of modern hormonal management and treatment with strontium-89 to control intractable bone pain. Newer treatment methods such as hyperthermia are currently being investigated. Major efforts are directed toward the reduction of short- and long-term treatment toxicity associated with surgery, radiotherapy, and hormonal management, thus improving patient quality of life.

Plaque radiotherapy for juxtapapillary choroidal melanoma. Visual acuity and survival outcome.

OBJECTIVES: To assess the effect of plaque radiotherapy on the visual acuity of patients with juxtapapillary choroidal melanoma and to determine the clinical predictive factors for radiation retinopathy, radiation papillopathy, local tumor recurrence, and distant metastasis. DESIGN: A retrospective review of the medical records of 93 patients with juxtapapillary choroidal melanoma who were treated initially with plaque radiotherapy. RESULTS: During a mean follow-up of 78 months, radiation retinopathy developed in 81 patients (87%) and radiation papillopathy developed in 48 patients (52%) after a mean interval of 21 and 27 months, respectively. The univariate variables that were significant predictors of radiation retinopathy were history of diabetes mellitus (P = .05) and use of a notched radioactive plaque (P = .04). The factors predictive of radiation papillopathy were age (> 45 years; P = .01), history of diabetes mellitus (P = .05), mushroom-shaped tumor configuration (P = .006), and nasal location of the tumor (P = .04). By using Kaplan-Meier survival curves, we found that the proportion of the 93 patients with radiation retinopathy was 87 (94%) at 5 years and with radiation papillopathy was 53 (57%) at 5 years. By using life-table analysis, we found that the proportion of the 93 patients who experienced a decrement of at least 3 lines of visual acuity was 67 (72%) by 50 to 60 months. Local tumor recurrence was documented in 14 patients (15%) after a mean interval of 41 months. The age of the patient (< 35 years; P = .02) and the superior (P = .004) and inferior (P = .05) locations of the tumor were predictive of local tumor recurrence. Distant metastasis developed in 11 patients (12%) after a mean interval of 44 months. The factors predictive of distant metastasis were a tumor with a basal diameter larger than 6.0 mm (P = .05), the superior location of the tumor (P = .01), and local tumor recurrence (P < .001). CONCLUSION: Based on these observations, plaque radiotherapy remains a potential option vs enucleation for the management of juxtapapillary choroidal melanoma.

External beam radiation for retinoblastoma: results, patterns of failure, and a proposal for treatment guidelines.

PURPOSE: To analyze treatment results and patterns of failure following external beam radiation for retinoblastoma and propose treatment guidelines according to specific clinical variables. METHODS AND MATERIALS: We analyzed 27 patients (34 eyes) with retinoblastoma who received external beam radiation as initial treatment at Hahnemann University Hospital from October 1980 to December 1991 and have been followed for at least 1 year. Of the 34 eyes, 14 were Groups I-II (Reese-Ellsworth classification), 7 were Group III, and 13 were Groups IV-V. Doses ranged from 34.5-49.5 Gy (mean 44.3 Gy, median 45 Gy) in 1.5-2.0 Gy fractions generally delivered through anterior and lateral wedged pair fields. RESULTS: At a mean follow up of 35.2 months (range 12-93 months), local tumor control was obtained in 44% (15 out of 34) of eyes with external beam radiation alone. Salvage therapy (plaque brachytherapy, cryotherapy, and/or photocoagulation) controlled an additional 10 eyes (29.5%), so that overall ocular survival has been 73.5%. Local tumor control with external beam radiotherapy alone was obtained in 78.5% (11 out of 14) of eyes in Groups I-II, but in only 20% (4 out of 20) of eyes in Groups III-V. A total of 67 existing tumors were identified prior to treatment in the 34 treated eyes and local control with external beam radiation alone was obtained in 87% (46 out of 53) of tumors measuring 15 mm or less and in 50% (7 out of 14) of tumors measuring more than 15 mm. When analyzing patterns of failure in the 19 eyes that relapsed, a total of 28 failure sites were identified and consisted of progression of vitreous seeds in seven instances (25% of failure sites) recurrences from previously existing tumors in 10 instances (36% of failure sites) and development of new tumors in previously uninvolved retina in 11 instances (39% of failure sites). CONCLUSIONS: 1) We find that external beam radiation to a dose of 45 Gy in fractions of 1.5 to 2.0 Gy provides adequate tumor control in retinoblastoma eyes Groups I-II (Reese-Ellsworth classification) or tumors measuring 15 mm in diameter or less. Eyes in more advanced group staging or containing tumors larger than the 15 mm seem to require higher radiation doses. We propose treatment guidelines for external beam radiation of retinoblastoma that specifically take into account the important clinical variables of tumor stage and patient age. 2) External beam radiation does not prevent the appearance of new tumors in clinically uninvolved retina. Therefore, the traditional belief that external beam radiation can treat the retina "prophylactically" should be seriously questioned. Due to this finding and their significant less morbidity, focal treatment modalities (plaque brachytherapy, photocoagulation, and/or cryotherapy), when clinically feasible, should be considered the treatment of choice for intraocular retinoblastoma. External beam radiation should be considered only when focal treatment modalities are not clinically indicated.

Initial clinical evaluation of iodine-125-labeled chimeric 17-1A for metastatic colon cancer.

UNLABELLED: The internalizing properties of murine antibody 17-1A in human colon cancer cells make it attractive as a carrier for radionuclides with short range emissions such as 125I. Murine 17-1A IgG2a antibody, which reacts against human gastrointestinal cancers, has been chimerized by joining its variable region with human IgG1 k constant region. A pilot clinical trial of increasing doses of 125I-chimeric 17-1A in patients with metastatic colorectal cancer has been conducted. METHODS: Patients were treated in groups of 2-4; 2 patients at Hahnemann University and 26 at the University of Alabama at Birmingham. Groups 1-5 received single administrations with 125I doses of 20, 40, 60, 80 or 100 mCi. Subsequent groups received therapeutic doses of 150, 200 or 250 mCi, with the dose subdivided into infusing of 50 or 100 mCi at 4-day intervals. All treatments were delivered in an outpatient setting using radiation precautions. Labeling at 10 mCi/mg antibody was performed on the day of treatment. RESULTS: Pharmocokinetics of circulating antibody was studied for initial patients, showing alpha T 1/2 of 17-27 hr and beta T 1/2 of 100-190 hr. Whole-body T 1/2 of radioactivity was determined by measuring urinary excretion or gamma emissions. Treatment was well tolerated without significant acute or late side effects. No significant bone marrow suppression or other dose-limiting toxicities were noted over this dose range. No objective responses were noted. CONCLUSION: These results show that high-dose outpatient radioimmunotherapy with an 125I-labeled internalizing antibody can be achieved without significant patient toxicity or radiation hazard.

Thermoradiotherapy for brain tumors. Three cases of recurrent malignant astrocytoma and review of clinical experience.

Three patients with symptomatic, recurrent supratentorial malignant astrocytoma were retreated with combined interstitial iridium-192 brachytherapy (RT) and hyperthermia (HT): 50 Gy at 50 cGy/h was delivered 10 mm outside the computed tomography (CT) enhancement border through stereotactically placed plastic tubes, and 915-MHz microwave antenna heating was done for 60 min within 30 min either before or after irradiation. Invasive thermometry data were obtained from the tumor and adjacent brain tissue. The patients tolerated the treatment well and two thirds improved. All patients developed cerebral edema, one also developed scalp infection, and another patient developed meningeal infection. Exceeding the expectancy without treatment, overall survival was 7, 12, and 15 months. On autopsy, two of the patients' brains revealed no active tumor in the treated regions, but one displayed tumor in untreated parts. The HT-RT treatment was very effective, but the original tumor extent was not apparent by the CT imaging technique. A postimplant resection approach may be advisable to minimize postimplant edema. Our data are in agreement with the available literature on more than 400 patients. However, our aim of extending survival decisively could not be realized.

Epidermal growth factor receptor 425 monoclonal antibodies radiolabeled with iodine-125 in the adjuvant treatment of high-grade astrocytomas.

Fifty-nine patients with primary presentation of high-grade gliomas of the brain, 13 with astrocytomas with anaplastic foci and 46 with glioblastoma multiforme, were treated with surgical intervention and definitive postoperative radiation therapy followed by multiple intravenous administration of iodine-125-labeled monoclonal antibody-425, which binds specifically to human epidermal growth factor receptor. The total cumulative labeled antibody doses ranged from 40 to 296 mCi. The administration of the radiolabeled antibody was performed in most instances within 3 months following completion of the primary surgery and radiation therapy. No significant life-threatening toxicities were observed during the trial. At one year, 34 (58%) of the 59 patients in the trial were alive. The median overall survival for both groups was 13.5 months.

Enhancement of monoclonal antibody efficacy: the effect of external beam radiation.

External beam irradiation has been shown to enhance accumulation of monoclonal antibodies (MAb) in tumors in vivo. This effect is mainly attributed to an unspecific damage of vascular endothelial cells resulting in an increased vascular leakage. The aim of our studies was to determine the effects of external beam radiation on the expression and function of the epidermal growth factor receptor (EGF-R) in vivo. Expression and internalization of EGF-R was tested in vivo, employing 125I-MAb 425 that binds specifically to the human EGF-R. Irradiation of human high-grade glioma cell lines U87-MG and A1207 with increasing doses (0-3600 Rad) of 240 kVp X-rays, markedly enhanced the binding of 125I-MAb 425 to the cell surface. This effect could only be observed for a few days following irradiation. No correlation of the radiation dose and overexpression of EGF-R were found. At the same time, irradiation stimulated significant and dose-dependent internalization of 125I-MAb. Internalization and intranuclear accumulation of 125I-MAb are necessary to explain the radiocytotoxic effects of 125I. The combination of external beam irradiation and labeled MAb 425 showed at least additive effects on tumor cell survival, when the interval between irradiation and MAb treatment was short. Our data support the clinical observations in the adjuvant treatment of high grade gliomas with 125I-MAb 425 following surgery and external beam radiation.

Multivariate analysis of prognostic parameters using interstitial thermoradiotherapy (IHT-IRT): tumor and treatment variables predict outcome.

PURPOSE: From January 1986 to October 1991, 90 patients with localized tumors were treated in a Phase I/II trial using low-dose 192Ir brachytherapy (IRT) plus interstitial 915 MHz microwave (MW) hyperthermia (IHT) and external beam radiotherapy (ERT). Tumors were classified as locally advanced primary (class 1: 27), recurrent (class 2: 40), metastatic (class 3: 10) and persistent (class 4: 13) lesions. The treatment sites included tumors of the head and neck (62), pelvis (26), and others (2). The mean cuboidal tumor volume was 63 cm3 (range: 8-288 cm3). Most recurrent and metastatic lesions (48) had received prior treatment including ERT. METHODS AND MATERIALS: The treatment protocol prescribed two heating sessions (each 60 min) at 41-44 degrees C before and after IRT. One hundred sixty-one IHT sessions were evaluated. Invasive thermal data were recorded at an average of 18 sites throughout the implant volume. Several thermal variables were analyzed (e.g., averaged parameters: Tmaxav, Tmean, Tminav; index parameters: T10, T50, T90). The study was evaluated with a minimum follow up (FU) of one year. Median follow-up was 19 months. RESULTS: At 3 months FU, a complete response (CR) was observed in 59 of 90 (66%) patients. At 12 months FU, local control (LC) was achieved in 54 of 84 (64%) evaluable patients. Ten patients developed a local and 14 a regional recurrence (REC) after achieving a CR and/or LC. At last FU, a total of 31 (34%) patients were still alive and 28 (31%) patients had relapse-free survival. For all 90 patients, the median overall survival was 20 months and the median relapse-free survival was 17 months. Overall and relapse-free survival was significantly longer for primary and persistent lesions as compared to recurrent and metastatic lesions (p = 0.002; p < 0.001). Totally 22 (24%) patients experienced acute or subacute side-effects (Grade 1: 12 patients; Grade 2: eight patients; Grade 3: two patients). CONCLUSION: Univariate logistic regression analysis revealed significant dependencies of CR, LC and REC upon tumor parameters as well as radiation and thermal parameters. The overall and relapse free survival was associated with tumor and radiation parameters. The multivariate analysis revealed two independent predictors of CR: tumor volume and minimum tumor temperature variables. We conclude, that IHT-IRT is a safe and effective treatment. The results provide important implications for planning HT-RT studies and for defining quality assurance (QA) criteria and thermal performance standards in HT studies.

Conservative treatment of retinoblastoma. The use of plaque brachytherapy.

Retinoblastoma is the most common intraocular malignancy in childhood. The tumor arises from multipotential retinal cells. Treatment options include enucleation, external beam radiotherapy, episcleral plaque radiotherapy, photocoagulation, cryotherapy or a combination of these modalities. In retinoblastoma 10% have a positive family history and of the remaining 90%, 35% represent germinal chromosomal mutations while 65% represent somatic chromosomal mutations. Therefore, approximately 40% of all retinoblastomas are hereditary and are transmitted as a highly penetrant autosomal dominant trait. In the Wills Eye/Hahnemann University experience an analysis of 400 consecutive patients, 103 tumors in 103 eyes were treated with solitary plaque radiotherapy. Tumor regression was observed in all patients initially. After 40 months mean follow-up, persistent regression was observed in 89 cases (87%) and recurrences in 13 cases (13%). Of the 13 recurrences, five were in the group treated primarily (5/31) and eight in the group treated after failing other modalities (8/72). Plaque brachytherapy is an important tool in the management of retinoblastoma. Our preliminary data suggest that plaque brachytherapy is an effective treatment modality for primary treatment as well as after failure using other modalities.

New trends in the treatment of benign prostatic hyperplasia and carcinoma of the prostate.

Benign prostatic hyperplasia (BPH) is a very common condition affecting over 800,000 American males each year. A standard, effective, and well-proven therapy is prostatectomy. This surgical procedure is used to treat, in the United States, approximately 400,000 BPH patients annually. Major treatment benefit is expected in 70% to 80% of patients. Complications are seen in 20% of the surgically treated patients. Due to the advanced age of BPH patients and the presence of other serious coexisting medical problems, surgical therapy may be difficult to utilize. These patients, who present a high risk for surgery, are in need of alternative treatments. Alternative therapy in BPH patients with clinically important symptoms and signs of urinary outflow obstruction include treatment with pharmacological agents, balloon dilatation, laser beam therapy, transurethral thermal therapy, transrectal microwave hyperthermia, and transurethral microwave hyperthermia. These alternative treatment modalities are currently under intensive study. These new treatment modalities ultimately must be compared with the standard treatment, which is prostatectomy. Due to the unpredictable natural history of BPH, it is desirable that each Phase III study should contain a no-treatment observation-only arm. Adenocarcinoma of the prostate (CaP) has become a tumor, which first in frequency, and second in importance in cancer mortality statistics of American males. Local tumor control rates and long-term survivals, with radical prostatectomy or radiation therapy, have been excellent. There was, however, recent concern regarding a high incidence of microscopic local tumor recurrence following a definitive course of irradiation. Deep regional or intracavitary hyperthermia (HT) with phase steering may be of value as an adjuvant treatment to radiotherapy. This HT may increase the incidence of local tumor control obtained with radiotherapy. Phase I-II clinical studies are currently underway.

Clinical experience with interstitial thermoradiotherapy for localized implantable pelvic tumors.

Twenty-six patients (20 females, 6 males) with localized tumors of the pelvis, including 3 primary advanced (PRIM), 7 persistent (PERS), 10 recurrent (REC), and 6 metastatic (MET) tumors, were treated with a combination of low-dose rate (LDR) iridium 192 interstitial radiotherapy (IRT), interstitial 915 MHz microwave hyperthermia (IHT), and external beam radiotherapy (RT). Histological diagnoses were squamous cell carcinoma in 13 (50%), adenocarcinoma in 12 (46%) and soft tissue sarcoma in 1 (4%) lesion. Tumor sites were cervix in 8 (31%), colorectum in 6 (23%), vagina in 4 (15%), anus in 3 (12%), ovary in 2 (8%), and other sites in 3 (12%) lesions. IHT was administered immediately before iridium 192 was placed and after its removal for 45-60 minutes at 41-44 degrees C. On December 31, 1991 median follow-up was 25 months (mean: 23 months; range: 5-65 months). At 3 months follow-up (FU), complete remission (CR) occurred in 17 (65%), partial remission (PR) in 7 (27%), and no change or progressive disease (NC/PD), in 2 (8%) lesions. At 12 months FU, in 16 of 21 patients (76%) local control (LC) was achieved, with 1 (5%) patient exhibiting a slow tumor regression. After combined IRT-IHT locoregional relapse or tumor regrowth occurred in 8/26 (31%): 5 (19%) outside and 3 (12%), inside the previously treated volume; relapses occurred within 8-30 (mean: 18) months of follow-up. Factors influencing initial (3 months FU) and long-term tumor response (12 months FU) included tumor class, tumor volume, total radiation dose, and thermal parameters with "good quality of heating" (TQ 41 degrees C > or = 75%) and high minimum tumor temperature (Tmin(av) > or = 41 degrees C). Treatment toxicity was acceptable: whereas 8 (31%) patients experienced acute side effects, which subsided within weeks, 7 (27%) developed long-term complications. Thermal damage was associated with IHT treatments exceeding maximum average temperatures of > or = 44 degrees C and maximum peak temperatures of > or = 45 degrees C.

Radiation therapy in the treatment of pituitary adenomas.

Seventy-eight patients with pituitary adenomas were seen in the Department of Radiation Oncology at Hahnemann University between 1961 and 1986. Most were treated with megavoltage photons with or without prior surgery. In this group, 68 patients were followed: 39 were treated with radiation therapy (RT) alone, and 29 were treated with a combination of surgery and RT (S/RT). Patients were followed for 2 to 20 years. Of 68 patients, (97%) experienced complete response to treatment; 86% of the RT patients remained free of disease at 5 and 10 years. In the S/RT group, 100% and 94% remained free of disease at 5 and 10 years, respectively. Total disease-free survivals at 5 and 10 years were, respectively, 91% and 89%. The majority of the failures occurring in the RT group were with growth hormone-secreting tumors and Cushing's disease. Of the 7 patients that failed or recurred (time to recurrence: 1-16 years posttreatment), 6 have been followed: 4 were treated with surgery, 1 with RT, and 1 with S/RT. All 6 have remained free of disease since salvage, with 2- to 14-year follow-up periods. Serious morbidity and mortality have been reported previously with bitemporal field radiation using kilovoltage and low megavoltage RT. However, there was no temporal lobe necrosis or death in any of the patients in this study.

Interstitial thermal radiation therapy: five-year experience with head and neck tumors.

Sixty-two patients with 24 primary advanced, six persistent, 28 locally recurrent, and four metastatic tumors of the head and neck were treated with combined interstitial low-dose iridium-192 radiation therapy, interstitial 915-MHz microwave hyperthermia (IHT), and external-beam radiation therapy. Diagnoses were squamous cell carcinoma in 56, adenocarcinoma in three, and soft-tissue sarcoma in three lesions. IHT was applied immediately before Ir-192 was placed and after its removal for 45-60 minutes at 41 degrees C-44 degrees C. At 3 months, complete remission had occurred in 39 lesions; partial remission, in 18; and no change or progressive disease, in five. At 12-month follow-up, local control was achieved in 29 of 50 patients; seven other patients had slow ongoing tumor regression with an unclear residual mass at computed tomography or magnetic resonance imaging. Lesion type, tumor volume, total radiation dose, and thermal parameters with "good quality of heating" at high minimum tumor temperature were identified as statistically significant (P less than .05) prognostic factors influencing initial and long-term tumor response. There was no prognostic factor for acute or late thermal damage.

Brachytherapy of choroidal melanomas.

In the management of patients with primary malignant melanoma of the uvea, treatment techniques have included not only enucleation but also photocoagulation, cryotherapy, photoradiation, a limited resection, as well as circumstances indicating exenteration of the orbit. Surgical management has been the primary treatment program for over 100 years. In a compilation of nine reported series consisting of 2,024 enucleations, the five- and ten-year survivals following surgery were 63% and 43%, respectively. The 25-year survival has been reported to be 40%. In 1974 at Wills Eye Hospital and Hahnemann University, the cobalt-60 plaques technique was introduced. During the following years, other radioactive isotopes were introduced including iridium-192, iodine-125, ruthenium-106/rhodium-106 and more recently palladium-103. At the present time, iodine-125 is the most widely used radionuclide. Until now, 302 patients treated with plaque brachytherapy showed an actuarial survival of 77% and 67.8% at five and eight years, respectively. There was no significant survival difference when compared with a similar group of patients undergoing enucleation. Other retrospective studies show similar excellent results. In spite of these convincing results, the decision making process in management melanoma remains unsettled primarily due to the absence of prospective randomized trials. Because of this, the Collaborative Ocular Melanoma Study was initiated. From the standpoint of toxicity, the data are available on ocular radiation toxicity. In an analysis of 77 patients from the Wills Eye Hospital with pretreatment visual acuities of 20/25 or better, it was noted that 90% of patients who had received less than 500 Gy to the fovea retained visual acuity of 20/200 or better while only 52% of patients receiving more than 5,000 Gy to the fovea had vision of 20/200 or better. A serious late effect of radioactivity plaque treatment is scleral necrosis which may require repair or enucleation even in the absence of tumor progression. Enucleation may be necessary in approximately 10% of patients. We conclude that malignant melanoma of the uvea can be safely treated with radioactive plaques.

External beam irradiation versus 125 iodine implant in the definitive treatment of prostate carcinoma.

We reviewed the record of all 983 patients seen at the Hahnemann University, Department of Radiation Oncology for evaluation of prostate cancer during the megavoltage era. We compared the results of 276 patients who were treated definitively with either external beam irradiation or Iodine 125 implantation. The groups were similar in most prognostic characteristics. Where appropriate, multivariate statistical techniques were used to compensate for the effects of differences in grade and stage between the two groups. There were striking differences between implant and external beam patients in both local failure rates and disease-free survival, mostly attributable to poor local control in the implant patients. Thirty-eight percent of the Stage A and B implant patients failed locally in the first 5 years whereas only 5% of a comparable group of external beam patients did so. A2 patients, however, exhibited similar disease-free survival in both cohorts. Complication rates were 11% in the implant group and 19% in the external beam group. We conclude that there are serious doubts about the efficacy of Iodine 125 implantation in maintaining local control, and that this translates into worse relapse-free survival. By contrast, local control and relapse-free survival may be satisfactory in the A2 patients, and complication rates may be lower with implant. The above suggests that Iodine 125 interstitial implantation is well suited to only a minority of early stage prostate cancer patients and that most patients with Stage B and C prostatic carcinoma should be treated with either external beam irradiation or with radical prostatectomy.

Total skin electron beam and total nodal irradiation of cutaneous T-cell lymphoma.

Nineteen patients with cutaneous T-cell lymphoma (CTCL) limited to the skin and/or lymph nodes were treated at Hahnemann University with a combination of total skin electron beam and total nodal irradiation (TSEB + TNI). The patients were classified as Stage Ib (1 patient), Stage IIa (8 patients), Stage IIb (5 patients), and Stage IVa (5 patients). Treatment resulted in a complete response in 100% (14/14) of patients with Stage Ib, IIa, and IIb disease, and a CR in 60% (3/5) of patients with Stage IVa disease. The Stage Ib and IIa patients had an overall survival of 100% and a disease-free survival of 44% at 6 years. Four of the five patients with Stage IIb CTCL relapsed within 3 months after completing TSEB + TNI with an overall survival in the group of 40% at 5 years. The Stage IVa patients all relapsed within 7 months and died of their disease within 50 months of completing treatment. The acute effects of TSEB + TNI were well tolerated, but three patients developed second malignancy (lung, kidney and skin) and one patient developed myelodysplasia, possibly the result of radiotherapy.