The prevention of relapse is the major therapeutic challenge in older patients with acute myeloid leukemia (AML) who have obtained a complete remission (CR) on intensive chemotherapy. In this randomized phase 3 study (HOVON97) in older patients (≥60 years) with AML or myelodysplastic syndrome with refractory anemia with excess of blasts, in CR/CR with incomplete hematologic recovery (CRi) after at least 2 cycles of intensive chemotherapy, we assessed the value of azacitidine as postremission therapy with respect to disease-free survival (DFS; primary end point) and overall survival (OS; secondary end point). In total, 116 eligible patients were randomly (1:1) assigned to either observation (N = 60) or azacitidine maintenance (N = 56; 50 mg/m2, subcutaneously, days 1-5, every 4 weeks) until relapse, for a maximum of 12 cycles. Fifty-five patients received at least 1 cycle of azacitidine, 46 at least 4 cycles, and 35 at least 12 cycles. The maintenance treatment with azacitidine was feasible. DFS was significantly better for the azacitidine treatment group (logrank; P = .04), as well as after adjustment for poor-risk cytogenetic abnormalities at diagnosis and platelet count at randomization (as surrogate for CR vs CRi; Cox regression; hazard ratio, 0.62; 95% confidence interval, 0.41-0.95; P = .026). The 12-month DFS was estimated at 64% for the azacitidine group and 42% for the control group. OS did not differ between treatment groups, with and without censoring for allogeneic hematopoietic cell transplantation. Rescue treatment was used more often in the observation group (n = 32) than in the azacitidine maintenance group (n = 9). We conclude that azacitidine maintenance after CR/CRi after intensive chemotherapy is feasible and significantly improves DFS. The study is registered with The Netherlands Trial Registry (NTR1810) and EudraCT (2008-001290-15).

To cite this article: van Doormaal FF, Terpstra W, van der Griend R, Prins MH, Nijziel MR, van de Ree MA, Bü ller HR, Dutilh JC, ten Cate-Hoek A, van den Heiligenberg SM, van der Meer J, Otten JM. Is extensive screening for cancer in idiopathic venous thromboembolism warranted? J Thromb Haemost 2011; 9: 79-84.Summary. Background: Patients with a first episode of idiopathic venous thromboembolism (IVTE) have an estimated 10% incidence of cancer within 12 months after diagnosis. However, the utility of screening for cancer in this population is controversial. Methods: In this prospective concurrently controlled cohort study, limited and extensive cancer screening strategies were compared. All 630 patients underwent baseline screening consisting of history, physical examination, basic laboratory tests and chest X-ray. In the extensive screening group abdominal and chest CT scan and mammography were added. Outcomes were incidence and curability of cancer, and cancer-related and overall mortality. Results: In 12 of the 342 (3.5%) patients in the extensive screening group malignancy was diagnosed at baseline compared with 2.4% (seven of 288 patients) in the limited screening group. Extensive screening detected six additional cancers (2.0%; 95% CI, 0.74-4.3), of which three were potentially curable. During a median 2.5 years of follow-up, cancer was diagnosed in 3.7% and 5.0% in the extensive and limited screening groups, respectively. In the extensive screening group 26 patients (7.6%) died compared with 24 (8.3%) in the limited screening group; adjusted hazard ratio 1.22 (95% CI, 0.69-2.22). Of these deaths 17 (5.0%) in the extensive screening group and 8 (2.8%) in the limited screening group were cancer related; adjusted hazard ratio 1.79 (95% CI, 0.74-4.35). Conclusions: The low yield of extensive screening and lack of survival benefit do not support routine screening for cancer with abdominal and chest CT scan and mammography in patients with a first episode of IVTE.

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ObjectiveTo explore the extent to which patients have a directing role in decisions about chemotherapy in the palliative phase of cancer and (want to) anticipate on the last stage of life.DesignQualitative interview study.MethodsIn depth-interviews with 15 patients with advanced colorectal or breast cancer at the medical oncology department in a Dutch teaching hospital; interviews were analysed following the principles of thematic content-analysis.ResultsAll patients reported to know that the chemotherapy they received was with palliative intent. Most of them did not express the wish for information about (other) treatment options and put great trust in their physicians’ treatment advice. The more patients were aware of the severity of their disease, the more they seemed to ‘live their life’ in the present and enjoy things besides having cancer. Such living in the present seemed to be facilitated by the use of chemotherapy. Patients often considered the ‘chemotherapy-free period’ more stressful than periods when receiving chemotherapy despite their generally improved physical condition. Chemotherapy (regardless of side-effects) seemed to shift patients’ attention away from the approaching last stage of life. Interestingly, although patients often discussed advance care planning, they were reluctant to bring on end-of-life issues that bothered them at that specific moment. Expressing real interest in people ‘as a person’ was considered an important element of appropriate care.ConclusionsFearing their approaching death, patients deliberately focus on living in the present. Active (chemotherapy) treatment facilitates this focus, regardless of the perceived side-effects. However, if anxiety for what lies ahead is the underlying reason for treatment, efforts should be made in assisting patients to find other ways to cope with this fear. Simultaneously, such an approach may reduce the use of burdensome and sometimes costly treatment in the last stage of life.

Renal failure is accompanied by endothelial activation of a different nature in CKD4 and PD patients compared to HD patients, and results in all subgroups in an increase of mainly platelet-derived MPs that appear to be less procoagulant than in other disease states, possibly because of the uraemic functional defect of their cellular source.