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Background Pain symptoms in the upper abdomen and back are prevalent in 80% of patients with metastatic pancreatic ductal adenocarcinoma (mPDAC), where the current standard treatment is a systemic therapy consisting of at least doublet-chemotherapy for fit patients. Palliative low-dose radiotherapy is a well-established local treatment option but there is some evidence for a better and longer pain response after a dose-intensified radiotherapy of the primary pancreatic cancer (pPCa). Stereotactic body radiation therapy (SBRT) can deliver high radiation doses in few fractions, therefore reducing chemotherapy-free intervals. However, prospective data on pain control after SBRT of pPCa is very limited. Therefore, we aim to investigate the impact of SBRT on pain control in patients with mPDAC in a prospective trial. Methods This is a prospective, double-arm, randomized controlled, international multicenter study testing the added benefit of MR-guided adaptive SBRT of the pPca embedded between standard of care-chemotherapy (SoC-CT) cycles for pain control and prevention of pain in patients with mPDAC. 92 patients with histologically proven mPDAC and at least stable disease after initial 8 weeks of SoC-CT will be eligible for the trial and 1:1 randomized in 3 centers in Germany and Switzerland to either experimental arm A, receiving MR-guided SBRT of the pPCa with 5 × 6.6 Gy at 80% isodose with continuation of SoC-CT thereafter, or control arm B, continuing SoC-CT without SBRT. Daily MR-guided plan adaptation intents to achieve good target coverage, while simultaneously minimizing dose to organs at risk. Patients will be followed up for minimum 6 and maximum of 18 months. The primary endpoint of the study is the “mean cumulative pain index” rated every 4 weeks until death or end of study using numeric rating scale. Discussion An adequate long-term control of pain symptoms in patients with mPDAC is an unmet clinical need. Despite improvements in systemic treatment, local complications due to pPCa remain a clinical challenge. We hypothesize that patients with mPDAC will benefit from a local treatment of the pPCa by MR-guided SBRT in terms of a durable pain control with a simultaneously favorable safe toxicity profile translating into an improvement of quality-of-life. Trial registration German Registry for Clinical Trials (DRKS): DRKS00025801. Meanwhile the study is also registered at ClinicalTrials.gov with the Identifier: NCT05114213.

BackgroundCareful selection of malignant pleural mesothelioma (MPM) patients for curative treatment is of highest importance, as the multimodal treatment regimen is challenging for patients and harbors a high risk of substantial toxicity. Radiomics—a quantitative method for image analysis—has shown its prognostic ability in different tumor entities and could therefore play an important role in optimizing patient selection for radical cancer treatment. So far, radiomics as a prognostic tool in MPM was not investigated.Materials and methodsThis study is based on 72 MPM patients treated with surgery in a curative intent at our institution between 2009 and 2017. Pre-treatment Fluorine-18 fluorodeoxyglucose (FDG) PET and CT scans were used for radiomics outcome modeling. After extraction of 1404 CT and 1410 FDG PET features from each image, a preselection by principal component analysis was performed to include only robust, non-redundant features for the cox regression to predict the progression-free survival (PFS) and the overall survival (OS). Results were validated on a separate cohort. Additionally, SUVmax and SUVmean, and volume were tested for their prognostic ability for PFS and OS.ResultsFor the PFS a concordance index (c-index) of 0.67 (95% CI 0.52–0.82) and 0.66 (95% CI 0.57–0.78) for the training cohort (n = 36) and internal validation cohort (n = 36), respectively, were obtained for the PET radiomics model. The PFS advantage of the low-risk group translated also into an OS advantage. On CT images, no radiomics model could be trained. SUV max and SUV mean were also not prognostic in terms of PFS and OS.ConclusionWe were able to build a successful FDG PET radiomics model for the prediction of PFS in MPM. Radiomics could serve as a tool to aid clinical decision support systems for treatment of MPM in future.

PurposeThe aim of this study was to evaluate interobserver agreement (IOA) on target volume definition for pancreatic cancer (PACA) within the Radiosurgery and Stereotactic Radiotherapy Working Group of the German Society of Radiation Oncology (DEGRO) and to identify the influence of imaging modalities on the definition of the target volumes.MethodsTwo cases of locally advanced PACA and one local recurrence were selected from a large SBRT database. Delineation was based on either a planning 4D CT with or without (w/wo) IV contrast, w/wo PET/CT, and w/wo diagnostic MRI. Novel compared to other studies, a combination of four metrics was used to integrate several aspects of target volume segmentation: the Dice coefficient (DSC), the Hausdorff distance (HD), the probabilistic distance (PBD), and the volumetric similarity (VS).ResultsFor all three GTVs, the median DSC was 0.75 (range 0.17–0.95), the median HD 15 (range 3.22–67.11) mm, the median PBD 0.33 (range 0.06–4.86), and the median VS was 0.88 (range 0.31–1). For ITVs and PTVs the results were similar. When comparing the imaging modalities for delineation, the best agreement for the GTV was achieved using PET/CT, and for the ITV and PTV using 4D PET/CT, in treatment position with abdominal compression.ConclusionOverall, there was good GTV agreement (DSC). Combined metrics appeared to allow a more valid detection of interobserver variation. For SBRT, either 4D PET/CT or 3D PET/CT in treatment position with abdominal compression leads to better agreement and should be considered as a very useful imaging modality for the definition of treatment volumes in pancreatic SBRT. Contouring does not appear to be the weakest link in the treatment planning chain of SBRT for PACA.

Pain symptoms in the upper abdomen and back are prevalent in 80% of patients with metastatic pancreatic ductal adenocarcinoma (mPDAC), where the current standard treatment is a systemic therapy consisting of at least doublet-chemotherapy for fit patients. Palliative low-dose radiotherapy is a well-established local treatment option but there is some evidence for a better and longer pain response after a dose-intensified radiotherapy of the primary pancreatic cancer (pPCa). Stereotactic body radiation therapy (SBRT) can deliver high radiation doses in few fractions, therefore reducing chemotherapy-free intervals. However, prospective data on pain control after SBRT of pPCa is very limited. Therefore, we aim to investigate the impact of SBRT on pain control in patients with mPDAC in a prospective trial. This is a prospective, double-arm, randomized controlled, international multicenter study testing the added benefit of MR-guided adaptive SBRT of the pPca embedded between standard of care-chemotherapy (SoC-CT) cycles for pain control and prevention of pain in patients with mPDAC. 92 patients with histologically proven mPDAC and at least stable disease after initial 8 weeks of SoC-CT will be eligible for the trial and 1:1 randomized in 3 centers in Germany and Switzerland to either experimental arm A, receiving MR-guided SBRT of the pPCa with 5 x 6.6 Gy at 80% isodose with continuation of SoC-CT thereafter, or control arm B, continuing SoC-CT without SBRT. Daily MR-guided plan adaptation intents to achieve good target coverage, while simultaneously minimizing dose to organs at risk. Patients will be followed up for minimum 6 and maximum of 18 months. The primary endpoint of the study is the \"mean cumulative pain index\" rated every 4 weeks until death or end of study using numeric rating scale. An adequate long-term control of pain symptoms in patients with mPDAC is an unmet clinical need. Despite improvements in systemic treatment, local complications due to pPCa remain a clinical challenge. We hypothesize that patients with mPDAC will benefit from a local treatment of the pPCa by MR-guided SBRT in terms of a durable pain control with a simultaneously favorable safe toxicity profile translating into an improvement of quality-of-life.

Rocket motor nozzle flow geometry is considered through its influence on the thrust vector control (TVC) performances. Extensive research is conducted using theoretical and software simulations and compared with experimental results. Cold and hot flow test equipments are used. The main objective of the research is to establish the methodology of flow geometry optimisation on the TVC hardware system. Several geometry parameters are examined in detail and their effects on the system performances are presented. The discovered effects are used as guidelines in the TVC system design process. A numerical method is presented for the determination of dynamic response time upper limit for the TVC system based on the gas flow dynamics performances.

BackgroundSubcutaneous TNFα blockers enable patients with inflammatory arthritis to better control their disease and subsequently improve the quality of their daily functioning. At our Department of Rheumatology trained nurses provide education about proper subcutaneous (s.c.) administration techniques and telephone counseling about different issues asked by patients concerning their treatment. One of the key components of patient education and counseling is to explain when to postpone the biologic therapy in case of infection or planned surgical procedure.ObjectivesThe aim of our study was to look at the most frequent questions raised by patients about their treatment. In addition we looked at a potential association between particular patient problem and specific subcutaneous TNFα blocker.MethodsData was collected between January 2013 and May 2014 and included demographic data, prescribed anti-TNF drug, and description of the patient reported query regarding their s.c. anti-TNF treatment. Patient queries were grouped into six topics: skin reactions, infections, vaccinations, drug interactions, planned surgical procedures and other (Table 1). Appropriate statistical methods were used to analyze data.ResultsDuring the observation period 98 patients (23% males, mean (SD) age 56.1 (13.9) years) treated with subcutaneous TNFα blocker asked for help using a telephone call. Patients were treated with the following s.c. anti-TNF drugs: certolizumab (9%), etanercept (27%), adalimumab (41%), and golimumab (23%). The most common patient problems on subcutaneous TNFα inhibitors are presented in Table 1.Table 1.The patient's inquiries grouped by topicsPatients queries%Patients queries%Skin reactions20%Drug interactions10%Infection36%Planned surgical procedures10%Vaccinations2%Other22%In 22% of cases patients seeked telephone advice for other different health problems (swollen joints, drug ineffectiveness, potential adverse effects).We did not find any significant difference concerning particular TNFα blocker and the pertinent patient problem.ConclusionsTelephone assistance is valuable for patients. Patients request more information about their treatment and continuous patient education could improve outcomes in the management of inflammatory rheumatic diseases.Disclosure of InterestNone declared

Clostridium difficile infection is associated with pediatric inflammatory bowel disease (IBD) in several ways. We sought to investigate C. difficile infection in pediatric patients with IBD in comparison with a group of children with celiac disease and to evaluate IBD disease course of C. difficile infected patients.MethodsIn this prospective, comparative, multicenter study, 211 pediatric patients with IBD were enrolled from October 2010 to October 2011 and tested for the presence of C. difficile toxins A and B in their stools at 0, 6, and 12 months. During the same study period, stool specimens for C. difficile toxins analysis were collected from 112 children with celiac disease as controls.Results Clostridium difficile occurrence was significantly higher in patients with IBD compared with patients with celiac disease (7.5% versus 0.8%; P = 0.008). Clostridium difficile was associated with active disease in 71.4% of patients with IBD (P = 0.01). Colonic involvement was found in 85.7% of patients with C. difficile. Antibiotics, proton pump inhibitors, hospitalization, and IBD therapies were not associated with increased C. difficile detection. At 12 months, a higher number of C. difficile–positive patients at the enrollment started immunosuppressant/biological therapy compared with patients without C. difficile (P = 0.01). At 6 and 12 months, patients with C. difficile were more frequently in active disease than patients without C. difficile (P = 0.04; P = 0.08, respectively). Hospitalizations were higher at 6 months in C. difficile group (P = 0.05).ConclusionsIn conclusion, this study demonstrates that pediatric IBD is associated with increased C. difficile detection. Patients with C. difficile tend to have active colonic disease and a more severe disease course.

Background Biological agents have expanded pharmacological options for treatment of rheumatic diseases and revolutionized the therapeutic landscape. Their use usually requires parenteral application and some of them can be self - administered by patients. Patient’s education regarding biologics, including self-administration learning techniques, is therefore vital. Nurses play an important role in this process. Objectives Patient education in Slovenia is performed individually in the outpatients’ clinic on the same day the treatment with biologics is introduced. The aim of our survey was to establish to what extentpatients understand their training and what additional information they miss. We tried to evaluate whether their training enables them for self-administration of biological medicines. Methods The questionnaire wassent to 205 patients on biological agents, who were educated at our outpatients’ clinic from August 2010 onwards. The survey consisted of 22 claims and questions regarding biologics use. The survey was filled in and returned by 149 patients, 123 questionnaires were fully completed and were therefore analyzed. 63% of participants were women and 37% men. The average age was 52 years (22–85). The majority of participants were between 51and 60-years old (33%). Results According to our survey 87% of the recipientsof subcutaneously administered biological medicines self-administered their medicine. Among the remaining 13%, 50% were injected by a district nurse at home, 37% by family members or friends and 13% went to the outpatients’ clinic for the administration (13%). The majority of patients (86%) conducted self-administration training on the same day they visited their rheumatologist. 75% of the patients had individual training and 25% of them group training. Most patients (86%) understood nurse’s explanation. 88% of the respondents completely agreed that the nurse answered all their questions. 63% were absolutely sure that they correctly injected their medicine. Handling the syringe seemed simple to most patients, only 2% found it complicated. The question:” What else would you like to know?” revealed that 39% of participants did not know the possible side effects, 24% wanted to know in which circumstances the biological agent should not be administered, 9% of patients did not know how to store medicines. 72% of patients knew whom to contact in case of further questions. 12% of patients did not know which documents were requiredto transfer biological medicines out of the country. 6% of patients claimed they did not receive written instructions. Conclusions Results of our surveysuggest a high level of confidence and knowledge in patients who self-administer biological agents in Slovenia. The information provided during training seems to be most insufficient in the fields of biological medicines side effects, and situations where biologics should be temporarily discontinued. Our results imply that Slovenian patients on biologics are well-trained to perform self-administration. In order to maintain this level, additional educational approach should be considered, that would allow patients to share their experiences and cope with the dilemmas that arise in their everyday life. Disclosure of Interest None Declared

Background Although Hizentra is indicated for immunoglobulin replacement therapy in patients with primary and secondary immunodeficiencies, phase III trials have focused on patients with primary immunodeficiencies. In this 9-month, real-life, prospective, non-interventional, longitudinal, multicenter study of patients with primary and secondary immunodeficiencies in France, treatment modalities (primary endpoint), efficacy, safety, tolerability, quality of life, and treatment satisfaction were evaluated using descriptive statistics. Results Starting in January 2012, 117 patients were enrolled (99 adults, 18 children). Secondary immunodeficiencies were present in 48.7 % of patients. At follow-up, injections were administered every 7 days in 92.2 % of patients. Nine patients (7.8 %) were taking Hizentra every 10–14 days. The median dose of Hizentra administered was 0.1 g/kg/injection. Fifty-six patients were administered doses <0.1 g/kg/injection and 13 patients were administered doses >0.2 g/kg/injection. Mean trough IgG titers were 9.0 ± 3.3 g/L (median 8.3 g/L). The mean yearly rate of infection was 1.2 ± 1.9. Mean scores on the Short Form-36 physical and mental component summaries were 46.3 ± 10.0 and 46.6 ± 9.3, respectively. Scores on the Treatment Satisfaction Questionnaire for Medication ranged from 69.9 ± 19.9 to 88.3 ± 21.2 depending on the domain. Treatment with Hizentra was well tolerated. No single drug-related systemic reaction occurred in more than one patient and few local reactions were reported ( n  = 5). Conclusions Under real-life conditions and in a cohort that included patients with primary and secondary immunodeficiencies, treatment with Hizentra was effective and well tolerated and patients were generally satisfied with the treatment.

In the phase 3 OPTIMISMM trial, pomalidomide, bortezomib, and dexamethasone (PVd) demonstrated superior efficacy vs bortezomib and dexamethasone (Vd) in patients with relapsed or refractory multiple myeloma previously treated with lenalidomide, including those refractory to lenalidomide. This analysis evaluated outcomes in patients at first relapse ( N  = 226) by lenalidomide-refractory status, prior bortezomib exposure, and prior stem cell transplant (SCT). Second-line PVd significantly improved PFS vs Vd in lenalidomide-refractory (17.8 vs 9.5 months; P  = 0.0276) and lenalidomide-nonrefractory patients (22.0 vs 12.0 months; P  = 0.0491), patients with prior bortezomib (17.8 vs 12.0 months; P  = 0.0068), and patients with (22.0 vs 13.8 months; P  = 0.0241) or without (16.5 vs 9.5 months; P  = 0.0454) prior SCT. In patients without prior bortezomib, median PFS was 20.7 vs 9.5 months ( P  = 0.1055). Significant improvement in overall response rate was also observed with PVd vs Vd in lenalidomide-refractory (85.9% vs 50.8%; P  < 0.001) and lenalidomide-nonrefractory (95.7% vs 60.0%; P  < 0.001) patients, with similar results regardless of prior bortezomib or SCT. No new safety signals were observed. These data demonstrate the benefit of PVd at first relapse, including immediately after upfront lenalidomide treatment failure and other common first-line treatments.