Difference In Median Dose Research Articles

Vancomycin Treatment Failure in Children With Methicillin-Resistant Staphylococcus aureus Bacteremia.

Limited data exist regarding clinical outcomes of invasive methicillin-resistant Staphylococcus aureus (MRSA) infections in children treated with vancomycin. Treatment success in adults correlates best with an area under the curve/minimum inhibitory concentration (AUC24/MIC) ratio ≥400. It is unknown if this relationship is useful in children. Charts of children who received vancomycin ≥5 days for MRSA bacteremia with a steady state trough were reviewed. AUC24/MIC ratios were estimated using 2 different vancomycin clearance equations. Vancomycin treatment failure was defined as persistent bacteremia ≥7 days, recurrent bacteremia within 30 days, or 30-day mortality. There were 67 bacteremia episodes in 65 patients. Nine (13.4%) met failure criteria: persistent bacteremia (n = 6), recurrent bacteremia (n = 2), 30-day mortality (n = 1). There were no differences between patients receiving <60 mg/kg/day and ≥60 mg/kg/day of vancomycin in median trough (11.9 versus 12.3 mg/L, p = 0.1). Troughs did not correlate well with AUC24/MIC ratios (R 2 = 0.32 and 0.22). Patients receiving ≥60 mg/kg/day had greater probability of achieving ratios ≥400. There were no significant differences in median dose (p = 0.8), trough (p = 0.24), or AUC24/MIC ratios (p = 0.07 and p = 0.6) between patients with treatment success and failure. Treatment failure was lower than previously reported in children. AUC24/MIC ratios ≥400 were frequently achieved but were not associated with treatment success, dose, or troughs. Prospective studies using standard definitions of vancomycin treatment failure are needed to understand treatment failure in children with MRSA bacteremia.

Transit and non-transit 3D EPID dosimetry versus detector arrays for patient specific QA.

PurposeDespite their availability and simplicity of use, Electronic Portal Imaging Devices (EPIDs) have not yet replaced detector arrays for patient specific QA in 3D. The purpose of this study is to perform a large scale dosimetric evaluation of transit and non‐transit EPID dosimetry against absolute dose measurements in 3D.MethodsAfter evaluating basic dosimetric characteristics of the EPID and two detector arrays (Octavius 1500 and Octavius 1000SRS), 3D dose distributions for 68 VMAT arcs, and 10 IMRT plans were reconstructed within the same phantom geometry using transit EPID dosimetry, non‐transit EPID dosimetry, and the Octavius 4D system. The reconstructed 3D dose distributions were directly compared by γ‐analysis (2L2 = 2% local/2 mm and 3G2 = 3% global/2 mm, 50% isodose) and by the percentage difference in median dose to the high dose volume (%∆HDVD 50).ResultsRegarding dose rate dependency, dose linearity, and field size dependence, the agreement between EPID dosimetry and the two detector arrays was found to be within 1.0%. In the 2L2 γ‐comparison with Octavius 4D dose distributions, the average γ‐pass rate value was 92.2 ± 5.2%(1SD) and 94.1 ± 4.3%(1SD) for transit and non‐transit EPID dosimetry, respectively. 3G2 γ‐pass rate values were higher than 95% in 150/156 cases. %∆HDVD 50 values were within 2% in 134/156 cases and within 3% in 155/156 cases. With regard to the clinical classification of alerts, 97.5% of the treatments were equally classified by EPID dosimetry and Octavius 4D.ConclusionTransit and non‐transit EPID dosimetry are equivalent in dosimetric terms to conventional detector arrays for patient specific QA. Non‐transit 3D EPID dosimetry can be readily used for pre‐treatment patient specific QA of IMRT and VMAT, eliminating the need of phantom positioning.

Predicting VMAT patient-specific QA results using a support vector classifier trained on treatment plan characteristics and linac QC metrics

The use of treatment plan characteristics to predict patient-specific quality assurance (QA) measurement results has recently been reported as a strategy to help facilitate automated pre-treatment verification workflows or to provide a virtual assessment of delivery quality. The goal of this work is to investigate the potential of using treatment plan characteristics and linac performance metrics (i.e. quality control test results) in combination with machine learning techniques to predict the results of VMAT patient-specific QA measurements.Using features that describe treatment plan complexity and linac performance metrics, we trained a linear support vector classifier (SVC) to classify the results of VMAT patient-specific QA measurements. The ‘targets’ in this model were simple classes representing median dose difference between measured and expected dose distributions—‘hot’ if the median dose deviation was >1%, ‘cold’ if it was <−1%, and ‘normal’ if it was within ±1%. A total of 1620 unique patient-specific QA measurements were available for model development and testing. 75% of the data were used to develop and cross-validate the model, and the remaining 25% were used for an independent assessment of model performance. For the model development phase, a recursive feature elimination (RFE) cross-validation technique was used to eliminate unimportant features. Model performance was assessed using receiver operator characteristic (ROC) curve metrics.Of the ten features found to be most predictive of patient-specific QA measurement results, half were derived from treatment plan characteristics and half from quality control (QC) metrics characterizing linac performance. The model achieved a micro-averaged area under the ROC curve of 0.93, and a macro-averaged area under the ROC curve of 0.88.This work demonstrates the potential of using both treatment plan characteristics and routine linac QC results in the development of machine learning models for VMAT patient-specific QA measurements.

Acetaminophen is Undetectable in Plasma From More Than Half of Patients Believed to Have Acute Liver Failure Due to Overdose

Evaluation of patients with acute liver injury (ALI) or acute liver failure (ALF) often includes measurement of plasma levels of acetaminophen, to determine exposure and/or toxicity. However, once liver injury has developed, acetaminophen might be undetectable in plasma. We investigated the association between level of acetaminophen measured and outcomes of patients designated as having ALF or ALI due to acetaminophen toxicity. We performed a retrospective analysis of data from 434 subjects in the Acute Liver Failure Study Group who met criteria for ALF (coagulopathy and hepatic encephalopathy within 26 weeks of the first symptoms, without pre-existing liver disease) or ALI (severe liver injury with coagulopathy but no encephalopathy) due to acetaminophen toxicity from January 1, 2010 through December 31, 2014. We collected data on patient demographics, biochemical features, reported acetaminophen use, N-acetylcysteine therapy, liver transplant, and outcomes. Descriptive statistics were used to assess patient demographics, clinical characteristics, and outcomes whereas differences in continuous variables between patients with vs without acetaminophen detection on admission were analyzed using the Wilcoxon rank-sum test. The primary aim was to determine the proportion of patients with detectable plasma levels of acetaminophen. Acetaminophen was undetectable in serum samples from 227 patients (52%). There were no significant differences between groups of patients with detectable vs undetectable levels in demographic features, alcohol use, median levels of alanine aspartate, or use of N-acetylcysteine (given to 94.7% of patients with detectable acetaminophen vs 95.9% of those with undetectable acetaminophen; P=.63). We observed a significant difference in median dose taken between patients with detectable (29,500 mg; interquartile range, 15,000 mg-50,007 mg) vs no detectable parent compound (14,950 mg; interquartile range, 3960 mg-25,000) (P=.003). A lower proportion of patients with detectable plasma levels of acetaminophen (72.3%) survived without a liver transplant than of patients with undetectable levels (86.3%) in univariate analysis (P=.0006), although this was not significant in multivariable analysis (P=.12). Although most patients had unintentional overdoses, a higher proportion of patients with suicidal overdoses (43%) had detectable levels of acetaminophen than patients with accidental overdoses (29.3%; P=.01). More than half of patients who present at the hospital with acetaminophen-induced ALI or ALF have undetectable levels of acetaminophen. Clinicians should not exclude acetaminophen toxicity because of undetectable levels or withhold N-acetylcysteine for patients with ALI or ALF when acetaminophen toxicity is suspected.

35 Monte Carlo dose calculation of VMAT clinical treatment plans for Novalis TrueBeam STx linac using PRIMO

Introduction The aim of patient specific QA is to check if calculated dose by TPS corresponds to delivered dose to patient by the linac. With complex techniques like VMAT this is both more important and more challenging. QA both focus on dose calculation and dose delivery. Regarding dose calculation, Monte Carlo methods are considered as golden standard. Methods We use PRIMO to calculate VMAT clinical plans, for a TrueBeam. PRIMO combines the PENELOPE Monte Carlo code, the geometry of some linacs including their MLC, and a graphical user interface. PRIMO is adapted to perform Monte Carlo simulation in a clinical environment. The main reason is the geometry definition. Version 0.1.5 officially doesn’t support VMAT plans calculation. With in-house additional scripts and huge efforts, we succeeded to calculate VMAT plans, on CT, with TrueBeam. Version 0.3.1 now allows VMAT plans calculation in a very simple way. This latest version discontinues the support of Elekta linacs. We compared dose from Eclipse (Acuros 13.7, dose to medium) with PRIMO. As the beam production geometry is not known for TrueBeam, we use phase space made available by Varian. PRIMO 0.3.1 includes an additional Monte Carlo code: DPM. It is optimized for radiotherapy but with a reduced accuracy in air. Results With PRIMO 0.3.1, we compared dose for 11 clinical plans. 3D gamma index (2%/2 mm) is always above 95%. For 2 lung cases, this required use of PENELOPE rather than DPM. Calculation time with DPM vary from 20 to 60 min, mainly depending on PTV size. Calculation time is 6 times longer with PENELOPE (24 cores workstation). Uncertainty (2 sigma) is about 2.5%. Median dose difference is lower than 1%. We also successfully calculated SRS plan from iPlan. Conclusions PRIMO is a valid tool to calculate VMAT clinical plan, for a TrueBeam. It is adapted for use in a clinical environment.

Impact of Multi-leaf Collimator Parameters on Head and Neck Plan Quality and Delivery: A Comparison between Halcyon™ and Truebeam® Treatment Delivery Systems.

PurposeA new dual-layer multi-leaf collimator (MLC) system with several improved characteristics was introduced with the Varian Halcyon™ treatment platform. This study evaluated this new MLC’s impact on head and neck plan quality and delivery efficiency.MethodsNine patients were retrospectively studied with Institutional Review Board (IRB) approval. To compare plan quality between the Halcyon dual-layer MLC and Truebeam® MLC, all patients were replanned with the same prescription and target coverage following the institutional clinical protocol for both platforms and using both intensity modulated radiation therapy (IMRT) or volumetrically modulated arc therapy (VMAT) techniques. Organs-at-risk (OAR) dose-volume histogram (DVH) statistics were compared along with total plan monitor units (MU). To evaluate delivery efficiency, actual beam-on time for five patients’ plans were recorded and compared. To evaluate the impact of MLC performance parameters on plan quality, virtual MLC models were generated by matching Truebeam MLC’s parameters to those of the Halcyon dual-layer MLC both individually and combined. OAR doses were then compared between these virtual MLCs, the Truebeam MLC, and the actual Halcyon MLC.ResultsOverall the Halcyon dual-layer MLC provided similar plan quality compared to Truebeam MLC for VMAT plans, and improved sparing for majority of the OARs when using IMRT. Paired comparison showed median dose differences in mean doses to the parotids, cochlea, esophagus, and larynx ranged from -0.83 Gy to 0.37 Gy for VMAT, and from -4.79 Gy to -0.04 Gy for IMRT, with negative values indicating improved performance by Halcyon. Despite a slight increase in plan MU, the Halcyon reduced the total beam-on time by 42.8 ± 8.5%. Virtual MLC simulations demonstrated that matching MLC transmission accounted for nearly half of the total dose difference between Halcyon and Truebeam IMRT plans.ConclusionWhen compared to the Truebeam, the Halcyon’s dual-layer MLC achieved similar plan quality using VMAT, and improved OAR sparing using IMRT, while providing nearly twice as fast treatment delivery. Reduction in MLC transmission is the dominating factor contributing to dosimetric differences in OAR sparing.

P154] Investigation of in vivo dosimetry for deep inspiration breath-hold technique in breast cancer radiotherapy

Purpose In this study, the availability of in vivo dosimetry was investigated for high accuracy applicability of the deep inspiration breathhold (DIBH) RT technique. Methods Early stage 10 left breast cancer patients underwent CT scans with breath control system and RT plans were created by using FinF technique.It was aimed to investigate the compliance of the doses received during the treatment with the intended doses of the patients by IVD. The skin depth was assumed to be 0.07 mm, the depth recommended in the ICRU 39 report. Doses calculated in TPS were compared by measured doses which were obtained by placing the TLDs and OSLs at 3, 5.5, 8 and 15 cm (contralateral breast) distances from the center of the beam on the patient’s skin and around the thyroid organ in every single fraction. Results In the study, the skin dose measurements were taken with TLD and OSL at all points. The average differences between the measured and calculated doses were found to be −15.88% and −15.65% for TLD and OSL, respectively. The average median dose differences were obtained for TLD and OSL, respectively; 2.99% (min: −83.59; max: 46.87) and −9.65% (min: −90.25; max: 57.56) for contralateral breast, 16.75% (min: −26.12; max: 91.35); −17.63% (min: −43.73; max: 84.79) for thyroid. Conclusions Measured and calculated contralateral breast dose differences change from patient to patient.Although the dose differences found for the thyroid are more or less different from each other, the values obtained by TLD were lower than the values calculated by TPS, whereas the values measured by OSL were found higher than the values calculated by TPS. Surface dose measurements by using OSL and TLD have been found to be approximately 15% greater than TPS and no superiority has been seen in the systems used in skin dosimetry. Besides, out of field doses found by OSL were higher than TPS.

Low‐cost Kinect Version 2 imaging system for breath hold monitoring and gating: Proof of concept study for breast cancer VMAT radiotherapy

Voluntary inspiration breath hold (VIBH) for left breast cancer patients has been shown to be a safe and effective method of reducing radiation dose to the heart. Currently, VIBH protocol compliance is monitored visually. In this work, we establish whether it is possible to gate the delivery of radiation from an Elekta linac using the Microsoft Kinect version 2 (Kinect v2) depth sensor to measure a patient breathing signal. This would allow contactless monitoring during VMAT treatment, as an alternative to equipment–assisted methods such as active breathing control (ABC). Breathing traces were acquired from six left breast radiotherapy patients during VIBH. We developed a gating interface to an Elekta linac, using the depth signal from a Kinect v2 to control radiation delivery to a programmable motion platform following patient breathing patterns. Radiation dose to a moving phantom with gating was verified using point dose measurements and a Delta4 verification phantom. 60 breathing traces were obtained with an acquisition success rate of 100%. Point dose measurements for gated deliveries to a moving phantom agreed to within 0.5% of ungated delivery to a static phantom using both a conventional and VMAT treatment plan. Dose measurements with the verification phantom showed that there was a median dose difference of better than 0.5% and a mean (3% 3 mm) gamma index of 92.6% for gated deliveries when using static phantom data as a reference. It is possible to use a Kinect v2 device to monitor voluntary breath hold protocol compliance in a cohort of left breast radiotherapy patients. Furthermore, it is possible to use the signal from a Kinect v2 to gate an Elekta linac to deliver radiation only during the peak inhale VIBH phase.

Prediction of GTV median dose differences eases Monte Carlo re-prescription in lung SBRT

Background and PurposeThe use of Monte Carlo (MC) dose calculation algorithm for lung patients treated with stereotactic body radiotherapy (SBRT) can be challenging. Prescription in low density media and time-consuming optimization conducted CyberKnife centers to propose an equivalent path length (EPL)-to-MC re-prescription method based on GTV median dose. Unknown at the time of planning, GTV D50% practical application remains difficult. The current study aims at creating a re-prescription predictive model in order to limit conflicting dose value during EPL optimization. Material and Methods129 patients planned with EPL algorithm were recalculated with MC. Relative GTV_D50% discrepancies were assessed and influencing parameters identified using wrapper feature selection. Based on best descriptive parameters, predictive nomogram was built from multivariate linear regression. EPL-to-MC OARs near max-dose discrepancies were reported. ResultsThe differences in GTV_D50% (median 10%, SD: 9%) between MC and EPL were significantly (p < .001) impacted by the lesion’s surface-to-volume ratio and the average relative electronic density of the GTV and the GTV’s 15 mm shell. Built upon those parameters, a nomogram (R2 = 0.79, SE = 4%) predicting the GTV_D50% discrepancies was created. Furthermore EPL-to-MC OAR dose tolerance limit showed a strong linear correlation with coefficient range [0.84–0.99]. ConclusionGood prediction on the required re-prescription can be achieved prior planning using our nomogram. Based on strong linear correlation between EPL and MC for OARs near max-dose, further restriction on dose constraints during the EPL optimization can be warranted. This a priori knowledge eases the re-prescription process in limiting conflicting dose value.

OC-0349: Prediction of GTV median dose differences benefit Monte Carlo re-prescription in lung SBRT

OC-0349: Prediction of GTV median dose differences benefit Monte Carlo re-prescription in lung SBRT

Prospective comparison of rectal dose reduction during intracavitary brachytherapy for cervical cancer using three rectal retraction techniques

PurposeTo compare three rectal retraction methods on dose to organs at risk, focusing on rectal dose, in cervix cancer patients treated with high-dose-rate intracavitary brachytherapy. Methods and MaterialsA prospective study was conducted on patients with cervical carcinoma treated with chemoradiotherapy, including external beam radiation and four fractions of high-dose-rate intracavitary brachytherapy prescribed to Point A using a ring and tandem applicator under conscious sedation. Rectal retraction methods included: a rectal retractor blade (RR), vaginal gauze packing (VP), and a tandem Foley balloon (FB). All three methods were used in all patients. The RR was used first, and the following applications were randomly assigned to VP or FB. CT planning was used to calculate D2cc for rectum, sigmoid, small bowel, and bladder. The Wilcoxon signed rank test was used to determine if the median dose differences between methods were statistically significant. ResultsIn these 11 patients, median dose (min, max) in cGy to the rectum using RR, FB, and VP was 131 (102, 165), 199 (124, 243), and 218 (149, 299), respectively. The RR demonstrated lower median intrapatient doses to rectum compared with FB and VP (−55 cGy; p = 0.014 and −76 cGy; p = 0.004, respectively). The RR also resulted in lower sigmoid doses. No differences in dose were observed between the VP and FB methods. ConclusionThe rectal retractor significantly reduced the dose to rectum and sigmoid compared with FP and VP. In patients treated under conscious sedation, the RR method provides the best rectal sparing. There were no significant differences in dose observed between the FB and VP techniques.

Voluntary breath-holding for breast cancer radiotherapy is consistent and stable.

To evaluate breath-hold stability and constancy for a voluntary breath-hold (VBH) technique in a retrospective analysis. Movie loop sequences of electronic portal image data from multiple breath holds in a cohort of 19 patients were used to assess within and between breath-hold stability. In vivo dosimetry data based on electronic portal imaging (EPI) were analysed for 31 VBH patients plus a cohort of free-breathing (FB) patients to provide a reference. A phantom experiment simulated the impact on dose of FB, breath hold and unplanned release of breath hold. 165/174 (93%) movie loop data sets had no detectable displacement. For the remaining 12, median displacement = 1.5 mm and maximum displacement = 3 mm (one patient on one fraction). In vivo dosimetry data analysis showed a median dose difference measured to planned of -0.2% (VBH) and -0.1% (FB). Dose distribution evaluation (γ) pass rates were 84% (VBH) and 91% (FB) including the lung region; 93% and 96% with a lung override. Unplanned release of phantom breath-hold position changed median dose by ≤1% and degraded γ pass rates to 79-62%. Failing regions were mostly in the periphery of the treated volume. The data confirmed that multiple VBHs using visual monitoring are stable; in vivo dose verification via EPI was within expected and acceptable levels. These data provide further reassurance that VBH is a safe technique for cardiac sparing breast radiotherapy and support its rapid, widespread implementation.

SU-E-T-138: Dosimetric Verification For Volumetric Modulated Arc Therapy Cranio-Spinal Irradiation Technique

Purpose: Dosimetric feasibility of cranio-spinal irradiation with volumetric modulated arc therapy (VMAT-CSI) technique in terms of dose distribution accuracy was investigated using a humanlike phantom. Methods: The OARs and PTV volumes for the Rando phantom were generated on supine CT images. Eclipse (version 8.6) TPS with AAA algorithm was used to create the treatment plan with VMAT-CSI technique. RapidArc plan consisted of cranial, upper spinal (US) and lower spinal (LS) regions that were optimized in the same plan. US field was overlapped by 3cm with cranial and LS fields. Three partial arcs for cranium and 1 full arc for each US and LS region were used. The VMAT-CSI dose distribution inside the Rando phantom was measured with thermoluminescent detectors (TLD) and film dosimetry, and was compared to the calculated doses of field junctions, target and OARs. TLDs were placed at 24 positions throughout the phantom. The measured TLD doses were compared to the calculated point doses. Planar doses for field junctions were verified with Gafchromic films. Films were analyzed in PTW Verisoft application software using gamma analysis method with the 4 mm distance to agreement (DTA) and 4% dose agreement criteria. Results: TLD readings demonstrated accurate dose delivery, with amore » median dose difference of -0.3% (range: -8% and 12%) when compared with calculated doses for the areas inside the treatment portal. The maximum dose difference was 12% higher in testicals that are outside the treatment region and 8% lower in lungs where the heterogeinity was higher. All planar dose verifications for field junctions passed the gamma analysis and measured planar dose distributions demonstrated average 97% agreement with calculated doses. Conclusion: The dosimetric data verified with TLD and film dosimetry shows that VMAT-CSI technique provides accurate dose distribution and can be delivered safely.« less

Primary squamous cell carcinoma of the vagina: Prognostic factors, treatment patterns, and outcomes

ObjectivePrimary squamous cell carcinoma (SCCA) of the vagina is a rare malignancy with limited data to guide treatment. We evaluated prognostic factors and outcomes for patients with primary vaginal SCCA treated with definitive radiation therapy at a single institution. MethodsA retrospective analysis was performed on patients treated for primary vaginal SCCA from 1959 to 2011. ResultsNinety-one patients with primary vaginal SCCA were treated with definitive radiation therapy. Thirty-eight patients had FIGO stage I, 28 stage II, 13 stage III, and 12 stage IV disease. The mean total dose was 70.1Gy. Two-year overall survival (OS), locoregional control rate (LRC), and distant metastasis-free survival by stage were, respectively: stage I: 96.2%, 80.6%, 87.5%; stage II: 92.3%, 64.7%, 84.6%; stage III: 66.6%, 44.4%, 50.0%; and stage IV: 25.0%, 14.3%, 25.0%. Treatment with total dose over 70Gy was associated with improved OS (p=0.0956) and LRC (p=0.055). There was a significant difference in median dose received by patients who developed grade 3/4 toxicity compared to those who did not (82.9Gy versus 70.0Gy, p=0.0019). None of the 10 patients treated with IMRT experienced locoregional recurrence or grade 3/4 toxicity. Tumor size larger than 4cm was associated with worse OS (p=0.0034) and LRC (p=0.006). ConclusionsOur analysis suggests that the optimal dose for definitive treatment of SCCA of the vagina lies between 70 and 80Gy. Treatment with IMRT may allow for dose escalation with reduced toxicity and excellent LRC. Tumor size over 4cm is associated with inferior outcomes and may require additional treatment modalities.

Plasma quetiapine in relation to prescribed dose and other factors: data from a therapeutic drug monitoring service, 2000–2011

Suggested predose plasma quetiapine target ranges for effective therapy in schizophrenia lie between 50 and 500 µg/l. We aimed to examine data from a quetiapine therapeutic drug monitoring (TDM) service to assess the plasma quetiapine concentrations attained at specified doses in clinical practice. We studied TDM data from patients given immediate-release quetiapine in the period 2000-2011. There were 946 samples from 487 patients (257 males, age at time of first sample, median [range] 34 [14-87] years, and 230 females, age at time of first sample, median [range] 38 [10-92] years). The plasma quetiapine concentration was <50 and <100 µg/l in 30% and 50% of samples, respectively (no quetiapine detected in 9% of samples). The relationship between dose and plasma quetiapine was poor. The mean (95% confidence interval [CI]) quetiapine dose was higher (t = 3.6, df = 446, p <0.01) in males versus females (641 [600-1240] and 548 [600-943] mg/day, respectively), although there was no difference in median dose (600 mg/day) or in the mean (95% CI) plasma quetiapine concentrations attained. Smoking habit had no discernible effect on plasma quetiapine concentration. There was a poor relationship between dose and plasma quetiapine concentration in this study, as found by others. This is probably because of the short plasma half-life of the drug, at least in part. Nevertheless, quetiapine TDM can help assess adherence and measurement of quetiapine metabolites, notably N-desalkylquetiapine, as well as quetiapine itself may enhance the value of quetiapine TDM in future.

Verification of dose distribution for volumetric modulated arc therapy total marrow irradiation in a humanlike phantom

Volumetric modulated arc therapy (VMAT) treatment planning studies have been reported to provide good target coverage and organs at risk (OARs) sparing in total marrow irradiation (TMI). A comprehensive dosimetric study simulating the clinical situation as close as possible is a norm in radiotherapy before a technique can be used to treat a patient. Without such a study, it would be difficult to make a reliable and safe clinical transition especially with a technique as complicated as VMAT-TMI. To this end, the dosimetric feasibility of VMAT-TMI technique in terms of treatment planning, delivery efficiency, and the most importantly three dimensional dose distribution accuracy was investigated in this study. The VMAT-TMI dose distribution inside a humanlike Rando phantom was measured and compared to the dose calculated using RapidArc especially in the field junctions and the inhomogeneous tissues including the lungs, which is the dose-limiting organ in TMI. Three subplans with a total of nine arcs were used to treat the planning target volume (PTV), which was determined as all the bones plus the 3 mm margin. Thermoluminescent detectors (TLDs) were placed at 39 positions throughout the phantom. The measured TLD doses were compared to the calculated plan doses. Planar dose for each arc was verified using mapcheck. TLD readings demonstrated accurate dose delivery, with a median dose difference of 0.5% (range: -4.3% and 6.6%) from the calculated dose in the junctions and in the inhomogeneous medium including the lungs. The results from this study suggest that RapidArc VMAT technique is dosimetrically accurate, safe, and efficient in delivering TMI within clinically acceptable time frame.

Randomized Controlled Trials of COX-2 Inhibitors

Naproxen, ibuprofen and diclofenac are frequently used as comparators in randomized controlled trials (RCTs) on the safety and efficacy of cyclooxygenase (COX)-2 inhibitors. Different comparator doses may influence the results of RCTs. It has been hypothesized that RCTs of COX-2 inhibitors where different doses were administered resulted in different conclusions about the cardiovascular safety of COX-2 inhibitors. High comparator doses may let COX-2 inhibitors look better in terms of safety, while low comparator doses may result in the opposite. The aim of the study was to compare doses of COX-2 inhibitors and comparator drugs used in RCTs, and to investigate dose changes over time. We searched the Cochrane Central Register of Controlled Trials, The Cochrane Library for published Cochrane reviews, Clinicaltrials.gov and PubMed, for RCTs between 1995 and 2009 in which celecoxib or rofecoxib were compared with naproxen, ibuprofen or diclofenac. All articles labelled as RCTs mentioning rofecoxib or celecoxib and one or more of the comparator drugs in the title and/or abstract were included. We extracted information on doses of both non-selective NSAIDs and selective COX-2 inhibitors used in the RCTs, and study year. The Mann-Whitney test was used to compare the difference in median dose in rofecoxib and celecoxib RCTs. Linear regression was performed to evaluate trends in dosage over time. For comparisons between COX-2-inhibitors, celecoxib trials after the 2004 market withdrawal of rofecoxib were excluded. Median defined daily dose (DDD) of celecoxib (2.00) was higher than the median DDD of rofecoxib (1.00; p < 0.001), whereas non-selective NSAID doses were comparable in rofecoxib (2.00) and celecoxib (2.00; p = 0.988) studies. In both groups, the non-selective NSAID doses decreased over time (B [regression coefficient] = -0.07; p = 0.28, and B = -0.054; p = 0.09, respectively). In contrast, the DDDs of rofecoxib increased slightly over time (B = 0.037; p = 0.28), whereas the celecoxib DDDs decreased over time (B = -0.081; p = 0.09). In due course, the contrasts between DDDs of COX-2 inhibitors and non-selective NSAIDs converged, both in rofecoxib and celecoxib RCTs; therefore, doses have become more comparable in recent years because of differences in steepness of two decreasing dose trends in the case of celecoxib, and opposing dose trends in the case of rofecoxib. Although the dose trends over time differed for RCTs comparing rofecoxib and celecoxib with diclofenac, ibuprofen or naproxen, the results of our study do not support the hypothesis that dose trends influenced the decision to continue marketing celecoxib after the withdrawal of rofecoxib because the overall median DDD of celecoxib was substantially higher than the median DDD of rofecoxib, while non-selective NSAID DDDs were comparable.

WE‐C‐BRB‐03: Feasibility Study for Total Marrow Irradiation with RapidArc Volumetric Arc Therapy (VMAT‐TMI)

Purpose: To investigate the dosimetric feasibility of VMAT‐TMI technique in terms of treatment planning and delivery efficiency and accuracy for a Rando phantom using Eclipse RapidArc technology. Methods: Total body irradiation (TBI) has been an integral part of pre‐conditioning regimens for the treatment of hematologic malignancies. Normal tissue toxicity is a common complication of TBI inclusive regimens especially at doses higher than 12 Gy due to inhomogeneous and excessive dose to organs at risk (OARs). Fixed gantry linear accelerator (linac) and Tomotherapy intensity modulated total bone marrow (IM‐TMI) techniques have been reported to reduce doses to OARs. However, the treatment time of more than one hour with both techniques may limit their clinical application. Volumetric modulated arc therapy (VMAT) may be able to increase the treatment delivery efficiency while increasing the target conformality and reducing the radiation dose to OARs. In order to treat all the bones in the Rando phantom, three sub‐plans with a total of nine arcs were used. A total of 100 thermoluminescent detectors (TLDs) were placed at 39 positions throughout the phantom. The measured TLD doses were compared to the calculated plan doses. Planar dose for each arc was verified using MapCheck and MapPhan. Results: Excellent target coverage with the prescription dose and dose reduction to the OARs were achieved similar to the fixed gantry linac IM‐TMI technique. The number of monitor units was decreased by 50%, while the delivery efficiency increased by more than 60%. TLD readings demonstrated accurate dose delivery, with a median dose difference of 0.5% from the calculated dose. Planar dose distributions of all arcs satisfied the 3% and 3 mm gamma criteria with an average pass rate of 97.8%. Conclusions: Results from this study suggest that RapidArc VMAT‐TMI technique is clinically feasible.This study is supported by Varian Medical Systems

Reduced Acute Bowel Toxicity in Patients Treated With Intensity-Modulated Radiotherapy for Rectal Cancer

We have previously shown that intensity-modulated radiotherapy (IMRT) can reduce dose to small bowel, bladder, and bone marrow compared with three-field conventional radiotherapy (CRT) technique in the treatment of rectal cancer. The purpose of this study was to review our experience using IMRT to treat rectal cancer and report patient clinical outcomes. A retrospective review was conducted of patients with rectal cancer who were treated at Mayo Clinic Arizona with pelvic radiotherapy (RT). Data regarding patient and tumor characteristics, treatment, acute toxicity according to the Common Terminology Criteria for Adverse Events v 3.0, tumor response, and perioperative morbidity were collected. From 2004 to August 2009, 92 consecutive patients were treated. Sixty-one (66%) patients were treated with CRT, and 31 (34%) patients were treated with IMRT. All but 2 patients received concurrent chemotherapy. There was no significant difference in median dose (50.4 Gy, CRT; 50 Gy, IMRT), preoperative vs. postoperative treatment, type of concurrent chemotherapy, or history of previous pelvic RT between the CRT and IMRT patient groups. Patients who received IMRT had significantly less gastrointestinal (GI) toxicity. Sixty-two percent of patients undergoing CRT experienced ≥Grade 2 acute GI side effects, compared with 32% among IMRT patients (p = 0.006). The reduction in overall GI toxicity was attributable to fewer symptoms from the lower GI tract. Among CRT patients, ≥Grade 2 diarrhea and enteritis was experienced among 48% and 30% of patients, respectively, compared with 23% (p = 0.02) and 10% (p = 0.015) among IMRT patients. There was no significant difference in hematologic or genitourinary acute toxicity between groups. In addition, pathologic complete response rates and postoperative morbidity between treatment groups did not differ significantly. In the management of rectal cancer, IMRT is associated with a clinically significant reduction in lower GI toxicity compared with CRT. Further study is needed to evaluate differences in late toxicity and long-term efficacy.

Consequences of leaf calibration errors on IMRT delivery

IMRT treatments using multi-leaf collimators may involve a large number of segments in order to spare the organs at risk. When a large proportion of these segments are small, leaf positioning errors may become relevant and have therapeutic consequences. The performance of four head and neck IMRT treatments under eight different cases of leaf positioning errors has been studied. Systematic leaf pair offset errors in the range of ±2.0 mm were introduced, thus modifying the segment sizes of the original IMRT plans. Thirty-six films were irradiated with the original and modified segments. The dose difference and the gamma index (with 2%/2 mm criteria) were used for evaluating the discrepancies between the irradiated films. The median dose differences were linearly related to the simulated leaf pair errors. In the worst case, a 2.0 mm error generated a median dose difference of 1.5%. Following the gamma analysis, two out of the 32 modified plans were not acceptable. In conclusion, small systematic leaf bank positioning errors have a measurable impact on the delivered dose and may have consequences for the therapeutic outcome of IMRT.