Daily Pretreatment Research Articles

Breast Cancer: Toxicity, QoL and Economy after External Beam APBI

Accelerated partial breast irradiation (APBI) is increasingly available approach in adjuvant RT of selected group of the early-stage breast cancer. Accumulating data are showing non-inferiority of both interstitial brachytherapy and external beam radiotherapy via stereotactic body radiotherapy (SBRT). The aim of this single institutional prospective randomized study is to compare the SBRT_APBI with accelerated whole breast irradiation (WBI). The main objective is to evaluate feasibility, safety, tolerance and cosmetic effects of SBRT. Patients with early breast carcinoma after partial mastectomy were screened for eligibility: age ˃ 50, NST histology, size ≤ 2 cm, negative margins ≥ 2 mm, no lymphovascular invasion, ER positive, BRCA negative. Randomization to: surgery bed SBRT (5x 6Gy) and accelerated WBI with tumor bed boost (15x 2.67Gy + 5x 2Gy). 4DCT-based planning, deep inspiration breath hold, daily pre-treatment positioning by cone-beam CT and volumetric arc therapy dose delivery were utilized. Quality of life (QoL) was evaluated by official translation of EORTC questionnaires (QLQ-C30 and QLQ-BR23). Cosmetics and toxicity were evaluated subjectively and objectively using questionnaires, CTCAE criteria and chest photodocumentation. Economy burden was evaluated at the end of radiotherapy by a 4-point graded scale. In this pilot report we present results of first 30/84 planned patients. Both groups (15 patients in each) were well balanced according to baseline characteristics. Median age 66 years, 66 % invasive ductal carcinoma, 70 % grade 1, median tumor size 9 mm. In SBRT group median PTV volume 52 ccm, minimum PTV dose median 29 Gy, maximum PTV dose median 32 Gy. 6 patients with no dermatitis, 9 patients with grade 1 dermatitis in SBRT group and 8 patients with grade 1, six with grade 2 and one with grade 3 skin toxicity in WBI group at the end of therapy. Significantly less skin sensitivity, dryness, pigmentation and fatigue in SBRT arm comparing to control arm. No differences between groups with respect to acute skin toxicity after 1 and 3 months. No significant difference in questionnaires evaluation. Cosmetic results as well as economic analysis favor SBRT technique. Description of two most common VMAT techniques with evaluation of dose coverage of the target and surrounding tissues parameters will be part of poster presentation. Feasibility, toxicity, cosmetic and financial influence of two radiotherapeutic regiments - the SBRT surgery bed radiotherapy and accelerated whole breast irradiation with the boost to tumor bed were compared. SBRT technique is less toxic and easier feasible approach for adjuvant treatment of selected early-stage breast cancer patients. We add to increase level of evidence for establishment of SBRT in indicated patients into daily clinical practice of APBI.

Prehabilitation for patient positioning: pelvic exercises assist in minimizing inter-fraction sacral slope variability during radiation therapy.

Reproducible patient positioning is essential for precision in radiation therapy (RT) delivery. We tested the hypothesis that a structured daily pre-treatment stretching regimen is both feasible and effective for minimizing variability in positioning, as measured by sacral slope angles (SSA). Eight female subjects undergoing pelvic radiotherapy performed a structured daily hip exercise regimen (extension and external rotation) immediately prior to both simulation imaging and daily treatment, throughout their RT course. This exercising cohort was compared to a retrospective review of 20 subjects (17 women and 3 men) undergoing RT, who had usual care. SSA measurements from daily pre-treatment imaging were compared to SSA measurements from the simulation CT. The average variation in SSA among the intervention subjects was 0.91° (± 0.58°), with a range among subjects of 0.57°-1.27°. The average variation for the control subjects was 2.27° (± 1.43°), ranging 1.22°-5.09°. The difference between the two groups was statistically significant (p = 0.0001). There was a statistically significant SSA variation between groups at each week of treatment. There was no significant variation among the intervention subjects between week 1 and later weeks, whereas subjects in the control group demonstrated significant SSA variation between week 1 and later weeks. We demonstrated a significant decrease in the variability of SSA by implementing a simple pre-treatment exercise program, while control subjects exhibited increasing variation in SSA over the course of treatment. We conclude that there is a potential benefit of prehabilitation during pelvic RT; however, a larger randomized control trial is required to confirm the findings.Clinical Trial: This research project was approved by the University of Massachusetts Medical School IRB (IRB ID H00012353) on January 21, 2017. The study is listed on ClinicalTrials.gov, provided by the U.S. National Library of Medicine, found with identifier NCT03242538.

Prehabilitation to Improve Positioning Reproducibility in Patients Undergoing Pelvic Radiation Therapy

Reproducible patient positioning is essential for precision in radiation therapy (RT) delivery. However, a retrospective review of pre-treatment imaging demonstrated variability in daily patient set-up. We tested the hypothesis that a structured daily pre-treatment stretching regimen is both feasible and effective for minimizing variability in positioning, as measured by sacral slope angles (SSA). After obtaining IRB approval, we had 8 female patients undergoing pelvic radiotherapy perform a structured daily hip exercise regimen (extension and external rotation) immediately prior to both simulation and daily treatment, throughout the RT course. The control group of 20 patients (17 female and 3 male) had usual care. SSA measurements on daily pre-treatment imaging were compared to SSA measurements from the simulation CT for 5 weeks. The extent of SSA variability between two groups and over time was analyzed using a linear mixed model. The same two readers independently measured SSA of all subjects, comparing SSA on the day of simulation to SSA measured on each day of RT. The average variation in SSA among the intervention subjects was 0.913° (±0.582°), with a range among subjects of 0.57°-1.3°. The average variation for the control subjects was 2.27° (±1.43°), with range among subjects of 1.22° - 5.09°. The difference between the two groups was statistically significant (p=0.002). There was a statistically significant SSA variation between groups at each week of treatment (Week (wk) 1: p = 0.007, wk 2: p = 0.008, wk 3: p = 0.01, wk 4: p = 0.005, wk 5: p = 0.008). There was no significant variation among the intervention subjects between week 1 and later weeks (wk 2: p = 0.88, wk 3: p = 0.74, wk 4: p = 0.97, wk 5: p = 0.40), whereas subjects in the control group demonstrated significant SSA variation between week 1 and the fourth week of therapy (wk 2: p = 0.87, wk 3: p = 0.92, wk 4: p = 0.02, wk 5: p = 0.22). There were no reported adverse effects of the stretching regimen. We demonstrated a significant decrease in the variability of SSA by implementing a simple pre-treatment stretching program, whereas control subjects exhibited an increasing variability of SSA over the course of treatment. We conclude that there is a potential benefit for prehabilitation during pelvic RT. A larger clinical trial is required to determine whether a pre-treatment stretching program would result in clinical benefit.

Estimation of Duration-Dependent Margins for Prostate Radiotherapy

Despite daily pre-treatment localisation and online corrections, intra-fraction motion uncertainties during prostate radiotherapy are expected. The magnitude of motion uncertainty is associated with the duration of the patient lying on the in-room treatment couch. This study reports a minute-by-minute association and calculates the impact of this motion on duration-dependent margins using real-time intra-fraction motion monitored by four-dimensional transperineal ultrasound (4D TPUS). A total of 55 patients were recruited prospectively. Intra-fraction motion of the prostate was monitored real-time using a 4D TPUS system. A total of 1745 monitoring sessions were analysed. Van Herk’s margin recipe (2.5∑+1.64((σ2 + σp2)1/2 - σp)) was used to estimate the duration-dependent margins for every minute, up to the 15th minute. The systematic component (∑) was derived from the standard deviation (SD) of the individual mean intra-fraction motion based on the average position across the entire imaging/treatment phase. Random error (σ) was calculated to include the root sum square of two components: 1) the root mean square (RMS) of the SD calculated from the mean intra-fraction motion for each patient; and 2) RMS of the average of the SD associated to the intra-fraction motion within each fraction for each patient. Linear regression analysis was then performed on the overall margins against time and direction. The mean intra-fraction motion was 0.8mm Inf, 0mm lateral and 0.9mm Post at the 15th minute. A minimum margin expansion of 2.4mm (Sup/Inf), 1mm (Lt/Rt) and 2.7mm (Ant/Post) was required for an 8-minute treatment compared to 4.1mm (Sup/Inf), 1.9mm (Lt/Rt) and 4.5mm (Ant/Post) for a 15-minute treatment. The required margin expansion increased linearly (R2 = 0.99) in all directions (p<0.01). However, while there was no statistical significant difference (p=0.09) in the required margin expansion in the Sup/Inf and Ant/Post directions respective of the time duration, the margins were much bigger compared to those in the Lt/Rt direction (p<0.01). We report our first experience in deriving the minimum duration-dependent margin expansion to generate the required planning target volume for prostate radiotherapy. The required margin expansion increases linearly in all directions within a 15-minute duration.

L-NAME releases nitric oxide and potentiates subsequent nitroglycerin-mediated vasodilation

L-NG-Nitro arginine methyl ester (L-NAME) has been widely applied for several decades in both basic and clinical research as an antagonist of nitric oxide synthase (NOS). Herein, we show that L-NAME slowly releases NO from its guanidino nitro group. Daily pretreatment of rats with L-NAME potentiated mesenteric vasodilation induced by nitrodilators such as nitroglycerin, but not by NO. Release of NO also occurred with the NOS-inactive enantiomer D-NAME, but not with L-arginine or another NOS inhibitor L-NMMA, consistent with the presence or absence of a nitro group in their structure and their nitrodilator-potentiating effects. Metabolic conversion of the nitro group to NO-related breakdown products was confirmed using isotopically-labeled L-NAME. Consistent with Fenton chemistry, transition metals and reactive oxygen species accelerated the release of NO from L-NAME. Both NO production from L-NAME and its nitrodilator-potentiating effects were augmented under inflammation. NO release by L-NAME can confound its intended NOS-inhibiting effects, possibly by contributing to a putative intracellular NO store in the vasculature.

Arachidonoyl‐2‐chloroethylamide alleviates inflammatory pain in a sex‐dependent manner using the formalin test

Previous studies have shown that certain cannabinoids have analgesic effects. Specifically, activation of cannabinoid receptor (CB) 1 has been demonstrated to produce analgesia in multiple animal models. Arachidonyl‐2‐chloroethylamide (ACEA) is a synthetic agonist for CB1 receptors. The activation of CB1 with ACEA could enable chronic inflammatory pain patients to manage this discomfort. ACEA has not been extensively studied in animal models; therefore, not much is known about the dose effectiveness, development of tolerance, or sex‐specific effects.To study the analgesic effects of ACEA, we treated male and female C57BL6J mice prior to the formalin pain test. Administration of formalin (2.5% intraplantar) produces a biphasic pain response, modeling both acute and inflammatory pain. We believe that administration of ACEA at a dose of 0.5 mg per kg intraperitoneal will reduce inflammatory pain in this model. Also, we suggest that daily pretreatment with ACEA prior to the formalin test will cause desensitization to this compound; therefore, the initial analgesic effect will not be seen. To examine sex‐specific effects, we also tested and compared male and female mice. Moreover, vaginal lavage was performed daily on female mice to track the estrous cycle.Preliminary data suggests that females experience higher pain sensitivity compared with males when ACEA 0.5 mg per kg was used. Furthermore, our preliminary data shows that chronic administration in females results in estrous cycle changes. We concluded that there is a sex‐dependent difference in analgesic response to ACEA, and that it may be hormonally‐mediated.Support or Funding InformationFunded by NIDA DA044999‐01A1 (JG) and Texas Tech University Health Sciences Center School of Medicine #121035 (JG).This abstract is from the Experimental Biology 2019 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.

Fiducial markers in prostate cancer image-guided radiotherapy.

Background: Image-guided radiotherapy (IGRT) is recommended to reduce the risk of geometrical miss when modern radiotherapy technologies with high grades of conformity are used. The purpose of this study was to evaluate the efficacy of fiducial markers (FMs) for electronic portal imaging in prostate cancer radiotherapy in term of evaluating the complications associated with FMs implantation, quantifying inter-fraction prostate motion, and determination of optimal planning target volume (PTV) margins. Methods: In this single institution, prospective, consecutive study, 27 patients underwent implantation of three-gold seed FMs into the prostate gland before prostate radiotherapy. Prior to computed tomography planning, all patients were asked to report any complication associated with FMs implantation that have experienced to date. Daily pre-treatment electronic portal images were captured, and prostate position errors were corrected if they were greater than 2 mm along three translational directions. Optimal PTV expansions were computed using van Herk formula [PTV-margin= 2.5Σ + 0.7σ]. Results: FMs implantation was successful with an acceptable toxicity profile in all patients. Without IGRT, margins of 5.4 mm, 5.8 mm and 5.5 mm, in vertical, longitudinal and lateral directions, respectively, are needed for a 95% confidence level of complete clinical target volume (CTV) coverage in each treatment session. The PTV margins of 3.0 mm, 3.3 mm and 4.0 mm in corresponding directions were calculated when FMs based electronic portal imaging was applied. Conclusion: FMs based electronic portal imaging is an effective tool for prostate cancer IGRT.

Crocin reverses unilateral renal ischemia reperfusion injury-induced augmentation of oxidative stress and toll like receptor-4 activity

Renal Ischemia (RI) usually develops as a secondary manifestation of hypertension, various cardiovascular disorders and renal transplantation. It exerts hypoxic oxidative stress to kidneys, together with stimulation of several immune-mediated inflammatory cascades. Such events eventually damage renal tubules and glomeruli, driving acute kidney injury (AKI) and ultimately, renal failure. Crocin; the main bioactive constituent of Crocus sativus extract has been reported to demonstrate numerous pharmacological merits. In the current study, unilateral renal ischemia reperfusion injury (URIRI) was induced in rats by unilateral clamping of the left renal pedicle for 45 min followed by 24 h of reperfusion. Daily pre-treatment with crocin (20 mg/kg, orally) for 7 days, significantly improved all signs of renal injury. Biochemically, kidney functions; including serum creatinine (Sr Cr), blood urea nitrogen (BUN), proteinuria and creatinine clearance (Cr Cl) significantly improved. Inflammatory biomarkers; serum lactate dehydrogenase (LDH) and kidney nitric oxide (Nos) contents significantly declined. Oxidant/antioxidant balance was significantly restored; manifested in recovery of renal superoxide dismutase (SOD) activity, glutathione (GSH) concentration, malondialdehyde (MDA) content and restoration of serum catalase activity. Kidney contents of inflammatory cytokine interleukin-6 (IL6) and toll-like receptors 4 (TLR4) significantly declined as well. Histopathologically, crocin pretreatment resulted in signs of improvement with minimal renal lesions with significant decrease in renal inflammatory cells count. In conclusion, crocin induced restoration of normal kidney functions is mediated through multiple mechanisms including mainly attenuation of oxidative stress and inflammation via down-regulation of renal TLR4 and IL6 expression.

Patterns of Practice in Canadian Radiation Treatment Centres: Results of a National Survey

PurposeRadiation therapy has changed rapidly over the past decade due to the application of technological advances. A survey was conducted of radiation treatment centres in Canada to establish current patterns of practice across the country. Areas of inquiry included treatment techniques and image verification, as well as roles and responsibilities of radiation therapists (RTs). Methods and MaterialsIn January 2016, a survey was sent to managers of the 46 radiation treatment centres in Canada. This survey sought information on a range of staffing and practice variables for the fiscal year 2014/2015. ResultsOf the 46 centres contacted, 37 centres responded, representing an 80.4% response rate. Survey results showed that the use of volumetric arc therapy and intensity-modulated radiation therapy is common across Canada for several anatomic sites, as well as the use of daily pretreatment image verification. A high degree of variability exists for imaging modality (two dimensional vs. three dimensional) for some sites, including brain, head and neck, and lung. RTs' responsibilities have expanded uniformly across the country, with RTs involved in organ-at-risk contouring and on-treatment image approval at the majority of centres. Despite this role expansion, specialty roles in areas of quality and applications expertise are still rare. ConclusionsRadiation therapy in Canada has transitioned to high-technology treatment techniques with relative consistency across the country. There is, however, variation in the imaging modality used for daily verification. Canada may benefit from consensus guidelines on the application of three-dimensional imaging for treatment verification. While RTs have expanded their responsibilities, role definition for RTs working in supervisory or supporting positions has not kept pace at many centres and it is unclear if RTs are supported in their expanded accountabilities.

Implementation of ultrasound bladder volume scanning for patients receiving intensity-modulated radiotherapy to the cervix or endometrium: clinical experiences from a United Kingdom radiotherapy department

AbstractBackground and purposeAchieving daily consistent bladder volume is acknowledged as challenging for patients undergoing radiotherapy to the cervix or endometrium. We investigated if use of an ultrasound bladder volume scanner (BioCon-700) improves bladder reproducibility when used during an active volume correction protocol.Materials and methodsDuring our method-comparison study, prospectively recruited patients (n=20) followed a fluid-loading protocol to achieve acceptable bladder volume. Bladder ultrasound was performed daily to verify planned volume, with patients actively correcting volumes outside a planned range up to a maximum of three times. Using the Bland–Altman method, we compared mean ultrasound readings (USMean) with mean cone-beam computed tomography (CBCT) volumes (CBCTMean). We also conducted staff focus groups exploring issues encountered during implementation of bladder scanning.ResultsComparing USMean with CBCTMean produced a mean of the differences −10±49·92 mL (1 SD), demonstrating that bladder volume scanning is equivalent to our standard measure for the stated confidence levels. The cohort mean bladder volume decrease from week 1 to 5 was only 8·4%. Mean USMean was 323 mL, mean CBCTMean was 313 mL. Staff experience with the scanner overall was positive.ConclusionsThe BioCon-700 is suitable for the purpose of daily pre-treatment volume verification, facilitating daily assessment and modification of bladder volume, resulting in reproducible treatment volumes.

A quantitative analysis of tumor site specific setup based on 1 485 daily MVCT scans from helical tomotherapy

Objective To assess the variation in patient setup corrections for three different anatomic treatment sites using daily pretreatment megavoltage CT(MVCT) in helical tomotherapy, and to analyze alternative reference margins for specific tumor site. Methods Sixty patients treated for three anatomical sites on helical tomotherapy were analyzed.Daily MVCT was carried out for registration and setup corrections before each treatment fraction.Setup errors and rotational setup corrections from 587 head and neck, 500 thoracic, 371 abdomen and gynecology MCVT imaging were input to statistical analysis.Incidences of three dimensional vector error lengths were calculated for each anatomic site.Overall distribution histograms of the three-dimensionally error was presented using GraphPad Prism 5.The distributions of systematic and random setup errors were quantitative analyzed and the additional margins required were also taken into account. Results 1 458 MVCT scans were implemented for sixty patients.Head and neck had lower frequencies of translational setup errors than others.Frequency of at least 3mm three-dimensional setup errors for head and neck, thoracic, abdomen and gynecology was 55.3%, 70.8%, 79.8%, respectively.This frequency decreased to 17.5%, 40.6%, 47.2% if 3D vector distance ≥5mm was scored.Overall systematic errors ranged from-1.4mm to 2.7mm, abdomen and gynecology had the largest setup errors in the vertical direction which was statistically significant(χ2=19.3, P<0.05). The suggested margins should be increased by 4-7 mm in three-dimensional direction for head and neck, 9-14mm for thoracic, 10-17mm for abdomen and gynecology. Conclusion Differences in setup corrections are perceived between head and neck, thoracic, abdomen and gynecology.The accuracy of patient positioning can be improved if pre-treatment daily MVCT scans are put into use.Results from setup correction can provide evidence for tumor treatment margin and improve the accuracy of regular radiotherapy. Key words: Tomography, spiral computed; Radiotherapy; Image processing, computer-assisted

Feasibility and full-course dosimetry of an intraoperatively placed multichannel brachytherapy catheter for accelerated partial breast irradiation

PurposeDetermine feasibility and resultant dosimetry of an intraoperatively placed multichannel intracavitary brachytherapy catheter for accelerated partial breast irradiation (APBI). MethodsPatients with breast cancer underwent intraoperative brachytherapy catheter placement based on frozen section analysis with immediate postoperative APBI. The planning target volume evaluation (PTVEval) and organs at risk were contoured on daily pretreatment CT scans for each patient, and the original treatment plan was applied to assess full-course dosimetry. ResultsOf the first 21 patients consented for intraoperative catheter placement, 20 (95%) were able to proceed with treatment as planned. The mean volume of PTVEval receiving 90% of prescription dose (V90%) and mean percentage of prescription dose to 90% of the PTVEval (D90%) on initial planning were 96.7 (±1.1%) and 100.2 (±2.1%), respectively. Full-course dose coverage remained excellent with a mean PTVEval V90% and D90% of 95.0 (±4.4%) and 100.2 (±9.6%), respectively. Mean full-course maximum dose constraints for chest wall and skin were met by 70% and 95% of patients, respectively. Air accumulation >1 cc during treatment increased the risk of a daily fraction with PTVEval coverage below goal (odds ratio, 9.8; p = 0.05), whereas those with applicators <0.5 cm from the chest wall at planning were at risk of exceeding that organ's maximum dose constraint on a daily fraction (odds ratio, 45; p = 0.02). ConclusionsIntraoperative catheter placement and early initiation of APBI based on frozen section pathology is feasible, yields acceptable dosimetry, and is an option for completing breast conserving therapy in less than 10 days.

Cardiac and respiration induced motion of mediastinal lymph node targets in lung cancer patients throughout the radiotherapy treatment course

Background and purposeInvolved mediastinal lymph nodes (LNs) are often included in the radiotherapy target for lung cancer patients. Their motion may differ from the primary tumor motion, possibly undermining the loco-regional control. This study determines the detailed differential target motion throughout the treatment course. Material and methodsTen lung cancer patients with 2–4 fiducial markers implanted in LN targets received IMRT with a daily pre-treatment cone-beam CT (CBCT) scan. Offline, the 3D trajectory of the markers was determined from their projected trajectory in the CBCT projections. Frequency analysis was performed to separate the intrafraction motion into a respiratory and cardiac component. The mean setup error of the markers and the motion range were used to calculate margins required for LN targets when setup is based on soft-tissue match. ResultsRespiration motion was largest in the CC direction and more prominent for more caudal LNs. Cardiac motion was often (73%) largest in the AP direction and tended to be largest for more cranial LNs. Margins for intrafraction motion and daily baseline shifts of LNs were 4.8mm (LR), 6.0mm (CC) and 6.7mm (AP). ConclusionsDetailed mapping showed that LN motion was in general governed by breathing, but some LNs had substantial cardiac induced motion.

SU‐F‐J‐24: Setup Uncertainty and Margin of the ExacTrac 6D Image Guide System for Patients with Brain Tumors

Purpose:This study evaluated the setup uncertainties for brain sites when using BrainLAB's ExacTrac X‐ray 6D system for daily pretreatment to determine the optimal planning target volume (PTV) margin.Methods:Between August 2012 and April 2015, 28 patients with brain tumors were treated by daily image‐guided radiotherapy using the BrainLAB ExacTrac 6D image guidance system of the Novalis‐Tx linear accelerator. DUONTM (Orfit Industries, Wijnegem, Belgium) masks were used to fix the head. The radiotherapy was fractionated into 27–33 treatments. In total, 844 image verifications were performed for 28 patients and used for the analysis. The setup corrections along with the systematic and random errors were analyzed for six degrees of freedom in the translational (lateral, longitudinal, and vertical) and rotational (pitch, roll, and yaw) dimensions.Results:Optimal PTV margins were calculated based on van Herk et al.'s [margin recipe = 2.5∑ + 0.7σ − 3 mm] and Stroom et al.'s [margin recipe = 2∑ + 0.7σ] formulas. The systematic errors (∑) were 0.72, 1.57, and 0.97 mm in the lateral, longitudinal, and vertical translational dimensions, respectively, and 0.72°, 0.87°, and 0.83° in the pitch, roll, and yaw rotational dimensions, respectively. The random errors (σ) were 0.31, 0.46, and 0.54 mm in the lateral, longitudinal, and vertical rotational dimensions, respectively, and 0.28°, 0.24°, and 0.31° in the pitch, roll, and yaw rotational dimensions, respectively. According to van Herk et al.'s and Stroom et al.'s recipes, the recommended lateral PTV margins were 0.97 and 1.66 mm, respectively; the longitudinal margins were 1.26 and 3.47 mm, respectively; and the vertical margins were 0.21 and 2.31 mm, respectively.Conclusion:Therefore, daily setup verifications using the BrainLAB ExacTrac 6D image guide system are very useful for evaluating the setup uncertainties and determining the setup margin.∑σ

Analysis of the Setup Uncertainty and Margin of the Daily ExacTrac 6D Image Guide System for Patients with Brain Tumors.

This study evaluated the setup uncertainties for brain sites when using BrainLAB’s ExacTrac X-ray 6D system for daily pretreatment to determine the optimal planning target volume (PTV) margin. Between August 2012 and April 2015, 28 patients with brain tumors were treated by daily image-guided radiotherapy using the BrainLAB ExacTrac 6D image guidance system of the Novalis-Tx linear accelerator. DUONTM (Orfit Industries, Wijnegem, Belgium) masks were used to fix the head. The radiotherapy was fractionated into 27–33 treatments. In total, 844 image verifications were performed for 28 patients and used for the analysis. The setup corrections along with the systematic and random errors were analyzed for six degrees of freedom in the translational (lateral, longitudinal, and vertical) and rotational (pitch, roll, and yaw) dimensions. Optimal PTV margins were calculated based on van Herk et al.’s [margin recipe = 2.5∑ + 0.7σ - 3 mm] and Stroom et al.’s [margin recipe = 2∑ + 0.7σ] formulas. The systematic errors (∑) were 0.72, 1.57, and 0.97 mm in the lateral, longitudinal, and vertical translational dimensions, respectively, and 0.72°, 0.87°, and 0.83° in the pitch, roll, and yaw rotational dimensions, respectively. The random errors (σ) were 0.31, 0.46, and 0.54 mm in the lateral, longitudinal, and vertical rotational dimensions, respectively, and 0.28°, 0.24°, and 0.31° in the pitch, roll, and yaw rotational dimensions, respectively. According to van Herk et al.’s and Stroom et al.’s recipes, the recommended lateral PTV margins were 0.97 and 1.66 mm, respectively; the longitudinal margins were 1.26 and 3.47 mm, respectively; and the vertical margins were 0.21 and 2.31 mm, respectively. Therefore, daily setup verifications using the BrainLAB ExacTrac 6D image guide system are very useful for evaluating the setup uncertainties and determining the setup margin.

Chemical composition and antioxidant activity of Carob pulp (Ceratonia Siliqua L.) extracts

The role of polyphenols and flavonoids in prevention of cellular damages carried out with the oxidative stress is well documented. In the present experiment, we determined the polyphenols and flavonoids concentrations of three extracts (ethanol 70%: V/V, methanol 80%: V/V and distilled water extracts) of carob pulp mature (Ceratonia siliqua L.) and their in vitro and in vivo antioxidant activity. A significant dose-dependent anti-free radical activ-ity of ethanolic extract of carob (EEC) was related to the highest polyphenol content (44.74 mg QE/mL) and to the in vitro antioxidant activity (EC50 = 0.28 mg/mL) of this extract. LC-MS /MS analysis of the EEC have shown the presence of several phenolic compounds as well as many types of flavonoids. The in vivo experiment brought out the significant effect of the daily EEC oral pre-treatment of rats, 30 min before AlCl3 administration for 28 d on the improvement of the total blood antioxidant capacity. These results suggest that the carob pulp contain many substances having in vitro and in vivo antioxidant effects, and which could be used as natural food additives in order to preserve food quality.

Internal target volume for post-hysterectomy vaginal recurrences of cervical cancers during image-guided radiotherapy.

The outcome of post-surgical recurrences of cervical cancer may be improved through radiation dose escalation, which hinges on accurate identification and treatment of the target. The present study quantifies target motion during course of image-guided radiotherapy (IGRT) for vault cancers. All patients underwent planning CT simulation after bladder-filling protocol. A daily pre-treatment megavoltage CT was performed. All translations and rotations were recorded. Post-registration displacement of gross tumour volume (GTV) and centre of mass (COM) of GTV was independently recorded by two observers for fractions one to seven. Day 1 image sets served as reference images against which the displacements of COM were measured. We calculated the displacements of common volume (CV) and encompassing volume (EV) of GTV for both the observers. A total of 90 image data sets of 15 patients were available for evaluation. Individual patient GTV and average GTV by both the observers were comparable. The average shifts for EV were 2.4 mm [standard deviation (SD) ±1.2] in the mediolateral, 4.2 mm (SD ±2.8) in the anteroposterior and 4.0 mm (SD ±2.1) in superoinferior directions. Similarly, the average shifts for CV were 1.9 mm (SD ±0.6) in the mediolateral, 3.7 mm (SD ±2.7) in the anteroposterior and 4.4 mm (SD ±2.7) in superoinferior directions. Using Stroom's/van Herk's formula, the minimum recommended margins would be 4.5/5.2, 8.2/9.4 and 7.3/8.3 mm, respectively, for lateral, anteroposterior and superoinferior directions. Differential directional internal margin is recommended in patients undergoing IGRT for post-surgical recurrence of cervical cancers. Internal organ motion of vault cancers can be accounted for by a directional margin to the gross tumour.

SU-C-210-06: Quantitative Evaluation of Dosimetric Effects Resulting From Positional Variations of Pancreatic Tumor Volumes

Purpose: The aim of this study is to quantify dosimetric effects resulting from variation in pancreatic tumor position assessed by bony anatomy and implanted fiducial markers Methods: Twelve pancreatic cancer patients were retrospectively analyzed for this study. All patients received modulated arc therapy (VMAT) treatment using fiducial-based Image Guided Radiation Therapy (IGRT) to the intact pancreas. Using daily orthogonal kV and/or Cone beam CT images, the shift needed to co-register the daily pre-treatment images to reference CT from fiducial to bone (Fid-Bone) were recorded as Left-Right (LR), Anterior-Posterior (AP) and Superior-Inferior (SI). The original VMAT plan iso-center was shifted based on KV bone matching positions at 5 evenly spaced fractions. Dose coverage of the planning target volumes (PTVs) (V100%), mean dose to liver, kidney and stomach/duodenum were assessed in the modified plans. Results: A total of 306 fractions were analyzed. The absolute fiducial-bone positional shifts were greatest in the SI direction, (AP = 2.7 ± 3.0, LR = 2.8 ± 2.8, and SI 6.3 ± 7.9 mm, mean ± SD). The V100% was significantly reduced by 13.5%, (Fid-Bone = 95.3 ± 2.0 vs. 82.3 ± 11.8%, p=0.02). This varied widely among patients (Fid-Bone V100% Range = 2–60%), where 33% ofmore » patients had a reduction in V100% of more than 10%. The impact on OARs was greatest to the liver (Fid-Bone= 14.6 vs. 16.1 Gy, 10%), and stomach, (Fid-Bone = 23.9 vx. 25.5 Gy, 7%), however was not statistically significant (p=0.10 both). Conclusion: Compared to matching by fiducial markers, matching by bony anatomy would have substantially reduced the PTV coverage by 13.5%. This reinforces the importance of online position verification based on fiducial markers. Hence, implantation of fiducial markers is strongly recommended for pancreatic cancer patients undergoing intensity modulated radiation therapy treatments.« less

SU-F-303-03: Auto-Alignment of 2D Cine Imaging Planes for Real-Time Motion Management During MRI-GRT

Purpose: Spatial-temporal-contrast resolution tradeoffs preclude acquisition of real-time 3D MRI volumes for exception gating and target tracking. Consequently, acquisition of 2D imaging planes has been proposed. However, to minimize through-plane motion the orientation of the 2D imaging planes must be chosen appropriately. The goal of this work was to develop a methodology to auto-align 2D cine imaging planes for real-time cine imaging on MRI-gRT systems. Methods: Phase-resolved 4D MR images of a healthy volunteer set up in treatment position were acquired at 3T. Following offline reconstruction in MATLAB, the binned 4D MR images were transferred to MIM (MIM Software, Cleveland, OH). To simulate target, a contour of the right kidney was generated on the 0% phase image and then deformably propagated to the remaining nine respiratory phase images. Dynamic, 3D centroid motion of the kidney target was calculated at each respiratory phase. Principal component analysis was used to determine the eigenvectors of maximal kidney motion. Direction cosines required to orient a 2D cine imaging plane in the MR scanner coordinate system along the lines of maximal kidney motion were calculated. The direction cosines were applied on the MR scanner during acquisition of 2D cine images to capture kidney motion. Results: Deformable propagation of kidney contours across binned 4D MR images was possible. Kidney centroid motion ranged from 0.8mm, 5.5mm, and 14.5mm in the right/left, anterior/posterior, and superior/inferior dimensions, respectively. Direction cosines required to align 2D cine imaging planes were 75.7 and 12.3 degrees along the sagittal-coronal and sagittal-transverse planes. Conclusions: Auto-alignment of 2D cine imaging planes based on centroid motions derived from daily pre-treatment phase-resolved 4D MR images is a feasible approach for motion monitoring on MRI-gRT systems. Elekta Instruments, AB

The Weekly Chart Check: How Much is Necessary?

The weekly chart check process at the North East Cancer Centre (NECC) was very long and had many redundant checks. Each unit was responsible for checking their own charts on a weekly basis. Looking back at the incidents and good catches that were reported over the last two years (at NECC), the majority were not caught on the chart check, but rather on the treatment unit, during daily pre-treatment checks. Those that were caught on the chart check were minor documentation errors (eg: forgot to initial a note). This brought up the question of whether the weekly chart check was the right place to catch an error. The radiation therapists at NECC formed a working group to recommend changes to the weekly chart check process. Using LEAN thinking to reduce waste within the system, all of the checks were reviewed using “value added” and risk/severity assessments, to ensure that any checks that were removed do not increase the chances of incidents occurring. A new weekly chart check work flow was created, ensuring that each check was done at the right place and at the right time. With the recommendations, the majority of the chart checks were completed, even during heavier workloads. Using a teamwork approach and optimizing resources, all chart checks are the responsibility of all units. LEAN thinking should be used when developing and assessing all practices. We need to encourage a culture amongst coworkers that the majority of incidents occur are a result of system failure (environment, system design, etc.) and not people. Creating a standard of work with clear roles and responsibilities has positively contributed to the work environment by optimizing quality, patient safety and efficiencies.