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The role of chemotherapy in the treatment of pancreatic cancer (PaC) has been well-established, while radiation plays ambiguous roles. This international large-scale population-based study aimed to investigate the real-world application of chemotherapy and radiotherapy for resected and unresected PaC in Europe and USA. Population-based data from multiple European national cancer registries and the US Surveillance, Epidemiology and End Results (SEER)-18 database during 2003-2014 were analyzed. Temporal trends and geographical variations in the application rates of chemotherapy and radiotherapy were quantified using age standardization. Associations of treatment with demographic and clinical characteristics were assessed using multivariable logistic regression. A total of 141,533 PaC patients were analyzed. From 2003-2005 to 2012-2014, chemotherapy administration rates increased in most countries and more strongly among resected patients, while radiation rates were generally low with a slight decline or no obvious trend. In 2012-2014, 12.5% (Estonia) to 61.7% (Belgium) of resected and 17.1% (Slovenia) to 56.9% (Belgium) of unresected patients received chemotherapy. Radiation was administered in 2.6% (Netherlands) to 32.6% (USA) of resected and 1.0% (USA) to 6.0% (Belgium) of unresected patients. Strong temporal and geographical variations were observed. Patterns and strengths of associations of treatment administration with various demographic and clinical factors differed substantially between resected and unresected cancers and varied greatly across countries. Conclusively, administration of chemotherapy but not radiotherapy for PaC increased during the last decade in Europe and USA. Treatment rates were low and the uptake strongly varied across countries, highlighting the need for standardization in PaC treatment to improve patient care., (© 2018 UICC.)

Hepatobiliary tract cancers (HBTCs) are a heterogeneous group of cancers with high mortality. Because most of these cancers, with the exception of hepatocellular carcinoma (HCC), are rare, few data are available concerning the population level survival expectations of patients with HBTC. Here, we describe survival of patients with HBTC in Germany with comparison to survival in the US. Therefore, data were extracted from 12 databases in Germany and the Surveillance, Epidemiology and End Results (SEER13) database in the US. Period analysis and modeled period analysis were used to calculate 5-year relative survival estimates for patients with HBTC diagnosed from 1997 to 2013. HCC was the most common HBTC in each database, accounting for over 1/3 of HBTC in Germany and about half of cases in the US. Overall age adjusted 5-year relative survival for HBTC in 2006-2013 was 19.1% in Germany and 20.6% in the US. Five-year relative survival increased by 3.8% units in Germany and 4.5% units in the US between 2002-2005 and 2010-2013. Five-year relative survival for individual types of HBTC ranged from 9.8% in Germany and 2.9% in the US for not otherwise specified biliary tract cancers to 44.4% and 50.1%, respectively, in Germany and the US for duodenal cancers. In conclusion, survival for HBTC remains poor in both Germany and the US, although a small increase in survival in the past decade was observed. Further work to find better treatment options for HBTC is needed to improve survival., (© 2018 UICC.)

Previous epidemiologic studies on AML have been limited by the rarity of the disease. Here, we present population level data on survival of patients with AML in Germany and the United States (US). Data were extracted from 11 population-based cancer registries in Germany and the Surveillance, Epidemiology, and End Results (SEER13) database in the US. Patients diagnosed with AML in 1997-2011 were included. Period analysis was used to estimate 5-year relative survival (RS) and trends in survival in the early 21st century. Overall 5-year age-adjusted RS for patients with AML in 2007-2011 was greater in Germany than in the US at 22.8% and 18.8%, respectively. Five-year RS was higher in Germany than in the US at all ages, with particularly large differences at ages 15-24 for whom 5-year RS was 64.3% in Germany and 55.0% in the US and 35-44, with 5-year RS estimates of 61.8% in Germany and 46.6% in the US. Most of the difference in 5-year RS was due to higher 1-year RS, with overall 1-year RS estimates of 47.0% in Germany and 38.5% in the US. A small increase in RS was observed between 2003-2005 and 2009-2011 in both countries, but no increase in survival was observed in either country for ages 75+. To our knowledge, this is the first detailed description of AML survival in Germany. Comparison to the US suggests that further analysis into risk factors for poor outcomes in AML in the US may be useful in improving survival., (© 2016 UICC.)

The human leukemic T-cell line Jurkat was used to define the role of the cellular stress pathway with its key player kinase JNK in cancer therapy-induced apoptosis. JNK activity was inhibited by stable transfection with a dominant negative mutant of the upstream kinase JNKK/MKK4 or with the novel, potent and selective JNK1, -2 and -3 inhibitor SP600125. Inhibition of JNK activity delayed the onset of apoptosis induced by cisplatin, doxorubicin, gamma-irradiation and CD95-L but did not prevent apoptosis per se. Early events during apoptosis such as induction of CD95-L, activation of caspase-8 and exposure of phosphatidylserine on the cell surface were strongly inhibited. Also, at early time points of apoptosis, loss of the mitochondrial membrane potential and release of cytochrome c were markedly impaired. However, late signaling events during apoptosis such as cleavage of PARP and DNA fragmentation apoptosis were only marginally affected. These findings are in accordance with the activity of initiator and effector caspases. Whereas activity of the initiator caspase-8 was strongly inhibited early and late after induction, an inhibition of caspase-3 activity was only observed early after induction of apoptosis. We therefore suggest that cellular stress signaling contributes to the initiation of apoptosis, whereas it might be dispensable for the progression of apoptosis. Dysfunction of this pathway under pathological conditions might contribute to therapy resistance of cancer cells., (Copyright 2003 Wiley-Liss, Inc.)