Ethical issues in oncology practice: a qualitative study of stakeholders' experiences and expectations.

BACKGROUND: Clinical Ethics Support Services (CESS) have been established to support healthcare professionals in addressing ethically sensitive issues in clinical practice and, in many countries, they are under development. In the context of growing CESS, exploring how healthcare professionals experience and address clinical ethics issues in their daily practice represents a fundamental step to understand their potential needs. This is even more relevant in the context of extremely sensitive diseases, such as cancer. On this basis, we carried out a qualitative study conducting in-depth semi-structured interviews with stakeholders of a major comprehensive cancer centre in Italy, with the twofold aim of investigating what ethical issues arise in the context of clinical oncology and how they are addressed, as well as stakeholders' expectations about a potential CESS to be implemented within the Institution. METHODS: The study was conducted within the theoretical framework of Grounded Theory. Participants were healthcare professionals and other key stakeholders working within the cancer centre. The semi-structured interview aimed at exploring common ethical aspects of oncology, investigating stakeholders' professional experience in dealing with clinical ethics issues, their expectations and requests regarding ethics support services. Transcripts of the interviews were coded and analysed according to the principles of Grounded Theory. RESULTS: Twenty-one stakeholders were interviewed. Our analysis showed a wide consensus on the identification of ethically relevant issues, above all those concerning communication, end-of-life, and resource allocation. The absence of institutional tools or strategies to address and manage ethical issues at the patient bedside emerged, and this is reflected in the widespread request for their development in the future. The ideal support service should be fast and flexible in order to adapt to different needs and clinical cases. CONCLUSIONS: The interviewees showed a limited degree of 'ethical awareness': despite having reported many issues in clinical practice, they could hardly identify and describe the ethical aspects, while  complaining about a lack of ethical resources in their management. To build a truly effective support service, it therefore seems appropriate to take such context into consideration and address the emerged needs. Ethical sensitivity seems to be key and it becomes even more relevant in critical clinical areas, such as the therapeutic pathways of terminally ill patients.

Role of Chemotherapy, VEGFR Inhibitors, and mTOR Inhibitors in Advanced Perivascular Epithelioid Cell Tumors (PEComas).

PURPOSE: Perivascular epitheliod cell tumors (PEComas) are rare mesenchymal neoplasms for which the role of systemic treatments is not established as there are no published prospective clinical trials or sufficiently large retrospective case series. The aim of this study is to clarify the activity of conventional chemotherapy and biological agents in advanced/metastatic PEComas. EXPERIMENTAL DESIGN: This was an observational, retrospective, international study that included patients with advanced/metastatic PEComa treated with systemic therapy at 5 European sarcoma reference centers and within the Italian Rare Cancer Network. Survival analyses were performed using the Kaplan-Meier method and the Cox hazards regression models. RESULTS: A total of 53 patients were included. Cytotoxic chemotherapy regimens were active only in a small proportion of PEComas. Gemcitabine-based regimens [objective response rate (ORR): 20%, median progression-free survival (PFS): 3.4 months] seemed to have the same activity of anthracycline-based regimens (ORR: 13%, median PFS: 3.2 months). Antiangiogenic agents resulted in disease stabilization in some patients, with a number having density changes/tissue response on imaging, with an ORR of 8.3% and a median PFS of 5.4 months. mTOR inhibitors were the most active agents, with an ORR of 41% and a median PFS of 9 months. CONCLUSIONS: Our study provides data for the selection of systemic therapy in patients with advanced/metastatic PEComa: mTOR inhibitors are the most active agents. Antiangiogenics and chemotherapy with gemcitabine-based regimens or anthracycline-based regimens are options in further line, but with a lower response rate and PFS.

Time to Definitive Failure to the First Tyrosine Kinase Inhibitor in Localized GI Stromal Tumors Treated With Imatinib As an Adjuvant: A European Organisation for Research and Treatment of Cancer Soft Tissue and Bone Sarcoma Group Intergroup Randomized Trial in Collaboration With the Australasian Gastro-Intestinal Trials Group, UNICANCER, French Sarcoma Group, Italian Sarcoma Group, and Spanish Group for Research on Sarcomas.

PURPOSE: In 2004, we started an intergroup randomized trial of adjuvant imatinib versus no further therapy after R0-R1 surgery patients with localized, high- or intermediate-risk GI stromal tumor (GIST). PATIENTS AND METHODS: Patients were randomly assigned to 2 years of imatinib 400 mg daily or no further therapy after surgery. The primary end point was overall survival; relapse-free survival (RFS), relapse-free interval, and toxicity were secondary end points. In 2009, given the concurrent improvement in prognosis of patients with advanced GIST, we changed the primary end point to imatinib failure-free survival (IFFS), with agreement of the independent data monitoring committee. We report on a planned interim analysis. RESULTS: A total of 908 patients were randomly assigned between December 2004 and October 2008: 454 to imatinib and 454 to observation. Of these, 835 patients were eligible. With a median follow-up of 4.7 years, 5-year IFFS was 87% in the imatinib arm versus 84% in the control arm (hazard ratio, 0.79; 98.5% CI, 0.50 to 1.25; P = .21); RFS was 84% versus 66% at 3 years and 69% versus 63% at 5 years (log-rank P < .001); and 5-year overall survival was 100% versus 99%, respectively. Among 528 patients with high-risk GIST by local pathologist, 5-year IFFS was 79% versus 73%; among 336 centrally reviewed high-risk patients, it was 77% versus 73%, respectively. CONCLUSION: This study confirms that adjuvant imatinib has an overt impact on RFS. No significant difference in IFFS was observed, although in the high-risk subgroup there was a trend in favor of the adjuvant arm. IFFS was conceived as a potential end point in the adjuvant setting because it is sensitive to secondary resistance, which is the main adverse prognostic factor in patients with advanced GIST.

Natural history of imatinib-naive GISTs: a retrospective analysis of 929 cases with long-term follow-up and development of a survival nomogram based on mitotic index and size as continuous variables.

Gastrointestinal stromal tumor (GIST) natural history per se has not been extensively investigated yet, with most data being drawn from large studies with a relevant referral bias. Hence, the estimation of prognosis still remains a critical issue. We retrospectively evaluated 929 GISTs resected between 1980 and 2000 in 35 Italian institutions. A total of 526 patients were found to be suitable for refining risk assessment through the development of a survival nomogram. Median follow-up was 126 months. On testing for potential prognostic parameters, age, tumor site, size, and mitotic index proved to be predictors of OS on both univariable and multivariable Cox model analyses, whereas necrosis and cytonuclear atypia were significant on univariable analysis only. The discriminative ability of the model, including the parameters selected after a backward procedure (C=0.72), improved compared with the National Institutes of Health 2002 (C=0.64) and the National Comprehensive Cancer Network 2007 (C=0.63). On the basis of these data we developed a prognostic nomogram for survival that considers site, size, and mitotic index as continuous variables, providing estimates stratified for patients aged ≤65 and >65 years. This nomogram is a tool based on survival. It overcomes problems that result from artificial categorization of continuous variables. We believe that in the future this should also be attempted by nomograms based on the risk of relapse.