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
Purpose: To determine the use of surgical clips as a surrogate for localization of the excision cavity and to quantify the stability of the clips' positions during the course of external beam... Show morePurpose: To determine the use of surgical clips as a surrogate for localization of the excision cavity and to quantify the stability of the clips' positions during the course of external beam radiotherapy for breast cancer patients, using cone beam computed tomography (CBCT) scans.Methods and Materials: Twenty-one breast cancer patients with surgical clips placed in the breast excision cavity were treated in a supine position with 28 daily fractions. CBCT scans were regularly acquired for a setup correction protocol. Retrospectively, the CBCT scans were registered to the planning CT scans, using gray-value registration of the excision cavity region and chamfer matching of the clips. Subsequently, residual setup errors (systematic [Sigma] and random [sigma]) of the excision cavity were estimated relative to the clips' registration. Finally, the stability of the clips' positions were quantified as the movement of each separate clip according to the center of gravity of the excision cavity.Results: When clips were used for online setup corrections, the residual errors of the excision cavity were Sigma(left-right) = 1.2, sigma(left-right) = 1.0; Sigma(cranial-caudal) = 1.3, sigma(cranial-caudal) = 1.2; and Sigma(anterior-posterior) = 0.7, sigma(anterior-posterior) = 0.9 mm. Furthermore, the average distance (over all patients) between the clips and centers of gravity of the excision cavities was 18.8 mm (on the planning CT) and was reduced to 17.4 mm (measured on the last CBCT scan).Conclusion: Clips move in the direction of the center of gravity of the excision cavity, on average, 1.4 mm. The clips are good surrogates for locating the excision cavity and providing small residual errors. (c) 2011 Elsevier Inc. Show less
This thesis consists of two parts. In part I, we have demonstrated that preoperatively administrated systemic (neoadjuvant) therapy is a feasible treatment strategy in early stage breast cancer to... Show moreThis thesis consists of two parts. In part I, we have demonstrated that preoperatively administrated systemic (neoadjuvant) therapy is a feasible treatment strategy in early stage breast cancer to achieve improved surgical options and to assess tumor response. We also demonstrated that overexpression of the breast cancer stem cell marker aldehyde dehydrogenase-1 in early stage breast cancer patients is inversely associated with age and is of prognostic importance. In part II, we have demonstrated proof-of-principle of intraoperative tumor detection and image-guided tumor resection by using the novel technique of near-infrared fluorescence imaging. We have performed two clinical trials to optimize the use of indocyanine green as a near-infrared fluorescence lymphatic tracer for the sentinel lymph node procedure in breast cancer patients. Show less
Women from families in which many individuals have developed breast and/or ovarian cancer may request for DNA-testing. A DNA-test result may disclose their own risks to develop cancer (again),... Show moreWomen from families in which many individuals have developed breast and/or ovarian cancer may request for DNA-testing. A DNA-test result may disclose their own risks to develop cancer (again), their relatives__ risks and subsequent options for medical surveillance. This thesis describes several multicenter studies in the Netherlands about the psychological and medical impact of DNA-testing on the lives of these women and their relatives. Despite their accurate understanding of the global meaning of DNA-test result, many participants interpreted the result differently from what the genetic-counselor had actually communicated. Like in a children__s whisper game, their relatives also misinterpreted the information communicated by the first messenger. The messengers__ misinterpretation was not only related to their inaccurate thoughts about heredity and cancer in general, but also to their feelings, and especially to their unfulfilled need for certainty, sense of self and unresolved existential issues. The presence of misinterpretations predicted the extent of the counselees' distress and the medical decisions after DNA-test result disclosure. The study results are described in their historical and theoretical context, followed by practical clinical suggestions for genetic-counselors and psychologists. For instance, we suggest that genetic-counselor try to avoid the communication of ambiguous DNA-test results that do not have medical consequences. Show less
Despite major advances in breast cancer diagnostics and treatment over the years, the disease is still a leading cause of death in women worldwide. Primary breast tumors can be treated relatively... Show moreDespite major advances in breast cancer diagnostics and treatment over the years, the disease is still a leading cause of death in women worldwide. Primary breast tumors can be treated relatively well with radiation, surgery, chemotherapy or a combination of these treatments. The occurrence of distant metastases derived from the primary tumor however, results in a considerable decrease in disease prognosis. Metastasis formation occurs through a series of distinct cell biological steps (outlined above). Understanding the molecular mechanisms that underlie each of these steps will help in the development of more successful anti-metastasis treatments. In this thesis, both in vitro and in vivo studies are described that aim at unraveling some of the processes involved in metastasis formation: signaling by components of the focal adhesions and cell migration. Show less
Topolnjak, R.; Sonke, J.J.; Nijkamp, J.; Rasch, C.; Minkema, D.; Remeijer, P.; Vliet-Vroegindeweij, C. van 2010
Purpose: To quantify the differences in setup errors measured with the cone-beam computed tomography (CBCT) and electronic portal image devices (EPID) in breast cancer patients.Methods and... Show morePurpose: To quantify the differences in setup errors measured with the cone-beam computed tomography (CBCT) and electronic portal image devices (EPID) in breast cancer patients.Methods and Materials: Repeat CBCT scan were acquired for routine offline setup verification in 20 breast cancer patients. During the CBCT imaging fractions, EPID images of the treatment beams were recorded. Registrations of the bony anatomy for CBCT to planning CT and EPID to digitally reconstructed-radiographs (DRRs) were compared. In addition, similar measurements of an anthropomorphic thorax phantom were acquired. Bland-Altman and linear regression analysis were performed for clinical and phantom registrations. Systematic and random setup errors were quantified for CBCT and EPID-driven correction protocols in the EPID coordinate system (U, V), with V parallel to the cranial-caudal axis and U perpendicular to V and the central beam axis.Results: Bland-Altman analysis of clinical EPID and CBCT registrations yielded 4 to 6-mm limits of agreement, indicating that both methods were not compatible. The EPID-based setup errors were smaller than the CBCT-based setup errors. Phantom measurements showed that CBCT accurately measures setup error whereas EPID underestimates setup errors in the cranial caudal direction. In the clinical measurements, the residual bony anatomy setup errors after offline CBCT-based corrections were Sigma(U) = 1.4 mm, Sigma(V) = 1.7 mm, and sigma(U) = 2.6 mm, sigma(V) = 3.1 mm. Residual setup errors of EPID driven corrections corrected for underestimation were estimated at Sigma(U) = 2.2mm, Sigma(V) = 3.3 mm, and sigma(U) = 2.9 mm, sigma(V) = 2.9 mm.Conclusion: EPID registration underestimated the actual bony anatomy setup error in breast cancer patients by 20% to 50%. Using CBCT decreased setup uncertainties significantly. (C) 2010 Elsevier Inc. Show less
In het proefschrift van Martine van Miltenburg wordt het onderzoek naar de rol van FAK en annexine A1 in borstkankerontwikkeling en uitzaaiing (metastasering) beschreven. E__n van de... Show moreIn het proefschrift van Martine van Miltenburg wordt het onderzoek naar de rol van FAK en annexine A1 in borstkankerontwikkeling en uitzaaiing (metastasering) beschreven. E__n van de sleutelprocessen bij de metastasering is de verandering van het rustige fenotype van kankercellen naar het beweeglijke fenotype. Een belangrijke ontdekking is dat het eiwit annexine A1 een belangrijke rol speelt in metastasering van basale borstkanker. Verhoogde expressie van annexine A1 draagt bij aan beweeglijkheid en daarmee agressief gedrag van tumorcellen. Hoe hoger de expressie van annexine A1, hoe meer uitzaaiingen, simpel gezegd. Wanneer annexine A1 wordt uitgeschakeld in deze cellen verandert de cel van het agressieve gedrag naar een ___rustige___ tumorcel, en ontstaan er beduidend minder uitzaaiingen. Ondanks de veelbelovende resultaten is het geen optie om remming van annexine A1 als anti-kanker therapie te gebruiken omdat annexine A1 ook in gezonde lichaamscellen een belangrijke functie heeft. Maar de onderzoekers denken wel dat annexine A1 een ___marker___ voor basale borstkanker kan worden. Doordat annexine A1 specifiek in basale borstkanker verhoogd tot expressie komt zou het als marker wellicht goed gebruikt kunnen worden om dit relatief agressieve type borstkanker type te bepalen bij pati__nten. Show less
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
Le, Dévédec S.E.; Roosmalen, W.P.E. van; Maria, N.; Grimbergen, M.; Pont, C.M.; Lalai, R.A.; Water, B. van de 2009