A Prospective, Randomized, Double-blind, Placebo-controlled Study of Orbital Radiotherapy for Graves' Ophthalmopathy.

CONTEXT: Although widely used for more than 85 years, the efficacy of radiotherapy for Graves' ophthalmopathy (GO) has not been established convincingly. OBJECTIVE: To evaluate the efficacy of radiotherapy for GO. DESIGN: Prospective, randomized, internally controlled, double-blind clinical trial in a tertiary care academic medical center. PARTICIPANTS: The patients were ethnically diverse males and females over age 30 seen in a referral practice. The patients had moderate, symptomatic Graves' ophthalmopathy (mean clinical activity score, 6.2) but no optic neuropathy, diabetes, recent steroid treatment, previous decompression, or muscle surgery. Forty-two of 53 consecutive patients were enrolled after giving informed consent and fulfilling study entry criteria. Eleven eligible patients declined to participate because of inconvenience, desire for alternative therapy, or concern about radiation. INTERVENTION: One randomly selected orbit was treated with 20 Gy of external beam therapy; sham therapy was given to the other side. Six months later, the therapies were reversed. MAIN OUTCOME MEASURES: Every 3 months for 1 year, we measured the volume of extraocular muscle and fat, proptosis, range of extraocular muscle motion, area of diplopia fields, and lid fissure width. Effective treatment for GO will modify one or more of these parameters. RESULTS: No clinically or statistically significant difference between the treated and untreated orbit was observed in any of the main outcome measures at 6 months. At 12 months, muscle volume and proptosis improved slightly more in the orbit that was treated first. CONCLUSIONS: In this group of patients, representative of those for whom radiotherapy is frequently recommended, we were unable to demonstrate any beneficial therapeutic effect. The slight improvement noted in both orbits at 12 months may be the result of natural remission or of radiotherapy, but the changes are of marginal clinical significance.

Neoniphonpencei, a new species of holocentrid (Teleostei: Beryciformes) from Rarotonga, Cook Islands.

Neoniphonpencei, n. sp., is described from thirteen specimens, 132-197 mm standard length (SL) collected from mesophotic coral ecosystems (MCEs) at Rarotonga, Cook Islands by divers using mixed-gas closed-circuit rebreathers. It differs from all other species of the genus in number of lateral line scales, scales above and below lateral line, elements of life color, and in COI and cytochrome b DNA sequences. Of the five other known species of Neoniphon, it is most similar to the Indo-Pacific N.aurolineatus and the western Atlantic N.marianus both morphologically and genetically.

Use of SLAM and PVRL4 and identification of pro-HB-EGF as cell entry receptors for wild type phocine distemper virus.

Signalling lymphocyte activation molecule (SLAM) has been identified as an immune cell receptor for the morbilliviruses, measles (MV), canine distemper (CDV), rinderpest and peste des petits ruminants (PPRV) viruses, while CD46 is a receptor for vaccine strains of MV. More recently poliovirus like receptor 4 (PVRL4), also known as nectin 4, has been identified as a receptor for MV, CDV and PPRV on the basolateral surface of polarised epithelial cells. PVRL4 is also up-regulated by MV in human brain endothelial cells. Utilisation of PVRL4 as a receptor by phocine distemper virus (PDV) remains to be demonstrated as well as confirmation of use of SLAM. We have observed that unlike wild type (wt) MV or wtCDV, wtPDV strains replicate in African green monkey kidney Vero cells without prior adaptation, suggesting the use of a further receptor. We therefore examined candidate molecules, glycosaminoglycans (GAG) and the tetraspan proteins, integrin ß and the membrane bound form of heparin binding epithelial growth factor (proHB-EGF),for receptor usage by wtPDV in Vero cells. We show that wtPDV replicates in Chinese hamster ovary (CHO) cells expressing SLAM and PVRL4. Similar wtPDV titres are produced in Vero and VeroSLAM cells but more limited fusion occurs in the latter. Infection of Vero cells was not inhibited by anti-CD46 antibody. Removal/disruption of GAG decreased fusion but not the titre of virus. Treatment with anti-integrin ß antibody increased rather than decreased infection of Vero cells by wtPDV. However, infection was inhibited by antibody to HB-EGF and the virus replicated in CHO-proHB-EGF cells, indicating use of this molecule as a receptor. Common use of SLAM and PVRL4 by morbilliviruses increases the possibility of cross-species infection. Lack of a requirement for wtPDV adaptation to Vero cells raises the possibility of usage of proHB-EGF as a receptor in vivo but requires further investigation.

Deficient eNOS phosphorylation is a mechanism for diabetic vascular dysfunction contributing to increased stroke size.

BACKGROUND AND PURPOSE: Phosphorylation of eNOS, an important post-translational modulator of its enzymatic activity, is reduced in diabetes mellitus. We hypothesized that modulation of eNOS phosphorylation could overcome diabetic vascular dysfunction and improves the outcome to stroke. METHODS: We used the db/db mouse model of type 2 diabetes mellitus. We mated db/db mice with eNOS knock-in mice that carry single amino acid mutations at the S1176 phosphorylation site; the phosphomimetic SD mutation (serine replaced by aspartate) shows increased eNOS enzymatic activity, whereas the unphosphorylatable SA mutation (serine replaced by alanine) shows decreased eNOS activity. We characterized the vascular anatomy, baseline physiological parameters, and vascular reactivity. We used the middle cerebral artery occlusion model of stroke and measured infarct volume and neurological deficits. RESULTS: db/db mice showed diminished eNOS phosphorylation at S1176. eNOS SD and SA mutations do not change the vascular anatomy at the Circle of Willis, brain capillary density, heart rate, or arterial blood gases of db/db mice. The eNOS SD mutation, but not the SA mutation, lowers blood pressure and improves vascular reactivity to acetylcholine in db/db mice. The eNOS SD mutation reduces stroke size and neurological deficit after middle cerebral artery occlusion. CONCLUSIONS: Diminished eNOS phosphorylation is a mechanism of vascular dysfunction in db/db mice. We show here that modulation of the eNOS S1176 phosphorylation site in db/db mice is associated with improved vascular reactivity and improved outcome to stroke after middle cerebral artery occlusion.

Xanthichthysgreenei, a new species of triggerfish (Balistidae) from the Line Islands.

Xanthichthysgreenei sp. n. is described from six specimens, 97-154 mm standard length (SL) collected from mesophotic coral ecosystems (90-100 m) at Kiritimati (Christmas Island), Line Islands, part of the Republic of Kiribati in the Central Pacific. Of the six species of Xanthichthys, it is most similar to the Atlantic Xanthichthysringens and the Indo-West Pacific Xanthichthyslineopunctatus, sharing with these species the character of three pigmented cheek grooves. It is distinctive in its low body scale row count (33-35, other Xanthichthys species with 39 or more), small size (maximum SL 154 mm, other species over 225 mm), and color pattern of scattered dark spots sub-dorsally and no other spots or lines on body.

Genetic consequences of introducing allopatric lineages of Bluestriped Snapper (Lutjanus kasmira) to Hawaii.

A half century ago the State of Hawaii began a remarkable, if unintentional, experiment on the population genetics of introduced species, by releasing 2431 Bluestriped Snappers (Lutjanus kasmira) from the Marquesas Islands in 1958 and 728 conspecifics from the Society Islands in 1961. By 1992 L. kasmira had spread across the entire archipelago, including locations 2000 km from the release site. Genetic surveys of the source populations reveal diagnostic differences in the mtDNA control region (d = 3.8%; phi(ST) = 0.734, P < 0.001) and significant allele frequency differences at nuclear DNA loci (F(ST) = 0.49; P < 0.001). These findings, which indicate that source populations have been isolated for approximately half a million years, set the stage for a survey of the Hawaiian Archipelago (N = 385) to determine the success of these introductions in terms of genetic diversity and breeding behaviour. Both Marquesas and Society mtDNA lineages were detected at each survey site across the Hawaiian Archipelago, at about the same proportion or slightly less than the original 3.4:1 introduction ratio. Nuclear allele frequencies and parentage tests demonstrate that the two source populations are freely interbreeding. The introduction of 2431 Marquesan founders produced only a slight reduction in mtDNA diversity (17%), while the 728 Society founders produced a greater reduction in haplotype diversity (41%). We find no evidence of genetic bottlenecks between islands of the Hawaiian Archipelago, as expected under a stepping-stone model of colonization, from the initial introduction site. This species rapidly colonized across 2000 km without loss of genetic diversity, illustrating the consequences of introducing highly dispersive marine species.

Sexual attitudes and behavior at four universities: do region, race, and/or religion matter?

This study sought to ascertain any differences in sexual attitudes, levels of premarital sexual involvement, and risk-taking sexual practices of college students at four distinctly different universities: a historic Black public university; a predominately white, Southern private university with a religious heritage; a Southwestern public university; and a Midwestern public university. An anonymous questionnaire was administered to a volunteer sample of 1,915 never-married women and 1,111 never-married men in select upper and lower division classes. Numerous significant differences among campuses were found regarding sexual history, first sexual intercourse, and sexual risk-taking. Religion, family background, and campus milieu were strong mediating variables, but race appeared as the single most influential factor differentiating the sexual attitudes and behavior of these college students. Implications are suggested for professionals in fields of research, education, and therapy.

Comparison of daily megavoltage electronic portal imaging or kilovoltage imaging with marker seeds to ultrasound imaging or skin marks for prostate localization and treatment positioning in patients with prostate cancer.

PURPOSE: To compare the accuracy of imaging modalities, immobilization, localization, and positioning techniques in patients with prostate cancer. METHODS AND MATERIALS: Thirty-five patients with prostate cancer had gold marker seeds implanted transrectally and were treated with fractionated radiotherapy. Twenty of the 35 patients had limited immobilization; the remaining had a vacuum-based immobilization. Patient positioning consisted of alignment with lasers to skin marks, ultrasound or kilovoltage X-ray imaging, optical guidance using infrared reflectors, and megavoltage electronic portal imaging (EPI). The variance of each positioning technique was compared to the patient position determined from the pretreatment EPI. RESULTS: With limited immobilization, the average difference between the skin marks' laser position and EPI pretreatment position is 9.1 +/- 5.3 mm, the average difference between the skin marks' infrared position and EPI pretreatment position is 11.8 +/- 7.2 mm, the average difference between the ultrasound position and EPI pretreatment position is 7.0 +/- 4.6 mm, the average difference between kV imaging and EPI pretreatment position is 3.5 +/- 3.1 mm, and the average intrafraction movement during treatment is 3.4 +/- 2.7 mm. For the patients with the vacuum-style immobilization, the average difference between the skin marks' laser position and EPI pretreatment position is 10.7 +/- 4.6 mm, the average difference between kV imaging and EPI pretreatment position is 1.9 +/- 1.5 mm, and the average intrafraction movement during treatment is 2.1 +/- 1.5 mm. CONCLUSIONS: Compared with use of skin marks, ultrasound imaging for positioning provides an increased degree of agreement to EPI-based positioning, though not as favorable as kV imaging fiducial seeds. Intrafraction movement during treatment decreases with improved immobilization.

Quality of life after iodine 125 brachytherapy vs enucleation for choroidal melanoma: 5-year results from the Collaborative Ocular Melanoma Study: COMS QOLS Report No. 3.

OBJECTIVE: To describe health- and vision-targeted quality of life following treatment with iodine 125 brachytherapy vs enucleation for choroidal melanoma in a subgroup of patients who were treated and observed prospectively as part of a large randomized clinical trial. MAIN OUTCOME MEASURES: Difficulty with driving, near vision activities, and activities using stereopsis or binocularity; anxiety; and depression. PARTICIPANTS: Two hundred nine patients who enrolled in the Collaborative Ocular Melanoma Study trial for medium-sized tumors between March 1995 and July 1998 and gave informed consent prior to randomization to participation in an ancillary study of quality of life. METHODS: Patients were interviewed by telephone by a trained interviewer from the Collaborative Ocular Melanoma Study Coordinating Center at baseline (prior to randomization), at 6 months, and on annual anniversaries of enrollment. The questionnaire battery included the Medical Outcomes Study Short Form 36, the Activities of Daily Vision Scale, the National Eye Institute Visual Function Questionnaire, and the Hospital Anxiety and Depression Scale. Additional questions concerning satisfaction with posttreatment appearance and concerns about cancer recurrence also were included in posttreatment interviews. RESULTS: There was a significant increase in both treatment groups in levels of reported difficulty for most vision-oriented activities, and in bodily and ocular pain, 6 months following treatment. Differences in visual function between treatment groups reported during follow-up were relatively small, but significant differences favoring brachytherapy-treated patients were observed for driving during the first year of follow-up and for peripheral vision during the first 2 years of follow-up. Anxiety levels in both groups decreased significantly following treatment, but patients treated with brachytherapy with symptoms of anxiety were less likely to report later resolution of symptoms than patients with symptoms of anxiety who were treated with enucleation. This study was unable to assess impact of treatment on satisfaction with appearance and concern about cancer recurrence during the first year after treatment, but no treatment-related differences were found on these measures at 2 years and later follow-up times. CONCLUSIONS: Patients treated with brachytherapy reported significantly better visual function than patients treated with enucleation with respect to driving and peripheral vision for up to 2 years following treatment. Differences between treatments in visual function diminished by 3 to 5 years posttreatment, paralleling decline in visual acuity in brachytherapy-treated eyes. Patients treated with brachytherapy were more likely to have symptoms of anxiety during follow-up than patients treated with enucleation. APPLICATION TO CLINICAL PRACTICE: Given that no significant differences in survival between enucleation and brachytherapy have been found, the differences demonstrated here for driving and anxiety will allow the individual patient and physician to make informed choices regarding treatment based on personal preferences.

Development of metastatic disease after enrollment in the COMS trials for treatment of choroidal melanoma: Collaborative Ocular Melanoma Study Group Report No. 26.

OBJECTIVE: To describe the time between treatment for choroidal melanoma and first diagnosis of metastatic disease, sites of metastasis, treatments for metastasis, and time between diagnosis of metastasis and death. DESIGN: Prospective, longitudinal follow-up of patients diagnosed with choroidal melanoma who were enrolled in 2 randomized trials conducted by the Collaborative Ocular Melanoma Study Group. METHODS: Systemic and laboratory evaluations were performed during follow-up according to a standard protocol for 2320 patients enrolled in the Collaborative Ocular Melanoma Study trials without evidence of melanoma metastasis or other primary cancer at baseline. RESULTS: Seven hundred thirty-nine patients were diagnosed with at least 1 site of metastasis during follow-up after treatment for choroidal melanoma. Five- and 10-year cumulative metastasis rates were 25% (95% confidence interval, 23%-27%) and 34% (95% confidence interval, 32%-37%), respectively. Liver was the most common site (89%). The death rate following the report of melanoma metastasis was 80% at 1 year (95% confidence interval, 77%-83%) and 92% at 2 years (95% confidence interval, 89%-94%). Overall survival after metastasis did not vary by baseline size of primary tumor nor treatment for metastasis (when known). Long-term survival after diagnosis of metastasis was uncommon; only 8 patients survived 5 or more years. CONCLUSION: Metastasis rate increased significantly with increasing primary tumor dimensions at time of patient enrollment. Prognosis after metastatic disease remains poor. Effective methods are needed to prevent, diagnose, and treat metastasis from choroidal melanoma.

Second primary cancers after enrollment in the COMS trials for treatment of choroidal melanoma: COMS Report No. 25.

OBJECTIVE: To report sites of second primary cancer and the time to first diagnosis during routine follow-up after treatment for choroidal melanoma. DESIGN: Prospective longitudinal follow-up of patients enrolled in 2 randomized trials conducted by the Collaborative Ocular Melanoma Study (COMS) Group. METHODS: Baseline and annual or semiannual systemic and laboratory evaluations were performed according to a standard protocol for 2320 patients enrolled in the COMS without evidence of melanoma metastasis or other primary cancer at baseline. Deaths were coded by a mortality coding committee. RESULTS: Subsequent to treatment for choroidal melanoma, a total of 222 patients were diagnosed with a second primary cancer other than basal or squamous cell skin cancer (5-year rate of 7.7% [95% confidence interval, 6.6%-9.0%]). The most common sites were prostate (23% of reported cases) and breast (17%); 12 of these 222 patients were diagnosed simultaneously with second primary cancers in 2 or more sites. Of these 222 patients, 113 died; 37 (33%) were coded as dead with melanoma metastasis, 33 (29%) as dead with a malignant tumor other than metastatic melanoma, and 13 (11%) as dead with a malignancy of uncertain origin. Radiotherapy did not significantly increase the development of second primary cancers. The rate of diagnosis of second primary cancer did not differ significantly by smoking status, although the rate in former smokers was increased vs that observed in either current smokers or those who never smoked. CONCLUSION: Routine medical surveillance for development of second primary cancers among patients treated for choroidal melanoma is important, especially for those with a history of smoking, regardless of the size of choroidal melanoma at the time of treatment.

Failure after primary radiation or surgery for prostate cancer: differences in response to androgen ablation.

PURPOSE: Androgen ablation is the standard treatment for recurrent and metastatic prostate cancer. Surprisingly few studies have documented the specific results for local and distant failure in patients treated primarily with radiation or radical prostatectomy. We report the long-term outcome of a series of those patients. MATERIALS AND METHODS: We followed until death 94 patients in whom primary radiation therapy failed and 67 in whom radical prostatectomy failed. All patients received androgen ablation. RESULTS: Statistically (p = 0.04) more patients in the radiation group (78%) died of prostate cancer than in the radical prostatectomy group (63%). Of the radiation group with local failure alone 63%, died of prostate cancer at a median of 5.03 years. Of the surgery group with isolated local failure 50% died of cancer at a median of 9.83 years. Of the patients treated with radiation with distant metastasis 93% died of cancer with a median time to death of 2.34 years. Of the patients treated with surgery 69% died of prostate cancer at a median of 3.27 years. The differences in survival between the 2 groups was significant. CONCLUSIONS: This study is unique in providing followup until death of patients treated with radical prostatectomy and radiation who had clinical failure and were treated with androgen ablation. Compelling is the finding that survival after androgen ablation after surgical failure is superior to that for radiation. If confirmed, this would be a significant consideration for future studies of patients in whom primary therapy fails.

Chemotherapy with or without radiotherapy in limited-stage diffuse aggressive non-Hodgkin's lymphoma: Eastern Cooperative Oncology Group study 1484.

PURPOSE: To compare low-dose (30 Gy) radiotherapy (RT) with observation (OBS) in limited-stage aggressive lymphoma patients achieving complete remission (CR) after chemotherapy, and to measure conversion from partial response (PR) to CR with high-dose (40 Gy) RT. PATIENTS AND METHODS: From 1984 to 1992, stage I (with risk factors) and II adults with diffuse aggressive lymphoma in CR after eight cycles of cyclophosphamide, doxorubicin, vincristine, and prednisone (CHOP) were randomly assigned to 30 Gy involved-field RT or OBS. PR patients received 40 Gy RT. RESULTS: Among 172 CR patients, the 6-year disease-free survival (DFS) was 73% for low-dose RT versus 56% for OBS (two-sided P = .05). Failure-free survival (two-sided P = .06), and time to progression (two-sided P = .06) also favored RT. Intent-to-treat analyses yielded similar results. No survival differences were observed. Three RT versus 15 OBS patients relapsed in initial disease sites. At 6 years, failure-free survival was 63% in PR patients; conversion to CR did not significantly influence clinical outcome. CONCLUSION: For patients in CR after CHOP, low-dose RT prolonged DFS and provided local control, but no survival benefit was observed. The majority of PR patients were event-free at 6 years despite residual radiographic abnormalities. Future efforts should be directed toward improved imaging and more effective systemic therapies.

Screening for metastasis from choroidal melanoma: the Collaborative Ocular Melanoma Study Group Report 23.

PURPOSE: To describe the predictive value of liver function tests (LFTs), chest x-ray, and diagnostic imaging for detecting melanoma metastasis during routine follow-up after treatment for choroidal melanoma. MATERIALS AND METHODS: Prospective longitudinal follow-up of patients enrolled onto two randomized trials was conducted by the Collaborative Ocular Melanoma Study (COMS) Group. Baseline and annual or semiannual systemic and laboratory evaluations were performed according to a standard protocol for 2320 patients enrolled on the COMS. RESULTS: COMS patients were screened annually for metastasis and new cancers using LFTs (alkaline phosphatase, AST, ALT, or bilirubin). Elevated findings (1.5 to 2 times upper limit of normal) on LFT prompted a diagnostic or imaging test to confirm or rule out cancer recurrence. Of 714 patients with clinical reports of metastasis, 675 patients died. Of these 675 patients, all but four had either histopathologically confirmed or clinically suspected metastatic melanoma present at the time of death. Among all patients, the 5-year cumulative diagnosis rate of metastatic melanoma was 24% (95% CI, 22% to 27%). Based on all patients with reported metastasis, the sensitivity, specificity, positive predictive value and negative predictive value associated with at least one abnormal LFT before first diagnosis of metastasis at any site was 14.7%, 92.3%, 45.7% and 71.0%, respectively. CONCLUSION: Use of LFTs results followed by diagnostic tests has high specificity and predictive values but low sensitivity. Better tests are needed to identify earlier metastatic disease associated with choroidal melanoma.

Functional p53 increases prostate cancer cell survival after exposure to fractionated doses of ionizing radiation.

External beam radiation therapy is an effective therapy for localized prostate cancer, although failures occur at high rates. One variable that may affect the radiosensitivity of prostate tumor cells is their p53 status because this gene controls radiation-induced cell cycle arrest, apoptosis, and the repair of DNA damage. Using a system in which p53 function was conditionally restored to p53-null PC3 prostate cancer cells by stable transfection with a human temperature-sensitive p53 mutant allele, we tested the hypothesis that functional p53 increases cell cycle arrest and contributes to increased clonogenic survival after ionizing radiation (IR) of prostate carcinoma cells. Cell cycle arrest and clonogenic survival in response to single and multiple daily exposures to clinically relevant 2-Gy doses of IR were examined. Whereas the temperature-sensitive p53 protein was activated by phosphorylation after IR exposure at both the restrictive and permissive temperatures, Cdkn1/p21 was only induced by functional p53 (at the permissive temperature). In the presence of functional p53, the maintenance of G(2) arrest was significantly longer (P < 0.01), and a small increase in cell survival measured by clonogenic assay was seen after exposure to a single 2-Gy dose of IR. However, functional p53 significantly increased clonogenic survival (P < 0.01) after exposure to daily doses of 2 Gy of IR and contributed to a more sustained G(2) arrest and increased G(1) arrest in response to the multifraction regimen. These studies implicate the presence of wild-type p53 with increased survival of prostate carcinoma cells after fractionated exposure to radiation. Additionally, the data provide evidence that wild-type p53 in prostate tumor cells may reduce the effectiveness of radiation therapy.

Retinal microvascular abnormalities in patients treated with external radiation for graves ophthalmopathy.

BACKGROUND: A prospective study was conducted to determine if external ionizing radiation could favorably influence the orbital manifestations of Graves ophthalmopathy. Diabetes and untreated systemic hypertension were exclusion criteria. Radiation was directed to the orbits of 42 affected patients using 0.2 rad (20 Gy) delivered in 10 doses of 0.02 rad (2 Gy). Patients were periodically examined during a 3-year interval. OBJECTIVE: To report retinal microvascular abnormalities observed in our study cohort. METHODS: Fundus findings documented with ophthalmoscopy, stereoscopic color photography, and stereoscopic fluorescein angiography prior to radiation were compared with similarly documented findings approximately 3 years following radiation. RESULTS: Prior to orbital radiation, retinal microvascular abnormalities were identified in 2 patients. The abnormalities were present bilaterally in one patient and unilaterally in the other. During the course of the study, microvascular abnormalities developed de novo in the unaffected retina of the latter patient while the retinopathy in the fellow eye progressed. Retinal microvascular abnormalities and their sequelae developed de novo in both eyes in 2 more patients. In addition to the radiation, other confounding factors known to be associated with microvascular retinopathy (uveitis, inadequately controlled systemic hypertension, and borderline blood glucose levels) were identified among the 3 patients whose eyes developed new retinal microvascular abnormalities. CONCLUSIONS: Whether the retinal microvascular abnormalities observed in these patients were caused or aggravated by external beam irradiation cannot be precisely ascertained. However, the observed progression and de novo development of retinal microvascular abnormalities within 3 years of orbital radiation raise concern that 0.2 rad (20 Gy) delivered to the orbit in 10 doses of 0.02 rad (2 Gy) may aggravate existing retinal microvascular abnormalities or cause radiation retinopathy in some patients with Graves disease. These findings and the failure of external beam radiation with 0.2 rad (2000 cGy) to favorably affect Graves ophthalmopathy, as demonstrated in a previous study, have led us to discourage further treatment of Graves ophthalmopathy with radiation.

The American Brachytherapy Society recommendations for brachytherapy of uveal melanomas.

PURPOSE: This article presents the American Brachytherapy Society (ABS) guidelines for the use of brachytherapy for patients with choroidal melanomas. METHODS: Members of the ABS with expertise in choroidal melanoma formulated brachytherapy guidelines based upon their clinical experience and a review of the literature. The Board of Directors of the ABS approved the final report. RESULTS: Episcleral plaque brachytherapy is a complex procedure and should only be undertaken in specialized medical centers with expertise in this sophisticated treatment program. Recommendations were made for patient selection, techniques, dose rates, and dosages. Most patients with very small uveal melanomas (<2.5 mm height and <10 mm in largest basal dimension) should be observed for tumor growth before treatment. Patients with a clinical diagnosis of medium-sized choroidal melanoma (between 2.5 and 10 mm in height and <16 mm basal diameter) are candidates for episcleral plaques if the patient is otherwise healthy and without metastatic disease. A histopathologic verification is not required. Small melanomas may be candidates if there is documented growth; some patients with large melanomas (>10 mm height or >16 mm basal diameter) may also be candidates. Patients with large tumors or with tumors at peripapillary and macular locations have a poorer visual outcome and lower local control that must be taken into account in the patient decision-making process. Patients with gross extrascleral extension, ring melanoma, and tumor involvement of more than half of the ciliary body are not suitable for plaque therapy. For plaque fabrication, the ophthalmologist must provide the tumor size (including basal diameters and tumor height) and a detailed fundus diagram. The ABS recommends a minimum tumor (125)I dose of 85 Gy at a dose rate of 0.60-1.05 Gy/h using AAPM TG-43 formalism for the calculation of dose. NRC or state licensing guidelines regarding procedures for handling of radioisotopes must be followed. CONCLUSIONS: Brachytherapy represents an effective means of treating patients with choroidal melanomas. Guidelines are established for the use of brachytherapy in the treatment of choroidal melanomas. Practitioners and cooperative groups are encouraged to use these guidelines to formulate their treatment and dose reporting policies. These guidelines will be modified as further clinical results become available.

Interim report of toxicity from 3D conformal radiation therapy (3D-CRT) for prostate cancer on 3DOG/RTOG 9406, level III (79.2 Gy).

PURPOSE: A prospective Phase I dose escalation study was conducted to determine the maximally tolerated radiation dose in men treated with three-dimensional conformal radiotherapy (3D-CRT) for localized prostate cancer. This is a preliminary report of toxicity at Level III (79.2 Gy) on 3D Oncology Group/Radiation Therapy Oncology Group (RTOG) 9406. METHODS AND MATERIALS: Between November 26, 1996 and October 1, 1998, 173 patients with clinically organ-confined prostate cancer (T1 and T2) were accrued to a Level III dose of 79.2 Gy. One hundred sixty-nine patients were available for analysis of toxicity. Patients were registered to two groups according to the risk of seminal vesicle invasion (SVI) on the basis of presenting PSA and Gleason score. Group 1 patients had a calculated risk of SVI <15%, and Group 2 patients had a risk of SVI > or = 15%. For Group 1 patients, the planning target volume (PTV) margins were 5-10 mm around the prostate only. For Group 2 patients, the same margins were applied to the prostate and seminal vesicles (PTV(1)) for the initial 55.8 Gy; then treatment volume was reduced to the prostate only (PTV(2)). To reduce the rectal dose on dose Level III, the minimum PTV dose was limited to 73.8 Gy, whereas the minimum gross target volume dose was 79.2 Gy, both in 44 fractions. The incidence of > or = 3 Grade late effects was compared to that in a similar group of patients treated on RTOG 7506 and 7706 studies. RESULTS: Acute tolerance to 79.2 Gy was excellent with no patients experiencing > or = Grade 3 acute toxicity. The acute toxicity rate was comparable to that reported for previous lower dose levels. With the median follow-up of 3.3 years (range: 0.4-4.4 years), a total of 4 patients (2.4%) experienced Grade 3 late toxicity, three cases of which were related to the bladder, and one related to the rectum. There were no Grade 4 or 5 late complications noted during the period of observation. These results are also comparable to those reported at dose Levels I and II. The expected incidence of > or = 3 Grade 3 late toxicity was calculated using historical data from two previous RTOG prostate cancer trials, 7506 and 7706. The calculated risk accounted for the difference in follow-up duration between patients in this study and the historical experience. The observed rate of > or = Grade 3 late effects for Group 1 (two cases) is significantly lower (p = 0.0002) than the 17.6 cases that would have been expected from the historical control. The observed rate for Group 2 (two cases) was also significantly lower (p = 0.0037) than the 12.1 cases expected. CONCLUSION: Based on excellent tolerance of 3D-CRT for stages T1 and T2 prostate cancer, further biological dose escalation has been pursued to Levels IV and V, 74 Gy and 78 Gy, respectively, at 2 Gy per day, in an attempt to reduce the total treatment duration. This trial has closed. A Phase III comparative RTOG trial is being developed to determine whether high-dose 3D-CRT improves efficacy.