Möglichkeiten der systemischen Therapie in metastasierten Stadien des Magenkarzinoms

Zusammenfassung: Die Ergebnisse mehrerer, in letzter Zeit publizierter Phase-III-Studien haben die therapeutischen Möglichkeiten in der Behandlung des metastasierten Magenkarzinoms deutlich erweitert. Die Dauerinfusion von 5-Fluorouracil (5-FU) kann ohne Verlust an Wirkung durch Capecitabin ersetzt werden, ebenso wie Cisplatin durch Oxaliplatin. Nach den Ergebnissen der REAL-2-Studie zeigt die Kombination aus Epirubicin, Oxaliplatin und Capecitabin (EOX) eine Verbesserung des Gesamtüberlebens (9,9 vs. 11,2Monate; HR 0,8) im Vergleich zu Epirubicin, Cisplatin und 5-FU (ECF). Die Frage, ob in der First-Line-Therapie eine Dreifachkombination oder eine Zweifachkombination eingesetzt werden sollte, ist allerdings weiterhin umstritten. Die Kombination aus Irinotecan und 5-FU stellt für solche Patienten, bei denen aufgrund von Komorbiditäten eine platinfreie Therapie bevorzugt wird, eine Alternative zur Kombination Cisplatin/5-FU dar. Docetaxel, 5-FU und Cisplatin (DCF) hat sich bezüglich des Überlebens in einer randomisierten Phase-III-Studie als statistisch signifikant überlegen erwiesen, allerdings besteht eine ausgeprägte hämatologische Toxizität, welche die Anwendbarkeit insbesondere bei den häufig älteren Patienten mit einem Magenkarzinom limitiert. Randomisierte Phase-III-Studien zum Vergleich von DCF mit anderen Dreierkombinationen, wie z.B. EOX, stehen au

Advanced gastric cancer: Current treatment landscape and future perspectives.

Gastric cancer currently ranks fourth in cancer-related mortality worldwide. In the western world, it is most often diagnosed at an advanced stage, after becoming metastatic at distant sites. Patients with advanced disease (locally advanced or metastatic) have a somber prognosis, with a median overall survival of 10-12 mo, and palliative chemotherapy is the mainstay of treatment. In recent years, novel approaches using inhibition of human epidermal growth factor receptor 2 (HER2) have demonstrated significant improvements in progression-free and overall survival, compared with chemotherapy alone, in first-line treatment of patients with overexpression of HER2. In addition, both second-line chemotherapy and treatment with the vascular endothelial growth factor receptor-inhibitor ramucirumab demonstrated significant benefits in terms of overall survival, compared with best supportive care, in randomized studies. Moreover, ramucirumab in combination with chemotherapy demonstrated further significant benefits in terms of progression-free and overall survival, compared with chemotherapy alone, in second-line treatment for patients with metastatic gastric cancer. A recently published molecular classification of gastric cancer is expected to improve patient stratification and selection for clinical trials and provide a roadmap for future drug development. Nevertheless, despite these developments the prognosis of patients with advanced gastric cancer remains poor. In this review we discuss current standards of care and outline major topics of drug development in gastric cancer

Initial Staging of Locally Advanced Rectal Cancer and Regional Lymph Nodes: Comparison of Diffusion-Weighted MRI With 18F-FDG-PET/CT.

The aim of the study was to compare diffusion-weighted MRI (DW-MRI) parameters with 18F-FDG PET/CT in primary locally advanced rectal cancer (LARC). From October 2012 to September 2014, 24 patients with histologically confirmed and untreated LARC (T3-T4) prospectively underwent a pelvic 1.5-T DW-MRI (b = 0 s/mm, b = 600 s/mm2) and a whole-body 18F-FDG PET/CT, before neoadjuvant therapy. The 2 examinations were performed on the same day. Two readers measured 18F-FDG SUVmax and SUVmean of the rectal tumor and of the pathological regional lymph nodes on PET/CT and compared these with minimum and mean values of the ADC (ADCmin and ADCmean) on maps generated from DW-MRI. The diagnostic performance of ADC values in identifying pathological lymph nodes was also assessed. Regarding tumors (n = 24), we found a significant negative correlation between SUVmean and corresponding ADCmean values (ρ = -0.61, P = 0.0017) and between ADCmin and SUVmax (ρ = -0.66, P = 0.0005). Regarding the lymph nodes (n = 63), there was a significant negative correlation between ADCmean and SUVmean values (ρ = -0.38, P = 0.0021), but not between ADCmin and SUVmax values (ρ = -0.11, P = 0.41). Neither ADCmean nor ADCmin values helped distinguish pathological from benign lymph nodes (AUC of 0.24 [confidence interval, 0.10-0.38] and 0.41 [confidence interval, 0.22-0.60], respectively). The correlations between ADCmean and SUVmean suggest an association between tumor cellularity and metabolic activity in untreated LARC and in regional lymph nodes. However, compared with 18F-FDG PET/CT, ADC values are not reliable for identifying pathological lymph nodes

Carbon nanotubes : from molecular to macroscopic sensors

The components that contribute to Raman spectral shifts of single-wall carbon nanotubes (SWNT’s) embedded in polymer systems have been identified. The temperature dependence of the Raman shift can be separated into the temperature dependence of the nanotubes, the cohesive energy density of the polymer, and the buildup of thermal strain. Discounting all components apart from the thermal strain from the Raman shift-temperature data, it is shown that the mechanical response of single-wall carbon nanotubes in tension and compression are identical. The stress-strain response of SWNT’s can explain recent experimental data for carbon nanotube-composite systems

Theory of Phase Ordering Kinetics

The theory of phase ordering dynamics -- the growth of order through domain coarsening when a system is quenched from the homogeneous phase into a broken-symmetry phase -- is reviewed, with the emphasis on recent developments. Interest will focus on the scaling regime that develops at long times after the quench. How can one determine the growth laws that describe the time-dependence of characteristic length scales, and what can be said about the form of the associated scaling functions? Particular attention will be paid to systems described by more complicated order parameters than the simple scalars usually considered, e.g. vector and tensor fields. The latter are needed, for example, to describe phase ordering in nematic liquid crystals, on which there have been a number of recent experiments. The study of topological defects (domain walls, vortices, strings, monopoles) provides a unifying framework for discussing coarsening in these different systems.Comment: To appear in Advances in Physics. 85 pages, latex, no figures. For a hard copy with figures, email [email protected]

Smallest small-world network

Efficiency in passage times is an important issue in designing networks, such as transportation or computer networks. The small-world networks have structures that yield high efficiency, while keeping the network highly clustered. We show that among all networks with the small-world structure, the most efficient ones have a single ``center'', from which all shortcuts are connected to uniformly distributed nodes over the network. The networks with several centers and a connected subnetwork of shortcuts are shown to be ``almost'' as efficient. Genetic-algorithm simulations further support our results.Comment: 5 pages, 6 figures, REVTeX

Precision oncology by point-of-care therapeutic drug monitoring and dosage adjustment of conventional cytotoxic chemotherapies: A perspective.

Therapeutic drug monitoring (TDM) of conventional cytotoxic chemotherapies is strongly supported yet poorly implemented in daily practice in hospitals. Analytical methods for the quantification of cytotoxic drugs are instead widely presented in the scientific literature, while the use of these therapeutics is expected to keep going for longer. There are two main issues hindering the implementation of TDM: turnaround time, which is incompatible with the dosage profiles of these drugs, and exposure surrogate marker, namely total area under the curve (AUC). Therefore, this perspective article aims to define the adjustment needed from current to efficient TDM practice for cytotoxics, namely point-of-care (POC) TDM. For real-time dose adjustment, which is required for chemotherapies, such POC TDM is only achievable with analytical methods that match the sensitivity and selectivity of current methods, such as chromatography, as well as model-informed precision dosing platforms to assist the oncologist with dose fine-tuning based on quantification results and targeted intervals