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The treatment of 783 keloid scars by iridium 192 interstitial irradiation after surgical excision.

PURPOSE: the aim of this study is to confirm the effectiveness of irradiation associated with surgery in the treatment of keloids, to precise the factors favoring the recurrence of these keloids, and to evaluate the risk of recurrence, according to their initial distinctive features. METHODS AND MATERIALS: between 1977 and 1988, 544 patients, with a total of 855 keloids, were treated by interstitial radiotherapy immediately following total excision. RESULTS: recurrence rate is 21%, as against 50 to 80% for surgery alone, according to most authors. This recurrence rate is about the same as for external radiotherapy, but we prefer our method for practical reasons (cost, equipment, radiobiology, technique). Ninety percent of recurrences occurred in the year following therapy, which proves that a follow-up time of at least 12 months is needed for a study of keloids. In our experience, the keloids that are the most likely to recur are the largest and those giving rise to most symptoms. Bruising and loosened stitches, but in particular infection during therapy, largely favor a recurrence. In our series, the symptoms disappeared or were much improved in 80% of cases, and the cosmetic result was judged good by 75% of the patients. CONCLUSION: the results of this study proves the effectiveness of the method linking surgical excision and Iridium 192 interstitial irradiation and shows the importance of the sterile conditions of the treatment.

Adolescent↗

Differential pH measurements of metabolic cellular activity in nl culture volumes using microfabricated iridium oxide electrodes.

In this paper we describe a new approach to measure pH differences in microfluidic devices and demonstrated acidification rate measurements in on-chip cell culture systems with nl wells. We use two miniaturized identical iridium oxide (IrOx) thin film electrodes (20 micromx400 microm), one as a quasi-reference electrode, the other as a sensing electrode, placed in two confluent compartments on chip. The IrOx electrodes were deposited onto microfabricated platinum (Pt) electrodes simultaneously using electrodeposition. Incorporating the electrodes into a microfluidic device allowed us to expose each electrode to a different solution with a pH difference of one pH unit maintaining a confluent connection between the electrodes. In this configuration, we obtained a reproducible voltage difference between the two IrOx thin film electrodes, which corresponds to the electrode sensitivities of -70 mV/pH at 22 degrees C. In order to measure the acidification rate of cells in nl cell culture volumes we placed one IrOx thin film electrode in the perfusion channel as a quasi-reference electrode and the other in the cell culture volume. We obtained an acidification rate of 0.19+/-0.02 pH/min for fibroblast cells using a stop flow protocol. These results show that we can use two identical miniaturized microfabricated IrOx electrodes to measure pH differences to monitor the metabolic activity of cell cultures on chip. Furthermore, our approach can also be applied in biosensor or bioanalytical applications.

Animals↗

High dose rate iridium-192 brachytherapy as a component of radical radiotherapy for the treatment of localised prostate cancer.

AIMS: To assess the treatment outcomes and toxicity of conformal high dose rate (HDR) brachytherapy boost as a means of radiation dose escalation in patients with localised prostate cancer. MATERIALS AND METHODS: Between December 1998 and July 2004, 65 consecutive patients with localised prostate cancer (magnetic resonance imaging-staged T1-3 N0 M0) were treated with external beam radiation therapy (EBRT) followed by two fractions of HDR iridium-192 brachytherapy. The patients selected this treatment modality in preference to entering an ongoing randomised phase 3 trial. Any pre-treatment serum prostate-specific antigen (PSA) and Gleason score were included. The primary end point was biochemical disease-free progression. Late treatment-related morbidity was graded according to the Radiation Therapy Oncology Group and the European Organization for Research and Treatment of Cancer criteria. RESULTS: The median patient age was 67.3 years (range 47.9-80). Sixty patients (92.3%) had intermediate- to high-risk disease defined by clinical stage, presenting PSA and Gleason score/World Health Organisation (WHO) grade. With a median follow-up of 3.5 years (range 0.6-5.8), two patients had died of metastatic disease and another four patients had PSA relapse, giving a 3-year actuarial biochemical disease-free progression of 90.8%. Three patients (4.6%) had acute grade 3 genitourinary toxicity, in the form of urinary retention. Late grade 3 and 4 genitourinary toxicities occurred in four patients (6.2%) and one patient (1.5%), respectively. No late gastrointestinal toxicities were observed. CONCLUSIONS: These results suggest that the combined modality of conformal HDR brachytherapy and EBRT is a feasible treatment modality with acceptable acute and late toxicities, comparable with those of EBRT alone. It offers an attractive conformal treatment modality with the potential of further dose escalation in the treatment of localised prostate cancer.

Aged↗

Measurement of dosimetric parameters for the Alpha-Omega high-dose-rate Iridium-192 source.

Thermoluminescent (TLD) measurements of dose-rate constant, anisotropy function, and radial dose function are reported for the Alpha-Omega high dose rate (HDR) Iridium-192 ((192)Ir) source, which has been available since 1998 for use in the MicroSelectron HDR afterloader manufactured by the Nucletron Corporation. Measurement results are compared with published or available Monte Carlo calculations for both sources. They are found in good agreement, and, within experimental accuracy, no difference is seen in the dosimetric parameters of both sources.

Iridium Radioisotopes↗

High-dose-rate iridium-192 afterloading therapy combined with external beam radiotherapy for T1c-T3bN0M0 prostate cancer.

OBJECTIVES: To determine the efficacy of radiotherapy (RT) for T1c-T3bN0M0 prostate cancer in a prospective clinical trial of concurrent external beam RT and fractionated iridium-192 high-dose-rate brachytherapy. METHODS: Included in the study were 98 patients with T1c-T3bN0M0 prostate cancer who were diagnosed between October 1997 and September 2002 and underwent high-dose-rate brachytherapy with external beam RT. Treatment consisted of external beam RT (four ports) to the prostate of 16 fractions of 2.3 Gy to a total dose of 36.8 Gy and high-dose-rate brachytherapy of 4 fractions of 6.0 Gy within 30 hours to a total dose of 24.0 Gy. No patient received adjuvant hormonal therapy after RT. RESULTS: The most recent prostate-specific antigen level was 0.0 to 3.9 ng/mL (median 0.4). Seven patients (7.1%) developed recurrence and treatment was considered a failure (bone metastasis in two and biochemical failure in five). The overall biochemical disease-free survival (bDFS) rate was 95.9% at 2 years and 92.9% at 5 years. The bDFS rate by T stage was 98.6% at 2 years and 95.9% at 5 years for Stage T1c-T2b and 88.0% and 84.0% for Stage T3a-b, respectively (P = 0.047). The 2-year and 5-year bDFS rate was better in patients with an initial prostate-specific antigen level of less than 20 ng/mL compared with 20 ng/mL or greater (98.6% and 97.1% versus 93.1% and 82.8%, respectively, P = 0.0261). Acute toxicity was mild to moderate (Radiation Therapy Oncology Group grade 1-2) and consisted of cystourethritis or proctitis in 29 (29.6%) of 98 patients. CONCLUSIONS: With a low complication rate and satisfactory bDFS rates, this combination therapy can be considered an alternative method for clinical Stage T1c-T3b prostate cancer and is expected to improve patient quality of life. Additional long-term follow-up is needed to confirm this treatment.

Adenocarcinoma↗

Effect of catheter-based iridium-192 gamma brachytherapy on the added risk of restenosis from diabetes mellitus after intervention for in-stent restenosis (subanalysis of the GAMMA I Randomized Trial).

Catheter-based intracoronary radiation therapy using iridium-192 (Ir-192) has been shown to be effective in reducing recurrent coronary restenosis after initial percutaneous treatment of in-stent restenosis. Patients with diabetes mellitus (DM) have a higher risk of recurrent restenosis than nondiabetics for nonstented and in-stent restenosis coronary lesions. The use of Ir-192 for preventing recurrent restenosis in such patients remains undefined. The GAMMA I trial was a prospective, randomized, double-blind, multicenter trial of 252 patients with in-stent restenosis who underwent percutaneous coronary intervention and were assigned to receive either Ir-192 (131 patients) or catheter-based placebo (121 patients). DM was present in 79 patients (31%) (41 patients received Ir-192 and 38 patients received placebo) and was absent in 173 patients (90 patients received Ir-192 and 83 patients received placebo). At 6-month follow-up in the GAMMA I trial, the angiographic in-lesion binary restenosis rate was lower in the Ir-192 arm than in the placebo arm (32.4 vs 55.3, p = 0.01). When patients were stratified by the presence of DM, the antirestenosis effect of Ir-192 was larger for diabetic patients than for nondiabetic patients (absolute in-lesion restenosis rate was reduced by 40% for diabetics and 16% for nondiabetics). Thus, adjunctive Ir-192 intracoronary radiation therapy reduces recurrent restenosis after intervention for in-stent restenosis in patients with and without DM. The relative impact of this treatment is more pronounced in diabetic patients because it appears to neutralize the added risk of recurrent restenosis seen in proliferative diabetic lesions.

Brachytherapy↗

A modified afterloading technique for small implants using iridium-192 wires for interstitial therapy.

A new method is described for small iridium-192 wire implants upon the skin of the face. The method is a miniaturisation of a technique described previously (Paine, 1972), and has the advantage that is results in less scarring and therefore a better cosmetic end-result than in the case when the more conventional wide-bore tubing is employed. This new method produces similar clinical results in terms of tumour cure to other methods, and a degree of after-loading helps in radiation protection.

Carcinoma, Squamous Cell↗

Problems associated with iridium-192 wire implants.

Three incidents are reported, from different radiotherapy centres, in which an implanted iridium-192 wire remained in the tissues of a patient after withdrawal of the plastic tubing in which it was contained. In each case the instrument used to cut the wire had probably formed a hook on the end of the wire which caused it to catch in the tissues. Detailed recommendations are made for avoiding such incidents in the future, the most important of which is that the patient should be effectively monitored after the supposed removal of all radioactive sources.

Aged↗

Internal biliary drainage and local radiotherapy with iridium-192 wire in treatment of hilar cholangiocarcinoma.

Curative surgery is not possible in the vast majority of patients who present with hilar cholangiocarcinoma. Palliative therapy to relieve jaundice, either at laparotomy or percutaneously, is therefore necessary. The mean survival of these patients is of the order of 8.5 months (Wheeler et al., 1981). We report a significant increase in mean survival to 16.8 months in patients treated with internal biliary drainage when combined with local irradiation to the tumour with iridium-192.

Adenoma, Bile Duct↗

Low radiation iridium 191m radionuclide angiography: detection and quantitation of left-to-right shunts in infants.

Radionuclide angiography using iridium 191m was carried out in 34 premature infants and young children for detection and quantitation of left-to-right shunts. Ir-191m has a physical half-life of 4.96 seconds and can be imaged with conventional gamma scintillation cameras. The whole body radiation absorbed dose from Ir-191m is 3.5 mrad/mCi, which is about 40 times less radiation than with technetium 99m. Other advantages of Ir-191m include high photon flux for improved imaging and the possibility of multiple studies within a short period of time without background. Nine patients had simultaneous measurement of pulmonary-to-systemic flow ratio by Ir-191m angiography and oxymetry during cardiac catheterization; the correlation coefficient was 0.90. Radionuclide angiography with Ir-191m is a method with virtually no risk, rapid, accurate, and reproducible, and is ideally suited for the evaluation of left-to-right shunts in small children.

Angiography↗

Biocompatibility and charge injection property of iridium film formed by ion beam assisted deposition.

Iridium thin film formed by electron-beam evaporation with simultaneous bombardment of Ar ion beam was evaluated for a stimulating neural electrode. The electrochemical behavior of as-deposited Ir film on Ni-Ti sample was almost identical to bulk Ir by producing much higher open-circuit corrosion potential and much lower anodic current density than the uncoated Ni-Ti in both 1N sulfuric acid and saline solution. The charge injection capability of Ir film was compared with that of Pt electrode currently used mostly as a stimulating neural electrode. The charge density of Pt was small and unchanged with increasing number of activating cycles in 0.1M H(2)SO(4), whilst the Ir film continuously produced increases in charge density. The charge injection density of Ir film in physiological solution was higher for the more activated sample under the identical stimulating condition. Attachment and proliferation with PC12 cells on Ir-coated CP Ti without applying electrical stimulation was similar to the polished CP Ti. A network of neurons and extending axons were formed on Ir film.

Animals↗

Possible impact of iridium-192 source centering on restenosis rate after femoro-popliteal angioplasty and endovascular brachytherapy in Vienna-2 study.

PURPOSE: Endovascular brachytherapy (EVBT) has been proven to significantly reduce restenosis after percutaneous transluminal angioplasty (PTA). The object of this analysis was to assess the possible correlation between iridium-192 source non-centering and angiographic-determined restenosis. MATERIALS AND METHODS: A total of 113 patients with long-segment lesions of the superficial femoro-popliteal artery (SFA) were randomized to receive either PTA alone or PTA followed by EVBT in the Vienna-2 study. This analysis was performed on a subgroup of 34 out of 57 patients, who received PTA+EVBT. Angiographic restenosis was defined as lumen reduction of more than 50%. Angiograms taken immediately after PTA (34 patients) and at follow-up (25 patients) were analyzed. The distance between the vessel wall and the actual position of the source at the time of EVBT was measured (in mm) and correlated with the follow-up vessel lumen diameter. Measurements were performed at points at a distance of 10 mm from each other. The dose was determined at the luminal surface and at the reference depth of 2 mm into the vessel wall for different distances from the source. RESULTS: Among the 622 measured points, 62 (10.0%) were within restenotic areas; 560 (90.0%) were in arterial segments without proven angiographic restenosis. As far as source centering is concerned, 7.9% of restenotic points were observed when the maximum distance to the arterial wall was <3 mm and 9.6% for 4 mm, respectively. The percentage of restenotic points increased up to 15.9% when the maximum distance to the arterial wall was 5 mm and reached 22.2% when it was >5 mm. CONCLUSIONS: The proportion of restenotic points significantly increased with source non-centering. This observation was interpreted as being related to a decrease in dose at the target. When the maximum distance between the source and the vessel surface was >5 mm, the dose at the reference depth (2 mm into the vessel wall) decreased to values lower than 5 Gy.

Angioplasty, Balloon, Coronary↗

Conservative treatment of early carcinoma of the breast: significance of axillary dissection and iridium implant.

One hundred and ninety five patients with T1T2 less than 3 cm N0 infiltrating carcinomas of the breast have been treated between 1973 and 1982 with local excision followed by cobalt irradiation and iridium boost. One hundred and sixty five underwent an elective axillary dissection. The overall survival at 5 years is 87% and the NED survival 81%. The size of the tumor on the mammogram and on the operative specimen is of significant prognostic value. At 5 years the probability of local relapse in the breast is 4% and the probability of axillary recurrence is 1.2% after axillary dissection. Comparison of these results with those of an historical group of 300 patients treated between 1950 and 1973 indicates an improvement in the local control with good cosmetic results and no obvious change in axillary recurrence and overall survival.

Adolescent↗

Iridium-192 brachytherapy in the management of 147 T2N0 oral tongue carcinomas treated with irradiation alone: comparison of two treatment techniques.

Our purpose is to analyse local control, complications relative to the proportion of total dose delivered by external beam irradiation versus interstitial implant in 147 patients with previously untreated T2N0 squamous cell carcinoma of the oral tongue, managed between 1973 and 1986 (UICC staging system). These T2N0 patients are part of a larger group of 430 patients with oral tongue carcinoma (T1, T2, T3) treated with irradiation alone. Of these 147 T2N0 patients, 70 were treated with interstitial implant alone and 77 with both external beam irradiation and implant. In the group treated with interstitial implant alone, the 5-year local control was 89.8% against 50.6% in those treated with external beam irradiation and interstitial implant (log-rank test, p = 0.00002); 67.6% versus 46.5% for locoregional control (p = 0.029); and 62.2% versus 34.7% for specific survival (p = 0.0015). Since 1980, all the patients treated by iridium implantation were protected with a leaded spacing device between the tongue and the mandible. Soft tissue necrosis and bone exposure following treatment were scored according to the following criteria: minor, moderate or severe. Seven moderate and one severe complications were recorded in the brachytherapy group. None of the patients required surgery. In the combined treatment group, six moderate and two severe complications were observed. Patients treated with interstitial implant alone, and showing moderate or severe complications had received an average brachytherapy dose of 7600 cGy. In the same group, the patients without complications had received an average dose of 6800 cGy.(ABSTRACT TRUNCATED AT 250 WORDS)

Brachytherapy↗

External irradiation and intraluminal irradiation using middle-dose-rate iridium in patients with roentgenographically occult lung cancer.

PURPOSE: Therapeutic results were analyzed in 39 patients with roentgenographically occult lung cancer (ROLC), and the significance and optimal dose of this therapy were evaluated. METHODS AND MATERIALS: The subjects were 39 patients who underwent intraluminal irradiation between May 1987 and August 1999. Radiotherapy was performed by combining external irradiation with intraluminal irradiation using middle-dose-rate iridium (four 370-MBq wires) through a catheter with a spacer, which held the source in the center of the bronchus. The doses of radiation were 22-66 Gy (median value 45 Gy) by external irradiation and 10-46 Gy (median value 28 Gy) by intraluminal irradiation. RESULTS: The therapeutic effect was CR in 38 patients and PR in 1, and local recurrence was observed in a PR case and 3 of the 38 patients who showed CR. The 3-year and 5-year relapse-free survival rates were both 87%. No severe radiation injury was observed. CONCLUSIONS: Considering that ROLC often occurs as multiple cancers and that many patients with ROLC have reduced lung function, radiation therapy by a combination of intraluminal irradiation and external irradiation is expected to replace surgery as the first choice for the treatment of this disease in the twenty-first century.

Aged↗

External radiation therapy and transcatheter iridium in the treatment of extrahepatic bile duct carcinoma.

PURPOSE/OBJECTIVE: Review survival, prognostic factors, and patterns of failure in patients with extrahepatic bile duct (EHBD) carcinoma treated with external beam irradiation (EBRT) and transcatheter iridium. METHODS AND MATERIALS: The charts of 24 patients with EHBD cancer treated with EBRT and transcatheter boost were reviewed. All patients had transhepatic biliary tubes or endoprostheses placed. Two patients underwent hemihepatectomy with hepaticojejunostomy formation but had residual disease. Two patients had biopsy proven adenopathy. Five patients had Grade 1 adenocarcinoma, nine Grade 2, six Grade 3, and one Grade 4 disease. Median EBRT dose was 50.4 Gy delivered in 1.8 Gy/day fractions. Median transcatheter boost at 1 cm radius was 20 Gy. Nine patients received concomitant 5-Fluorouracil (5-FU) during EBRT. RESULTS: Median survival was 12.8 months (range 7.5 months to 9 years). Overall 2- and 5-year survival rates were 18.8 and 14.1%, respectively (three disease-free survivors > or =5 years). One patient is still alive without relapse 10 years from diagnosis and 5 years after liver transplantation for liver failure (no cancer in specimen, underlying sclerosing cholangitis). Two additional long-term survivors had no evidence of relapse 6.9 and 8.2 years after diagnosis. Histologic grade, lymph node status, cystic, hepatic, common hepatic or common bile duct involvement, surgical resection, radiation therapy dose, and chemotherapy did not significantly effect survival due to the number of patients analyzed. There was a trend towards improved survival with the addition of 5-FU chemotherapy (5-year survival in two of nine patients, or 22%). Eight of 24 patients (33%) demonstrated radiographic evidence of local recurrence. Distant metastases developed in 6 of 24 (25%) patients. The most common complications were tube related cholangitis (50%) and gastric/duodenal ulceration or bleeding (42%). CONCLUSION: External beam irradiation combined with a transcatheter boost can result in long-term survival of patients with EHBD cancer. Both distant metastases and local recurrence develop in 25-30% of patients despite irradiation. Survival may be improved by using chemotherapy in combination with EBRT to impact disease relapse (local and distant). Because there may be a dose response with irradiation, survival may also be improved by increasing the dose of radiation delivered by transcatheter boost. A Phase II trial is being developed using a combination of 45-50 Gy EBRT with concomitant 5-FU delivered by protracted venous infusion followed by a 25-30 Gy transcatheter boost.

Adult↗

Muscle invasive bladder cancer treated by transurethral resection, followed by external beam radiation and interstitial iridium-192.

PURPOSE: To evaluate the results of transurethral resection (TUR), external beam radiotherapy (EBRT), and interstitial radiation (IRT) with iridium-192, using the afterloading technique in patients with muscle invasive bladder cancer. METHODS AND MATERIALS: From May 1989 until September 1995, 66 patients with primary, solitary muscle invasive bladder cancer were treated with TUR, EBRT, and IRT, aiming at bladder preservation. According to the protocol, in three patients low-dose EBRT was applied, whereas 63 patients received high-dose EBRT. Immediately prior to IRT, 42 patients underwent a lymphnode dissection, and in 16 cases a partial cystectomy was performed. For IRT, two to five catheters were used and IRT was started within 24 h after surgery. The majority of patients received 30 Gy of IRT, with a mean dose rate of .58 Gy/h. In three patients, additional EBRT was applied following IRT. Follow-up consisted of regular cystoscopies, mostly done during joint clinics of urologist and radiation oncologist, with urine cytology routinely performed. The median follow-up period was 26 months. The Kaplan-Meier method was used for the determination of survival rates. RESULTS: In seven patients, a bladder relapse developed. The probability of remaining bladder relapse free at 5 years was 88%. The bladder was preserved in 98% of the surviving patients. Metastases developed in 16 patients, and the probability of remaining metastasis free at 5 years was 66%. The cumulative 5-year overall and bladder and distant relapse free survival were 48% and 69%, respectively. Acute toxicity was not serious in the majority of cases; surgical correction of a persisting vesicocutaneous fistula was necessary in two patients, whereas a wound toilet had to be performed in another patient. Serious late toxicity (bladder, RTOG Grade 3) was experienced by only one patient. CONCLUSIONS: Interstitial radiation preceded by TUR and EBRT, in a selected group of patients with muscle invasive bladder cancer, yields an excellent bladder tumor control rate with a high probability of bladder preservation. Survival was mainly dependent on the development of distant metastases. Serious acute and late toxicity was rare.

Adenocarcinoma↗

Iridium-192 high dose rate brachytherapy combined with external beam irradiation in non-resectable oesophageal cancer.

Forty-eight patients with non-resectable cancer of the oesophagus and oesophagogastric junction (group A: Stage I/II: n = 32; group B: Stage III/IV: n = 16) underwent intralumenal iridium-192 high dose-rate afterloading brachytherapy (5-7 Gy/session, total dose 5-21 Gy, mean 12.4 Gy) and external beam irradiation (Karnofsky > or = 80%: 50-60 Gy/2 Gy per day; Karnofsky 60%-79%: 30 Gy/3 per day). Prolonged satisfactory palliation (intake of at least semi-solid food) was demonstrated in 96% of patients. The mean survival for group A was 19.1 months and that for group B 6.9 months, with a 12-month survival rate of 66% for group A and 0% for group B (P < 0.001). Local tumour response and complication rate were significantly dose related with a predicted response rate of 70.5% and a complication rate of 50% at extrapolated response dose (ERD) 129.3 GY3 (Gy at alpha/beta = 3).

Adult↗