Global patterns of care in advanced stage mycosis fungoides/Sezary syndrome: a multicenter retrospective follow-up study from the Cutaneous Lymphoma International Consortium

ABSTRACT Background Advanced-stage mycosis fungoides (MF)/Sezary syndrome (SS) patients are weighted by an unfavorable prognosis and share an unmet clinical need of effective treatments. International guidelines are available detailing treatment options for the different stages but without recommending treatments in any particular order due to lack of comparative trials. The aims of this second CLIC study were to retrospectively analyze the pattern of care worldwide for advanced-stage MF/SS patients, the distribution of treatments according to geographical areas (USA versus non-USA), and whether the heterogeneity of approaches has potential impact on survival. Patients and methods This study included 853 patients from 21 specialist centers (14 European, 4 USA, 1 each Australian, Brazilian, and Japanese). Results Heterogeneity of treatment approaches was found, with up to 24 different modalities or combinations used as first-line and 36% of patients receiving four or more treatments. Stage IIB disease was most frequently treated by total-skin-electron-beam radiotherapy, bexarotene and gemcitabine; erythrodermic and SS patients by extracorporeal photochemotherapy, and stage IVA2 by polychemotherapy. Significant differences were found between USA and non-USA centers, with bexarotene, photopheresis and histone deacetylase inhibitors most frequently prescribed for first-line treatment in USA while phototherapy, interferon, chlorambucil and gemcitabine in non-USA centers. These differences did not significantly impact on survival. However, when considering death and therapy change as competing risk events and the impact of first treatment line on both events, both monochemotherapy (SHR = 2.07) and polychemotherapy (SHR = 1.69) showed elevated relative risks. Conclusion This large multicenter retrospective study shows that there exist a large treatment heterogeneity in advanced MF/SS and differences between USA and non-USA centers but these were not related to survival, while our data reveal that chemotherapy as first treatment is associated with a higher risk of death and/or change of therapy and thus other therapeutic options should be preferable as first treatment approach

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Working Paper; n. 1

Geology and Geochemistry of the Hydrocarbon Compositional Changes in the Triassic Montney Formation, Western Canada

The geochemistry of produced fluids has been investigated in the Triassic Montney Formation in the Western Canadian Sedimentary Basin (WCSB). Understanding the geochemistry of produced fluids is a valuable tool in the exploration and development of a complex petroleum system such as the Montney Formation. The petroleum system changes from in situ unconventional reservoirs in the west to more conventional reservoirs that contain migrated hydrocarbons to the east. The workflow of basin modeling and mapping of isomer ratio calculations for butane and pentane as well as the mapping of excess methane percentage was used to highlight areas of gas compositional changes in the Montney Formation play area. This workflow shows the migration of hydrocarbons from deeper, more mature areas to less mature areas in the east through discrete pathways. Methane has migrated along structural elements such as the Fort St. John Graben as well as areas that have seen changes in higher permeability lithologies (i.e., well 14-23-74-8W6M). Excess methane percentage calculations highlight changes due to fluid mixing from hydrocarbon migration. The regional maturation polynomial regression line was used to determine the gas dryness percentage for each well on the basis of its maturation level determined by the butane isomer ratio. The deviation from the calculated gas dryness according to the regression was determined as an excess methane percentage. The British Columbia (BC) Montney play appears to have hydrocarbon compositions that reflect an in situ generation, while the Montney play in Alberta (AB) has a higher proportion of its hydrocarbon volumes from migrated hydrocarbons. The workflow provides a better understanding of the hydrocarbon system to optimize operations and increase production efficiency. Understanding the distribution of gas compositions within a play area will provide key information on the liquid and gas phases present and an understanding of how gas composition may change over the well life, as well as helping to maximize liquid recovery during well operations.Science, Faculty ofNon UBCEarth, Ocean and Atmospheric Sciences, Department ofReviewedFacultyResearcherGraduat

Reliability of new three-dimensional ultrasound technique for pelvic hiatal area measurement

Objective To assess the reproducibility of a new technique for three-/four-dimensional (3D/4D) ultrasound imaging of the pelvic floor: OmniView\u2122 volume contrast imaging (VCI) for measurement of the pelvic hiatal area on maximum contraction and Valsalva maneuver. In addition, we aimed to study the intermethod agreement between the new technique and the 3D/4D render method. Methods We acquired one static 3D and two dynamic 4D transperineal volumes (one obtained during contraction and one during Valsalva maneuver) from 35 nulliparous asymptomatic healthy volunteers and 35 women with symptoms of pelvic floor dysfunction. Each 3D dataset was analyzed using the OmniView-VCI technique to measure the pelvic hiatal area at rest, on maximum contraction and on maximum Valsalva. Analysis was performed twice by the same operator and once by another operator in order to assess intra- and interobserver reproducibility. All measurements were repeated by one operator using the 3D/4D render method to evaluate the intermethod agreement. Reproducibility and intermethod agreement were studied by means of intraclass correlation coefficients (ICC) and the Bland-Altman method. Results Measurement of hiatal area using the OmniView-VCI technique showed excellent intraobserver and interobserver reproducibility in both asymptomatic and symptomatic women at rest, on contraction and on Valsalva maneuver. In addition, excellent agreement was demonstrated between OmniView-VCI and 3D/4D render in both groups (ICCs on Valsalva in asymptomatic and symptomatic women were 0.894 and 0.975, respectively). No systematic difference was noted in any of the reliability studies performed. Conclusions OmniView-VCI is a reliable method for pelvic hiatal area measurement. Both rendering mode and OmniView-VCI can be used interchangeably for assessing pelvic hiatal area

A new simple technique for 3-dimensional sonographic assessment of the pelvic floor muscles

OBJECTIVES: The purpose of this study was to assess the reproducibility of a new technique for 3-dimensional (3D) pelvic floor sonography: OmniView combined with Volume Contrast Imaging (VCI; GE Healthcare, Kretz Ultrasound, Zipf, Austria) for pelvic hiatal area measurement. In addition, we aimed to study the intermethod agreement between the new technique and the standard 3D rendering method. METHODS: We acquired a static 3D sonographic transperineal volume from 124 nulliparous asymptomatic women and 118 women with symptoms of pelvic floor dysfunction. Each 3D data set was analyzed by the OmniView-VCI technique to measure the pelvic hiatal area twice by one operator and once by another to assess intraobserver and interobserver reproducibility. The first operator later measured the hiatal area using the 3D rendering method to evaluate intermethod agreement. Reproducibility and intermethod agreement were studied by the intraclass correlation coefficient and Bland-Altman method. RESULTS: Hiatal area measurements by the OmniView-VCI technique showed high intraobserver and interobserver reproducibility in both asymptomatic and symptomatic women. In addition, high agreement was shown between the new technique and 3D rendering in both groups. No systematic differences were noted in any of the reliability studies performed. The new technique took slightly less time to calculate the hiatal area than the standard rendering method in both asymptomatic and symptomatic women. CONCLUSIONS: OmniView-VCI is a reliable method for pelvic hiatal area measurement. Further studies are needed to assess its reliability under contraction and the Valsalva maneuver and to evaluate its usefulness and reproducibility for diagnosis of levator ani lesions