Work-based learning, role extension and skills mix within dose planning: target volume definition for carcinoma of the prostate by non-clinicians.
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Clinical Competence↗
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Results for “Targeted dosing”
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Long-term results (10 years) of intensive breast conserving therapy including a high-dose and large-volume interstitial brachytherapy boost (LDR/HDR) for T1/T2 breast cancer.
BACKGROUND AND PURPOSE: During the past 15 years many retrospective studies and prospective randomized trials have been published supporting the use of breast conserving treatment (BCT) including surgery and radiotherapy. However, there are still many controversies on the necessary amount of resection, the width of the resection margins and the optimal radiation technique, dose and volume, in particular of the boost. In this retrospective study a large cohort of 410 women with early breast cancer treated with BCT including an interstitial brachytherapy (BT) boost is evaluated after a long follow-up period. MATERIAL AND METHODS: In order to clarify the impact of the different treatment-related factors on local control, these were carefully discriminated, based on widely accepted classification and reporting systems for surgery as well as for radiotherapy. The surgical approach was classified according to EORTC criteria and a high rate of quadrantectomies (60%) was found. Dose and volume of interstitial BT is reported according to recommendations of ICRU 58, and reveals a significant radiation dose and volume: minimum target dose, mean central dose (MCD) and '85% of MCD' for low-dose rate (LDR) BT was mean 20, 28 and 24 Gy, for high-dose rate (HDR) BT it was mean '10, 15 and 13 Gy, respectively; the treated volume was 104 cc for LDR BT and 83 cc for HDR BT. RESULTS: The actuarial rates for overall survival, disease-free survival and disease-specific survival were 97, 90 and 98% at 5 years and 85, 79 and 92% at 10 years. There have been only 16 breast recurrences in 410 treated patients resulting in a 5- and 10-year actuarial local recurrence rate of 2 and 3.9%, respectively; six recurrences (1.5%) were in the original quadrant. Except age and menopausal status, all tumour- and patient-related risk factors had no significant impact on local control. CONCLUSIONS: Our data confirm that intensive BCT leads to excellent long-term results in terms of local control, masking classical risk factors. This high-dose and large-volume interstitial BT seems to be superior to classical BCT without BT.
Adult↗
Sertraline treatment of obsessive-compulsive disorder: efficacy and tolerability of a rapid titration regimen.
The objective of this study was to compare in a single blind manner, over a period of 12 weeks, the efficacy and tolerability of two different titration regimens of sertraline in the treatment of OCD: 150 mg/day reached at day five from the beginning of therapy (rapid titration regimen) versus 150 mg/day reached at day 15 from the beginning (slow titration regimen). Patients with a DSM-IV diagnosis of OCD and a Y-BOCS greater or equal to 16 were randomly assigned to receive one of the two dosing regimens; an upper target dose of 150 mg/day was selected on the basis of a review of mean dosages used in flexible-dose sertraline studies. The primary efficacy measure was the Y-BOCS, which was completed at baseline and every 2 weeks. Thirty-two patients referred to the Anxiety and Mood Disorders Unit of the University of Turin were included in the study. Seventeen were assigned to the rapidly escalating dose regimen and 15 to the other titration regimen. Twenty-seven (84.4%) patients completed the 12 weeks of the study: 14 (82.4%) patients in the rapid and 13 (86.7%) in the slow titration regimen. The ANOVA analysis showed a significant difference between treatment groups at week 4 and 6 in favor of the rapid titration regimen group; this difference faded afterwards. Both titration regimens were effective in reducing OC symptoms and were well tolerated: no differences in drop-out or in adverse event rates emerged between the two groups. Limitations of the present study are the single-blind design and the lack of power to detect differences in tolerability.
Analysis of Variance↗
No induction of thiopurine methyltransferase during thiopurine treatment in inflammatory bowel disease.
The aim of this study was to follow, during standardized initiation of thiopurine treatment, thiopurine methyltransferase (TPMT) gene expression and enzyme activity and thiopurine metabolite concentrations, and to study the role of TPMT and ITPA 94C > A polymorphisms for the development of adverse drug reactions. Sixty patients with ulcerative colitis or Crohn's disease were included in this open and prospective multi-center study. Thiopurine naïve patients were prescribed azathioprine (AZA), patients previously intolerant to AZA received 6-mercaptopurine (6-MP). The patients followed a predetermined dose escalation schedule, reaching target dose at Week 3; 2.5 and 1.25 mg/kg body weight for AZA and 6-MP, respectively. The patients were followed every week during Weeks 1-8 from baseline and then every 4 weeks until 20 weeks. TPMT activity and thiopurine metabolites were determined in erythrocytes, TPMT and ITPA genotypes, and TPMT gene expression were determined in whole blood. One homozygous TPMT-deficient patient was excluded. Five non compliant patients were withdrawn during the first weeks. Twenty-seven patients completed the study per protocol; 27 patients were withdrawn because of adverse events. Sixty-seven percent of the withdrawn patients tolerated thiopurines at a lower dose at Week 20. There was no difference in baseline TPMT enzyme activity between individuals completing the study and those withdrawn for adverse events (p = 0.45). A significant decrease in TPMT gene expression (TPMT/huCYC ratio, p = 0.02) was found, however TPMT enzyme activity did not change. TPMT heterozygous individuals had a lower probability of remaining in the study on the predetermined dose (p = 0.039). The ITPA 94C > A polymorphism was not predictive of adverse events (p = 0.35).
Alleles↗
Beam delivery sequencing for intensity modulated proton therapy.
Methods of beam fluence sequencing for intensity modulated proton therapy (IMPT) using the beam scanning technique are presented. Proton beam weight maps optimized by the treatment planning system (TPS) for a discrete set of regularly spaced narrow pencil beams were interpolated, using convolution with various kernel functions, to simulate continuous beam scanning on a raster pattern. Expected dose distributions at the proton Bragg peak range were then calculated and compared to those planned by the TPS, to evaluate the discrepancy due to the differences between the treatment planning and delivery approaches. An iteratively optimized adjustment was applied to the simulated continuous beam fluence profiles to reduce such discrepancy. Calculation showed that by accounting for the specifics of the scanning method, the planned dose distribution on the target may be reproduced to within 0.5% of the maximum target dose, given the pencil beam spacing smaller or equal to the beam sigma is used for treatment planning. For the beam weight maps generated using a spot spacing larger than sigma, a substantial reduction in the calculated dose discrepancy may be attained by applying an iterative adjustment of fluence profiles obtained by interpolating over artificially expanded set of beam spots.
Biophysical Phenomena↗
Behavioural effects of the newer antiepileptic drugs: an update.
The negative and positive effects of the nine newer antiepileptic drugs that have received a product licence in the UK or in the US are reviewed. The importance of avoiding misinterpretation of the data because of confounding factors such as alternative psychosis, the release phenomenon or drug interactions is emphasised. Vigabatrin has been associated with both psychosis and depression. Due to the concentric visual field defects that may occur with vigabatrin, its use is now limited, although it remains the drug of choice for infantile spasms. Lamotrigine seems to be largely associated with improvement rather than deterioration of mood and behaviour. It may have a role in treating affective disorder. Gabapentin probably has relatively little effect on behaviour but may exacerbate behavioural problems in some children with pre-existing difficulties. Topiramate may precipitate both psychosis and depression, but these are less likely to occur if the currently recommended lower starting doses, escalation rates and target doses are used. The data for tiagabine are limited, but there is no clear evidence for psychosis or depression being caused by this drug. Oxcarbazepine may be of value in treating mood disorder, but the information is very limited. There are few reports of behavioural disturbances with levetiracetam, but the data suggest that there is no significant increase in psychosis or depression. There are some reports of psychosis and other behavioural disturbances with felbamate, but the use of this drug is limited by the serious adverse effects of hepatotoxicity and aplastic anaemia. There is some evidence for psychosis with zonisamide, but there is also a suggestion that this drug may be of benefit in treating psychiatric disorders. Careful individual assessment of each patient should enable the clinician to determine whether the medication or some other factor is responsible for any behavioural disturbance.
Anticonvulsants↗
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↗
What to do when SSRIs fail: eight strategies for optimizing treatment of panic disorder.
Selective serotonin reuptake inhibitors (SSRIs) are the drug of choice for treatment of patients with panic disorder. Most patients have a favorable response to SSRI therapy; however, 30 percent will not be able to tolerate these drugs or will have an unfavorable or incomplete response. Strategies to improve management of such patients include optimizing SSRI dosing (starting at a low dose and slowly increasing the dose to reach the target dose) and ensuring an adequate trial before switching to a different drug. Benzodiazepines should be avoided but, when necessary, may be used for a short duration or may be used long-term in patients for whom other treatments have failed. Slower-onset, longer-acting benzodiazepines are preferred. All patients should be encouraged to try cognitive behavior therapy. Augmentation therapy should be considered in patients who do not have a complete response. Drugs to consider for use in augmentation therapy include benzodiazepines, buspirone, beta blockers, tricyclic antidepressants, and valproate sodium.
Algorithms↗
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↗
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↗
Pseudo beam's-eye-view as applied to beam orientation selection in intensity-modulated radiation therapy.
PURPOSE: To introduce the concept of pseudo beam's-eye-view (pBEV), to establish a framework for computer-assisted beam orientation selection in intensity-modulated radiation therapy (IMRT), and to evaluate the utility of the proposed technique. METHODS AND MATERIALS: To facilitate the selection of beam orientations for IMRT treatment planning, a scoring of beam direction was introduced. The score function was based on the maximum target dose deliverable by the beam without exceeding the tolerance doses of the critical structures. For the score function calculation, the beam portal at given gantry and couch angles was divided into a grid of beamlets. Each beamlet crossing the target was assigned the maximum intensity that could be used without exceeding the dose tolerances of the organs at risk (OARs) and normal tissue. Thereafter, a score was assigned to the beam according to the target dose delivered. The beams for the treatment were selected among those with the highest scores. In a sense, this technique is similar to the beam's-eye-view approach used in conventional radiation therapy, except that the evaluation by a human is replaced by a score function, and beam modulation is taken into account. RESULTS: The pBEV technique was tested on two clinical cases: a paraspinal treatment and a nasopharyngeal cancer with both coplanar and noncoplanar beam configurations. The plans generated under the guidance of pBEV for the paraspinal treatment offered superior target dose uniformity and reduced OAR doses. For the nasopharyngeal cancer case, it was also found that the pBEV-selected coplanar and noncoplanar beams significantly improved the target coverage without compromising the sparing of the OARs. CONCLUSIONS: The pBEV technique developed in this work provides a comprehensive tool for beam orientation selection in IMRT. It is especially valuable for complicated cases, where the target is surrounded by several sensitive structures and where it is difficult to select a set of good beam orientations. The pBEV technique has considerable potential for simplifying the IMRT treatment planning process and for maximizing the technical capacity of IMRT.
Humans↗
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↗
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↗
Three-dimensional conformal radiation therapy may improve the therapeutic ratio of high dose radiation therapy for lung cancer.
PURPOSE: The specific aim of 3-dimensional conformal radiation therapy is to improve the target dose distribution while concomitantly reducing normal tissue dose. Such an approach should permit dose escalation until the limits of acceptable normal tissue toxicity are reached. To evaluate the feasibility of tumor dose escalation for nine patients with lung cancer, we determined the dose distribution to the target and normal tissues with 3-dimensional conformal radiation therapy and conventional planning. METHODS AND MATERIALS: Plans were compared to assess adequacy of dose delivery to target volumes, dose-volume histograms for normal tissue, and normal tissue complication probabilities (NTCP) for nine patients with lung tumors. RESULTS: The mean percentage of gross disease which received < or = 70.2 Gy with 3-dimensional conformal radiation therapy (3DCRT) was 40% of the mean percentage of gross disease which received < or = 70.2 Gy with conventional treatment planning (CTP). The mean NTCP for lung parenchyma with 3DCRT was 36% of the mean NTCP with CTP. The mean esophageal NTCP with 3DCRT was 88% of the mean NTCP with CTP. CONCLUSION: This preliminary analysis suggests that three dimensional conformal radiation therapy may provide superior delivery of high dose radiation with reduced risk to normal tissue, suggesting that this approach may have the potential to improve the therapeutic ratio of high dose radiation therapy for lung cancer.
Adenocarcinoma↗
Angiotensin-converting enzyme inhibitor dosages in elderly patients with heart failure.
BACKGROUND: We sought to describe the dosages of angiotensin-converting enzyme (ACE) inhibitor prescribed to elderly patients with heart failure at hospital discharge, the factors associated with dosing level, and the association of these dosages with 1-year outcomes. METHODS: Demographic, procedural, and medication data were collected retrospectively from medical records at 18 Connecticut hospitals. Information on mortality and readmission was obtained from the Health Care Financing Administration administrative databases. Dosages of ACE inhibitor were grouped into 3 categories: dosages recommended in practice guidelines or higher (target dose), dosages used in clinical trials but lower than guideline recommendations (subtarget dose), and dosages lower than those used in clinical trials (low dose). RESULTS: A total of 554 patients, 65 years old or less with confirmed heart failure and systolic dysfunction, were prescribed an ACE inhibitor at discharge. Target, subtarget, and low doses were given in 19%, 63%, and 18% of the patients, respectively. Few demographic or clinical factors were related to lower dosages. Both subtarget and target doses of ACE inhibitors were associated with a significantly lower adjusted 1-year mortality (relative risk 0.67, P =.04; relative risk 0.51, P =.02, respectively) compared with low doses of ACE inhibitors. CONCLUSIONS: In a representative elderly cohort of patients with heart failure with systolic dysfunction, the majority (82%) were discharged on doses of ACE inhibitors consistent with those used in clinical trials. We observed a dose-response relationship between higher doses and lower mortality. Future studies will need to determine whether this association is causal.
Aged↗
Inhibition of acetyl- and butyryl-cholinesterase in the cerebrospinal fluid of patients with Alzheimer's disease by rivastigmine: correlation with cognitive benefit.
Cholinesterase (ChE) inhibition represents the most efficacious treatment approach for Alzheimer's disease (AD) to date. This multiple-dose study has examined the relationship between inhibition of acetylcholinesterase (AChE) and butyrylcholinesterase (BuChE) activities in the cerebrospinal fluid (CSF) and cognitive change (measured by the Computerised Neuropsychological Test Battery [CNTB]) following administration of the ChE inhibitor, rivastigmine (Exelon). In 18 patients with mild to moderate AD, CNTB scores, activities of AChE and BuChE in the CSF, and plasma BuChE activity were determined prior to treatment with rivastigmine. Doses of rivastigmine were then titrated (1 mg b.i.d./week) to final doses of 1, 2, 3, 4, 5 or 6 mg b.i.d. (n = 3 per dose). Following treatment with the target dose of rivastigmine for at least 3 days, CNTB scores were re-determined. CSF samples were continuously collected together with plasma samples prior to and for 12 hours after the final dose of rivastigmine, and AChE and BuChE activities determined.AChE in CSF and BuChE in plasma were dose-dependently inhibited by rivastigmine treatment. The inhibition of BuChE in CSF was not clearly dose-dependent. A statistically significant correlation was observed between the change in CNTB summary score and inhibition of AChE activity (r = -0.56, p < 0.05) and BuChE activity (r = -0.65, p < 0.01) in CSF. Improvement in speed-, attention- and memory-related subtests of the CNTB correlated significantly with inhibition of BuChE but not AChE activity in CSF. Weak or absent correlation with change in cognitive performance was noted for inhibition of plasma BuChE. These results indicate that cognitive improvement with rivastigmine in AD is associated with central inhibition of ChEs and support a role for central BuChE in addition to AChE inhibition in modulating cholinergic function in AD.
Acetylcholinesterase↗
Intensity-modulated radiotherapy technique for three-field breast treatment.
PURPOSE: To develop a simplified intensity-modulated radiotherapy (IMRT) algorithm for three-field breast treatment using a single isocenter setup. The algorithm aims to deliver a uniform dose throughout the breast volume. Special attention was paid to the highly divergent nature of the beam configuration. METHODS AND MATERIALS: Computed tomography (CT) image setup of the patient was acquired. On each CT slice, the computer automatically generated lines parallel to the posterior edge of the tangent field. The mid-point of each line segment that intersected the breast was determined and the dose from an open field calculated. The intensity of the divergent pencil beam corresponding to the mid-point was set to be inversely proportional to the open field dose to the mid-point. Forward dose calculation was then performed using this intensity distribution. RESULTS: A total of 15 breast cancer patients undergoing three-field IMRT who underwent planning and treatment with this algorithm were included in this study. Compared with standard wedged pair tangents, the IMRT plan produced statistically significant better dose distributions in terms of target coverage and target dose uniformity, as well as reduced dose to the contralateral breast and reduced hot spots to the ipsilateral lung. CONCLUSION: Since March 2004, the new IMRT algorithm has been used for planning and treatment of > 20 patients undergoing three-field treatment, as well as >200 patients undergoing regular two-field tangent treatment, all with excellent dose distributions throughout the breast volume.
Algorithms↗
Rapid inpatient/outpatient desensitization for chemotherapy hypersensitivity: standard protocol effective in 57 patients for 255 courses.
OBJECTIVES: Hypersensitivity reactions (HR) to chemotherapy often prompt permanent discontinuation and deprive the patient of the most active regimen. We investigated the safety and effectiveness of a rapid desensitization protocol used in inpatient and outpatient settings for patients with HR to various chemotherapy and related agents. METHODS: A 3-solution, 12-step protocol delivered doubling drug doses by step, infusing the target dose over 5.8 h for inpatient and 3.8 h for outpatient administration. RESULTS: 57 consecutive patients who had moderate to severe HR to chemotherapy were evaluated for desensitization. All 57 patients successfully completed 255 courses of desensitization (127 to carboplatin, 114 to paclitaxel, and 14 to four other agents) where 16 patients received 51 courses in the outpatient setting (34 to carboplatin and 17 to paclitaxel). 225 courses (88.2%) were completed without any HR. 18 patients had breakthrough symptoms (BS) over 30 courses (11.8%) that were less severe than their initial HR. After management of breakthrough symptoms, these patients finished all 30 courses and tolerated subsequent desensitizations on a modified protocol. 21 of 26 patients (81%) with HR to carboplatin had positive skin tests to carboplatin. Cancer response to chemotherapy administered by desensitization was within the expected range after 1-3 years of follow-up. CONCLUSION: The rapid desensitization protocol was safe and effective in both the inpatient and outpatient settings and allowed appropriate patients with moderate to severe HR to continue chemotherapy. This study warrants the incorporation of the protocol into standard clinical practice.
Adult↗