SEARCH · PubMed Health

Results for “Targeted dosing”

Explore indexed PubMed citations for clinical trials, systematic reviews and public health research. Read source abstracts and follow each citation to its original PubMed record.

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

At least 91 records · Page 5Linked to original sources

PubMed1998

Measured lung dose correction factors for 50 MV photons.

Some clinically relevant measurements of lung tissue/water equivalent interfaces have been performed for a 50 MV therapeutic x-ray beam. The purpose was to investigate the severity of dose perturbation effects in lung tissue and adjacent tissues using an energy well above the common clinical practice in thoracic irradiations. The phantoms were constructed of solid water, PMMA and white polystyrene as soft tissue (water) equivalents, and cork was used as the lung tissue equivalent. Measurements were performed using radiographic film and a cylindrical ionization chamber. The results show that the degradation of the 20/80% beam penumbra in the lung region is severe, up to 2.5 times the penumbra in water for a 10 cm thick lung with a density of 0.30 x 10(3) kg m(-3). The lack of electronic equilibrium in the low-density region can cause underdosage at the lung/tumour interface of up to 30% of maximum target dose, and the build-up depth to 95% of target dose in unit density tissue behind the lung may be as large as 22 mm. It is also shown that these figures strongly depend on patient anatomy and beam size and why a careful calculation of the individual dose distribution is needed for optimal choice of photon beam energy in thoracic treatments.

Biophysical Phenomena↗

PubMed1995

Hemoglobin adducts for in vivo dose monitoring and cancer risk estimation.

For the estimation of cancer risks from environmental chemicals, knowledge of the target dose is essential, dose being defined as the time integral of concentration in target tissues. In vivo doses from chronic or intermittent exposures are best determined from established steady-state levels of macromolecule adducts of reactive compounds or intermediates. For dose monitoring, hemoglobin (Hb) is preferred to DNA for several reasons: accessibility in large amounts, availability of methods for chemical identification, and well-determined life span due to absence of repair. For these reasons, and because of the proportionality of rates of DNA and Hb adduct formation, Hb adduct levels give better information on cumulative DNA adduct levels than do direct measurement of DNA adducts. The scientific background of Hb adduct measurement, target dose determination, and risk estimation based on the relative genotoxic potency, with gamma-radiation as reference standard, is reviewed and exemplified. The sensitivity of the method for Hb adduct measurement permits determination of exposures where the associated annual cancer risk is less than 1 per million. Besides application for studies of metabolism by determination of in vivo doses in exposed animals and humans, as a basis for risk estimation, Hb adduct measurement is used for hygienic surveillance of occupational exposures. Determination of Hb adducts by mass-spectrometric techniques gives a tool for identification of reactive metabolites, not only in individuals with known exposure, but also for characterization of adducts to Hb from compounds acting as mutagens (initiators) in the background carcinogenesis. This is the large fraction of the total number of cancer cases that occur among individuals without known exposure.

Carcinogens↗

PubMed1997

Behavioral, situational, and temporal effects of treatment of ADHD with methylphenidate.

OBJECTIVE: To determine the behavioral, situational, and temporal effects of 4 months of methylphenidate (MPH) treatment for attention-deficit hyperactivity disorder (ADHD). METHOD: Ninety-one children with ADHD were randomly assigned to receive either MPH (titrated to a target dose of 0.7 mg/kg twice a day) or a placebo. Treatment effects were investigated with measures sensitive to various behaviors (core and associated symptoms), situations (home and school), time periods (morning and afternoon, after reaching the target dose, and after 4 months of treatment), and side effects. RESULTS: MPH treatment improved symptoms of ADHD and oppositional behavior at school, both in the morning and afternoon, but not at home. Side effects (increase in physiological and effective symptoms, lack of weight gain) were significantly more frequent with MPH than with placebo treatment. Benefit was evident after titration, but the onset of some side effects was delayed. Side effects were reported by parents but not by teachers. CONCLUSIONS: Positive effects of MPH on behavior are evident in the classroom, but with MPH given twice daily, parents do not report that MPH improves behavior at home. Greater impact on home behavior may require three times daily MPH and combined treatments.

Affect↗

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↗

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↗

PubMed1996

Angiotensin-converting enzyme inhibition after myocardial infarction: the Trandolapril Cardiac Evaluation Study.

To study the importance of giving an angiotensin-converting enzyme (ACE) inhibitor to patients with reduced systolic function after an infarction, the Trandodolapril Cardiac Evaluation study was designed to include the majority of patients with echocardiographic signs of left ventricular dysfunction among consecutively screened patients with infarctions. A total of 2606 consecutive patients with left ventricular systolic dysfunction corresponding to an ejection fraction < or = 35% were identified. Of these patients, 1749 (67%) were randomly assigned to receive oral trandolapril or placebo beginning on day 3 to 7 after the infarction. The follow-up period was 2 to 4 years. Trandolapril reduced all-cause mortality, with a relative risk reduction associated with trandolapril treatment of 0.78 (p = 0.0013). Benefit was seen within 1 month of treatment. Trandolapril also reduced cardiovascular death (relative risk 0.75, p = 0.001), sudden death (relative risk 0.76, p = 0.03), and progression to severe/ resistant heart failure (relative risk 0.71, p = 0.003). Recurrent myocardial infarction (fatal or nonfatal) was not significantly reduced (relative risk 0.86, p = 0.29). More than 80% of patients in both treatment groups reached the target dose of 4 mg trandolapril or placebo at the end of dose titration. Nearly half of the patients in both treatment groups discontinued taking study medication before death or trial closure. The need for open-label ACE inhibition was the reason for discontinuation for 48 and 75 patients in the trandolapril and placebo groups, respectively. In conclusion, long-term treatment with trandolapril in patients with reduced left ventricular function shortly after myocardial infarction significantly reduced mortality and morbidity. Most patients received the target dose of 4 mg trandolapril daily. The benefit observed is likely to reflect the benefit in clinical practice because the majority of eligible patients were randomized and the difference in patients leaving the trial to receive open-label ACE inhibition was moderate.

Aged↗

PubMed1987

Amphotericin-B nephrotoxicity in humans decreased by sodium supplements with coadministration of ticarcillin or intravenous saline.

Previous observations suggest that salt loading can help reverse amphotericin-B induced nephrotoxicity. Evidence is presented indicating that sodium supplements provide prophylaxis against the development of amphotericin-B nephrotoxicity. In a retrospective study at Vanderbilt University, 14/21 patients receiving amphotericin B (target dose, 25 mg/day) without salt supplements developed impaired renal function; in 10 instances amphotericin B was temporarily withdrawn. In contrast, only 2/17 patients who received amphotericin B with ticarcillin (with its obligatory sodium supplement) developed nephrotoxicity (P less than 0.01). All four patients, who were receiving the combination of amphotericin B and ticarcillin and who had their ticarcillin therapy stopped, developed nephrotoxicity in the subsequent week. In a prospective observational study at Essen, 20 patients had 24 courses of amphotericin B (target dose, 40 mg/day) with routine supplementation of 1 liter of 0.9% sodium chloride daily. Only two patients showed evidence of nephrotoxicity and no dosage modification of amphotericin B was required in any patient. Four patients with initial evidence of mildly impaired renal function received full supplements without adverse effects or the development of nephrotoxicity. These observations suggest that routine parenteral administration of sodium supplements can help minimize the nephrotoxic potential of amphotericin B.

Amphotericin B↗

PubMed1990

[Long-term results of postoperative and primary radiotherapy of carcinoma of the salivary glands: importance of dosage and target volume].

Longterm results in 92 patients after primary or postoperative irradiation for carcinoma of the major or minor salivary glands of the head are analyzed. Target volume included the region of the primary tumor; ipsilateral cervical lymph nodes were included in patients with metastases of the lymph nodes. Target doses were 25 to 35 X 2.0 Gy or in some cases 16 to 18 X 3.30 Gy. Local control was 93% in tumors of limited extension (I), 84% in extensive but macroscopically complete resected tumors (II) and 26% in biopsied or partially resected tumors (III). There were no major complications. Recurrence in the lymph nodes were observed in less than 5% of the group I + II NO and could be controlled permanently by secondary surgery plus irradiation. According to the own and published results the following target volumes are adequate: region of the primary tumor in adenoid-cystic carcinoma NO plus the ipsilateral cervical-supraclavicular region in patients with other high grade cancers or evidence for metastases. Target doses between 5940 and 7020 cGy are recommended.

Adenocarcinoma↗

PubMed1998

Toxicokinetics of organic solvents: a review of modifying factors.

This article reviews, with an emphasis on human experimental data, factors known or suspected to cause changes in the toxicokinetics of organic solvents. Such changes in the toxicokinetic pattern alters the relation between external exposure and target dose and thus may explain some of the observed individual variability in susceptibility to toxic effects. Factors shown to modify the uptake, distribution, biotransformation, or excretion of solvent include physical activity (work load), body composition, age, sex, genetic polymorphism of the biotransformation, ethnicity, diet, smoking, drug treatment, and coexposure to ethanol and other solvents. A better understanding of modifying factors is needed for several reasons. First, it may help in identifying important potential confounders and eliminating negligible ones. Second, the risk assessment process may be improved if different sources of variability between external exposures and target doses can be quantitatively assessed. Third, biological exposure monitoring may be also improved for the same reason.

Age Factors↗

PubMedDate not supplied

The AHCPR guidelines on heart failure: comparison of a family medicine and an internal medicine practice with the guidelines and an educational intervention to modify behavior.

OBJECTIVES: The objectives of this study were to apply the Agency for Health Care Policy and Research (AHCPR) guideline for heart failure to the measurement of quality of care in the ambulatory setting, to compare the results for two large practices and to design an educational intervention for the two practices being studied. METHODS: A retrospective chart review was conducted on a random sample of 50 patients with heart failure selected from each of two outpatient practices: the general internal medicine practice and the family medicine practice at a large academic medical center. Five medical review criteria were developed from the AHCPR guideline for heart failure to compare the two practices with each other and the guidelines. An educational intervention was developed to modify physician behavior in regard to compliance with guidelines. RESULTS: Assessment of left ventricular function occurred in 79% of all cases. Of eligible patients, 68% were treated with angiotensin-converting enzyme inhibitors (ACE-Is). Of those patients treated with enalapril and captopril, 30% and 12%, respectively, were receiving the target dose as defined in the AHCPR guidelines. Of patients not eligible for treatment with ACE-Is, none were treated with hydralazine and nitrates. When the ejection fraction was less than or equal to 40%, 81% of eligible patients were treated with ACE-Is, whereas 59% were treated with ACE-Is when the ejection fraction was greater than 40%. Calcium channel blockers were used in the treatment of 42% of patients. A statistical difference (P = .05) was found between the two practices for documentation of left ventricular function, the use of ACE-Is for patients with ejection fraction less than or equal to 40%, and the use of calcium channel blockers and beta blockers. CONCLUSIONS: In the practices studied, there is underutilization of the documentation of left ventricular function, ACE-Is in eligible patients, target doses of ACE-Is, and the use of hydralazine and nitrates for ineligible patients. A higher proportion of patients receive ACE-I therapy when the ejection fraction is less than or equal to 40%. There may be inappropriate use of calcium channel blockers in some patients. There is unexplained clinical variation between the two practices studied.

Adrenergic beta-Antagonists↗

PubMed1991

The objective evaluation of alternative treatment plans: II. Score functions.

A series of six patients with adenocarcinoma of the prostate, Stages A2, B1, or B2, were planned for treatment using a four-field box technique at 25 MV. Plans were prepared by three techniques: composite, mid-plane, and conformal. The dose distributions at the central plane and at two planes offset by +/- 2 cm were evaluated by means of score functions which quantify the magnitude of regret for target dose gradient, target over- and under-dose, non-target tissue overdose, and for overdose to the rectum, bladder, and femoral heads. The score functions are normalized to give values in the range from 10 (ideal) to zero (limit of acceptability), with negative values indicating unacceptable deviations from the prescribed dose limits. The scores for off-axis conformal plans were found to be essentially the same as for mid-plane plans on the central plane. However, mid-plane planning was shown to be totally inadequate for off-axis planes, where the average target gradient and underdose scores were reduced by 10 units. Composite planning resulted in adequate target coverage on all planes, but at the expense of unacceptable overdose to non-target tissue. The effect of reducing the posterior beam weight to half that of the other three beams was to reduce the target gradient score by 1.6 +/- 0.5 units and to increase the rectal score by 0.9 +/- 0.3 units.

Adenocarcinoma↗

PubMed1992

The clinical application of a non-axial treatment plan for pancreatic and biliary malignancies.

Standard radiation therapy for adenocarcinoma of the pancreas treats a substantial portion of the renal parenchyma. It was hypothesized that rotating the plane of treatment to a non-axial orientation, with the anterior field entering the patient from an inferior oblique direction, would decrease the renal dose of radiation without increasing the liver dose or compromising the target dose. To test this hypothesis, patients referred for radical radiation treatment for tumors of the pancreas or distal common bile duct were prospectively evaluated by performing treatment planning using axial and non-axial field arrangements. Treatment plans were compared using dose volume histograms (DVHs) of both kidneys and the liver. In all 15 cases analyzed, the non-axial plan was superior to the axial plan with respect to renal dose, without significantly increasing the hepatic dose and was used for treatment. Treatment was not significantly more complex nor was gastrointestinal toxicity increased. These findings show that non-axial field arrangements can be used on a routine basis to decrease the renal dose of radiation for the treatment of pancreatic and biliary malignancies. It is anticipated that in the future, a combination of DVH-guided treatment planning and sophisticated renal function studies will be necessary to permit a more accurate prediction of the probability of renal complications resulting from radiation therapy.

Aged↗

PubMed1994

Organ-sparing treatment of advanced bladder cancer: a 10-year experience.

PURPOSE: Radical cystectomy is considered as standard therapy for muscle-invasive bladder cancer. We present 10-year results of bladder-sparing treatment by conservative surgery and radiotherapy +/- chemotherapy. METHODS AND MATERIALS: From 1982 through 1991, 245 consecutive patients, mean age 66 years, with invasive bladder cancer (T2-3 or poor prognostic T1, no distant metastases) entered a prospective protocol with the objective of bladder preservation. Treatment consisted of transurethral resection (complete, if possible) and definitive radiotherapy with 56 Gy maximum dose (50.4 Gy minimum target dose) in 28 fractions. Since 1985, 139 patients received a simultaneous chemotherapy on 5 days in the first and fifth treatment week with either 25 mg/m2 cisplatin daily (79 patients) or 65 mg/m2 carboplatin (60 patients). Cystectomy was performed as salvage treatment for residual or recurrent invasive disease. The median follow-up at the date of analysis (12-31-92) was 5.9 years. RESULTS: The overall survival was 47% after 5 years and 26% after 10 years. The 5-year survival according to the initial T-category was 60% for T1 (44 patients), 64% for T2 (47 patients), 43% for T3 (127 patients), and 16% for T4 (23 patients). The most important single prognostic factor was the amount of residual tumor after TUR (5-year survival 80% after R0, 53% after R1, and 31% after R2 resection, p < 0.01). Chemotherapy increased the rate of complete remission, but had no impact on 5-year survival (52% vs. 50%). Fifty-three salvage cystectomies were performed, all without severe complications, and 192 patients (79%) maintained a normal functioning bladder. The bladder preservation rate in 5-year survivors was 83%. CONCLUSIONS: Organ-sparing treatment of advanced bladder cancer by transurethral surgery and definitive radiotherapy or radiochemotherapy is feasible and effective. The survival in this series is as good as in any comparable cystectomy series. Eighty-three percent of long-term survivors maintained their functioning bladders.

Aged↗

PubMed1996

Can caretakers of children with IDDM accurately measure small insulin doses and dose changes?

OBJECTIVE: To determine if caretakers of young children with IDDM could consistently reproduce small incremental measurements of insulin (U100). RESEARCH DESIGN AND METHODS: Fifteen caretakers of children with IDDM were asked to deliver repeated small doses of insulin, including doses separated by only 0.25 U of insulin. A sensitive gravimetric technique was used to determine the error in measurement of these low doses of insulin. Statistical analysis was used to evaluate accuracy and internal consistency of each caretaker at each dose. RESULTS: The means +/- SD at each dose level were as follows: 2.75 +/- 0.13 U at 2.5 U, 3.19 +/- 0.13 U at 3.0 U, 3.55 +/- 0.13 U at 3.25 U, and 3.70 +/- 0.11 U at 3.5 U. All doses were biased toward overadministration. There was as statistically significant difference in the dose delivered when the target doses were varied by only 0.25 U. The average differences and standard errors between 2.5 U and 3.0 U, 3.0 U and 3.25 U, and 3.25 U and 3.5 U were 0.44 +/- 0.20 U, 0.36 +/- 0.018 U, and 0.15 +/- 0.017 U, respectively. CONCLUSIONS: Participants were not accurate in measuring small insulin doses, consistently overdrawing insulin by an average of 0.22 U. Caretakers are reasonably internally consistent with a given dose, since participants were able to measure statistically significant differences in 0.25 U dose changes. The error in insulin measurement does not vary with the intended dose level. Caretakers in the same family deliver insulin doses as variable from each other as they are from the population as a whole; however, when two or more individuals are responsible for one insulin dose in a child with IDDM, they have a combined variability that is approximately 40% greater than a single individual's variability.

Caregivers↗

PubMed1981

Chemical attraction in the absence of worm-mediated tactile behavior in Trichinella spiralis.

In vitro chemical attraction of Trichinella spiralis was studied using as migrators individual male or female worms. Both male and female worms exhibited a dose-dependent behavior at target doses of 20 to 80 worms, no significant differences in response at doses of 80 to 200 worms, and an inhibition of movement at doses of 200 to 400 worms. Single males were attracted less to a mixture of males and females as the source of pheromone than single males to a female source. Single females did not move significantly towards a mixture of males and females. Adult males and fourth-state, juvenile males were significantly attracted to fourth-stage females as the pheromone source. Fourth-stage males attracted adult females but not forth-stage juvenile females. Adult males and females and third-stage, juvenile males and females were not significantly attracted to a pheromone source from third-stage juvenile males and females. We postulate that the onset of pheromone production in T spiralis is during the fourth developmental stage.

Animals↗

PubMed1999

Evaluation of polymer gels and MRI as a 3-D dosimeter for intensity-modulated radiation therapy.

BANG gel (MGS Research, Inc., Guilford, CT) has been evaluated for measuring intensity-modulated radiation therapy (IMRT) dose distributions. Treatment plans with target doses of 1500 cGy were generated by the Peacock IMRT system (NOMOS Corp., Sewickley, PA) using test target volumes. The gels were enclosed in 13 cm outer diameter cylindrical glass vessels. Dose calibration was conducted using seven smaller (4 cm diameter) cylindrical glass vessels irradiated to 0-1800 cGy in 300 cGy increments. Three-dimensional maps of the proton relaxation rate R2 were obtained using a 1.5 T magnetic resonance imaging (MRI) system (Siemens Medical Systems, Erlangen, Germany) and correlated with dose. A Hahn spin echo sequence was used with TR = 3 s, TE = 20 and 100 ms, NEX = 1, using 1 x 1 x 3 mm3 voxels. The MRI measurements were repeated weekly to identify the gel-aging characteristics. Ionization chamber, thermoluminescent dosimetry (TLD), and film dosimetry measurements of the IMRT dose distributions were obtained to compare against the gel results. The other dosimeters were used in a phantom with the same external cross-section as the gel phantom. The irradiated R2 values of the large vessels did not precisely track the smaller vessels, so the ionization chamber measurements were used to normalize the gel dose distributions. The point-to-point standard deviation of the gel dose measurements was 7.0 cGy. When compared with the ionization chamber measurements averaged over the chamber volume, 1% agreement was obtained. Comparisons against radiographic film dose distribution measurements and the treatment planning dose distribution calculation were used to determine the spatial localization accuracy of the gel and MRI. Spatial localization was better than 2 mm, and the dose was accurately determined by the gel both within and outside the target. The TLD chips were placed throughout the phantom to determine gel measurement precision in high- and low-dose regions. A multidimensional dose comparison tool that simultaneously examines the dose-difference and distance-to-agreement was used to evaluate the gel in both low-and high-dose gradient regions. When 3% and 3 mm criteria were used for the comparisons, more than 90% of the TLD measurements agreed with the gel, with the worst of 309 TLD chip measurements disagreeing by 40% of the criteria. All four MRI measurement session gel-measured dose distributions were compared to evaluate the time behavior of the gel. The low-dose regions were evaluated by comparison with TLD measurements at selected points, while high-dose regions were evaluated by directly comparing measured dose distributions. Tests using the multidimensional comparison tool showed detectable degradation beyond one week postirradiation, but all low-dose measurements passed relative to the test criteria and the dose distributions showed few regions that failed.

Biophysical Phenomena↗

PubMed1998

Quality assurance of serial tomotherapy for head and neck patient treatments.

PURPOSE: A commercial serial tomotherapy intensity-modulated radiation therapy (IMRT) treatment planning (Peacock, NOMOS Corp., Sewickley, PA) and delivery system is in clinical use. The dose distributions are highly conformal, with large dose gradients often surrounding critical structures, and require accurate localization and dose delivery. Accelerator and patient-specific quality assurance (QA) procedures have been developed that address the localization, normalization, and delivery of the IMRT dose distributions. METHODS AND MATERIALS: The dose distribution delivered by serial tomotherapy is highly sensitive to the accuracy of the longitudinal couch motion. There is also an unknown sensitivity of the dose distribution on the dynamic mutlileaf collimator alignment. QA procedures were implemented that assess these geometric parameters. Evaluations of patient positioning accuracy and stability were conducted by exposing portal films before (single exposure) and after (single or double exposure) treatments. The films were acquired with sequential exposures using the largest available fixed multileaf portal (3.36 x 20 cm2). Comparison was made against digitally reconstructed radiographs generated using independent software and appropriate beam geometries. The delivered dose was verified using homogeneous cubic phantoms. Radiographic film was used to determine the localization accuracy of the delivered isodose distributions, and ionization chambers and thermoluminescent dosimetry (TLD) chips were used to verify absolute dose at selected points. Ionization chamber measurements were confined to the target dose regions and TLD measurements were obtained throughout the irradiated volumes. Because many more TLD measurements were made, a statistical evaluation of the measured-to-calculated dose ratio was possible. RESULTS: The accelerator QA techniques provided adequate monitoring of the geometric patient movement and dynamic multileaf collimator alignment and positional stability. The absolute delivered dose as measured with the ionization chamber varied from 0.94 to 0.98. Based on these measurements, the delivered monitor units for both subsequent QA measurements and patient treatments were adjusted by the ratio of measured to calculated dose. TLD measurements showed agreement, on average, with the ionization chamber measurements. The distribution of TLD measurements in the high-dose regions indicated that measured doses agreed within 4.2% standard deviation of the calculated doses. In the low-dose regions, the measured doses were on average 5% greater than the calculated doses, due to a lack of leakage dose in the dose calculation algorithm. CONCLUSIONS: The QA system provided adequate determination of the geometric and dosimetric quantities involved in the use of IMRT for the head and neck. Ionization chamber and TLD measurements provided accurate determination of the absolute delivered dose throughout target volumes and critical structures, and radiographic film yielded precise dose distribution localization verification. Portal film acquisition and subsequent portal film analysis using 3.36 x 20 cm2 portals proved useful in the evaluation of patient immobilization quality. Adequate bony landmarks were imaged when carefully selected portals were used.

Algorithms↗

PubMed1995

Biomarkers as tools in human health risk assessment.

Evaluation of occupational or environmental risk due to exposure to chemicals requires sufficient information on the toxic profiles, mechanisms of action, toxicokinetics, dose-response relation, exposure, and the target dose. Usually exposure is estimated by measuring concentrations of the agent in air, food, water, soil, dust, or other media with which a population or an individual is in contact. However, this external exposure is only a rough estimate for the internal exposure (agent dose or its metabolite at the critical target in the organism). Factors of influence are bioavailability of the chemicals, variations in concentrations and routes of exposure, physical activity, and individual variation in rates of metabolism, distribution, and excretion. All these affect the concentration of the toxic agent at the critical target, which is the most precise information for risk assessment. Thus, internal exposure is best measured by determining the concentration of the toxicant or its ultimate metabolite at the critical site in the target organ or by determining adducts with cellular macromolecules such as proteins, amino acids, DNA, or its bases. The latter are easily available in experimental toxicology from animal experiments but only occasionally from humans. For health surveillance such data usually are not available, because they require invasive procedures such as biopsies. Therefore, more accessible body fluids or tissue are used, such as blood, urine, or adipose tissue, or adducts with macromolecules such as albumin or hemoglobin in the blood, DNA adducts in peripheral lymphocytes, or altered DNA bases in urine such as 8-hydroxyguanine. All of these are indicators for exposure, whereas risk can only be estimated if the correlation between their deviations from normal and the dose-response at the critical target is known.

Animals↗