A Phantom Study on Feasibility of Manual Field-in-Field Clinical Implementation for Total Body Irradiation and Comparison of Midplane Dose with Different Bilateral TBI Techniques.

Objective: The aim of this study is to implement a new treatment technique in total body irradiation (TBI) using the manual field-in-field-TBI (MFIF-TBI) technique and dosimetrically verifying its results with respect to compensator-based TBI (CB-TBI) and open field TBI technique. Materials and Methods: A rice flour phantom (RFP) was placed on TBI couch with knee bent position at 385 cm source to surface distance. Midplane depth (MPD) was calculated for skull, umbilicus, and calf regions by measuring separations. Three subfields were opened manually for different regions using the multi-leaf collimator and jaws. The treatment Monitor unit (MU) was calculated based on each subfield size. In the CB-TBI technique, Perspex was used as a compensator. Treatment MU was calculated using MPD of umbilicus region and the required compensator thickness was calculated. For open field TBI, treatment MU was calculated using MPD of umbilicus region, and the treatment was executed without placing compensator. The diodes were placed on the surface of RFP to measure the delivered dose and the results were compared. Results: The MFIF-TBI results showed that the deviation was within ± 3.0% for the different regions, except for the neck for which the deviation was 8.72%. In the CB-TBI delivery, the dose deviation was ± 3.0% for different regions in the RFP. The open field TBI results showed that the dose deviation was not within the limit ± 10.0%. Conclusion: The MFIF-TBI technique can be implemented for TBI treatment as no TPS is required, and laborious process of making a compensator can be avoided while ensuring that the dose uniformity in all the regions within the tolerance limit.

Drug development and novel therapeutics to ensure a personalized approach in the treatment of systemic sclerosis.

INTRODUCTION: Systemic sclerosis (SSc) is a systemic disease encompassing autoimmunity, vasculopathy, and fibrosis. SSc is still burdened by high mortality and morbidity rates. Recent advances in understanding the pathogenesis of SSc have identified novel potential therapeutic targets. Several clinical trials have been subsequently designed to evaluate the efficacy of a number of new drugs. The aim of this review is to provide clinicians with useful information about these novel molecules. AREA COVERED: In this narrative review, we summarize the available evidence regarding the most promising targeted therapies currently under investigation for the treatment of SSc. These medications include kinase inhibitors, B-cell depleting agents, and interleukin inhibitors. EXPERT OPINION: Over the next five years, several new, targeted drugs will be introduced in clinical practice for the treatment of SSc. Such pharmacological agents will expand the existing pharmacopoeia and enable a more personalized and effective approach to patients with SSc. Thus, it will not only possible to target a specific disease domain, but also different stages of the disease.

Fabrication and Dosimetric Characteristics of Silicon Elastomer-Based Bolus Using External Beam Radiotherapy.

OBJECTIVE: A study on dosimetric characteristics of silicon elastomer-based bolus was carried out using a Linear accelerator (Varian - Unique Performance). The study is performed to know if the silicone elastomer based bolus can be used in the radiotherapy. A bolus is a tissue equivalent material used to provide uniform dose to the uneven surface contours. It is exposed during the radiation therapy and also provides maximum dose (dmax) to treat surface tumors in case of high energy photons like megavoltage therapy photons. It is used in the case of external beam radiation therapy. METHODS: In this study, the bolus was fabricated using PDMS substrate with a curing agent by the ratio of 10:1. The bolus was fabricated in two thicknesses 0.5cm and 1cm. The dosimetric characteristics like transmission factor, mass attenuation coefficient, durability, homogeneity, density test of the fabricated bolus were studied. RESULTS: The dosimetric characteristics of the silicone elastomer based bolus were studied over a period of one month by exposing it in a 6MV photon. The result of the study shows that the silicone elastomer based bolus fabricated, satisfies the dosimetric characteristics needed for a tissue equivalent bolus to be used in the radiation therapy. CONCLUSIONS: The fabricated bolus could increase the percentage surface dose, reduce skin-sparing effect, and protect OAR. The aim of this is to provide an adjustable, transparent, and easily fabricated, less expensive, nontoxic bolus which can be used in the radiotherapy.

Comparison of Progressive Resolution Optimizer and Photon Optimizer algorithms in RapidArc delivery for head and neck SIB treatments.

Background: The aim of this study is to analyze and verify characterization of two different algorithms using simultaneous integrated boost (SIB) in head and neck (H&N) plans. Materials and methods: In our study 15 patients were selected, who received radiation therapy by using Eclipse volumetric modulated arc therapy (VMAT) Progressive Resolution Optimizer (PRO) algorithm 15.1. The same cases were re-optimized using a Photon Optimizer (PO) algorithm 15.6.A total of 30 treatment plans (15 PRO-VMAT plans and 15 PO-VMAT plans) were produced in the present study. All plans were created using double full arcs, keeping the identical constraints, cost functions and optimization time. Plan evaluation was done using planning target volume (PTV) parameters (D98%, D95%, D50%, D2% mean dose and V105%), homogeneity index (HI), conformity index (CI), Monitor unit (MU) per degree with control points (CP), organ at risk (OAR) doses and gamma verification (Portal dosimetry and ArcCHECK) values were evaluated. Treatment was delivered in Varian Truebeam 2.5, energy 6 MV with Millennium 120 multileaf collimator (MLC). Results: The PTV coverage (D95%) for PRO and PO were 98.7 ± 0.8 Gy, 98.8 ± 0.9 Gy, HI were 0.09 ± 0.02 and 0.09 ± 0.02, CI were 0.98 ± 0.01 and 0.99 ± 0.01. Monitor units (MU) for PRO and PO were 647.5 ± 137.9, 655.2 ± 138.4. The Portal dose results were [3%, 3mm (%) & 1 %, 1 mm (%)] for PO and PRO 100 ± 0.1, 95.1 ± 1.4 and 100 ± 0.1, 95.2 ± 1.3. For ArcCHECK were 99.9 ± 0.1, 94.7 ± 3.0 and 99.9 ± 0.1, 93.5 ± 3.9, respectively. Conclusion: Results showed that PTV coverage and OAR doses were comparable. For individual patients CI and HI of PO showed slightly higher values than PRO. MUs for PO were slightly increased as compared to PRO. MU per degree with each individual control points generated by PO showed a high degree of modulation compared to PRO. Hence, new PO optimizer can produce a comparable degree of plan while using the same PRO objectives.

Evaluation of Surface Dose and Commissioning of Compensator-Based Total Body Irradiation.

Purpose: The aim of the current study is to commission compensator-based total body irradiation (TBI) and to compare surface dose using percentage depth dose (PDD) while varying the distance between beam spoiler and phantom surface. Materials and Methods: TBI commissioning was performed on Elekta Synergy® Platform linear accelerator for bilateral extended source to surface distance treatment technique. The PDD was measured by varying the distance (10 cm, 20 cm, 30 cm, and 40 cm) between the beam spoiler and the phantom surface. Beam profile and half-value layer (HVL) measurement were carried out using the FC65 ion-chamber. Quality assurance (QA) was performed using an in-house rice-flour phantom (RFP). In-vivo diodes (IVD) were placed on the RFP at various regions to measure the delivered dose, and it was compared to the calculated dose. Results: An increase in Dmax and surface dose was observed when beam spoiler was moved away from the phantom surface. The flatness and symmetry of the beam profile were calculated. The HVL of Perspex and aluminum is 17 cm and 8 cm, respectively. The calculated dose of each region was compared to the measured dose on the RFP with IVD, and the findings showed that the variation was <4.7% for both Perspex and Aluminum compensators. Conclusion: The commissioning of the compensator-based TBI technique was performed and its QA measurements were carried out. The Mayneord factor corrected PDD and measured PDD values were compared. The results are well within the clinical tolerance limit. This study concludes that 10 cm -20 cm is the optimal distance from the beam spoiler to phantom surface to achieve prescribed dose to the skin.

Dosimetric Importance of Implementing Jaw Tracking Technique in Radiotherapy Treatment Plan Execution.

OBJECTIVE: To study the dosimetric importance of Jaw tracking technique in reducing the doses to organs at risk (OAR) while achieving the optimal dose coverage for the target. METHODS: We retrospectively selected ten Glioblastoma cases and for each patient, two plans were created namely Static Jaw Technique Dynamic Intensity Modulated Radiotherapy plan and Jaw Tracking Technique D-IMRT plan with 6 MV for Varian Truebeam™ STx machine using Eclipse Treatment planning system. Both plans were analyzed and compared based on various dosimetric parameters for Planning Target Volume (PTV) and OARs. The dose agreement between the Portal dose image prediction and the portal dosimetry measurement was also analysed  using gamma analysis criteria of 3%/3mm, 2%/2mm and 1%/1mm of dose distance/distance-to-agreement. RESULTS: The dosimetric parameters evaluated for both plans showed that most of the parameters gave significant P values, where D50% of PTV showed a mean difference (Δ) of 0.45 with significant P value, 0.0104. Similarly mean dose, D2%, D98%, D80% to PTV, Conformity Index and Conformation number showed Δ values of 0.45, 0.51, 0.41, 0.40, 0.02 and 0.01 with their significant P values as 0.0138, 0.0172, 0.0313, 0.0466, 0.0279, 0.0561 respectively. The Δ values and significant P values obtained among OARs are 0.54;0.0224 for brainstem, 0.54;0.0017 for RT optic nerve, 0.52;0.0001 for LT optic nerve, 0.59;0.0040 for optic chiasm and for the healthy tissues it showed the values with their mean dose, V5 and V30 parameters as 0.19;0.0115, 0.59;0.0067 and 0.25;0.0125 respectively. The JTT plans showed better passing results of gamma analysis criteria when compared to SJT plans. CONCLUSION: The findings in the studies emphasize the importance of using JTT technique in the radiotherapy treatment plans as it lowers the risk of acute or late toxicity and secondary radiogenic cancers in patients by reducing the OAR doses and achieves better tumor control.

Dosimetric Importance of the Implementation of Daily Image Guidance in Radiotherapy Practice.

BACKGROUND: The purpose of this study is to show the dosimetric importance of using daily image guidance in radiotherapy treatment. METHODS: A sample of 30 patients with various head and neck cancers were retrospectively selected for the studies. The prescribed dose, 66 Gy/33 fractions was used for all patients who received 7 to 9 beams, 6 MV Intensity Modulated Radiation Therapy (IMRT) plan delivered by Varian Truebeam STx. Before the first fraction of the treatment, the patient's shift corresponds to isocenter was noted and corrected. Subsequently, the images were taken daily for all 30 patients and the maximum, mode, median and mean of all shifts were recorded and applied to the base plan and recalculated for quantitative analysis of tumour coverage and Organ at Risk's (OARs) doses using various dosimetric parameters such as Homogeneity Index (HI), Conformation Number (CN), Conformity Index (CI), Coverage Index (COVI), Dose Gradient Index (DGI) and Unified Dosimetry Index (UDI) of shift plan. RESULTS: The results showed the Planning Target Volume (PTV) and the OARs values deteriorated from its base plan values in the various shift plans created by applying the patient setup errors analyzed using image guidance. Mean dose of maximum shift plan with a significant P value of 0.002, D2% of maximum shift plan with a significant P value 0.028, the D98% Values of maximum and mode plans with the significant P value 0.004 each, the D50% and D80% values of the maximum shift plans with their significant P values 0.001 and 0.002 respectively. Also, HI95%, CN95% and COVI values of the maximum shift plan showed much variation with significant P values of 0.004, 0.040 and 0.0004 respectively from their base plan values. There were significant changes observed in OARs values between base plan and shift plans. CONCLUSION: Implementation of daily image guidance in radiotherapy is mandatory taking into account of its dosimetric importance and to achieve the goal of radiotherapy practice of sparing the critical organs without compromising the target coverage.

Evaluation of Dosimetric Effect of Millennium and High Definition Multi Leaf Collimator Using 6 MV Photon Beams.

PURPOSE: The present study aims to compare different dosimetric parameters from field sizes defined by secondary and tertiary collimators. A comparison has been drawn between two types of Multi Leaf Collimator (MLC) designs. MATERIALS AND METHODS: The measurements were obtained using Millennium MLC (Mi-MLC) from Varian Unique™ linear accelerator (LINAC-1) and compared with measurements from Varian Truebeam™ linear accelerator (LINAC-2) using High Definition MLC (HD-MLC). Dosimetric analysis included percentage depth dose (PDD), cross profile, dosimetric leaf gap (DLG) and scatter factor (SF) that were taken for different field sizes defined by both the MLC design and jaw. For beam data measurement PTW Radiation field analyse (RFA) was utilized. RESULTS: When the surface dose for MLC field for linac 1 and linac 2 were compared with jaws they were found to be on the higher side that is 2.8% to 4.9% and 2.2% to 3.6% respectively. The SF was found to vary from -3.2% to 0.73% for LINAC-1 with Mi-MLC when compared with jaws. Similarly, the SF variation from -2.4% to 1.1% was observed for LINAC-2 with HD-MLC as compared with jaw. Larger field sizes gave increased SF while smaller field sizes showed the opposite for HD-MLC. The penumbra was found to be less in HD-MLC as compared to Mi-MLC. Similarly, DLG was found to reduce by 0.056 mm in Mi-MLC when compared with HD-MLC. The results of symmetry and flatness were seen within the limits for both MLC designs. CONCLUSION: It can be concluded from the results that both the MLC designs have merits and demerits that are based on their effectiveness and clinical use. However, higher surface dose was found in HD-MLC in contrast to Mi-MLC.

Analysis of normal lung irradiation in radiosurgery treatments: a comparison of lung optimized treatment (LOT) on cyberknife, 4D target volume on helical tomotherapy, and DIBH on linear accelerator.

Quantitative retrospective analysis of the normal lung irradiation due to the variations of the ITV volume based on the techniques used for upper lobe (UL), mid lobe (ML), and lower lobe (LL) lung tumours when used with 2-view, 1-view, 0-view based LOT technique on Cyberknife, AveIP on Helical Tomotherapy, and DIBH on VMAT systems. In the treatment of lung tumours, patients medically inoperable or those who are unwilling to undergo surgery have the option to be treated using radiation therapy. There are many motion control techniques available for the treatment of the moving target, such as movement encompassment, respiratory gating, breath-hold, motion reduction, and tumour monitoring. ITV generation is dependent on technique and hence the volume of the PTVs will differ based on the technique used. This study aimed to determine the influence of these ITVs on the irradiated normal lung volume for UL, ML, and LL lung tumours for 23 patients. The mean difference in the PTV volumes generated with the 0-view technique was significant with that of 2-view and DIBH techniques (p-value < 0.04). The mean difference in the PTV volumes generated by 2-view and DIBH was small for UL, ML, and LL tumours. V5 of the combined lung with the 0-view method was 5% compared to the 2-view method for UL tumours (p-value = 0.04) and the same was 9.5%, and 16.8% for ML and LL tumours (p-value < 0.04). In contrast to all other techniques, lung volume parameters V5, V10, V20, and V30 for the 0-view technology were consistently higher irrespective of the tumour location in the lung. The observed maximum mean lung dose (MLD) was 6.2 Gy ± 2.7 Gy with the 0-view technique and the minimum was 3.85 Gy ± 1.75 Gy with the DIBH technique. The difference in MLD between DIBH and 2-view was negligible (p-value = 0.67). The MLD increased for LL tumours from 4 Gy to 6.5 Gy from the 2-view to 0-view technique (p-value = 0.009). There was a significant increase in MLD for LL tumours with the 0-view technique compared to AveIP (1.9 Gy, p-value = 0.04) and DIBH (2.0 Gy, p-value = 0.003) technique. For ML and UL tumours, except for 0-view and 1-view, the difference in the MLD between the rest of the methods was not significant (p-value > 0.11). In the treatment of lung tumour patients with SBRT, this study has demonstrated 2-view with Cyberknife and DIBH with VMAT treatment techniques have optimal normal lung tissue sparing. There was a significant increase in the average lung volume receiving 5%,10%, 20%, and 30% dose when comparing the 1-view, 0-view, AveIP, and DIBH techniques to the 2-view technique. However, DIBH with VMAT was dosimetrically advantageous for ML and LL tumours, while providing significantly shorter treatment times than any other technique studied.

Mn-doped nickeltitanate (Ni1-x Mn x TiO3) as a promising support material for PdSn electrocatalysts for methanol oxidation in alkaline media.

Nickeltitanate (Ilmenite) has been prepared with stoichiometric variation by substituting Mn in the 'A' site, using the sol-gel method in a highly active form. The PdSn electrocatalyst was then impregnated with nickeltitanate by a microwave-assisted polyol method. The physiochemical characterisation of the synthesized electrocatalyst PdSn-Ni1-x Mn x TiO3 was done by X-ray diffractometry, UV-visible spectrophotometry, Raman spectroscopy and transmission electron microscopy. The elemental composition was obtained using energy dispersive spectra which confirmed the presence of Ni, Mn, Ti, O, Pd and Sn. Electrochemical characterization using cyclic voltammetry and polarization experiments showed that the synthesized PdSn-Ni1-x Mn x TiO3 exhibited an enhanced catalytic activity and better stability in the alkaline medium, compared to conventional PdSn/C catalysts. It was observed that the charge transfers from the support material (Ni1-x Mn x TiO3) to the PdSn electrocatalyst boosted the oxidation reaction. By varying the methanol concentration from 0.5 M to 2.0 M, the resulting current density also varied from 129 to 151 mA cm-2. This result demonstrated that the prepared material PdSn-Ni1-x Mn x TiO3/C electrocatalyst is an excellent candidate for the methanol oxidation reaction.

IMPACT OF THREE DIFFERENT MATCHING METHODS ON PATIENT SET-UP ERROR IN X-RAY VOLUMETRIC IMAGING FOR HEAD AND NECK CANCER.

Impact of three different matching methods for delivery of Volumetric Modulated Arc Therapy (VMAT) in Cone-beam computed tomography (CBCT) on patient set-up error. As per institutional imaging protocol, 300 CBCT scans of 20 VMAT head and neck cancer patients treated with 60 Gy/30 fractions were chosen for the present study. Approved CT images of the plan were registered as a reference with the CBCT images on board. Grey-scale matching (GM), manual matching (MM), and bone matching (BM) between on-board CBCT and reference CT images were used to assess patient translation errors. Patient positioning verification was evaluated using the Clip-box registration in all three matching methods. Using the GM approach as a reference point, two additional matchings were rendered in offline mode using BM and MM. For analysis, random error (σ), systematic error (∑), maximum error (E) mean set-up error (M), mean displacement vector (R), matching time (Mt), and multiple comparisons using Post hoc Tukey's HSD test were performed. In MM, less random and systematic errors were found than in GM and BM with an insignificant difference (p > 0.05) Compared to BM and GM, the maximum error, mean set-up error, and displacement vector were marginally less in MM (p > 0.05). In MM, an increased Mt relative to BM and GM was observed (p > 0.05). Furthermore, an insignificant difference in set-up error was revealed in a multiple comparison test (p > 0.05). Any of the three matching methods can be used during CBCT to check patient translation errors for the delivery of the VMAT head and neck patients.

Managing gastrointestinal complications in patients with systemic sclerosis.

OBJECTIVE: We sought to critically evaluate the literature published over the past 3 years on the management of gastrointestinal complications in systemic sclerosis (SSc). We emphasize interesting and important new findings to bring the reader up-to-date. We also discuss controversial discoveries and hypotheses currently of interest. METHODS: We conducted a literature search on PubMed over the last 3 years using the key words "systemic sclerosis," "gastrointestinal," "scleroderma," and "treatment." We also screened clinicaltrials.gov for ongoing trials relevant to the gastrointestinal complications of SSc. Reference lists from recent reviews on the management of gastrointestinal complications of SSc to identify articles that might have been missed in the initial search. RESULTS: 103 publications and ongoing clinical trials were identified. We eliminated all case reports and review articles. Ultimately we had 58 articles remaining and we prioritized what we found to be the strongest and/or novel findings to discuss in this review. CONCLUSIONS: Advances in the management of gastrointestinal disease in SSc continue to evolve. The application of novel therapies and the repurposing of existing therapies for the management of gastrointestinal involvement are shaping the therapeutic arsenal so that we can more effectively manage these complex patients.

An Experimental Slope Method for a More Accurate Measurement of Relative Radiation Doses using Radiographic and Radiochromic Films and Its Application to Megavoltage Small-Field Dosimetry.

PURPOSE: An experimental method using the linear portion of the relative film dose-response curve for radiographic and radiochromic films is presented, which can be used to determine the relative depth doses in a variety of very small, medium, and large radiation fields and relative output factors (ROFs) for small fields. MATERIALS AND METHODS: The film slope (FS) method was successfully applied to obtain the percentage depth doses (PDDs) for external beams of photon and electrons from a Synergy linear accelerator (Elekta AB, Stockholm, Sweden) under reference conditions of 10 cm × 10 cm for photon beam and nominal 10 cm × 10 cm size applicator for electron beam. For small-field dosimetry, the FS method was applied to EDR2 films (Carestream Health, Rochester, NY) for 6 MV photon beam from a linac (Elekta AB, Stockholm, Sweden) and small, circular radiosurgery cones (Elekta AB, Stockholm, Sweden) with diameters of 5, 7.5, 10, 12.5, and 15 mm. The ROFs for all these cones and central axis PDDs for 5, 10, and 15 mm diameter cones were determined at source-to-surface distance of 100 cm. The ROFs for small fields of CyberKnife system were determined using this technique with Gafchromic EBT3 film (Ashland, NJ, USA). The PDDs and ROFs were compared with ion chamber (IC) and Monte Carlo (MC) simulated values. RESULTS: The maximum percentage deviation of PDDFS with PDDIC for 4, 6, and 15 MV photon beams was within 1.9%, 2.5%, and 1.4%, respectively, up to 20-cm depth. The maximum percentage deviation of PDDFS with PDDIC for electron beams was within 3% for energy range studied of 8-15 MeV. The gamma passing rates of PDDFS with PDDIC were above 96.5% with maximum gamma value of >2, occurring at the zero depths for 4, 6, and 15 MV photons. For electron beams, the gamma passing rates between PDDFS with PDDIC were above 97.7% with a maximum gamma value of 0.9, 1.3, and 0.7 occurring at the zero depth for 8, 12, and 15 MeV. For small field of 5-mm cone, the ROFFS was 0.665 ± 0.021 as compared to 0.674 by MC method. The maximum percentage deviation between PDDFS and PDDMC was 3% for 5 mm and 10 mm and 2% for 15 mm cones with 1D gamma passing rates, respectively, of 95.5%, 96%, and 98%. For CyberKnife system, the ROFFS using EBT3 film and MC published values agrees within 0.2% for for 5 mm cone. CONCLUSIONS: The authors have developed a novel and more accurate method for the relative dosimetry of photon and electron beams. This offers a unique method to determine PDD and ROF with a high spatial resolution in fields of steep dose gradient, especially in small fields.

Investigation of Internal Target Volumes Using Device and Deviceless Four-dimensional Respiratory Monitoring Systems for Moving Targets in Four-dimensional Computed Tomography Acquisition.

AIMS AND OBJECTIVES: The influence of target motion on the reconstructed internal target volume (ITV) for device-based (DB) external surrogate system and Smart deviceless (DL) 4-dimensional (4D) system were compared in a controlled phantom experiment. The volumetric changes in reconstructed ITVs from the average intensity projection (AveIP) images using DB method (Anzai Respiratory Gating System, ANZAI MEDICAL CO., LTD, Japan) and DL method (Smart deviceless 4D system by GE Medical Systems (Chicago, USA)) with the theoretical true volume (ITVth) for moving target with the increasing target motion in anterior-posterior (A-P), lateral (left-right [L-R]) and inferior-superior (S-I) directions were assessed. MATERIALS AND METHODS: 4D computed tomography (4DCT) of CIRS dynamic phantom (Computerized Imaging Reference Systems Inc., Norfolk, VA, USA) with 2.5 cm diameter spherical target of volume 8.2 cc programmed to move in a cos4(x) motion pattern placed in the lung volume were acquired for various target motion pattern using DB and DL method of gating. AveIP images of 10 phase binned image sets were generated and ITVs were delineated. RESULTS: The maximum absolute percent differences between ITVave and ITVth for DL and DB methods were 15.91% and 4.94 % respectively for target motion of 5 mm in AP with 15 mm S-I direction. When the S-I motion was decreased to 10 mm, the observed % difference of the ITVs were also decreased to 12.5% and 0.3% for DL and DB method. When the lateral [L-R] motion was varied from 0 mm to 5 mm for S-I motion of 5 mm to 15 mm, the differences in the ITVs were significant (P = 0.004) with the maximum absolute percent difference of 18.61% and 4.94 % for DL and DB gating. With the simultaneous motion of the target in all the 3 directions, the difference in the reconstructed ITVs were statistically significant for DL method (P = 0.0002) and insignificant for DB method (P = 0.06) with an average increase of 10% in ITVDL against 2% in the ITVDB. The difference in ITVDL was significant for the target motion above 3 mm in A-P and L-R directions for S-I movement of above 10 mm (P = 0.0002). However, for low excursions of the target movement, no significant difference in the ITVs were observed (P > 0.06). In general, ITVDBs were closer to the ITVth (within 7.8%) than ITVDL (18.61%). CONCLUSION: The results showed that the DL method is an effective way of image sorting in 4D acquisition for smaller target excursion. When the target motion exceeds 3 mm in A-P and L-R directions with S-I more than 10 mm, DB method is the choice due to its accuracy in reproducing the absolute target volume.

Validation of a Software Upgrade in a Monte Carlo Treatment Planning System by Comparison of Plans in Different Versions.

PURPOSE: Validation of a new software version of a Monte Carlo treatment planning system through comparing plans generated by two software versions in volumetric-modulated arc therapy (VMAT) for lung cancer. MATERIALS AND METHODS: Three patients who were treated with 60 Gy/30 fractions in Elekta Synergy™ linear accelerator by VMAT technique with 2% statistical uncertainty (SU) were chosen for the study. Multiple VMAT plans were generated using two different software versions of Monaco treatment planning system TPS (V5.10.02 and V5.11). By keeping all other parameters constant, originally accepted plans were recalculated for the SUs of 0.5%, 1%, 2%, 3%, 4%, and 5%. For plan evaluation, the metrics compared were conformity Index (CI), homogeneity Index (HI), dose coverage to planning target volume (PTV), organ at risk (OAR) doses to spinal cord, pericardium, bilateral lungs-PTV, esophagus, liver, normal tissue integral dose (NTID), volumes receiving dose >5 and >10 Gy, calculation time (tCT), and gamma pass rates. RESULTS: In both versions, CI and HI improved as the SU increased from 0.5% to 5%. No significant dose difference was observed in Dmean to PTV, bilateral lungs-PTV, pericardium, esophagus, liver, normal tissue volume receiving >5, and >10 Gy and NTID. It was observed that while the tCT and gamma pass rates decreased, the maximum dose to PTV increased as the SU increased. No other significant dose differences were observed between the two MC versions compared. CONCLUSION: For lung VMAT plans, in both versions, SU could be accepted up to 3% per plan with reduced tCT without compromising plan quality and deliverability by accepting variations in point dose and an inhomogeneous dose within the target. The plan quality of Monaco™V5.10.02 was similar to Monaco™TPS-V5.11 except for tCT.

There is a need for new systemic sclerosis subset criteria. A content analytic approach.

OBJECTIVES: Systemic sclerosis (SSc) is heterogenous. The objectives of this study were to evaluate the purpose, strengths and limitations of existing SSc subset criteria, and identify ideas among experts about subsets. METHODS: We conducted semi-structured interviews with randomly sampled international SSc experts. The interview transcripts underwent an iterative process with text deconstructed to single thought units until a saturated conceptual framework with coding was achieved and respondent occurrence tabulated. Serial cross-referential analyses of clusters were developed. RESULTS: Thirty experts from 13 countries were included; 67% were male, 63% were from Europe and 37% from North America; median experience of 22.5 years, with a median of 55 new SSc patients annually. Three thematic clusters regarding subsetting were identified: research and communication; management; and prognosis (prediction of internal organ involvement, survival). The strength of the limited/diffuse system was its ease of use, however 10% stated this system had marginal value. Shortcomings of the diffuse/limited classification were the risk of misclassification, predictions/generalizations did not always hold true, and that the elbow or knee threshold was arbitrary. Eighty-seven percent use more than 2 subsets including: SSc sine scleroderma, overlap conditions, antibody-determined subsets, speed of progression, and age of onset (juvenile, elderly). CONCLUSIONS: We have synthesized an international view of the construct of SSc subsets in the modern era. We found a number of factors underlying the construct of SSc subsets. Considerations for the next phase include rate of change and hierarchal clustering (e.g. limited/diffuse, then by antibodies).

Study to Compare the Effect of Different Registration Methods on Patient Setup Uncertainties in Cone-beam Computed Tomography during Volumetric Modulated Arc Therapy for Breast Cancer Patients.

PURPOSE: This study compared three different methods used in registering cone-beam computed tomography (CBCT) image set with planning CT image set for determining patient setup uncertainties during volumetric modulated arc therapy (VMAT) for breast cancer patients. MATERIALS AND METHODS: Seven breast cancer patients treated with 50 Gy in 25 fractions using VMAT technique were chosen for this study. A total of 105 CBCT scans were acquired by image guidance protocol for patient setup verification. Approved plans' CT images were used as the reference image sets for registration with their corresponding CBCT image sets. Setup errors in mediolateral, craniocaudal, and anteroposterior direction were determined using gray-scale matching between the reference CT images and onboard CBCT images. Patient setup verification was performed using clip-box registration (CBR) method during online imaging. Considering the CBR method as the reference, two more registrations were performed using mask registration (MR) method and dual registration (DR) (CBR + MR) method in the offline mode. For comparison, systematic error (∑), random error (σ), mean displacement vector (R), mean setup error (M), and registration time (R t) were analyzed. Post hoc Tukey's honest significant difference test was performed for multiple comparisons. RESULTS: Systematic and random errors were less in CBR as compared to MR and DR (P > 0.05). The mean displacement error and mean setup errors were less in CBR as compared to MR and DR (P > 0.05). Increased R t was observed in DR as compared to CBR and MR (P < 0.05). In addition, multiple comparisons did not show any significant difference in patient setup error (P > 0.05). CONCLUSION: For breast VMAT plan delivery, all three registration methods show insignificant variation in patient setup error. One can use any of the three registration methods for patient setup verification.

Defining Skin Ulcers in Systemic Sclerosis: Systematic Literature Review and Proposed World Scleroderma Foundation (WSF) definition.

PURPOSE: There is a lack of a valid, definition for skin ulcers in SSc to be used in clinical trials. Our aim was to develop a consensus definition for SSc-skin ulcers based on the results of a systematic literature review (SLR) for skin ulcer definitions and expert opinion; and to evaluate its face validity, reliability and feasibility. METHODS: SLR for skin ulcer definitions was conducted using PubMed, Web of Science, and Cochrane library for articles published from inception to January 1st, 2016. SSc experts were to discuss the definitions' categories and vote for the relevant terms. Reliability of the definition were tested in a second expert meeting, seven SSc experts evaluated 7 SSc pts with skin lesions twice. Face validity and feasibility evaluated by sending out case report forms(CRFs) to 4 SSc experts, they were asked to use the definition in 5 pts each. RESULTS: A total of 3464 abstracts and titles were screened, and 446 articles were fully evaluated. Of these, 66 met eligibility criteria and skin ulcer definitions were extracted. SSc experts discussed, refined and voted on the consensus definition using nominal process. Kappa for inter-, intra-rater rater agreement was 0.51, 0.90 respectively. The mean time to decide if the lesion is an ulcer was 7.4 sec. All investigators endorsed the face validity of the new definition in the CRFs. CONCLUSION: Using a SLR and a nominal technique, we developed a preliminary consensus-based definition of SSc-skin ulcers. Face validity, feasibility and reliability were demonstrated for the developed definition.

Gastrointestinal symptom severity in irritable bowel syndrome, inflammatory bowel disease and the general population.

BACKGROUND: Irritable bowel syndrome (IBS) and inflammatory bowel disease (IBD) patients report similar gastrointestinal (GI) symptoms, yet comparisons of symptom severity between groups and with the general population (GP) are lacking. METHODS: We compared Patient-Reported Outcomes Measurement Information System (PROMIS® ) GI symptom scales measuring gastro-esophageal reflux (GER), disrupted swallowing, diarrhea, bowel incontinence, nausea/vomiting, constipation, belly pain, and gas/bloating in: (i) USA GP sample, (ii) IBS patients, and (iii) IBD patients from tertiary care and community populations. Symptom severity scores were based on T-score metric with mean 50±10 (standard deviation) relative to the GP. KEY RESULTS: Of 1643 patients enrolled, there were 253 IBS patients (68% F, mean age 45±15 years), 213 IBD patients (46% F, mean age 41±14 years), and 1177 GP subjects (57% F, mean age 46±16 years). IBS patients reported greater severity of GER, disrupted swallowing, nausea/vomiting, belly pain, gas/bloating, and constipation symptoms than their IBD counterparts (all P<.05). Compared to the GP, IBD patients had worse belly pain, gas/bloating, diarrhea, and bowel incontinence, but less severe GER and disrupted swallowing (all P<.05), and IBS patients had more severe nausea/vomiting, belly pain, gas/bloating, and constipation (all P<.05). Women had more severe belly pain and gas/bloating than men, whereas men had more severe bowel incontinence (all P<.05). CONCLUSION & INFERENCES: IBS and IBD are associated with more severe GI symptoms compared to the GP excluding esophageal symptoms. Unlike IBD, IBS is not characterized by observable GI inflammation but patients report more severe upper and lower GI symptoms.

Surgical site infection rates in six cities of India: findings of the International Nosocomial Infection Control Consortium (INICC).

BACKGROUND: Surgical site infections are a threat to patient safety. However, in India, data on their rates stratified by surgical procedure are not available. METHODS: From January 2005 to December 2011, the International Nosocomial Infection Control Consortium (INICC) conducted a cohort prospective surveillance study on surgical site infections in 10 hospitals in 6 Indian cities. CDC National Healthcare Safety Network (CDC-NHSN) methods were applied and surgical procedures were classified into 11 types, according to the ninth edition of the International Classification of Diseases. RESULTS: We documented 1189 surgical site infections, associated with 28 340 surgical procedures (4.2%; 95% CI: 4.0-4.4). Surgical site infections rates were compared with INICC and CDC-NHSN reports, respectively: 4.3% for coronary bypass with chest and donor incision (4.5% vs 2.9%); 8.3% for breast surgery (1.7% vs 2.3%); 6.5% for cardiac surgery (5.6% vs 1.3%); 6.0% for exploratory abdominal surgery (4.1% vs 2.0%), among others. CONCLUSIONS: In most types of surgical procedures, surgical site infections rates were higher than those reported by the CDC-NHSN, but similar to INICC. This study is an important advancement towards the knowledge of surgical site infections epidemiology in the participating Indian hospitals that will allow us to introduce targeted interventions.