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Evidence is accumulating that radiotherapy of non-small cell lung cancer patients can be optimized by escalating the tumour dose until the normal tissue tolerances are met. To further improve the therapeutic ratio between tumour control probability and the risk of normal tissue complications, we firstly need to exploit inter patient variation. This variation arises, e.g. from differences in tumour shape and size, lung function and genetic factors. Secondly improvement is achieved by taking into account intra-tumour and intra-organ heterogeneity derived from molecular and functional imaging. Additional radiation dose must be delivered to those parts of the tumour that need it the most, e.g. because of increased radio-resistance or reduced therapeutic drug uptake, and away from regions inside the lung that are most prone to complication. As the delivery of these treatments plans is very sensitive for geometrical uncertainties, probabilistic treatment planning is needed to generate robust treatment plans. The administration of these complicated dose distributions requires a quality assurance procedure that can evaluate the treatment delivery and, if necessary, adapt the treatment plan during radiotherapy.

Missing data is a given in the medical domain, so machine learning models should have satisfactory performance even when missing data occurs. Our previous work has focused on support vector machines (SVM), but we hypothesize that Bayesian networks (BN) can handle missing data better. To test the hypothesis, we trained a BN and SVM model for 2 year survival on 322 lung cancer patients and compared their performance in three separate external datasets (35, 47, 33 patients), each with their own characteristics in terms of missing data. The models used tumor size, clinical T and N stage, involved lymph nodes and WHO performance as prognostic features. We found that the BN model performed better than SVM (AUC 0.77, 0.72. 0.70 vs. 0.71, 0.68, 0.69), especially if tumor size was missing. We conclude that BN models are better suited for the medical domain, as they can handle missing data better.

Purpose To characterize the relationship between pre-radiotherapy 18Fluorodeoxyglucose (FDG) uptake in a tumour voxel, radiation dose and the probability to achieve metabolic control in the tumour voxel after radiotherapy. Materials and methods Thirty-nine patients with inoperable stage I-III non-small cell lung cancer, treated with radiotherapy (RT) alone or sequential chemo radiation were analysed retrospectively. Twenty-two showed metabolic active areas in the tumour 3 months post-radiotherapy, which is known to be a surrogate for persistent local tumour failure and worse survival. Pre- and post-RT FDG-PET-CT scans were registered and the metabolic active zones within the tumour after RT were projected on the pre-RT scan. Multi-level logistic regression was performed to determine the relation between the FDG uptake if a voxel pre-RT and its metabolic state after RT. Results The probability that a voxel is metabolically controlled (mVCP), decreased significantly with increasing FDG uptake in a voxel (SUV) (OR = 0.72), increasing tumour volume (20 cm3) (OR = 0.89) and increasing dose (Gy) (OR = 0.99). Inter-patient differences in mVCP were substantial. Conclusion A methodology was presented to derive relationships between FDG uptake, dose and metabolic control. Although no strong dose effect relation was demonstrated, mVCP decreased with increasing FDG uptake and tumour volume.

Accurate volume contouring in PET is now considered crucial in radiotherapy as the use of functional imaging allows improved gross tumour volume (GTV) definition. On the other hand, an accurate delineation of the GTV as well as the definition of variable activity accumulation regions inside the tumour itself may facilitate the applications of “dose painting” for optimization of dosimetry. The objectives of such optimization include lower doses delivered to healthy surrounding tissues and higher doses delivered to malignant ones. Current state of the art algorithms for functional volume segmentation consist of adaptive threshold approaches. We have developed a segmentation approach for inhomogeneous tumours in PET, namely the FLAB (Fuzzy Locally Adaptive Bayesian), that was previously validated on simulated images. In this study, we investigated the accuracy of this algorithm in comparison to threshold-based approaches, applied to images of lung cancer patients scanned with FDG PET/CT. Simulated tumours were generated based on the activity distribution and shapes of the real lesions imaged on these patients in order to establish a “ground truth” as far as functional tumour volume is concerned. In addition, some of the patients were subsequently operated with the tumours removed and a subsequent macroscopic investigation performed to determine the true tumour sizes. These were compared to those from the segmented volumes obtained using the different algorithms under investigation. The FLAB algorithm is able to accurately extract the overall tumour from the healthy background tissues, as well as precisely delineate variable activity concentration regions of interest inside the tumours, whereas the other methodologies fail to do so. In addition, the FLAB results were systematically closer to the histology results than the other methodologies considered. Future studies will investigate the impact of the use of FLAB in radiotherapy treatment planning.

Purpose To determine what the influence is of dyspnea (CTCAE3.0) before high-dose radiotherapy (RT) on the incidence and severity of subsequent lung toxicity in patients with non-small cell lung cancer (NSCLC). Methods In 197 patients with stage I-III NSCLC maximal dyspnea scores (CTCAE3.0) were obtained prospectively at three time periods: before RT, the first 6 months post-RT and 6–9 months post-RT. Only patients who were clinically progression-free 12 months or more after RT were included, thus minimizing dyspnea due to tumor progression. Time-trends of dyspnea as a function of baseline dyspnea were investigated and correlated with gender, age, chemotherapy, mean lung dose (MLD), lung function parameters (FeV1 and DLCO), stage, PTV dose, overall treatment time and smoking habits. Results The proportion developing less, the same or more dyspnea 6–9 months post-treatment according to their baseline dyspnea scores was: Grade 0: none, 82.9%, 17.1%; Grade 1: 21.2%, 51.9%, 26.9%; Grade 2: 27.3%, 54.5%, 18.2%, respectively. Only age was associated with increased dyspnea after RT. Conclusions Patients with dyspnea before therapy have a realistic chance to improve after high-dose radiotherapy. Reporting only dyspnea at one time-point post-RT is insufficient to determine radiation-induced dyspnea.

Purpose In vivo dosimetry during brachytherapy of the prostate with 125 I seeds is challenging because of the high dose gradients and low photon energies involved. We present the results of a study using metal-oxide-semiconductor field-effect transistor (MOSFET) dosimeters to evaluate the dose in the urethra after a permanent prostate implantation procedure. Methods and Materials Phantom measurements were made to validate the measurement technique, determine the measurement accuracy, and define action levels for clinical measurements. Patient measurements were performed with a MOSFET array in the urinary catheter immediately after the implantation procedure. A CT scan was performed, and dose values, calculated by the treatment planning system, were compared to in vivo dose values measured with MOSFET dosimeters. Results Corrections for temperature dependence of the MOSFET array response and photon attenuation in the catheter on the in vivo dose values are necessary. The overall uncertainty in the measurement procedure, determined in a simulation experiment, is 8.0% (1 SD). In vivo dose values were obtained for 17 patients. In the high-dose region (> 100 Gy), calculated and measured dose values agreed within 1.7% ± 10.7% (1 SD). In the low-dose region outside the prostate ( Conclusions MOSFET detectors are suitable for in vivo dosimetry during 125 I brachytherapy of prostate cancer. An action level of ± 16% (2 SD) for detection of errors in the implantation procedure is achievable after validation of the detector system and measurement conditions.

Background: Canine idiopathic immune-mediated hemolytic anemia (IMHA) is associated with a high mortality, especially in the 1st 2 weeks after diagnosis despite treatment. Objectives: To determine treatment outcome and identify prognostic variables in order to define areas of future research. Animals: One hundred forty-nine dogs with hematocrit < 30% and either a positive Coombs' test or spherocytosis and with no evidence of disease that can trigger IMHA were included. Methods: Retrospective cohort study. All dogs were treated with prednisolone and azathioprine according to a standard protocol. Survival analysis was performed by the Kaplan-Meier method. Variables recorded at the time of diagnosis were tested as possible prognostic variables in a univariate and multivariate Cox proportional hazard model. Results: The main predictors for mortality in dogs with idiopathic IMHA are the presence of increased plasma urea concentration, bands, thrombocytopenia, and petechiae at the time of diagnosis. The estimated Kaplan-Meier half-year survival was 72.6% (95% confidence interval [CI]: 64.9-81.3%). Mortality occurred mostly within the 1st 2 weeks. Cox proportional hazards analysis indicated that increased plasma urea concentration, icterus, and petechiae were the major independent predictors of mortality in the 1st 2 weeks. In most dogs that survived IMHA, a 3-month protocol of azathioprine with prednisolone maintained clinical remission. The estimated half-year survival for dogs that survived the 1st 2 weeks was 92.5% (95% CI: 86-99.3%). Conclusions and Clinical Importance: If the dogs survived IMHA, a 3-month protocol of prednisolone and azathioprine was effective with regard to survival and clinical outcome. Future research should be directed at identifying whether thrombotic tendency in dogs with IMHA is the main contributor to the development of increased plasma urea concentration, icterus, thrombocytopenia, and petechiae.

During the past years, many different registration methods have emerged. These usually lead to different results and one faces the problem of choosing the most appropriate. To mitigate this issue, several algorithms have been developed to include prior knowledge in order to force the registration to have a physical behavior. The use of most of these methods in daily practice is cumbersome because of the need to create data-specific meshes. This paper introduces a local convolutive filter in order to iteratively make the result of any registration method converge towards a linear elastic solution. This method was tested and validated on virtual data and on a real silicone rubber cube.

Background and purpose To investigate the influence of selective irradiation of 18FDG-PET positive mediastinal nodes on radiation fields and normal tissue exposure in limited disease small cell lung cancer (LD-SCLC). Material and methods Twenty-one patients with LD-SCLC, of whom both CT and PET images were available, were studied. For each patient, two three-dimensional conformal treatment plans were made with selective irradiation of involved lymph nodes, based on CT and on PET, respectively. Changes in treatment plans as well as dosimetric factors associated with lung and esophageal toxicity were analyzed and compared. Results FDG-PET information changed the treatment field in 5 patients (24%). In 3 patients, this was due to a decrease and in 2 patients to an increase in the number of involved nodal areas. However, there were no significant differences in gross tumor volume (GTV), lung, and esophageal parameters between CT- and PET-based plans. Conclusions Incorporating FDG-PET information in radiotherapy planning for patients with LD-SCLC changed the treatment plan in 24% of patients compared to CT. Both increases and decreases of the GTV were observed, theoretically leading to the avoidance of geographical miss or a decrease of radiation exposure of normal tissues, respectively. Based on these findings, a phase II trial, evaluating PET-scan based selective nodal irradiation, is ongoing in our department.

Background and purpose: A method was evaluated to reconstruct the 3D dose distribution in patients using their planning CT-scan in combination with a Monte Carlo calculation, and the energy fluence of the actual treatment beams measured pre-treatment with an EPID without the patient or a phantom in the beam. Materials and methods: Nine plans of lung cancer patients treated with a 3D conformal technique, calculated using a simple convolution algorithm (CA), as well as five IMRT treatments of head-and-neck cancer patients, calculated with a more advanced superposition algorithm (SA), were verified. Differences between planned and reconstructed dose distributions were quantified in terms of DVH parameters. Results: For the lung cancer group, differences between the reconstructed mean PTV dose and the values calculated with the TPS were 5.0 ± 4.2% (1SD) and 1.4 ± 1.5% for the CA and SA algorithm, respectively. No large differences in the lung and spinal cord DVH parameters were found. For the IMRT treatments, the average dose differences in the PTV were generally below 3%. The reconstructed mean parotid gland dose was 3.2 ± 1.2% lower, while the maximum spinal cord dose was on average 3.1 ± 1.9% higher. Conclusions: EPID dosimetry combined with 3D dose reconstruction is a useful procedure for patient-specific QA of complex treatments. DVH parameters can be used to interpret the dose distribution delivered to the patient in the same way as during standard treatment plan evaluation. c 2007 Elsevier Ireland Ltd. All rights reserved. Radiotherapy and Oncology 86 (2008) 86‐92.

Purpose Because individual tumors are heterogeneous, including for 18 F-deoxyglucose (FDG) uptake and, most likely, for radioresistance, selective boosting of high FDG uptake zones within the tumor has been suggested. To do this, it is critical to know whether the location of these high FDG uptake patterns within the tumor remain stable during radiotherapy (RT). Methods and Materials Twenty-three patients with Stage I-III non–small-cell lung cancer underwent repeated FDG positron emission tomography computed tomography scans before radical RT (Day 0) and at Days 7 and 14 of RT. On all scans, the high and low FDG uptake regions were autodelineated using several standardized uptake value thresholds, varying from 34% to 80% of the maximal standardized uptake value. The volumes and overlap fractions of these delineations were calculated to demonstrate the stability of the high FDG uptake regions during RT. Results The mean overlap fraction of the 34% uptake zones at Day 0 with Days 7 and 14 was 82.8% ± 8.1% and 84.3% ± 7.6%, respectively. The mean overlap fraction of the high uptake zones (60%) was 72.3% ± 15.0% and 71.3% ± 19.7% at Day 0 with Days 7 and 14, respectively. The volumes of the thresholds varied markedly ( e.g., at Day 0, the volume of the 60% zone was 16.8 ± 20.3 cm 3 ). In contrast, although the location of the high FDG uptake patterns within the tumor during RT remained stable, the delineated volumes varied markedly. Conclusion The location of the low and high FDG uptake areas within the tumor remained stable during RT. This knowledge may enable selective boosting of high FDG uptake areas within the tumor.

Purpose Local recurrence is a major problem after (chemo-)radiation for non–small-cell lung cancer. We hypothesized that for each individual patient, the highest therapeutic ratio could be achieved by increasing total tumor dose (TTD) to the limits of normal tissues, delivered within 5 weeks. We report first results of a prospective feasibility trial. Methods and Materials Twenty-eight patients with medically inoperable or locally advanced non–small-cell lung cancer, World Health Organization performance score of 0–1, and reasonable lung function (forced expiratory volume in 1 second > 50%) were analyzed. All patients underwent irradiation using an individualized prescribed TTD based on normal tissue dose constraints (mean lung dose, 19 Gy; maximal spinal cord dose, 54 Gy) up to a maximal TTD of 79.2 Gy in 1.8-Gy fractions twice daily. No concurrent chemoradiation was administered. Toxicity was scored using the Common Terminology Criteria for Adverse Events criteria. An 18F-fluoro-2-deoxy-glucose–positron emission tomography–computed tomography scan was performed to evaluate (metabolic) response 3 months after treatment. Results Mean delivered dose was 63.0 ± 9.8 Gy. The TTD was most often limited by the mean lung dose (32.1%) or spinal cord (28.6%). Acute toxicity generally was mild; only 1 patient experienced Grade 3 cough and 1 patient experienced Grade 3 dysphagia. One patient (3.6%) died of pneumonitis. For late toxicity, 2 patients (7.7%) had Grade 3 cough or dyspnea; none had severe dysphagia. Complete metabolic response was obtained in 44% (11 of 26 patients). With a median follow-up of 13 months, median overall survival was 19.6 months, with a 1-year survival rate of 57.1%. Conclusions Individualized maximal tolerable dose irradiation based on normal tissue dose constraints is feasible, and initial results are promising.

PURPOSE: To improve treatment planning in radiotherapy for non-small cell lung cancer by including Respiratory Correlated-Computed Tomography (RC-CT) information in tumour delineation and dose planning. METHODS AND MATERIALS: Dense displacement fields were computed using a combination of rigid and non-rigid registrations between RC-CT phases. These registrations have been performed independently between each phase of the respiratory cycle and a reference phase for 13 patients. A manual delineation in the reference frame was propagated to every other phase according to the deformation fields recovered from the inter-phase registrations. Resulting delineations were compared to two manual delineations drawn by two physicians at each phase. On the other hand, dose distributions computed for every phase were deformed towards the reference phase. These distributions were then added on the reference phase to estimate the total dose received by each voxel through the whole respiratory cycle. RESULTS: The overlap between the deformed and the manual delineations was not significantly different than the overlap between the delineations made by the two physicians for 11 out of 13 patients thus proving that the method accuracy is comparable to inter-observer variability. Calculation of the effective dose distributions showed that these were conserved after deformation. CONCLUSION: We developed a method to use RC-CT information into the radiation treatment planning, including semi-automatic segmentation of lung tumours on each phase of the respiratory cycle and a total received dose per voxel estimation.

Objective: To simultaneously improve patient care processes and clinical research activities by starting a hypothesis-driven reorganization trajectory mimicking the rigorous methodology of a prospective clinical trial. Methods: The design of this reorganization trajectory was based on the model of a prospective trial. It consisted of (1) listing problems and analysing their potential causes, (2) defining interventions, (3) defining end points and (4) measuring the effect of the interventions (i.e. at baseline and after 1 and 2 years). The primary end point for patient care was the number of organizational root causes of incidents/near incidents; for clinical research, it was the number of patients in trials. There were several secondary end points. We analysed the data using two sample z-tests, x(2) test, a Mann-Whitney U test and the one-way analysis of variance with Bonferroni correction. Results: The number of organizational root causes was reduced by 27% (p

18F-fluoro-2-deoxy-glucose (FDG) uptake on PET scan is a prognostic factor for outcome in NSCLC. We investigated changes in FDG uptake during fractionated radiotherapy in relation to metabolic response with the ultimate aim to adapt treatment according to early response.Twenty-three patients, medically inoperable or with advanced NSCLC, underwent four repeated PET-CT scans before, during and after radiotherapy. Changes in maximal standardized uptake value (SUVmax) were described. Patients were treated with accelerated radiotherapy with a total tumour-dose depending on normal tissue dose constraints.The most striking result was the large intra-individual heterogeneity in the evolution of SUVmax. For the total group a non-significant increase in the first week (p=0.05), and a decrease in the second week (p=0.02) and after radiotherapy (p0.01) was observed. Different time trends were shown for responders (no change during radiotherapy) and non-responders (48% increase during first week, p=0.02 and 15% decrease in the second week, p=0.04). Non-responders had a higher SUVmax on all time points investigated.Time trends in SUVmax showed a large intra-individual heterogeneity and different patterns for metabolic responders and non-responders. These new findings may reflect intrinsic tumour characteristics and might finally be useful to adapt treatment.

Objective: A new pulsatile extracorporeal life support (pECLS) system has entered the market. We wanted to investigate what potential advantages pECLS may have over current non-pulsatile systems (NPS). Our research was focused on the pump’s functional interaction with the left ventricle and the coronary circulation.Methods: Extensive hemodynamic measurements were performed during asynchronous and synchronous pECLS in 10 calves. The two extremes regarding LV afterload, namely systolic arrival (SA) and diastolic arrival (DA) of the pump pulse were studied. Results: SA was associated with increased oxygen consumption (+57%) and decreased diastolic coronary perfusion(43%). DA increased left ventricular output (DA: 4.5 2.4 l/min vs SA: 3.5 2.2 l/min), LVejection fraction (+10%), and ventricular efficiency (+17%). Mean aortic pressure and mean coronary flow were only marginally affected by pulse incidence. Systolic impairment was more pronounced with higher bypass flows. These results indicate that myocardial working conditions can be optimized by phasing pECLS ejection into cardiac diastole. Conclusion: We conclude that during pECLS, myocardial working conditions can be improved by avoidance of systolic impairment. Synchronously counterpulsating pECLS could be a more economic and versatile alternative to NPS or NPS combined with intra-aortic balloon pumping. The potential benefits of synchronously counterpulsating pECLS over the current alternatives remain to be investigated. # 2005 Elsevier B.V. All rights reserved.

In patients with aortic stenosis, the left ventricular afterload is determined by the degree of valvular obstruction and the systemic arterial system. We developed an explicit mathematical model formulated with a limited number of independent parameters that describes the interaction among the left ventricle, an aortic stenosis, and the arterial system. This ventricular-valvular-vascular (V3) model consists of the combination of the time-varying elastance model for the left ventricle, the instantaneous transvalvular pressure-flow relationship for the aortic valve, and the three-element windkessel representation of the vascular system. The objective of this study was to validate the V3 model by using pressure-volume loop data obtained in six patients with severe aortic stenosis before and after aortic valve replacement. There was very good agreement between the estimated and the measured left ventricular and aortic pressure waveforms. The total relative error between estimated and measured pressures was on average (standard deviation) 7.5% (SD 2.3) and the equation of the corresponding regression line was y = 0.99 x − 2.36 with a coefficient of determination r2 = 0.98. There was also very good agreement between estimated and measured stroke volumes ( y = 1.03 x + 2.2, r2 = 0.96, SEE = 2.8 ml). Hence, this mathematical V3 model can be used to describe the hemodynamic interaction among the left ventricle, the aortic valve, and the systemic arterial system.

Right-sided circulatory failure (RSCF) is a serious complication in 15–30% of patients receiving a left ventricular assist device (LVAD). It is hypothesized that left ventricular support which lacks physiologic properties predisposes to RSCF. An integral computer simulation and experimental validation protocol was performed. The results suggest that with conventional insensitive left ventricular support right-sided circulatory function is compromised, which may form a substrate for the onset or progress of RSCF. Feedback control of the LVAD could provide a means to counter this problem. A control concept for the LVAD which aims to preserve right-sided circulatory function, while supporting peripheral perfusion, is proposed

The generation and detection of broadband photoacoustic (PA) transients may be used for on-axis monitoring or for imaging of optically different structures in the interior of diffuse bodies such as biological tissue. Various piezoelectric sensors are characterized and compared in terms of sensitivity, depth response, and directivity with respect to spherical broadband acoustic pulses. The influence on the sensor output of acoustic interference and refraction of the PA transients at the sample-sensor interface is discussed. Ring detectors are suitable for deep on-axis detection thanks to their strong directional sensitivity, and small disk sensors are most suited for 3-D imaging of microstructures such as the (micro) vascular system. Voltage and charge preamplification schemes are compared in terms of the signal-to-noise ratio (SNR). In all cases, the preamplifier noise turns out to be the limiting factor for the sensitivity. Based on experimental data, for several sensor types and optical wavelengths, the theoretical detectability of PA signals generated by blood-like absorbers in biological tissue is discussed.

Objectives: Tilting the heart during off-pump coronary artery bypass grafting (OPCABG) causes a strong decrease in cardiac output. It is hypothesized that this decrease is caused by reduced right ventricular filling and that right ventricular support is thus the best way to restore cardiac output. Simultaneous left and right ventricular pressure‐volume loops were used to test this hypothesis. Methods: In seven sheep, the heart was tilted with the use of an Octopus device. After unsupported tilting, a novel right ventricular support, the Enabler, was activated at a pulsatile flow of 1.6 l/min. Pressure‐volume loops of both ventricles were obtained using conductance catheters, and cardiac output was monitored with an aortic flow probe. Results: Tilting reduced cardiac output by 31% (4.4‐3.1 l/min, Pa 0:001) and right ventricular enddiastolic volume by 44% (86‐51 ml, Pa 0:005), while right ventricular end-diastolic pressure did not decrease. Left ventricular systolic pressure was not significantly reduced upon tilting and even increased in two animals. During Enabler right ventricular support, the cardiac output remained 23% lower than pre-tilting values (3.4 vs. 4.4 l/min, Pa 0:001). Conclusions: Restricted right ventricular filling is the primary cause of the strong decrease in cardiac output during tilting. The Enabler right ventricular support can currently not restore cardiac output to pre-tilting values, mainly caused by its limited output and a decrease in right ventricular output upon Enabler activation. Constant monitoring of cardiac output is crucial during (unsupported or supported) tilting as blood pressure alone may not reflect the extent of the reduction in cardiac function. q 2001 Elsevier Science B.V. All rights reserved.

Background . Beating heart coronary artery bypass graft surgery of the left anterior descending, diagonal, and right coronary artery can be performed safely with the Octopus Stabilization System. However, tilting of the heart, which is necessary to reach the obtuse marginal and distal right coronary arteries, causes hemodynamic instability. This study was performed to investigate the possible role of the Enabler right ventricular circulatory support system in counteracting this instability. Methods . In 8 sheep, the Enabler cannula was introduced via the jugular vein and positioned with the inlet valve in the right atrium and outlet valve in the pulmonary artery. The Octopus was used to expose the inferior wall and the posterior wall of the left ventricle. The hemodynamic effects of this tilting with and without Enabler right ventricular support were recorded, including Pressure Volume (PV) loops measured by conductance catheters in both ventricles. Results . Tilting caused a reduction in stroke volume (inferior 31%, posterior 17%) and Enabler activation increased stroke volume (inferior 13%, posterior 31%). Conclusions . Tilting the heart has severe hemodynamic consequences that can be partially counteracted by the use of the Enabler for right ventricle support.

We used Photoacoustics to image optically absorbing structures (blood vessels) in tissue samples. With 532 nm light depths down to 6-9 mm were reached. Samples were a 10 % solution of Intralipid-10% or real tissue (chicken breast), containing capillaries with blood or a variable dilution of Evans blue. Small PVdF piezoelectric hydrophones were used for detection in scanning mode. The sensitivity of the technique was demonstrated by the detection of two single red blood cells situated on a glass plate. The lateral resolution is limited by the diameter of the detector (200 pm in our case). The depth resolution is about 10 μm.This study was undertaken to develop Photoacoustic Tomography of tissue for the localisation of blood vessels, e.g. for the detection of blood concentrations (angiogenesis) around tumors.

316 Background: Due to the low dose tolerance of the organs at risk (OARs) in the abdomen the tumor dose for pancreatic cancer patient is restricted to 50-60 Gy in 1.8-2.0 Gy fractions when combined with chemotherapy. The goal of this study was to develop a system that can determine the minimal radiation dose to the OARs of each individual patient that is achievable while maintaining adequate tumor coverage. This could guide treatment planners to spare the OARs to the fullest extent. When the minimal doses to the OAR are achieved, the total plan can be upscaled until the normal tissue dose constraints are met, allowing for an increase in tumor dose without increased normal tissue toxicity. Methods: The minimal achievable dose to the OARs depends on its proximity to the planning target volume (PTV). The overlap volume histogram (OVH) was used to describe the spatial relation of each OAR to the PTV. A database of 33 patients, treated with IMRT, was queried to find the lowest achieved dose to an organ for any of the prior patients with less favorable PTV-OAR configurations than the current patient. This minimal dose must also be achievable for the OAR of the new patient. For 25 randomly chosen patients the lowest achievable dose to the liver and kidneys was predicted this way. Then the patients were replanned to verify if this dose could be achieved. The new plans were compared to the original clinical plans. Results: After replanning the predicted achievable dose to the liver was realized within 1 and 2 Gy for more than 86% and 96% of the patients respectively. For the kidneys these numbers were 83% and 96%. The average improvement in terms of mean dose was 1.4 Gy (range 0 – 4.6 Gy) for the liver and 1.7 Gy (range 0 – 6.3 Gy) for the kidneys. This would have allowed an increase in PTV dose of on average 5 Gy (range 0-13 Gy) based on the liver and 8.5 Gy (range 0-38 Gy) based on the kidneys compared to the original plan, without an increase in dose to the bowel, cord, and stomach. Conclusions: The lowest achievable dose to the OARs could accurately be predicted for pancreatic cancer patients within seconds. This can guide dosimetrists to spare the OARs or increase the PTV dose by 5 Gy without increased toxicity. [Table: see text]

It is widely anticipated that the use of health-related big data will enable further understanding and improvements in human health and wellbeing. Our current project, funded through the Dutch National Research Agenda, aims to explore the relationship between the development of diabetes and socio-economic factors such as lifestyle and health care utilization. The analysis involves combining data from the Maastricht Study (DMS), a prospective clinical study, and data collected by Statistics Netherlands (CBS) as part of its routine operations. However, a wide array of social, legal, technical, and scientific issues hinder the analysis. In this paper, we describe these challenges and our progress towards addressing them., Comment: 6 pages, 1 figure, preliminary result, project report

Evidence-based Medical guidelines are developed based on the best available evidence in biomedical science and clinical practice. Such evidence-based medical guidelines should be regularly updated, so that they can optimally serve medical practice by using the latest evidence from medical research. The usual approach to detect such new evidence is to use a set of terms from a guideline recommendation and to create queries for a biomedical search engine such as PubMed, with a ranking over a selected subset of terms to search for relevant new evidence. However, the terms that appear in a guideline recommendation do not always cover all of the information we need for the search, because the contextual information (e.g. time and location, user profile, topics) is usually missing in a guideline recommendation. Enhancing the search terms with contextual information would improve the quality of the search results. In this paper, we propose a topic-centric approach to detect new evidence for updating evidence-based medical guidelines as a context-aware method to improve the search. Our experiments show that this topic centric approach can find the goal evidence for 12 guideline statements out of 16 in our test set, compared with only 5 guideline statements that were found by using a non-topic centric approach.

* Correspondence: s.klein@erasmusmc.nl Biomedical Imaging Group Rotterdam, Departments of Medical Informatics & Radiology, Erasmus MC, 3000CA Rotterdam, the Netherlands Full list of author information is available at the end of the article Figure 1 XNAT user interface. Example project with magnetic resonance imaging (MRI) data of the brain. Klein et al. Journal of Clinical Bioinformatics 2015, 5(Suppl 1):S18 http://www.jclinbioinformatics.com/content/5/S1/S18 JOURNAL OF CLINICAL BIOINFORMATICS