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At least 217 records · Page 12Linked to original sources

PubMed2002

[Inversely planned intensity modulated radiotherapy for irradiation of a woman with breast cancer and funnel chest].

BACKGROUND: A 44-year old woman with breast cancer was transferred to our institution for irradiation. Due to a pronounced funnel chest no satisfying dose distribution was obtained by conventional techniques. Thus an intensity-modulated radiotherapy (IMRT) based on inverse optimisation was carried out. IMRT was compared to conventional techniques regarding dose distribution and feasibility. PATIENT AND METHODS: Tumor site was in the right middle lower quadrant. Target volume included the right breast and the parasternal lymph nodes. Target dose was 50.4 Gy. Based on inverse optimisation irradiation was carried out in "step-and-shoot"-technique with twelve intensity modulated beams with six intensity steps. Additionally, treatment plans were calculated using conventional techniques (technique A with two tangential wedged 6-MV photon beams, technique B with additional oblique 15-MeV electron portal). We analysed conformality and homogeneity of target volume and dose distribution within normal tissue. RESULTS: Dose conformality was substantially improved by IMRT. Dose homogeneity was slightly decreased compared to technique A. Lung volume irradiated with a dose higher than 20 Gy was reduced from 56.8% with technique A and 40.1% with technique B, respectively to 22.1% with IMRT. Treatment was tolerated well by the patient without relevant side effects. Mean treatment time was 19.5 min. CONCLUSION: The inversely planned IMRT using multiple beam directions is suitable for breast irradiation following breast conserving surgery. In the present case of a woman with funnel chest lung dose was substantially reduced without reduction of target dose. In which was the complex treatment technique leads to a clinically detectable advantage is examined at present, in the context of a study.

Adult↗

PubMed2005

Predictors of tumor control in patients treated with linac-based stereotactic radiosurgery for metastatic disease to the brain.

OBJECTIVE: The objective of this study was to determine predictive factors for local control (LC) of brain metastases (BM) treated with Linac-based stereotactic radiosurgery (LB-SRS). METHODS: Between January 1994 and July 2001, 80 patients (126 BM) underwent LB-SRS. All patients had follow-up imaging with computed tomography (40%) or magnetic resonance imaging (60%). Most patients had either lung (41%) or renal cell (20%) cancer. The median SRS prescription dose was 18 Gy (range, 10-21 Gy). Most patients (86%) also received whole-brain radiotherapy (WBRT). LC was defined as the absence of enlargement of the BM on follow-up scans. Actuarial LC analyses were performed by the method of Kaplan-Meier and compared with the log-rank test. Factors analyzed included histology, volume, prescription dose, maximum and minimum tumor dose, target volume ratio, number of arcs and isocenters, total degrees, and WBRT. Multivariate analysis was accomplished. RESULTS: At a median follow up of 8.8 months, 11 BM failed (8.7%). The 1-and 2-year actuarial LC rates were 88.6% and 77.2%, respectively. The most significant factors correlated with LC were prescription (P = 0.0004) and minimum tumor (P = 0.002) doses, and tumor volume (P = 0.04). On multivariate analysis, the sole factor correlated with LC was minimum tumor dose (P = 0.03). CONCLUSION: Our results confirm that LB-SRS is associated with excellent LC rates in the majority of patients treated. However, particular attention should be given to minimum target dose to ensure optimal outcome.

Adult↗

PubMed2005

Thiopurine methyltransferase enzyme activity determination before treatment of inflammatory bowel disease with azathioprine: effect on cost and adverse events.

BACKGROUND: Azathioprine (AZA), used to treat inflammatory bowel disease (IBD), is metabolized by thiopurine methyltransferase (TPMT). The accumulation of individual metabolites varies because humans display genetic polymorphism for TPMT expression. Deficiencies in TPMT result in accumulation of toxic metabolites, followed by neutropenia and hepatic inflammation. Concern over acute toxicity frequently leads to under dosing and frequent monitoring tests and visits. OBJECTIVE: To determine whether assessment of TPMT activity before the administration of AZA would predict acute toxicity and, thus, allow for reductions in health care costs related to biochemical screening for, and management of, AZA-induced adverse events. METHODS: Before AZA treatment, 29 patients with IBD were prospectively randomized to one of two groups: group 1, in which no TPMT assay was performed, was started on AZA at 1 mg/kg/day and then titrated every two weeks to a target dose of 2.5 mg/kg/day; and group 2, in which TPMT assays were performed, was started on AZA at the target dose of 2.5 mg/kg/day. For both groups, complete blood count and liver enzymes were monitored weekly for six weeks and at monthly intervals thereafter. Additional tests and health care interventions were undertaken at the discretion of the attending physicians. RESULTS: Of the 29 patients in the study, 15 were randomly assigned to group 1 and 14 to group 2. Demographics and disease activity were similar for both groups. Mean follow-up time was 7.1 months (range 3.5 to 10.7 months). Eight patients from group 1 and six patients from group 2 withdrew as a result of AZA-induced adverse events. There was no correlation between the TPMT activity and the development of AZA-induced adverse events. The direct health care costs for group 1 (300.11 dollars per patient) were lower than in group 2 (348.87 dollars per patient). CONCLUSION: The prospective assessment of TPMT enzyme activity before initiating AZA therapy in IBD patients incurred additional cost and did not predict AZA-induced toxicity.

Adolescent↗

PubMed2003

The ajmaline challenge in Brugada syndrome: diagnostic impact, safety, and recommended protocol.

AIMS: The diagnostic ECG pattern in Brugada syndrome (BS) can transiently normalize and may be unmasked by sodium channel blockers such as ajmaline. Proarrhythmic effects of the drug have been well documented in the literature. A detailed protocol for the ajmaline challenge in Brugada syndrome has not yet been described. Therefore, we prospectively studied the risks of a standardized ajmaline test. METHODS AND RESULTS: During a period of 60 months, 158 patients underwent the ajmaline test in our institution. Ajmaline was given intravenously in fractions (10mg every two minutes) up to a target dose of 1mg/kg. In 37 patients (23%) the typical coved-type ECG pattern of BS was unmasked. During the test, symptomatic VT appeared in 2 patients (1.3%). In all other patients, the drug challenge did not induce VT if the target dose, QRS prolongation >30%, presence/appearance of the typical ECG, or the occurrence of premature ventricular ectopy were considered as end points of the test. A positive response to ajmaline was induced in 2 of 94 patients (2%) with a normal baseline ECG, who underwent evaluation solely for syncope of unknown origin. CONCLUSION: The ajmaline challenge using a protocol with fractionated drug administration is a safe method to diagnose BS. Because of the potential induction of VT, it should be performed under continuous medical surveillance with advanced life-support facilities. Due to the prognostic importance all patients with aborted sudden death or unexplained syncope without demonstrable structural heart disease and family members of affected individuals should presently undergo drug testing for unmasking BS.

Adolescent↗

PubMed2005

Comparing step-and-shoot IMRT with dynamic helical tomotherapy IMRT plans for head-and-neck cancer.

PURPOSE: The goal of this planning study was to compare step-and-shoot intensity-modulated radiotherapy (IMRT) plans with helical dynamic IMRT plans for oropharynx patients on the basis of dose distribution. METHODS AND MATERIALS: Five patients with oropharynx cancer had been previously treated by step-and-shoot IMRT at the University Medical Centre Utrecht, The Netherlands, applying five fields and approximately 60-90 segments. Inverse planning was carried out using Plato, version 2.6.2. For each patient, an inverse IMRT plan was also made using Tomotherapy Hi-Art System, version 2.0, and using the same targets and optimization goals. Statistical analysis was performed by a paired t test. RESULTS: All tomotherapy plans compared favorably with the step-and-shoot plans regarding sparing of the organs at risk and keeping an equivalent target dose homogeneity. Tomotherapy plans in particular realized sharper dose gradients compared with the step-and-shoot plans. The mean dose to all parotid glands (n = 10) decreased on average 6.5 Gy (range, -4 to 14; p = 0.002). The theoretical reduction in normal tissue complication probabilities in favor of the tomotherapy plans depended on the parotid normal tissue complication probability model used (range, -3% to 32%). CONCLUSION: Helical tomotherapy IMRT plans realized sharper dose gradients compared with the clinically applied step-and shoot plans. They are expected to be able to reduce the parotid normal tissue complication probability further, keeping a similar target dose homogeneity.

Head and Neck Neoplasms↗

PubMed2006

Levosimendan and prostaglandin E1 for uptitration of beta-blockade in patients with refractory, advanced chronic heart failure.

BACKGROUND: In advanced chronic heart failure (CHF) 20% of patients do not tolerate beta-blockers and 50% do not reach target doses. AIM: To test whether levosimendan or prostaglandin E1 (PGE1) can facilitate uptitration of beta-blockers in advanced CHF. METHODS AND RESULTS: Seventy-five advanced CHF patients (LVEF<35%, NYHA class IIIb or IV) intolerant to beta-blocker uptitration to target doses (10 mg bisoprolol/day) were randomised to a monthly 24 h infusion with levosimendan (n=39) or a chronic infusion with PGE1 (n=36) for 3 months. Bisoprolol was uptitrated following predefined criteria. At 12 weeks, bisoprolol dose increased from 4 mg to 10 mg in both groups. Heart failure worsening occurred in 29 levosimendan patients (74%) versus 16 PGE1 patients (44%, p=0.008). Uptitration was impossible in 9 levosimendan patients (23%) versus 2 PGE1 patients (6%, p=0.03). The combined endpoint of death or urgent heart transplantation or implantation of a ventricular assist device was reached by 12 levosimendan patients (31%) versus 4 PGE1 patients (11%, p=0.04). After 1 year, LVEF increased from 23+/-7% to 28+/-11% (p=0.0004), and BNP decreased from 994+/-806 to 659+/-564 pg/ml (p=0.03). CONCLUSION: Levosimendan and PGE1 facilitate uptitration of beta-blockers in previously intolerant CHF patients. PGE1 treatment allowed uptitration in more patients and resulted in a better clinical outcome compared to levosimendan. This approach increased LVEF and decreased BNP after 1 year.

Adrenergic beta-Antagonists↗

PubMed1999

Clinical and pharmacokinetic results with a new ultrashort-acting calcium antagonist, clevidipine, following gradually increasing intravenous doses to healthy volunteers.

AIMS: To investigate the tolerability and safety of clevidipine in healthy male volunteers during intravenous infusion at gradually increasing dose rates and to obtain preliminary information on the pharmacokinetics and pharmacodynamic effects of the drug. METHODS: Twenty-five subjects were enrolled in the study and twenty-one of them were included twice, resulting in a total of forty-six study entries encompassing 20 min infusions of clevidipine at target dose rates ranging from 0.12 to 48 nmol min-1 kg-1. Haemodynamic variables and adverse events were recorded throughout the study. Concentrations of clevidipine and its primary metabolite, H 152/81, were followed in whole blood, and the pharmacokinetics were evaluated by non-compartmental and compartmental analysis. An Emax model was fitted to the effect on mean arterial pressure (MAP) over heart rate (HR) and the corresponding blood concentrations of clevidipine. RESULTS: Clevidipine was administered up to a target dose rate of 48 nmol min-1 kg-1, where a pre-determined escape criterion was reached (HR>120 beats min-1 ) and the study was stopped. The most common adverse events were flush and headache, which can be directly related to the mechanism of action of clevidipine. There was a linear relationship between blood concentration and dose rate in the range studied. The median clearance value determined by non-compartmental analysis was 0.125 l min-1 kg-1. Applying the population approach to the sparse data on clevidipine concentrations, an open two compartment pharmacokinetic model was found to be the best model in describing the disposition of the drug. The population mean clearance value determined by this method was 0.121 l min-1 kg-1, and the volume of distribution at steady state was 0.56 l kg-1. The initial half-life, contributing by more than 80% to the total area under the blood concentration-time curve following i.v. bolus administration, was 1.8 min, and the terminal half-life was 9.5 min. At the highest dose rates, MAP was reduced by approximately 10%, and the HR reached the pre-determined escape criterion for this study (>120 beats min-1 ). CONCLUSIONS: Clevidipine is well tolerated and safe in healthy volunteers at dose rates up to at least 48 nmol min-1 kg-1. The pharmacokinetics are linear over a wide dose range. Clevidipine is a high clearance drug with extremely short half-lives. The effect of clevidipine on the blood pressure was marginal, probably due to a compensatory baroreflex activation in this population of healthy volunteers. A simple Emax model adequately describes the relationship between the pharmacodynamic response (MAP/HR) and the blood concentrations of clevidipine.

Adult↗

PubMed2004

Ewing sarcoma: radiation dose and target volume.

BACKGROUND: The outcome of children and adolescents with Ewing sarcoma is impacted by many prognostic factors and often measured by estimates of: event-free, relapse-free, disease-free, or overall survival. However, the preferred assessment following radiation therapy is local control. PROCEDURE: A review of large group experiences over the past several decades was undertaken to assess the optimal radiation dose and volume for patients with localized, osseous Ewing sarcoma. New approaches and techniques to improve local control were also investigated. RESULTS: With multidisciplinary therapy, 5-year overall local control rates range from 58 to 93%. Following definitive irradiation, they are 53-86%. Recommended radiation therapy doses are 55.8-60.0 Gy. In the postoperative setting, gross disease requires 55.8 Gy; microscopic disease requires 45 Gy. Altered fractionation schemes have not improved local control. The appropriate irradiated volume is an involved field to the pretreatment tumor volume plus 2.0-2.5 cm margin, followed by a boost to the post-induction chemotherapy tumor volume with margin. Good radiation quality control with central review improves local control. Use of an involved radiation field requires accuracy in defining tumor volume. Techniques to improve local control include risk-adapted multidisciplinary therapy, intraoperative boost radiation, and high radiation doses as delivered by 3-dimensional conformal radiation. Intensity modulated and proton beam radiotherapy may offer an advantage at special sites. CONCLUSIONS: Innovative uses of radiation in the multidisciplinary setting will continue to provide excellent local control, improved function, and quality of life for young patients with localized Ewing sarcoma of bone.

Child↗

PubMed2001

Hypothalamic/pituitary function following high-dose conformal radiotherapy to the base of skull: demonstration of a dose-effect relationship using dose-volume histogram analysis.

PURPOSE: To evaluate the incidence and pattern of hypopituitarism from hypothalamic (HT) and pituitary gland (PG) damage following high-dose conformal fractionated proton-photon beam radiotherapy (PPRT) to the base of skull (BOS) region in adults. The relationship between dose, volume, and PG function is explored. METHODS AND MATERIALS: Between May 1982 to October 1997, 107 adults with non-PG and non-HT neoplasms (predominantly chordoma and chondrosarcomas) of the BOS were treated with PPRT after subtotal resection(s). The median age was 41.2 years (range, 17-75) with 58 males and 49 females. Median prescribed target dose was 68.4 cobalt gray equivalent (CGE) (range, 55.8-79 CGE) at 1.80-1.92 CGE per fraction per day (where CGE = proton Gy x 1.1). The HT and PG were outlined on planning CT scans to allow dose-volume histograms (DVH) analysis. All patients had baseline and follow-up clinical testing of anterior and posterior pituitary function including biochemical assessment of thyroid, adrenal, and gonadal function, and prolactin secretion. RESULTS: The 10-year actuarial overall survival rate was 87%, with median endocrine follow-up time of 5.5 years, thus the majority of patients were available for long-term follow-up. Five-year actuarial rates of endocrinopathy were as follows: 72% for hyperprolactinemia, 30% for hypothyroidism, 29% for hypogonadism, and 19% for hypoadrenalism. The respective 10-year endocrinopathy rates were 84%, 63%, 36%, and 28%. No patient developed diabetes insipidus (vasopressin deficiency). Growth hormone deficiency was not routinely followed in this study. Minimum target dose (Dmin) to the PG was found to be predictive of endocrinopathy: patients receiving 50 CGE or greater at Dmin to the PG experiencing a higher incidence and severity (defined as the number of endocrinopathies occurring per patient) of endocrine dysfunction. Dmax of 70 CGE or greater to the PG and Dmax of 50 CGE or greater to the HT were also predictive of higher rates of endocrine dysfunction. CONCLUSION: Radiation-induced damage to the HT & PG occurs frequently after high-dose PPRT to the BOS and is manifested by anterior pituitary gland dysfunction. Hyperprolactinemia was detected in the majority of patients. Posterior pituitary dysfunction, represented by vasopressin activity with diabetes insipidus, was not observed in this dose range. Limiting the dose to the HT and PG when feasible should reduce the risk of developing clinical hypopituitarism.

Adolescent↗

PubMed2006

Intensity modulated photon and proton therapy for the treatment of head and neck tumors.

PURPOSE: A comparative treatment planning study has been performed between intensity modulated photon and proton therapy to investigate the ability of both modalities to spare organs at risk in the head and neck region while keeping target dose homogeneous. Additional advantage of reducing the spot size for IMPT was also investigated. The treatment planning comparison was extended by varying the number of fields to study its effect on the performance of each modality. Risks of secondary cancer induction were also calculated for all modalities. MATERIALS AND METHODS: Five planning CTs were selected for the study. Four different constraints were set to the organs at risk in order to measure the resulting dose homogeneity in the target volume. Five and nine field plans were made for IMXT and 3, 5 and 9 field plans were made for IMPT, for both spot sizes. Dose homogeneity as a function of the mean parotid dose was visualized using a 'pseudo' Pareto-optimal front approach. Risks of secondary cancer were estimated using the organ equivalent dose model. RESULTS: Critical organs were best spared using 3-field IMPT and, at least for IMPT, little advantage was seen with increasing field numbers. Reducing the spot size does give an advantage. In contrast, there was a significant advantage in going from 5 to 9 fields for IMXT. Secondary cancer risk was lowest for the IMPT plans with reduced spot size, for which normal tissue received the lowest integral dose. Interestingly, although integral dose remained the same, increasing the number of IMPT fields increased the secondary cancer risk, due to the increased volume of tissue irradiated to low dose. CONCLUSIONS: IMPT has a better ability to spare organs at risk than IMXT for the same dose homogeneity. It also significantly reduced the estimated risk of secondary cancer induction and the use of small numbers of fields further increased this advantage. Given that target homogeneity and normal tissue sparing were equally good with the 3 field IMPT, there appears to be a clear rationale to deliver small numbers of fields for IMPT.

Carcinoma, Squamous Cell↗

PubMed2006

Variations in quality of care for heart failure.

BACKGROUND: The objective of our study was to assess hospital-to-hospital variations for the management and treatment of heart failure (HF) patients. METHODS: We performed a cross-sectional study among randomly selected patients with ICD-10 (International Classification of Disease, 10th revision) HF hospitalised in three Swiss university hospitals in 1999. Demographic characteristics, risk factors, symptoms and findings at admission and discharge medications were abstracted. The main outcome measure was the percentage of patients receiving appropriate management and treatment as defined by quality of care indicators derived from evidence-based guidelines. Quality indicators were considered only when they could be applied (no contra-indications). RESULTS: Among 1153 eligible patients with HF the mean age (SD) was 75.3 (12.7), 54.3% were male. Among potential candidates for specific interventions left ventricular function (LVF) was determined in 68.5% of patients; 53.8% received target dose of angiotensin converting enzyme inhibitors (ACEI), 86.0% any dose of angiotensin receptor blockers; 21.9% b-blockers, and 62.1% anticoagulants at discharge. Compared to hospital B (reference), the adjusted odds ratios (OR) (95% CI) for LVF not determined were 3.82 (2.50 to 5.85) in hospital A and 3.25 (1.78 to 5.93) in hospital C. The adjusted OR (95% CI) for not receiving target dose ACEI was 1.76 (0.95 to 3.26) for hospital A and 3.20 (1.34 to 7.65) for hospital C compared to hospital B. CONCLUSIONS: Apparently, important hospital-to-hospital variations in the quality of care given to patients with HF could have existed between three academic medical centers.

Adrenergic beta-Antagonists↗

PubMed2001

Intensity modulated proton therapy: a clinical example.

In this paper, we report on the clinical application of fully automated three-dimensional intensity modulated proton therapy, as applied to a 34-year-old patient presenting with a thoracic chordoma. Due to the anatomically challenging position of the lesion, a three-field technique was adopted in which fields incident through the lungs and heart, as well as beams directed directly at the spinal cord, could be avoided. A homogeneous target dose and sparing of the spinal cord was achieved through field patching and computer optimization of the 3D fluence of each field. Sensitivity of the resultant plan to delivery and calculational errors was determined through both the assessment of the potential effects of range and patient setup errors, and by the application of Monte Carlo dose calculation methods. Ionization chamber profile measurements and 2D dosimetry using a scintillator/CCD camera arrangement were performed to verify the calculated fields in water. Modeling of a 10% overshoot of proton range showed that the maximum dose to the spinal cord remained unchanged, but setup error analysis showed that dose homogeneity in the target volume could be sensitive to offsets in the AP direction. No significant difference between the MC and analytic dose calculations was found and the measured dosimetry for all fields was accurate to 3% for all measured points. Over the course of the treatment, a setup accuracy of +/-4 mm (2 s.d.) could be achieved, with a mean offset in the AP direction of 0.1 mm. Inhalation/exhalation CT scans indicated that organ motion in the region of the target volume was negligible. We conclude that 3D IMPT plans can be applied clinically and safely without modification to our existing delivery system. However, analysis of the calculated intensity matrices should be performed to assess the practicality, or otherwise, of the plan.

Adult↗

PubMed1998

Feasibility of high-dose chemotherapy and autologous peripheral blood stem cell transplantation in children with high grade osteosarcoma.

An Italian-Scandinavian treatment and research protocol with high-dose chemotherapy and double peripheral blood stem cell (PBSC) transplantation has been designed in an attempt to improve overall results of children with metastatic osteosarcoma (OST). Six patients, aged 12-17 years, underwent PBSC mobilization with CY 4 g/m2 and VP-16 600 mg/m2 followed by G-CSF (n = 4 with recurrent disease) or ifosfamide 15 g/m2 plus G-CSF (n = 2 with synchronous metastases). The target dose of CD34+ cells for two transplant procedures was 8 x 10(6)/kg or more; conditioning regimen for both the grafts consisted of carboplatin 375 mg/m2/day for 4 days and VP16 450 mg/m2/day for 4 days. The first transplant was planned 2-4 weeks after the mobilization, the second transplant 4-6 weeks after the first graft. In three patients a single course of CY-VP16 mobilised a total number of CD34+ sufficient for two transplants; in the patient who did not obtain the target dose of CD34+ cells a bone marrow harvest was added. In the two other children high-dose ifosfamide failed to achieve the required CD34+ number: one patient underwent a single transplant procedure, one patient was successfully mobilized with doxorubicin 90 mg/m2 plus G-CSF. Patients underwent a median of two collections (range 2-4). Leukapheresis resulted in the collection of a median of 8.9 CD34+ cells/kg (range 1.3-14.8). The median time to granulocyte count recovery to more than 0.5 x 10(9)/l was 10 days (range 9-14 days) after the first graft and 11 days (range 10-12 days) after the second graft, respectively. Platelets recovered to 50 x 10(9)/l at a median of 11 (range 10-30 days) and 13 days (range 10-28) respectively after the first and the second graft. Conditioning regimen was well tolerated in all patients with mild extra haematological toxicity, also following the second transplant. Two patients grafted with metastases at diagnosis are alive and disease free 3 and 7 months from the transplant. One of the four patients transplanted for recurrent disease developed pulmonary metastases 2 months after the procedure; one patient is alive with significant reduction of tumor mass 1 month after the first transplant, one patient is alive without evidence of disease 9 months from the second transplant and one after a complete metastasectomy (tumor necrosis >90%) which followed the second transplant. With the limits of the small number of cases and the short follow-up, these preliminary results show that this approach may be promising for the treatment of patients with metastatic OST who currently are not cured by conventional-dose regimens.

Adolescent↗

PubMed2006

What is the best pre-therapeutic dosimetry for successful radioiodine therapy of multifocal autonomy?

PURPOSE: Dose calculation for radioiodine therapy (RIT) of multifocal autonomies (MFA) is a problem as therapeutic outcome may be worse than in other kinds of autonomies. We compared different dosimetric concepts in our patients. PATIENTS, METHODS: Data from 187 patients who had undergone RIT for MFA (Marinelli algorithm, volumetric compromise) were included in the study. For calculation, either a standard or a measured half-life had been used and the dosimetric compromise (150 Gy, total thyroid volume). Therapeutic activities were calculated by 2 alternative concepts and compared to therapeutic success achieved (concept of TcTUs-based calculation of autonomous volume with 300 Gy and TcTUs-based adaptation of target dose on total thyroid volume). RESULTS: If a standard half-life is used, therapeutic success was achieved in 90.2% (hypothyroidism 23,1%, n = 143). If a measured half-life was used the success rate was 93.1% (13,6% hypothyroidism, n = 44). These differences were statistically not significant, neither for all patients together nor for subgroups eu-, hypo-, or hyperthyroid after therapy (ANOVA, all p > 0.05). The alternative dosimetric concepts would have resulted either in significantly lower organ doses (TcTUs-based calculation of autonomous volume; 80.76 +/- 80.6 Gy versus 125.6 +/- 46.3 Gy; p < 0.0001) or in systematic over-treatment with significantly higher doses (TcTUs-adapted concept; 164.2 +/- 101.7 Gy versus 125.6 +/- 46.3 Gy; p = 0.0097). CONCLUSIONS: TcTUsbased determination of the autonomous volume should not be performed, the TcTUs-based adaptation of the target dose will only increase the rate of hypothyroidism. A standard half-life may be used in pre-therapeutic dosimetry for RIT of MFA. If so, individual therapeutic activities may be calculated based on thyroid size corrected to the 24h ITUs without using Marinelli's algorithm.

Dose-Response Relationship, Radiation↗

PubMed2001

Quality of congestive heart failure treatment at a Canadian teaching hospital.

BACKGROUND: Practice guidelines for the management of congestive heart failure (CHF) emphasize the need for assessment of left ventricular function and treatment with angiotensin-converting enzyme (ACE) inhibitors. However, previous studies have shown that many patients do not receive these tests or medications. The objective of this study was to evaluate the compliance of physicians at a large Canadian teaching hospital with published CHF management guidelines. METHODS: We conducted a retrospective review of the charts of 200 patients admitted to Sunnybrook & Women's College Health Sciences Centre, Toronto, in 1997 for whom CHF was the diagnosis most responsible for the hospital admission. Quality of care was measured with 3 indicators: the use of left ventricular function testing to determine systolic versus diastolic dysfunction; the prescription of ACE inhibitors to appropriate patients (those with systolic dysfunction, no contraindications to ACE inhibitor therapy and no angiotensin II receptor blocker use); and the prescription of target doses of ACE inhibitors. RESULTS: Of the 200 patients 177 (88.5%) received left ventricular function testing before or during their hospital stay; of the 177, 117 (66.1%) had systolic dysfunction. A total of 100 patients were considered to be ideal candidates for ACE inhibitor treatment. Of the 100, 89 (89.0%) received ACE inhibitors; however, only 23 (23.0%) were prescribed target doses. INTERPRETATION: Most patients who had CHF at this Canadian hospital received left ventricular function testing and ACE inhibitor therapy. Future educational efforts should focus on the importance of adequate dosing of ACE inhibitors.

Aged↗

PubMed2006

Dose optimisation in single plane interstitial brachytherapy.

BACKGROUND AND PURPOSE: Brachytherapy dose distributions can be optimised by modulation of source dwell times. In this study dose optimisation in single planar interstitial implants was evaluated in order to quantify the potential benefit in patients. MATERIAL AND METHODS: In 14 patients, treated for recurrent rectal and cervical cancer, flexible catheters were sutured intra-operatively to the tumour bed in areas with compromised surgical margin. Both non-optimised, geometrically and graphically optimised CT -based dose plans were made. The overdose index (OI), homogeneity index (HI), conformal index (COIN), minimum target dose, and high dose volumes were evaluated. The dependence of OI, HI, and COIN on target volume and implant regularity was evaluated. In addition, 12 theoretical implant configurations were analyzed. RESULTS: Geometrical and graphical optimisation improved the dose plans significantly with graphical optimisation being superior. Graphically optimised dose plans showed a significant decrease of 18%+/-9% in high dose volume (p<0.001). HI, COIN, and OI were significantly improved from 0.50+/-0.05 to 0.60+/-0.05, from 0.65+/-0.04 to 0.71+/-0.04, and from 0.19+/-0.03 to 0.15+/-0.03, respectively (p<0.001 for all). Moreover, minimum target dose increased significantly from 71%+/-5% to 80%+/-5% (p<0.001). The improvement in OI and HI obtained by optimisation depended on the regularity of the implant, such that the benefit of optimisation was larger for irregular implants. OI and HI correlated strongly with target volume limiting the usability of these parameters for comparison of dose plans between patients. CONCLUSIONS: Dwell time optimisation significantly improved the dose distribution regarding homogeneity, conformity, minimum target dose, and size of high dose volumes. Graphical optimisation is fast, reproducible and superior to geometric optimisation.

Brachytherapy↗

PubMed2004

Applicability and dosimetric impact of ultrasound-based preplanning in high-dose-rate brachytherapy of prostate cancer.

BACKGROUND AND PURPOSE: Analyses of permanent brachytherapy seed implants of the prostate have demonstrated that the use of a preplan may lead to a considerable decrease of dosimetric implant quality. The authors aimed to determine whether the same drawbacks of preplanning also apply to high-dose-rate (HDR) brachytherapy. PATIENTS AND METHODS: 15 patients who underwent two separate HDR brachytherapy implants in addition to external-beam radiation therapy for advanced prostate cancer were analyzed. A pretherapeutic transrectal ultrasound was performed in all patients to generate a preplan for the first brachytherapy implant. For the second brachytherapy, a subset of patients were treated by preplans based on the ultrasound from the first brachytherapy implant. Preplans were compared with the respective postplans assessing the following parameters: coverage index, minimum target dose, homogeneity index, and dose exposure of organs at risk. The prostate geometries (volume, width, height, length) were compared as well. RESULTS: At the first brachytherapy, the matching between the preplan and actual implant geometry was sufficient in 47% of the patients, and the preplan could be applied. The dosimetric implant quality decreased considerably: the mean coverage differed by -0.11, the mean minimum target dose by -0.15, the mean homogeneity index by -0.09. The exposure of organs at risk was not substantially altered. At the second brachytherapy, all patients could be treated by the preplan; the differences between the implant quality parameters were less pronounced. The changes of prostate geometry between preplans and postplans were considerable, the differences in volume ranging from -8.0 to 13.8 cm(3) and in dimensions (width, height, length) from -1.1 to 1.0 cm. CONCLUSION: Preplanning in HDR brachytherapy of the prostate is associated with a substantial decrease of dosimetric implant quality, when the preplan is based on a pretherapeutic ultrasound. The implant quality is less impaired in subsequent implants of fractionated brachytherapy.

Brachytherapy↗

PubMed2000

Management of atypical and malignant meningiomas: role of high-dose, 3D-conformal radiation therapy.

OBJECTIVE: Atypical and malignant meningiomas are at high risk for local failure. The role of radiation therapy (RT) and dose levels required to improve tumor control are poorly defined. This study reviews our experience with RT. MATERIAL AND METHODS: Thirty-one patients underwent fractionated RT for atypical (AM, 15 patients) or malignant meningioma (MM, 16 patients) of the cranium. Sixteen patients presented with primary and 15 with recurrent disease. Eight patients received RT following total resection, 21 patients after subtotal resection and 2 patient following biopsy only. RT was given using megavoltage photons in 15 patients and combined photons and 160 MeV protons in 16 patients. Total target doses ranged from 50 to 68 (AM, mean 62) and from 40 to 72 (MM, mean 58) Gy or CGE (= cobalt-gray-equivalent). RESULTS: With mean observation time of 59 months (range: 7-155 months) actuarial local control rates at 5- and 8-years were similar for both histologies (38% and 19% for AM and 52 and 17% for MM). However, significantly improved local control was observed for proton versus photon RT (80% versus 17% at 5 years, p = 0.003) and target doses > or = 60 Gy for both, atypical (p = 0.025) and malignant meningioma (p = 0.0006). At time of analysis, 14/15 patients (93%) with AM and 6/16 (38%) with MM were alive. Three patients (19%) with MM developed distant metastasis. Actuarial 5- and 8-year survival rates for MM were significantly improved by use of proton over photon RT and radiation doses > 60 CGE. Three patients developed symptomatic radiation damage after 59.3, 68.4 and 72 Gy/CGE. CONCLUSION: Conformal, high dose RT resulted in significant improvement of local control for atypical and malignant meningiomas. Increased local control resulted also in improved rates of survival for patients with malignant meningioma.

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