Quality of transition to end-of-life care for cancer patients in the intensive care unit

Open Access This article is distributed under the terms of the Creative Commons Attribution 4.0 International License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made.BACKGROUND: There have been few studies that have evaluated the quality of end-of-life care (EOLC) for cancer patients in the ICU. The aim of this study was to explore the quality of transition to EOLC for cancer patients in ICU. METHODS: The study was undertaken on medical patients admitted to a specialist cancer hospital ICU over 6 months. Quantitative and qualitative methods were used to explore quality of transition to EOLC using documentary evidence. Clinical parameters on ICU admission were reviewed to determine if they could be used to identify patients who were likely to transition to EOLC during their ICU stay. RESULTS: Of 85 patients, 44.7% transitioned to EOLC during their ICU stay. Qualitative and quantitative analysis of the patients' records demonstrated that there was collaborative decision-making between teams, patients and families during transition to EOLC. However, 51.4 and 40.5% of patients were too unwell to discuss transition to EOLC and DNACPR respectively. In the EOLC cohort, 76.3% died in ICU, but preferred place of death known in only 10%. Age, APACHE II score, and organ support, but not cancer diagnosis, were identified as associated with transition to EOLC (p = 0.017, p < 0.0001 and p = 0.001). CONCLUSIONS: Advanced EOLC planning in patients with progressive disease prior to acute deterioration is warranted to enable patients' wishes to be fulfilled and ceiling of treatments agreed. Better documentation and development of validated tools to measure the quality EOLC transition on the ICU are needed.Peer reviewe

Inhibition of transforming growth factor α (TGF-α)-mediated growth effects in ovarian cancer cell lines by a tyrosine kinase inhibitor ZM 252868

The modulating effects of the epidermal growth factor (EGF) receptor-specific tyrosine kinase inhibitor ZM 252868 on cell growth and signalling have been evaluated in four ovarian carcinoma cell lines PE01, PE04, SKOV-3 and PE01CDDP. Transforming growth factor α (TGF-α)-stimulated growth was completely inhibited by concentrations ≥ 0.3 μM in the PE01 and PE04 cell lines and by ≥ 0.1 μM in SKOV-3 cells. TGF-α inhibition of PE01CDDP growth was reversed by concentrations ≥ 0.1 μM ZM 252868. TGF-α-stimulated tyrosine phosphorylation of both the EGF receptor and c-erbB2 receptor in all four cell lines. The inhibitor ZM 252868, at concentrations ≥ 0.3 μM, completely inhibited TGF-α-stimulated tyrosine phosphorylation of the EGF receptor and reduced phosphorylation of the c-erbB2 protein. EGF-activated EGF receptor tyrosine kinase activity was completely inhibited by 3 μM ZM 252868 in PE01, SKOV-3 and PE01CDDP cells. These data indicate that the EGF receptor-targeted TK inhibitor ZM 252868 can inhibit growth of ovarian carcinoma cells in vitro consistent with inhibition of tyrosine phosphorylation at the EGF receptor. © 1999 Cancer Research Campaig

Red cell distribution width as predictor for mortality in critically ill patients

Background: The objective of this study was to evaluate whether the red cell distribution width (RDW) is a significant risk factor for hospital mortality in critically ill patients and to investigate whether RDW is a parameter indicating inflammation, or a risk factor independent of inflammation. Methods: We studied all patients admitted to a ten-bed mixed intensive care unit in the Netherlands between May 2005 and December 2011 for whom RDW was available, and who had not received a blood transfusion in the preceding three months. Inflammation was measured by C-reactive protein and leucocyte count. Analyses included correlation, logistic regression analysis, and receiver-operating characteristic (ROC) curves. Results: We included 2915 patients, of whom 387 (13.3%) did not survive to hospital discharge. In univariate analysis higher RDW values were associated with increased hospital mortality. In multivariate analysis RDW remained an independent risk factor for mortality after correction for APACHE II score, age, admission type and mechanical ventilation (odds ratio 1.04, 95% confidence interval 1.02-1.06, for each femtolitre of RDW). Adding RDW to APACHE II, however, increased the area under the ROC Conclusion: In critically ill patients, the RDW on ICU admission was an independent predictor of mortality. Since RDW was not correlated with inflammation, the underlying mechanism of this association warrants further investigation

Randomized Phase II Study Comparing Efficacy and Safety of Combination-Therapy Trastuzumab and Docetaxel vs. Sequential Therapy of Trastuzumab Followed by Docetaxel Alone at Progression As First-Line Chemotherapy in Patients with HER2(+) Metastatic Breast Cancer: HERTAX Trial

Background: Because chemotherapy for metastatic breast cancer (MBC) is associated with relevant toxicity, sequential monotherapy trastuzumab followed by cytotoxic therapy at disease progression might be an attractive approach. Methods: In a multicenter phase II trial, 101 patients with overexpression of human epidermal growth factor receptor 2 (HER2(+)) MBC were randomized between combination-therapy trastuzumab (Herceptin) plus docetaxel (H+D) and sequential therapy of single-agent trastuzumab followed at disease progression by docetaxel alone (H -> D) as first-line chemotherapy for metastatic disease. The primary endpoint was progression-free survival (PFS) after completed sequential or combination therapy. Results: For the H+D group the median PFS was 9.4 vs, 9.9 months for the H -> D group and 1-year PFS rates were 44% vs. 35%, respectively. However the overall response rates (ORRs) were 79% vs. 53%, respectively (P = .016), and overall survival was 30.5 vs. 19.7 months, respectively (P = .11). In the H -> D group, response rates to monotherapy trastuzumab and subsequent docetaxel were 34% and 39%, respectively, with a median PFS during single-agent trastuzumab of 3.9 months. The incidence and severity of neuropathy were significantly higher in the H+D group. Retrospective analysis of trastuzumab treatment beyond progression (applied in 46% of patients in the H+D group and 37% in the H -> D group) showed a correlation with longer overall survival in both treatment arms (36.0 vs. 18.0 months and 30.3 vs. 18.6 months, respectively). Conclusion: First-line treatment in patients with MBC with H -> D resulted in a similar PFS compared with H+D, but the response rate was lower and the overall survival nonsignificantly shorter

Difficult Decisions in Colorectal Cancer in Emergency Settings

Critically ill patients and pregnant patients with colorectal cancer represent a group where management decisions are difficult. Critically ill patients with colorectal cancer have been described to be admitted electively after surgery or urgently, with elective admission associated with improved outcomes. Patients with a considerable lifespan should be admitted without limitations as prognosis has been improving, but intensive care admission may be considered for a period (ICU trial) for patients with more stringent criteria. End-of-life discussions should take place as they are an important part of care. Colorectal cancer diagnosed during pregnancy is generally associated with advanced disease and carries a poor prognosis. There is no consensual management algorithm and decisions made in this context should be multidisciplinary. Communication between surgeon and patient is a cornerstone of treatment in these complex scenarios. A framework for this discussion is presented in the end of this chapter