Search

Introduction: PD-1 blockade is effective in relapsed/refractory classical Hodgkin lymphoma (R/R cHL). To date, early metabolic response has been the best predictor of outcome in this setting. In this study, we explored additional baseline and early FDG PET-CT parameters as potential prognosticators in patients with R/R cHL treated with single agent nivolumab in the CHECKMATE 205 trial. Methods: Available PET-CT scans from patients without progression (by IRC Lugano 2007 criteria) by week (wk) 17 were retrospectively reviewed by 2 readers blinded to outcome. Baseline and wk17 metabolic parameters in tumour and healthy tissues uninvolved by lymphoma were examined for their association with PFS using Cox regression. Results: Baseline scans have been reviewed to date for 57 patients, and 49 patients at wk17 from 19 centres, with median follow up 60.7 months. There was a significant association between baseline maximum standardised uptake value (SUV) and PFS [HR 1.48 (95% CI 1.09–2.02) p = 0.012], wk17 Deauville score (DS) [Log-rank trend p = 0.0008] and Lugano response [HR 4.83 PMR vs. CMR (1.37–17.03) p = 0.014]. There was possible but non-significant association between the maximum distance between lesions at baseline and PFS (p = 0.07), but not for baseline metabolic tumour volume (MTV), wk17 MTV, change in MTV or change in SUVmax. Interestingly, baseline bone marrow and splenic uptake in uninvolved organs were associated with PFS, but not uptake in other uninvolved organs (liver, mediastinal blood pool, bowel, skeletal muscle and adipose tissue). The effect of baseline SUVmax remained very similar even in Lugano responders (CMR/PMR, n = 33) at wk17 HR 1.45 (95% CI 0.90—2.33) 1.45 (95% CI 0.90–2.33), though with the reduced sample size (n = 33) did not reach significance p = 0.13. Conclusion: Baseline SUVmax and week 17 PET-CT response in this prospectively acquired clinical trial dataset, but not MTV, were significantly associated with PFS

Metal artefacts in PET/CT images hamper diagnostic accuracy in head and neck cancer (HNC). The aim of this study is to characterise the clinical effects of metal artefacts on PET/CT in HNC and to inform decision-making concerning implementation of MAR techniques. We study a combined dual energy CT and inpainting-based metal artefact reduction (DECT-I-MAR) technique for PET/CT in three settings: (A) A dental phantom with a removable amalgam-filled tooth to evaluate the PET error in comparison to a known reference. (B) PET-positive patients with metallic implants to demonstrate the relationship between CT metal artefacts and PET error. (C) Metabolic tumour volumes delineated in PET-positive patients with metal implants to evaluate the clinical impact. In (A) DECT-I-MAR reduced the PET error significantly. In (B) we demonstrate an increasing PET error with increasing CT artefact severity in patients. In (C) it is shown that the presence of artefacts in the same axial slices as the tumour significantly decreases biomarker stability and increase delineation variability. This work shows the practical feasibility of DECT-I-MAR-based PET/CT imaging, and indicates a positive clinical impact of using the technique routinely for HNC patients. The impact of CT artefacts on PET is considerable, especially in workflows where quantitative PET biomarkers and tumour volumes are used. In such cases, and for patients with tumours in proximity of metals, we recommend that a MAR technique for PET/CT is employed.

Background: Although autoimmunity and hyperinflammation secondary to recombination activating gene (RAG) deficiency have been associated with delayed diagnosis and even death, our current understanding is limited primarily to small case series. Objective: Understand the frequency, severity, and treatment responsiveness of autoimmunity and hyperinflammation in RAG deficiency. Methods: In reviewing the literature and our own database, we identified 85 patients with RAG deficiency, reported between 2001 and 2016, and compiled the largest case series to date of 63 patients with prominent autoimmune and/or hyperinflammatory pathology. Results: Diagnosis of RAG deficiency was delayed a median of 5 years from the first clinical signs of immune dysregulation. Most patients (55.6%) presented with more than 1 autoimmune or hyperinflammatory complication, with the most common etiologies being cytopenias (84.1%), granulomas (23.8%), and inflammatory skin disorders (19.0%). Infections, including live viral vaccinations, closely preceded the onset of autoimmunity in 28.6% of cases. Autoimmune cytopenias had early onset (median, 1.9, 2.1, and 2.6 years for autoimmune hemolytic anemia, immune thrombocytopenia, and autoimmune neutropenia, respectively) and were refractory to intravenous immunoglobulin, steroids, and rituximab in most cases (64.7%, 73.7%, and 71.4% for autoimmune hemolytic anemia, immune thrombocytopenia, and autoimmune neutropenia, respectively). Evans syndrome specifically was associated with lack of response to first-line therapy. Treatment-refractory autoimmunity/hyperinflammation prompted hematopoietic stem cell transplantation in 20 patients. Conclusions: Autoimmunity/hyperinflammation can be a presenting sign of RAG deficiency and should prompt further evaluation. Multilineage cytopenias are often refractory to immunosuppressive treatment and may require hematopoietic cell transplantation for definitive management.

PURPOSE: The purpose of this study was to assess the use of 18F-FDG PET/CT scans for detecting distant metastases in patients with recurrent head and neck squamous cell carcinoma (HNSCC) and investigate the treatment and survival of patients with recurrence.METHODS: In this retrospective study, consecutive head and neck cancer patients referred for FDG PET/CT scan between 2012 and 2014 were included. Patient records were reviewed and only patients with recurrence of HNSCC were enrolled for further analysis. Information on distant metastases, surgery and survival was collected. A Kaplan-Meier analysis was used to report survival.RESULTS: Overall 275 PET/CT scans were performed due to suspected recurrence, and in 166 scans (144 patients), recurrence of HNSCC was confirmed, making them eligible for further analysis. Distant metastases were revealed in 29.8% of the scans (n = 51) and the proportion of revealed metastases remained constant at approximately 30% each year. Although the number of performed scans increased twofold each year, there was no statistically significant change in the proportion of scans with distant metastasis (p = 0.55). The distant metastases were most often seen in the lungs (n = 44) and bone (n = 15). A few patients had widespread dissemination to other areas. Salvage surgery was performed following 81 of the 166 PET/CT scans. Seven of the patients who underwent salvage surgery had M-site oligo-metastases. Patients who underwent salvage surgery had a median survival of 22 months whereas patients not treated with salvage surgery had a median survival of 6 months. After 5 years, 21% of the patients selected for salvage surgery were alive.CONCLUSIONS: Distant metastases occur frequently in patients with recurrent HNSCC disease and the proportion of revealed distant metastases remained the same (30%). Imaging with FDG PET/CT can be recommended in patients with recurrent HNSCC prior to putative salvage surgery.

Runoff generation mechanisms vary between catchments and despite decades of research in many catchments, these mechanisms are still not fully understood. In this paper, runoff generation mechanisms in the steep pre-alpine catchments in the Alptal, Switzerland, are discussed. These fast responding catchments are characterized by low permeability soils on top of flysch bedrock. In combination with the high and frequent precipitation, this results in predominantly wet conditions. In many areas, the water table is close to the surface. We review the main results of recent (2009-2016) studies in these catchments that used isotope, stream chemistry and hydrometric data. These field studies focused on the spatial and temporal patterns in groundwater levels, spatial patterns in the isotopic composition and chemistry of streamflow during baseflow conditions, as well as the responses of streamflow and its isotopic composition during rainfall events. The combined results of these studies highlight the establishment of connectivity of areas with different topographic positions and areas with a different land use during rainfall events. They also show the importance of flow in higher conductivity near surface soil layers for runoff generation, as well as the frequent occurrence of surface runoff. Spatial differences in groundwater dynamics are related to topography. Streamflow responses are mainly affected by the rainfall characteristics; differences in streamflow and hydrochemistry between catchments with different portions of forest, meadows and wetlands, were relatively small. However, variations in the chemistry of baseflow along stream reaches within a catchment were considerable. Above all, these studies highlight the value of combining data on spatial patterns of groundwater levels and stream chemistry with long term data on streamflow to derive a more complete picture of the dominant runoff generation mechanisms.

PURPOSE: Solid organ transplant (SOT) recipients are at high risk of developing infections and malignancies.18F-FDG PET/CT may enable timely detection of these diseases and help to ensure early intervention. We aimed to describe the clinical utility of FDG PET/CT in consecutive, diagnostic unresolved SOT recipients transplanted from January 2004 to May 2015.METHODS: Recipients with a post-transplant FDG PET/CT performed as part of diagnostic work-up were included. Detailed chart reviews were done to extract relevant clinical information and determine the final diagnosis related to the FDG PET/CT. Based on á priori defined criteria and the final diagnosis, results from each scan were classified as true or false, and diagnostic values determined.RESULTS: Among the 1,814 recipients in the cohort, 145 had an FDG PET/CT performed; 122 under the indication of diagnostically unresolved symptoms with a suspicion of malignancy or infection. The remaining (N = 23) had an FDG PET/CT to follow-up on a known disease or to stage a known malignancy. The 122 recipients underwent a total of 133 FDG PET/CT scans performed for a suspected malignancy (66 %) or an infection (34 %). Sensitivity, specificity, and positive and negative predictive values of the FDG PET/CT in diagnosing these conditions were 97, 84, 87, and 96 %, respectively.CONCLUSION: FDG PET/CT is an accurate diagnostic tool for the work-up of diagnostic unresolved SOT recipients suspected of malignancy or infection. The high sensitivity and NPV underlines the potential usefulness of PET/CT for excluding malignancy or focal infections in this often complex clinical situation.

OBJECTIVE: To investigate reproducibility of fluorine-18 fludeoxyglucose ((18)F-FDG) uptake on (18)F-FDG positron emission tomography (PET)/CT and (18)F-FDG PET/MR scans in patients with head and neck squamous cell carcinoma (HNSCC).METHODS: 30 patients with HNSCC were included in this prospective study. The patients were scanned twice before radiotherapy treatment with both PET/CT and PET/MR. Patients were scanned on the same scanners, 3 days apart and according to the same protocol. Metabolic tumour activity was measured by the maximum and peak standardized uptake value (SUVmax and SUVpeak, respectively), and total lesion glycolysis from the metabolic tumour volume defined from ≥50% SUVmax. Bland-Altman analysis with limits of agreement, coefficient of variation (CV) from the two modalities were performed in order to test the reproducibility. Furthermore, CVs from SUVmax and SUVpeak were compared. The area under the curve from cumulative SUV-volume histograms were measured and tested for reproducibility of the distribution of (18)F-FDG uptake.RESULTS: 24 patients had two pre-treatment PET/CT scans and 21 patients had two pre-treatment PET/MR scans available for further analyses. Mean difference for SUVmax, peak and mean was approximately 4% for PET/CT and 3% for PET/MR, with 95% limits of agreement less than ±20%. CV was small (5-7%) for both modalities. There was no significant difference in CVs between PET/CT and PET/MR (p = 0.31). SUVmax was not more reproducible than SUVpeak (p = 0.09).CONCLUSION: (18)F-FDG uptake in PET/CT and PET/MR is highly reproducible and we found no difference in reproducibility between PET/CT and PET/MR.ADVANCES IN KNOWLEDGE: This is the first report to test reproducibility of PET/CT and PET/MR.

Terahertz time-domain spectroscopy (THz-TDS) systems traditionally operate in a single mode, either in reflection or transmission. In cases where the sample has nonunity permeability, measurements in both reflection and transmission geometries are required. The process of shifting and swapping the samples during an experiment increases the measurement uncertainty. This paper therefore presents a system where both reflection and transmission measurements can be performed simultaneously to reduce both experimental error and acquisition time. The measurement results are validated against findings in literature.

Optimal focusing of surface plasmon polaritons in the center of a metal disc illuminated by radially polarized terahertz pulses is demonstrated. Due to the cylinder symmetrical structure surface plasmons can be excited along the entire circumference, which interfere constructively in the center of the disk forming a sharp frequency-depended focal spot. We map the field distribution on the disk by THz near-field microscopy and compare our result to numerical simulations. For comparison, behavior under linearly polarized THz illumination is characterized. Furthermore, first results of semiconducting plasmonic lenses are presented.

With a growing world population and a trend towards more resource-intensive diets, pressure on land and water resources for food production will continue to increase in the coming decades. Large parts of the world rely on rainfed agriculture for their food security. In Africa, 90 % of the food production is from rainfed agriculture, generally with low yields and a high risk of crop failure. One of the main reasons for crop failure is the occurrence of dry spells during the growing season. Key indicators are the critical dry spell duration and the probability of dry spell occurrence. In this paper a new Markov-based framework is presented to spatially map the length of dry spells for fixed probabilities of non-exceedance. The framework makes use of spatially varying Markov coefficients that are correlated to readily available spatial information such as elevation and distance to the sea. The dry spell map thus obtained is compared to the spatially variable critical dry spell duration, based on soil properties and crop water requirements, to assess the probability of crop failure in different locations. The results show that in the Makanya catchment the length of dry spell occurrence is highly variable in space, even over relatively short distances. In certain areas the probability of crop failure reaches levels that make rainfed agricultural unsustainable, even close to areas where currently rainfed agriculture is successfully being practised. This method can be used to identify regions that are vulnerable to dry spells and, subsequently, to develop strategies for supplementary irrigation or rainwater harvesting.

Liquid crystals (LCs) are becoming increasingly important for applications in the terahertz frequency range. A detailed understanding of the spectroscopic parameters of these materials over a broad frequency range is crucial in order to design customized LC mixtures for improved performance. We present the frequency dependent index of refraction and the absorption coefficients of the nematic liquid crystal 5CB over a frequency range from 0.3 THz to 15 THz using a dispersion-free THz time-domain spectrometer system based on two-color plasma generation and air biased coherent detection (ABCD). We show that the spectra are dominated by multiple strong spectral features mainly at frequencies above 4 THz, originating from intramolecular vibrational modes of the weakly LC molecules.

While soil moisture patterns can be interesting traits to investigate spatio-temporal heterogeneity of catchments relevant for various physical processes of soil-atmosphere interaction and soil water redistribution, many of the existing methods to capture spatial patterns are time consuming, expensive or need site-specific calibration. In this study we present a quick and inexpensive supplementary field method for classifying soil wetness in wet environments. The seven wetness classes are based on qualitative indicators, which one can touch, hear or see on the soil surface. To counter critics that such qualitative methods are considerably affected by subjectivity, we performed systematic testing of the method by taking qualitative measurements in the field with 20 non-expert raters. We then analyzed these in terms of degree of agreement and assessed the results against gravimetric sampling and time domain reflectometry measurements. In 70% of all classifications raters agreed on the wetness class assigned to the marked sampling locations and in 95% they were not off by more than one wetness class. The seven quantitative wetness classes agreed with gravimetric and time domain reflectometry measurements, although intermediate to wet classes showed an overlap of their range whereas the driest classes showed considerable spread. Despite some potential to optimize the method, it has been shown to be a reliable supplement to existing quantitative techniques for assessing soil moisture patterns in wet environments.