Pazopanib with 5‐FU and oxaliplatin as first line therapy in advanced gastric cancer: A randomized phase‐II study—The PaFLO trial. A study of the Arbeitsgemeinschaft Internistische Onkologie AIO‐STO‐0510

VEGF inhibition in gastric cancer has a proven benefit in the second line setting. Pazopanib, an oral tyrosine kinase inhibitor, selectively inhibits VEGFR-1, -2 and -3, c-kit and PDGF-R resulting in inhibition of angiogenesis. This open-label randomized phase II trial (2:1) investigated the efficacy of combining pazopanib with FLO (5-fluorouracil, oxaliplatin) vs FLO alone (internal control arm) as first-line treatment in patients with advanced adenocarcinoma of the stomach and gastroesophageal junction (GEJ). Eighty-seven patients were randomized and 78 patients were eligible and evaluable (PaFLO arm 51 patients, FLO arm 27 patients). The PFS rate at 6 months (primary endpoint) was 34% in the PaFLO arm vs 30% in the FLO arm. Comparing PaFLO with FLO median PFS was 4.66 months (95% confidence interval [CI] 2.87-6.46) vs 4.47 months (95% CI 1.79-7.14) (95% CI, hazard ratio [HR] 0.96 (0.60-1.55), P = .882 [exploratory]); median OS was 10.19 months (95% CI 5.46-14.92) vs 7.33 months (95% CI 4.93-9.73), (95% CI HR 1.01 [0.62-1.65], P = .953, exploratory), disease control rate was 72% vs 59%. PaFLO was well tolerable, toxicities were slightly higher in the PaFLO arm. Major adverse events were loss of appetite, nausea, fatigue, diarrhea, neutropenia and thrombocytopenia. Adding pazopanib to chemotherapy shows signs of efficacy but no major improvement in this randomized phase 2 trial. The PFS at 6 months in both arms was lower than expected from the literature. Biomarkers identifying subgroups who benefit and novel combinations are needed. ClinicalTrials.gov: NCT01503372

Standardized flow cytometry for highly sensitive MRD measurements in B-cell acute lymphoblastic leukemia

A fully-standardized EuroFlow 8–color antibody panel and laboratory procedure was stepwise designed to measure minimal residual disease (MRD) in B-cell precursor (BCP) acute lymphoblastic leukemia (ALL) patients with a sensitivity of £1025, comparable to real-time quantitative polymerase chain reaction (RQ-PCR)–based MRD detection via antigen-receptor rearrangements. Leukocyte markers and the corresponding antibodies and fluorochromes were selected based on their contribution in separating BCP-ALL cells from normal/regenerating BCP cells in multidimensional principal component analyses. After 5 multicenter design-test-evaluate-redesign phases with a total of 319 BCP-ALL patients at diagnosis, two 8-color antibody tubes were selected, which allowed separation between normal and malignant BCP cells in 99% of studied patients. These 2 tubes were tested with a new erythrocyte bulk-lysis protocol allowing acquisition of high cell numbers in 377 bone marrow follow-up samples of 178 BCP-ALL patients. Comparison with RQ-PCR–based MRD data showed a clear positive relation between the percentage concordant cases and the number of cells acquired. For those samples with >4 million cells acquired, concordant results were obtained in 93% of samples. Most discordances were clarified upon high-throughput sequencing of antigen-receptor rearrangements and blind multicenter reanalysis of flow cytometric data, resulting in an unprecedented concordance of 98% (97% for samples with MRD 98% of patients with sensitivities at least similar to RQ-PCR (£1025), if sufficient cells (>4 3 106, preferably more) are evaluated

Cognitive and social aspects of adaptation to a communication partner

Thiele K, Foltz A, Bartels M, Stenneken P. Cognitive and social aspects of adaptation to a communication partner. In: 17th Meeting of The European Society For Cognitive Psychology. 2011.Communication is a socially highly relevant form of joint action. Adaptation of interlocutors to each other’s verbal behavior, e.g. by using identical lexical expressions or syntactic structures, is a well-studied phenomenon. Such adaptation can be found on various linguistic levels and may contribute to communicative success. But to what extent do situational aspects, cognitive capacities, social skills etc. influence adaptation on these different linguistic levels? We present a series of experiments, using the confederate scripting technique with children and adults, investigating the potential influence of cognitive factors (e.g. working memory) and social factors (e.g. interlocutor’s native language) on the strength of linguistic adaptation. Results showed that participants adapted to their interlocutor’s lexical terms, even if these were unconventional (e.g. saying telephone for a cell phone), and did so to a greater extent if their conversational partner was a non-native speaker. General language capabilities had no effect on adaptation at the syntactic level, while lower working memory capacity decreased adaptation strength. The results suggest that social-strategic and cognitive factors influence the amount of adaptation that may contribute to successful communication. In addition, top-down factors may influence adaptation behavior more strongly than general language capabilities

Eine Untersuchung zur kommunikativen Anpassung der Gesprächspartner in einem Dialogspiel

Thiele K, Bartels M, Ho WM, Stenneken P. Eine Untersuchung zur kommunikativen Anpassung der Gesprächspartner in einem Dialogspiel. Presented at the Fourth International Conference of the German Cognitive Linguistics Association, Bremen

Prognostic Relevance of Weight and Weight Loss during Multimodal Therapy for Oesophagogastric Tumours

The prognostic meaning of weight loss (WL) during standard treatment for operable oesophagogastric cancer is still unclear. The aim of this study is to analyse the prognostic effect of WL during perioperative chemotherapy (PC) for gastric cancer (GC) and oesophageal adenocarcinomas (OAC). We retrospectively analysed data from 128 patients (pts) with GC and OAC who underwent surgery in the context of multimodal treatment with PC. We collected data on WL during different steps of therapy together with other histopathologic and demographic information. We analysed the effects on overall survival (OS) and disease-free survival (DFS). Results: Pts with WL ≥ 5% during neoadjuvant chemotherapy exhibited significantly worse OS compared with pts with WL < 5% (median OS: 23.6 months [95% CI: 4.4–42.9] vs. 63.5 months [95% CI: 50.7–76.2], p = 0.007) and DFS (median DFS: 12.5 months [95% CI: 2.9–22.1] vs. 63.5 months [95% CI: 31.6–95.4], p = 0.016). Pts with WL ≥ 14% during the whole treatment exhibited significantly worse OS compared with pts with WL < 14% (median OS: 43.7 months [95% CI: 13.2–74.2] vs. not reached, p = 0.028) and DFS (median DFS: 34.3 months [95% CI: 14.0–54.5] vs. not reached, p = 0.038). Conclusion: WL patterns during neoadjuvant chemotherapy and during the whole treatment correlate with a significantly worse prognosis in operated pts with curative GC or OAC in the context of a multimodal treatment with PC. A validation of this prognostic effect in prospective studies is warranted

Impact of Postoperative Chemotherapy in Patients with Gastric/Gastroesophageal Adenocarcinoma Treated with Perioperative Chemotherapy

Perioperative chemotherapy is the standard of care for patients undergoing curative resection for gastroesophageal adenocarcinoma. However, less than 50% of patients complete postoperative chemotherapy, and the added benefit to preoperative chemotherapy remains unclear. The aim of this study was to compare disease-free and overall survival (DFS and OS) in patients with perioperative chemotherapy to those who received preoperative chemotherapy only. In addition, a current literature overview is included. This multicenter, retrospective case series included 124 patients with gastroesophageal adenocarcinoma undergoing potentially curative resection and receiving pre- or perioperative chemotherapy between 2006 and 2010. Histopathological, demographic, clinical, and survival data were used to identify the impact of perioperative vs. preoperative chemotherapy on DFS and OS. Patients with perioperative chemotherapy had significantly improved DFS and OS (median DFS 28.0 months; 95%CI 0–62.4 vs. 19.0 months; 95%CI 10.5–27.5; p = 0.008 and median OS 35.7 months; 95%CI 0–73.6 vs. 19.2 months; 95%CI 7.8–30.4; p = 0.002). However, in contrast to patients with tumor-free lymph nodes at the time of resection, patients with positive lymph node status did not significantly benefit from additional postoperative chemotherapy in subgroup analysis. Further studies are encouraged to investigate optimal adjuvant treatment strategies for primary chemotherapy-resistant patients

Prognostic Relevance of Weight and Weight Loss during Multimodal Therapy for Oesophagogastric Tumours

The prognostic meaning of weight loss (WL) during standard treatment for operable oesophagogastric cancer is still unclear. The aim of this study is to analyse the prognostic effect of WL during perioperative chemotherapy (PC) for gastric cancer (GC) and oesophageal adenocarcinomas (OAC). We retrospectively analysed data from 128 patients (pts) with GC and OAC who underwent surgery in the context of multimodal treatment with PC. We collected data on WL during different steps of therapy together with other histopathologic and demographic information. We analysed the effects on overall survival (OS) and disease-free survival (DFS). Results: Pts with WL ≥ 5% during neoadjuvant chemotherapy exhibited significantly worse OS compared with pts with WL p = 0.007) and DFS (median DFS: 12.5 months [95% CI: 2.9–22.1] vs. 63.5 months [95% CI: 31.6–95.4], p = 0.016). Pts with WL ≥ 14% during the whole treatment exhibited significantly worse OS compared with pts with WL p = 0.028) and DFS (median DFS: 34.3 months [95% CI: 14.0–54.5] vs. not reached, p = 0.038). Conclusion: WL patterns during neoadjuvant chemotherapy and during the whole treatment correlate with a significantly worse prognosis in operated pts with curative GC or OAC in the context of a multimodal treatment with PC. A validation of this prognostic effect in prospective studies is warranted

Examining the cost effectiveness of interventions to promote the physical health of people with mental health problems: a systematic review

Recently attention has begun to focus not only on assessing the effectiveness of interventions to tackle mental health problems, but also on measures to prevent physical co-morbidity. Individuals with mental health problems are at significantly increased risk of chronic physical health problems, such as cardiovascular disease or diabetes, as well as reduced life expectancy. The excess costs of co-morbid physical and mental health problems are substantial. Potentially, measures to reduce the risk of co-morbid physical health problems may represent excellent value for money