Characteristics of critically ill cancer patients in the Netherlands

The care for acute complications occurring in cancer patients has changed dramatically in recent decades, not only for direct post-operative care following major cancer surgery, but also for cancer patients in need of organ function replacement due to the manifestation of their malignancy or toxicity of the therapies provided. This thesis studies the epidemiology and outcome of critical illness associated with cancer and/or its treatment in the Netherlands. Chapters 2-5 describe the proportion of cancer patients that requires admission to an Intensive Care Unit (ICU) during the course of their disease and their characteristics and outcome once in the ICU. Chapters 6 and 7 focus on infectious complications in cancer patients. Chapter 8 & 9 contains the summary, general discussion and future perspectives.UBL - phd migration 201

Secondary analyses of the randomized phase III Stop&Go study: efficacy of second-line intermittent versus continuous chemotherapy in HER2-negative advanced breast cancer

Background: Previously, we showed that reintroduction of the same (first-line) chemotherapy at progression could only partially make up for the loss in efficacy as compared to continuously delivered first-line chemotherapy. Here, we report the probability of starting second-line study chemotherapy in the Stop&Go trial, and the progression-free survival (PFS) and overall survival (OS) of patients who received both the first- and second-line treatment in an intermittent versus continuous schedule. Methods: First-line chemotherapy comprised paclitaxel plus bevacizumab, second-line capecitabine or non-pegylated liposomal doxorubicin, given per treatment line as two times four cycles (intermittent) or as eight consecutive cycles (continuous). Results: Of the 420 patients who started first-line treatment within the Stop&Go trial (210:210), a total of 270 patients continued on second-line study treatment (64% of all), which consisted of capecitabine in 201 patients and of non-pegylated liposomal doxorubicin in 69 patients, evenly distributed between the treatment arms. Median PFS was 3.7 versus 5.0 months (HR 1.07; 95% CI: 0.82–1.38) and median OS 10.9 versus 12.4 months (HR 1.27; 95% CI: 0.98–1.66) for intermittent versus continuous second

Adjuvant dose-dense doxorubicin-cyclophosphamide versus docetaxel-doxorubicin-cyclophosphamide for high-risk breast cancer: First results of the randomised MATADOR trial (BOOG 2004-04)

Background: Dose-dense administration of chemotherapy and the addition of taxanes to anthracycline-based adjuvant chemotherapy have improved breast cancer survival substantially. However, clinical trials directly comparing the additive value of taxanes with dose-dense anthracycline-based chemotherapy are lacking. Patients and methods: In the multicentre, randomised, biomarker discovery Microarray Analysis in breast cancer to Tailor Adjuvant Drugs Or Regimens (MATADOR) trial, patients with pT1-3, pN0-3 breast cancer were randomised (1:1) between six adjuvant cycles of doxorubicin 60 mg/m2 and cyclophosphamide 600 mg/m2 every 2 weeks (ddAC) and six cycles of docetaxel 75 mg/m2, doxorubicin 50 mg/m2 and cyclophosphamide 500 mg/m2 every 3 weeks (TAC). The primary objective was to discover a predictive gene expression profile for ddAC and TAC benefit. Here we report the preplanned secondary end-point recurrence-free survival (RFS) and overall survival (OS). Results: Between 2004 and 2012, 664 patients were randomised. At 5 years, RFS was 87% (95% confidence interval [CI] 83%–91%) in the ddAC-treated patients and 88% (84–92%) in the TAC-treated subgroup (hazard ratio [HR] 0.89, 95% CI 0.62–1.28, P = 0.53). OS at 5 years was 93% (90%–96%) in the ddAC-treated and 94% (91%–97%) in the TAC-treated patients (HR 0.89, 95% CI 0.57–1.39, P = 0.61). Anaemia was more frequent in ddAC-treated patients (62/327 patients [18.9%] versus 15/319 patients [4.7%], P < 0.001) and diarrhoea (21 [6.4%] versus 53 [16.6%], P<0.001) and peripheral neuropathy (15 [4.6%] versus 46 [14.4%], P < 0.001) were observed more often in TAC-treated patients. Conclusions: With a median follow-up of 7 years, no significant differences in RFS and OS were observed between six adjuvant cycles of ddAC and TAC in high-risk breast cancer patients. Trial registration numbers: ISRCTN61893718 and BOOG 2004-04

Differences in Trial and Real-world Populations in the Dutch Castration-resistant Prostate Cancer Registry

__Background:__ Trials in castration-resistant prostate cancer (CRPC) treatment have shown improved outcomes, including survival. However, as trial populations are selected, results may not be representative for the real-world population. The aim of this study was to assess the differences between patients treated in a clinical trial versus standard care during the course of CRPC in a real-world CRPC population. __Design, setting, and participants:__ Castration-resistant Prostate Cancer Registry is a population-based, observational, retrospective registry. CRPC patients from 20 hospitals in the Netherlands have been included from 2010 to 2013. __Outcome measurements and statistical analysis:__ Baseline characteristics, systemic treatment, and overall survival were the main outcomes. Descriptive statistics, multivariate Cox regression, and multiple imputations with the Monte Carlo Markov Chain method were used. __Results and limitations:__ In total, 1524 patients were enrolled of which 203 patients had participated in trials at any time. The median follow-up period was 23 mo. Patients in the trial group were significantly younger and had less comorbidities. Docetaxel treatment was more freque

Bloodstream infections in patients with or without cancer in a large community hospital

PURPOSE\nCancer is associated with an increased risk of acquiring bloodstream infection (BSIs). Most knowledge on pathogens and outcome are derived from specialised cancer centres. We here sought to compare causative micro-organisms in BSIs in patients with or without cancer in a 600-bed teaching community hospital.\nMETHODS\nWe analysed all positive blood cultures from adult patients between January 2005 and January 2011.\nRESULTS\nA total of 4,918 episodes of BSI occurred in 2,891 patients, of whom 13.4% had a diagnosis of cancer (85.5% with a solid tumour). In both patient groups, Gram-positive isolates were more prevalent (58.7 and 61.4% in patients with and without cancer, respectively) than Gram-negative isolates (31.8 and 32.3%, respectively). Amongst Gram-positive organisms, coagulase-negative staphylococci, Staphylococcus aureus and enterococci were the most frequently isolated in both patient groups; in cancer patients, twice as many BSIs were caused by Enterococcus faecalis and E. faecium. Amongst Gram-negative organisms, Escherichia coli was the most common isolate; in cancer patients, twice as many BSIs were caused by Pseudomonas aeruginosa and Enterobacter cloacae. Yeasts were grown from 3.0% of blood cultures from cancer patients compared to 1.5% of cultures from non-cancer patients. Cancer patients had a 90-day mortality of 35.8% following BSI compared to 23.5% in patients without cancer.\nCONCLUSION\nThese data demonstrate distinct BSI pathogens and impaired outcomes in patients with cancer in the setting of a large community teaching hospital.Perioperative Medicine: Efficacy, Safety and Outcom

Low complication rates in the use of port-a-caths in oncology patients

Perioperative Medicine: Efficacy, Safety and Outcom

Safety and efficacy of the addition of simvastatin to panitumumab in KRAS mutant metastatic colorectal cancer patients

Personalised Therapeutic

Outcomes of cancer patients after unplanned admission to general intensive care units

Perioperative Medicine: Efficacy, Safety and Outcom

Safety and efficacy of the addition of simvastatin to panitumumab in KRAS mutant metastatic colorectal cancer patients

Personalised Therapeutic

The role of chemotherapy in treatment of advanced breast cancer: an overview for clinical practice

This review aims to evaluate the role of chemotherapy-containing regimens in the treatment of advanced breast cancer (ABC), with the purpose to optimize selection, sequencing and duration of treatment with the currently available agents for clinical practice. Data from observational as well as randomized phase II and III studies were included. Chemotherapy yielded a median overall survival (OS) of 2 years in registration studies, with comparable efficacy of different agents. Combining chemotherapy agents did not yield OS improvement and caused greater toxicity compared with single-agent chemotherapy. Continuing chemotherapy till progression or unacceptable toxicity generated greater efficacy without detrimental impact on quality of life compared with a limited amount of cycles. In real-world studies, benefits after third-line chemotherapy were modest compared with first- and second-line. Furthermore, effects of previous chemotherapy predicted effects of next-line therapy in real-world. Physicians increasingly prescribed capecitabine or taxanes as first- or second-line chemotherapy over time