Gemcitabine/cisplatin versus 5-fluorouracil/mitomycin C chemoradiotherapy in locally advanced pancreatic cancer: a retrospective analysis of 93 patients

<p>Abstract</p> <p>Background</p> <p>Despite of a growing number of gemcitabine based chemoradiotherapy studies in locally advanced pancreatic cancer (LAPC), 5-fluorouracil based regimens are still regarded to be standard and the debate of superiority between the two drugs is going on. The aim of this retrospective analysis was to evaluate the effect of two concurrent chemoradiotherapy regimens using 5-fluorouracil or gemcitabine to compare their effect and tolerance.</p> <p>Methods</p> <p>We have performed a single centre retrospective analysis of 93 patients treated with conventionally fractionated radiotherapy of 55.8 Gray using either concurrent 5-fluorouracil, 1 g/m² on days 1-5 and 29-33 of radiotherapy and 10 mg/m² of mitomycin C on day 1, 29 of radiotherapy (FM group, 35 patients) versus gemcitabine (300 mg/m²) and cisplatin, (30 mg/m²) on days 1, 8, 22, and 29 (GC group, 58 patients). Primary endpoint was the median overall survival (OS) rate.</p> <p>Results</p> <p>The median OS rate was 12.7 months in the GC group and 9.7 months in the FM group. The 1-year OS rate was 53% versus 40%, respectively (p = 0.009). GC led to more grade 3 leukocytopenia and thrombocytopenia than FM, but not to more grade 4 myelosuppression. Thrombocytopenia was the most frequently observed grade 4 toxicity in both groups (11% after FM versus 12% after GC). No grade 3/4 febrile neutropenia was observed. Grade 3 nausea was more common in the FM group (20% versus 9%) and grade 4 nausea was observed in one patient per group only.</p> <p>Conclusions</p> <p>GC was superior to FM for overall survival and both regimens were similar in terms of tolerance. We conclude that GC leads to encouraging results and that the use of FM for chemoradiotherapy in LAPC cannot be recommended without concerns.</p

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New Data on Pancreatic Cancer In pancreatic cancer there is a marked discrepancy between the recorded R0 resection rates and the long-term clinical outcome. Therefore, it seems to be necessary to find additional parameters that will be of more prognostic value here. Differences in how the R classification is applied within the studies are conspicuous. It would seem important to examine standards in histopathological preparation and to return to the `classical' R classification and, if appropriate, in line with experiences in rectum cancer, to introduce a `circumferential resection margin'. To obtain optimum long-term survival, a distance of >1.0 mm or even >1.5 mm between tumor and resection margin is required. In too few patients with vascular invasion is the tumor properly removed surgically, even though infiltration of the portal vein or the superior mesenteric vein is not an exclusion criterion according to the S3 guideline. An improvement in the quality of treatment might be achieved by establishing `high-volume' pancreas centers. The value of perioperative radiochemotherapy (RCT) is currently being examined in several large studies. Adjuvant chemotherapy is standard and is well established in routine clinical practice

Long-Term Experience of Chemoradiotherapy Combined with Deep Regional Hyperthermia for Organ Preservation in High-Risk Bladder Cancer (Ta, Tis, T1, T2).

BackgroundThe aim of this study was to evaluate the efficacy and safety of chemoradiotherapy (RCT) combined with regional deep hyperthermia (RHT) of high-risk bladder cancer after transurethral resection of bladder tumor (TUR-BT).Materials and methodsBetween 1982 and 2016, 369 patients with pTa, pTis, pT1, and pT2 cN0-1 cM0 bladder cancer were treated with a multimodal treatment after TUR-BT. All patients received radiotherapy (RT) of the bladder and regional lymph nodes. RCT was administered to 215 patients, RCT + RHT was administered to 79 patients, and RT was used in 75 patients. Treatment response was evaluated 4-6 weeks after treatment with TUR-BT.ResultsComplete response (CR) overall was 83% (290/351), and in treatment groups was RT 68% (45/66), RCT 86% (178/208), and RCT + RHT 87% (67/77). CR was significantly improved by concurrent RCT compared with RT (odds ratio [OR], 2.32; 95% confidence interval [CI], 1.05-5.12; p = .037), less influenced by hyperthermia (OR, 2.56; 95% CI, 0.88-8.00; p = .092). Overall survival (OS) after RCT was superior to RT (hazard ratio [HR], 0.7; 95% CI, 0.50-0.99; p = .045). Five-year OS from unadjusted Kaplan-Meier estimates was RCT 64% versus RT 45%. Additional RHT increased 5-year OS to 87% (HR, 0.32; 95% CI, 0.18-0.58; p = .0001). RCT + RHT compared with RCT showed a significantly better bladder-preservation rate (HR, 0.13; 95% CI, 0.03-0.56; p = .006). Median follow-up was 71 months. The median number of RHT sessions was five.ConclusionThe multimodal treatment consisted of a maximal TUR-BT followed by RT; concomitant platinum-based chemotherapy combined with RHT in patients with high-grade bladder cancer improves local control, bladder-preservation rate, and OS. It offers a promising alternative to surgical therapies like radical cystectomy.Implications for practiceRadical cystectomy with appropriate lymph node dissection has long represented the standard of care for muscle-invasive bladder cancer in medically fit patients, despite many centers reporting excellent long-term results for bladder preserving strategies. This retrospective analysis compares different therapeutic modalities in bladder-preservation therapy. The results of this study show that multimodal treatment consisting of maximal transurethral resection of bladder tumor followed by radiotherapy, concomitant platinum-based chemotherapy combined with regional deep hyperthermia in patients with Ta, Tis, T1-2 bladder carcinomas improves local control, bladder-preservation rate, and survival. More importantly, these findings offer a promising alternative to surgical therapies like radical cystectomy. The authors hope that, in the future, closer collaboration between urologists and radiotherapists will further improve treatments and therapies for the benefit of patients

Gewinnt soviel ihr könnt! Entscheidungsverhalten in Intergruppenkonflikten ; eine experimentelle Untersuchung von Entrapment-Strategien

"Entscheidungen in informellen politischen Verfahren (z.B. Mediation) sind durch komplexe Interaktionen zwischen Gruppen und durch eine relative Offenheit in der Wahl der verfolgten Ziele und Interaktionsmuster durch die Beteiligten gekennzeichnet. Herkömmliche experimentelle Analysen von Entscheidungsprozessen bilden dies nur bedingt ab. Die Studie dient vorrangig der Entwicklung einer Forschungsmethodik: Mit Hilfe des gruppendynamischen Entscheidungsspiels 'Gewinnt soviel ihr könnt!' wurde eine in dieser Hinsicht repräsentativere experimentelle Situation erzeugt. Untersucht wurden Entrapment-Strategien. Hierbei handelt es sich um ein Entscheidungsmuster, in dem Menschen oder Gruppen trotz erkennbarer eigener Verluste ihr Verhalten nicht ändern. Es wurde bei vielen politischen Fehlentscheidungen beobachtet. Ein besseres Verständnis dieses Phänomens könnte einen Betrag zur konstruktiven Gestaltung politischer Entscheidungsprozesse leisten. In der Untersuchung konnten (neben anderen Entscheidungsmustern) Entrapment-Strategien bei Intergruppenentscheidungen mit Hilfe des genannten Spiels realisiert werden. Es ließ sich zeigen, daß bei den Spielteilnehmern Einschränkungen in der Wahrnehmung von Zieloptionen und Kooperationsmöglichkeiten existierten. Bei Teilgruppen mit Entrapment-Strategien wurde trotz einer Eskalation der Verluste eine relative Zufriedenheit mit ihrer Entscheidungsfindung innerhalb der Teilgruppe festgestellt." (Autorenreferat)"Decision making as part of informal political procedures such as mediation is not only characterized by complex interaction between different groups, but also by relative freedom of choice regarding aims and interactive patterns. Past research has met these criteria only to a limited extent. First, this study was designed to develop a method that would enable research of group decision-making processes in a more realistic setting. For this reason, a game widely used in the field of group dynamics ('Win as much as you can!') was chosen. Second, this study focused on the entrapment phenomenon, i.e., a pattern of decision making that does not change, despite an escalation of loss. Entrapment has been observed previously in conjunction with faulty decision making in the political arena ; an enhanced understanding of it may contribute to an improved design for political decision making. In addition to other patterns, entrapment occurred in the process of inter-group decision making once the game was implemented. This study indicates that the participants' perception of opportunities for cooperation was limited. Also apparent was the failure to represent all alternative goal options available in the game. Participants belonging to groups that pursued entrapment strategies expressed satisfaction with their internal decision-making processes in the face of escalating loss." (author's abstract

Interaktionsmuster in einem Diskursverfahren zur Indikatorenentwicklung im Umweltbereich

"Informelle Diskurse haben Konjunktur: Runde Tische, Mediationsverfahren, partizipative Dialoge und Beratungsgremien aller Art begleiten die politische oder gesellschaftliche Entscheidungsfindung. Durch geordnete und faire Kommunikation sollen sachgerechte Entscheidungen ermöglicht werden. Gleichwohl gibt es nur wenige Studien, in denen Kommunikationsstruktur und -verlauf in politikbezogenen Diskursen systematisch beschrieben werden. Dieser Bericht versteht sich als Beitrag zur systematischen Analyse politischer Diskurse. Empirischer Beispielfall ein Diskursverfahren zur Entwicklung von Umweltindikatoren. Mit Hilfe der Konferenzkodierung wurden die sprachlichen Äußerungen der Beteiligten ausgewertet. Es konnte nachgewiesen werden, dass im Verlauf eines viertägigen moderierten Diskurses die Art der Auseinandersetzung versachlicht werden kann. Die Besonderheit des hier untersuchten Diskurses, Wissenschaftler befragen Vertreter gesellschaftlicher Interessengruppen, spiegelt sich in den Interaktionen wider. Es war durch entsprechende Einstimmungen vorab sowie durch eine gezielte Moderation möglich, forschungsrelevante Fragen in einer politischen Fachöffentlichkeit konstruktiv zu diskutieren. Parallelen mit anderen Studien der empirischen Diskursforschung sowie Implikationen für die Moderation von Diskursverfahren werden diskutiert." (Autorenreferat)"Informal discourses are a current trend. Roundtable discussions, mediation procedures, state-of-the-future workshops and consultative bodies of every sort accompany political decision-making. Proper decisions are supposed to be ensured through ordered and fair communication. At the same time, however, only very few studies are available, which describe systematically communications structures and procedures directly related to a policy discourse. On the basis of surveyed verbal indicators gathered in the course of a four-day, moderated debate on the development of environmental indicators, the researchers were able to show that it was possible to objectify the form of the dispute. The characteristic feature of the discourse under investigation here (scientists posing questions to representatives of various organizations and associations) is reflected in the interactions, as was revealed by means of an interaction process analysis. Thus, as a result of corresponding preparations and well-directed moderation, it was possible to hold a constructive discussion of research-relevant issues within a political setting among an expert public. Parallels with other findings in small group and discourse research as well as implications for the practice of moderators are discussed." (author's abstract

MAX-DOAS measurements of atmospheric trace gases in Ny-Ålesund - Radiative transfer studies and their application

International audienceA new approach to derive tropospheric concentrations of some atmospheric trace gases from ground-based UV/vis measurements is described. The instrument, referred to as the MAX-DOAS, is based on the well-known UV/vis instruments, which use the sunlight scattered in the zenith sky as the light source and the method of Differential Optical Absorption Spectroscopy (DOAS) to derive column amounts of absorbers like ozone and nitrogen dioxide. Substantial enhancements have been applied to this standard setup to use different lines of sight near to the horizon as additional light sources (MAX - multi axis). Results from measurements at Ny-Ålesund (79° N, 12° E) are presented and interpreted with the full-spherical radiative transfer model SCIATRAN. In particular, measurements of the oxygen dimer O4 which has a known column and vertical distribution in the atmosphere are used to evaluate the sensitivity of the retrieval to parameters such as multiple scattering, solar azimuth, surface albedo and refraction in the atmosphere and also to validate the radiative transfer model. As a first application, measurements of NO2 emissions from a ship lying in Ny-Ålesund harbour are presented. The results of this study demonstrate the feasibility of long term UV/vis multi axis measurement that can be used to derive not only column amounts of different trace gases but also some information on the vertical location of these absorbers

CD8+ and Regulatory T cells Differentiate Tumor Immune Phenotypes and Predict Survival in Locally Advanced Head and Neck Cancer

Background: The tumor immune status “inflamed”, “immune excluded”, and “desert” might serve as a predictive parameter. We studied these three cancer immune phenotypes while using a simple immunohistochemical algorithm. Methods: Pre-treatment tissue samples of 280 patients with locally advanced HNSCC treated with radiochemotherapy were analyzed. A double staining of CD8+ cytotoxic T cells (CTL) and FoxP3+ (Treg) was performed and the cell density was evaluated in the intraepithelial and stromal compartment of the tumor. Results: The classification of tumors as “immune desert” when stromal CTL were ≤ 50 cells/mm2, “inflamed” when intraepithelial CTL were > 500 cells/mm2, and as “excluded” when neither of these definitions met these cut off values allowed the best discrimination regarding overall survival. These groups had median OS periods of 37, 61, and 85 months, respectively. In “immune desert” and “immune excluded” tumors high Treg tended to worsen OS, but in “inflamed” tumors high Treg clearly improved OS. Conclusions: We propose that, in locally advanced HNSCC, the tumor immune state “inflamed”, “immune excluded”, and “immune desert” can be defined by intraepithelial and stromal CTL. Tregs can further subdivide these groups. The opposing effects of Tregs in the different groups might be the reason for the inconsistency of Tregs prognostic values published earlier

Deep Learning for Cancer Prognosis Prediction Using Portrait Photos by StyleGAN Embedding

Survival prediction for cancer patients is critical for optimal treatment selection and patient management. Current patient survival prediction methods typically extract survival information from patients' clinical record data or biological and imaging data. In practice, experienced clinicians can have a preliminary assessment of patients' health status based on patients' observable physical appearances, which are mainly facial features. However, such assessment is highly subjective. In this work, the efficacy of objectively capturing and using prognostic information contained in conventional portrait photographs using deep learning for survival predication purposes is investigated for the first time. A pre-trained StyleGAN2 model is fine-tuned on a custom dataset of our cancer patients' photos to empower its generator with generative ability suitable for patients' photos. The StyleGAN2 is then used to embed the photographs to its highly expressive latent space. Utilizing the state-of-the-art survival analysis models and based on StyleGAN's latent space photo embeddings, this approach achieved a C-index of 0.677, which is notably higher than chance and evidencing the prognostic value embedded in simple 2D facial images. In addition, thanks to StyleGAN's interpretable latent space, our survival prediction model can be validated for relying on essential facial features, eliminating any biases from extraneous information like clothing or background. Moreover, a health attribute is obtained from regression coefficients, which has important potential value for patient care