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.

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.

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).

A cautionary tale: dealing with missing data in clinical trials for rheumatic diseases.

OBJECTIVES: Missing data are found in nearly all clinical trials and it is important to use appropriate statistical techniques to analyse clinical trials with missing data. We discuss common statistical methods for tackling missing data and how to handle results when the analyses give different results. METHODS: Using data from a placebo-controlled, randomised bovine Type I collagen (CI) study in diffuse cutaneous systemic sclerosis (dcSSc), we apply different statistical approaches to handling missing data. We also describe simple ways to ascertain the type of missing data in the data set, to the extent possible. RESULTS: We examine eleven different methods to impute missing data. An analysis based on completers alone (complete case analysis and available case analysis) and the last observation carried forward (LOCF) methods require underlying assumptions which are rarely met in practice. Multiple imputation, mixed effects, and repeated measures try to account for the differences among patients and account for patient's specific response patterns, although the assumption that the missing data is directly related to the observed characteristics may well not be true. The joint likelihood based model combines the mixed effect model and logistic regression model to explicitly handle data not missing at random and so it is more realistic and potentially takes an additional step toward decreasing bias. CONCLUSIONS: We discussed various ways of handling missing data and provide recommendations on how to arrive at a conclusion when different statistical approaches to analyse missing data analysis in clinical trials give conflicting answers.

Recognition of pulmonary hypertension in the rheumatology community: lessons from a Quality Enhancement Research Initiative.

OBJECTIVES: The aim of this study was to utilise the Quality Enhancement Research Initiative in Systemic Sclerosis (QuERI-SSc) to measure and reduce a perceived gap in the diagnosis of pulmonary arterial hypertension (PAH) associated with systemic sclerosis (SSc). METHODS: Rheumatologists enrolled patients with SSc (aged ≥ 18 years) and provided data on a panel of diagnostic tests over 3 years. Pulmonary function testing, echocardiography, 6-minute walk distance, N-terminal pro-brain natriuretic peptide assays, high-resolution computed tomography of the lungs, and ventilation/perfusion scan plus right heart catheterisation (RHC; when appropriate) were emphasised. Exclusion criteria included previously documented PAH, interstitial lung disease, and SSc overlapping with other connective tissue disease. RESULTS: Participating rheumatologists enrolled 207 patients with SSc (90% female; 80% white), with a median age of 57 years and median disease duration of 5 years. A total of 82% of patients were classified as New York Heart Association functional class I and II; of these patients, 177 had an echocardiogram at enrolment and 191 at any time during the study. Of those who met study-specified criteria for RHC at enrolment, only 3 of 7 patients underwent RHC. CONCLUSIONS: The screening algorithm was successful in identifying patients with mild impairment. Although specific tools were recommended for screening PAH in patients with SSc, results indicate that significant diagnostic care gaps still exist in the general rheumatology community. Better understanding and adherence to guidelines could improve the care and, ideally, outcomes of these high-risk patients.

Brief report: effect of ambrisentan treatment on exercise-induced pulmonary hypertension in systemic sclerosis: a prospective single-center, open-label pilot study.

OBJECTIVE: Exercise-induced pulmonary hypertension (ePH) may represent an early, clinically relevant phase in the spectrum of pulmonary vascular disease. The purpose of this pilot study was to describe the changes in hemodynamics and exercise capacity in patients with systemic sclerosis (SSc) spectrum-associated ePH treated with open-label daily ambrisentan. METHODS: Patients were treated with ambrisentan, 5 mg or 10 mg once daily, for 24 weeks. At baseline and 24 weeks, patients with SSc spectrum disorders exercised in a supine position, on a lower extremity cycle ergometer. All patients had normal hemodynamics at rest. We defined baseline ePH as a mean pulmonary artery pressure of >30 mm Hg with maximum exercise and a transpulmonary gradient (TPG) of >15 mm Hg. The primary end point was change in pulmonary vascular resistance (PVR) with exercise. Secondary end points included an improvement from baseline in 6-minute walking distance, health-related quality of life assessments, and cardiopulmonary hemodynamics. RESULTS: Of the 12 enrolled patients, 11 completed the study. At 24 weeks there were improvements in mean exercise PVR (85.8 dynes × second/cm(5) ; P = 0.003) and mean distance covered during 6-minute walk (44.5 meters; P = 0.0007). Improvements were also observed in mean exercise cardiac output (1.4 liters/minute; P = 0.006), mean pulmonary artery pressure (-4.1 mm Hg; P = 0.02), and total pulmonary resistance (-93.0 dynes × seconds/cm(5) ; P = 0.0008). Three patients developed resting pulmonary arterial hypertension during the 24 weeks. CONCLUSION: Exercise hemodynamics and exercise capacity in patients with SSc spectrum-associated ePH improved over 24 weeks with exposure to ambrisentan. Placebo-controlled studies are needed to confirm whether this is a drug-related effect and to determine optimal therapeutic regimens for patients with ePH.

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.

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.

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 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.

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.

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.

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.

Systemic sclerosis and bilateral lung transplantation: a single centre experience.

Lung involvement is the leading cause of death in systemic sclerosis (SSc), but lung transplantation (LT) for systemic disease remains controversial. Our objective was to comprehensively evaluate post-LT outcomes for SSc compared to idiopathic pulmonary fibrosis (IPF). We retrospectively evaluated bilateral LT recipients (LTRs) with SSc or IPF at our centre between January 1, 2003 and December 31, 2007. The primary end-point was all-cause mortality at 1 yr post-LT. Secondary end-points included assessments of acute rejection (AR), pulmonary function, infection and chronic rejection. 14 patients with SSc and 38 patients with IPF underwent LT. Apart from a younger SSc cohort (53.2 versus 58.8 yrs; p = 0.02), the two groups were well matched. 1-yr all-cause mortality was no different between SSc (6.6%) and IPF (13.1%) groups, after adjusting for age (p = 0.62). Rates of (AR) ≥2 were significantly increased for the SSc compared with the IPF group (hazard ratio (HR) 2.91; p = 0.007). Other end-points, including chronic rejection, infection and pulmonary function, showed no differences. SSc LTRs experience similar survival 1 yr post-LT when compared to IPF. AR rates may be significantly higher in the SSc group. Longer follow-up is necessary to determine the effects of gastrointestinal dysfunction and AR on late allograft function in SSc LTR.

Differences in presentation of younger and older systemic sclerosis patients in clinical trials.

OBJECTIVES: To compare the characteristics of younger and older subjects with diffuse cutaneous systemic sclerosis (SSc) entering clinical trials. METHODS: Subjects were participants in three randomised interventional trials that shared relative uniformity of demographics and disease characteristics. Only subjects with diffuse cutaneous systemic sclerosis were evaluated. To maximise possible differences, the lowest (age<38 years) and highest quartiles (age>53 years) were used, and a total of 264 diffuse cutaneous SSc (dcSSc) subjects were identified. For the comparison between the two age groups, generalised linear mixed or linear models with adjustment for population norms, demographics and medications were employed to assess differences attributable to subject age. RESULTS: After adjustment for population norms and study effects, differences in diastolic blood pressure, alkaline phosphatase, AST, and creatinine phosphokinase (CK) were found between the two age groups. After further adjustment for demographics, disease duration and medications, older SSc patients still had significantly higher alkaline phosphatase (11 U/L higher), and lower CK (76 U/L lower) than younger patients (p<0.003 for all). All other variables were not significantly different in the two age groups. CONCLUSIONS: Clinical baseline differences exist between younger and older patients with SSc. However, after adjustment for population norms and potential confounders, including medications, only differences in alkaline phosphatise (only 11U/L) and CK (76 U/L) remain. Overall, older patients with SSc in clinical trials seem to be more similar to younger patients than was previously thought.

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.

Use of "spydergrams" to present and interpret SF-36 health-related quality of life data across rheumatic diseases.

The Medical Outcomes Study Short Form-36 (SF-36) is a generic measure of health-related quality of life (HRQOL), validated and cross-culturally translated, which has been extensively utilised in rheumatology. In randomised controlled trials and observational studies, SF-36 provides rich data regarding HRQOL; but as typically portrayed, patterns of disease and treatment-associated effects can be difficult to discern. "Spydergrams" offer a simplified means to visualise complex results across all domains of SF-36 in a single figure: depicting disease and population-specific patterns of decrements in HRQOL compared with age and gender-matched normative data, as well as providing a tool for interpreting complex treatment-associated or longitudinal changes. Utilising spydergrams as a standard format to illustrate and report changes in SF-36 across different rheumatic diseases can greatly facilitate analyses and interpretations of clinical trial results, as well as providing patients an accessible means to compare baseline scores and treatment-associated improvements with normative data from individuals without arthritis. Furthermore, SF-6D utility scores based on mean changes across all eight domains of SF-36 are suggested as a quantitative means of summarising changes illustrated by spydergrams, offering a universal metric for cost-effectiveness analyses of therapeutic interventions.