CT scans are the gold standard to measure treatment success of Non-Small Cell Lung Cancer (NSCLC) therapies. In recent years, liquid biopsies became an adequate diagnostic tool especially in advanced disease stages. Here, we investigated very early tumor response of patients receiving chemotherapy or targeted therapies using a panel of already established and explorative liquid biomarkers. Blood samples from patients were taken at baseline and day + 1 for the chemotherapy cohort (n = 25) and at baseline, day +7 and +14 for the targeted therapy cohort (n = 25). DNA mutational load, a panel of 17 microRNAs, glycodelin, glutathione disulfide, glutathione, soluble caspase-cleaved keratin 18 (M30 antigen) and soluble keratin 18 (M65 antigen) were measured using serum and plasma from patients. Baseline and first follow-up CT scan were evaluated by an experienced radiologist and correlated with biomarker data. In the majority of patients a decrease in glycodelin abundance as well as mutational load coincided with clinical response as assessed by CT scan. Consequently, an increase of these biomarkers implicated progressive disease. Among the measured miRNAs, miR-103, miR-628-3p, and let-7e showed largely similar behavior within individual patients upon treatment initiation. The abundance of these miRNAs increased in responding patients and in a subset of patients experiencing tumor progression. Similar observations were seen for the apoptosis markers while the best results were obtained with the detection of M65. Taken together, several investigated biomarkers showed high potential for an early response capturing in defined NSCLC cohorts.

Background: Currently, there is no possibility to detect early tumor response in lung cancer patients within the first days after chemotherapy (CTx) or tyrosine kinase inhibitor (TKI) therapy induction. Using the current gold standard for therapy monitoring, i.e. the measurement of morphologic differences according to RECIST 1.1 by CT and MRI, changes are detected only after weeks or months. Thus, patients may undergo eventually ineffective treatment and suffer from unnecessary toxicity, with both causing relevant costs. This highlights the importance of early response detection to guide and optimize therapy. Monitoring treatment response with diffusion-weighted and dynamic contrast perfusion MR imaging has been proposed for some time as a new powerful tool that will allow determining tumor response much earlier than RECIST. Trial design: This is an observational, prospective, multicenter, non-randomized, open clinical study. 150 patients with non-squamous NSCLC undergoing systemic treatment receive MRI before and after 1st-line therapy. The first follow-up (FU) MRI for patients undergoing chemotherapy is performed 24 hours post treatment. Patients treated with TKIs undergo MRI at days 7 and 14 after therapy induction. A thoracic MRI protocol is performed, including navigated diffusion-weighted imaging with the acquisition of 6 b-values, while the evaluation will focus on the non-perfusion sensitive b-values 400 and 800 (online calculated trace images) and the apparent diffusion coefficient (ADC). Software-based analysis of user-defined ROIs is used to assess the ADC value inside the tumor. ROIs are put in the solid part of the tumorous lesion. So far, 54 patients (28 TKI, 26 CTx) have been included. Findings will be correlated with routinely performed FU CT-imaging and the clinical outcome during FU visits. Further, an accompanying biomarker program aims to elucidate ultra-early blood-bound signs of apoptosis in correlation with MRI signals. This multicenter study will address the unmet clinical need of ultra-early detection of therapy response in NSCLC in order to translate this promising approach into broad clinical practice. Legal entity responsible for the study: Claus Peter Heussel. Funding: German Center for Lung Research (DZL). Disclosure: H-U. Kauczor: Grant: Siemens; Speakers bureau: Boehringer Ingelheim, Philips; Grant, speakers' bureau: Bracco, Bayer. M. Thomas: Speaker: Lilly, BMS, MSD, Roche, Pfizer, AstraZeneca; Advisory board: Lilly, BMS, MSD, Roche, Pfizer, AstraZeneca, Cellgene, Mediolanum. H. Golpon: Advisory boards: Roche, AstraZeneca, Boehringer Ingelheim, BMS. A. Tufman: Advisory boards: Roche, AstraZeneca, Boehringer Ingelheim. C.P. Heussel: Consultation or other fees: Schering-Plough, Pfizer, Basilea, Boehringer Ingelheim, Novartis, Roche, Astellas, Gilead, MSD, Lilly, Intermune, Fresenius; Research funding: Siemens, Pfizer, MeVis, Boehringer Ingelheim; Lecture fees: Gilead, Essex, Schering-Plough, AstraZeneca, Lilly, Roche, MSD, Pfizer , Bracco, Meda Pharma, Intermune, Chiesi, Siemens, Covidien, Pierre Fabre, Boehringer Ingelheim, Grifols, Novartis, Basilea, Bayer. F. Bozorgmehr: Research funding: BMS; Honoraria: MSD, Novartis. All other authors have declared no conflicts of interest.

Sepsis in chemotherapy-associated neutropenia is a major cause of mortality in the treatment of acute myeloid leukemia (AML). Early diagnosis of sepsis is crucial for patient survival. We analyzed the value of prospectively measuring serum concentrations of soluble tumor necrosis factor receptor type II (sTNF-RII) in patients with AML for early diagnosis of sepsis in neutropenia. Therefore, 54 adult patients with AML and neutropenia were followed around the onset of fever. A total of 59 febrile episodes were documented. We could not demonstrate a significant increase in sTNF-RII levels prior to fever. sTNF-RII concentrations were not predictive of the severity of a febrile episode. Based on these data, we cannot recommend the routine screening of sTNF-RII for early detection of septic complications in patients undergoing cytoreductive therapy of AML.

Drug Prescribing for Patients with Chronic Kidney Disease in General Practice: a Cross-Sectional Study

Drug Prescribing for Patients with Chronic Kidney Disease in General Practice: a Cross-Sectional Study

Drug Prescribing for Patients with Chronic Kidney Disease in General Practice: a Cross-Sectional Study

PURPOSE: To obtain statistical data on the use of high-resolution computed tomography (HRCT) for early detection of pneumonia in febrile neutropenic patients with unknown focus of infection. MATERIALS AND METHODS: One hundred eighty-eight HRCT studies were performed prospectively in 112 neutropenic patients with fever of unknown origin persisting for more than 48 hours despite empiric antibiotic treatment. Fifty-four of these studies were performed in transplant recipients. All patients had normal chest roentgenograms. If pneumonia was detected by HRCT, guided bronchoalveolar lavage was recommended. Evidence of pneumonia on chest roentgenograms during follow-up and micro-organisms detected during follow-up were regarded as documentation of pneumonia. RESULTS: Of the 188 HRCT studies, 112 (60%) showed pneumonia and 76 were normal. Documentation of pneumonia was possible in 61 cases by chest roentgenography or micro-organism detection (54%) (P < 10-6). Sensitivity of HRCT was 87% (88% in transplant recipients), specificity was 57% (67%), and the negative predictive value was 88% (97%). A time gain of 5 days was achieved by the additional use of HRCT compared to an exclusive use of chest roentgenography. CONCLUSION: The high frequency of inflammatory pulmonary disease after a suspicious HRCT scan (> 50%) proves that pneumonia is not excluded by a normal chest roentgenogram. Given the significantly longer duration of febrile episodes in transplant recipients, HRCT findings are particularly relevant in this subgroup. Patients with normal HRCT scans, particularly transplant recipients, have a low risk of pneumonia during follow-up. All neutropenic patients with fever of unknown origin and normal chest roentgenograms should undergo HRCT.

PURPOSE:To examine the advantage of liver and brain MRI in clinically anomalous haematological patients with fever of unknown origin.MATERIAL AND METHODS:Twenty liver MRI (T2-TSE, T2-HASTE, T1-FLASH +/- Gd dynamic) and 16 brain MRI (T2-TSE, FLAIR, T1-TSE +/- Gd) were performed searching for a focus of fever with a suspected organ system. Comparison with clinical follow-up.RESULTS:A focus was detected in 11/20 liver MRI. Candidiasis (n = 3), mycobacteriosis (n = 2), relapse of haematological disease (n = 3), graft versus host disease (n = 1), non-clarified (n02). The remaining 9 cases with normal MRI were not suspicious of infectious hepatic disease during follow-up. In brain MRI, 3/16 showed a focus (toxoplasmosis, aspergillosis, mastoiditis). Clinical indication for an infectious involvement of the brain was found in 4/16 cases 2-5 months after initially normal brain MRI. No suspicion of an infectious involvement of brain was present in the remaining 9/16 cases.CONCLUSION:In case of fever of unknown origin and suspicion of liver involvement, MRI of the liver should be performed due to data given in literature and its sensitivity of 100%. Because of the delayed detectability of cerebral manifestations, in cases of persisting suspicion even a previously normal MRI of the brain should be repeated.

Renal insufficiency or allergic reactions for X-ray contrast agents are frequent limitations in immunocompromised hosts such as neutropenic or AIDS patients. Due to a better tolerance of contrast agents in MRI, this technique is well suited for investigation of parenchymal organs. We demonstrate an allergic AIDS patient who presented with fever and flank pain. At sonography, anechoic renal lesions were supposed to be non-complicated cysts; however, on T2-weighted MRI, the center was of high signal. Dynamic contrast-enhanced MRI of the kidneys demonstrated an enhancing rim with ill-defined margins. The lesions were supposed to be multiple bilateral abscesses. Due to the multiple dynamic contrast series, a delayed enhancement of renal parenchyma was detectable adjacent to the lesion. This was suggested as accompanying local pyelonephritis and an infectious etiology became more reliable. Aspergillus fumigatus was identified by CT-guided biopsy as the underlying microorganism. The MR appearance of this manifestation has not been described previously.

Die moderne Tumortherapie ist durch die zunehmende Zahl von Hochdosisprotokollen immer häufiger mit einer lang andauernden Neutropenie und der daraus resultierenden Immunabwehrschwäche verbunden [11, 16, 24]. Die Infektionshäufigkeit liegt bei einer Neutropeniedauer von mehr als 8–10 Tagen bei über 85% [23]. Bei etwa der Hälfte der Patienten kommt es nach empirischer Therapie und initialer Entfieberung im weiteren Verlauf erneut zu einem Temperaturanstieg und damit wiederum zu einem Infektionsverdacht [16, 38, 47]. Dabei sind neben disseminierten Infektionen hauptsächlich Lunge, Nasennebenhöhlen, Darm, Leber, Milz, Gehirn und Nieren betroffen [23, 24].

To compare the efficacy and toxicity of triple antibiotic therapy in patients undergoing autologous peripheral blood-stem-cell transplantation (PBSCT) with literature data.