DNA dosimeter measurements of beam profile using a novel simultaneous processing technique.

A DNA dosimeter (DNAd) was previously developed that uses double-strand breaks (DSB) to measure dose. This dosimeter has been tested to measure dose in scenarios where transient-charged particle equilibrium (TCPE) has been established. The probability of double strand break (PDSBo), which is the ratio of broken double-stranded DNA (dsDNA) to the initial unbroken dsDNA in the dosimeter, was used to quantify DSBs and related to dose. The goal of this work is to produce a new technique to process and analyze the DNAd and quantify DNA-DSBs. This technique included simultaneously processing multiple DNAds and also establishing a new form to the probability of double strand break (PDSBn), which was then used to test the DNAd in a non-TCPE condition by taking beam penumbra measurements. The technique utilized a 384-well plate, and the measurements were made at the edge of a 10 × 10 cm field and compared to film measurements. During these penumbra measurements, while observing the positional differences in the higher gradient region at 4.1 and 4.55 cm from the center of the radiation field, the distance to agreement of PDSBo to film were 0.38 cm and 0.26 cm while the distance to agreement of PDSBn to film were 0.11 cm and 0.06 cm, respectively. Finally, the developed new separation technique reduced the time needed for the analysis of 25 samples from 200 min to 30 min.

Characterization of a novel 3D printed patient specific phantom for quality assurance in cranial stereotactic radiosurgery applications.

In single-isocenter stereotactic radiosurgery/radiotherapy (SRS/SRT) intracranial applications, multiple targets are being treated concurrently, often involving non-coplanar arcs, small photon beams and steep dose gradients. In search for more rigorous quality assurance protocols, this work presents and evaluates a novel methodology for patient-specific pre-treatment plan verification, utilizing 3D printing technology. In a patient's planning CT scan, the external contour and bone structures were segmented and 3D-printed using high-density bone-mimicking material. The resulting head phantom was filled with water while a film dosimetry insert was incorporated. Patient and phantom CT image series were fused and inspected for anatomical coherence. HUs and corresponding densities were compared in several anatomical regions within the head. Furthermore, the level of patient-to-phantom dosimetric equivalence was evaluated both computationally and experimentally. A single-isocenter multi-focal SRS treatment plan was prepared, while dose distributions were calculated on both CT image series, using identical calculation parameters. Phantom- and patient-derived dose distributions were compared in terms of isolines, DVHs, dose-volume metrics and 3D gamma index (GI) analysis. The phantom was treated as if the real patient and film measurements were compared against the patient-derived calculated dose distribution. Visual inspection of the fused CT images suggests excellent geometric similarity between phantom and patient, also confirmed using similarity indices. HUs and densities agreed within one standard deviation except for the skin (modeled as 'bone') and sinuses (water-filled). GI comparison between the calculated distributions resulted in passing rates better than 97% (1%/1 mm). DVHs and dose-volume metrics were also in satisfying agreement. In addition to serving as a feasibility proof-of-concept, experimental absolute film dosimetry verified the computational study results. GI passing rates were above 90%. Results of this work suggest that employing the presented methodology, patient-equivalent phantoms (except for the skin and sinuses areas) can be produced, enabling literally patient-specific pre-treatment plan verification in intracranial applications.

Optimizing the response, precision, and cost of a DNA double-strand break dosimeter.

We developed a dosimeter that measures biological damage following delivery of therapeutic beams in the form of double-strand breaks (DSBs) to DNA. The dosimeter contains DNA strands that are labeled on one end with biotin and on the other with fluorescein and attached to magnetic microbeads. Following irradiation, a magnet is used to separate broken from unbroken DNA strands. Then, fluorescence is utilized to measure the relative amount of broken DNA and determine the probability for DSB. The long-term goal for this research is to evaluate whether this type of biologically based dosimeter holds any advantages over the conventional techniques. The purpose of this work was to optimize the dosimeter fabrication and usage to enable higher precision for the long-term research goal. More specifically, the goal was to optimize the DNA dosimeter using three metrics: the response, precision, and cost per dosimeter. Six aspects of the dosimeter fabrication and usage were varied and evaluated for their effect on the metrics: (1) the type of magnetic microbeads, (2) the microbead to DNA mass ratio at attachment, (3) the type of suspension buffer used during irradiation, (4) the concentration of the DNA dosimeter during irradiation, (5) the time waited between fabrication and irradiation of the dosimeter, and (6) the time waited between irradiation and read out of the response. In brief, the best results were achieved with the dosimeter when attaching 4.2 µg of DNA with 1 mg of MyOne T1 microbeads and by suspending the microbead-connected DNA strands with 200 µl of phosphate-buffered saline for irradiation. Also, better results were achieved when waiting a day after fabrication before irradiating the dosimeter and also waiting an hour after irradiation to measure the response. This manuscript is meant to serve as guide for others who would like to replicate this DNA dose measurement technique.

Evaluation and comparison of second-check monitor unit calculation software with Pinnacle3 treatment planning system.

The purpose of this study was to evaluate and compare the accuracy of dose calculations in second check softwares (Diamond, IMSure, MuCheck, and RadCalc) against the Phillips Pinnacle3 treatment planning system. Eighteen previously treated patients' treatment planning files consisting of a total of 204 beams were exported from the Pinnacle3 TPS to each of the four second check software. Of these beams, 145 of the beams used were IMRT plans while 59 were VMAT arcs. The values were represented as a percent difference between primary and secondary calculations and used for statistical analysis. Box plots, Pearson Correlation, and Bland-Altman analysis were performed in MedCalc. The mean percent difference in calculated dose for Diamond, IMSure, MuCheck, and RadCalc from Pinnacle3 were -0.67%, 0.31%, 1.51% and -0.36%, respectively. The corresponding variances were calculated to be 0.07%, 0.13%, 0.08%, and 0.03%; and the largest percent differences were -7.9%, 9.70%, 9.39%, and 5.45%. The dose differences of each of the second check software in this study can vary considerably and VMAT plans have larger differences than IMRT. Among the four second check softwares, RadCalc values has shown a high agreement on average with low variation, and had the smallest percent range from Pinnacle3 values. The closest in average percent difference from the Pinnacle3data was the IMSure software, but suffered from significantly larger variance and percent range. The values reported by Diamond and MuCheck had significantly high percent differences with TPS values.

Quality of life and depression in chronic sexually transmitted infections in UK and Greece: The use of WHOQOL-HIV/STI BREF.

This is a comparative study aiming to investigate quality of life (QoL) and depression in individuals diagnosed either with human immunodeficiency virus/acquired immune deficiency syndrome (HIV/AIDS), or genital warts (GW) and genital herpes (GH), in two healthcare settings, in the United Kingdom (UK) or in Greece (Gr). Using a matched-pairs design, two equalized patient samples with sexually transmitted infections (STI) were recruited: from UK (n=43) and from Greece (n=43). QoL was assessed with WHOQOL-HIV BREF for HIV patients and WHOQOL-STI BREF -a newly adapted instrument- for genital warts and genital herpes patients. Depressive symptomatology was measured by the Centre for Epidemiological Studies- Depression Scale (CES-D) along with sociodemographic data. Results indicate that in both country- healthcare settings, a high percentage of individuals diagnosed with any type of STI, reported considerable depressive symptomatology: 35.7% for UK and 41.5% for Greek participants respectively. Regarding QoL, participants in the Greek healthcare settings reported significantly lower scores in the environment domain, and even lower scores were reported by the GW/GH group, in comparison to HIV. Specifically, these groups indicated significantly lower values in the following WHOQOL-BREF environment facets: (i) physical safety and security, (ii) participation in and opportunities for recreation/leisure activities, (iii) home environment, (iv) accessibility and quality in health and social care, and (v) transport facilities. Regarding correlation of QoL and depression, regression analysis provided significant evidence for depression having a differential effect on WHOQOL-BREF QoL domains. Evidence of increased depressive symptomatology in both STI patient- cohorts may shed light into unmet healthcare needs that should be addressed by healthcare providers in UK and Greece respectively. Furthermore, all types of Greek STI participants reported lower QoL, particularly the GW/GH group, indicating important unmet QoL needs in the environment domain, such as health and social care accessibility and quality, or environmental and social resources, all lowering everyday QoL. The present findings may provide guidelines for tailored mental health interventions alleviating depressive symptomatology in STI patients. Provision of targeted-interventions at healthcare and social-environmental levels will contribute to QoL/ health improvement in STI patients.

Dosimetric quantification of dose fall-off in liver SBRT planning using dual photon energy IMRT.

INTRODUCTION: The purpose of this study was to dosimetrically compare 6 MV, 10 MV and a hybrid of 6 and 10 MV photon beam energies in liver stereotactic body radiotherapy (SBRT) patients using a fixed-field IMRT technique. The objectives of the study were to evaluate dosimetric differences in the target volume and investigate if dose fall-off could be improved with 10MV beam energy. METHODS AND MATERIALS: Sixteen (n=16) liver SBRT patients previously treated using a non-coplanar, fixed-field IMRT technique with 6 MV were replanned using 10 MV and dual photon energy (DE). Plans were generated in Pinnacle3 using a Novalis Tx with HD120 MLC. For each patient, three plans with the same beam geometry were created using 6 MV, 10 MV and DE. For DE plans, the central axis effective depth from each beam was calculated and the values averaged. Beams with an effective depth greater than the average were assigned to 10 MV. All patients were optimized with the same planning objectives and normalized such that 98% of the target received 100% of prescription dose. Metrics used for comparison were the homogeneity index, conformity indices, and dose fall-off parameters at various isodose levels. RESULTS: The three techniques showed comparable PTV conformity and inhomogeneity for all patients-differences in the median values 「0.6%. With regard to dose fall-off, no statistically significant differences were noted among the techniques for R80, R60 and R50; however, 10 MV showed statistical significance in the lowest median values of R40, R30, and R20. Ten MV and DE plans also demonstrated a statistically significant reduction in the total number of monitor units (MU) of 14.9% (p 「0.01) and 12.0% (p 「0.01) as compared to 6 MV, respectively. CONCLUSION: Both dual energy and 10 MV photon beams had similar PTV dosimetric characteristics to 6 MV for liver SBRT but findings show faster dose fall-off for 10 MV and DE plans at the 40%, 30%, and 20% prescription isodose levels.

Radiobiological evaluation of intensity modulated radiation therapy treatments of patients with head and neck cancer: A dual-institutional study.

In clinical practice, evaluation of clinical efficacy of treatment planning stems from the radiation oncologist's experience in accurately targeting tumors, while keeping minimal toxicity to various organs at risk (OAR) involved. A more objective, quantitative method may be raised by using radiobiological models. The purpose of this work is to evaluate the potential correlation of OAR-related toxicities to its radiobiologically estimated parameters in simultaneously integrated boost (SIB) intensity modulated radiation therapy (IMRT) plans of patients with head and neck tumors at two institutions. Lyman model for normal tissue complication probability (NTCP) and the Poisson model for tumor control probability (TCP) models were used in the Histogram Analysis in Radiation Therapy (HART) analysis. In this study, 33 patients with oropharyngeal primaries in the head and neck region were used to establish the correlation between NTCP values of (a) bilateral parotids with clinically observed rates of xerostomia, (b) esophagus with dysphagia, and (c) larynx with dysphagia. The results of the study indicated a strong correlation between the severity of xerostomia and dysphagia with Lyman NTCP of bilateral parotids and esophagus, respectively, but not with the larynx. In patients without complications, NTCP values of these organs were negligible. Using appropriate radiobiological models, the presence of a moderate to strong correlation between the severities of complications with NTCP of selected OARs suggested that the clinical outcome could be estimated prior to treatment.

Dosimetric effect of photon beam energy on volumetric modulated arc therapy treatment plan quality due to body habitus in advanced prostate cancer.

PURPOSE: The purpose of this study was to dosimetrically compare 6- and 10-MV photon beam energies in high-risk prostate cancer patients of various body habitus using a volumetric modulated arc therapy (VMAT) radiation delivery technique. The objectives of the study were to evaluate whether dosimetric differences exist and to investigate whether differences are dependent on patient body habitus. METHODS AND MATERIALS: Forty patients with various body habitus who had previously received treatment to the prostate and pelvic lymph nodes with VMAT techniques were chosen. Patients were planned in the Pinnacle(3) treatment planning system with double or triple SmartArc plans with 6- and 10-MV photon energies. All patients were optimized with the same planning objectives and normalized such that 95% of the planning target volume (PTV) received the prescription dose. Patients were evaluated for PTV and organ at risk (OAR) parameters for the bladder, rectum, small bowel, penile bulb, and sigmoid colon. Metrics used for comparison were D2%, D98%, homogeneity, conformity, and dose falloff for the PTV and D(2%), D(mean), V(80%), V(60%), and V(40%) for OARs. Statistical differences were evaluated with a paired-sample Wilcoxon signed rank test with a significance level of .05. RESULTS: For the PTV, there were no statistically significant differences in D(mean), D(2cc), conformation number, and homogeneity index values, but the dose falloff parameters, R50 and R25, showed a median improvement of 6.7% (P<.01) and 6.2% (P<.01), respectively, with 10 MV. A correlation between patient anterior-posterior distance (d(AP)) and percentage reduction in R50 of 0.436% per centimeter (P<.01) was determined. For OARs, statistically significant reductions in dose metrics were found in the small bowel and bladder, but increases in the D(2cc) of 3.5% in the penile bulb (P<.01) and 0.2% in the rectum (P=.02) were shown with 10 MV. The use of 10 MV also demonstrated a statistically significant reduction in the total number of monitor units of 15.9% (P<.01) compared with 6 MV. CONCLUSIONS: The study showed that 10 MV provides a faster dose falloff than 6 MV for patients whose prostate and pelvic lymph nodes are treated using a VMAT technique irrespective of body habitus; however, the improvement in dose falloff is dependent on body habitus and increases as the patient body habitus increases.

Treatment of Experimental Candida Sepsis with a Janus Kinase Inhibitor Controls Inflammation and Prolongs Survival.

Janus kinases (JAK) are intracellular tyrosine kinases that transduce cytokine-mediated signals to the nucleus, promoting gene expression. Cytokines play a major role in microbial sepsis, which is often associated with uncontrolled inflammation leading to death. JAK inhibitors have been used for the treatment of several autoimmune diseases by modulating immune response, but they have never been tested against microbial sepsis. Ruxolitinib is a small-molecule inhibitor of JAK1/2 proteins, which are involved in the downstream signaling pathway of the vast majority of proinflammatory and anti-inflammatory cytokines. We therefore studied the effect of ruxolitinib in a mouse model of sepsis due to Candida albicans. When ruxolitinib therapy (50 mg/kg [of body weight]/day) was started 1 day before infection, the median survival time was reduced by 3 days, the fungal loads in all organs were higher, the inflammation was significantly less, and serum tumor necrosis factor alpha (TNF-α) and interleukin 10 (IL-10) levels and IL-10/TNF-α ratios were higher than in controls. When ruxolitinib therapy (50 to 1.5 mg/kg/day) was started 1 day after infection, an inverted-U relationship was found, with 6.25 mg/kg/day prolonging median survival time by 6 days, resulting in similar fungal loads, less inflammation, and similar cytokine levels but higher IL-10/TNF-α ratios than the controls. The optimal dose of ruxolitinib controlled infection and prolonged survival with less inflammation than in control animals. Administration of JAK inhibitors may be a promising therapeutic adjunct that needs further investigation.

Optical properties of high aspect ratio plasma etched silicon nanowires: fabrication-induced variability dramatically reduces reflectance.

In this work we investigate both experimentally and theoretically the optical properties of aligned, perpendicular to the substrate, high aspect ratio (AR), plasma etched Si nanowires (SiNWs) with controlled variability. We focus on the role of imperfections in fabrication, which manifest themselves as dimensional variability of SiNW, lattice defects or positional randomization. SiNW arrays are fabricated by e-beam lithography (perfectly ordered array) or colloidal particle self-assembly (quasi-ordered array) followed by cryogenic Si plasma etching, which offers fast etch rate (up to 3 µm min(-1)) combined with clean, smooth, and controllable sidewall profile, but induces some dimensional variability on the diameters of the SiNWs. Sub-200 nm diameter SiNWs having AR as high as 37:1 are demonstrated. The total reflectance of SiNWs is below 2% in a wide range of the optical spectrum. We experimentally demonstrate improved light absorption when moving from a perfectly ordered (after e-beam lithography) to a defective and quasi-ordered (after colloidal self-assembly) SiNW array. In addition our measured reflectivity (for both ordered and quasi-ordered SiNWs) is much lower compared to the one predicted theoretically for a perfect SiNWs array, using full-electrodynamic calculations with the layer-multiple-scattering method. To explain such low reflectivity, we model the influence of disorder using the average T-matrix approximation and show that even small dimensional variability (10-20%) leads to dramatic reduction of the reflectance (matching the experimental results) and increased light trapping inside the SiNW justifying their possible application in photovoltaic devices.

Pediatric Cranio-spinal Axis Irradiation: Comparison of Radiation-induced Secondary Malignancy Estimations Based on Three Methods of Analysis for Three Different Treatment Modalities.

Pediatric cranio-spinal axis irradiation (CSI) is a valuable treatment for many central nervous system (CNS) diseases, but due to the life expectancies and quality of life expectations for children, the minimization of the risk for radiation-induced secondary malignancies must be a high priority. This study compared the estimated CSI-induced secondary malignancy risks of three radiation therapy modalities using three different models. Twenty-four (n = 24) pediatric patients previously treated with CSI for tumors of the CNS were planned using three different treatment modalities: three-dimensional conformal radiation therapy (3D-CRT), volume modulated arc therapy (VMAT), and Tomotherapy. Each plan was designed to deliver 23.4 Gy (1.8 Gy/fraction) to the target which was defined as the entire brain and spinal column with a 0.7 cm expansion. The mean doses as well as the dose volume histograms (DVH) of specific organs were analyzed for secondary malignancy risk according to three different methods: the effective dose equivalent (EDE), the excess relative risk (ERR), and the linear quadratic (LQ) models. Using the EDE model, the average secondary risk was highest for the 3D-CRT plans (37.60%), compared to VMAT (28.05%) and Tomotherapy (27.90%). The ERR model showed similarly that the 3D-CRT plans had considerably higher risk (10.84%) than VMAT and Tomotherapy, which showed almost equal risks (7.05 and 7.07%, respectively). The LQ model requires organ-specific cell survival parameters, which for the lungs, heart, and breast relevant values were found and applied. The lung risk for secondary malignancy was found to be 1.00, 1.96, and 2.07% for 3D-CRT, VMAT, and Tomotherapy, respectively. The secondary cancer risk for breast was estimated to be 0.09, 0.21, and 0.27% and for heart it was 9.75, 6.02 and 6.29% for 3D-CRT, VMAT, and Tomotherapy, respectively. Based on three methods of secondary malignancy estimation, the 3D-CRT plans produced highest radiation-induced secondary malignancy risk, and the VMAT and Tomotherapy plans had nearly equal risk. Pediatric patients must be treated with reducing long term sequelae as a priority.

A gEUD-based inverse planning technique for HDR prostate brachytherapy: feasibility study.

PURPOSE: The purpose of this work was to study the feasibility of a new inverse planning technique based on the generalized equivalent uniform dose for image-guided high dose rate (HDR) prostate cancer brachytherapy in comparison to conventional dose-volume based optimization. METHODS: The quality of 12 clinical HDR brachytherapy implants for prostate utilizing HIPO (Hybrid Inverse Planning Optimization) is compared with alternative plans, which were produced through inverse planning using the generalized equivalent uniform dose (gEUD). All the common dose-volume indices for the prostate and the organs at risk were considered together with radiobiological measures. The clinical effectiveness of the different dose distributions was investigated by comparing dose volume histogram and gEUD evaluators. RESULTS: Our results demonstrate the feasibility of gEUD-based inverse planning in HDR brachytherapy implants for prostate. A statistically significant decrease in D10 or/and final gEUD values for the organs at risk (urethra, bladder, and rectum) was found while improving dose homogeneity or dose conformity of the target volume. CONCLUSIONS: Following the promising results of gEUD-based optimization in intensity modulated radiation therapy treatment optimization, as reported in the literature, the implementation of a similar model in HDR brachytherapy treatment plan optimization is suggested by this study. The potential of improved sparing of organs at risk was shown for various gEUD-based optimization parameter protocols, which indicates the ability of this method to adapt to the user's preferences.

An unusual presenting symptom of graves' disease: myalgia.

A 50-year-old female patient presented with severe myalgia involving her proximal muscles for 3-4 weeks. She also reported mild thyrotoxic symptoms over the same time period. Examination revealed mild thyrotoxicosis, a moderate diffuse goiter and no eye signs. The clinical picture was dominated by muscle pain and tenderness involving mainly her proximal arms and legs, her calves and her fingers, requiring opiate analgesia. Muscle power and tendon reflexes were normal. Laboratory evaluation revealed undetectable serum thyroid stimulating hormone (TSH) with raised FT4, FT3 and positive TSH receptor antibodies. Treatment with carbimazole was started. Additional laboratory investigations were negative (inflammatory markers, creatine kinase and antibodies to antinuclear antibodies, gastric parietal cell, smooth muscle, mitochondrial, dsDNA, centromere, extractable nuclear antigen (ENA) ribonucleoprotein, ENA Sm, ENA Ro, ENA Anti-La, ENA Scl70, ENA Jo-1, anti-CCP and rheumatoid factor). Further assessment in the rheumatology clinic confirmed there was no small joint tenderness or loss of range of movement of her limbs, but widespread and profound muscle tenderness of the common extensors of the forearms, biceps, trapezius, calves and thighs. She was treated symptomatically with analgesic medication and continued on carbimazole. A month later she was euthyroid and her myalgia had resolved. Hyperthyroidism has a profound effect on skeletal muscle and often leads to myopathy. Severe myalgia in association with Graves' disease is rare and resolves with the restoration of euthyroidism.

Radiobiological evaluation of breast cancer radiotherapy accounting for the effects of patient positioning and breathing in dose delivery. A meta analysis.

In breast cancer radiotherapy, significant discrepancies in dose delivery can contribute to underdosage of the tumor or overdosage of normal tissue, which is potentially related to a reduction of local tumor control and an increase of side effects. To study the impact of these factors in breast cancer radiotherapy, a meta analysis of the clinical data reported by Mavroidis et al. (2002) in Acta Oncol (41:471-85), showing the patient setup and breathing uncertainties characterizing three different irradiation techniques, were employed. The uncertainties in dose delivery are simulated based on fifteen breast cancer patients (5 mastectomized, 5 resected with negative node involvement (R-) and 5 resected with positive node involvement (R1)), who were treated by three different irradiation techniques, respectively. The positioning and breathing effects were taken into consideration in the determination of the real dose distributions delivered to the CTV and lung in each patient. The combined frequency distributions of the positioning and breathing distributions were obtained by convolution. For each patient the effectiveness of the dose distribution applied is calculated by the Poisson and relative seriality models and a set of parameters that describe the dose-response relations of the target and lung. The three representative radiation techniques are compared based on radiobiological measures by using the complication-free tumor control probability, P(+) and the biologically effective uniform dose, (BEUD)concepts. For the Mastectomy case, the average P(+) values of the planned and delivered dose distributions are 93.8% for a (BEUD)(CTV) of 51.8 Gy and 85.0% for a (BEUD)(CTV) of 50.3 Gy, respectively. The respective total control probabilities, P(B) values are 94.8% and 92.5%, whereas the corresponding total complication probabilities, P(1) values are 0.9% and 7.4%. For the R- case, the average P(+) values are 89.4% for a (BEUD)(CTV) of 48.9 Gy and 88.6% for a (BEUD)(CTV) of 49.2 Gy and 85.5% for a (BEUD)(CTV) of 49.1 Gy, respectively. The respective PB values are 90.2% and 90.1%, whereas the corresponding P(+) values are 4.1% and 4.6%. The combined effects of positioning uncertainties and breathing can introduce a significant deviation between the planned and delivered dose distributions in lung in breast cancer radiotherapy. The positioning and breathing uncertainties do not affect much the dose distribution to the CTV. The simulated delivered dose distributions show larger lung complication probabilities than the treatment plans. This means that in clinical practice the true expected complications are underestimated. Radiation pneumonitis of Grade 1-2 is more frequent and any radiotherapy optimization should use this as a more clinically relevant endpoint.

Diffractive chains of plasmonic nanolenses: combining near-field focusing and collective enhancement mechanisms.

We study, by means of full-electrodynamic calculations using the layer-multiple-scattering method, the effect of diffractive coupling on the enhancement of the local electromagnetic field in periodic arrays of nanolenses consisting of three silver spheres with progressively decreasing sizes and separations. The interaction between the hot-spot modes of an isolated nanolens with the Rayleigh-Wood anomalies of the periodic lattice leads to a further enhancement of the local field intensity, which can be controlled by an appropriate choice of the geometrical parameters involved.

3D dose reconstruction of pretreatment verification plans using multiple 2D planes from the OCTAVIUS/Seven29 phantom array.

The purpose of this study is to evaluate 3D dose reconstruction of pretreatment verification plans using multiple 2D planes acquired from the OCTAVIUS phantom and the Seven29 detector array. Eight VMAT patient treatment plans of different sites were delivered onto the OCTAVIUS phantom. The plans span a variety of tumor site locations from low to high plan complexity. A patient specific quality assurance (QA) plan was created and delivered for each of the 8 patients using the OCTAVIUS phantom in which the Seven29 detector array was placed. Each plan was delivered four times by rotating the phantom in 45° increments along its longitudinal axis. The treatment plans were delivered using a Novalis Tx with the HD120 MLC. Each of the four corresponding planar doses was exported as a text file for further analysis. An in-house MATLAB code was used to process the planar dose information. A cylindrical geometry-based, linear interpolation method was utilized to generate the measured 3D dose reconstruction. The TPS calculated volumetric dose was exported and compared against the measured reconstructed volumetric dose. Dose difference, dose area histograms (DAH), isodose lines, profiles, 2D and 3D gamma were used for evaluation. The interpolation method shows good agreement (<2%) between the planned dose distributions in the high dose region but shows discrepancies in the low dose region. Horizontal profiles, dose area histograms and isodose lines show good agreement for the sagittal and coronal planes but demonstrate slight discrepancies in the transverse plane. The 3D gamma index average was 92.4% for all patients when a 5%/5 mm gamma passing rate criteria was employed but dropped to <80.1% on average when parameters were reduced to 2%/2 mm. A simple cylindrical geometry-based, linear interpolation method is able to predict good agreement in the high dose region between the reconstructed volumetric dose and the planned volumetric dose. It is important to mention that the interpolation algorithm introduces dose discrepancies in small regions within the high dose gradients due to the interpolation itself. However, the work presented serves as a good starting point to establish a benchmark for the level of manipulation necessary to obtain 3D dose delivery quality assurance using current technology.

SU-E-T-562: Reducing the Arc Span for CSA VMAT Delivery.

PURPOSE: To dosimetrically evaluate advantages and disadvantages of using multiple, shorter, sub-arcs versus full arc deliveries for treatment of cranio-spinal axis (CSA) irradiation. METHODS: Five (n=5) cranio-spinal axis irradiation patients were planned using 2 complete arcs, one superior and one inferior; with gantry rotations from 1 to 359 degrees. Due to supine patient setup, each original full arc was then replanned split into two sub arcs with gantry rotations from 1 to 100 and 260 to 359 degrees creating 4 smaller arcs. The PTV was normalized such that 95% received at least 23.4 Gy in 13 fractions. The PTV was evaluated based on conformity number and homogeneity index. The normal structures were evaluated based on maximum and mean doses. Beam on times and monitor units were compared. RESULTS: Averaged over all patients, conformity number was calculated to be approximately 0.86 and 0.82 for full arc and sub arc plans respectively. The homogeneity index was approximately 1.07 and 1.06 for full arc and sub arc plans. This indicates better target conformity but less homogeneous dose distribution for full arc plans as compared with sub arc plans. With the exception of the eyes, each normal structure evaluated had lower maximum doses with subarc plans. All normal structures, with the exception of the left kidney, had lower mean doses using sub arc deliveries. Beam on times were shorter on average for full arcs, but the monitor units were lower on average for sub arcs. CONCLUSIONS: Overall, CSA patients would benefit from the use of sub arc treatment deliveries versus full arc deliveries. Nearly all normal structure doses were lower for sub arcs, while the PTV was still adequately covered and beam on times and monitor units were similar.

SU-E-T-387: Validation of a New System for Patient Specific IMRT QA and Comparison with Other Commerical Systems.

PURPOSE: The focus of this project is to compare the Octavius 4D with current commercial available dose validation systems: MatriXX MultiCube and Delta4. METHODS AND MATERIALS: Many challenges are faced with properly measuring Intensity Modulated Radiotherapy (IMRT). It has become common practice for clinics to use film, arrays, or multiple detectors to validate dose measurements pretreatment for static and dynamic treatments. IMRT QAs for various treatment sites were measured for patients using three different dose validation systems. All measurements were taken on a Varian CLinac 2100 C/D, SN-757, 80 MLC with 6MV. The treatment plans evaluated were Step-N-Shoot. Data analysis was performed using the software provided with each dose validation system. Detailed information was gathered from each system with their perspective advantages. The latest system, Octavius 4D, allows one to calculate the Gamma Index for Coronal, Sagittal, and Transversal views for every slice included in the measurement along with the traditional data analysis provided; histograms, horizontal and vertical profiles, DTA. RESULTS AND DISCUSSION: The Gamma Index values were observed using the MatriXX Multicube, Delta4, and Octavius 4D. The treatment plan included five fields at various gantry angles. Also the gamma index and profiles were calculated for various treatment sites. Delta 4 and the Octavius 4D appears to be quite comparable. Each device has the ability to allow one to verify segmented and composite fields, measure dose profiles and analysis using the Gamma Method. ConclusionsSimilar IMRT QA measurements will be made for more Step-N-Shoot cases with the addition of SmartArcs. The limitations of each system will be determined for each system using the Gamma Index as a reference while varying the Region of Interest, Threshold, and Gamma Method (local, normalization, and maximum dose), as well as the 2D- profiles for these cases.

SU-E-T-465: Exploring the Dosimetric and Tumor Control Consequences of Prostate Seed Loss and Migration.

PURPOSE: Once implanted, prostate brachytherapy seeds are vulnerable to loss and movement. A general estimation of these effects may be useful for making patient care decisions when seeds are lost after the post-implant scan. The goal of this work was to explore the dosimetric and radiobiological effects of the types of seed loss and migration common in prostate brachytherapy. METHODS: This study evaluates five patients. For each, three treatment plans were created using Iodine-125, Palladium-103 and Cesium-131. The three seeds closest to the urethra were identified and modeled as seeds lost through the urethra. The three seeds closest to the exterior of prostatic capsule were identified and modeled as those lost from the prostate periphery. The seed locations and organ contours were exported from Prowess and used by in-house software to perform the dosimetric and radiobiological evaluation. The radiobiological evaluation was based on the linear-quadratic model. Seed loss was simulated by removing 1, 2 or 3 seeds near the urethra 0, 2 or 4 days after the implant or removing seeds near the exterior of the prostate 14, 21 or 28 days after the implant. RESULTS: Loss of 1, 2 or 3 seeds through the urethra resulted in D90 reduction of 2%, 5% and 7% loss respectively. Due to delayed loss of peripheral seeds, effects were less severe than for loss through the urethra. However, while the dose reduction is modest for multiple lost seeds, the reduction in tumor control probability was minimal. CONCLUSIONS: The goal of this work was to explore the dosimetric and radiobiological effects of the types of seed loss and migration commonly seen in prostate brachytherapy. The results presented show that loss of multiple seeds can cause a substantial reduction of D90 coverage. However, the dose reduction was not seen to significantly reduce tumor control probability.

SU-E-T-458: Radiobiological Comparison of Single and Dual-Isotope Prostate Seed Implants.

PURPOSE: Several isotopes are available for low dose-rate brachytherapy of the prostate. Currently, most implants use a single isotope. However, the use of dual-isotope implants may yield an advantageous combination of characteristics such as half-life and relative biological effectiveness. However, the use of dual-isotope implants complicates treatment planning and quality assurance. Do the benefits of dual-isotope implants outweigh the added difficulty? The goal of this work was to use a linear-quadratic model to compare single and dual-isotope implants. METHODS: Ten patients were evaluated in this study. For each patient, six treatment plans were created with single or dual-isotope combinations of 1251, 103Pd and 131Cs. For each plan the prostate, urethra, rectum and bladder were contoured by a physician. The biologically effective dose was used to determine the tumor control probability and normal tissue complication probabilities for each plan. Each plan was evaluated using favorable, intermediate and unfavorable radiobiological parameters. The results of the radiobiological analysis were used to compare the single and dual-isotope treatment plans. RESULTS: Iodine-125 only implants were seen to be most affected by changes in tumor aggressiveness. Significant differences in organ response probabilities were seen at common dose levels. It was recognized that these differences were likely a result of suboptimal initial seed strengths. After adjusting the initial seed strength to maximize complication-free tumor control the differences between isotope combinations were minimal. This result was true even for unfavorable tumors. CONCLUSIONS: The objective of this work was to perform a radiobiologically based comparison of single and dual-isotope prostate seed implant plans. For all isotope combinations, the plans were improved by varying the initial seed strength. For the minimally-optimized treatment plans, no substantial differences in predicted treatment outcomes were seen among the different isotope combinations.