Search PubMed⌕ Search

SEARCH · Search PubMed

Results for “Dose reduction”

Search indexed PubMed citations on genomics, clinical trials, systematic reviews and public health. Explore titles, authors and supplied subject terms, then open the PubMed record.

Quote a phrase for an exact phrase match. Source license links do not imply unrestricted reuse.

At least 505 records · Page 28Linked to original sources
PubMedDate not supplied

Rational approach to the clinical protocol design for drug combinations: a review.

Based on the median-effect equation of Chou and the combination index (CI) equation of Chou-Talalay, a computer software for automated dose-effect analysis has been developed. This method provides quantitation of synergism (CI < 1) and antagonism (CI > 1) at different dose and effect levels. Therefore, it allows the selection of the best pair (or triplet) of combination, optimal combination ratio, and the best schedule of treatment. These analyses has been shown to be useful for the clinical protocol design. (Chang et al. Cancer Res. 45: 2434-2439, 1985). The user-friendly computer program also gives dose-reduction index (DRI) which determines how many fold of dose-reduction is allowed for each drug in synergistic combinations. Dose reduction leads to reduced toxicity while maintaining the desired efficacy (Chou et al. Encyclopedia of Human Biology 2:675-683, 1997; Encyclopedia of Cancer 1:368-379, 1997). The Chou-Talalay method distincts from all other methods by the fact that it not only takes into account the "potency" but also the "shape" of dose-effect curves of each drug and their combinations (Chou & Hayball, CalcuSyn for Windows, Biosoft, Cambridge UK, 1996). This method has been applied in combination of anticancer agents, anti-HIV agents, purging leukemic cells for autologous bone marrow transplantation (Chang et al. Cancer Res. 47:119-122, 1987) and combination of immunosuppressants for organs transplants. Specific examples of the theoretical equations, the median-effect plot, the CI plot, the isobologram, and the polygonogram are illustrated.

Antineoplastic Combined Chemotherapy Protocols↗
PubMed1999

The effects of chronic prostacyclin therapy on cardiac output and symptoms in primary pulmonary hypertension.

OBJECTIVES: This study evaluated the response to prostacyclin dose reduction in patients with primary pulmonary hypertension (PPH) who developed high cardiac outputs. BACKGROUND: Patients on prostacyclin require chronic upward dose titration to overcome tolerance to the medication. No upper limit of effective dose has been described. METHODS: We studied 12 patients with PPH treated with chronic prostacyclin therapy who presented in high cardiac output states. Each patient underwent prostacyclin dose reduction under hemodynamic guidance targeted to reduce the cardiac index to < or =4 liter/min/M2, unless rebound pulmonary hypertension occurred. Following dose reduction, patients were observed for changes in the effectiveness of the prostacyclin. RESULTS: Patients were treated for 39 +/- 20 months, resulting in a 71% reduction in pulmonary vascular resistance compared to baseline. At the time of their most recent evaluation their cardiac outputs were increased to 10.1 +/- 2.3 liter/min. The patients underwent a 39% dose reduction (range 12% to 78%) resulting in a change of mean PAP from 45 to 46 mm Hg (p = NS), cardiac index from 7.4 +/- 1.4 to 4 +/- 0.74 liter/min/M2 (p = 0.01), and pulmonary vascular resistance from 3.7 +/- 1.7 to 4.7 +/- 1.5 units (p < 0.001). In no instance did rebound pulmonary hypertension occur. However, the patients all retained their clinical benefit without a return of tolerance. CONCLUSIONS: Excessive prostacyclin in PPH can lead to a high cardiac output state, suggesting it has important positive inotropic effects. In this circumstance, reducing the dose can allow the cardiac output to return to normal without worsening the clinical state.

Adult↗
PubMed2005

Clinical experience with everolimus (Certican): optimizing dose and tolerability.

BACKGROUND: Everolimus (Certican), a novel proliferation signal inhibitor, allows calcineurin inhibitor dose reduction in transplant patients, minimizing risk of nephrotoxicity without loss of immunosuppressive efficacy. As a result of its mode of action, this class of agent (i.e., everolimus and sirolimus) is associated with certain adverse events (e.g., lymphocele, arthralgia, edema and hyperlipidemia). METHODS: Three case studies from within an everolimus Phase III trial (A2306) are presented with the aim of illustrating how treatment-related adverse events can be managed. RESULTS: The combination of everolimus with reduced-exposure cyclosporine was efficacious in these patients. One experienced mild acute rejection that was managed with steroid boluses. All have acceptable graft function during follow-up to date. Moderate lymphocele either resolved spontaneously or was easily managed by povidine-iodine instillations. One patient developed serious early lymphocele that, unusually, required surgical intervention. Everolimus dose reduction or withdrawal was not necessary to effectively manage lymphocele of any severity. A case of bilateral multiple arthralgia was effectively managed with everolimus dose reduction, but still maintained everolimus trough blood levels at approximately 3 ng/ml. Eyelid and ankle edemas were also easily managed with low dose furosemide, preferably coupled with cyclosporine and everolimus dose reduction. Hyperlipidemia responded to statin therapy. CONCLUSIONS: Everolimus-related adverse events can be effectively managed either with other treatments or, where necessary, by everolimus dose reduction, without loss of efficacy. Discontinuing everolimus therapy is generally not necessary.

Adult↗
PubMed2003

Tacrolimus dosage requirements after initiation of azole antifungal therapy in pediatric thoracic organ transplantation.

Azole antifungals inhibit the metabolism of tacrolimus mediated by CYP3A4. Upon initiation of azole therapy, the required dose reduction of tacrolimus is unknown. We reviewed our experience with azole antifungals in our pediatric thoracic transplant population receiving tacrolimus. Tacrolimus levels and dosage requirements were compared before and during azole therapy. Thirty-one patients received both tacrolimus and an azole antifungal (fluconazole = 9, itraconazole = 22). The tacrolimus dose was empirically reduced by approximately one-third when azole therapy was initiated. Mean tacrolimus dose requirements decreased by 68% within the first month of therapy (pre-azole: 0.27 +/- 0.14 mg/kg/day; 30 day post-azole: 0.087 +/- 0.069 mg/kg/day; p < 0.001). Despite a mean decrease in tacrolimus dose from baseline of 33, 42, and 55% on day 1, 2, and 4 of azole therapy, respectively, there was still an unintended 38% increase in tacrolimus levels during the first month of azole therapy. A calculated dose-reduction protocol of 50% on day of azole initiation, 70% on day 3, and 75% on day 14 should result in minimal mean changes in the tacrolimus levels. There was no difference in tacrolimus dose reduction between fluconazole and itraconazole groups. Azole antifungals markedly decrease tacrolimus requirements within the first few days of therapy. An initial reduction in tacrolimus dose by one-third is insufficient, and dose reduction of at least 50% upon azole initiation seems warranted. Once azole antifungal therapy is initiated, frequent therapeutic drug monitoring is required.

Analysis of Variance↗
PubMed1997

Effect of renal impairment on the pharmacokinetics and pharmacodynamics of desirudin.

OBJECTIVE: To investigate the pharmacokinetics and pharmacodynamics of desirudin in subjects with various degrees of renal impairment in comparison with subjects with normal renal function. METHODS: Eight subjects with normal renal function (creatinine clearance > 90 ml/min) received 0.5 mg/kg desirudin intravenously over 30 minutes. Four subjects with mild renal failure (creatinine clearance between 61 and 90 ml/min) received 0.5 mg/kg. Five subjects with moderate renal failure (creatinine clearance between 31 and 60 ml/min) received 0.25 mg/kg. Six subjects with severe renal failure (creatinine clearance < 31 ml/min) received 0.125 mg/kg. RESULTS: Specific maximum concentration values (maximum concentrations corrected to a dose of 1 mg/kg) increased slightly with decreasing creatinine clearance. Mean specific area under the plasma concentration-time curve increased by a factor of 1.15, 2.83, and 7.0 for subjects with mild, moderate, and severe renal failure, respectively, compared with healthy subjects. Total urinary excretion of desirudin was about 55% to 60% of the dose in all four groups; elimination was delayed for subjects with moderate and severe renal failure. Total and renal clearance of desirudin were proportional to creatinine clearance. Total plasma clearance of desirudin was proportional to renal clearance of the drug. Prolongation of activated partial thromboplastin time was increased among subjects with moderate and severe renal failure despite a dose reduction. Area under the dynamic activated partial thromboplastin time curve for subjects with moderate renal failure remained the same as that for healthy subjects despite a dose reduction by a factor of two. Area under the dynamic curve increased by a factor of about 1.5 for subjects with severe renal failure despite a dose reduction by a factor of four. CONCLUSION: A dose reduction by a factor of six is recommended for persons with severe renal failure.

Adult↗
PubMed2006

Ifn/Rbv treatment induced anemia and its correction with epoetin alpha in patients with hepatitis C.

The aim of the 18 months follow up study was to assess the frequency of anemia during IFN/RBV therapy in patients with chronic hepatitis C; to manage anemia either with recombinant human erythropoietin (rHuEPO)--epoetin alpha or with RBV dose reduction and to compare the rate of SVR in patients with RBV dose reduction and with administration of epoetin alpha. Study enrolled 61 patients with chronic active hepatitis C aged 33-61 years. All patients had HCV genotype 1b. Out of them 41 were male and 20 female. Anemia (Hb <10 or >2 g/dL Hgb drop from baseline) developed in 41 patients out of 61 (67,21%) during the therapy. These 41 patients were randomized into two groups: 21 patients who received 40 000 IU epoetin alpha weekly (I group) and 20 patients in whom for managing anemia we used standard of care (SOC) or RBV dose reductions from 1000/1200 to 800/600 mg (II group). In all 21 patients of the I group the Hb level normalized without reduction of RBV dose. In this group of patients SVR at 6 months after completion of full course of treatment was achieved in 17 (66%) patients. Improvement of quality of life (QOL) was observed in all 21 patients. Out of 20 patients of II group with standard of care (SOC) 5 patients developed symptomatic anemia with fatigue and dyspnoea; RBV was stopped temporarily. In 15 patients RBV dose was reduced from 1200 mg to 600 mg for correction of anemia. In this group of patients SVR at 6 months after treatment completion was achieved in 7 (25%) patients. Lower RBV doses yield a lower treatment response in patients with HCV genotype 1. In anemic HCV-infected patients on RBV/PEG-IFN therapy, EPO maintains RBV dose and significantly improves anemia and QOL. EPO has the potential to improve adherence rate, which may in turn improve SVR.

Adult↗
PubMed2006

Pretransplant pulmonary function tests predict risk of mortality following fractionated total body irradiation and allogeneic peripheral blood stem cell transplant.

PURPOSE: To determine the value of pulmonary function tests (PFTs) done before peripheral blood stem cell transplant (PBSCT) in predicting mortality after total body irradiation (TBI) performed with or without dose reduction to the lung. METHODS AND MATERIALS: From 1997 to 2004, 146 consecutive patients with hematologic malignancies received fractionated TBI before PBSCT. With regimen A (n=85), patients were treated without lung dose reduction to 13.6 gray (Gy). In regimen B (n=35), total body dose was decreased to 12 Gy (1.5 Gy twice per day for 4 days) and lung dose was limited to 9 Gy by use of lung shielding. In regimen C (n=26), lung dose was reduced to 6 Gy. All patients received PFTs before treatment, 90 days after treatment, and annually. RESULTS: Median follow-up was 44 months (range, 12-90 months). Sixty-one patients had combined ventilation/diffusion capacity deficits defined as both a forced expiratory volume in the first second (FEV1) and a diffusion capacity of carbon dioxide (DLCO)<100% predicted. In this group, there was a 20% improvement in one-year overall survival with lung dose reduction (70 vs. 50%, log-rank test p=0.042). CONCLUSION: Among those with combined ventilation/diffusion capacity deficits, lung dose reduction during TBI significantly improved survival.

Adult↗
PubMed2001

Vagus nerve stimulation and drug reduction.

The authors prospectively assessed drug reduction and patient satisfaction in 21 patients using vagus nerve stimulation (VNS) for refractory epilepsy and compared results to a case-matched control group with a mean follow-up of 13.2 months. Significant antiepileptic drug (AED) reduction occurred in 9/21 (42.9%) of VNS patients averaging 0.43 AED/patient, with dose reduction in four patients (19.0%). For 12/21 (57.1%) patients not reducing AED, dose reduction occurred in 6/21 (28.6%). Drug and dose reduction of AED is possible in patients using VNS for refractory epilepsy without loss of seizure control and with improved patient satisfaction.

Adolescent↗
PubMed2002

Storage phosphor radiography of wrist fractures: a subjective comparison of image quality at varying exposure levels.

Image quality of storage phosphor radiographs acquired at different exposure levels was compared to define the minimal radiation dose needed to achieve images which allow for reliable detection of wrist fractures. In a study on 33 fractured anatomical wrist specimens image quality of storage phosphor radiographs was assessed on a diagnostic PACS workstation by three observers. Images were acquired at exposure levels corresponding to a speed classes 100, 200, 400 and 800. Cortical bone surface, trabecular bone, soft tissues and fracture delineation were judged on a subjective basis. Image quality was rated according to a standard protocol and statistical evaluation was performed based on an analysis of variance (ANOVA). Images at a dose reduction of 37% were rated sufficient quality without loss in diagnostic accuracy. Sufficient trabecular and cortical bone presentation was still achieved at a dose reduction of 62%. The latter images, however, were considered unacceptable for fracture detection. To achieve high-quality storage phosphor radiographs, which allow for a reliable evaluation of wrist fractures, a minimum exposure dose equivalent to a speed class of 200 is needed. For general-purpose skeletal radiography, however, a dose reduction of up to 62% can be achieved. A choice of exposure settings according to the clinical situation (ALARA principle) is recommended to achieve possible dose reductions.

Fractures, Bone↗
PubMed2002

Situation and problem of administration methods and the intermission of hypnotics.

The results of a questionnaire survey suggested four problems that might prolong the administration of benzodiazepine hypnotics without suspending the medication. First, psychiatrists did not actively consider the necessity of suspension of medication with hypnotics. Second, the period between improvement of insomnia and initiation of dose reduction was long, whereas the period between initiation of dose reduction and discontinuation was short. Third, to suspend medication of a hypnotic, every-other-day administration was used for the very short-acting and short-acting types, and substitution of the intermediate-acting or long-action type for the drugs with a short half-life were performed frequently. Finally, dose reduction and intermission of medication induced rebound insomnia, withdrawal symptoms, and recurrence of insomnia.

Adult↗
PubMed2000

A new three-dimensional dose distribution reduction scheme for tubular organs.

In tubular structures, spatial aspects of the dose distribution may be important in determining the normal tissue response. Conventional dose-volume-histograms (DVHs) and dose-surface-histograms (DSHs) lack spatial information and may not be adequate to represent the three-dimensional (3D) dose data. A new 3D dose distribution data reduction scheme which preserves its longitudinal and circumferential character is presented. Dose distributions were generated at each axial level for esophagus or rectum in 123 patients with lung cancer or prostate cancer. Dose distribution histograms at each axial level were independently analyzed along the esophageal or rectal circumference to generate dose-circumference-histogram (DCH) sheets. Two types of plots were then generated from the DCH sheet. The first considered the percentage of the circumference at each axial level receiving various doses. The second considered the minimum dose delivered to any percentage of the circumference at each axial level. The DCH as a treatment planning tool can be easily implemented in a 3D planing system and is potentially useful for the study of the relationship between the complication risk and the longitudinal and circumferential dose distributions.

Dose-Response Relationship, Radiation↗
PubMed2006

Treatment of relapsers after combination therapy for chronic hepatitis C.

Sustained virologic response rates are significantly higher in patients who have relapsed after a previous course of therapy compared with patients who did not respond. A meta-analysis of combination therapy in patients who failed IFN monotherapy reported SVR rates of 52% in relapsers to prior therapy and 16% in nonresponders. Similarly, relapsers after combination standard IFN and RBV therapy have higher SVR rates than combination of therapy nonresponders when treated with pegylated interferon and ribavirin. For this reason, patients who relapse after a previous course of therapy should be considered potential candidates for retreatment. Factors that have been associated with SVR in these patients include genotype non-I, low viral loads, and lesser degrees of fibrosis. The course of treatment in all patients who have relapsed after prior therapy should be reviewed to identify possible reasons for failure to achieve an SVR. In particular, optimal dosing of PEG IFN and RBV and the occurrence and timing of treatment dose reductions during prior therapy should be reviewed. The reasons for dose reduction should be addressed before initiating another course of therapy in an effort to optimize the chance for a SVR. Patients who had dose reduction for depression, anemia, or neutropenia, should be considered for antidepressants, erythropoietin, or, if neutropenia is severe, granulocyte colony stimulating factor therapy, respectively, during retreatment. Prolongation of therapy beyond 48 weeks in patients with relapse after a standard course of PEG IFN and RBV may offer a chance of SVR. Novel agents currently in development, including protease and polymerase inhibitors, may prove to be therapeutic options for these patients in the future.

Journal Article↗
PubMed2005

Open-field behavioural alterations in liver-impaired and sham-operated rats after acute exposure to the antidepressant venlafaxine.

Patients with chronic liver impairment often display symptoms of affective psychiatric nature where the choice for antidepressant treatment is rational. Since caution is recommended when these drugs are used in such patients, a dose reduction is usually performed. We have previously reported that a dose reduction to liver-impaired portacaval shunted rats has resulted in similar brain concentrations of venlafaxine as compared to sham-operated control rats that received a two times higher dose. The main aim of the present study was therefore to investigate if this "normalisation" in pharmacokinetics of the portacaval-shunted rats also was true for the pharmacodynamic response in terms of drug effect on spontaneous open-field behaviour. Thus, portacaval-shunted rats received a single reduced dose (5 mg/kg) of venlafaxine or saline, whereas sham-operated rats received either 10 mg/kg or saline. Thereafter, central and peripheral arena locomotor and rearing activities were recorded during 60 min. The venlafaxine-treated portacaval-shunted and sham rats displayed reduced and unchanged overall behavioural activities compared with corresponding controls, respectively. However, the ratios between centrally and peripherally performed behavioural activities were higher in the venlafaxine-treated sham rats, indicating an increase in central arena activity as compared to the sham-saline and portacaval-shunted rats. The present study indicates that, despite a 50% dose reduction, caution still is necessary when antidepressants are used in liver insufficient subjects. This study also shows the importance of detailed open-field behavioural studies in which both central and peripheral activities are recorded for measurement of open-field behavioural drug effects.

Animals↗
PubMed1999

A phase I/II dose escalation study of carboplatin in the treatment of newly diagnosed patients with advanced ovarian cancer receiving paclitaxel.

The objective of this study was to determine the maximum tolerated dose of carboplatin when administered with paclitaxel in previously untreated patients with ovarian cancer. Patients were treated with paclitaxel at 225 mg/m2 for 3 hours followed by carboplatin at an area under the curve (AUC) of 6, 7, 8, or 9 every 3 weeks. Granulocyte colony-stimulating factor was added if needed to maintain dose intensity before dose reductions were used for grade 4 hematologic toxicity or febrile neutropenia. Twenty-two patients were enrolled in the study. At the AUC 6 level, five of six patients finished all six cycles. At the AUC 7 level, four of five patients completed six cycles, although three required dose reductions for toxicity. At the AUC 8 level, all four patients completed six cycles and two required dose reductions. The AUC 9 level was not well tolerated. Only four of seven patients completed six cycles. Neutropenia was common, and transient thrombocytopenia was more severe and required dose reduction, especially in later cycles. An AUC of 8 is the maximum tolerated dose of carboplatin in combination with paclitaxel at 225 mg/m2 for 3 hours.

Adult↗
PubMed1993

Prolonged subcutaneous administration of recombinant alpha 2b interferon in patients with previously untreated Philadelphia chromosome-positive chronic-phase chronic myelogenous leukemia: effect on remission duration and survival: Cancer and Leukemia Group B study 8583.

We investigated whether recombinant alpha 2b interferon (r alpha 2bIFN) would reduce the proportion of bone marrow Philadelphia chromosome (Ph) cells in chronic-phase chronic myelogenous leukemia (CML) by treating 107 previously untreated patients daily with r alpha 2bIFN at 5 x 10(6)IU/m2 subcutaneously. Patients with complete remission, partial remission, or partial hematologic remission received treatment until progression; those with progressive disease were taken off study and observed for survival. Sixty-three (59%) of the patients achieved at least a partial hematologic remission (24 complete remissions and 39 partial remissions). The median time to response for the 63 responders was 3.4 months, with a median duration of remission of 52 months and with 81% of responders continuing in remission beyond 12 months. The median survival for the 107 patients was 66 months. Of 78 patients with cytogenetic follow-up data, 31 (40%) achieved a partial cytogenetic response (n = 17) or a complete cytogenetic response (n = 14). The percentage of cytogenetic responders among all patients was 29% (31 of 107 patients). The median time to first cytogenetic response was 9 months. A major dose reduction of r alpha 2bIFN (> or = 50%) was required at some time during treatment in 38% of patients, 26% required 10% to 49% dose reductions, and 36% had minor dose reductions of < or = 10%. No association was observed between dose received and the attainment of a cytogenetic response. None of the usual prognostic factors (sex, race, performance status, weight loss, time from diagnosis to treatment, hepatosplenomegaly, age, symptoms, hemoglobin, or platelet, blast, basophil, or white blood cell count) were significantly related to survival. These data provide confirmation that major cytogenetic responses to prolonged administration of subcutaneous r alpha 2bIFN occur in 20% to 38% (95% confidence interval) of chronic-phase Ph-positive patients. Although it is hypothesized that patients achieving major cytogenetic responses to r alpha 2bIFN should have prolonged remission duration and survival compared with nonresponders, analyses of the effect of cytogenetic responders by both "landmark" and time-dependent covariate techniques fail to provide statistically significant evidence for an effect of cytogenetic response on remission duration or survival. This may be due in part to an effect size insufficiently large to be detected with the number of patients treated in this study. Thus, confirmation of remission duration or survival benefit, if any, of r alpha 2bIFN therapy in Ph-positive chronic-phase CML must await the outcome of randomized trials comparing IFN with conventional agents.

Adolescent↗
PubMed2005

Use of growth factors with antiviral therapy for chronic hepatitis C.

Interferon (IFN)-based regimens for the treatment of chronic hepatitis C virus (HCV) infection have become increasingly effective and are able to eradicate virus in more than one half of treated individuals. Treatment strategies are complex and involve self-administration of injectable IFN and oral ribavirin medication, frequent office visits, and laboratory testing. Current therapies have significant side effects that may impair performance and quality of life (QOL), necessitating dose reductions or interruption of therapy. As a consequence of these dose reductions or treatment interruptions, patients may not achieve a sustained virologic response (SVR). Recent data suggest that aggressive management of side effects may improve QOL and therefore patient adherence to therapy. Use of antidepressant and anxiolytic medications and off-label use of hemopoietic stem cell growth factors are increasing in the daily management of HCV therapy. Although these therapies may improve QOL, prevent dose reductions, and increase the number of patients completing therapy, there are no data available to definitively show that such tactics are associated with improvement in SVR rates in individual patients.

Anemia↗
PubMed2006

Comparison of transplanted kidney function in patients on two different doses of mycophenolate mofetil.

INTRODUCTION: Mycophenolate mofetil (MMF), an immunosuppressant that is widely used in renal transplant recipients, is associated with several dose-dependent hematologic and gastrointestinal side effects that lead to drug dose reduction or even discontinuation. The aim of this study was to compare the renal function and acute rejection rates of kidney allograft recipients who were on two different mycophenolate mofetil doses. METHODS: In a prospective study, 59 allograft kidney recipients who were on MMF 2 g/d were randomly selected and followed for evidences of acute rejection or drug side effects. Four patients were excluded from the study due to noncompliance, graft loss, and patient loss from opportunistic infection. Of the remaining 55 patients, 22 patients (40%) underwent MMF dose reduction to 1.35 +/- 0.23 g/d due to perceived side effects or economic reasons (group 1). The mean time for this change was 4.2 +/- 2.1 months after the kidney transplantation. The remaining patients (group 2, n = 33, 60%) had no change in MMF 2 g/d drug dosage. All patients were followed for at least 30 months after transplantation. Renal function tests (blood urea and serum creatinine) were measured monthly. Statistical analysis was performed using SPSS 11.0 (Student t test). A P value < .05 was considered significant. RESULTS: The two groups were comparable regarding age, gender, other immunosuppressive medications, and the time after transplantation. There were no episodes of acute rejection in group 1 after MMF dose reduction. The renal function (blood urea or serum creatinine levels) was comparable between the two groups at the end of study (P = .846 and .610, respectively). CONCLUSION: MMF dose reduction was not associated with an increased risk of acute renal allograft rejection or impaired graft function.

Adult↗
PubMed2000

Beta versus gamma for catheter-based intravascular brachytherapy: dosimetric perspectives in the presence of metallic stents and calcified plaques.

PURPOSE: Both beta and gamma emitters are currently used in the catheter-based intravascular brachytherapy. The dosimetric effects due to the presence of metallic stents and calcified plaques have not been fully addressed. This work compares these effects for two most commonly used beta and gamma sources ( (90)Sr and (192)Ir). MATERIALS AND METHODS: An EGS4 Monte Carlo package was used to calculate dose in water for a (90)Sr (supplied by NOVOSTE) and an (192)Ir (Supplied by BEST) source, with or without the presence of a calcified plaque or a metallic stent. Plaques of different shape (shell and disk), size and density, and two types of stainless-steel stents (ring or mesh stent) were studied. The ring stent consists of identical rings stacked along the long axis of the sources. The gap between two rings is 0.3 mm. The mesh stents are made of identical square (0.1 x 0.1 or 0.2 x 0.2 mm(2)) holes separated from each other by stainless-steel wire. The cross section of wire for both ring and mesh stents is 0.1 x 0.1 mm(2). A dose perturbation factor (DPF), defined as the ratio of the doses with and without the presence of a plaque or a stent, was introduced to quantify the effects. A carefully chosen set of EGS4 transport parameters for the small geometry in question was used in the calculation. RESULTS: The radial and axial dose distributions calculated in water were found to agree with the published measurements to within 3%. The dose perturbations due to the presence of calcified plaques or metallic stents were found far more significant for the (90)Sr source than those for the (192)Ir source. Up to 30% dose reduction behind a plaque were observed for the (90)Sr source, while the dose reduction for the (192)Ir source was found to be negligible. The dose enhancement inside a plaque was as high as 10% for the beta source or 6% for the gamma source. In the presence of a stent, the DPF was in the range of 1.15-0.75 for the beta source, while it was almost equal to 1.0 for the gamma source. CONCLUSION: The dose perturbation due to the presence of a calcified plaque or a metallic stent is significant for the beta source. The dose reduction in the region beyond a plaque or a stent could be more than 20%. For the gamma source, the dose effect behind a plaque or a stent is practically negligible. These dosimetric differences between the beta and gamma sources in the presence of a calcified plaque or metallic stent should be considered in the dose prescription of intravascular brachytherapy.

Beta Particles↗