Beta radiation as an adjunct to low-risk trabeculectomy. Randomized controlled clinical trial of beta irradiation as an adjunct to trabeculectomy in open-angle glaucoma. Effect of beta radiation on success of glaucoma drainage surgery in South Africa: randomised controlled trial. The Advanced Glaucoma Intervention Study (AGIS): 11. Risk factors for failure of trabeculectomy and argon laser trabeculoplasty. Postoperative radiotherapy after radical prostatectomy: a randomised controlled trial (EORTC trial 22911). Intra-arterial preoperative cytostatic treatment versus preoperative irradiation: A prospective, randomized study of lingual and sublingual carcinomas. Randomized, controlled study of low-dose 5-fluorouracil in primary trabeculectomy. A fluorophotometric study of corneal endothelium after trabeculectomy using different concentrations of Mitomycin-C. Randomised phase 2 trial of SIR-Spheres plus fluorouracil/leucovorin chemotherapy versus fluorouracil/leucovorin chemotherapy alone in advanced colorectal cancer.
To assess a single dose of intraoperative beta radiation used to enhance the success rate of trabeculectomy in a population of low-risk glaucoma patients in whom antimetabolites might not be indicated.
                A prospective randomized trial of 65 eyes was designed, with 31 eyes receiving 750 rads of intraoperative beta radiation (group 1), and 34 eyes receiving no supplementation (group 2).
                Mean follow-up time was 24 months. Mean postoperative intraocular pressure was 12.2 mmHg in group 1, and 13.7 mmHg in group 2 (P = 0.16). Mean decrease in intraocular pressure was 10.3 mmHg in group 1, and 9.3 mmHg in group 2 (P = 0.49). The two groups were not significantly different in terms of surgical complications.
                For this population of low-risk patients, there was no significant difference in outcome after applications of a single intraoperative dose of beta radiation. To assess the effect of a single intraoperative application of 750 cGy of beta irradiation on the outcome of trabeculectomy for uncontrolled open-angle glaucoma.
                A prospective, randomized, double-blind, placebo-controlled clinical trial.
                Sixty-one eyes of 61 Caucasian patients at low risk of filtering surgery failure, with poorly controlled primary or secondary open-angle glaucoma undergoing routine trabeculectomy.
                Patients were randomly assigned to control or beta irradiation groups. All patients underwent standard trabeculectomy with fornix-based conjunctival incision. Eyes assigned to beta irradiation received 750 cGy of beta irradiation directly over the sclerostomy site on completion of conjunctival suturing. An identical but inactive applicator was applied to control eyes, delivering no radiation. Both operator and patient remained masked to the assignment for the 12-month follow-up period.
                The main outcome measure was intraocular pressure (IOP) control. Complete success of IOP control was defined as an IOP less than 21 mmHg at 12 months without need for additional medication. Qualified success was defined as an IOP less than 21 mmHg at 12 months where additional medication was required.
                Complete success of IOP control was achieved in 19 (86%) control eyes and 35 (90%) irradiated eyes (P = 1.0). Qualified success of IOP control was achieved in 21 (95%) control eyes and 39 (100%) irradiated eyes at 12 months follow-up (P = 1.0)
                We experienced a very high success rate of filtration surgery in this select population without adjunctive irradiation. Our sample size was too small to show any improvement in success with use of beta irradiation in this group. Other studies would have to be done to determine whether it may have measurable benefit in cases with a high risk of filtration failure. To evaluate whether beta radiation may offer a practical method of improving surgical success for glaucoma drainage surgery in South Africa.
                Double blind, randomised controlled trial.
                Three public hospitals in South Africa.
                450 black Africans with primary glaucoma.
                Trabeculectomy with 1000 cGy beta radiation or standard trabeculectomy without beta radiation (placebo).
                Primary outcome measure was surgical failure within 12 months (intraocular pressure > 21 mm Hg while receiving no treatment for ocular hypotension). Secondary outcomes were visual acuity, surgical reintervention for cataract, and intraoperative and postoperative complications.
                320 people were recruited. beta radiation was given to 164; 20 (6%) were not seen again after surgery. One year after surgery the estimated risk of surgical failure was 30% (95% confidence interval 22% to 38%) in the placebo arm compared with 5% (2% to 10%) in the radiation arm. The radiation group experienced a higher incidence of operable cataract (18 participants) than the placebo group (five participants; P = 0.01). At two years the estimated risks with placebo and beta radiation were, respectively, 2.8% (0.9% to 8.3%) and 16.7% (10.0% to 27.3%).
                beta radiation substantially reduced the risk of surgical failure after glaucoma surgery. Some evidence was, however, found of an increased risk for cataract surgery (a known complication of trabeculectomy) in the beta radiation arm during the two years after surgery.
                ISRCTN62430622 [controlled-trials.com]. To investigate the association of pre-intervention and post-intervention patient and eye characteristics with failure of argon laser trabeculoplasty (ALT) and trabeculectomy.
                Cohort study of participants in the Advanced Glaucoma Intervention Study.
                This multicenter study took place between 1988 and 2001. Between 1988 and 1992, 789 eyes of 591 patients aged 35 to 80 years with advanced glaucoma were randomized into one of two surgical treatment sequences: argon laser trabeculoplasty (ALT)-trabeculectomy-trabeculectomy or trabeculectomy-ALT-trabeculectomy. Upon study-defined failure (based on maximum medications, sustained intraocular pressure (IOP) elevation, visual field defect, and disk rim deterioration) of each intervention, patients were offered the subsequent intervention. Potential follow-up was 8 to 13 years. This report is based on data from 779 eyes that had at least 3 months of follow-up. The main outcome measures are failure of ALT and trabeculectomy, whether as first or second interventions. Effect size is measured by the hazard ratio (HR) and its corresponding 95% confidence interval (CI) obtained from Cox multiple regression analysis, where HR corresponds to the coefficient of change in risk associated with a unit increase in a factor. For binary factors, this corresponds to the change in risk in eyes with the factor relative to the risk in eyes without the factor.
                Pre-intervention factors associated with failure of ALT are younger age (HR = 0.98, CI = 0.96-0.99, P =.009) and higher IOP (1.11, 1.08-1.15, P <.001). Pre-intervention factors associated with failure of trabeculectomy are younger age (HR = 0.97, CI = 0.95-0.99, P =.005) and higher IOP (1.04, 1.01-1.06, P =.002), as well as diabetes (2.86, 1.88-4.36, P <.001) and any postoperative complication (1.99, 1.35-2.93, P <.001). Individual postoperative complications significantly associated with increased risk of failure of trabeculectomy are elevated IOP (3.4, 1.9-6.1, P <.001) and marked inflammation (2.4, 1.3-4.6, P =.006).
                In this study, ALT failure was associated with younger age and higher pre-intervention IOP. Trabeculectomy failure was associated with younger age, higher pre-intervention IOP, diabetes, and one or more postoperative complications, particularly elevated IOP and marked inflammation. Local failure after prostatectomy can arise in patients with cancer extending beyond the capsule. We did a randomised controlled trial to compare radical prostatectomy followed by immediate external irradiation with prostatectomy alone for patients with positive surgical margin or pT3 prostate cancer.
                After undergoing radical retropubic prostatectomy, 503 patients were randomly assigned to a wait-and-see policy, and 502 to immediate postoperative radiotherapy (60 Gy conventional irradiation delivered over 6 weeks). Eligible patients had pN0M0 tumours and one or more pathological risk factors: capsule perforation, positive surgical margins, invasion of seminal vesicles. Our revised primary endpoint was biochemical progression-free survival. Analysis was by intention to treat.
                The median age was 65 years (IQR 61-69). After a median follow-up of 5 years, biochemical progression-free survival was significantly improved in the irradiated group (74.0%, 98% CI 68.7-79.3 vs 52.6%, 46.6-58.5; p<0.0001). Clinical progression-free survival was also significantly improved (p=0.0009). The cumulative rate of locoregional failure was significantly lower in the irradiated group (p<0.0001). Grade 2 or 3 late effects were significantly more frequent in the postoperative irradiation group (p=0.0005), but severe toxic toxicity (grade 3 or higher) were rare, with a 5-year rate of 2.6% in the wait-and-see group and 4.2% in the postoperative irradiation group (p=0.0726).
                Immediate external irradiation after radical prostatectomy improves biochemical progression-free survival and local control in patients with positive surgical margins or pT3 prostate cancer who are at high risk of progression. Further follow-up is needed to assess the effect on overall survival. For several decades, both preoperative intra-arterial chemotherapy and preoperative irradiation have been accepted treatments for patients with tumors of the head and neck. Unfortunately, arguments have often been put forward in favor of one or other of the two methods, but without the performance of an objective, randomized investigation. To resolve this situation, the authors have carried out a multicenter, randomized prospective study of selected patients with a view to deciding which method affords better results in complex tumor therapy from the aspects of survival and postoperative quality of life.
                One hundred thirty-one patients with operable sublingual or lingual squamous cell carcinoma in stages T2NXM0 to T4MXM0 were randomized into 2 groups: 1 group participated in preoperative chemotherapy with cisplatin and epirubicin (total doses: 200 mg cisplatin, 120 mg epirubicin) via the external carotid artery, whereas the other group received preoperative radiation therapy (46 grays). Following subsequent radical surgery, the patients received regular follow-up for 5 years.
                By the end of the 5 years, 95 of the 131 patients had conformed to the protocol. Of those 95, 47 had received preoperative chemotherapy and 48 preoperative irradiation. After 5 years, 18 of the 47 patients who received chemotherapy and 15 of the 48 patients who received irradiation were still alive and tumor free. A few more patients had died of recurrence or regional metastasis in the chemotherapy group (23 patients) than in the irradiation group (20 patients). Occurrence of a second carcinoma was 3 times as frequent in the irradiation group (9 patients) as in the chemotherapy group (3 patients). Overall, the survival rates were by-and-large the same for the two groups. Regarding postoperative quality of life, the chemotherapy group presented a more favorable picture.
                The long term survival results subsequent to preoperative intra-arterial chemotherapy or preoperative radiotherapy were practically the same. Regarding postoperative quality of life, patients who underwent intra-arterial chemotherapy appeared to be in a slightly more favorable situation. The authors consider it important to stress these findings, as they are not aware of a similar randomized study of patients with tumors of the oral cavity.
                Copyright 1999 American Cancer Society. To report a randomized clinical trial of postoperative subconjunctival injections of low-dose 5-fluorouracil in patients undergoing primary trabeculectomy.
                In a prospective, randomized clinical trial, 40 eyes of 40 patients were randomized to the low-dose 5-fluorouracil group and received three subconjunctival injections of 5 mg each over 11 postoperative days, and 40 eyes of 40 patients were randomized to trabeculectomy without 5-fluorouracil.
                Mean (+/-SD) preoperative and 1-year postoperative intraocular pressures in the 5-fluorouracil group were 26.9 (+/-9.5) and 15.3 (+/-5.8) mm Hg, respectively. In the control group these were 25.9 (+/-8.1) mm Hg, and 15.8 (+/-5.1) mm Hg, respectively. The patients who received 5-fluorouracil had a mean reduction in intraocular pressure of 11.5 (+/-9.1) mm Hg at a median follow-up of 52.3 weeks. The control group had a mean reduction in intraocular pressure of 10.2 (+/-8.7) mm Hg at a median follow-up of 52.6 weeks. These differences were not statistically significant.
                Three postoperative subconjunctival 5-fluorouracil injections of 5 mg each after trabeculectomy in eyes at low risk for failure had no statistically or clinically significant effect on reduction of intraocular pressure with 1-year follow-up. Enhancement of success in this group of patients may require a larger total dose of 5-fluorouracil. The aim of the study was to determine the corneal endothelial permeability coefficient (Pac) in subjects after trabeculectomies using different concentrations of Mitomycin-C (MMC). MMC, a highly toxic drug, is not without drawbacks and complications such as corneal damage. To ascertain a possible relationship between a level of endothelial permeability (Pac) and concentrations of MMC used, we performed, in a prospective study, trabeculectomies in cases of primary open-angle glaucoma (POAG), younger than 50 years, with either concentrations of 0.5 mg/ml of MMC (group 1: 11 eyes) or 0.2 mg/ml of MMC (group 2: 10 eyes). Group 3 consisted of 8 patients after a typical trabeculectomy without MMC and served as a control group (8 eyes). In all groups, before surgery and again 1, 3 and 6 months after surgery, corneal endothelial permeability (Pac) was determined by using anterior segment fluorophotometry (Fluorotron Master). The thickness of the cornea (CT) was measured with a DGH Technology ultrasonic pachymeter. One month after surgery the mean values of Pac were statistically significantly higher in groups 1 and 2 (group 1: 4.78 x 10(-4) cm/min, group 2: 4.67 x 10(-4) cm/min) in comparison with the control group (group 3: 3.37 x 10(-4) cm/min), but the differences between groups 1 and 2 were not statistically significant (p = 0.05). Six months after operation the mean values of Pac in all groups were normalized. In eyes that underwent trabeculectomy with MMC, higher concentrations of MMC were likely to have a transient adverse effect on corneal endothelial permeability. In light of the resulting toxic intraocular effect of MMC, the damage in the function of the corneal endothelial barrier is greater with greater concentrations of MMC. Selective internal radiation therapy (SIRT) with SIR-Spheres(R) is a new technique for selectively targeting high doses of radiation to tumours within the liver. The primary objectives of this randomised trial were to compare the response rate, time to progressive disease (PD), and toxicity of a regimen of systemic fluorouracil/leucovorin chemotherapy versus the same chemotherapy plus a single administration of SIR-Spheres in patients with advanced colorectal liver metastases. The trial was designed to presage a larger trial that would have survival as the primary outcome.
                Twenty-one patients with previously untreated advanced colorectal liver metastases, with or without extrahepatic metastases, were randomised into the study.
                Using RECIST criteria, the response rate for 11 patients receiving the combination treatment was significantly greater than for 10 patients receiving chemotherapy alone (First Integrated Response; 10 PR, 1 SD vs. 0 PR, 6 SD, 4 PD, P < 0.001 and Best Confirmed Response; 8 PR, 3 SD vs. 0 PR, 6 SD, 4 PD P < 0.001). The time to PD was greater for patients receiving the combination treatment (18.6 months vs. 3.6 months, P < 0.0005). Median survival was significantly longer for patients receiving the combination treatment (29.4 months vs. 12.8 months, P = 0.02). One patient in the combination arm died from chemotherapy induced neutropenic sepsis after the fourth chemotherapy cycle. There were more Grade 3 and 4 toxicity events in patients receiving the combination treatment. There was no difference in quality-of-life over a 3 month period between the two treatments when rated by patients (P = 0.96) or physicians (P = 0.98).
                This small phase 2 randomised trial demonstrated that the addition of a single administration of SIR-Spheres to a regimen of systemic fluorouracil/leucovorin chemotherapy significantly increased both treatment related response, time to PD, and survival with acceptable toxicity. The combination of SIR-Spheres plus systemic chemotherapy is now the subject of ongoing trials to further define patient benefit.
                (c) 2004 Wiley-Liss, Inc.
Trabeculectomy with beta irradiation has a lower risk of surgical failure compared to trabeculectomy alone. A trial of beta irradiation versus anti-metabolite is warranted.