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Wu H.,University of Edinburgh | Walker J.,University of Edinburgh | Damhuis R.A.,Netherlands Comprehensive Cancer Organisation | Brewster D.H.,Scottish Cancer Registry | Wild S.H.,University of Edinburgh
Lung Cancer

Objectives This study aimed to investigate the effect of metformin on survival of people with type 2 diabetes and pleural mesothelioma. Materials and methods We conducted a retrospective cohort study of people with type 2 diabetes diagnosed with pleural or unspecified mesothelioma between 1993 and 2014 using linked Scottish population-based diabetes and cancer datasets. Kaplan-Meier plots, log-rank tests, and Cox proportional hazards regression models were used to describe the association between use of metformin and all-cause mortality following diagnosis of pleural mesothelioma. Results There were 300 people with type 2 diabetes and pleural or unspecified mesothelioma of whom 148 had ever used metformin and 290 died during follow up. The median survival time was 8.8 months and 6.5 months for metformin users and non-users respectively (p = 0.37, log-rank test). After adjusting for age, sex, diabetes duration, socio-economic status, and other anti-diabetic medications the hazard ratio for mortality associated with metformin was 0.99 (95% confidence intervals: 0.76–1.28; p = 0.92). Similar non-statistically significant associations were obtained in sensitivity analyses based on metformin use in year prior to diagnosis of mesothelioma, use of metformin for more than one year, in people below the mean age at diagnosis of mesothelioma (74 years) and 74 years of age or older, limitation to pleural mesothelioma and following further adjustment for body mass index and smoking. Conclusion There was no evidence that metformin improved survival among people with type 2 diabetes and pleural mesothelioma or to support trials of metformin in people with mesothelioma. © 2016 Elsevier Ireland Ltd Source

Elferink M.A.G.,Netherlands Comprehensive Cancer Organisation | de Jong K.P.,University of Groningen | Klaase J.M.,Spectrum | Siemerink E.J.,Ziekenhuis Groep Twente | de Wilt J.H.W.,Radboud University Nijmegen
International Journal of Colorectal Disease

Purpose: The main cause of death of colorectal cancer patients is metastatic disease. Approximately 20–25 % of the patients present with metastases at time of diagnosis. The clinical course of patients who develop metachronous metastases, however, is less clear. The aims of this study were to describe the incidence, treatment and survival of patients with metachronous metastases from colorectal cancer and to determine risk factors for developing metachronous metastases.Methods: From the Netherlands Cancer Registry, patients diagnosed with colorectal carcinoma in the period 2002–2003 in North-East Netherlands were selected. Patients were followed for 5 years after diagnosis of the primary tumour. Kaplan-Meier method and Cox regression analyses were used to determine predictors for developing metastases and to analyse overall survival.Results: In total, 333 of 1743 (19 %) patients developed metachronous metastases. The majority (83 %) of these metastases were diagnosed within 3 years, and the most frequent site was the liver. Patients with advanced stage and patients with tumours in the descending colon or in the rectum were more likely to develop metastases. Approximately 10 % of all patients underwent intentionally curative treatment for their metastases, with a 5-year survival rate of 60 %. Treatment of metastases and pathologic N (pN) status were independent prognostic factors for overall survival.Conclusions: Site and stage of the primary tumour were predictors for developing metachronous metastases. A limited number of patients with metastatic disease were treated with a curative intent. These patients had a good prognosis. Therefore, focus should be on identifying more patients who could benefit from curative treatment. © 2014, Springer-Verlag Berlin Heidelberg. Source

Rombouts A.J.M.,Radboud University Nijmegen | Hugen N.,Radboud University Nijmegen | Elferink M.A.G.,Netherlands Comprehensive Cancer Organisation | Nagtegaal I.D.,Radboud University Nijmegen | de Wilt J.H.W.,Radboud University Nijmegen
Annals of Surgical Oncology

Background: Neoadjuvant chemoradiation therapy (CRT) has been widely implemented in the treatment of rectal cancer patients, but optimal timing of surgery after neoadjuvant therapy is unclear. The purpose of this study was to evaluate the effects of prolonged intervals between long-course CRT and surgery in rectal cancer patients. Methods: Data on all rectal cancer patients diagnosed between 2006 and 2011 were retrieved from the population-based Netherlands Cancer Registry; the main outcome parameters were pathologic complete response (pCR) and overall survival (OS). Outcomes were reported separately for patients with early tumors (ETs; N = 217) and locally advanced rectal cancer (LARC; N = 1073). Patients were divided into 2-week interval groups according to treatment interval, ranging from 5–6 to 13–14 weeks. Kaplan–Meier curves, and logistic regression and Cox regression models were used for data analysis. Results: No significant difference in pCR rate was observed for ET patients according to treatment interval. Compared with a treatment interval of 7–8 weeks, pCR rates in LARC patients were higher after 9–10 weeks (18.4 %; odds ratio [OR] 1.56, 95 % CI 1.03–2.37) and 11–12 weeks of treatment interval (20.8 %; OR 1.94, 95 % CI 1.15–3.26). Treatment interval did not influence OS in ET or LARC patients. Conclusions: Treatment intervals of 9–12 weeks between surgery and CRT seem to improve the chances of pCR in LARC patients, without an effect on OS. The length of treatment interval did not affect outcomes in patients with ET. The ongoing search for minimally invasive surgery drives the need for exploration of factors that improve pathologic response. © 2016 The Author(s) Source

Simkens L.H.J.,University of Amsterdam | Van Tinteren H.,Netherlands Cancer Institute | May A.,University Utrecht | Ten Tije A.J.,Amphia Hospital | And 19 more authors.
The Lancet

Background The optimum duration of first-line treatment with chemotherapy in combination with bevacizumab in patients with metastatic colorectal cancer is unknown. The CAIRO3 study was designed to determine the efficacy of maintenance treatment with capecitabine plus bevacizumab versus observation. Methods In this open-label, phase 3, randomised controlled trial, we recruited patients in 64 hospitals in the Netherlands. We included patients older than 18 years with previously untreated metastatic colorectal cancer, with stable disease or better after induction treatment with six 3-weekly cycles of capecitabine, oxaliplatin, and bevacizumab (CAPOX-B), WHO performance status of 0 or 1, and adequate bone marrow, liver, and renal function. Patients were randomly assigned (1:1) to either maintenance treatment with capecitabine and bevacizumab (maintenance group) or observation (observation group). Randomisation was done centrally by minimisation, with stratification according to previous adjuvant chemotherapy, response to induction treatment, WHO performance status, serum lactate dehydrogenase concentration, and treatment centre. Both patients and investigators were aware of treatment assignment. We assessed disease status every 9 weeks. On first progression (defined as PFS1), patients in both groups were to receive the induction regimen of CAPOX-B until second progression (PFS2), which was the study's primary endpoint. All endpoints were calculated from the time of randomisation. Analyses were done by intention to treat. This trial is registered with ClinicalTrials.gov, number NCT00442637. Findings Between May 30, 2007, and Oct 15, 2012, we randomly assigned 558 patients to either the maintenance group (n=279) or the observation group (n=279). Median follow-up was 48 months (IQR 36-57). The primary endpoint of median PFS2 was significantly improved in patients on maintenance treatment, and was 8·5 months in the observation group and 11·7 months in the maintenance group (HR 0·67, 95% CI 0·56-0·81, p<0·0001). This difference remained significant when any treatment after PFS1 was considered. Maintenance treatment was well tolerated, although the incidence of hand-foot syndrome was increased (64 [23%] patients with hand-foot skin reaction during maintenance). The global quality of life did not deteriorate during maintenance treatment and was clinically not different between treatment groups. Interpretation Maintenance treatment with capecitabine plus bevacizumab after six cycles of CAPOX-B in patients with metastatic colorectal cancer is effective and does not compromise quality of life. Funding Dutch Colorectal Cancer Group (DCCG). The DCCG received financial support for the study from the Commissie Klinische Studies (CKS) of the Dutch Cancer Foundation (KWF), Roche, and Sanofi-Aventis. © 2015 Elsevier Ltd. Source

van den Hurk C.J.G.,Netherlands Comprehensive Cancer Organisation | Winstanley J.,University of Sydney | Young A.,University of Warwick | Boyle F.,University of Sydney
Supportive Care in Cancer

Data on chemotherapy-induced alopecia (CIA) as a side effect of cancer treatment are scarce. CIA is given minimal attention in clinical trials and in the literature. However, when asking the patients with cancer for their opinion, CIA appears to have a major impact, particularly on body image and quality of life. Currently, there is no commonly used measure to evaluate CIA; It is time to improve the management and measurement of CIA. © 2015, Springer-Verlag Berlin Heidelberg. Source

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