Increase In Mean Dose Research Articles

Strict bladder filling and rectal emptying during prostate SBRT: Does it make a dosimetric or clinical difference?

BackgroundTo evaluate inter-fractional variations in bladder and rectum during prostate stereotactic body radiation therapy (SBRT) and determine dosimetric and clinical consequences.MethodsEighty-five patients with 510 computed tomography (CT) images were analyzed. Median prescription dose was 40 Gy in 5 fractions. Patients were instructed to maintain a full bladder and empty rectum prior to simulation and each treatment. A single reviewer delineated organs at risk (OARs) on the simulation (Sim-CT) and Cone Beam CTs (CBCT) for analyses.ResultsBladder and rectum volume reductions were observed throughout the course of SBRT, with largest mean reductions of 86.9 mL (19.0%) for bladder and 6.4 mL (8.7%) for rectum noted at fraction #5 compared to Sim-CT (P < 0.01). Higher initial Sim-CT bladder volumes were predictive for greater reduction in absolute bladder volume during treatment (ρ = − 0.69; P < 0.01). Over the course of SBRT, there was a small but significant increase in bladder mean dose (+ 4.5 ± 12.8%; P < 0.01) but no significant change in the D2cc (+ 0.8 ± 4.0%; P = 0.28). The mean bladder trigone displacement was in the anterior direction (+ 4.02 ± 6.59 mm) with a corresponding decrease in mean trigone dose (− 3.6 ± 9.6%; P < 0.01) and D2cc (− 6.2 ± 15.6%; P < 0.01). There was a small but significant increase in mean rectal dose (+ 7.0 ± 12.9%, P < 0.01) but a decrease in rectal D2cc (− 2.2 ± 10.1%; P = 0.04). No significant correlations were found between relative bladder volume changes, bladder trigone displacements, or rectum volume changes with rates of genitourinary or rectal toxicities.ConclusionsDespite smaller than expected bladder and rectal volumes at the time of treatment compared to the planning scans, dosimetric impact was minimal and not predictive of detrimental clinical outcomes. These results cast doubt on the need for excessively strict bladder filling and rectal emptying protocols in the context of image guided prostate SBRT and prospective studies are needed to determine its necessity.

Intellectual changes after radiation for children with brain tumors: which brain structures are most important?

The objective of this study was to evaluate the contribution of radiation dose to different intracranial structures on changes in intellectual function for children with brain tumors. We evaluated children with brain tumors treated in 2005-2017 who had longitudinal neuropsychological assessments and available photon dosimetric data (if radiation therapy [RT] given). Full Scale Intelligence Quotient (FSIQ) and index scores were evaluated (perceptual reasoning index [PRI], processing speed index [PSI], verbal comprehension index [VCI], and working memory index [WMI]). Multivariable linear mixed effects models were used to model endpoints, with age at RT and dose to different brain regions as fixed effects and patient-specific random intercepts. P-values (P*) were adjusted for multiple comparisons. Sixty-nine patients were included, 56 of whom received RT. Median neuropsychological follow-up was 3.2 years. Right temporal lobe mean dose was strongly associated with decline in FSIQ (P* = 0.005); with each gray increase in mean dose, there was a decrease of 0.052 FSIQ points per year. Dose to 50% (D50) of the supratentorial brain was associated with decline in PSI (P* = 0.006) and WMI (P* = 0.001). Right and left hippocampus D50 were individually strongly associated with declines in VCI (P* = 0.009 for each). Presence of a ventriculoperitoneal shunt decreased FSIQ by 10 points. We reported associations between dosimetry to specific brain regions and intellectual outcomes, with suggested avoidance structures during RT planning. These models can help clinicians anticipate changes in neurocognition post-RT and guide selection of an optimal RT plan.

Cardiac Irradiation Predicts Activity Decline in Patients Receiving Concurrent Chemoradiation for Locally Advanced Lung Cancer

Many patients with lung cancer are inactive due to their disease and underlying comorbidities, and activity levels can decline further during cancer therapy. Here we explore dosimetric predictors of activity decline in a cohort of patients who underwent continuous activity monitoring during definitive concurrent chemoradiotherapy (CRT) for locally advanced lung cancer. We identified patients who participated in prospective clinical trials involving the use of a commercial fitness tracker throughout the course of CRT. For each patient, we applied linear regression to log-transformed daily step counts to compute the weekly rate of activity change from 1 week before radiation therapy (RT) initiation to 2 weeks after RT completion. Clinical and dosimetric factors were tested as predictors of activity change using linear regressions. Forty-six patient met the eligibility criteria. Median age was 66 years (range, 38-90). Pretreatment Eastern Cooperative Oncology Group performance status was 0, 1, and 2 for 17%, 70%, and 13%, respectively. Mean lung dose ranged from 5.0 to 23.5 Gy, mean esophagus dose from 1.1 to 39.6 Gy, and mean heart dose from 0.6 to 31.5 Gy. Median daily step count average was 5861 (interquartile range, 3540-8282) before RT and 3422 (interquartile range, 2364-5395) 2 weeks after RT completion. Rate of activity change was not significantly associated with age, performance status, or mean RT dose received by lungs or esophagus. In multivariate analysis, mean heart dose was significantly associated with rate of activity decline, with a 3.1% reduction in step count per week for every 10 Gy increase in mean heart dose (95% confidence interval: 0.5-5.7, P = .023). Extent of cardiac irradiation is associated with the rate of physical activity decline during CRT for lung cancer. Our novel finding contributes to the growing body of evidence that adverse effects of cardiac irradiation may be manifested at early time points.

Dosimetric accuracy of delivering SBRT using dynamic arcs on Cyberknife.

PurposeSeveral studies have demonstrated potential improvements in treatment time through the use of dynamic arcs for delivery of stereotactic body radiation therapy (SBRT) on Cyberknife. However, the delivery system has a finite accuracy, so that potential exists for dosimetric uncertainties. This study estimates the expected dosimetric accuracy of dynamic delivery of SBRT, based on realistic estimates of the uncertainties in delivery parameters.MethodsFive SBRT patient cases (prostate A — conventional, prostate B — brachytherapy‐type, lung, liver, partial left breast) were retrospectively studied. Treatment plans were produced for a fixed arc trajectory using fluence optimization, segmentation, and direct aperture optimization. Dose rate uncertainty was modeled as a smoothly varying random fluctuation of ± 1.0%, ±2.0% or ± 5.0% over a time period of 10, 30 or 60 s. Multileaf collimator uncertainty was modeled as a lag in position of each leaf up to 0.25 or 0.5 mm. Robot pointing error was modeled as a shift of the target location, with the direction of the shift chosen as a random angle with respect to the multileaf collimator and with a random magnitude in the range 0.0–1.0 mm at the delivery nodes and with an additional random magnitude of 0.5–1.0 mm in between the delivery nodes. The impact of the errors was investigated using dose‐volume histograms.ResultsUncertainty in dose rate has the effect of varying the total monitor units delivered, which in turn produces a variation in mean dose to the planning target volume. The random sampling of dose rate error produces a distribution of mean doses with a standard deviation proportional to the magnitude of the dose rate uncertainty. A lag in multileaf collimator position of 0.25 or 0.5 mm produces a small impact on the delivered dose. In general, an increase in the PTV mean dose of around 1% is observed. An error in robot pointing of the order of 1 mm produces a small increase in dose inhomogeneity to the planning target volume, sometimes accompanied by an increase in mean dose by around 1%.ConclusionsBased upon the limited data available on the dose rate stability and geometric accuracy of the Cyberknife system, this study estimates that dynamic arc delivery can be accomplished with sufficient accuracy for clinical application. Dose rate variation produces a change in dose to the planning target volume according to the perturbation of total monitor units delivered, while multileaf collimator lag and robot pointing error typically increase the mean dose to the planning target volume by up to 1%.

Quel impact de la RCMI des carcinomes nasopharyngés sur les structures glandulaires ?

PurposeThe aim of this work is to evaluate the anatomical changes of the glandular structures during the NPC IMRT and to study their dosimetric impacts. Patients and methodsTwenty patients receiving IMRT for NPC were included. For each patient, a second dosimetric CT was performed at a dose of 38Gy, which was fused with the initial planning dosimetric CT. We calculated the volume percent change, the positional and dosimetric variation between the 2 scanners for the glandular structures (parotid, submaxillary, thyroid and pituitary). ResultsWe observed a decrease in the volume of right and left parotids (−27.9% and −27.54%). It was correlated with the initial dose planned at its level. For the sub maxillary glands, the decrease was −36.1% on the right and −27.28% on the left. The value of reduction of the thyroid gland was −18.01%. A medial supra-millimeter migration of 2 and 1.15mm was found for right and left parotid glands respectively, correlated with GTV N reduction volume. We found a significant increase in mean doses for the parotid glands. It was 1.8±2.3Gy for the right and 1.5±2.7Gy for the left. For the right sub maxillary gland, the increase was about 0.35±2Gy and 3.79±5.2Gy for the thyroid. ConclusionThe modifications observed for glandular structures during NPC IMRT can explain the different toxicities caused by radiation. It seems also that a careful adaptation of the treatment plan should be considered during therapy.

Conversion of Intrathecal Opioids to Fentanyl in Chronic Pain Patients With Implantable Pain Pumps: A Retrospective Study

Conversion between routes such as intravenous (IV), epidural (EP), and intrathecal (IT) routes for morphine is well established. Conversion ratios for IV:EP:IT fentanyl and conversion from IT morphine/hydromorphone to IT fentanyl have been challenging given the lipophilic nature of fentanyl. Our study reviews the outcomes and conversion ratios reached after converting IT opioids from morphine/hydromorphone to fentanyl in patients with IT pumps. After Institutional Review Board approval at Henry Ford Health System, a chart review was performed on all patients who had Synchromed II IT pumps implanted 2009-2016 and were converted from morphine/hydromorphone to fentanyl. The chart review included the initial fentanyl dose and fentanyl IV:IT conversion ratio, eventual IT fentanyl dose, and IV:IT conversion ratio reached to give superior VAS from previous IT opioid. Wilcoxon non-paired signed rank test was used to examine the change in fentanyl dosage and IV:IT conversion ratio. The mean IT morphine equivalent dose at initial conversion was 15.8 mg/day, and the mean fentanyl IT starting dose was 0.73 mg/day (SD = 1.37 mg). The mean fentanyl dose at the end of titration was 0.94 mg/day (SD = 2.05 mg) which represented a significant 25.1% mean dose increase (P = 0.004). The initial mean IV:IT fentanyl conversion ratio was 38.7:1 (SD = 33.01), but the mean IV:IT fentanyl conversion ratio at end of titration with better analgesia was significantly lower at 32.9:1 (SD = 27.1) (P = 0.016). Given the pharmacokinetics of lipophilic fentanyl compared to hydrophilic morphine/hydromorphone, the current conversion ratio of IV fentanyl to IT fentanyl and IV morphine to IT fentanyl appears to be conservative.

Pilot Study Comparing the Efficacy, Safety, Convertibility, and Tacrolimus Trough Levels of Twice-Daily Tacrolimus (Prograf) to Once-Daily Tacrolimus (Advagraf) Among Standard-Risk Kidney Transplant Patients at the National Kidney and Transplant Institute

BackgroundRecently, a once-daily formulation of tacrolimus (Advagraf) was released in the Philippines. Studies have shown that these 2 formulations are bioequivalent at a 1:1 conversion. This study aims to determine the efficacy, safety, convertibility, and tacrolimus trough level of once-daily tacrolimus at the end of 6 months post transplant. MethodsThis is a randomized study among standard-risk primary kidney transplant patients performed at the National Kidney and Transplant Institute, Philippines. A total of 40 patients completed the 6-month follow-up. Patients in Group A who failed to meet the criteria for conversion to once-daily tacrolimus were considered to have reached the end of the study, while patients who satisfied the conversion criteria will be followed up for an additional 6 months. ResultsBaseline characteristics were similar in both groups. The area under the curve, maximum concentration, time to achieve the maximum concentration, and the coefficient of variation were similar. The twice-daily tacrolimus (Prograf) group patients had significantly higher mean tacrolimus trough levels than the Group B once-daily tacrolimus patients. An increase of a once-daily tacrolimus mean dose of 8% was required to achieve a therapeutic drug level post conversion. The graft and patient survival were 100%. There was no biopsy-proven acute rejection noted either both group. ConclusionIn conclusion, conversion from twice-daily tacrolimus to once-daily tacrolimus in kidney transplant in both de novo and converted patients after KT is safe, ensuring greater stability of drug blood concentrations than the standard form. The results also suggest an 8% increase when converting stable KT patients from twice-daily tacrolimus to once-daily tacrolimus.

Dose to Pharyngeal Constrictors and Esophagus Is Associated with Activity Decline during Concurrent Chemoradiation for Head and Neck Cancer

While concurrent chemoradiation (CCRT) for head and neck cancer (HNC) has been successful in achieving high cure rates, it is often accompanied by significant morbidity and declining quality of life. In this study, we explore dosimetric predictors of activity decline in a cohort of patients who prospectively underwent activity monitoring during concurrent chemoradiotherapy for locally advanced cancers of the head and neck. We identified patients treated with CCRT for HNC from three prospective studies in which fitness trackers were used to measure step count. In each subject, we measured the mean dose delivered to organs at risk in the head and neck including the oral cavity, parotid glands, and pharyngeal constrictors and esophagus as one structure. Mean doses were compared to the percentage change in mean weekly step count. Linear regression was used to evaluate dosimetric data as a predictor of activity change. Fifty-five subjects met eligibility criteria. Nineteen subjects were treated for oropharyngeal cancer, 14 for laryngeal cancer, 8 for nasopharyngeal cancer, 6 for hypopharyngeal cancer, 6 for oral cavity cancer, and 2 for other cancers of the head and neck. Median age was 61 (interquartile range [IQR]: 51 to 66). Median daily step count average was 5,319 (IQR: 2,830 to 7,486) before starting chemoRT and fell to 3,798 (IQR: 2,321 to 5,107) five weeks into chemoRT. Median mean dose to the pharyngeal constrictors and esophagus was 45 Gy (IQR: 39 to 49 Gy). Mean dose to the pharyngeal constrictors and esophagus was associated with the rate of activity decline, with a 3.8% reduction in step count per week for every 10 Gy increase in mean dose (p=0.019, 95% CI: 0.6 to 7.0%). Mean dose to other structures evaluated did not significantly correlate with rate of activity decline. For a patient who averages 6,000 steps per day at baseline and is treated with a 7-week course of CCRT, the predicted daily step count post-treatment with a mean dose of 30 Gy to the pharyngeal constrictors and esophagus is approximately 2,600, compared to 1400 with a mean dose of 50 Gy. The mean dose to the pharyngeal constrictors and esophagus was associated with the rate of physical activity decline during CCRT for head and neck cancer. This data provides additional support that lowering mean dose to the pharyngeal constrictors and esophagus without compromising target volume coverage is key to minimizing treatment toxicities and improving tolerability of treatment.

Abstract P3-12-25: Dosimetric impact of patient rotation during prone breast radiotherapy

Abstract Purpose Prone positioning has been used as a viable alternative to conventional supine position for patients receiving breast radiation therapy. However, little research has been done exploring the axial rotation of patients toward the treated breast when “sinking” into the opening of the breast board and its potentially negative effects on dosimetric outcomes, which may include increased heart and lung dose. The physician may need to move the posterior border away from the chest wall to reduce heart and lung dose. Methodology 49 consecutive female patients with left sided early stage breast cancer treated at University of California Davis Medical Center were assessed from 2015 to 2018 (age range: 42-84 years, median age: 62 years). All patients underwent prone whole breast therapy with conventional external beam radiation therapy (EBRT) at doses of 50 Gy (n = 12) or hypofractionated at 42.56 Gy (n = 37). Treatment plans and dose volumes were retrospectively analyzed for each patient. Standard tangents were designed for each patient using clinical landmarks of the midaxillary line and midsternal line, which were then compared to the delivered tangent beams. The angle created between a vertical line centered on center sternum and a line drawn from center sternum to center spinal cord served to define degree of axial rotation. Breast depth was defined by the longest horizontal length from outer rib to edge of breast on sagittal view. Patients were divided into subgroups by degree of rotation and absolute breast depth. A two tailed paired Student's t-test was used for analysis. Results Overall mean heart and lung dose were 82.2 cGy and 50.43 cGy for the entire cohort, respectively. For standard tangents, patients with degree of rotation &amp;lt; 5 degrees in the prone position (n = 23) had significant lung sparing as compared to patients with degree of rotation &amp;gt; 5 cm (n = 26) (mean lung dose: 61.8 cGy vs 129.6 cGy, p = 0.00329). This was also seen for cardiac sparing (mean heart dose: 105.9 cGy vs 183.9 cGy, p = 0.000235). Even with reduction of posterior border for treatment delivery, there remained a significant increase in mean heart and lung dose with increased rotation (p = 0.038, p = 0.046). Although not statistically significant, for patients with &amp;gt; 5 degrees of rotation there was a trend toward increased reduction of the posterior border of the tangent (13 mm vs. 7.5 mm, p = 0.13). A significant predictor of increased rotation was breast depth &amp;gt; 10 cm (p = 0.01). Patients with absolute breast depth &amp;gt; 10 cm (n = 23) in the prone position had significant lung sparing as compared to patients with absolute breast depth &amp;lt; 10 cm (n = 26) (mean lung dose: 58.6 cGy vs 40.8 cGy, p = 0.042). Conclusion To our knowledge, this is the first dosimetric comparison of prone breast therapy exploring the degree of patient roll into the prone-breast setup cavity. This study demonstrates a significant increase in mean lung and heart dose when patient rotation is greater than 5 degrees. Given this, the posterior border may have to be reduced to prevent a higher than intended dose to the heart and lung. Proper attention during simulation is important to allow for optimal dose distribution and special attention should be paid to women with smaller breast size. Citation Format: Cheng K, Hoopingarner S, Wright C, Daly M, Fragoso R, Zhao X. Dosimetric impact of patient rotation during prone breast radiotherapy [abstract]. In: Proceedings of the 2018 San Antonio Breast Cancer Symposium; 2018 Dec 4-8; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2019;79(4 Suppl):Abstract nr P3-12-25.

Analysis of dose distribution between contemporary and standard planning in high-dose-rate endobronchial brachytherapy based on three-dimensional imaging.

PurposeThe treatment planning (TP) in high-dose-rate (HDR) endobronchial brachytherapy (EB) can be based on various forms of imaging. In the case of lung cancer, one-dimensional or two-dimensional imaging is standard. The dose coverage of the target (planning target volume – PTV) and organs at risk (OAR) is unknown, because the doses are calculated on the basis of the dose points. In modern brachytherapy, TP can be based on three-dimensional (3D) images. A plan created in this way contains information about the dose distribution in the PTV and OAR. Treatment plans based on standard planning (SP) and contemporary planning (CP) may differ in dose distribution in the patient’s body. Those differences between SP and CP may have an effect on the dose distribution in PTV, OAR and follow-up.Material and methodsThe study involved a group of 31 patients prospectively treated with advanced, inoperable, non-small cell lung cancer. As many as 76 treatment fractions were analyzed. Firstly, the coverage of the PTV parameter in 2D and 3D for V85, V100 and V115 was analyzed. Secondly, the dosage that OAR would take in was evaluated. In the cases of the heart, spinal cord and esophagus, the examined dosage equaled D0.1cm3, D1cm3 and D2cm3 for each of the structures. Also, heart D20 was examined as well as D5 for the healthy lung.ResultsThe median dose to the target volume was on average 43.33% higher for V85 with the contemporary planning method when compared to standard planning, with statistical significance. This came with the cost of an OAR mean dose increase of 1 Gy in D0.1cm3 for the heart.ConclusionsContemporary TP in EB allows one to adjust the dose distribution for individual clinical situations and allows one to improve clinical target volume (CTV) coverage, increase doses to the OAR and increase overall survival. The use of new methods of treatment plans in EB has significantly increased the follow-up to 21 months in a treated group of patients.

Evaluation of the effect of dental filling material on IMRT treatment planning in patient with nasopharyngeal cancer

Introduction: Presence of dental filling material (DFM) such as amalgam in treatment patient with nasopharyngeal cancer (NPC) is common. Streaking artifact Arising from this high density material in computed tomography (scan), may lead to perturbation in dose calculation and dose delivery. Widespread performance of intensity-modulated radiotherapy (IMRT) for NPC using anterior beams that pass through the part severely affected by artefacts prior to reaching the target volume, raise concern about the effect of dental amalgam. This study quantifies the effect of dental amalgam on dose distribution target volume and organ at risk, normal tissue complication probability (NTCP) and tumor control probability (TCP). Materials and Methods: IMRT optimization two groups of 15 early-stage NPC patients with or without dental amalgam by prescribe 70 Gy to planning target volume performed by using the prowess panther treatment planning system. We used one plan nine field arrangement (F9E) and three plan of seven field (F7, F7E, F7P) arrangement with different angle. The dose volume histograms (DVHs), monitor units (MUs), Homogeneity index (HI), conformity index (CI) and TCP of PTVs, NTCP spinal cord, brain stem and parotid gland were analyzed. Results: Mean dose PTV in F7, FVE, F7P and F9E plan were 71.25±1.55, 72.06±0.96, 71.65 ±1.28 and 71.82±0.53 respectively in patients with DFM and 71.52±1.02, 71.51 ± 0.61, 71.30 ± 0.61 and 71.95 ± 0.80 in patient without DFM, Showing slight increase in mean dose of target volume. V95 of PTV shows insignificant different in two group. Mean TCP in F7, FVE, F7P and F9E plan were 95.06±0.45%, 95.18±0.54%, 94.93 ±0.68% and 95.05±0.42% in patient with DFM and 94.86±0.62%, 94.74 ± 0.43%, 94.80 ± 0.58% and 95.50 ± 0.40% in patient without DFM that shows insignificant different in two group. Mean HI of PTV-70 in four plans in presence of DFM shows a slight decrease compared than the other. Mean and maximum dose Spinal cord, brain stem and parotid and their NTCP in presence of DFM show a slight decrease. Conclusion: According to the results, dental amalgam led to slight increase in TCP, mean dose target volume and slight decrease in mean dose some OARs and their NTCP. Average dose target volume and some organ at risk that consider for this study demonstrates no meaningful difference exist in DVH and biological parameter in two group of patient.

Does Modern Mediastinal Irradiation Cause Acute Subclinical Cardiac Toxicity? The Final Results of the MEDICATE Study (Mediastinal Irradiation and Cardio-Toxic Effects)

Radiation-induced heart disease (RIHD) is a late effect of cardiac irradiation (RT), and has been demonstrated in Hodgkin and non-Hodgkin lymphoma (HL and NHL), as well as in other thoracic cancers. There is no established measurement tool to detect acute cardiac damage, however high sensitivity troponin I and T (HsTnI and HsTNT) and imaging modalities such as echocardiograms have shown promise in some studies. We conducted a prospective trial to characterize acute and subacute cardiac damage in patients with thoracic cancers receiving cardiac radiation therapy. Patients were recruited from Hematology or Lung clinics at our institution if they were to receive cardiac RT of at least 30Gy to 5% of cardiac volume or a mean dose of 4Gy. Following consent and CT simulation, conformal (3D) and intensity modulated radiation therapy (IMRT) plans were created and cardiac structures were contoured. Patients had blood drawn for C-reactive protein (systemic inflammatory marker), HsTnI, HsTnT prior to RT and at 2 and 4 weeks into radiation therapy and completed 3D echocardiograms (3D) prior to RT and one year post-RT. Serum markers levels, imaging results and cardiac RT dose-volume data were analyzed for association. Twenty patients were recruited (including one who withdrew consent). The median value for “mean LV dose” was 3.1 Gy, and the median value for “mean total cardiac dose” was 8.6 Gy. Statistically significant positive associations between hsTnI and hsTnT at all time points, with an apparent decrease in mean value over time, and therewas a positive association between hsTnI increase between week 2 to 4 and maximum cardiac LV dose (ρ= 0.66, p=0.027). Although overall the mean change in LVEF for the whole cohort was non-significant (57.57 pre-RT and 56.4 post –RT), the mean dose to the left ventricle was associated with decrease in ejection fraction from pre-RT to one year echocardiograms (ρ= -0.46, p=0.054). An association was also seen between increase in left ventricular strain (LVS) and cardiac mean dose (ρ= 0.46, p=0.058), and cardiac dose to maximum 5% volume (ρ= 0.48, p=0.043). Our study suggests that hsTnI and hsTnT are intimately related, but detection of acute cardiac damage was not demonstrated potentially due to limitations of these markers, or low radiation therapy doses using modern techniques. Our results also suggest 3D echocardiogram findings may detect subacute damage at one year depending on dose to cardiac volumes. Given limitations of our study, we suggest that techniques to measure subacute cardiac damage including serum biomarkers and imaging modalities require further characterization to optimize their use. Identification early damage could facilitate the ability to closely monitor and intervene in patients at risk for RIHD. The current study is reassuring that modern quality-assured radiation techniques can prevent acute cardiac damage, even after anthracycline chemotherapy.

Creating and validating a warfarin pharmacogenetic dosing algorithm for Colombian patients.

PurposeWarfarin is an oral anticoagulant associated with adverse reaction to drugs due to wide inter- and intra-individual dosage variability. Warfarin dosage has been related to non-genetic and genetic factors. CYP2C9 and VKORC1 gene polymorphisms affect warfarin metabolism and dosage. Due to the central role of populations’ ethnical and genetic origin on warfarin dosage variability, novel algorithms for Latin American subgroups are necessary to establish safe anticoagulation therapy.Patients and methodsWe genotyped CYP2C9*2 (c.430C > T), CYP2C9*3 (c.1075A > C), CYP4F2 (c.1297G > A), and VKORC1 (−1639 G > A) polymorphisms in 152 Colombian patients who received warfarin. We evaluated the impact on the variability of patients’ warfarin dose requirements. Multiple linear regression analysis, using genetic and non-genetic variables, was used for creating an algorithm for optimal warfarin maintenance dose.ResultsMedian weekly prescribed warfarin dosage was significantly lower in patients having the VKORC1-1639 AA genotype and poor CYP2C9*2/*2,*2/*3 metabolizers than their wild-type counterparts. We found a 2.3-fold increase in mean dose for normal sensitivity patients (wild-type VKORC1/CYP2C9 genotypes) compared to the other groups (moderate and high sensitivity); 31.5% of the patients in our study group had warfarin sensitivity-related genotypes. The estimated regression equation accounted for 44.4% of overall variability in regard to warfarin maintenance dose. The algorithm was validated, giving 45.9% correlation (R2=0.459).ConclusionOur results describe and validate the first algorithm for predicting warfarin maintenance in a Colombian mestizo population and have contributed toward the understanding of pharmacogenetics in a Latin American population subgroup.

Detection of dose delivery variations on TomoTherapy using on-board detector based verification

A clinical case of delivery dose deviations on a TomoTherapy treatment was discovered during a patient specific treatment quality assurance (QA) verification. An in-house developed QA system, MCLogQA, for TomoTherapy has been implemented in our clinic for patient specific treatment QA. The MCLogQA system utilizes the log file and detector-based multileaf collimator (MLC) leaf opening time (LOT) to assess accuracy of treatment plan delivery. Recently, the MCLogQA system discovered >10% dose deviation for a low dose/fraction treatment plan. To verify the adequacy of the MCLogQA result, a delivery quality assurance (DQA) plan was created and performed. The treatment plan was also transferred to a second TomoTherapy unit and planning system to investigate if the plan-delivery deviation was unit dependent. Further testing was carried out in phantom plans. MCLogQA showed MLC LOT was on average 2.4% higher than the planned LOT, resulting in 3.5% increase in mean dose, and 14% increase in dose to 1 cc volume of max dose in PTV. Independent DQA verification confirmed the MCLogQA result. For the transferred treatment plan delivery, the MCLogQA also showed an average increase of 6.6% in MLC LOT, resulting in increases in mean dose by 9.3% and dose to 1 cc volume of max dose in PTV by 16%. The inaccurate MLC LOT was a result of a poor latency model at very small LOT. Phantom testing confirmed low LOT will result in relatively large dosimetric variation, and detector-based MCLogQA will detect differences in planned and measured LOT. Accuracy in TomoTherapy treatment delivery can be susceptible to LOT uncertainty. Using MCLogQA for QA verification not only validates the treatment delivery, but also provides information on LOT variation and comprehensive dose distribution. This information can help decision making when large plan-delivery deviation occurs.

A retrospective comparison of intensity-modulated arc therapy and 3-dimensional conformal approaches in the planning of grade 3 gliomas

AbstractPurposeTo evaluate the extent to which intensity-modulated arc therapy (IMAT) for high-grade gliomas is comparable with three-dimensional conformal radiotherapy (3DCRT) in relation to the dose delivered to normal brain tissue (NBT), planning target volume (PTV) conformity and the dose delivered to brainstem and optic chiasma.MethodA total of 16 randomly selected 3DCRT treatment plans of grade 3 gliomas were re-planned using an IMAT planning technique and dose–volume histograms were compared. Primary outcomes were maximum, mean, 1/3 and 2/3 doses to NBT outside the PTV. Also the maximum, mean, D50 and D20 doses to PTV. Secondary outcomes were maximum and mean doses to the brainstem and optic chiasm. Wilcoxon signed rank test was used to compare data.ResultsIMAT led to a statistically significant increase in mean dose to NBT (34·4 versus 33·3 Gy, (p=0·047) but a statistically significant reduction in maximum dose to NBT (62·7 versus 63·8 Gy, p=0·004) compared with 3DCRT. IMAT led to statistically significant reductions in maximum, D50 and D20 doses to the PTV (63·3 versus 64·7 Gy, p=0·001; 60·0 versus 60·7 Gy, p=0·001 and 60·5 versus 61·8 Gy, p=0·002, respectively). No statistically significant differences were seen in doses to brainstem and optic chiasm.ConclusionIMAT is at least comparable with 3DCRT in relation to minimising dose to NBT and ensuring good PTV conformity. Doses delivered to organs at risk using IMAT were also comparable with 3DCRT. This study supports the continued use of IMAT for the treatment of high-grade gliomas.

Pregnancy after heart transplantation: a well-thought-out decision? The Quebec provincial experience - a multi-centre cohort study.

Despite reports of successful pregnancies in heart transplant (HTx) recipients, many centers recommend their patients against maternity. We reviewed our provincial experience of pregnancy in HTx recipients by performing charts review of all known gestations following HTx in the province of Quebec (Canada), stratified between planned and unplanned pregnancies. Long-term survival was compared to HTx recipient women of childbearing age who did not become pregnant. Eighteen pregnancies, 56% unplanned, occurred in eight patients, 10.1 (2.6-27.0) years after HTx. Immunosuppression was CNI-based, with a mean dose increase of 48.3% (tacrolimus) and 26.5% (cyclosporine), without rejection. Cardiometabolic complications were high compared to the general Canadian population, including preeclampsia (15.4% vs. 5.5%), hypertension (38.5% vs. 4.6%), and diabetes (15.4% vs. 5.6%). Mean gestational age was 35.1 (23.4-39.6) weeks (72.2% live births; 53.8% prematurity). Mean birthweight was 2418 (660-3612) g. Serum creatinine increased during pregnancy, becoming significant after delivery (P=0.0239), and returning to preconception level in all but three patients within a year. After 4.6 (1.2-17.2) years of follow-up, two rejection episodes occurred in one patient. Long-term mortality was similar to overall HTx women (Kaplan-Meier; P=0.8071). Pregnancy in HTx carries high cardiometabolic complications and decreased kidney function, but is feasible with acceptable outcomes and no impact on mother's survival.

Dosimetric feasibility of the hybrid Magnetic Resonance Imaging (MRI)-linac System (MRL) for brain metastases: The impact of the magnetic field

Background and purposeWe aimed to investigate the suitability of treating patients with single brain metastases using stereotactic radiosurgery (SRS) with the MRL and to characterize the dosimetric impact at tissue-air interfaces resulting primarily from the electron return effect (ERE). Material and methods24 patients treated for intact single brain metastases were analyzed. Three radiotherapy plans with the same prescribed dose were generated for each case: (1) noncoplanar volumetric modulated arc therapy (VMAT), (2) coplanar step-and-shoot intensity modulated radiotherapy (IMRT) on the MRL in the absence (MRLB=0), and (3) in the presence of the transverse magnetic field (MRLB=1.5). The plans were evaluated using cumulative dose–volume histograms and by calculation of Paddick conformity index (CI), V100%, V12Gy minus gross tumor volume (V12Gy – GTV), and V2Gy. At tissue-air boundaries, the dosimetric impact of the magnetic field was quantified using a 5 mm rim of tissue. ResultsAll plans met the target coverage and organs-at-risk planning objectives. Differences between all investigated dosimetric parameters significantly favored the VMAT plans as compared to the MRLB=0 and MRLB=1.5 plans, except for V2Gy. The mean V12Gy – GTV and V2Gy marginally favored the MRLB=0 plans compared to the MRLB=1.5 plans (mean difference: 0.45 cm3, p = 0.0019 and 16.46 cm3, p < 0.0001, respectively). The presence of the magnetic field resulted in a statistically significant but small increase in mean dose and D2cc in the skin (0.08 Gy, p < 0.0001 and 0.6 Gy, p < 0.0001, respectively) and around air cavities (0.07 Gy, p = 0.0092 and 0.3 Gy, p = 0.0004, respectively). ConclusionsIt is feasible to generate stereotactic radiation plans that satisfy clinical requirements using the MRL in the setting of single brain metastases. The dosimetric impact of the magnetic field including the ERE at tissue-air boundaries is minor and does not negatively impact target conformity or dose gradient.

Dosimetric Analysis of Individual Liver Metastases from Colorectal Cancer Following 90 y Microsphere Selective Internal Radiation Therapy

Colorectal cancer (CRC) is a common cause of cancer-related deaths (12.2% overall mortality, GLOBOCAN 2012 v1.0). Approximately half of CRC patients develop or present with metastasis (mCRC) to the liver. Selective internal radiation therapy (SIRT) involves injection of yttrium-90 (90Y) radiolabelled microspheres into the arterial blood supply of tumours in the liver. Radioactivity prescription for 90Y SIRT is currently based on a body surface area (BSA) formula. The purpose of this study was to conduct a lesion-by-lesion analysis to establish a dose-response relationship. A retrospective review of 24 patients (99 lesions) treated with resin 90Y microspheres was conducted. All patients had inoperable liver metastases refractory to standard chemotherapies. Single photon emission computed tomography (SPECT) images were transformed into dose maps using an in-house MATLAB script and the direct deposition dosimetry method. The 90Y S-value was generated by Monte Carlo-simulation using the EGSnrc/EGS++ code. Baseline and follow-up CT scans were segmented to derive liver and lesion volumes. Mean, median, and D70 (minimum dose to 70% of lesion volume) values derived from dose maps were correlated to change in lesion volume and RECIST 1.1 outcome using linear and logistic regression, respectively. The median administered radioactivity was 1513 MBq (range 847-2185) for lobar and bilobar administrations. The median uniform normal liver dose was 26.3 Gy (range 15.4-41.3, IQR 22.3-30.6) and median lesion dose was 32.8 Gy (range 2.3-90.0, IQR 23.4-48.2). Stable disease or partial response was observed in 17 (71%) patients. Median survival from the date of administration was 313 days. Radiation absorbed dose correlated with lesion response (i.e. a 1 Gy increase in mean, median, and D70 dose resulted in reduction in lesion volume by 2.7%, 2.7%, and 2.3%, respectively, p < 0.02). Higher doses were associated with a decrease in total (combined) lesion volume (by 2.3% and 1.9% for a 1 Gy increase in mean and D70 doses respectively, p < 0.04). Higher lesion doses were associated with a higher probability of RECIST response (odds ratio of 1.05, 1.05, and 1.04 for a 1 Gy increase in mean, median, and D70 doses, respectively, p < 0.2). Higher mean, median, and D70 doses are associated with a decrease in lesion volume and an increased probability of RECIST response. The type of analysis presented here will allow suboptimally treated liver lesions to be managed by a multi-modality approach.

Changes in pharyngeal constrictor volumes during head and neck radiation therapy: Implications for dose delivery.

The objective of this study was to evaluate the anatomical changes and associated dosimetric consequences to pharyngeal constrictor muscles (PCMs) that occur during head and neck (H and N) radiotherapy (RT). A cohort of 13 oropharyngeal cancer patients with daily cone beam computed tomography (CBCT) was retrospectively studied. On every 5th CBCT image, PCM was manually delineated by a radiation oncologist. The anterior-posterior PCM thickness was measured at the midline level of C3 vertebral body. Delivered dose to PCM was estimated by calculating dose on daily images and performing dose accumulation on corresponding planning CT images using a parameter-optimized B-spline-based deformable image registration algorithm. The mean and maximum delivered dose (Dmean, Dmax) to PCM were determined and compared with the corresponding planned quantities. The average (±standard deviation) volume increase (ΔV) and thickness increase (Δt) over the course of 35 total fractions were 54 ± 33% (11.9 ± 7.6 cc) and 63 ± 39% (2.9 ± 1.9 mm), respectively. The resultant cumulative mean dose increase from planned dose to PCM (ΔDmean) was 1.4 ± 1.3% (0.9 ± 0.8 Gy), while the maximum dose increase (ΔDmax) was 0.0 ± 1.6% (0.0 ± 1.1 Gy). Patients who underwent adaptive replanning (n = 6) showed a smaller mean dose increase than those without (n = 7); 0.5 ± 0.2% (0.3 ± 0.1 Gy) versus 2.2 ± 1.4% (1.4 ± 0.9 Gy). There were statistically significant (P = 0.001) strong correlations between ΔDmean and Δt (Pearson coefficient r = 0.78), as well as between ΔDmean and ΔV (r = 0.52). The patients underwent considerable anatomical changes to PCM during H and N RT. However, the resultant increase in dose to PCM was minor to moderate. PCM thickness measured at C3 level is a good predictor for the mean dose increase to PCM.

Optimization of photon beam energies in gold nanoparticle enhanced arc radiation therapy using Monte Carlo methods

As a recent area of development in radiation therapy, gold nanoparticle (GNP) enhanced radiation therapy has shown potential to increase tumour dose while maintaining acceptable levels of healthy tissue toxicity. In this study, the effect of varying photon beam energy in GNP enhanced arc radiation therapy (GEART) is quantified through the introduction of a dose scoring metric, and GEART is compared to a conventional radiotherapy treatment. The PENELOPE Monte Carlo code was used to model several simple phantoms consisting of a spherical tumour containing GNPs (concentration: 15 mg Au g−1 tumour, 0.8 mg Au g−1 normal tissue) in a cylinder of tissue. Several monoenergetic photon beams, with energies ranging from 20 keV to 6 MeV, as well as 100, 200, and 300 kVp spectral beams, were used to irradiate the tumour in a 360° arc treatment. A dose metric was then used to compare tumour and tissue doses from GEART treatments to a similar treatment from a 6 MV spectrum. This was also performed on a simulated brain tumour using patient computed tomography data. GEART treatments showed potential over the 6 MV treatment for many of the simulated geometries, delivering up to 88% higher mean dose to the tumour for a constant tissue dose, with the effect greatest near a source energy of 50 keV. This effect is also seen with the inclusion of bone in a brain treatment, with a 14% increase in mean tumour dose over 6 MV, while still maintaining acceptable levels of dose to the bone and brain.