Use of EORTC Target Definition Guidelines for Dose-Intensified Salvage Radiation Therapy for Recurrent Prostate Cancer: Results of the Quality Assurance Program of the Randomized Trial SAKK 09/10

PURPOSE Different international target volume delineation guidelines exist and different treatment techniques are available for salvage radiation therapy (RT) for recurrent prostate cancer, but less is known regarding their respective applicability in clinical practice. METHODS AND MATERIALS A randomized phase III trial testing 64 Gy vs 70 Gy salvage RT was accompanied by an intense quality assurance program including a site-specific and study-specific questionnaire and a dummy run (DR). Target volume delineation was performed according to the European Organisation for the Research and Treatment of Cancer guidelines, and a DR-based treatment plan was established for 70 Gy. Major and minor protocol deviations were noted, interobserver agreement of delineated target contours was assessed, and dose-volume histogram (DVH) parameters of different treatment techniques were compared. RESULTS Thirty European centers participated, 43% of which were using 3-dimensional conformal RT (3D-CRT), with the remaining centers using intensity modulated RT (IMRT) or volumetric modulated arc technique (VMAT). The first submitted version of the DR contained major deviations in 21 of 30 (70%) centers, mostly caused by inappropriately defined or lack of prostate bed (PB). All but 5 centers completed the DR successfully with their second submitted version. The interobserver agreement of the PB was moderate and was improved by the DR review, as indicated by an increased κ value (0.59 vs 0.55), mean sensitivity (0.64 vs 0.58), volume of total agreement (3.9 vs 3.3 cm(3)), and decrease in the union volume (79.3 vs 84.2 cm(3)). Rectal and bladder wall DVH parameters of IMRT and VMAT vs 3D-CRT plans were not significantly different. CONCLUSIONS The interobserver agreement of PB delineation was moderate but was improved by the DR. Major deviations could be identified for the majority of centers. The DR has improved the acquaintance of the participating centers with the trial protocol.

„Es war, als hätte das Virus mich geschwängert.“ Vertextungsformen in Aids-Autobiographien

Die vorliegende Untersuchung der Vertextung von Aids in Autobiografien fokussiert die Frage, welcher Darstellungsstrategien diese sich bedienen und welche Funktionen sie in den westlichen Kulturen übernehmen. Vier Autobiografien werden exemplarisch mit Hilfe der Systemtheorie und der Diskursanalyse analysiert und auf folgende Leitfragen hin untersucht: Sind die AutorInnen an Aids erkrankt oder nicht? Welche Lebenszeit steht ihnen zur Verfügung? Sind sie professionelle Schriftsteller oder Laien? Welche Rolle spielt ihr Geschlecht? Welche Werte werden wie vermittelt? Wird Akzeptabilität geschaffen? Wie wird mit den Grenzen des Akzeptablen umgegangen? Wie wird die Konstruktion und Destruktion des schreibenden Subjektes angesichts der Krankheitserfahrung verhandelt? Das untersuchte Material umfasst ein Spektrum, das • das schnelle Sterben an Aids, das lange Leben mit Aids sowie das Leben als HIV-Negativer in Gegenwart von Aids zeigt. • von gesellschaftlich orientierter Bewältigung der Krankheitserfahrung über individuelle Bewältigung bis hin zur Verweigerung der gesellschaftlichen Integration reicht. • den unterschiedlichen Einsatz von Metaphern bei der Sinngebung und der Vertextung von Körpererfahrung aufzeigt: Sterben als Geburt (Normalisierungsrhetorik), Sterben als Holocaust (Eskalationsrhetorik), Krankheitserfahrung als Generator immer neuer, überbordender Sprachbilder.

Delivery of health care at the end of life in cancer patients of four swiss cantons a retrospective database study (SAKK 89/09)

Background The use of cancer related therapy in cancer patients at the end-of-life has increased over time in many countries. Given a lack of published Swiss data, the objective of this study was to describe delivery of health care during the last month before death of cancer patients. Methods Claims data were used to assess health care utilization of cancer patients (identified by cancer registry data of four participating cantons), deceased between 2006-2008. Primary endpoints were hospitalization rate and delivery of cancer related therapies during the last 30 days before death. Multivariate logistic regression assessed the explanatory value of patient and geographic characteristics. Results 3809 identified cancer patients were included. Hospitalization rate (mean 68.5%, 95%CI 67.0-69.9) and percentage of patients receiving anti-cancer drug therapies (ACDT, mean 14.5%, 95%CI 13.4-15.6) and radiotherapy (mean 7.7%, 95%CI 6.7-8.4) decreased with age. Canton of residence and insurance type status most significantly influenced the odds for hospitalization or receiving ACDT. Conclusions The intensity of cancer specific care showed substantial variation by age, cancer type, place of residence and insurance type status. This may be partially driven by cultural differences within Switzerland and the cantonal organization of the Swiss health care system.

Ferney: Voltaire en son château

Pressé de trouver un refuge pour fuir ses détracteurs, le philosophe jette son dévolu sur un petit coin de l'Ain. Après avoir entrepris un véritable chantier dont il est l'architecte, il va faire de Ferney le haut lieu de la pensée des Lumières.

Cancer-related therapies at the end of life in hospitalized cancer patients from four Swiss cantons: SAKK 89/09.

The use of cancer-related therapies in cancer patients hospitalized at the end of life has increased in many countries over time. Given the scarcity of published Swiss data, the objective of this study was to evaluate the influence of hospital type and other factors on the delivery of health care during the last month before death. Claims data were used to assess health care utilization of cancer patients (identified by cancer registry data of four participating Swiss cantons) who deceased between 2006 and 2008. Primary endpoints were delivery of cancer-related therapies during the last 30 days before death. Multivariate logistic regression assessed the explanatory value of hospital type, patient and geographic characteristics. Of 3,809 identified cancer patients in the claims database, 2,086 patients dying from cancer were hospitalized during the last 30 days before death, generating 2,262 inpatient episodes. Anticancer drug therapy was given in 22.2% and radiotherapy in 11.7% of episodes. Besides age and cancer type, the canton of residence and hospital type showed independent, statistically significant associations with intensity of care, which was highest in university hospitals. These results should initiate a discussion among oncologists in Switzerland and may question the compliance with standard of care guidelines for terminal cancer patients.

Michel Butor à la frontière

Dans l’œuvre de Michel Butor, la frontière peut être considérée comme un équivalent de la césure, comme le pli de la double page constituait un équivalent de la césure dans Un coup de dés chez Mallarmé. Elle se retrouve dans de très nombreuses œuvres, des romans au Génie du lieu, et dans de nombreuses œuvres poétiques, dont À la frontière et Frontières. Chez Butor, la frontière a un rôle d’articulateur ; mais cette articulation ne va pas de soi, et il faut passer par des «méditations» sur la frontière, qui permettent d’établir une typologie des diverses fonctions de la frontière.]

Bevacizumab, Pemetrexed, and Cisplatin, or Bevacizumab and Erlotinib for Patients With Advanced Non-Small-Cell Lung Cancer Stratified by Epidermal Growth Factor Receptor Mutation: Phase II Trial SAKK19/09

Treatment allocation by epidermal growth factor receptor mutation status is a new standard in patients with metastatic nonesmall-cell lung cancer. Yet, relatively few modern chemotherapy trials were conducted in patients characterized by epidermal growth factor receptor wild type. We describe the results of a multicenter phase II trial, testing in parallel 2 novel combination therapies, predefined molecular markers, and tumor rebiopsy at progression. Objective: The goal was to demonstrate that tailored therapy, according to tumor histology and epidermal growth factor receptor (EGFR) mutation status, and the introduction of novel drug combinations in the treatment of advanced nonesmall-cell lung cancer are promising for further investigation. Methods: We conducted a multicenter phase II trial with mandatory EGFR testing and 2 strata. Patients with EGFR wild type received 4 cycles of bevacizumab, pemetrexed, and cisplatin, followed by maintenance with bevacizumab and pemetrexed until progression. Patients with EGFR mutations received bevacizumab and erlotinib until progression. Patients had computed tomography scans every 6 weeks and repeat biopsy at progression. The primary end point was progression-free survival (PFS) ≥ 35% at 6 months in stratum EGFR wild type; 77 patients were required to reach a power of 90% with an alpha of 5%. Secondary end points were median PFS, overall survival, best overall response rate (ORR), and tolerability. Further biomarkers and biopsy at progression were also evaluated. Results: A total of 77 evaluable patients with EGFR wild type received an average of 9 cycles (range, 1-25). PFS at 6 months was 45.5%, median PFS was 6.9 months, overall survival was 12.1 months, and ORR was 62%. Kirsten rat sarcoma oncogene mutations and circulating vascular endothelial growth factor negatively correlated with survival, but thymidylate synthase expression did not. A total of 20 patients with EGFR mutations received an average of 16.

Acute Toxicity and Quality of Life After Dose-Intensified Salvage Radiation Therapy for Biochemically Recurrent Prostate Cancer After Prostatectomy: First Results of the Randomized Trial SAKK 09/10

PURPOSE Patients with biochemical failure (BF) after radical prostatectomy may benefit from dose-intensified salvage radiation therapy (SRT) of the prostate bed. We performed a randomized phase III trial assessing dose intensification. PATIENTS AND METHODS Patients with BF but without evidence of macroscopic disease were randomly assigned to either 64 or 70 Gy. Three-dimensional conformal radiation therapy or intensity-modulated radiation therapy/rotational techniques were used. The primary end point was freedom from BF. Secondary end points were acute toxicity according to the National Cancer Institute Common Terminology Criteria for Adverse Events (version 4.0) and quality of life (QoL) according to the European Organisation for Research and Treatment of Cancer Quality of Life Questionnaires C30 and PR25. RESULTS Three hundred fifty patients were enrolled between February 2011 and April 2014. Three patients withdrew informed consent, and three patients were not eligible, resulting in 344 patients age 48 to 75 years in the safety population. Thirty patients (8.7%) had grade 2 and two patients (0.6%) had grade 3 genitourinary (GU) baseline symptoms. Acute grade 2 and 3 GU toxicity was observed in 22 patients (13.0%) and one patient (0.6%), respectively, with 64 Gy and in 29 patients (16.6%) and three patients (1.7%), respectively, with 70 Gy (P = .2). Baseline grade 2 GI toxicity was observed in one patient (0.6%). Acute grade 2 and 3 GI toxicity was observed in 27 patients (16.0%) and one patient (0.6%), respectively, with 64 Gy, and in 27 patients (15.4%) and four patients (2.3%), respectively, with 70 Gy (P = .8). Changes in early QoL were minor. Patients receiving 70 Gy reported a more pronounced and clinically relevant worsening in urinary symptoms (mean difference in change score between arms, 3.6; P = .02). CONCLUSION Dose-intensified SRT was associated with low rates of acute grade 2 and 3 GU and GI toxicity. The impact of dose-intensified SRT on QoL was minor, except for a significantly greater worsening in urinary symptoms.

Givenness, procedural meaning and connectives: The case of French puisque

I argue that the communication of given information is part of the procedural instructions conveyed by some connectives like the French puisque. I submit in addition that the encoding of givenness has cognitive implications that are visible during online processing. I assess this hypothesis empirically by comparing the way the clauses introduced by two French causal connectives, puisque and parce que, are processed during online reading when the following segment is ‘given’ or ‘new’. I complement these results by an acceptability judgement task using the same sentences. These experiments confirm that introducing a clause conveying given information is a core feature characterizing puisque, as the segment following it is read faster when it contains given rather than new information, and puisque is rated as more acceptable than parce que in such contexts. I discuss the implications of these results for future research on the description of the meaning of connectives.

Car, parce que, puisque’ revisited: Three empirical studies on French causal connectives

In French, a causal relation is often conveyed by the connectives car, parce que or puisque. Since the seminal work of the Lambda-l Group (1975), it has generally been assumed that parce que, used to relate semantic content, contrasts with car and puisque, both used to connect either speech act or epistemic content. However, this analysis leaves a number of questions unanswered. In this paper, I present a reanalysis of this trio, using empirical methods such as corpus analysis and constrained elicitation. Results indicate that car and parce que are interchangeable in many contexts, even if they are still prototypically used in their respective domain in writing. As for puisque, its distribution does not overlap with car, despite their similar domains of use. I argue that the specificity of puisque with respect to the other two connectives is to introduce a cause with an echoic meaning.

Connecteurs pragmatiques et métareprésentation: l’exemple de parce que

L’objectif principal de cet article est de montrer que certains emplois des connecteurs pragmatiques nécessitent la construction d’une métareprésentation. Nous verrons d’abord que les capacités humaines de métareprésentation sont diverses et montrerons ensuite que cette diversité se retrouve dans les différents types d’emplois des connecteurs. Nous proposerons une esquisse de modèle qui rend compte de cette propriété des connecteurs dans le cadre de la théorie de la pertinence. Enfin, nous testerons la validité de notre modèle en présentant des données dans le domaine de l’acquisition du langage, plus particulièrement sur la production de parce que chez des enfants entre deux et quatre ans.