The aim of this work was to develop methods to measure structural changes in the skeleton using MicroCT. In addition, these new methods should be able to quantify biologically relevant changes. In... Show moreThe aim of this work was to develop methods to measure structural changes in the skeleton using MicroCT. In addition, these new methods should be able to quantify biologically relevant changes. In order to do this, normalized methods to analyse MicroCT scans and perform quantitative measurements within these datasets are described in this thesis. These techniques were combined with a biological angiogenesis assay and used as research tools in a study comparing various different combination treatments of bone metastases. Show less
Lips, I.M.; Gils, C.H. van; Kotte, A.N.T.J.; Leerdam, M.E. van; Franken, S.P.G.; Heide, U.A. van der; Vulpen, M. van 2012
Purpose: To investigate whether magnesium oxide during external-beam radiotherapy for prostate cancer reduces intrafraction prostate motion in a double-blind, placebo-controlled randomized trial... Show morePurpose: To investigate whether magnesium oxide during external-beam radiotherapy for prostate cancer reduces intrafraction prostate motion in a double-blind, placebo-controlled randomized trial.Methods and Materials: At the Department of Radiotherapy, prostate cancer patients scheduled for intensity-modulated radiotherapy (77 Gy in 35 fractions) using fiducial marker-based position verification were randomly assigned to receive magnesium oxide (500 mg twice a day) or placebo during radiotherapy. The primary outcome was the proportion of patients with clinically relevant intrafraction prostate motion, defined as the proportion of patients who demonstrated in >= 50% of the fractions an intrafraction motion outside a range of 2 mm. Secondary outcome measures included quality of life and acute toxicity.Results: In total, 46 patients per treatment arm were enrolled. The primary endpoint did not show a statistically significant difference between the treatment arms with a percentage of patients with clinically relevant intrafraction motion of 83% in the magnesium oxide arm as compared with 80% in the placebo arm (p = 1.00). Concerning the secondary endpoints, exploratory analyses demonstrated a trend towards worsened quality of life and slightly more toxicity in the magnesium oxide arm than in the placebo arm; however, these differences were not statistically significant.Conclusions: Magnesium oxide is not effective in reducing the intrafraction prostate motion during external-beam radiotherapy, and therefore there is no indication to use it in clinical practice for this purpose. (C) 2012 Elsevier Inc. Show less
Once prostate cancer has spread to the skeleton, patients cannot be cured from their disease. Identification of the cell(s) of origin of prostate cancer as well as the neoplastic cell(s) involved... Show moreOnce prostate cancer has spread to the skeleton, patients cannot be cured from their disease. Identification of the cell(s) of origin of prostate cancer as well as the neoplastic cell(s) involved in the formation of distant metastases is, therefore, fundamental to understanding of carcinogenesis and metastasis. The functional identification of metastasis-initiating cells is a prerequisite for properly targeted therapy of metastatic disease in advanced prostate cancer. In chapter 2 of this thesis, the possible use of aldehyde dehydrogenase (ALDH) as marker for the identification and isolation of tumor-initiating and metastasis-initiating cells in prostate cancer is studied. In chapter 3, the functional role of a single ALDH isoform (ALDH7A1) in metastatic prostate cancer is investigated by knockdown studies in vitro and in vivo. In chapter 4, the functional involvement of _v integrins in the formation of a metastatic stem/progenitor prostate cancer phenotype is studied. Subsequently, in chapter 5, the targeting of integrins by a novel non-peptide integrin antagonist is evaluated in vitro and in preclinical models of prostate cancer progression and metastasis. Finally, general conclusions and discussions are described in chapter 6. Show less
Lips, I.M.; Kotte, A.N.T.J.; Gils, C.H. van; Leerdam, M.E. van; Heide, U.A. van der; Vulpen, M. van 2011
Purpose: To evaluate the effect of an antiflatulent dietary advice on the intrafraction prostate motion in patients treated with intensity-modulated radiotherapy (IMRT) for prostate cancer.Methods... Show morePurpose: To evaluate the effect of an antiflatulent dietary advice on the intrafraction prostate motion in patients treated with intensity-modulated radiotherapy (IMRT) for prostate cancer.Methods and Materials: Between February 2002 and December 2009, 977 patients received five-beam IMRT for prostate cancer to a dose of 76 Gy in 35 fractions combined with fiducial markers for position verification. In July 2008, the diet, consisting of dietary guidelines to obtain regular bowel movements and to reduce intestinal gas by avoiding certain foods and air swallowing, was introduced to reduce the prostate motion. The intrafraction prostate movement was determined from the portal images of the first segment of all five beams. Clinically relevant intrafraction motion was defined as >= 50% of the fractions with an intrafraction motion outside a range of 3 mm.Results: A total of 739 patients were treated without the diet and 105 patients were treated with radiotherapy after introduction of the diet. The median and interquartile range of the average intrafraction motion per patient was 2.53 mm (interquartile range, 2.2-3.0) without the diet and 3.00 mm (interquartile range, 2.4-3.5) with the diet (p < .0001). The percentage of patients with clinically relevant intrafraction motion increased statistically significant from 19.1% without diet to 42.9% with a diet (odds ratio, 3.18; 95% confidence interval, 2.07-4.88; p < .0001).Conclusions: The results of the present study suggest that antiflatulent dietary advice for patients undergoing IMRT for prostate cancer does not reduce the intrafraction movement of the prostate. Therefore, antiflatulent dietary advice is not recommended in clinical practice for this purpose. (C) 2011 Elsevier Inc. Show less
Hoogen, C. van den; Horst, G. van der; Cheung, H.; Buijs, J.T.; Pelger, R.C.M.; Pluijm, G. van der 2011
The skeleton is one of the most common organs to be affected by metastatic disease. However, only a restricted number of solid cancers, especially those of the breast and prostate, are responsible... Show moreThe skeleton is one of the most common organs to be affected by metastatic disease. However, only a restricted number of solid cancers, especially those of the breast and prostate, are responsible for the majority of the bone metastases. Bone metastases are a major cause of morbidity, characterized by severe pain and high incidence of fractures, spinal cord compression and bone marrow aplasia requiring hospitalization. Despite the high frequency of skeletal metastases, the molecular mechanisms underlying the predisposition for tumors to colonize bone are poorly understood and treatment options are often unsatisfactory. The focus of this thesis was to better understand the processes that contribute to the formation of distant metastasis (chapter 2), particularly to bone (chapter 4__7), as well as to explore new treatment strategies with conventional (chapter 4 and 5) and novel therapeutic molecules (chapter 6 and 7) using optical imaging to sensitively monitor growth, dissemination and metastasis in mouse models (chapter 3__7). Show less
