Please direct correspondence to florentine.maier@wu.ac.at.Abstract: NPOs and their funders are increasingly drawn to the Social Return on Investment (SROI) method to evaluate the social impact of programs, organizations or organization networks. While many claims about the benefits of SROI have been expressed, various points of criticism have also been raised.On the basis of both current research and our own experience in conducting SROI analyses, we develop a comprehensive assessment of this method, which is structured along two dimensions: the observer's paradigmatic perspective, on the one hand, and positive or negative valuation, on the other. We identify two major merits: SROI analysis can provide legitimacy to NPOs or their funders, and it can assist in allocating resources. We identify limitations from three perspectives: From an interpretative-sociological perspective, criticism of commensuration and utilitarianism calls the method as a whole into question.From a technical-instrumental perspective, there are a number of difficulties that could however be overcome as the method matures. From an intermediary perspective, a number of limitations become apparent that, while inherent to SROI analysis, are no reason for abandoning it, as long as they are thoroughly understood. We conclude by providing suggestions for the responsible use of SROI analysis.The question of how to advance the common good is increasingly seen as a matter of finding out and implementing "what works" rather than of following ideologies. Among NPOs and government institutions that consider themselves cutting-edge, the formulation of explicit theories of change (see, for example, Fulbright-Anderson & Auspos, 2006) as well as the regular development of evidence-based policies (Pawson, 2006:vii) are expected. In managing performance, the focus has clearly shifted from inputs and outputs to impacts and public value (Barman, 2007; Lynch-Cerullo & Cooney, 2011; Moore, 2013). On the one 1 hand, these developments are to be welcomed as progress towards more open-mindedness and discursive rationality. On the other hand, the ideology of anti-ideology comes with its own trappings. The old quip that "[p]ractical men, who believe themselves to be quite exempt from any intellectual influence, are usually the slaves of some defunct economist" (Keynes, 1965:383) still applies. The present article contributes to a deeper understanding of this dilemma by focusing on a particular method that is widely used in the search for impact and evidence: the analysis of Social Return on Investment (SROI). It is the aim of this paper to contribute to a balanced and comprehensive understanding of its merits and limitations.Out of more than 40 approaches that have been developed for measuring social impact (Stevenson, Taylor, Lyon, & Rigby, 2010), SROI analysis is one of the most widespread. It is a mixed-method-approach to assess the social, economic, and environmental impact of interventions. Its most prominent feature is the SROI ratio. This ratio aims to dete...

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Background. Cardiotoxicity related to the widely used cytotoxic compound 5‐fluorouracil (5‐FU) is rare compared with the frequency observed with the use of anthracyclines. More effective protocols incorporating active biomodulatory compounds like folinic acid (FA) or combination chemotherapy change type and severity of toxicity as well. The objective of the current study was to assess cardiotoxicity of the combination 5‐FU and folinic acid. Methods. The authors' multicenter experience with 390 patients treated for advanced gastrointestinal cancer with intermediate‐dose folinic acid and 5‐FU was reviewed. Results. The overall risk of cardiotoxicity was 3%, which is not significantly higher than that reported with 5‐FU alone. Eight of 53 patients with a history of cardiac disease reported cardiac symptoms (15.1%), compared with 5 of 337 patients (1.5%) with a no history of cardiac disease. Median time to symptoms was 3 days (range, 2–6). Nine patients had symptoms resembling myocardial ischemia, one patient died due to assumed myocardial infarction related closely to fluorouracil treatment, four patients had supraventricular arrhythmia, and one patient had congestive heart failure. A history of cardiac disease was the only risk factor associated with cardiotoxicity. Relapses were frequent on reinstitution of therapy despite cardiac symptoms in the preceding cycle. Therapeutically or prophylactically administered nitrates had no significant effect. Conclusion. Physicians should be aware of the cardiotoxic properties of active fluorouracil treatment. The combination of 5‐FU and leucovorin does not differ from single‐agent therapy in frequency or type of cardiotoxicity. Close monitoring of patients is mandatory, especially for those patients at high risk for cardiac side effects. Treatment should be discontinued if coronary symptoms develop, because neither effective treatment nor prophylaxis exists for such symptoms.

Insulin-like growth factor I (IGF-I) exerts pleiotropic effects on mammalian cells via stimulation of its receptor (IGF-IR), a receptor tyrosine kinase. In vivo, IGF-I acts both as a local tissue growth factor and as a circulating hormone. In oncological research, IGF-I has received increased attention as the activated IGF-I/IGF-IR system displays mitogeneic, transforming, and anti-apoptotic properties in various cell types by stimulating distinct intracellular signaling pathways. Recent data suggest that the anti-apoptotic effect of IGF-I may mediate decreased sensitivity to chemotherapeutic drugs in vitro and in vivo. Thus, targeting the IGF-I/IGF-IR system could serve as an approach to overcome clinical drug resistance in certain tumors.

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Thirty patients with metastatic progressive germ cell carcinoma who failed to be cured with first-line cisplatin chemotherapy were treated with a salvage regimen consisting of cisplatin 20 mg/m2, etoposide 100 mg/m2, and ifosfamide 1.2 g/m2 (PEI) intravenously (IV), days 1 to 5 every 3 weeks. Ten patients (33%) were tumor-free at the end of therapy. Complete response (CR) was achieved with chemotherapy alone in four patients and with additional surgery in six patients (two necroses, two mature teratomas, two carcinomas). Six patients (20%) had normalization of tumor markers but unresectable residual disease (Rm-), and the remaining 14 patients (46%) failed to respond. Of 10 patients with CR, nine (90%) relapsed again (eight carcinomas, one mature teratoma). The median duration of CR was 3.5 months. The median survival of the whole group was 311 days (range, 110 to 996+). Currently, seven of 30 patients are alive, and five of them are without signs of progressive tumor. The response to prior cisplatin therapy predicted for response and survival after PEI salvage therapy. Of 14 patients with prior CR, eight (57%) achieved a second CR compared with one of 11 (9%) with prior unfavorable response (P = .039). The median survival for patients with prior favorable response was 400 days, compared with 251 days for patients with prior unfavorable response (P less than .001). Myelosuppression was dose-limiting, with leukopenia greater than grade 2 in 84% and thrombocytopenia greater than grade 2 in 51% of all cycles. This three-drug regimen can induce a second CR in one third of patients with relapsed or refractory germ cell carcinoma. Only those patients with prior favorable responses can expect to be cured by this salvage regimen, while patients with prior unfavorable response should be considered for alternative salvage approaches.

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