Newly introduced hybrid systems that combine an MRI scanner with a linear accelerator for radiation treatment, called MR-linacs, provide an opportunity for the daily acquisition of quantitative MRI... Show moreNewly introduced hybrid systems that combine an MRI scanner with a linear accelerator for radiation treatment, called MR-linacs, provide an opportunity for the daily acquisition of quantitative MRI (qMRI) without increasing patient burden. This allows for the measurement of changes in quantitative MRI biomarkers over time, that may indicate a response to the radiation treatment. In this thesis, the performance of the Unity MR-linac with regards to several qMRI sequences was characterized, showing results similar to diagnostic systems in terms of accuracy and repeatability. Additionally, we found changes in qMRI parameters in patients early during treatment, which indicates potential as biomarkers for treatment outcome. Show less
Bone and joint disorders have an enormous personal- and societal impact. Diagnosis and treatment of these disorders are most efficient if targeted screening, accurate diagnosis, and targeted... Show moreBone and joint disorders have an enormous personal- and societal impact. Diagnosis and treatment of these disorders are most efficient if targeted screening, accurate diagnosis, and targeted treatment are available. To enable targeted screening, the population at risk must be well-defined, and categorized if required. Subsequently, screening- and diagnostic methods must have good, or excellent predictive value and finally, treatment must target the disease, thus spare healthy tissues and processes and thereby avoid adverse events.The aim of this thesis is to gain new insights about the diagnostic process- and treatment of pathological conditions of the bone and joints, namely male urological cancer-induced bone loss and inflammatory arthritis. Show less
The recent FLAME trial has demonstrated improved local control of intermediate to high-risk prostate cancer after focal dose escalation of the visible tumor. To visualize the tumor, MRI... Show moreThe recent FLAME trial has demonstrated improved local control of intermediate to high-risk prostate cancer after focal dose escalation of the visible tumor. To visualize the tumor, MRI examinations were taken in which prostate tissue characteristics were visualized. Since this treatment strategy improves the clinical outcome of the patient, a technical analysis of the FLAME dataset is useful for the further optimization of focal dose escalation strategies.Delineation of the prostate tumor appeared to be performed differently in the participating radiotherapy departments. Considering the impact on the realized tumor dose, this analysis demonstrated the need for guidelines of tumor delineation on MRI. Due to the complex nature of the treatment plans, in addition a prediction model was developed, which identified patients for which a higher tumor dose could be planned.The application of MRI was also investigated for ‘dose painting by numbers’, in which MRI values are translated to prescription dose without interference of manual tumor delineations. Dose prescription based on MRI appeared robust to daily patient variations, a prerequisite for further development of ‘dose painting by numbers’. However, because of the absence of significant tumor changes during the treatment course, MRI was considered not suitable for early adaptive treatment. Show less
Over recent years, several new anti-cancer agents, like enzalutamide, abiraterone and radium-223 were introduced for treatment of patients with metastatic castration-resistant prostate cancer ... Show moreOver recent years, several new anti-cancer agents, like enzalutamide, abiraterone and radium-223 were introduced for treatment of patients with metastatic castration-resistant prostate cancer (mCRPC). The phase-3 studies evaluating these agents were primarily performed in patients only treated with docetaxel, because the studies were performed in parallel to each other. The efficacy and safety of sequentially treating patients with these new agents was unknown. This thesis describes the efficacy and tolerability of enzalutamide in patients pretreated with docetaxel and abiraterone. Because the response chance of enzalutamide in this cohort was significantly lower, an analysis of patient- and disease characteristics was performed to identify the responders. Also, the efficacy and tolerability of enzalutamide in heavily pretreated patients was also evaluated.Radium-223 is the first radionuclide with a survival benefit in mCRPC patients, this was concluded based on a study performed in patients treated with docetaxel or treatment-naïve patients. Even though painful bone metastases are the main reason for treatment with radionuclides, the effect of radium-223 on pain was not properly evaluated. This thesis describes the results of the observational ROTOR-registry, which evaluated the efficacy, tolerability, effect on pain and quality of life of Radium-223 in contemporary extensively pretreated mCRPC patients. Show less
Since cancer survival rates are rising, there is growing attention for longterm side effects of cancer and its treatment. A common side effect is the negative impact of treatment on sexuality of... Show moreSince cancer survival rates are rising, there is growing attention for longterm side effects of cancer and its treatment. A common side effect is the negative impact of treatment on sexuality of patients and their partners. Patient and partners as well as healthcare professionals experience several barriers to discuss this topic, like lack of time and lack of knowlegde. Two-thirds of the cancer patients reported to be in need of information regarding sexual health; especially those who were younger, who reported a negative impact of cancer on sexuality and those who were diagnosed less than two years ago. Patients and partners reported to prefer to discuss sexual health with nurse practitioners throughout the treatment proces. Besides, satisfaction with sexual life after treatment is related to satisfaction before treatment, not only with current sexual function.Widely available information and defining responsibility within the oncology treatment team would be helpful to improve communication around sexual health in cancer care. Additionally, specialized clinics would tackle soms frequently reported barriers of discussing sexuality. More reseach is needed on the implementation of sexual healthcare in oncology practice to deliver continuum of care, which will ultimately improve patient care. Show less
In the quest for precision surgery, this thesis introduces several novel detection and navigation modalities for the localization of cancer-related tissues in the operating room. The engineering... Show moreIn the quest for precision surgery, this thesis introduces several novel detection and navigation modalities for the localization of cancer-related tissues in the operating room. The engineering efforts have focused on image-guided surgery modalities that use the complementary tracer signatures of nuclear and fluorescence radiation. The first part of the thesis covers the use of “GPS-like” navigation concepts to navigate fluorescence cameras during surgery, based on SPECT images of the patient. The second part of the thesis introduces several new imaging modalities such as a hybrid 3D freehand Fluorescence and freehand SPECT imaging and navigation device. Furthermore, to improve the detection of radioactive tracer-emissions during robot-assisted laparoscopic surgery, a tethered DROP-IN gamma probe is introduced. The clinical indications that are used to evaluate the new technologies were all focused on sentinel lymph node procedures in urology (i.e. prostate and penile cancer). Nevertheless, all presented techniques are of such a nature, that they can be applied to different surgical indications, including sentinel lymph node and tumor-receptor-targeted procedures, localization the primary tumor and metastatic spread. This will hopefully contribute towards more precise, less invasive and more effective surgical procedures in the field of oncology. Show less
