How Do Elderly Poor Prognosis Patients Tolerate Palliative Concurrent Chemoradiotherapy for Locally Advanced Non–Small-Cell Lung Cancer Stage III? A Subset Analysis From a Clinical Phase III Trial

AbstractBackgroundIn a phase III trial of patients with unresectable, locally advanced, stage III non–small-cell lung cancer (NSCLC) with a poor prognosis, palliative concurrent chemoradiotherapy (CRT) provided a significantly better outcome than chemotherapy alone, except among performance status (PS) 2 patients. In the present subgroup analysis, we evaluated the effect on patients aged ≥ 70 years (42% of all included) compared with patients aged < 70 years enrolled in the trial.Patients and MethodsAll patients received 4 courses of intravenous carboplatin and oral vinorelbine. The experimental arm also received radiotherapy (42 Gy in 15 fractions). The included patients were required to have large tumors (> 8 cm), weight loss (> 10% within the previous 6 months) and/or PS 2.ResultsThe overall survival was increased among the CRT patients in both age groups, but the difference was significant only in patients aged < 70 years (median survival, 14.8 vs. 9.7 months; P = .001; age ≥ 70 years, median survival, 10.2 vs. 9.1 months; P = .09). Patients aged ≥ 70 years experienced better preserved health-related quality of life (QOL) and significantly less hematologic toxicity. The 2- and 3-year survival was significantly increased in both age groups receiving CRT.ConclusionElderly patients aged ≥ 70 years with unresectable, stage III, locally advanced, NSLCL and a poor prognosis can tolerate CRT with the doses adjusted to age and palliative intent. These results indicate that CRT can provide both survival and QOL benefits in elderly patients, except for those with PS 2 or worse. The male predominance in the ≥ 70-year-age group and the reduced chemotherapy intensity for the patients aged > 75 years might explain the lack of significant survival improvement among those patients aged ≥ 70 years

Does chemotherapy improve Quality of Life in NSCLC PS 2?

Introduction Nearly 40% of patients with advanced NSCLC are in performance status (PS) 2. These patients have a shorter life expectancy than PS 0/1 patients and they are underrepresented in clinical trials. Data on how platinum-based combination chemotherapy affects Health Related Quality of Life (HRQOL) of patients with PS 2 are scarce and the treatment of this important group of patients is controversial. Methods A national multicenter phase III study on platinum based chemotherapy to 432 advanced NSCLC patients included 123 patients with PS 2. To explore the treatment impact on HRQOL, the development of HRQOL during the first nine weeks were compared between PS 2 and PS 0/1 patients. We used the EORTC QLQ-C30 and QLQ-LC13 questionnaires. Standardized area under the curve for all HRQOL items, and HRQOL responses classified as better, stable or worse, were compared between the groups. Results Whereas the demographic data at baseline were well balanced between the groups, the PS 2 patients had significantly worse function and more severe symptoms than the PS 0/1 patients. In response to combination chemotherapy, the PS 2 patients had a more profound improvement of global QOL, cognitive function, fatigue, dyspnea, sleeping problems and appetite loss in comparison to the PS 0/1 group. Conclusions PS 2 NSCLC patients seem to achieve valuable HRQOL benefits from platinum-based combination therapy. Prospective clinical studies with predefined HRQOL outcomes in PS 2 patients are needed to confirm these findings

Parties and government: Incumbency and representation in parliamentary democracies

In spite of large electoral changes since the 1990s, party composition of government changes less and established parties stay longer in office than others regardless their electoral fortunes. This development is conducive to incongruence between the parties represented in parliament and those in government. It is argued that office-seeking behaviour tends to become more prominent, resulting in dominant (strongest parliamentary party) and central parties show a prolonged incumbency. If dominance and centrality occur simultaneously a pivot party emerges. This type of party is indeed characterized by prolonged incumbency of government that is often considered as political stability. This development is analysed for 16 West European democracies (before and after 1990). I contend that a representative bias has emerged that could signify a change in the representative quality of representative government in Western Europe. Stable government, when based upon less correspondence between party representation in parliament and party representation in government, may have come at a price for overall representative of democracy. © 2011 Macmillan Publishers Ltd

Democratic performance of parties and legitimacy in Europe

This article analyses the development of legitimacy across 20 European democracies (1990-2010). The claim is that the democratic performance of parties affects levels of legitimacy. A conceptual and empirical discussion is presented to establish this relationship. Democratic performance is characterised by trusting parties to be responsive to the electorate and responsible in government. Legitimacy is defined as a composite measure representing satisfaction with parties, compliance with the rule of law as well as voter turnout and willingness to protest. The responsiveness of parties appears less representative on public concerns and governmental responsibility appears closer to party interests than to the general interest. Hence, a 'democratic deficit' seems to have emerged across Europe, manifested by more electoral volatility, new parties and alternation in government and lower survival rates of governments. This negatively affects trust in parties, parliament and government efficacy. Hence, party behaviour has not strongly contributed to political legitimacy since the 1990s. © 2014 © 2014 Taylor & Francis

Consociational and rational coalitions: Norm-based government formation and the case of the Dutch provinces

Following conventional models of coalition formation, parties should prefer coalitions that have a parliamentary majority, preferably with few parties that are very similar in ideological terms. However, empirically, we observe astonishing systematic deviations from this prediction. In some countries, coalition formation can hardly be explained on the basis of the rational-choice paradigm. An example of this is the Dutch system of consociational democracy where we observe a prominent role of parties that represent the social pillars. In this article, we analyze coalition formation in the Dutch provinces over the last 20 years and supplement established theories of coalition formation by a consociational democratic perspective. In accordance with this perspective, we find that more inclusive coalitions as well as coalitions that include the three pillar parties are indeed more likely to be formed. However, we detect considerable temporal variation. Coalition formation in the Dutch provinces can increasingly be explained with the help of conventional models, whereas norm-based deviations are less common than in the past. We attempt a pragmatist interpretation of this change. More generally, we join a recent move in the literature showing how more fine-tuned explanations can lead to a more complete picture of coalition formation

Bovine and human lactoferricin peptides: chimeras and new cyclic analogs

Lactoferrin (LF) is an important antimicrobial and immune regulatory protein present in neutrophils and most exocrine secretions of mammals. The antimicrobial activity of LF has been related to the presence of an antimicrobial peptide sequence, called lactoferricin (LFcin), located in the N-terminal region of the protein. The antimicrobial activity of bovine LFcin is considerably stronger than the human version. In this work, chimera peptides combining segments of bovine and human LFcin were generated in order to study their antimicrobial activity and mechanism of action. In addition, the relevance of the conserved disulfide bridge and the resulting cyclic structure of both LFcins were analyzed by using "click chemistry" and sortase A-catalyzed cyclization of the peptides. The N-terminal region of bovine LFcin (residues 17-25 of bovine LF) proved to be very important for the antimicrobial activity of the chimera peptides against E. coli, when combined with the C-terminal region of human LFcin. Similarly the cyclic bovine LFcin analogs generated by "click chemistry" and sortase A preserved the antimicrobial activity of the original peptide, showing the significance of these two techniques in the design of cyclic antimicrobial peptides. The mechanism of action of bovine LFcin and its active derived peptides was strongly correlated with membrane leakage in E. coli and up to some extent with the ability to induce vesicle aggregation. This mechanism was also preserved under conditions of high ionic strength (150 mM NaCl) illustrating the importance of these peptides in a more physiologically relevant system